FN ISI Export Format VR 1.0 PT J AU Bonne, G Mercuri, E Muchir, A Urtizberea, A Becane, HM Recan, D Merlini, L Wehnert, M Boor, R Reuner, U Vorgerd, M Wicklein, EM Eymard, B Duboc, D Penisson-Besnier, I Cuisset, JM Ferrer, X Desguerre, I Lacombe, D Bushby, K Pollitt, C Toniolo, D Fardeau, M Schwartz, K Muntoni, F TI Clinical and molecular genetic spectrum of autosomal dominant Emery-Dreifuss muscular dystrophy due to mutations of the lamin A/C gene SO ANNALS OF NEUROLOGY ID INTERMEDIATE FILAMENT PROTEINS; CHROMATIN BINDING-SITE; NUCLEAR-MEMBRANE; ROD DOMAIN; CARDIOMYOPATHY; ENVELOPE; INTERACTS; DISEASE AB Emery-Dreifuss muscular dystrophy (EDMD) is characterized by early contractures of the elbows and Achilles tendons, slowly progressive muscle wasting and weakness, and life-threatening cardiomyopathy with conduction blocks. We recently identified LMNA encoding two nuclear envelope proteins, lamins A and C, to be implicated in the autosomal dominant form of EDMD. Here, we report on the variability of the phenotype and spectrum of LMNA mutations in 53 autosomal dominant EDMD patients (36 members of 6 families and 17 sporadic cases). Twelve of the 53 patients showed cardiac involvement exclusively, although the remaining 41 all showed muscle weakness and contractures. We were able to identify a common phenotype among the patients with skeletal muscle involvement, consisting of humeroperoneal wasting and weakness, scapular winging, rigidity of the spine, and elbow and Achilles tendon contractures. The disease course was generally slow, but we observed either a milder phenotype characterized by late onset and a mild degree of weakness and contractures or a more severe phenotype with early presentation and a rapidly progressive course in a few cases. Mutation analysis identified 18 mutations in LMNA tie, 1 nonsense mutation, 2 deletions of a codon, and 15 missense mutations). All the mutations were distributed between exons 1 and 9 in the region of LMNA that is common to lamins A and C. LMNA mutations arose de novo in 76% of the cases; 2 of these de novo mutations were typical hot spots, and 2 others were identified in 2 unrelated cases. There was no clear correlation between the phenotype and type or localization of the mutations within the gene. Moreover, a marked inter- and intra-familial variability in the clinical expression of LMNA mutations exists, racing from patients expressing the full clinical picture of EDMD to those characterized only by cardiac involvement, which points toward a significant role of possible modifier genes in the course of this disease. In conclusion, the high proportion of de novo mutations together with the large spectrum of both LMNA mutations and the expression of the disease should now prompt screening for LMNA in familial and sporadic cases of both EDMD and dilated cardiomyopathy associated with conduction system disease. C1 Grp Hosp Pitie Salpetriere, Inst Myol, INSERM, UR523, F-75651 Paris 13, France. Hop Cochin, Genet Mol Lab, F-75674 Paris, France. Hop St Vincent de Paul, Serv Neurol, F-75674 Paris, France. Dept Neurol, Angers, France. Dept Child Neurol, Lille, France. Hop Haut Leveque, Serv Neurol, Pessac, France. CHU Bordeaux, Serv Pediat, Bordeaux, France. Hammersmith Hosp, Imperial Sch Med, Dept Paediat, London, England. Univ Newcastle Upon Tyne, Dept Human Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. Ist Ortoped Rizzoli, Neuromuscular Unit, Bologna, Italy. CNR, Ist Genet, I-27100 Pavia, Italy. Inst Human Genet, Greifswald, Germany. Univ Mainz Klinikum, Mainz, Germany. Neurol Klin & Poliklin, Dresden, Germany. Ruhr Univ Bochum, Neurol Klin & Poliklin, D-4630 Bochum, Germany. Univ Hamburg, Krankenhaus Eppendorf, Psychiat Klin, D-2000 Hamburg, Germany. RP Bonne, G, Grp Hosp Pitie Salpetriere, Inst Myol, INSERM, UR523, 47 Blvd Hop, F-75651 Paris 13, France. TC 133 PD AUG PY 2000 VL 48 IS 2 BP 170 EP 180 UT ISI:000088564700006 ER PT J AU Elson, GCA Lelievre, E Guillet, C Chevalier, S Plun-Favreau, H Froger, J Suard, I de Coignac, AB Delneste, Y Bonnefoy, JY Gauchat, JF Gascan, H TI CLF associates with CLC to form a functional heteromeric ligand for the CNTF receptor complex SO NATURE NEUROSCIENCE ID CILIARY NEUROTROPHIC FACTOR; AMYOTROPHIC-LATERAL-SCLEROSIS; LEUKEMIA INHIBITORY FACTOR; MOTOR-NEURONS; MICE LACKING; LIFR-BETA; CYTOKINE; FAMILY; SURVIVAL; DISEASE AB Ciliary neurotrophic factor (CNTF) is a cytokine supporting the differentiation and survival of various cell types in the peripheral and central nervous systems. Its receptor complex consists of a non-signaling alpha chain, CNTFR, and two signaling beta chains, gp130 and the leukemia inhibitory factor receptor (LIFR). Striking phenotypic differences between CNTF- and CNTFR-deficient mice suggest that CNTFR serves as a receptor for a second, developmentally important ligand. We have identified this factor as a stable secreted complex of cardiotrophin-like cytokine (CLC) and the soluble receptor cytokine-like factor-1 (CLF). CLF expression was required for CLC secretion, and the complex acted only on cells expressing functional CNTF receptors. The CLF/CLC complex activated gp130, LIFR and signal transducer and activator of transcription 3 (STAT3) and supported motor neuron survival. Our results indicate that the CLF/CLC complex is a second ligand for CNTFR with potentially important implications in nervous system development. C1 Ctr Immunol Pierre Fabre, F-74164 St Julien Genevois, France. CHU Angers, INSERM, E9928, F-49033 Angers, France. RP Gauchat, JF, Ctr Immunol Pierre Fabre, 5 Ave Napoleon III, F-74164 St Julien Genevois, France. TC 98 PD SEP PY 2000 VL 3 IS 9 BP 867 EP 872 UT ISI:000167177400012 ER PT J AU Roncali, J TI Oligothienylenevinylenes as a new class of multinanometer linear pi-conjugated systems for micro- and nanoelectronics SO ACCOUNTS OF CHEMICAL RESEARCH ID SOLUBLE THIENYLENEVINYLENE OLIGOMERS; BOND-LENGTH ALTERNATION; CONDUCTING POLYMERS; MOLECULAR WIRES; BANDGAP CONTROL; OLIGOTHIOPHENES; TETRATHIAFULVALENE; MACROMOLECULES; DONORS; UV/VIS AB This Account deals with the synthesis and characterization of monodisperse soluble oligothienylenevinylenes with chain lengths up to 100 Angstrom. The chain length dependence of the electronic and electrochemical properties both in solution and in the solid state are analyzed and discussed in the context of the potential use of oligothienylenevinylenes as molecular wires. Problems related to interchain interactions are illustrated by the analysis of the effects of structure on the reversible dimerization of cation radicals and by the synthesis of new series of end-substituted oligomers. C1 Univ Angers, CNRS, UMR 6501, F-49045 Angers, France. RP Roncali, J, Univ Angers, CNRS, UMR 6501, 2 Blvd Lavoisier, F-49045 Angers, France. TC 90 PD MAR PY 2000 VL 33 IS 3 BP 147 EP 156 UT ISI:000086154500003 ER PT J AU Legrand, E Chappard, D Pascaretti, C Duquenne, M Krebs, S Rohmer, V Basle, MF Audran, M TI Trabecular bone microarchitecture, bone mineral density, and vertebral fractures in male osteoporosis SO JOURNAL OF BONE AND MINERAL RESEARCH DE osteoporosis; men; bone histomorphometry; bone microarchitecture; bone mineral density; vertebral fractures ID SPINAL OSTEOPOROSIS; PATTERN FACTOR; ILIAC CREST; MEN; WOMEN; HISTOMORPHOMETRY; ARCHITECTURE; MECHANISMS; PREDICTION; PREVALENCE AB Some studies have indicated that the risk of fragility fractures in men increases as bone mineral levels decrease, but there is an overlap in the bone mineral density (BMD) measurements between patients with or without fractures. Furthermore, it has been suggested that the biomechanical competence of trabecular bone is dependent not only on the absolute amount of bone present but also on the trabecular microarchitecture. In the present study, 108 men (mean age 52.1 years) with lumbar osteopenia (T score < -2.5) were recruited to examine the relationships between BMD, architectural changes in trabecular bone, and the presence of vertebral fractures. Lumbar BMD was assessed from L2 to L4 in the anteroposterior view with dual-energy X-ray absorptiometry. At the upper left femur, hip BMD was measured at the transcervical site. Spinal X-ray films were analyzed independently by two trained investigators, and vertebral fracture was defined as a reduction of at least 20% in the anterior, middle, or posterior vertebral height. Transiliac bone biopsy specimens were obtained for all patients. Histomorphometric studies were performed on an image analyzer, and the following parameters were determined: trabecular bone volume (BV/TV), trabecular thickness (Tb.Th), number (Tb.N), and separation (Tb.Sp), interconnectivity index (ICI), characterization of the trabecular network (node count and strut analysis), and star volume of the marrow spaces. Spinal radiographs evidenced at least one vertebral crush fracture in 62 patients (group LI) and none in 46 patients (group I). After adjusting for age, body mass index, and BMD, there were no significant differences between the two groups in BV/TV, Tb.Th, or star volume. In contrast, the mean values of ICI, free end-to-free end struts (FF/TSL), and Tb.Sp were significantly higher, whereas Tb.N and node-to-node struts (NN/TSL) were lower in patients with at least one vertebral fracture. Logistic regression analysis showed that only ICI, FF/TSL, NN/TSL, and Tb.N were significant predictors of the presence of vertebral fracture: odds ratios for an alteration of 1 SD ranged from 1.7 (1.0-3.2) for NN/TSL to 3.2 (1.1-10.1) for ICI. Patients with at least three vertebral fractures (n = 23) were categorized as "multiple fractures." The results of logistic regression showed that spine BMD, BV/TV, and all architectural parameters were significant predictors of multiple vertebral fractures: odds ratios for an alteration of I SD ranged from 2.2 (1.1-4.6) for star volume to 3.7 (1.4-9.7) for ICI. These results strongly suggest that bone trabecular microarchitecture is a major and independent determinant of vertebral fractures in middle-aged men with osteopenia. C1 Univ Angers, Ctr Hosp, Lab Histol Embryol, Fac Med, Angers, France. Univ Angers, Ctr Hosp, Serv Med Interne & Endocrinol, Angers, France. Univ Angers, Ctr Hosp, Serv Rhumatol, Angers, France. RP Legrand, E, CHU Angers, Serv Rhumatol, F-49033 Angers, France. TC 89 PD JAN PY 2000 VL 15 IS 1 BP 13 EP 19 UT ISI:000084420800004 ER PT J AU Graham, MA Lockwood, GF Greenslade, D Brienza, S Bayssas, M Gamelin, E TI Clinical pharmacokinetics of oxaliplatin: A critical review SO CLINICAL CANCER RESEARCH ID METASTATIC COLORECTAL-CANCER; CARCINOMA CELL-LINES; FOLINIC ACID; PLATINUM COMPLEXES; PHASE-I; CISPLATIN; TRIAL; 5-FLUOROURACIL; CYTOTOXICITY; RESISTANT AB Oxaliplatin (cis-[(1R,2R)-1,2-cyclohexanediamine-N,N'] oxalato(2-)-O,O'] platinum; Eloxatine) is a novel platinum coordination complex used for the treatment of metastatic colorectal carcinoma in combination with fluoropyrimidines. The objective of this review is to integrate the key data from multiple studies into a single, comprehensive overview of oxaliplatin disposition in cancer patients. The pharmacokinetics (PKs) of unbound platinum in plasma ultrafiltrate after oxaliplatin administration was triphasic, characterized by a short initial distribution phase and a long terminal elimination phase (t(1/2) 252-273 h). No accumulation was observed in plasma ultrafiltrate after 130 mg/m(2) every 3 weeks or 85 mg/m(2) every 2 weeks. Interpatient and intrapatient variability in platinum exposure (area under the curve(0-48)) is moderate to low (33 and 5% respectively). In the blood, platinum binds irreversibly to plasma proteins (predominantly serum albumin) and erythrocytes. Accumulation of platinum in blood cells is not considered to be clinically significant. Platinum is rapidly cleared from plasma by covalent binding to tissues and renal elimination. Urinary excretion (53.8 +/- 9.1%) was the predominant route of platinum elimination, with fecal excretion accounting for only 2.1 +/- 1.9% of the administered dose 5 days postadministration. Tissue binding and renal elimination contribute equally to the clearance of ultrafilterable platinum from plasma. Renal clearance of platinum significantly correlated with glomerular filtration rate, indicating that glomerular filtration is the principal mechanism of platinum elimination by the kidneys. Clearance of ultrafilterable platinum is lower in patients with moderate renal impairment; however, no marked increase in drug toxicity was reported. The effect of severe renal impairment on platinum clearance and toxicity is currently unknown. Covariates such as age, sex, and hepatic impairment had no significant effect on the clearance of ultrafilterable platinum, and dose adjustment due to these variables is not required. Oxaliplatin undergoes rapid and extensive nonenzymatic biotransformation and is not subjected to CYP450-mediated metabolism. Up to 17 platinum-containing products have been observed in plasma ultrafiltrate samples from patients, These include several proximate cytotoxic species, including the monochloro-, dichloro-, and diaquo-diaminocyclohexane platinum complexes, along with several other noncytotoxic products. Oxaliplatin does not inhibit CYP450 isoenzymes in vitro, Platinum was not displaced from plasma proteins by a variety of concomitant medications tested in vitro, and no marked PK interactions between oxaliplatin, 5-fluorouracil, and irinothecan have been observed. These results indicate that the additive/synergistic antitumor activity observed with these agents is not due to major alterations in drug exposure, and the enhanced efficacy is likely to be mechanistically based. Together, these PK, biotransformation, drug-drug interaction analyses and studies in special patient populations provide a firm scientific basis for the safe and effective use of oxaliplatin in the clinic. These analyses also reveal that the pharmacological activity of oxaliplatin may be attributable, at least in part, to the unique pattern of platinum disposition observed in patients. C1 Sanofi Synthelabo, Dept Clin Pharmcokinet & Drug Metab, Malvern, PA 19355 USA. Ctr Paul Papin, F-49033 Angers, France. Debiopharm SA, CH-1003 Lausanne, Switzerland. RP Graham, MA, Sanofi Synthelabo, Dept Clin Pharmcokinet & Drug Metab, 9 Great Valley Pkwy, Malvern, PA 19355 USA. TC 82 PD APR PY 2000 VL 6 IS 4 BP 1205 EP 1218 UT ISI:000086633500002 ER PT J AU Abenhaim, L Rossignol, M Valat, JP Nordin, M Avouac, B Blotman, F Charlot, J Dreiser, RL Legrand, E Rozenberg, S Vautravers, P CA Paris Task Force TI The role of activity in the therapeutic management of back pain - Report of the International Paris Task Force on Back Pain SO SPINE ID RANDOMIZED CLINICAL-TRIAL; PHYSICAL-ACTIVITY; RISK-FACTORS; PRIMARY-CARE; FOLLOW-UP; BEHAVIORAL-THERAPY; EXERCISE PROGRAM; NATURAL-HISTORY; HEALTHY-ADULTS; SICK LEAVE C1 Montreal Dept Publ Hlth, Montreal, PQ, Canada. McGill Univ, Ctr Clin Epidemiol & Community Studies, Montreal, PQ, Canada. Univ Tours, Hop Trousseau, Tours, France. NYU, Hosp Joint Dis, Inst Orthopaed, Occupat & Ind Orthopaed Ctr, New York, NY USA. Hop Henri Mondor, F-94010 Creteil, France. CHU Montpellier, Hop Lapeyronie, Montpellier, France. Ctr Hosp Emile Roux, Limeil Brevannes, France. CHU Bichat, Paris, France. Hop Hotel Dieu, Angers, France. Hop La Pitie Salpetriere, Paris, France. Hop Hautepierre, Strasbourg, France. RP Rossignol, M, Montreal Dept Publ Hlth, 1301 Sherbrooke St E, Montreal, PQ, Canada. TC 65 PD FEB 15 PY 2000 VL 25 IS 4 SU Suppl. S BP 1S EP 33S UT ISI:000085530600001 ER PT J AU Chaillous, L Lefevre, H Thivolet, C Boitard, C Lahlou, N Atlan-Gepner, C Bouhanick, B Mogenet, A Nicolino, M Carel, JC Lecomte, P Marechaud, R Bougneres, P Charbonnel, B Sai, P CA Diabete Insuline Orale grp TI Oral insulin administration and residual beta-cell function in recent-onset type 1 diabetes: a multicentre randomised controlled trial SO LANCET ID NOD MICE; T-CELLS; AUTOIMMUNE-DISEASES; ADOPTIVE TRANSFER; TRANSFER MODEL; B-CHAIN; SUPPRESSION; PREVENTION; TOLERANCE; MOUSE AB Background Oral administration of autoantigens can slow the progression of beta-cell destruction in non-obese diabetic mice. We investigated whether oral administration of recombinant human insulin could protect residual beta-cell function in recent-onset type 1 diabetes. Methods We enrolled 131 autoantibody-positive diabetic patients aged 7-40 years within 2 weeks of diagnosis (no ketoacidosis at diagnosis, weight loss <10%, polyuria for <6 weeks). They were randomly assigned 2.5 mg or 7.5 mg oral insulin daily or placebo for 1 year, in addition to subcutaneous insulin therapy, Serum C-peptide concentrations were measured in the fasting state and after stimulation, to assess beta-cell function. Autoantibodies to beta-cell antigens were assayed. Analyses were by intention to treat. Findings Baseline C-peptide and haemoglobin A(1c) concentrations were similar in the three groups. During follow up, there were no differences between the groups assigned 2.5 mg or 7.5 mg oral insulin or placebo in subcutaneous insulin requirements, haemoglobin A(1c) concentrations, or measurements of fasting (mean at 12 months 0.18 [SD 0.17], 0.17 [0.17], and 0.17 [0.12] nmol/L) or stimulated C-peptide concentrations (glucagon-stimulated 0.39 [0.38], 0.37 [0.39], and 0.33 [0.24] nmol/L; meal-stimulated 0.72 [0.60], 0.49 [0.49], and 0.57 [0.51 nmol/L]. Neither age nor C-peptide concentration at entry influenced treatment effects. No differences were seen in the time-course or titres of antibodies to insulin, glutamic acid decarboxylase, or islet antigen 2, Interpretation At the doses used in this trial, oral administration of insulin initiated at clinical onset of type 1 diabetes did not prevent the deterioration of beta-cell function. C1 CHU Nantes, F-44035 Nantes 01, France. CHU St Vincent de Paul, Paris, France. CHU Lyon, Lyon, France. CHU Necker, Paris, France. CHU Marseille, Marseille, France. CHU Angers, Angers, France. CHU Tours, Tours, France. CHU Poitiers, Poitiers, France. RP Chaillous, L, Hotel Dieu, Pl Alexis Ricordeau, F-44093 Nantes 01, France. TC 64 PD AUG 12 PY 2000 VL 356 IS 9229 BP 545 EP 549 UT ISI:000088820800011 ER PT J AU Bataille, B Delwail, V Menet, E Vandermarcq, P Ingrand, P Wager, M Guy, G Lapierre, F TI Primary intracerebral malignant lymphoma: report of 248 cases SO JOURNAL OF NEUROSURGERY DE primary central nervous system lymphoma; brain neoplasm; non-Hodgkin's lymphoma ID CENTRAL-NERVOUS-SYSTEM; NON-HODGKINS-LYMPHOMA; RETICULUM-CELL SARCOMA; HIGH-DOSE METHOTREXATE; PRIMARY CNS LYMPHOMA; RADIATION-THERAPY; INCREASING INCIDENCE; PROGNOSTIC FACTORS; CEREBRAL LYMPHOMA; BRAIN AB Object. The authors present a retrospective analysis of 248 immunocompetent patients with primary intracerebral lymphoma treated at 19 French and Belgian medical centers between January 1980 and December 1995. Methods. This study involved 127 female and 121 male patients with a median age of 61 years (range 2-88 years). All tumors available for review were classic diffuse non-Hodgkin's lymphoma, for which the phenotype was determined in 220 patients: 212 (96.4%) were B-cell and eight (3.6%) were T-cell type tumors. According to the Revised European-American classification of lymphoid neoplasms, most lesions were diffuse large cell rumors (62%). A total of 196 turners were reviewed in 127 patients for whom preoperative computerized tomography and magnetic resonance studies were available. There was a single lesion in 66% of the cases, with a supratentorial location in 87%. Tumor location in the basal ganglia, corpus callosum, or fornix, infiltration of the periventricular ependyma, or a mirror pattern, were strongly suggestive of a lesion of lymphomatous origin. The histological diagnosis was obtained after surgical resection in 116 patients, with the remainder undergoing biopsy sampling only. Of the 248 patients studied, 129 (52%) received chemotherapy plus radiation therapy, 60 (24%) received radiation therapy alone, 35 (14%) received chemotherapy alone? and 24 (10%) received no postsurgical treatment. Conclusions. Using univariate analysis, the authors determined prognostic factors that were significantly associated with a favorable impact on survival including age younger than 60 years, radiation therapy (without evidence of a dose-response relationship), radiation therapy combined with chemotherapy, and chemotherapy consisting of anthracycline. Partial surgical resection was all unfavorable prognostic factor. Multivariate analysis was used to confirm the independent prognostic value of radiation therapy, age, chemotherapy consisting of anthracyclines or methotrexate, and partial surgical resection. This European survey provides a reasonable basis for the treatment of primary intracerebral lymphoma with the following sequence: stereotactic biopsy sampling, chemotherapy with a methotrexate- and anthracycline-based regimen; followed by cranial irradiation. C1 Univ Poitiers, Sch Med, Dept Neurol Surg Radiat Oncol Radiol & Pathol, Poitiers, France. Univ Angers, Sch Med, Dept Neurol Surg, Angers, France. RP Bataille, B, Cite Hosp La Miletrie, Serv Neurochirurg, 350 Ave Jacques Coeur,BP 577, F-86021 Poitiers, France. TC 64 PD FEB PY 2000 VL 92 IS 2 BP 261 EP 266 UT ISI:000085032900005 ER PT J AU Claustres, M Guittard, C Bozon, D Chevalier, F Verlingue, C Ferec, C Girodon, E Cazeneuve, C Bienvenu, T Lalau, G Dumur, V Feldmann, D Bieth, E Blayau, M Clavel, C Creveaux, I Malinge, MC Monnier, N Malzac, P Mittre, H Chomel, JC Bonnefont, JP Iron, A Chery, M Des Georges, M TI Spectrum of CFTR mutations in cystic fibrosis and in congenital absence of the vas deferens in France SO HUMAN MUTATION DE congenital absence of the vas deferens; CBAVD; cystic fibrosis; CF; CFTR; ABCC7; France ID CHLORIDE CHANNEL ACTIVITY; COMPLETE CODING REGION; BILATERAL ABSENCE; PARTIAL PENETRANCE; MOLECULAR-BASIS; GENE-MUTATIONS; GEOGRAPHIC-DISTRIBUTION; CYTOPLASMIC LOOP; MESSENGER-RNA; DISEASE AB We have collated the results of cystic fibrosis (CF) mutation analysis conducted in 19 laboratories in France. We have analyzed 7,420 CF alleles, demonstrating a total of 310 different mutations including 24 not reported previously, accounting for 93.56% of CF genes, The most common were F508del (67.18%; range 61-80), G542X (2.86%; range 1-6.7%), N1303K (2.10%; range 0.75-4.6%), and 1717-1G>A (1.31%; range 0-2.8%). Only 11 mutations had relative frequencies > 0.4%, 140 mutations were found on a small number of CF alleles (from 29 to two), and 154 were unique. These data show a clear geographical and/or ethnic variation in the distribution of the most common CF mutations. This spectrum of CF mutations, the largest ever reported in one country, has generated 481 different genotypes, We also investigated a cohort of 800 French men with congenital bilateral absence of the vas deferens (CBAVD) and identified a total of 137 different CFTR mutations. Screening for the most common CF defects in addition to assessment for IVS8-5T allowed us to detect two mutations in 47.63% and one in 24.63% of CBAVD patients, In a subset of 327 CBAVD men who were more extensively investigated through the scanning of coding/flanking sequences, 516 of 654 (78.90%) alleles were identified, with 15.90% and 70.95% of patients carrying one or two mutations, respectively, and only 13.15% without any detectable CFTR abnormality. The distribution of genotypes, classified according to the expected effect of their mutations on CFTR protein, clearly differed between both populations. CF patients had two severe mutations (87.77%) or one severe and one mild/variable mutation (11.33%), whereas CBAVD men had either a severe and a mild/variable (87.89%) or two mild/variable (11.57%) mutations. Hum Mutat 16:143-156, 2000. (C) 2000 Wiley-Liss, Inc. C1 CHU Montpellier, Mol Genet Lab, CNRS, UPR 1142,Inst Biol, F-34060 Montpellier, France. Hop Debrousse, Lab Biochim Pediat, Lyon, France. Ctr Biogenet, Brest, France. Hop Henri Mondor, Biochim Lab, F-94010 Creteil, France. Grp Hosp Cochin, Lab Biochim & Genet Mol, Paris, France. Hop Calmette, Lab Biochim & Biol Mol, Lille, France. Hop Trousseau, Lab Biochim & Biol Mol, F-75571 Paris, France. Hop Purpan, Med Genet Lab, Toulouse, France. CHU Pontchaillou, Genet Mol Lab, Rennes, France. CHR Maison Blanche, INSERM, U314, Reims, France. Fac Med, Lab Biochim Biol Mol & Enzymol, Clermont Ferrand, France. CHU Angers, Serv Genet, Angers, France. Hop Tronche, Grenoble, France. Hop Timone, Ctr Diagnost Prenatal, Marseille, France. CHU Georges Clemenceau, Lab Biochim B, Caen, France. CHU Poitiers, Lab Genet Cellulaire & Mol, Poitiers, France. Hop Necker Enfants Malad, Paris, France. Grp Hosp Pellegrin, Bordeaux, France. CHU Brabois, Genet Lab, Vandoeuvre Nancy, France. RP Claustres, M, CHU Montpellier, Mol Genet Lab, CNRS, UPR 1142,Inst Biol, Blvd Henry IV, F-34060 Montpellier, France. TC 61 PY 2000 VL 16 IS 2 BP 143 EP 156 UT ISI:000088473500006 ER PT J AU Vilmer, E Suciu, S Ferster, A Bertrand, Y Cave, H Thyss, A Benoit, Y Dastugue, N Fournier, M Souillet, G Manel, AM Robert, A Nelken, B Millot, F Lutz, P Rialland, X Mechinaud, F Boutard, P Behar, C Chantraine, JM Plouvier, E Laureys, G Brock, P Uyttebroeck, A Margueritte, G Plantaz, D Norton, L Francotte, N Gyselinck, J Waterkeyn, C Solbu, G Philippe, N Otten, J TI Long-term results of three randomized trials (58831,58832,58881) in childhood acute lymphoblastic leukemia: a CLCG-EORTC report SO LEUKEMIA DE long-term follow-up; acute lymphoblastic leukemia; childhood; EORTC ID CHILDREN; METHOTREXATE; CHEMOTHERAPY AB We present here the long-term results of three randomized clinical trials conducted on children with newly diagnosed acute lymphoblastic leukemia (ALL) between 1983 and 1998 by the Children Leukemia Cooperative Group (CLCG) from EORTC. In study 58831/32, the overall event-free survival (EFS) rates (+/- s.e.) at 6 and 10 years were 66% +/-1.8% and 65% +/-1.8%, respectively, and the risk of isolated central nervous system (CNS) relapse was 6%+/-1% and 7%+/-1%, respectively. In patients with a standard risk of relapse the omission of cyclophosphamide had no adverse effect on disease-free survival rates at 10 years (trial 58831). In medium- and high-risk patients the omission of radiotherapy did not increase the risk of CNS or systemic relapse (trial 58832). In study 58881 (1989-1998) the overall EFS rate at 8 years was 68.4% +/- 1.2% and the risk of isolated CNS relapse was 4.2% +/- 0.5%. In this trial which adressed three randomized questions, the following results were obtained: the combination of cytarabine at high doses with methotrexate at high doses during interval therapy did not improve prognosis. The addition of g-mercaptopurine iv during maintenance increased the risk of late relapse. E. coli asparaginase was more toxic and has a higher efficacy than Erwinia asparaginase. Leukocyte counts >100 x 10(9)/1, specific genetic abnormalities, a poor initial response to steroids or a high level of minimal residual disease at early time points were consistently associated with an adverse prognosis in the 58881 trial. C1 Hop Robert Debre, Dept Hematoimmunol, F-75019 Paris, France. Eortc Data Ctr, Brussels, Belgium. HUDE, Dept Hematooncol, Brussels, Belgium. Debrousse Hosp, Dept Immunohematopediatry, Lyon, France. Hop Robert Debre, Lab Genet Biochem, F-75019 Paris, France. Ctr Antoine Lacassagne, Dept Hematooncol, F-06054 Nice, France. Univ Ziekenhuis, Dept Pediat Hematooncol, Ghent, Belgium. CHU Purpan, Hematol Lab, Toulouse, France. CHR, Hematol Lab, Lille, France. Debrousse Hosp, Hematol Lab, Lyon, France. Childrens Hosp, Dept Hematol, Toulouse, France. CHR, Dept Hematol, Lille, France. J Bernard Hosp, Dept Hematol, Poitiers, France. Hautepierre, Dept Hematol, Strasbourg, France. CHU Angers, Dept Hematol, Angers, France. CHR Hotel Dieu, Dept Hematol, Nantes, France. CHRU, Dept Hematol, Caen, France. Amer Hosp, Dept Hematol, Reims, France. CHR La Citadelle, Dept Pediatry, Liege, Belgium. Hop St Jacques, Dept Hematol, F-25030 Besancon, France. UZ Gasthuisberg, Dept Pediat, Louvain, Belgium. A Villeneuve Hosp, Dept Oncohematol, Montpellier, France. CHR La Tronche, Dept Pediat, Grenoble, France. Escolar San Joao Hosp, Dept Pediat, Porto, Portugal. Esperance Clin, Dept Pediat, Montegnee, Belgium. AZ Middelheim, Dept Pediat, Antwerp, Belgium. AZ VUB, Dept Pediat, Brussels, Belgium. RP Vilmer, E, Hop Robert Debre, Dept Hematoimmunol, 48 Bd Serrurier, F-75019 Paris, France. TC 58 PD DEC PY 2000 VL 14 IS 12 BP 2257 EP 2266 UT ISI:000166207000031 ER PT J AU Bibby, DC Davies, NM Tucker, IG TI Mechanisms by which cyclodextrins modify drug release from polymeric drug delivery systems SO INTERNATIONAL JOURNAL OF PHARMACEUTICS DE cyclodextrin; microspheres; polymer; modified release; mechanism ID IN-VITRO EVALUATION; ZERO-ORDER RELEASE; BETA-CYCLODEXTRIN; PHARMACEUTICAL APPLICATIONS; INCLUSION COMPLEXES; POLY(ACRYLIC ACID); SUSTAINED-RELEASE; ALPHA-CYCLODEXTRIN; SOLUTE SOLUBILITY; MICROSPHERES AB For many drug candidates a modified in vivo drug release is desired to improve efficacy, sustain effect or minimise toxicity. Polymeric delivery systems, such as microspheres, nanospheres and polymeric films, have been extensively researched in an attempt to achieve modified drug release. Cyclodextrins offer an alternative approach. These cyclic oligosaccharides have the ability to form non-covalent complexes With a number of drugs and in so doing alter their physicochemical properties. In addition, the primary and secondary hydroxyl groups of the native (alpha, beta, gamma-) cyclodextrins are potential sites for chemical modification. It follows that the incorporation of these agents into polymeric drug delivery systems, as physical mixtures, covalently bound conjugates or cross-linking agents, frequently permits a greater degree of control of drug release. This paper reviews the incorporation of Various cyclodextrins into polymeric formulations. The mechanisms by which cyclodextrin/polymer formulations act to modify drug release are considered. (C) 2000 Published by Elsevier Science B.V. All rights reserved. C1 Univ Otago, Sch Pharm, Formulat & Drug Delivery Grp, Dunedin, New Zealand. RP Bibby, DC, Univ Angers, Fac Pharm, UPRES EA 2169, 16 Bd Daviers, F-49100 Angers, France. TC 54 PD MAR 20 PY 2000 VL 197 IS 1-2 BP 1 EP 11 UT ISI:000085847300001 ER PT J AU Delabaere, E Trinh, DT TI Spectral analysis of the complex cubic oscillator SO JOURNAL OF PHYSICS A-MATHEMATICAL AND GENERAL ID PERTURBATION-THEORY; REAL SPECTRUM; PT-SYMMETRY; HAMILTONIANS; EIGENVALUES; RESURGENCE AB Using the 'exact semiclassical analysis', we study the spectrum of a one-parameter family of complex cubic oscillators. The PT-invariance property of the complex Hamiltonians and the reality property of the spectrum are discussed. Analytic continuations of the spectrum in the complex parameter and their connections with the resonance problem for the real cubic oscillator are investigated. The global analytic structure of the spectrum yields a branch point structure similar to the multivalued analytic structure discovered by Bender and Wu for the quartic oscillator. C1 Univ Angers, Dept Math, CNRS, UMR 6093, F-49045 Angers 01, France. Coll Dalat, Dept Math, Dalat, Vietnam. RP Delabaere, E, Univ Angers, Dept Math, CNRS, UMR 6093, 2 Blvd Lavoisier, F-49045 Angers 01, France. TC 51 PD DEC 8 PY 2000 VL 33 IS 48 BP 8771 EP 8796 UT ISI:000165998400019 ER PT J AU Roche, PH Regis, J Dufour, H Fournier, HD Delsanti, C Pellet, W Grisoli, F Peragut, JC TI Gamma knife radiosurgery in the management of cavernous sinus meningiomas SO JOURNAL OF NEUROSURGERY DE cavernous sinus; cranial nerve; meningioma; gamma knife; radiosurgery; skull base ID CRANIAL BASE MENINGIOMAS; STEREOTAXIC RADIOSURGERY; SKULL BASE; RECURRENCE; NERVES AB Object. The authors sought to assess the functional tolerance and tumor control rate of cavernous sinus meningiomas treated by gamma knife radiosurgery (GKS). Methods. Between July 1992 and October 1998, 92 patients harboring benign cavernous sinus meningiomas underwent GKS. The present study is concerned with the first 80 consecutive patients (63 women and 17 men). Gamma knife radiosurgery was performed as an alternative to surgical removal in 50 cases and as an adjuvant to microsurgery in 30 cases. The mean patient age was 49 years (range 6-71 years). The mean tumor volume was 5.8 cm(3) (range 0.9-18.6 cm(3)). On magnetic resonance (MR) imaging the tumor was confined in 66 cases and extensive in 14 cases. The mean prescription dose was 28 Gy (range 12-50 Gy), delivered with an average of eight isocenters (range two-18). The median peripheral isodose was 50% (range 30-70%). Patients were evaluated at 6 months, and at 1, 2, 3, 5, and 7 years after GKS. The median follow-up period was 30.5 months (range 12-79 months). Tumor stabilization after GKS was noted in 51 patients, tumor shrinkage in 25 patients, and enlargement in four patients requiring surgical removal in two cases. The 5-year actuarial progression-free survival was 92.8%. No new oculomotor deficit was observed. Among the 54 patients with oculomotor nerve deficits, 15 improved, eight recovered, and one worsened. Among the 13 patients with trigeminal neuralgia, one worsened (contemporary of tumor growing), five remained unchanged, four improved, and three recovered. In a patient with a remnant surrounding the optic nerve and preoperative low vision (3/10) the decision was to treat the lesion and deliberately sacrifice the residual visual acuity. Only one transient unexpected optic neuropathy has been observed. One case of delayed intracavernous carotid artery occlusion occurred 3 months after GKS, without permanent deficit. Another patient presented with partial complex seizures 18; months after GKS. All cases of tumor growth and neurological deficits observed after GKS occurred before the use of GammaPlan. Since the initiation of systematic use of stereotactic MR imaging and computer-assisted modern dose planning, no more side effects or cases of tumor growth have occurred. Conclusions. Gamma knife radiosurgery was found to be an effective low morbidity-related tool for the treatment of cavernous sinus meningioma. In a significant number of patients, oculomotor functional restoration was observed. The treatment appears to be an alternative to surgical removal of confined enclosed cavernous sinus meningioma and should be proposed as an adjuvant to surgery in case of extensive meningiomas. C1 CHU Timone, Serv Neurochirurg Fonctionnelle & Stereotax, F-13385 Marseille 05, France. CH St Marguerite, Serv Neurochirurg, Marseille, France. CH Timone, Serv Neurochirurg, Marseille, France. CH Larrey, Serv Neurochirurg, Angers, France. RP Roche, PH, CHU Timone, Serv Neurochirurg Fonctionnelle & Stereotax, 264 Blvd St Pierre, F-13385 Marseille 05, France. TC 51 PD DEC PY 2000 VL 93 SU Suppl. 3 BP 68 EP 73 UT ISI:000165730500015 ER PT J AU Michallet, M Tanguy, ML Socie, G Thiebaut, A Belhabri, A Milpied, N Reiffers, J Kuentz, M Cahn, JY Blaise, D Demeocq, F Jouet, JP Michallet, AS Ifrah, N Vilmer, E Molina, L Michel, G Lioure, B Cavazzana-Calvo, M Pico, JL Sadoun, A Guyotat, D Attal, M Cure, H Bordigoni, P Sutton, L Buzyn-Veil, A Tilly, M Leporrier, M Fegueux, N Dreyfus, F Rio, B Lutz, P Vernant, JP TI Second allogeneic haematopoietic stem cell transplantation in relapsed acute and chronic leukaemias for patients who underwent a first allogeneic bone marrow transplantation: a survey of the Societe Francaise de Greffe de Moelle (SFGM) SO BRITISH JOURNAL OF HAEMATOLOGY DE second allogeneic haematopoietic stem cell; transplantation; acute leukaemia; chronic leukaemia ID CHRONIC MYELOGENOUS LEUKEMIA; GRAFT-VERSUS-LEUKEMIA; PERIPHERAL-BLOOD LYMPHOCYTES; CHRONIC MYELOID-LEUKEMIA; 2ND TRANSPLANTS; THERAPY; IMMUNOTHERAPY; RECURRENCE; REMISSION AB Although recurrent malignancy is the most frequent indication for second stem cell transplantation (2nd SCT), there are few reports that include sufficiently large numbers of patients to enable prognostic factor analysis. This retrospective study includes 150 patients who underwent a 2nd SCT for relapsed acute myeloblastic leukaemia (n = 61), acute lymphoblastic leukaemia (n = 47) or chronic myeloid leukaemia (n = 42) after a first allogeneic transplant (including 26 T-cell-depleted). The median interval between the first transplant and relapse, and between relapse and second transplant was 17 months and 5 months respectively. After the 2nd SCT, engraftment-occurred in 93% of cases, 32% of patients developed acute graft-vs.-host disease (GVHD) greater than or equal to grade II and 38% chronic GVHD. The 5-year overall and disease-free survival were 32 +/- 8% and 30 +/- 8%, respectively with a risk of relapse of 44 +/- 12% and a transplant-related mortality of 45 +/- 9%. In a multivariate analysis, ave factors were associated with a better outcome after 2nd SCT: age <16 years at second transplant; relapse occurring more than 12 months after the first transplant: transplantation from a female donor: absence of acute GVHD; and the occurrence of chronic GVHD. The best candidates for a second transplant are likely to be patients with acute leukaemia, in remission before transplant, in whom the HLA-identical donor was female and who relapsed more than 1 year after the first transplant. C1 Hop Edouard Herriot, Unite Greffe Cellules Souches Hematopoiet, Hematol Serv, F-69437 Lyon, France. Soc Greffe de Moelle, Unite Stat, Paris, France. Hop St Louis, Hematol Serv, Paris, France. Ctr Hosp Hotel Dieu, Hematol Serv, Nantes, France. Ctr Hosp Haut Leveque, Hematol Serv, Pessac, France. Hop Henri Mondor, Hematol Serv, F-94010 Creteil, France. Hop Jean Minjoz, Serv Hematol Adulte, F-25030 Besancon, France. Inst J Paoli I Calmettes, Unite Transplantat Medullaire, F-13009 Marseille, France. CHU Hotel Dieu, Serv Hematol Pediat, Clermont Ferrand, France. CHU Huriez, Hematol Serv, Lille, France. CHU Angers, Hematol Serv, Angers, France. Hop Robert Debre, Unite Hematol Immunol, F-75019 Paris, France. CHU Albert Michallon, Hematol Serv, Grenoble, France. Hop Enfants La Timone, Hematol Serv, Marseille, France. Hop Hautepierre, Serv Oncohematol, Strasbourg, France. Hop Necker Enfants Malad, Hematol Serv, Paris, France. Inst Gustave Roussy, Serv Hematol Adulte, Villejuif, France. Hop Jean Bernard, Hematol Serv, Poitiers, France. Hop Nord, Hematol Serv, St Etienne, France. CHU Purpan, Hematol Serv, Toulouse, France. Ctr Jean Perrin, Serv Oncohematol, Clermont Ferrand, France. Hop Brabois, Unite Transplantat Medullaire, Nancy, France. Hop La Pitie Salpetriere, Hematol Serv, Paris, France. Hop Necker Adultes, Hematol Serv, Paris, France. Ctr Henri Becquerel, Hematol Serv, F-76038 Rouen, France. CHU Caen, Hematol Serv, F-14000 Caen, France. CHU Montpellier, Hematol Serv, Montpellier, France. Hop Cochin, Serv Hematol, F-75674 Paris, France. Hop Hotel Dieu, Serv Hematol, F-75181 Paris, France. RP Michallet, M, Hop Edouard Herriot, Unite Greffe Cellules Souches Hematopoiet, Hematol Serv, F-69437 Lyon, France. TC 45 PD FEB PY 2000 VL 108 IS 2 BP 400 EP 407 UT ISI:000085970600030 ER PT J AU Benoit, JP Faisant, N Venier-Julienne, MC Menei, P TI Development of microspheres for neurological disorders: From basics to clinical applications SO JOURNAL OF CONTROLLED RELEASE DE anticancer drugs; biodegradable polymer; chemotherapy; drug delivery; microspheres; neuro-oncology; neurotrophic factors; transmitters ID NERVE GROWTH-FACTOR; BLOOD-BRAIN-BARRIER; MICROENCAPSULATED MONOSIALOGANGLIOSIDE GM1; BIODEGRADABLE POLYMER MICROSPHERES; CONTROLLED-RELEASE POLYMER; SOLVENT EVAPORATION METHOD; BCNU-LOADED MICROSPHERES; DRUG-CARRIER MATRICES; BIOERODIBLE POLYANHYDRIDES; POLY(D,L-LACTIDE-CO-GLYCOLIDE) MICROSPHERES AB Drug delivery to the central nervous system remains a challenging area of investigation for both basic and clinical neuroscientists. Numerous drugs are generally excluded from blood to blain transfer due to the negligible permeability of the brain capillary endothelial wall, which makes up the blood brain barrier in vivo. For several years, we have explored the potential applications of the microencapsulation of therapeutic agents to provide local controlled drug release in the central nervous system. Due to their size, these microparticles can be easily implanted by stereotaxy in discreet, precise and functional areas of the brain without damaging the surrounding tissue. This type of implantation avoids the inconvenient insertion of large implants by open surgery and can be repeated if necessary. We have established the compatibility of poly(lactide-co-glycolide) microspheres with brain tissues. Presently, the most developed applications concern Neurology and Neuro-oncology, with local delivery of neurotrophic factors and antimitotic drugs into neurodegenerative lesions and brain tumours, respectively. The drugs that had been encapsulated by our group included nerve growth factor (NGF), 5-fluorouracil (5-FU), idoxuridine and BCNU. Preclinical studies have been performed with each drug. Studies with NGF are reported as an example. A phase I/II clinical trial has been carried out in patients with newly diagnosed glioblastomas to assess the potentialities of 5-FU-loaded microspheres when intracranially implanted. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ Angers, Fac Pharm, UPREA EA 2169, Angers, France. Univ Angers, Ctr Hosp, Serv Neurochirurg, Angers, France. RP Benoit, JP, Univ Angers, Fac Pharm, UPREA EA 2169, Angers, France. TC 44 PD MAR 1 PY 2000 VL 65 IS 1-2 BP 285 EP 296 UT ISI:000085933700026 ER PT J AU Escorsell, A Del Arbol, LR Planas, R Albillos, A Banares, R Cales, P Pateron, D Bernard, B Vinel, JP Bosch, J CA TEST Study Members TI Multicenter randomized controlled trial of terlipressin versus sclerotherapy in the treatment of acute variceal bleeding: The TEST study SO HEPATOLOGY ID PLACEBO-CONTROLLED TRIAL; ESOPHAGEAL-VARICES; DOUBLE-BLIND; PORTAL-HYPERTENSION; SOMATOSTATIN; CIRRHOSIS; HEMORRHAGE; LIGATION; NITROGLYCERIN; EFFICACY AB Failure to control bleeding and early rebleeding account for the high mortality associated with variceal hemorrhage in cirrhosis. We compared endoscopic sclerotherapy to terlipressin, a drug that effectively controls acute bleeding while reducing in-hospital mortality. This multicenter randomized controlled trial included 219 cirrhotic patients admitted for endoscopy-proven acute variceal bleeding and randomized to receive repeated injections of terlipressin during 6 days (n = 105) or emergency sclerotherapy (n = 114). Success was defined as obtaining control of bleeding (24-hour bleeding-free period during the first 48 hours) and lack of early rebleeding (any further bleeding from initial control to 5 days later) and survival during the study. Both groups were similar at inclusion. Failure rate for terlipressin was 33% and 32% for sclerotherapy (not significant [NS]). Early rebleeding was responsible for 43% and 44% of failures, respectively. This high efficacy was observed in both Child-Pugh class A + B and Child-Pugh class C patients. Both treatments were similar regarding transfusion requirements, in-hospital stay, and 6-week mortality (26 vs. 19 patients). Side effects appeared in 20% of patients receiving terlipressin and in 30% of those on sclerotherapy (P = .06); being serious in 4% and 7%, respectively (NS). In conclusion, terlipressin and sclerotherapy are equally highly effective therapies achieving the initial control of variceal bleeding and preventing early rebleeding. Both treatments are safe, but terlipressin is better tolerated. Therefore, terlipressin may represent a first-line treatment in acute variceal bleeding until the administration of elective therapy, especially in hospitals where a skilled endoscopist is not available 24 hours a day. C1 Univ Barcelona, Hosp Clin, Dept Med, IDIBAPS,Liver Unit,IMD, E-08036 Barcelona, Spain. Univ Barcelona, Hosp Clin, Dept Med, IDIBAPS,Endoscopy Unit, E-08036 Barcelona, Spain. Univ Alcala de Henares, Hosp Ramon y Cajal, Dept Gastroenterol, Madrid, Spain. Univ Alcala de Henares, Clin Puerta Hierro, Dept Gastroenterol, Madrid, Spain. Hosp Univ Germans Trias & Pujol, Dept Gastroenterol, Badalona, Spain. Univ Complutense Madrid, Hosp Gen Gregorio Maranon, Dept Gastroenterol, Madrid, Spain. CHU Angers, Angers, France. CHU Jean Verdier, Intens Care Unit, Bondy, France. CHU Pitie Salpetriere, Paris, France. CHU Purpan, Toulouse, France. RP Bosch, J, Univ Barcelona, Hosp Clin, Dept Med, IDIBAPS,Liver Unit,IMD, C Villarroel 170, E-08036 Barcelona, Spain. TC 43 PD SEP PY 2000 VL 32 IS 3 BP 471 EP 476 UT ISI:000089091000004 ER PT J AU Coqueret, O Gascan, H TI Functional interaction of STAT3 transcription factor with the cell cycle inhibitor p21(WAF1/CIP1/SD11) SO JOURNAL OF BIOLOGICAL CHEMISTRY ID PROTEIN-TYROSINE-PHOSPHATASE; CILIARY NEUROTROPHIC FACTOR; DEPENDENT KINASES; INDUCED-DIFFERENTIATION; SIGNAL-TRANSDUCTION; CDK INHIBITORS; TGF-BETA; ACTIVATION; P21; CBP AB Signal transducers and activators of transcription (STAT) factors are cytoplasmic proteins that induce gene activation in response to cytokine receptor stimulation, Following tyrosine phosphorylation, STAT proteins dimerize, translocate into the nucleus, and activate specific target genes. Activation is transient, and down-regulation of STAT signaling occurs within a few hours. In the present study, we show that the cyclin-dependent kinase inhibitor p21(WAF1/CIP1/SD11) inhibits STAT3 transcriptional activation. Following leukemia inhibitory factor stimulation, p21(WAF1/CIP1/SD11) was found to associate with STAT3 proteins in coimmunoprecipitation and pull down assays. In vivo, overexpression of p21(WAF1/CIP1/SD11) reduced transcriptional activation by STAT3 proteins but did not modify DNA binding activity. Interestingly, pull down experiments showed that p21(WAF1/CIP1/SD11) could interact with the CREB-binding coactivator protein, and inhibition of STAT3 activity by p21(WAF1/CIP1/SD11) did not occur when CREB-binding protein was overexpressed, These results suggest a model by which p21(WAF1/CIP1/SD11) functions as an inhibitor of STAT3 signaling and highlight a new activity for this cyclin-dependent kinase inhibitor. C1 CHU Angers, INSERM, F-49033 Angers, France. RP Coqueret, O, CHU Angers, INSERM, E-9928,4 Rue Larrey, F-49033 Angers, France. TC 43 PD JUN 23 PY 2000 VL 275 IS 25 BP 18794 EP 18800 UT ISI:000087815900026 ER PT J AU Sainte-Laudy, J Sabbah, A Drouet, M Lauret, MG Loiry, M TI Diagnosis of venom allergy by flow cytometry. Correlation with clinical history, skin tests, specific IgE, histamine and leukotriene C4 release SO CLINICAL AND EXPERIMENTAL ALLERGY DE venom allergy; allergy diagnosis; histamine release; leukotriene release; flow cytometry; CD63 ID HUMAN BASOPHIL ACTIVATION; INTERLEUKIN-3; GENERATION; STINGS; BEE AB Background Potent allergens such as hymenoptera venoms are capable of inducing severe and life threatening clinical reactions. Percentage of false negative results obtained by the usual diagnostical methods is comprised between 10 and 25% Objective Evaluation of the sensitivity and the specificity of cellular tests and particularly evaluation of a new flow cytometric method. Methods Forty-five allergic patients having experienced a local, a systemic reaction or an anaphylactic shock and 10 controls having undergone hymenoptera stings without clinical reactions were selected on the basis of the clinical history, skin tests and specific IgE. Three cellular tests were performed on the same cell suspensions and in the presence of 2 ng/mL of rIL3: histamine release (RIA), leukotriene C4 release (ELISA) and basophil activation test (flow cytometry after double anti-IgE FITC, anti-CD63 PE labelling). Results As compared to the clinical history, sensitivities of skin tests, specific IgE, flow cytometry, histamine release and leukotriene release were, respectively; 85%, 88%, 100%, 89% and 100%. Flow cytometric analysis of basophil activation showed a significant decrease of the mean fluorescence density and number of IgE positive cells and a significant increase of the number of CD63 positive cells. The 10 controls tested by flow cytometry were negative. Conclusion As compared to the clinical history and to the other parameters tested here, flow cytometry showed a high sensitivity and a high specificity. The excellent correlation observed between this method and the other cellular tests such as histamine and leukotriene release are in favour of the specificity of flow cytomery and in favour of the use of this method for venom allergy diagnosis. C1 Lab Pasteur Cerba, Unite Immunoallergol, Cergy Pontoise, France. Hop Angers, Dept Allergol, Angers, France. RP Sainte-Laudy, J, Lab Pasteur Cerba, Unite Immunoallergol, F-95066 Val Doise 09, France. TC 40 PD AUG PY 2000 VL 30 IS 8 BP 1166 EP 1171 UT ISI:000088445600016 ER PT J AU Debillon, T Gras-Leguen, C Verielle, V Winer, N Caillon, J Roze, JC Gressens, P TI Intrauterine infection induces programmed cell death in rabbit periventricular white matter SO PEDIATRIC RESEARCH ID TUMOR-NECROSIS-FACTOR; AMNIOTIC-FLUID INTERLEUKIN-6; CEREBRAL HYPOXIA-ISCHEMIA; FACTOR-ALPHA; RISK-FACTORS; HISTOLOGIC CHORIOAMNIONITIS; INTRAVENTRICULAR HEMORRHAGE; CLINICAL CHORIOAMNIONITIS; AMPICILLIN-SULBACTAM; PRETERM LABOR AB An association between chorioamnionitis and periventricular leukomalacia has been reported in human preterm infants. However, whether this link is causal has not been convincingly established, and the underlying molecular mechanisms remain unclear. The objective of this study was to establish a reproducible model of cerebral white matter disease in preterm rabbits after intrauterine infection. Escherichia coli was inoculated into both uterine horns of laparotomized pregnant rabbits when gestation was 80% complete. The fetuses were delivered by cesarean section and killed 12, 24, or 48 h after the inoculation. Programmed cell death in the white matter was evaluated by hematoxylin-eosin-saffron staining and in situ fragmented DNA labeling (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling). In a first group of 14 pregnant rabbits not treated with antibiotics, all fetuses delivered 48 h after inoculation were stillborn, whereas fetuses extracted 12 or 24 h after inoculation were alive. No significant cell death was detected in the live fetuses compared with the control noninfected rabbits. In a second group of five pregnant rabbits treated with ceftriaxone initiated 24 h after the inoculation and continued until cesarean section was performed 48 h after inoculation, 13 fetuses were alive, but all showed evidence of extensive programmed cell death in the white matter by hematoxylin-eosin-saffron staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. White matter damage became histologically detectable only 48 h after inoculation. Three of the 13 brains displayed periventricular white matter cysts mimicking human cystic periventricular leukomalacia. The high reproducibility of white matter damage in our model should permit further studies aimed at unraveling the molecular mechanisms of periventricular leukomalacia. C1 Hop Mere Enfant, Dept Perinatol, F-44093 Nantes 1, France. Univ Med, Lab Antibiol, F-44093 Nantes, France. Ctr Paul Papin, Lab Anatomopathol, F-49033 Angers 1, France. Hop Robert Debre, Serv Neurol Pediat, F-75019 Paris, France. Hop Robert Debre, INSERM, E9935, F-75019 Paris, France. RP Debillon, T, CHU Nantes, Hop Mere Enfant, Serv Reanimat Neonatale, F-44093 Nantes 1, France. TC 39 PD JUN PY 2000 VL 47 IS 6 BP 736 EP 742 UT ISI:000087127600008 ER PT J AU Grolleau, F Lapied, B TI Dorsal unpaired median neurones in the insect central nervous system: Towards a better understanding of the ionic mechanisms underlying spontaneous electrical activity SO JOURNAL OF EXPERIMENTAL BIOLOGY DE insect; dorsal unpaired median neurones; pacemaker activity; electrophysiology; ionic current ID COCKROACH PERIPLANETA-AMERICANA; CELLS DUM NEURONS; LOCUST METATHORACIC GANGLION; ADULT AMINERGIC NEURONS; NEUROSECRETORY-CELLS; SCHISTOCERCA-GREGARIA; MIGRATORY LOCUST; NEUROHORMONE-D; CA2+ CURRENTS; PHYSIOLOGICAL-CHARACTERISTICS AB The efferent dorsal unpaired median (DUM) neurones, which include octopaminergic neurones, are among the most intensively studied neurones in the insect central nervous system. They differ from other insect neurones in generating endogenous spontaneous overshooting action potentials. The second half of the 1980s is certain to be considered a turning point in the study of the ion channels underlying the electrical activity of DUM neurones. Recent advances made using the patch-clamp technique have stimulated an increasing interest in the understanding of the biophysical properties of both voltage-dependent and voltage-independent ion channels. Patch-clamp studies of DUM neurones in cell culture demonstrate that these neurones express a wide variety of ion channels. At least five different types of K+ channel have been identified: inward rectifier, delayed rectifier and A-like channels as well as Ca2+- and Na+-activated K+ channels. Moreover, besides voltage-dependent Na+ and Ca2+-sensitive Cl(-)channels, DUM neurones also express four types of Ca2+ channel distinguished on the basis of their kinetics, voltage range of activation and pharmacological profile. Finally, two distinct resting Ca2+ and Na+ channels have been shown to be involved in maintaining the membrane potential and in regulating the firing pattern. In this review, we have also attempted critically to evaluate these existing ion channels with regard to their specific functions in the generation of the different phases of the spontaneous electrical activity of the DUM neurone. C1 Univ Angers, UPRES EA 2647, RCIM, Neurophysiol Lab, F-49045 Angers, France. RP Lapied, B, Univ Angers, UPRES EA 2647, RCIM, Neurophysiol Lab, Rue Haute Reculee, F-49045 Angers, France. TC 37 PD JUN PY 2000 VL 203 IS 11 BP 1633 EP 1648 UT ISI:000087629000001 ER PT J AU Kaassis, M Oberti, F Burtin, P Boyer, J TI Argon plasma coagulation for the treatment of hemorrhagic radiation proctitis SO ENDOSCOPY ID PROCTOSIGMOIDITIS; EXPERIENCES; SUCRALFATE; THERAPY; APC AB Background and Study Aims: Chronic radiation proctitis is a complication of radiotherapy for malignant pelvic diseases. Rectal bleeding caused by radiation proctitis is difficult to manage. Argon plasma coagulation (APC) is an electrocoagulation technique that appears to be an effective and low-cost alternative to the use of lasers in gastrointestinal endoscopy, The aim of this study was to evaluate the efficacy of APC, as well as patients' tolerance of the procedure, in the treatment of bleeding radiation-induced proctitis, Patients and Methods: The charts of 16 patients with chronic radiation proctitis were analyzed retrospectively. Their average age was 73.5 (range 62-80), Fifteen patients had prostate cancer, and one had uterine cancer. The average time to onset of symptoms after radiotherapy was 15 months (range 6-36 months), All patients had intermittent or daily rectal bleeding, and three patients needed blood transfusions. The severity of bleeding was graded from 0 to 4, APC treatment was administered every month; the argon gas flow was set at 0.6 l/min with an electrical power setting of 40 W. Results: All patients were improved with APC treatment. A mean of 3.7 sessions was necessary to relieve symptoms. APC therapy resulted in a reduction in the mean severity score from 2.4 to 0.6. Seven patients had no recurrent rectal bleeding, and the bleeding was significantly reduced to occasional and negligible spotting (less than one bleeding episode per week) in nine patients. None of the patients required transfusions after treatment. During the follow-up period (average 10.7 months, range 8-28 months), one patient had a recurrence of rectal bleeding that required two repeat sessions. The tolerance was good, with no long-term treatment-related complications. Conclusions: APC is an effective, safe and well-tolerated treatment for rectal bleeding caused by chronic radiation proctitis, It should be considered as a first-line therapy for radiation proctitis. C1 Univ Hosp, Gastroenterol Unit, F-49033 Angers, France. RP Boyer, J, Univ Hosp, Gastroenterol Unit, 4 Rue Larrey, F-49033 Angers, France. TC 35 PD SEP PY 2000 VL 32 IS 9 BP 673 EP 676 UT ISI:000089092700002 ER PT J AU Lafont, A Dubois-Rande, JL Steg, PG Dupouy, P Carrie, D Coste, P Furber, A Beygui, F Feldman, LJ Rahal, S Tron, C Hamon, M Grollier, G Commeau, P Richard, P Colin, P Bauters, C Karrillon, G Ledru, F Citron, B Marie, FN Kern, M CA FROST Study Grp TI The French Randomized Optimal Stenting Trial: A prospective evaluation of provisional stenting guided by coronary velocity reserve and quantitative coronary angiography SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY ID BALLOON ANGIOPLASTY; ARTERY DISEASE; BENESTENT-II; RESTENOSIS; IMPLANTATION; STENOSIS AB OBJECTIVES We sought to make a prospective comparison of systematic stenting with provisional stenting guided by Doppler measurements of coronary velocity reserve and quantitative coronary angiography. BACKGROUND Despite the increasing use of stents during percutaneous transluminal coronary angioplasty, it is unclear whether systematic stenting is superior to a strategy of provisional stenting in which stents are placed only in patients with unsatisfactory results or as a hail-out procedure. METHODS Two hundred fifty-one patients undergoing elective coronary angioplasty were randomly assigned either to provisional stenting (group 1, in which stenting was performed if postangioplasty coronary velocity reserve was <2.2 and/or residual stenosis greater than or equal to 35% or as hail-out) or to systematic stenting (group 2). The primary end point was the six-month angiographic minimal lumen diameter (MLD). Major adverse cardiac events were secondary end points (death, acute myocardial infarction and target lesion revascularization), RESULTS Stenting was performed in 48.4% of patients in group 1 and 100% of patients in group 2 (p < 0.01). Six months after angioplasty, the MLD did not differ between groups (1.90 +/- 0.79 mm vs. 1.99 +/- 0.70 mm, p = 0.39), as was the rate of binary restenosis (27.1% vs. 21.4%, p = 0.37). Among patients with restenosis, 13/32 (40.6%) in group 1 but 100% (25/25) in group 2 had in-stent restenosis (p < 0.01). Target lesion revascularization (15.1% vs. 14.4% in groups 1 and 2 respectively, p = 0.89) and major adverse cardiac events (15.1% vs. 16.0%, p 0.85) were not significantly different. CONCLUSIONS Systematic stenting does not provide superior angiographic results at six months as compared with provisional stenting. (C) 2000 by the American College of Cardiology. C1 Univ Paris 05, Hop Boucicaut, Dept Cardiol, F-75015 Paris, France. Hop Henri Mondor, F-94010 Creteil, France. Hop Bichat, F-75877 Paris, France. Hop Purpan, Toulouse, France. Hop Bordeaux Pessac, Bordeaux, France. Hop Angers, Angers, France. Hop Necker Enfants Malad, Paris, France. Hop Charles Nicolle, F-76031 Rouen, France. Hop Emile Muller, Mulhouse, France. Hop Cote Nacre, Caen, France. Clin St Martin, Caen, France. Hop Brabois, Nancy, France. Hop Antoine Beclere, Paris, France. Hop Cardiol, F-59037 Lille, France. Hop Lariboisiere, F-75475 Paris, France. Hop Broussais, F-75674 Paris, France. Hop Gabriel Montpied, Clermont Ferrand, France. St Louis Univ Ctr, St Louis, MO USA. RP Lafont, A, Univ Paris 05, Hop Boucicaut, Dept Cardiol, 78 Rue Convent, F-75015 Paris, France. TC 33 PD AUG PY 2000 VL 36 IS 2 BP 404 EP 409 UT ISI:000088491800007 ER PT J AU Spanggaard, H Prehn, J Nielsen, MB Levillain, E Allain, M Becher, J TI Multiple-bridged bis-tetrathiafulvalenes: New synthetic protocols and spectroelectrochemical investigations SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY ID CESIUM TETRATHIAFULVALENE; CATION RADICALS; TWIN DONOR; SALTS; ISOMERIZATION; CATENANES; DESIGN; UNITS AB Synthetic strategies for preparing dimeric tetrathiafulvalenes (TTFs) linked by either one, two, or four bridges have been developed. In particular, we report efficient few-step protocols for the preparation of face-to-face overlapped quadruple-bridged bis-TTFs. The ready interconversion of cis and trans TTFs in the presence of catalytic amounts of acid was implemented in one synthetic protocol as a way to control the isomeric outcome. The compounds were characterized by NMR spectroscopy, mass spectrometry, and elemental analysis. Moreover, the X-ray crystal structure of the macrocycle 4b is presented and compared to semiempirical (PM3) geometry optimizations. Cyclic voltammetry and spectroelectrochemistry were used to describe the interactions established between two TTF units upon oxidation, that is, their ability to form mixed-valence complexes and pi-dimers either intra- or intermolecularly. The length, flexibility, and number of bridging units in a bis-TTF, as well as the specific TTF positions being connected, determine the extent of these interactions. Thus, rigid linkers enhance the formation of intermolecular mixed-valence complexes. For 4b, the absorption spectrum of this mixed-valence stale of TTF in solution has been recorded for the first time. Finally, preliminary complexation experiments with different electron-deficient molecules are described. C1 Odense Univ, Univ So Denmark, Dept Chem, DK-5230 Odense, Denmark. ETH Zurich, Organ Chem Lab, CH-8092 Zurich, Switzerland. Univ Angers, CNRS, UMR 6501, F-49045 Angers, France. RP Nielsen, MB, Odense Univ, Univ So Denmark, Dept Chem, Campusvej 55, DK-5230 Odense, Denmark. TC 32 PD OCT 4 PY 2000 VL 122 IS 39 BP 9486 EP 9494 UT ISI:000089690600017 ER PT J AU Raimundo, JM Blanchard, P Brisset, H Akoudad, S Roncali, J TI Proquinoid acceptors as building blocks for the design of efficient pi-conjugated fluorophores with high electron affinity SO CHEMICAL COMMUNICATIONS ID NARROW-BANDGAP; POLYMERS; THIOPHENE; LIGHT; OLIGOTHIOPHENES; COPOLYMERS; OLIGOMERS; UNITS AB The association of aromatic electron donor groups with proquinoid acceptors leads to pi-conjugated fluorophores combining tunable emission wavelength at constant geometry, high fluorescence efficiency and high electron affinity. C1 Univ Angers, CNRS, UMR 6501, F-49045 Angers, France. RP Roncali, J, Univ Angers, CNRS, UMR 6501, 2 Bd Lavoisier, F-49045 Angers, France. TC 31 PY 2000 IS 11 BP 939 EP 940 UT ISI:000087163600025 ER PT J AU Hideur, A Chartier, T Ozkul, C Sanchez, F TI Dynamics and stabilization of a high power side-pumped Yb-doped double-clad fiber laser SO OPTICS COMMUNICATIONS DE fiber lasers; high power; side-pumping; dynamics; nonlinear effects ID MU-M; OUTPUT AB We present an experimental study of the dynamics of a high power Yb3+-doped double-clad fiber laser in various optical configurations operating in the 1.08 mum wavelength. The fiber is side-pumped with a high power laser diode using the V-groove technique. Different self-pulsing regimes are identified resulting from third-order nonlinear effects. The influence of the cavity losses on the dynamical behavior is also investigated. In addition, we show that the system is efficiently stabilized in a unidirectional ring cavity where Brillouin backscattering is suppressed. (C) 2000 Published by Elsevier Science B.V. C1 Univ Rouen, CNRS CORIA UMR 6614, Grp Opt Optron, F-76821 Mt St Aignan, France. RP Sanchez, F, Univ Angers, Lab POMA, 2 Bd Lavoisier, F-49000 Angers, France. TC 29 PD DEC 15 PY 2000 VL 186 IS 4-6 BP 311 EP 317 UT ISI:000165983200012 ER PT J AU Benaouf, G Parisi, L TI Genetics of host-pathogen relationships between Venturia inaequalis races 6 and 7 and Malus species SO PHYTOPATHOLOGY DE Malus x domestica ID SCAB RESISTANCE; AVIRULENCE GENE; LINKAGE MAPS; VF GENE; APPLE; POPULATIONS; MARKERS AB Resistance to scab originating from Malus floribunda clone 821 is the most widely form of resistance used in apple breeding programs. A dominant gene, named Vf, was introgressed from this clone into recent cultivars, although the genetic determinants of the resistance of M. floribunda 821 are apparently more complex than a single gene. The appearance of new races overcoming the resistance of cultivars with the Vf gene, the parental clone, or both made it possible to undertake a genetic analysis of host-pathogen interactions. The segregation of resistance in progenies of crosses from 'Golden Delicious' x M. floribunda 821 and 'Golden Delicious' x 'Idared' into five strains of Venturia inaequalis-races 1 (strains 104, 1093, and 301), 6 (strain 302), and 7 (strain 1066)-demonstrated the existence of a second dominant gene in M. floribunda 821. This gene, independent of Vf, was named Vfh because it seemed to induce a hypersensitive reaction. The results obtained with strain 1066, virulent to M, floribunda 821, allowed identification of another dominant gene, Vg, responsible for the resistance of 'Golden Delicious' to this strain. Vg is also carried by 'Florina', which was selected for its Vf resistance. The pathogenicity of a progeny originating from a cross between V. inaequalis strains 1066 and 301, characterized in vitro on leaf disks of differential genotypes, revealed two independent avirulence genes involved in the pathogenicity toward the Vg and VS genes, respectively. These avirulence genes were named Avr Vg and Avr Vf. The host-pathogen interactions detected are consistent with a gene-for-gene relationship. C1 INRA, Ctr Angers, Unite Pathol Vegetale & Phytobacteriol, F-49071 Beaucouze, France. RP Parisi, L, INRA, Ctr Angers, Unite Pathol Vegetale & Phytobacteriol, BP 57, F-49071 Beaucouze, France. TC 29 PD MAR PY 2000 VL 90 IS 3 BP 236 EP 242 UT ISI:000085499400005 ER PT J AU Hunault, M Bauer, KA TI Recombinant factor VIIa for the treatment of congenital factor VII deficiency SO SEMINARS IN THROMBOSIS AND HEMOSTASIS DE factor VIIa; factor VII deficiency; bleeding disorder ID COAGULATION-FACTOR-VII; ACTIVATED FACTOR-VII; BOVINE FACTOR-VII; TISSUE FACTOR; FACTOR-IX; CONTINUOUS-INFUSION; BLOOD-COAGULATION; HAGEMAN-FACTOR; PLASMA; QUANTITATION AB Factor VII deficiency is a rare autosomal bleeding disorder with a highly variable hemorrhagic predisposition, Severe bleeding, including hemarthroses, may be encountered when plasma factor VII levels are below 1%, Patients have prolonged prothrombin times, and the final diagnosis is established by quantitative factor VII assays. Some patients have true deficiencies, that is, very low factor VII activity and low factor VII antigen (crossreacting material) levels (CRM-); others have normal antigen levels but low activity (CRM+). Still others have reduced antigen levels (CRMR). There is a rather poor correlation between clinical symptoms and factor VII activity levels in plasma. Treatment of these patients consists of fresh frozen plasma, prothrombin complex concentrates, or factor VII concentrates. Recombinant activated factor VII (rFVIIa) is a very useful alternative, and several patients have been treated successfully. Because of the short half-life of factor VIIa, repeated doses have to be administered, and continuous infusion may be even better, Antibodies to factor VII have been reported but seem to be rather rare. From the available data it appears that rFVIIa is a safe and effective treatment modality for patients with congenital factor VII deficiency. C1 VA Boston Healthcare Syst, Dept Med, Hematol Oncol Sect, Boston, MA USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02115 USA. CHU Angers, Serv Malad Sang, Angers, France. RP Bauer, KA, Vet Adm Med Ctr W Roxbury, 1400 VFW Pkwy, Boston, MA 02132 USA. TC 28 PY 2000 VL 26 IS 4 BP 401 EP 405 UT ISI:000165399900008 ER PT J AU Chanson, P Boerlin, V Ajzenberg, C Bachelot, Y Benito, P Bringer, J Caron, P Charbonnel, B Cortet, C Delemer, B Escobar-Jimenez, F Foubert, L Gaztambide, S Jockenhoevel, F Kuhn, JM Leclere, J Lorcy, Y Perlemuter, L Prestele, H Roger, P Rohmer, V Santen, R Sassolas, G Scherbaum, WA Schopohl, J Torres, E Varela, C Villamil, F Webb, SM TI Comparison of octreotide acetate LAR and lanreotide SR in patients with acromegaly SO CLINICAL ENDOCRINOLOGY ID LONG-TERM TREATMENT; SLOW-RELEASE LANREOTIDE; GROWTH-HORMONE; SOMATOSTATIN; TOLERABILITY; PHARMACOKINETICS; EPIDEMIOLOGY; MULTICENTER; MANAGEMENT; BIM-23014 AB BACKGROUND AND OBJECTIVE The most effective option for the medical treatment of patients with acromegaly is the use of somatostatin analogues. Long-acting depot formulations for intramuscular injection of two somatostatin analogues have recently become available: octreotide acetate LAR (Sandostatin(R) LAR(R), Novartis Pharma AG) and lanreotide SR (Somatuline(R), Ipsen Biotech). We wished to compare efficacy of octreotide LAR and lanreotide SR in acromegalic patients. PATIENTS AND METHODS A group of 125 patients with acromegaly (67 females; mean age, 47 years; 59 patients had previous pituitary irradiation) from 26 medical centres in France, Spain and Germany were studied. Before the study, all patients had been treated with intramuscular injections of lanreotide SR (mean duration, 26 months) at a dose of 30 mg which was injected every 10 days in 64 and every 14 days in 61 patients, respectively. All patients were switched from lanreotide SR to intramuscular injections of 20 mg of octreotide LAR once monthly for three months. In order to obtain efficacy and safety data of lanreotide SR under study conditions, it was decided to randomly assign at day 1, in a 3 : 1 ratio, the time point of the treatment switch; 27 of the patients were randomly assigned to continue the lanreotide SR treatment for the first 3 months of the study (group A); they were on octreotide LAR 20 mg from month 4-6. The other 98 patients were assigned to be switched to treatment with octreotide LAR 20 mg at day 1 (group B). In group B patients, octreotide LAR treatment was continued until month 6, with an adjustment of the dose based on GH levels obtained at month 3. RESULTS The mean GH concentration decreased from 9.6 +/- 1.3 mU/l at the last evaluation on lanreotide SR to 6.8 +/- 1.0 mU/l after three injections of octreotide LAR (P < 0.001). The percentages of patients with mean GH values less than or equal to 6.5 mU/l (2.5 mug/l) and less than or equal to 2.6 mU/l (1.0 mug/l) at the last evaluation on lanreotide SR were 54% and 14%, and these values increased after 3 months treatment with octreotide LAR to 68% and 35% (P < 0.001), respectively. IGF-I levels were normal in 48% at the last evaluation on lanreotide SR and in 65% after 3 months on octreotide LAR (P < 0.001). Patients with pre-study pituitary irradiation had lower mean GH and IGF-I concentrations. But the effects of the treatment change did not differ between the irradiated and the nonirradiated patients. In general both drugs were well tolerated. CONCLUSION Octreotide LAR 20 mg administered once monthly was more effective than lanreotide SR 30 mg administered 2 or 3 times monthly in reducing GH and IGF-I in patients with acromegaly. C1 CHU Bicetre, Serv Endocrinol & Malad Reprod, F-94275 Le Kremlin Bicetre, France. Novartis Pharma AG, Clin Res & Dev, Basel, Switzerland. Hop Lariboisiere, F-75475 Paris, France. Hop La Pitie Salpetriere, Paris, France. CHU Grenoble, F-38043 Grenoble, France. Hop Lapeyronie, Montpellier, France. CHU Rangueil, F-31054 Toulouse, France. Hotel Dieu, Nantes, France. Ctr Hosp Reg & Univ Lille, F-59037 Lille, France. Hop Maison Blanche, Reims, France. Hop Bois Guillaume, Bois Guillaume, France. Hop Brabois, Vandoeuvre Nancy, France. Hop Sud, Rennes, France. Ctr Hosp Henri Mondor, Creteil, France. Hop Haut Leveque, Pessac, France. Ctr Hosp Reg & Univ, Angers, France. Hop Neurocardiol, Lyon, France. Univ Klin Koln, Klin & Poliklin Innere Med 2, Cologne, Germany. Univ Klin Dusseldorf, Dusseldorf, Germany. LMU, Klinikum Innenstadt, Med Klin, Munich, Germany. Hosp Reina Sofia, Cordoba, Spain. Hosp Clin San Cecilio, Granada, Spain. Hosp Cruces, Baracaldo, Spain. Hosp Ramon y Cajal, E-28034 Madrid, Spain. Hosp Univ Virgen Rocio, Dept Endocrinol, Seville, Spain. Hosp Santa Cruz & San Pablo, E-08025 Barcelona, Spain. RP Chanson, P, CHU Bicetre, Serv Endocrinol & Malad Reprod, 78 Rue Gen Leclerc, F-94275 Le Kremlin Bicetre, France. TC 28 PD NOV PY 2000 VL 53 IS 5 BP 577 EP 586 UT ISI:000165401500006 ER PT J AU Cimon, B Carrere, J Vinatier, JF Chazalette, JP Chabasse, D Bouchara, JP TI Clinical significance of Scedosporium apiospermum in patients with cystic fibrosis SO EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES ID PSEUDALLESCHERIA-BOYDII; DISEASE; FUNGI AB The incidence of airway colonization by Scedosporium apiospermum and of related sensitization was investigated prospectively in 128 patients with cystic fibrosis over a 5-year period, and results were compared with clinical data. Scedosporium apiospermum, recovered from sputum samples in 11 of 128 (8.6%) patients, was the most frequent filamentous fungus after Aspergillus fumigatus. Counterimmunoelectrophoresis, used to detect scedosporiosis serologically, was positive in 27 of 128 (21.1%) patients. The discrepancy between the mycological and serological results may be related to immune cross-reactions between Scedosporium apiospermum and Aspergillus fumigatus. However, symptoms of allergic bronchopulmonary disease were observed in two patients chronically colonized by Scedosporium apiospermum. The results clearly demonstrate that the frequency of this fungus is largely underestimated and that it may trigger an inflammatory response, thus suggesting a pathogenic role in patients with cystic fibrosis. C1 CHU Angers, Lab Parasitol Mycol, F-49033 Angers 01, France. Hop Renee Sabran, F-83406 Hyeres, France. RP Cimon, B, CHU Angers, Lab Parasitol Mycol, 4 Rue Larrey, F-49033 Angers 01, France. TC 28 PD JAN PY 2000 VL 19 IS 1 BP 53 EP 56 UT ISI:000085351300011 ER PT J AU Menei, P Pean, JM Nerriere-Daguin, V Jollivet, C Brachet, P Benoit, JP TI Intracerebral implantation of NGF-releasing biodegradable microspheres protects striatum against excitotoxic damage SO EXPERIMENTAL NEUROLOGY DE drug delivery; microsphere; nerve growth factor; striatum; excitotoxic injury; Huntington's disease ID NERVE GROWTH-FACTOR; BASAL FOREBRAIN NEURONS; HUNTINGTONS-DISEASE; QUINOLINIC ACID; RODENT MODEL; CHOLINERGIC NEURONS; MESSENGER-RNA; RAT STRIATUM; POLY(D,L-LACTIDE-CO-GLYCOLIDE) MICROSPHERES; STEREOTAXIC IMPLANTATION AB Intrastriatal implantation of genetically modified cells synthesizing nerve growth factor (NGF) constitutes one way to obtain a long-term supply of this neurotrophic factor and a neuronal protection against an excitotoxic lesion. We have investigated if NGF-loaded poly (D,L-lactide-co-glycolide) microspheres could represent an alternative to cell transplantations. These microspheres can be implanted stereotaxically and locally release the protein in a controlled and sustained way. In order to test this paradigm, the NGF release kinetics were characterized in vitro using radiolabeled NGF, immunoenzymatic assay, and PC-12 cells bioassay and then in vivo after implantation in the intact rat striatum, These microspheres were thus implanted into the rat striatum 7 days prior to infusing quinolinic acid. Control animals were either not treated or implanted with blank microspheres. The extent of the lesion and the survival of ChAT-, NADPH-d-, and DARPP-32-containing neurons were analyzed, In vitro studies showed that microspheres allowed a sustained release of bioactive NGF for at least 1 month. Microspheres implanted in the intact striatum still contained NGF after 2.5 months and they were totally degraded after 3 months. After quinolinic acid infusion, the lesion size in the group treated with NGF-releasing microspheres was reduced by 40% when compared with the control groups. A marked neuronal sparing was noted, principally concerning the cholinergic interneurons, but also neuropeptide Y/somatostatin interneurons and GABAergic striatofuge neurons, These results indicate that implantation of biodegradable NGF-releasing microspheres can be used to protect neurons from a local excitotoxic lesion and that this strategy may ultimately prove to be relevant for the treatment of various neurological diseases. (C) 2000 Academic Press. C1 CHU Angers, Serv Neurochirurg, Dept Neurosurg, INSERM U298, F-49033 Angers 01, France. Sch Pharm, UPRES EA 2169, Angers, France. INSERM U437, Nantes, France. RP Menei, P, CHU Angers, Serv Neurochirurg, Dept Neurosurg, INSERM U298, F-49033 Angers 01, France. TC 27 PD JAN PY 2000 VL 161 IS 1 BP 259 EP 272 UT ISI:000085666300024 ER PT J AU Mouneyrac, C Geffard, A Amiard, J Amiard-Triquet, C TI Metallothionein-like proteins in Macoma balthica: effects of metal exposure and natural factors SO CANADIAN JOURNAL OF FISHERIES AND AQUATIC SCIENCES ID OYSTERS CRASSOSTREA-GIGAS; SCALLOP MIZUHOPECTEN-YESSOENSIS; BINDING PROTEINS; CADMIUM ACCUMULATION; MOLECULAR WEIGHT; MYTILUS-EDULIS; BIOACCUMULATION; MERCURY; SILVER; CONTAMINATION AB Biological processes involved in the tolerance acquired by populations chronically exposed to metal pollution in the environment were examined in baltic clams (Macoma balthica) originating from both industrialized and clean areas and in clams exposed experimentally to metals. It has been shown previously that clams surviving Ag and Hg exposure at LT50 did not protect themselves by accumulating smaller amounts of metals than clams that failed to survive, so attention was focussed on the physicochemical forms of storage of the accumulated metals. Silver was found to be predominantly bound to insoluble forms and Cd and Hg to soluble forms. In both controls and contaminated clams, a metallothionein-like protein (MTLP) has been shown to be present, the concentrations of which did not depend on the geographical origin of the clams. The significant relationship between metal and MTLP concentrations shown in the baltic clams suggests that the induction of this protein could provide a useful tool for the biomonitoring of metal pollution. The influence of natural factors (season, weight), however, must be taken into account when interpreting such data. C1 Univ Nantes, ISOMer, Fac Pharm, Serv Ecotoxicol, F-44035 Nantes 1, France. IRFA Dept Sci Vie & Terre, Lab Ecol Anim, F-49100 Angers, France. RP Amiard-Triquet, C, Univ Nantes, ISOMer, Fac Pharm, Serv Ecotoxicol, EA 2663,1 Rue Gaston Veil, F-44035 Nantes 1, France. TC 27 PD JAN PY 2000 VL 57 IS 1 BP 34 EP 42 UT ISI:000084870600005 ER PT J AU Siepmann, J Peppas, NA TI Hydrophilic matrices for controlled drug delivery: An improved mathematical model to predict the resulting drug release kinetics (the "sequential layer" model) SO PHARMACEUTICAL RESEARCH DE controlled release; diffusion; hydrophilic matrix; hydroxypropyl methylcellulose (HPMC); modeling; swelling ID POLYMER DISENTANGLEMENT CONCENTRATION; DIFFUSION LAYER; DOSAGE FORMS; FORMULATION VARIABLES; HPMC GELS; TABLETS; DISSOLUTION; MECHANISMS; NMR; COEFFICIENTS AB Purpose. The aims of this study were (i)to elucidate the transport mechanisms involved in drug release from hydrophilic matrices; and (ii) to develop an improved mathematical model allowing quantitative predictions of the resulting release kinetics. Methods. Our previously presented model has been substantially modified, by adding: (i) inhomogeneous swelling; (ii) poorly water-soluble drugs; and (iii) high initial drug loadings. The validity of the improved model has been tested experimentally using hydroxypropyl methylcellulose (HPMC)-matrices, containing either a poorly or a freely water-soluble drug (theophylline or chlorpheniramine maleate) at various initial loadings in phosphate buffer pH 7.4 and 0.1 N HCl, respectively. Results. By overcoming the assumption of homogeneous swelling we show that the agreement between theory and experiment could be significantly improved. Among others, the model could describe quantitatively even the very complex effect on the resulting relative release rates (first slowing down, then accelerating drug release) observed when increasing the initial loading of poorly water-soluble drugs. Conclusions. The practical benefit of this work is an improved design model that can be used to predict accurately the required composition and dimensions of drug-loaded hydrophilic matrices in order to achieve desired release profiles, thus facilitating the development of new pharmaceutical products. C1 Free Univ Berlin, Coll Pharm, D-12169 Berlin, Germany. Purdue Univ, Sch Chem Engn, W Lafayette, IN 47907 USA. RP Siepmann, J, Univ Angers, Fac Pharm, Pharm Galen Lab, 16 Blvd Daviers, F-49100 Angers, France. TC 26 PD OCT PY 2000 VL 17 IS 10 BP 1290 EP 1298 UT ISI:000165879700019 ER PT J AU Tuech, JJ Pessaux, P Rouge, C Regenet, N Bergamaschi, R Arnaud, JP TI Laparoscopic vs open colectomy for sigmoid diverticulitis - A prospective comparative study in the elderly SO SURGICAL ENDOSCOPY-ULTRASOUND AND INTERVENTIONAL TECHNIQUES DE laparoscopy; colon; elderly patients; sigmoid diverticulitis; high-risk patients ID COLORECTAL SURGERY; CHOLECYSTECTOMY; PNEUMOPERITONEUM; HEMODYNAMICS; RISK AB Background: The aim of this prospective comparative study was to assess the outcome of laparoscopic and open colectomy for sigmoid diverticulitis in patients aged greater than or equal to 75 years. Methods: From January 1993 to December 1998, all patients 75 years of age and older undergoing an elective colectomy for sigmoid diverticulitis were included in the study. The patients were divided into the following two groups: group 1 (n = 22) consisted of patients who underwent a laparoscopic procedure; group 2 (n = 24) consisted of patients who underwent an open procedure. Results: In group 1, there were 12 women and 10 men with a mean age of 77.2 years (range, 75-82); in group 2, there were 14 women and 10 men with a mean age of 78 years (range, 76-84) (p = 0.37). There was no difference between the groups in ASA classification. The operative time was shorter in group 2 (136 vs 234 mins). The postoperative period during which parenteral analgesics were required (5.4 vs 8.2 days, p = 0.001), postoperative morbidity (18% vs 50%, p = 0.02), postoperative length of hospital stay (13.1 vs 20.2 days, p = 0.003), and the inpatient rehabilitation (6 vs 15 patients, p = 0.01) were significantly shorter for group 1 than for group 2. There were no perioperative deaths. The conversion rate was 9% in group 1. Conclusion: The data from the present study suggest that laparoscopic colectomy for sigmoid diverticulitis can be applied safely to older patients with fewer complication, less pain, shorter hospital stay, and a more rapid return to preoperative activity levels than that seen with open colorectal resection. C1 Angers Univ Hosp, Dept Digest Surg, F-49000 Angers, France. RP Tuech, JJ, Angers Univ Hosp, Dept Digest Surg, 4 Rue Larrey, F-49000 Angers, France. TC 26 PD NOV PY 2000 VL 14 IS 11 BP 1031 EP 1033 UT ISI:000165706100012 ER PT J AU Barrat, JA Blichert-Toft, J Gillet, P Keller, F TI The differentiation of eucrites: The role of in situ crystallization SO METEORITICS & PLANETARY SCIENCE ID RARE-EARTH ELEMENTS; DIOGENITE PARENT BODY; CUMULATE EUCRITES; SOLAR-SYSTEM; PARTITION-COEFFICIENTS; GENETIC-IMPLICATIONS; MINERAL CHEMISTRY; ALKALI ELEMENTS; CORE FORMATION; PIPLIA-KALAN AB We report on major and trace element analyses of 17 eucrites, including three cumulate eucrites (Binda, Moore County, and Serra de MagC), determined by, respectively, inductively-coupled plasma atomic emission spectrometry and inductively-coupled plasma mass spectrometry. The results obtained for Binda and Moore County are consistent with the model of Treiman (1997) for the formation of cumulate eucrites, which holds that these meteorites were produced from a eucritic melt. Our sample of Serra de Mage contains unusually large amounts of pyroxene and probably an accessory phase rich in heavy rare earth elements and is therefore not representative of this eucrite as known from literature data. Our results for the noncumulate eucrites Bereba, Bouvante, Cachari, Caldera, Camel Donga, Ibitira, Jonzac, Juvinas, Lakangaon, Millbillillie, Padvarninkai, Pasamonte, Sioux County, and Stannern are in good agreement with literature data. The observed decoupling between major and trace elements for noncumulate eucrites can be explained by in situ crystallization during the differentiation of an asteroidal magma ocean. This model can further account for both the Nuevo Laredo and the Stannern trends but has as a consequence that none of the analyzed eucrites represents a primary melt. C1 Univ Angers, Fac Sci, F-49045 Angers, France. Ecole Normale Super Lyon, CNRS UMR 8515, Lab Sci Terre, F-69364 Lyon 7, France. Inst Dolomieu, CNRS UMR 5025 UJF, F-38031 Grenoble, France. RP Barrat, JA, Univ Angers, Fac Sci, 2 Bd Lavoisier, F-49045 Angers, France. TC 26 PD SEP PY 2000 VL 35 IS 5 BP 1087 EP 1100 UT ISI:000089736400021 ER PT J AU Corzo, G Escoubas, P Stankiewicz, M Pelhate, M Kristensen, CP Nakajima, T TI Isolation, synthesis and pharmacological characterization of delta-palutoxins IT, novel insecticidal toxins from the spider Paracoelotes luctuosus (Amaurobiidae) SO EUROPEAN JOURNAL OF BIOCHEMISTRY DE baculovirus; insecticidal toxins; scorpion toxins; sodium channel; spider toxins ID FUNNEL-WEB SPIDER; IMPROVED BACULOVIRUS INSECTICIDE; SODIUM CURRENT INACTIVATION; PLECTREURYS-TRISTIS SIMON; PRIMITIVE HUNTING SPIDER; SCORPION ALPHA-TOXIN; AMINO-ACID-SEQUENCE; TIME-OF-FLIGHT; MU-AGA-IV; RECOMBINANT BACULOVIRUS AB Four novel insecticidal toxins were isolated from the venom of the spider Paracoelotes luctuosus (Araneae: Amaurobiidae) and named delta-palutoxins IT1 to IT4. The four toxins are homologous 36-37 amino acid peptides reticulated by four disulfide bridges and three have amidated C-terminal residues. The delta-palutoxins are highly homologous with the previously described mu-agatoxins and curtatoxins (77-97%). The four peptides demonstrated significant toxicity against larvae of the crop pest Spodoptera litura (Lepidoptera: Noctuidae) in a microinjection bioassay, with LD50 values in the 9-50 mu g per g of insect range. This level of toxicity is equivalent to that of several of the most active scorpion toxins used in the development of recombinant baculoviruses, and the delta-palutoxins appear to be insect specific. Electrophysiological experiments demonstrated that delta-palutoxin IT1, the most active toxin acts by affecting insect sodium channel inactivation, resulting in the appearance of a late-maintained sodium current, in a similar fashion to insecticidal scorpion alpha and alpha-like toxins and is thus likely to bind to channel receptor site 3. However, delta-palutoxin IT1 was distinguished by its lack of effect on peak sodium conductance, on the early phase of sodium current inactivation and the absence of a shift in the activation voltage of the sodium channels. delta-Palutoxins are thus proposed as new insecticidal toxins related to the alpha and alpha-like scorpion toxins. They will be useful both in the development of recombinant baculoviruses in agrochemical applications and also as molecular probes for the investigation of molecular mechanisms of insect selectivity and structure and function of sodium channels. C1 Suntory Inst Bioorgan Res, Shimamoto, Osaka 6188503, Japan. Univ Angers, Neurophysiol Lab, Angers, France. Nicholas Copernicus Univ, Biophys Lab, Torun, Poland. Amer Cyanamid Co, Princeton, NJ 08540 USA. RP Corzo, G, Suntory Inst Bioorgan Res, Wakayamadai 1-1-1, Shimamoto, Osaka 6188503, Japan. TC 26 PD SEP PY 2000 VL 267 IS 18 BP 5783 EP 5795 UT ISI:000089715100016 ER PT J AU Turbiez, M Frere, P Blanchard, P Roncali, J TI Mixed pi-conjugated oligomers of thiophene and 3,4-ethylenedioxythiophene (EDOT) SO TETRAHEDRON LETTERS DE oligomers; oligothiophene; electrochemistry; optical properties ID CONDUCTING POLYMERS; BANDGAP; POLY(THIOPHENES) AB Conjugated oligomers based on various combinations of thiophene and 3,4-ethylenedioxythiophene (EDOT) moieties have been synthesised. Comparison of the optical and electrochemical properties shows that the introduction of a bis-EDOT core in the middle of the system produces a decrease of the HOMO-LUMO gap which is attributed to an enhancement of the planarity and rigidity of the pi-conjugated system. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 CNRS, UMR 6501, Inst Mol & Mat Organ, F-49045 Angers, France. RP Frere, P, CNRS, UMR 6501, Inst Mol & Mat Organ, 2 Blvd Lavoisier, F-49045 Angers, France. TC 26 PD JUL 15 PY 2000 VL 41 IS 29 BP 5521 EP 5525 UT ISI:000088200200019 ER PT J AU Siepmann, J Kranz, H Peppas, NA Bodmeier, R TI Calculation of the required size and shape of hydroxypropyl methylcellulose matrices to achieve desired drug release profiles SO INTERNATIONAL JOURNAL OF PHARMACEUTICS DE controlled release; geometry; hydrophilic matrix; hydroxypropyl methylcellulose; modeling ID SWELLING-CONTROLLED RELEASE; PENETRANT DIFFUSION; SWELLABLE POLYMERS; DISSOLUTION; DISENTANGLEMENT; REPTATION; SOLUTE; MODELS AB The aim of this study was to develop methods for the design of hydroxypropyl methylcellulose (HPMC) tablets with specified drugs profiles. This was achieved by the use of a mathematical model developed to predict the release kinetics of water-soluble drugs from HPMC matrices. The required model parameters were determined experimentally for propranolol HCl and chlorpheniramine maleate in 0.1 N HCl and phosphate buffer pH 7.4, respectively. Then, the effects of the dimensions and aspect ratio (radius/height) of the tablets on the drug release rate were evaluated. Independent experiments were conducted to verify the theoretical predictions. Acceptable agreement between theory and experiment was found, irrespective of the type of release medium and drug. However, statistical analysis revealed a structure in the resulting residuals. Drug release rates are overestimated at the beginning and underestimated at the end of the process. Possible explanations and modifications of the model are thoroughly discussed. Both. theoretical and experimental data showed that a broad spectrum of drug release patterns can be achieved by varying the size and shape of the tablet. The effect of the initial matrix radius on release was found to be more pronounced than the effect of the initial thickness. The practical benefit of the proposed method is to predict the required size and shape of new controlled drug delivery systems to achieve desired release profiles. thus significantly facilitating the development of new pharmaceutical products. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Free Univ Berlin, Coll Pharm, D-12169 Berlin, Germany. Purdue Univ, Sch Chem Engn, W Lafayette, IN 47907 USA. RP Siepmann, J, Univ Angers, Pharm Galen Lab, Fac Pharm, 16 Blvd Daviers, F-49100 Angers, France. TC 26 PD MAY 25 PY 2000 VL 201 IS 2 BP 151 EP 164 UT ISI:000087826200002 ER PT J AU Modrowski, D Basle, M Lomri, A Maric, PJ TI Syndecan-2 is involved in the mitogenic activity and signaling of granulocyte-macrophage colony-stimulating factor in osteoblasts SO JOURNAL OF BIOLOGICAL CHEMISTRY ID HEPARAN-SULFATE PROTEOGLYCAN; FIBROBLAST GROWTH-FACTOR; CELL-SURFACE; MOLECULAR-CLONING; GM-CSF; N-SYNDECAN; MEMBRANE; BINDING; KINASE; PHOSPHORYLATION AB We previously showed that granulocyte-macrophage colony-stimulating factor (GM-CSF) binds to heparan sulfate proteoglycans expressed at the surface of osteoblastic cells and that the mitogenic activity of this cytokine is dependent on the presence of fully sulfated proteoglycans, In this study, we determined if GM-CSF interacts with syndecans, a family of cell surface heparan sulfate proteoglycans. Human primary osteoblasts were found to express syndecan-2 and -4 but few syndecan-1 transcripts and proteins. Recombinant human GM-CSF coupled to biotin was found to bind to syndecan-2. Immunocytochemical transmission electron microscope analysis showed co-localization of syndecan-2 and GM-CSF at the cell membrane surface. Syndecan-2 also co-localized at the cell surface and co-immunoprecipitated with the GM-CSF receptor alpha chain, suggesting a strong interaction between the cytokine, its receptor, and syndecan-2, Phosphorylation of tyrosine residues in syndecan-2 associated with the alpha chain of the GM-CSF receptor was increased after cell stimulation by GMCSF. Antisense oligonucleotides that reduced specifically the expression of syndecan-2 inhibited the mitogenic activity of GM-CSF and the activation of extracellular signal-regulated kinase-l induced by the cytokine. Our results indicate functional interactions between syndecan-2 and GM-CSF in osteoblasts, and we propose that syndecan-2 plays a role as a co-receptor for this cytokine. C1 Hop Lariboisiere, INSERM, CNRS, Unite 349, F-75475 Paris 10, France. Univ Angers, Lab Histol Embryol, F-49045 Angers, France. RP Modrowski, D, INSERM, U349, 2 Rue Ambroise Pare, F-75475 Paris 10, France. TC 25 PD MAR 31 PY 2000 VL 275 IS 13 BP 9178 EP 9185 UT ISI:000086206500017 ER PT J AU Harousseau, JL Witz, B Lioure, B Hunault-Berger, M Desablens, B Delain, M Guilhot, F Le Prise, PY Abgrall, JF Deconinck, E Guyotat, D Vilque, JP Casassus, P Tournilhac, O Audhuy, B Solary, E TI Granulocyte colony-stimulating factor after intensive consolidation chemotherapy in acute myeloid leukemia: Results of a randomized trial of the Groupe Ouest-Est Leucemies Aigues Myeloblastiques SO JOURNAL OF CLINICAL ONCOLOGY ID BONE-MARROW TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; STEM-CELL TRANSPLANTATION; HEMATOPOIETIC GROWTH-FACTORS; 1ST COMPLETE REMISSION; ELDERLY PATIENTS; PHASE-III; POSTREMISSION CHEMOTHERAPY; INDUCTION TREATMENT; COOPERATIVE GROUP AB Purpose: Ten years after the first clinical studies, the clinical impact of myeloid growth factors in acute myeloid leukemia is still unclear. One of the objectives of the Groupe Ouest-Est Leucemies Aigues Myeloblastiques (GOELAM) 2 trial was to evaluate the benefit of granulocyte colony-stimulating factor (GCSF) given only after the two courses of intensive consolidation chemotherapy (ICC) used to maintain complete remission (CR). Patients and Methods: One hundred ninety-four patients who were in CR after induction treatment were randomly assigned to receive G-CSF (100 patients) or no G-CSF (94 patients) after two courses of ICC (ICC 1, high-dose cytarabine plus mitoxantrone; ICC 2, amsacrine plus etoposide). G-CSF (filgrastim) was administered from the day after chemotherapy until granulocyte recovery at a daily dose of 5 mu g/kg. Results: In the G-CSF group, the median duration of neutropenia (< 0.5 x 10(9)/L) was dramatically reduced, both after ICC 1 (12 v 19 days, P < .001) and after ICC 2 (20 v 28 days, P < .001). The median duration of hospitalization was also significantly shorter in the G-CSF group (24 v 27 days after ICC 1, P < .001; 29 v 34 days after ICC 2, P < .001). The median duration of intravenous antibiotics was significantly reduced after ICC 1 and ICC 2, and the median duration of antifungal therapy was significantly reduced after ICC 1. However, the incidence of microbiologically documented infections, the toxic death rate, the 2-year disease-free survival, and the 2-year overall survival were not affected by G-CSF administration. Moreover, the median interval between ICC 1 and ICC2 was reduced by only 2 days, and the number of patients undergoing ICC2 was not increased in the G-CSF arm. Conclusion: G-CSF should be administered routinely after ICC to reduce the duration of neutropenia and hospitalization. However, G-CSF did not seem to significantly increase the feasibility of this two-course program or modify overall outcome. (C) 2000 by American Society of Clinical Oncology. C1 Univ Nantes, Dept Hematol, F-44035 Nantes 1, France. Univ Hosp, Dept Hematol, Nancy, France. Univ Hosp, Strasbourg, France. Univ Hosp, Angers, France. Univ Hosp, Amiens, France. Univ Hosp, Tours, France. Univ Hosp, Poitiers, France. Univ Hosp, Rennes, France. Univ Hosp, Brest, France. Univ Hosp, Besancon, France. Univ Hosp, St Etienne, France. Univ Hosp, Reims, France. Univ Hosp, Bobigny, France. Univ Hosp, Clermont Ferrand, France. Ctr Hosp, Colmar, France. Univ Hosp, Dijon, France. RP Harousseau, JL, Univ Nantes, Dept Hematol, 1 Pl Alexis Ricordeau, F-44035 Nantes 1, France. TC 24 PD FEB PY 2000 VL 18 IS 4 BP 780 EP 787 UT ISI:000085401800010 ER PT J AU Metais, I Aubry, C Hamon, B Jalouzot, R Peltier, D TI Description and analysis of genetic diversity between commercial bean lines (Phaseolus vulgaris L.) SO THEORETICAL AND APPLIED GENETICS DE genetic diversity; molecular markers; common bean; germplasm ID FRAGMENT-LENGTH-POLYMORPHISMS; VNTR CORE SEQUENCES; DNA MARKERS; PCR; AMPLIFICATION; PRIMERS; WILD; SIMILARITY; ORIGIN; PROBES AB The effectiveness of RFLP, DAMD-PCR, ISSR and RAPD markers in assessing polymorphism and relationships between 24 commercial lines of Phaseolus vulgaris L.was evaluated. We have used a Phaseolus-specific minisatellite sequence as a probe, which enabled 23 of the bean lines tested to be fingerprinted. Based on the sequence information obtained, primers corresponding to the bean-specific minisatellite core sequence were used in subsequent PCR amplifications. Our observations indicated that while the DAMD-PCR was sensitive in detecting genetic variation between bean species and between accessions of P. vulgaris, when used alone it may be limited in its ability to detect genetic variation among cultivated bean lines due to the low number of loci amplified. Only one out of the five ISSR primers tested was efficient in generating multiple band profiles, which was insufficient to distinguish all the different bean lines. Reproducible RAPD profiles were obtained, and these allowed us to differentiate all the genotypes tested with seven primers. We ultimately used only results from RFLP and RAPD markers to explore the genetic diversity among commercial bean lines. Both analyses led to the same clustering of the bean lines according to their geographical origins (United States or Europe). With respect to the European lines, the results obtained from RAPD data also enable the lines to be clustered according to their creators. C1 UFR Sci, Genet Lab, F-49045 Angers, France. RP Peltier, D, UFR Sci, Genet Lab, 2 Bd Lavoisier, F-49045 Angers, France. TC 23 PD DEC PY 2000 VL 101 IS 8 BP 1207 EP 1214 UT ISI:000166060400006 ER PT J AU Pessaux, P Arnaud, JP Ghavami, B Flament, JB Trebuchet, G Meyer, C Huten, N Champault, G CA Soc Francaise Chirurgie Laparoscop TI Laparoscopic antireflux surgery: comparative study of Nissen, Nissen-Rossetti, and Toupet fundoplication SO SURGICAL ENDOSCOPY-ULTRASOUND AND INTERVENTIONAL TECHNIQUES DE fundoplication; gastroesophageal reflux diesase; laparoscopy; Nissen; Nissen-Rossetti; Toupet ID GASTROESOPHAGEAL REFLUX DISEASE; RANDOMIZED TRIAL; FLOPPY NISSEN AB Background: The aim of this retrospective study was to compare the results of Nissen, Nissen-Rossetti, and Toupet laparoscopic fundoplication in terms of gastroesophageal reflux disease (GERD). Methods: From 1992 to 1996, 1,470 laparoscopic fundoplications were performed using one of three procedures: Nissen (n = 655), Nissen-Rossetti (n = 423), and Toupet(n = 392). Preoperative checkup included esophagogastroduodenoscopy in 1,437 patients (97.7%), esophageal manometry in 934 patients (63.5%), and 24-h pH-metry in 799 patients (54.3%). The results were estimated at 1 month, 3 months, and 2 years. Patients unable to visit the hospital center were contacted by telephone. Results: The three groups were quite similar regarding demographic data such as age, gender, preoperative clinical symptoms, and duration of GERD. One death (0.07%) occurred. At 3 months, there were no differences among the three groups concerning conversion, morbidity, dysphagia, early reintervention, or postoperative length of stay. The length of surgery was more important in the Toupet procedure. In the Nissen group, there were fewer Visick grade I patients but more Visick grade III patients. At 2 years, the recurrence and reintervention rates were similar. The overall residual severe dysphagia rate was 0.35% (n = 5). In the Nissen group, there were fewer Visick grade I patients but more in Visick grade II patients. There was no difference in Visick grade III and IV among the groups. More than 90% of the patients were satisfied (Visick I + Visick II), with no significant difference among the three groups. Conclusions: The results of this study do not differ significantly from the data reported in the Literature, suggesting such surgical techniques are effective and well tolerated, and that both can be properly used in the treatment of GERD. C1 CHU Angers, Dept Visceral Surg, F-49033 Angers 01, France. RP Arnaud, JP, CHU Angers, Dept Visceral Surg, 4 Rue Larrey, F-49033 Angers 01, France. TC 23 PD NOV PY 2000 VL 14 IS 11 BP 1024 EP 1027 UT ISI:000165706100010 ER PT J AU Pessaux, P Tuech, JJ Derouet, N Rouge, C Regenet, N Arnaud, JP TI Laparoscopic cholecystectomy in the elderly - A prospective study SO SURGICAL ENDOSCOPY-ULTRASOUND AND INTERVENTIONAL TECHNIQUES DE elderly; high-risk patients; laparoscopic cholecystectomy ID ACUTE CHOLECYSTITIS; MANAGEMENT AB Background: The aim of this prospective study was to determine the feasability and the complications or benefits of laparoscopic cholecystectomy (LC) in the patients older than 75 years. Methods: From January 1992 to July 1998, a total of 863 patients underwent LC, of these patients, 102 patients older than 75 years (group 1) were compared with 761 younger patients (group 2). Results: In the elderly, 35.3% were at high surgical risk (American Society of Anesthesiology [ASA] III and ASA TV). The conversion rate to open cholecystectomy (OC) was 21.6%. The mean length of hospital stay was 6.9 days for both laparoscopy and conversion. Morbidity and mortality rates were 13.7% and 1%, respectively. No patient suffered intraoperative cardiopulmonary complication, and there was no reoperation in the elderly. Conclusions: Elderly patients experience more complications and longer duration of hospital stay than younger patients. However, our results compare favorably with other OC studies in elderly patients. C1 CHU Angers, Dept Visceral Surg, F-49033 Angers 01, France. RP Tuech, JJ, CHU Angers, Dept Visceral Surg, 4 Rue Larrey, F-49033 Angers 01, France. TC 23 PD NOV PY 2000 VL 14 IS 11 BP 1067 EP 1069 UT ISI:000165706100021 ER PT J AU Lievre, M Gueyffier, F Ekbom, T Fagard, R Cutler, J Schron, E Marre, M Boissel, JP CA The INDANA Steering Comm TI Efficacy of diuretics and beta-blockers in diabetic hypertensive patients - Results from a meta-analysis SO DIABETES CARE ID RANDOMIZED CLINICAL-TRIALS; ISOLATED SYSTOLIC HYPERTENSION; CORONARY HEART-DISEASE; HIGH BLOOD-PRESSURE; ANTIHYPERTENSIVE THERAPY; CARDIOVASCULAR EVENTS; INTERVENTION TRIAL; MILD HYPERTENSION; METAANALYSIS; MORTALITY AB OBJECTIVE - To review the effectiveness of diuretic or beta-blocker-based treatment of hypertension in diabetic patients. RESEARCH DESIGN AND METHODS - A meta-analysis on individual patient data was performed on four trials of the treatment of hypertension in which diabetic patients were included and treated with first-line diuretics or beta-blockers. The main outcomes were the relative risk of death, fatal or nonfatal stroke, fatal or nonfatal coronary events, and major cardiovascular events. RESULTS - There were 92 diabetic patients who received first-line beta-blockers and 1,008 who received diuretics. In the control groups, diabetic patients had nearly twice the risk of any outcome when compared with nondiabetic patients. The same blood pressure reduction was achieved under treatment in the diabetic and nondiabetic patients, except for systolic pressure, which decreased more in the nondiabetic patients at 1 year. In the 15,843 nondiabetic patients, the risk of all four outcomes was reduced significantly in the treated group. In the 2,254 diabetic patients, the risk reduction was significant only for fatal and nonfatal stroke (36%, P = 0.011) and major cardiovascular events (20%, P = 0.032),but not for death (5%, P = 0.65) and fatal or nonfatal coronary events (15%, P = 0.23). However, no heterogeneity was detected between diabetic patients and nondiabetic patients for any outcome. The numbers of outcomes avoided for 1,000 patients treated for 5 years were higher in diabetic patients (e.g., 38 major cardiovascular events) than with nondiabetic patients (e.g., 28 major cardiovascular events). CONCLUSIONS - These results show that hypertensive diabetic patients benefit from first-line treatment with diuretics. No conclusion can be drawn for beta-blockers, owing to the small sample size. C1 Univ Lyon 1, Lyon Hosp, Dept Clin Pharmacol, Equipe Accueil 643, Lyon, France. Dept Community Hlth Sci, Dalby Lund, Sweden. Hypertens & Cardiovasc Rehabil Unit, Louvain, Belgium. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Hosp Angers, Angers, France. RP Lievre, M, Fac Med HRT Laennec, Serv Pharmacol Clin, Rue Guillaume Paradin,BP 8071, F-69376 Lyon 08, France. TC 23 PD APR PY 2000 VL 23 SU Suppl. 2 BP B65 EP B71 UT ISI:000086273600011 ER PT J AU Allain, P Heudi, O Cailleux, A Le Bouil, A Larra, F Boisdron-Celle, M Gamelin, E TI Early biotransformations of oxaliplatin after its intravenous administration to cancer patients SO DRUG METABOLISM AND DISPOSITION ID MASS-SPECTROMETRY; IN-VITRO; PLATINUM; PHARMACOKINETICS; CARBOPLATIN; BINDING; PLASMA; LEAD AB This article deals with the fate of oxaliplatin 1 and 3 h after its i.v. administration (130 mg/m(2)) to three patients. Its binding to plasma proteins and penetration into red blood cells were monitored by chromatography on-line with inductively coupled plasma mass spectrometry. Oxaliplatin biotransformations in plasma ultrafiltrate (PUF) and in urine were studied by chromatography coupled to inductively coupled plasma mass spectrometry or to electrospray ionization mass spectrometry. In plasma, four platinum (Pt) compounds were found. The peaks at 200 and 160 kDa corresponding to gamma-globulins contained 40% of the Pt bound; the peak at 60 kDa corresponding to albumin contained 40% of the Pt found. The peak <2 kDa could correspond to oxaliplatin, to its degradation products, or to adducts between Pt compounds and low-molecular-weight species such as glutathione, L-methionine, and L-cysteine. In PUF and urine, oxaliplatin itself, its degradation products, Pt-(dach)Cl-2, [Pt(dach)(OH2)Cl](+), and species that have the same retention times as Pt(dach)(methionine) and [Pt(dach)](2)(glutathione) were found. One hour after infusion, oxaliplatin in PUF and urine represented 12 and 50% of the total Pt, respectively. Three hours after infusion, oxaliplatin, undetectable in PUF, represented 10% of total Pt in urine. Inside red blood cells, two Pt compounds were found. The Pt peak at 60 kDa corresponding to hemoglobin and the peak <2 kDa corresponding to low-molecular species contained, respectively, 60% and 40% of Pt found. This study demonstrates that in the first hours after its infusion, oxaliplatin, in addition to other Pt compounds, is present in plasma and urine and that Pt is bound to albumin, gamma-globulins, and hemoglobin. C1 CHU Angers, Lab Pharmacol & Toxicol, F-49033 Angers 01, France. Ctr Reg Lutte Contre Canc, Ctr Paul Papin, Dept Med Oncol, Angers, France. Ctr Reg Lutte Contre Canc, Ctr Paul Papin, Dept Clin Pharmacol, Angers, France. RP Allain, P, CHU Angers, Lab Pharmacol & Toxicol, F-49033 Angers 01, France. TC 22 PD NOV PY 2000 VL 28 IS 11 BP 1379 EP 1384 UT ISI:000089909400019 ER PT J AU Raimundo, JM Blanchard, P Ledoux-Rak, I Hierle, R Michaux, L Roncali, J TI Huge enhancement of the quadratic nonlinear optical susceptibility in push-pull chromophores based on bridged dithienylethylene spacers SO CHEMICAL COMMUNICATIONS ID BOND-LENGTH ALTERNATION; HIGHLY EFFICIENT; THERMAL-STABILITY; BANDGAP; HYPERPOLARIZABILITIES; DERIVATIVES; ACCEPTOR; POLYENES; POLYMERS; DONOR AB Replacement of the open chain dithienylethylene pi-conjugating spacer by its bridged analog in push-pull NLO-phores produces a dramatic increase of the quadratic hyperpolarisability. C1 Univ Angers, CNRS, UMR 6501, F-49045 Angers, France. Ecole Normale Super, Lab Photon Quant & Mol, F-94235 Cachan, France. RP Roncali, J, Univ Angers, CNRS, UMR 6501, 2 Bd Lavoisier, F-49045 Angers, France. TC 22 PY 2000 IS 17 BP 1597 EP 1598 UT ISI:000088914800019 ER PT J AU Alexander, J Hirschowitz, A TI An asymptotic vanishing theorem for generic unions of multiple points SO INVENTIONES MATHEMATICAE ID LINEAR-SYSTEMS; INVERSE SYSTEM; SYMBOLIC POWER; HORACE METHOD; INTERPOLATION; SINGULARITIES; SURFACES; CURVES C1 Univ Angers, Dept Math, F-49000 Angers, France. Univ Nice, Dept Math, F-06034 Nice, France. RP Alexander, J, Univ Angers, Dept Math, F-49000 Angers, France. TC 22 PD MAY PY 2000 VL 140 IS 2 BP 303 EP 325 UT ISI:000087197000003 ER PT J AU Lunel, F Cadranel, JF Rosenheim, M Dorent, R Di-Martino, V Payan, C Fretz, C Ghoussoub, JJ Bernard, B Dumont, B Perrin, M Gandjbachkh, I Huraux, JM Stuyver, L Opolon, P TI Hepatitis virus infections in heart transplant recipients: Epidemiology, natural history, characteristics, and impact on survival SO GASTROENTEROLOGY ID POLYMERASE CHAIN-REACTION; NON-B-HEPATITIS; C VIRUS; LIVER-DISEASE; NON-A; BIOPSY PROCEDURES; VIRAL-B; TRANSMISSION; RNA; PREVALENCE AB Background & Aims: We have observed a high prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in heart transplant recipients (HTRs). The aim of this study was to assess the epidemiology, natural history, and clinical and biological characteristics of viral hepatitis in HTRs. Methods: From 1983 to 1992, 874 patients underwent heart transplantation at the Pitie-Salpetriere Hospital, Paris, France, 459 of whom qualified for analysis. A total of 140 patients had posttransplantation hepatitis B, C, or non-A-E. Sixty-nine patients developed HBV infection, 49 HCV infection, 11 HBV-HCV coinfection, and 11 non-A-E hepatitis, Results: HBV was transmitted nosocomially from patient to patient, most likely during endomyocardial biopsies. HCV was mainly transmitted through blood transfusions or the transplanted organ. Clinical and biological findings after 2 years of follow-up showed that 3 patients with an HBV genotype A precore mutant had severe or subfulminant hepatitis and that patients with HBV and HCV infection always progressed to chronicity. In general, patients had mild alanine aminotransferase level increases, a high level of viral replication, and few severe histologic Lesions, except for patients infected by precore HBV mutants. Patients coinfected by HBV and HCV tended to have more severe liver lesions. The survival rate 5 years after transplantation in patients with viral hepatitis (HBV, 81%; HCV, 89%; HBV and HCV coinfection, 100%; non-A-E hepatitis, 73%) was similar to that in patients without liver test abnormalities (76%). The actuarial survival curve was also similar in patients with or without liver test abnormalities. Conclusions: In our experience, histologic liver lesions do not progress rapidly in patients with post-heart transplant infection caused by HBV or HCV. HBV or HCV infection seems to have little impact on the 5-year survival rate of HTRs. C1 CHU Angers, Serv Bacteriovirol, F-49033 Angers, France. Ctr Hosp Creil, Hepatol Unit, Creil, France. Hop Paris, Estab Transfus Sanguine Assistance Publ, Paris, France. Hop La Pitie Salpetriere, Paris, France. Innogenet, Ghent, Belgium. Sante Publ, Paris, France. Chirurg Cardiaque, Paris, France. Hepatogastroenterol, Paris, France. RP Lunel, F, CHU Angers, Serv Bacteriovirol, 4 Rue Larrey, F-49033 Angers, France. TC 21 PD OCT PY 2000 VL 119 IS 4 BP 1064 EP 1074 UT ISI:000089847800022 ER PT J AU Brisset, MN Cesbron, S Thomson, SV Paulin, JP TI Acibenzolar-S-methyl induces the accumulation of defense-related enzymes in apple and protects from fire blight SO EUROPEAN JOURNAL OF PLANT PATHOLOGY DE chemical control; Erwinia amylovora; beta-1,3-glucanases; peroxidases; systemic resistance; CGA 245704 ID SYSTEMIC ACQUIRED-RESISTANCE; DISEASE RESISTANCE; BENZOTHIADIAZOLE; PATHOGENS; CUCUMBER; PLANTS; BETA-1,3-GLUCANASE; ASSOCIATION; PEROXIDASE; INDUCTION AB Acibenzolar-S-methyl (Novartis) is a chemical inducer of systemic acquired resistance in several annual plants. The ability of this novel chemical to induce resistance was studied in a perennial plant (apple) affected by fire blight caused by Erwinia amylovora. Acibenzolar-S-methyl (100 and 200 mg/l active ingredient) protected Golden Delicious seedlings, scions and trees from artificial infection when applied before inoculation. The protection of apple seedlings was similar to the protection obtained with the standard for fire blight control, plantomycin (100 mg/l streptomycin sulfate), applied immediately before inoculation. The mean levels of control in scions in the greenhouse and in trees in orchards were approximately 69% and 50%, respectively. The protection of apple seedlings was constantly associated with the activation of two families of defense-related enzymes, peroxidases and beta-1,3-glucanases. Accumulation of both enzymes was induced locally in treated leaves and systemically, especially for beta-1,3-glucanases, in upper untreated leaves, and was sustained for at least 17 days. These results suggest that acibenzolar-S-methyl promotes induced systemic resistance in apple by increasing defense-related compounds. This chemical could provide a new approach of control of fire blight but its practical use needs further investigation. C1 INRA, Ctr Angers, Unite Ameliorat Especes Fruitieres & Ornementales, F-49071 Beaucouze, France. INRA, Ctr Angers, Unite Pathol Vegetale & Phytobacteriol, F-49071 Beaucouze, France. Utah State Univ, Dept Biol, Logan, UT 84322 USA. RP Brisset, MN, INRA, Ctr Angers, Unite Ameliorat Especes Fruitieres & Ornementales, 42 Rue Georges Morel,BP 57, F-49071 Beaucouze, France. TC 21 PD JUL PY 2000 VL 106 IS 6 BP 529 EP 536 UT ISI:000088588100004 ER PT J AU Hambli, R Potiron, A TI Finite element modeling of sheet-metal blanking operations with experimental verification SO JOURNAL OF MATERIALS PROCESSING TECHNOLOGY DE Von Mises yield criterion; finite element modeling; material shearing mechanisms AB In order to accurately simulate sheet-metal cutting processes by material shearing mechanisms, such as blanking and punching processes, a finite element model valid for the numerical description of such processes has been developed. Damage and crack propagation have been taken into account by means of an elastoplastic constitutive law. To study the effects of variation of processes parameters on the geometry of sheared edges and the force-punch penetration evolution, we have implemented the algorithm of calculation by means of users routine (UMAT) of ABAQUS/Standard finite element code. Final results of the FEM simulation agree with the experimental ones. (C) 2000 Published by Elsevier Science S.A. All rights reserved. C1 ISTIA, LASQUO, F-49000 Angers, France. ENSAM, LPMI, F-49035 Angers, France. RP Hambli, R, ISTIA, LASQUO, 62 Ave Notre Dame Lac, F-49000 Angers, France. TC 21 PD MAY 15 PY 2000 VL 102 IS 1-3 BP 257 EP 265 UT ISI:000086949300039 ER PT J AU Pessaux, P Tuech, JJ Rouge, C Duplessis, R Cervi, C Arnaud, JP TI Laparoscopic cholecystectomy in acute cholecystitis - A prospective comparative study in patients with acute vs chronic cholecystitis SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES DE acute cholecystitis; gallbladder; laparoscopic cholecystectomy; optimal timing ID RANDOMIZED TRIAL; CHOLELITHIASIS; MANAGEMENT AB Background: The aim of this prospective study was to compare the outcome of laparoscopic cholecystectomy (LC) in patients with acute cholecystitis versus those with chronic cholecystitis and to determine the optimal timing for LC in patients with acute cholecystitis. Methods: From January 1991 to July 1998, 796 patients (542 women and 254 men) underwent LC. In 132 patients (67 women and 65 men), acute cholecystitis was confirmed via histopathological examination. These patients were divided into two groups. Group 1 (n = 85) had an LC prior to 3 days after the onset of the symptoms of acute cholecystitis, and group 2 (n = 47) had an LC after 3 days. Results: There were no mortalities. The conversion rates were 38.6% in acute cholecystitis and 9.6% in chronic cholecystitis (p < 10(-8)). Length of surgery (150.3 min vs 107.8 min; p < 10(-9)) postoperative morbidity (15% vs 6.6%; p = 0.001), and postoperative length of stay (7.9 days vs 5 days; p < 10(-9)) were significantly different between LC for acute cholecystitis and elective LC, For acute cholecystitis, we found a statistical difference between the successful group and the conversion group in terms of length of surgery and postoperative stay. The conversion rates in patients operated on before and after 3 days following the onset of symptoms were 27% and 59.54b, respectively (p = 0.0002). There was no statistical difference between early and delayed surgery in terms of operative time and postoperative complications. However, total hospital stay was significantly shorter for group 1. Conclusions: LC for acute cholecystitis is a safe procedure with a shorter postoperative stay, lower morbidity, and less mortality than open surgery. LC should be carried out as soon as the diagnosis of acute cholecystitis is established and preferably before 3 days following the onset of symptoms. Early laparoscopic cholecystectomy can reduce both the conversion rate and the total hospital stay as medical and economic benefits. C1 Dept Visceral Surg, F-49100 Angers, France. RP Arnaud, JP, Dept Visceral Surg, 4 Rue Larrey, F-49100 Angers, France. TC 21 PD APR PY 2000 VL 14 IS 4 BP 358 EP 361 UT ISI:000086678300010 ER PT J AU Pean, JM Menei, P Morel, O Montero-Menei, CN Benoit, JP TI Intraseptal implantation of NGF-releasing microspheres promote the survival of axotomized cholinergic neurons SO BIOMATERIALS DE cholinergic neuron; drug delivery; microsphere; nerve growth factor; neuroprotection; eurotrophic factor ID NERVE-GROWTH-FACTOR; BIODEGRADABLE MICROSPHERES; POLY(D,L-LACTIDE-CO-GLYCOLIDE) MICROSPHERES; STEREOTAXIC IMPLANTATION; BRAIN; RATS; STABILITY; DELIVERY; LESIONS; PATHWAY AB Neurotrophic factors therapy requires their precise delivery to the targeted neuronal population. For this purpose, a wide range of strategies have been developed, and among them the stereotaxic implantation of biodegradable microparticles. To assess the in vivo activity of NGF-releasing PLGA microspheres, unloaded and NGF-loaded microparticles were implanted in the rat brain, near the septal cholinergic neurons, axotomized by an unilateral transection of the fornix-fimbria. Histological analysis at two and six weeks after implantation revealed a non-specific astro- and micro-glial reaction around the microspheres, identical for both unloaded and NGF-loaded microspheres. No neuronal toxicity was noticed, and healthy looking neurons were observed in contact with the microspheres. In the non-treated animals, the percentage of axotomized surviving neurons, when compared to the controlateral intact side, was 31 +/- 2 and 27 +/- 1% at two and six weeks, respectively. Unloaded microspheres caused no protective nor neurotoxic effects (40 +/- 9 and 39 +/- 6% of surviving cholinergic neurons at two and six weeks, respectively). In contrast, NGF-loaded microspheres showed a significant effect on the survival of axotomized cholinergic neurons at two and six weeks after implantation (66 +/- 9 and 61 +/- 5% when compared to the controlateral intact side, respectively). These results show that PLGA microparticles present no neurotoxicity and release sufficient amounts of bioactive NGF to significantly limit the lesion-induced disappearance of cholinergic neurons in the septum during at least six weeks. PLGA microparticles can be used in the future to administer neurotrophic factors in central nervous system disorders. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Fac Pharm, UPRES EA 2169, F-49100 Angers, France. CHU Angers, Serv Neurochirurg, F-40033 Angers, France. RP Menei, P, Fac Pharm, UPRES EA 2169, 16 Blvd Daviers, F-49100 Angers, France. TC 20 PD OCT PY 2000 VL 21 IS 20 BP 2097 EP 2101 UT ISI:000088712700011 ER PT J AU King, GJ Maliepaard, C Lynn, JR Alston, FH Durel, CE Evans, KM Griffon, B Laurens, F Manganaris, AG Schrevens, T Tartarini, S Verhaegh, J TI Quantitative genetic analysis and comparison of physical and sensory descriptors relating to fruit flesh firmness in apple (Malus pumila Mill.) SO THEORETICAL AND APPLIED GENETICS DE apple; fruit; firmness; texture; QTL analysis; genes ID TRAIT LOCI; TOMATO; QTLS AB Texture is a major component of consumer preference for eating-quality in apple. A quantitative genetic analysis of traits associated with fruit-flesh firmness was carried out. This was based on segregation in an unselected mapping population replicated at six sites and harvested over 2 years. Different methods of assessment were compared, and a principal components analysis carried out. Instrumental measures used were Magness-Taylor penetrometer readings, stiffness by acoustic resonance, and a range of sensory descriptors assessed by a trained panel. There were good correlations between some measures, although stiffness was poorly correlated. Whilst genotype by environment effects were large, significant effects were attributable to the genotype, and these were used to detect QTLs. Significant QTLs were detected on seven linkage groups, with large effects on linkage groups L01, L10 and L16. Whilst there was a pool: correlation between acoustic stiffness and other measures, the significant and suggestive QTL detected for stiffness on linkage group L10 did represent a subset of significant QTLs detected for the penetrometer measure. The use of sensory assessment proved valuable in detecting QTLs representing different attributes of fruit texture. The possibility of interaction between significant QTLs: fur fruit texture and other strongly selected traits such as scab resistance and fruit acidity is addressed. C1 Hort Res Int, Warwick CV35 9EF, England. DLO, CPRO, Ctr Plant Breeding & Reprod Res, NL-6700 AA Wageningen, Netherlands. Hort Res Int, Maidstone ME19 6BJ, Kent, England. Ctr Rech Angers, INRA, Stn Ameliorat Especes Fruitieres & Ornamentales, F-49070 Beaucouze, France. Pomol Inst Naoussa, Naoussa 59200, Makedonia, Greece. Katholieke Univ Leuven, Louvain, Belgium. Univ Bologna, Dipartimento Colture Arboree, I-40126 Bologna, Italy. RP King, GJ, Hort Res Int, Warwick CV35 9EF, England. TC 20 PD MAY PY 2000 VL 100 IS 7 BP 1074 EP 1084 UT ISI:000087586500010 ER PT J AU Moreau, MF Gallois, Y Basle, MF Chappard, D TI Gamma irradiation of human bone allografts alters medullary lipids and releases toxic compounds for osteoblast-like cells SO BIOMATERIALS DE bone allograft; lipids; peroxidated lipids; lipofuschine; osteoblast; bone bank; biomaterial; bone substitute ID FREE-RADICALS; TRABECULAR BONE; RABBITS; BANK; ACID; RESORPTION; PRODUCTS; BIOLOGY; DISEASE; GRAFTS AB The uncertainties about the transmission of prion proteins from xenogenic grafts prepared from bovine bone has led to the reconsideration of allogenic bone as a grafting material. Allografting is a complementary technique to autografting nowadays when large bone volumes are necessary. Several preparation techniques have been proposed. Fresh-frozen, freeze-dried and gamma irradiation are the most common. However, a large amount of lipids is present in the medullary spaces (near 70% in weight for a human femoral head). They are known to strongly influence the biocompatibility of the bone graft. The exact changes of lipids upon the sterilization and storage processes are poorly known. The aims of the present study were to appreciate the effects of gamma irradiation on medullary lipids and to identify the cytotoxicity of gamma-irradiated bank bone with/without lipid on cultures of osteoblast-like cells. Bone cores from 8 femoral heads retrieved during prosthesis surgery for arthritis were prepared with a drilling trephine. Cores were either sterilized by gamma radiations (25000 gray) or kept frozen until lipid extraction and lipofuschine-like dosage by Folch's method and fluorometric study. Peroxidated lipids appeared 2 to 3-fold higher in the gamma-irradiated cores than in frozen ones; Slices were prepared from bone cores and were transferred on confluent osteoblast-like cell layers (Saos-2). The raw slices (containing lipids) did not induce cell death. On the other hand, cell death was dramatically increased around the gamma-irradiated slices. Defatted slices which had been sterilized by gamma radiations or UV did not induce cell death. Defatting procedures should be added when preparing bone allografts in human bone banks. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 CHU Angers, Lab Histol Embryol, F-49045 Angers, France. Fac Med, Lab Biochim, F-49045 Angers, France. RP Chappard, D, CHU Angers, Lab Histol Embryol, F-49045 Angers, France. TC 20 PD FEB PY 2000 VL 21 IS 4 BP 369 EP 376 UT ISI:000084833500006 ER PT J AU Franconi, F Lemaire, L Marescaux, L Jallet, P Le Jeune, JJ TI In vivo quantitative microimaging of rat spinal cord at 7T SO MAGNETIC RESONANCE IN MEDICINE DE quantitative microimaging; rat spinal cord; relaxometry; apparent diffusion coefficient; magnetization transfer ID MAGNETIZATION-TRANSFER; RELAXATION-TIMES; DIFFUSION; RESONANCE; GRADIENT; INJURY; MODEL; MRI AB In vivo T-2, ADC, and MT properties of the GM and WM of the rat spinal cord were measured at 7T in the cervical region, The GM T-2, T-2GM = 43.2 +/- 1,0 msec is significantly reduced compared to the WM T-2, T-2WM = 57.0 +/- 1.6 msec. Diffusion is anisotropic for both GM and WM, with a larger ADC value along the cord axis (ADC(GM)//, = 1.05 +/- 0.09 10(-9) m(2) sec(-1) and ADC(WM//) = 1.85 +/- 0.18 10(-9) m(2) sec(-1)) than perpendicular to this plane (ADC(GM perpendicular to) similar to 0.50 * 10(-9) m(2) sec(-1) and ADC(WM perpendicular to) similar to 0.18 * 10(-9) m(2) sec(-1)).The MT properties do not significantly differ between the WM and the GM, but allow one to distinguish the thin CSF layer from the WM, DWI with the sensitizing gradient perpendicular to the cord axis leads to the best contrast between GM and WM in the cervical region. (C) 2000 Wiley-Liss, Inc. C1 Univ Angers, UPRES EA 2169 Vectorisat Particulaire, Angers, France. Univ Angers, Serv Commun RMN, Angers, France. Ecole Natl Vet, Unite Pathol Chirurg, Nantes, France. RP Lemaire, L, Fac Med, Lab Biophys Med, Pavillon Olliver,2 Rue Haute Reculee, F-49045 Angers, France. EM laurent.lemaire@univ-angers.fr TC 19 PD DEC PY 2000 VL 44 IS 6 BP 893 EP 898 UT ISI:000165551700010 ER PT J AU Bouchara, JP Zouhair, R Le Boudouil, S Renier, G Filmon, R Chabasse, D Hallet, JN Defontaine, A TI In-vivo selection of an azole-resistant petite mutant of Candida glabrata SO JOURNAL OF MEDICAL MICROBIOLOGY ID BROTH MACRODILUTION METHOD; FLUCONAZOLE RESISTANCE; ANTIFUNGAL SUSCEPTIBILITY; MULTIDRUG-RESISTANCE; MOLECULAR ANALYSIS; AMPHOTERICIN-B; DRUG EFFLUX; ALBICANS; GENE; MUTATION AB Two isolates of Candida glabrata from the same stool sample from a bone marrow transplant recipient treated with fluconazole, and designated 1084-L for large colonies on yeast extract-peptone-dextrose-agar and 1084-S for small colonies, were analysed. In-vitro susceptibility tests with a commercially available disk diffusion procedure showed that isolate 1084-L had a susceptibility pattern typical of wild-type strains of C, glabrata with sensitivity to polyenes and the presence of resistant colonies randomly distributed within the inhibition zones for all azole compounds except tioconazole, In contrast, isolate 1084-S, which was found by pulsed-field gel electrophoresis and random amplification of polymorphic DNA to be genetically closely related to isolate 1084-L, exhibited cross-resistance to the azole compounds except tioconazole. Determination of MICs by the E-test method confirmed these results, showing that isolate 1084-S had greater sensitivity to amphotericin B and complete resistance to ketoconazole and fluconazole, Growth on agar plates containing glucose or glycerol as the sole carbon source suggested that the resistant isolate had a respiratory deficiency, which was further demonstrated by flow cytometric analysis of the fluorescence of rhodamine 123-stained blastoconidia, Restriction endonuclease analysis of mitochondrial DNA (mtDNA) established the mitochondrial origin of the respiratory deficiency. However, PCR amplification of the mtDNA with primers ML1 and ML6, as well as transmission electron microscopy, suggested a partial deletion of the mtDNA analogous to that described for rho(-) petite mutants of Saccharomyces cerevisiae, Together, these results provided evidence that the selection of azole-resistant petite mutants of C, glabrata may occur in vivo after fluconazole administration, which might explain, therefore, clinical failure of antifungal therapy. C1 CHU Angers, Lab Parasitol Mycol, Grp Etud Interact Hote Parasite, F-49033 Angers 01, France. Biotechnol Lab, UPRES Biocatalyse 2161, F-44322 Nantes, France. CHU Angers, Immunol Lab, F-49033 Angers 01, France. Fac Med, Serv Commun Microscopie Electron, F-49045 Angers, France. RP Bouchara, JP, CHU Angers, Lab Parasitol Mycol, Grp Etud Interact Hote Parasite, 4 Rue Larrey, F-49033 Angers 01, France. TC 19 PD NOV PY 2000 VL 49 IS 11 BP 977 EP 984 UT ISI:000165064100004 ER PT J AU Gouello, JP Asfar, P Brenet, O Kouatchet, A Berthelot, G Alquier, P TI Nosocomial endocarditis in the intensive care unit: An analysis of 22 cases SO CRITICAL CARE MEDICINE DE endocarditis; nosocomial infection; intensive care; echocardiography; Staphylococcus; Candida; intravascular catheter; mortality; prevention ID STAPHYLOCOCCUS-AUREUS BACTEREMIA; PROSTHETIC VALVE ENDOCARDITIS; INFECTIVE ENDOCARDITIS; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; MULTICENTER; ABSCESSES; DIAGNOSIS; THERAPY; STATES AB Objectives: To review the intensive care unit experience of patients with admitted or acquired nosocomial endocarditis (NE) defined according to the Duke criteria. Design: Prospective, cohort study, Setting: University teaching hospital. Patients: We reviewed the records of 22 patients documented with NE during a 6-yr period from 1992 to 1997, Interventions: None. Measurements and Main Results: Twenty-two patients (9 women/13 men) aged 38-83 yrs (mean 65 +/- 9 yrs) had a NE (prevalence of 5 per 1,000 admissions). For six patients, NE was the reason for the admission to the intensive care unit. For 17 patients, the time elapsed between admission and diagnosis of ME was 39 +/- 25 days. Sixteen patients were predisposed to infection and seven had underlying heart conditions that put them at risk for acute endocarditis: three prosthetic valves, two valvular diseases, and two cardiac pacemakers, In 21 cases (one unknown portal of entry), NE was the consequence of bacteremia related to a medical or surgical procedure: 11 intravascular devices, eight surgical wounds, one tracheal procedure, and one leg ulceration. The bacteriologic agents detected in blood cultures were: staphylococci (n = 17), Strepfococcus (n = 2), Pseudomonas aeruginoss (n = 2), and Candida (n = 2), Fourteen patients underwent echocardiography according to cardiac signs (cardiac failure, new cardiac murmur, or embolic event), For the eight remainders, echocardiography was performed systematically because of fever and positive blood cultures. The lesions detected by 21 transthoracic and 17 transesophageal echocardiographs were the following: vegetations (n = 19), myocardial abscesses (n = 5), and valvular perforation (n = 1), On 16 surgical indications, only five patients underwent surgery because the others were in too poor of a condition. The overall mortality was 68% (n = 15) and was directly associated with NE in 36% of cases (n = 8), Seven patients (28%) were discharged 34 days after the diagnosis of endocarditis, Conclusions: NE is a frequent nosocomial infection that occurs late during hospitalization. Persistent fever with positive blood cultures is sufficient symptomology to promptly perform an echocardiogram, The poor prognosis is related to the poor condition of those patients who cannot be referred for surgical treatment. C1 CHU Angers, Serv Reanimat Med, Angers, France. RP Gouello, JP, Ctr Hosp Broussais, Serv Reanimat Polyvalente, 1 Rue MARNE, F-35403 St Malo, France. TC 19 PD FEB PY 2000 VL 28 IS 2 BP 377 EP 382 UT ISI:000085543300015 ER PT J AU Baron, S Battin, J David, A Limal, JM TI Early pubertal development in children adopted from abroad. SO ARCHIVES DE PEDIATRIE DE adoption; puberty, precocious ID GONADOTROPIN-RELEASING-HORMONE; CENTRAL PRECOCIOUS PUBERTY; LEPTIN; GROWTH; GIRLS; AGE; MENARCHE AB Aims. - Precocious puberty has been more frequently observed in the population of children adopted from abroad. A study was therefore carried out to assess the prevalence of this early onset of puberty. Population and methods. - In this study, 13 cases of precocious puberty have been examined in ten adopted girls and three adopted boys, and the clinical characteristics and other contributing factors have been described. In this study group, three of the cases were familial. In addition, a questionnaire was also completed by 99 French families with children adopted from abroad, and analyzed to determine the frequency of early pubertal development. The parameters included were age, weight and height at the time of adoption, date of onset of puberty for the girls age at first menstruation, and current height and weight. Results. - It was determined that the 13 children had a very high growth recovery rate from the time that they arrived in France. For the period from time of adoption to the onset of puberty, mean height increased from -1.3 to +1.5 standard deviation score (SDS) and the mean weight-for-height factor increased from +1.2 to 1.9 SDS. The weight-height recovery rate following adoption seems to be the direct cause of early pubertal development in certain children, notably in those with a particularly rapid growth rate (between 6 years 6 months and 8 years 9 months for the girls, and between 8 and 10 years for the boys). In children adopted at an early age, a 'biological memory' seems to exist regarding the renutrition phenomenon which was instrumental in accelerating the onset of puberty some years after adoption. An analysis of the survey on the adoptive families showed that the frequency of precocious puberty was 44.9% in the group of 49 girls compared to only 8.6% in the group of 35 adopted boys, and that it mainly concerned children from Africa (57%), followed by those from South and Central America (57%), Asia (45%), and Eastern Europe (29%). Conclusion. - A higher rate of precocious puberty was found in the adopted girls, with a significantly lower rate in the adopted boys. The etiological factors involved seemed to be mainly nutritional, and influenced by leptin and insulin-like growth factor I (IGF1) levels. The role of the latter and their interaction with other factors, particularly the ethnic aspect, remains to be determined via the study of a larger series of adopted children. (C) 2000 Editions scientifiques et medicales Elsevier SAS. C1 CHU, Hop Mere & Enfant, Clin Med Pediat, F-44093 Nantes, France. CHU Pellegrin, Hop Enfants, Pediat Clin, F-33076 Bordeaux, France. CHU Angers, Ctr Robert Debre, Dept Pediat, F-49033 Angers, France. RP Baron, S, CHU, Hop Mere & Enfant, Clin Med Pediat, F-44093 Nantes, France. TC 18 PD AUG PY 2000 VL 7 IS 8 BP 809 EP 816 UT ISI:000089447900002 ER PT J AU Romain, S Spyratos, F Descotes, F Daver, A Rostaing-Puissant, B Bougnoux, P Colonna, M Bolla, M Martin, PM TI Prognostic of DNA-synthesizing enzyme activities (thymidine kinase and thymidylate synthase) in 908 T1-T2, N0-N1, M0 breast cancers: A retrospective multicenter study SO INTERNATIONAL JOURNAL OF CANCER ID S-PHASE FRACTION; FLOW-CYTOMETRY; GENE AMPLIFICATION; LABELING INDEX; MITOTIC INDEX; CELL-LINES; KI-67; PROLIFERATION; TISSUE; CARCINOMAS AB Among the methodological approaches of tumor proliferation, thymidine kinase (TK) and thymidylate synthase (TS) assays take into account the specific pathways of pyrimidine synthesis. Studies pointing to a prognostic value of TK and TS in breast cancer involved small numbers of patients. We investigated the prognostic value of these enzymes and their combination in a large retrospective multicenter study. Nine hundred eight T1T2, N0N1, M0 primary breast cancer samples (median follow-up 68 months) were tested. TK and TS were measured in cytosols by using standardized radioenzymatic methods. Although a positive correlation was obtained between TK and TS (p<10(-5)), major discrepancies were observed in some tumors. High levels of both enzymes were associated with large tumor size, histological grade III and steroid receptor-negative tumors. Univariate analysis showed that TK, TS and their combination were predictive of poor metastasis free (MFS) (p < 10(-4); p = 0.004 p < 10(-4)) and disease-free survival (DFS) (p <10(-4) p=0.007; p=0.0001). TK was selected as an independent factor for MFS Cox analysis. It was the only variable selected in node-negative patients. Subgroups with specific outcomes, with possible therapeutic implications, were identified: a) in node-negative patients not receiving adjuvant treatment, TK values in the 4th quartile were associated with poor MFS (p=0.0002) and DFS (p=0.0005) as compared to the other quartiles; b) in node-positive patients receiving adjuvant chemotherapy, low levels of both TK and TS were associated with the highest survival rates (MFS: p=0.04; DFS: p=0.03). Int. J. Cancer 87:860-868, 2000. (C) 2000 Wiley-Liss, Inc. C1 Fac Med Nord, Lab Transfert Oncol Biol, APHM, F-13916 Marseille 20, France. Ctr Rene Huguenin, St Cloud, France. CHU Lyon Sud, Pierre Benite, France. Ctr Paul Papin, Angers, France. CHU, Grenoble, France. CHU, Tours, France. RP Romain, S, Fac Med Nord, Lab Transfert Oncol Biol, APHM, Blvd Pierre Dramard, F-13916 Marseille 20, France. TC 18 PD SEP 15 PY 2000 VL 87 IS 6 BP 860 EP 868 UT ISI:000088874800016 ER PT J AU Penisson-Besnier, I Reynier, P Asfar, P Douay, O Sortais, A Dubas, F Emile, J Malthiery, Y TI Recurrent brain hematomas in MELAS associated with an ND5 gene mitochondrial mutation SO NEUROLOGY ID ENCEPHALOMYOPATHIES C1 CHU Angers, Hop Larrey, Serv Neurol A, Dept Neurol, F-49033 Angers 01, France. CHU Angers, Lab Biochim & Biol Mol, F-49033 Angers, France. CHU Angers, Serv Reanimat Med, F-49033 Angers 01, France. Ctr Hosp Laval, Laval, France. RP Penisson-Besnier, I, CHU Angers, Hop Larrey, Serv Neurol A, Dept Neurol, 4 Rue Larrey, F-49033 Angers 01, France. TC 18 PD JUL 25 PY 2000 VL 55 IS 2 BP 317 EP 318 UT ISI:000088345700036 ER PT J AU Vaillant, JC Nordlinger, B Deuffic, S Arnaud, JP Pelissier, E Favre, JP Jaeck, D Fourtanier, G Grandjean, JP Marre, P Letoublon, C TI Adjuvant intraperitoneal 5-fluorouracil in high-risk colon cancer - A multicenter phase III trial SO ANNALS OF SURGERY ID PROSPECTIVE RANDOMIZED TRIAL; COLORECTAL-CANCER; GASTROINTESTINAL CANCER; LIVER METASTASES; CHEMOTHERAPY; THERAPY; FLUOROURACIL; INFUSION; SURGERY; TUMOR AB Objective To evaluate the results of a prospective multicenter randomized study of adjuvant intraperitoneal 5-fluorouracil (5-FU) administered during 6 days shortly after resection of stages II and III colon cancers. Summary Background Data Systemic adjuvant chemotherapy improves the survival of patients with stage III colon cancer receiving treatment for 6 months. Intraperitoneal chemotherapy theoretically combines peritoneal and hepatic effects. Methods After resection, 267 patients were randomized into two groups. Patients in group 1 (n = 133) underwent resection followed by intraperitoneal administration of 5-FU (0.6 g/m(2)/ day) for 6 days (day 4 to day 10). These patients also received intravenous 5-FU (1 g) during surgery. Patients in group 2 underwent resection alone (n = 134). Results In group 1, 103 patients received the total dose, 18 received a partial dose as a result of technical or tolerance problems, and 12 did not receive the chemotherapy. Rates of surgical death and complications were similar in both groups. Tolerance to treatment was excellent or fair in 97% of the patients and poor in 3%. After a median follow-up of 58 months, 5-year overall survival rates were 74% in group 1 and 69% in group 2; disease-free survival rates were 68% and 62%, respectively. Survival curves were superimposed until 3 years after treatment and began diverging thereafter. Among patients receiving the full treatment, the 5-year disease-free survival rate was improved in the treatment group in patients with stage II cancers but was unchanged in patients with stage III cancers. Conclusions Chemotherapy with intraperitoneal 5-FU administered during a short period after surgery was well tolerated but was not sufficient to reduce the risk of death significantly. However, it reduced the risk of recurrence in stage II cancers. These results suggest that it should be associated with systemic chemotherapy to reduce both local and distant recurrences. C1 Hop Ambroise Pare, Serv Chirurg Digest & Oncol, F-92104 Boulogne, France. Grp Hosp Pitie Salpetriere, Serv Chirurg Digest & HepatoBillaire, F-75634 Paris, France. Hop St Antoine, Ctr Chirurg Digest, F-75571 Paris, France. Fac Med St Antoine, Unite Rech Biomath & Biostat, INSERM, U444, Paris, France. CHU Angers, Serv Chirurg Viscerale, Angers, France. Clin St Vincent, Besancon, France. Hop Bocage, Serv Chirurg Digest Thorac & Cancerol, Dijon, France. Hop Hautepierre, Serv Chirurg Gen Hepat & Endocrinienne, Strasbourg, France. Hop Rangueill, Serv Chirurg Gen & Digest, Toulouse, France. Clin St Marie Therese, Bron, France. Hop St Germain Laye, Serv Chirurg Viscerale & Vasc, St Germain En Laye, France. Hop Michallon, Serv Chirurg Gen & Digest, Grenoble, France. RP Nordlinger, B, Hop Ambroise Pare, Serv Chirurg Digest & Oncol, 9 Ave Charles de Gaulle, F-92104 Boulogne, France. TC 18 PD APR PY 2000 VL 231 IS 4 BP 449 EP 456 UT ISI:000086277400001 ER PT J AU Mendes-Giannini, MJS Taylor, ML Bouchara, JB Burger, E Calich, VLG Escalante, ED Hanna, SA Lenzi, HL Machado, MP Miyaji, M Da Silva, JLM Mota, EM Restrepo, A Restrepo, S Tronchin, G Vincenzi, LR Xidieh, CF Zenteno, E TI Pathogenesis II: Fungal responses to host responses: interaction of host cells with fungi SO MEDICAL MYCOLOGY DE Aspergillus fumigatus; fungus interaction; Histoplasma capsulatum; Paracoccidioides brasiliensis ID ASPERGILLUS-FUMIGATUS CONIDIA; PARACOCCIDIOIDES-BRASILIENSIS CONIDIA; EXTRACELLULAR-MATRIX PROTEINS; ACID-DEPENDENT RECOGNITION; HISTOPLASMA-CAPSULATUM; PULMONARY FIBROSIS; MEMBRANE PROTEINS; GLYCOPROTEIN GP43; CANDIDA-ALBICANS; EUTHYMIC MICE AB Most of our knowledge concerning the virulence determinants of pathogenic fungi comes from the infected host, mainly from animal models and more recently from in vitro studies with cell cultures. The fungi usually present intra- and/or extracellular host-parasite interfaces, with the parasitism phenomenon dependent on complementary surface molecules. Among living organisms, this has been characterized as a cohabitation event, where the fungus is able to recognize specific host tissues acting as an attractant, creating stable conditions for its survival. Several fungi pathogenic for humans and animals have evolved special strategies to deliver elements to their cellular targets that may be relevant to their pathogenicity. Most of these pathogens express surface factors that mediate binding to host cells either directly or indirectly, in the latter case binding to host adhesion components such as extracellular matrix (ECM) proteins, which act as 'interlinking' molecules. The entry of the pathogen into the host cell is initiated by fungal adherence to the cell surface, which generates an uptake signal that may induce its cytoplasmic internalization. Once this is accomplished, some fungi are able to alter the host cytoskeletal architecture, as manifested by a rearrangement of microtubule and microfilament proteins, and this can also induce epithelial host cells to become apoptotic. It is possible that fungal pathogens induce modulation of different host cell pathways in order to evade host defences and to foster their own proliferation. For a number of pathogens, the ability to bind ECM glycoproteins, the capability of internalization and the induction of apoptosis are considered important factors in virulence. Furthermore, specific recognition between fungal parasites and their host cell targets may be mediated by the interaction of carbohydrate-binding proteins, e.g., lectins on the surface of one type of cell, probably a parasite, that combine with complementary sugars on the surface of host-cell. These interactions supply precise models to study putative adhesins and receptor-containing molecules in the context of the fungus-host interface. The recognition of the host molecules by fungi such as Aspergillus fumigatus, Paracoccidioides brasiliensis and Histoplasma capsulatum, and their molecular mechanisms of adhesion and invasion, are reviewed in this paper. C1 Univ Estadual Paulista, Fac Ciencias Farmaceut, Araraquara, SP, Brazil. Univ Nacl Autonoma Mexico, Fac Med, Mexico City 04510, DF, Mexico. CHU Angers, Lab Parasitol Mycol, Grp Etud Interact Hote Parasite, Angers, France. Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05508 Sao Paulo, Brazil. Inst Oswaldo Cruz, Dept Patol, BR-20001 Rio De Janeiro, Brazil. Chiba Univ, Pathogen Fungi & Microbial Toxicoses Res Ctr, Chiba 280, Japan. Corp Invest Biol, Medellin, Colombia. RP Mendes-Giannini, MJS, Fac Ciencias Farmaceut Araraquara, Dept Anal Clin, Rua Expedicionarios Brasil 1621, BR-14801902 Araraquara, Brazil. TC 17 PY 2000 VL 38 SU Suppl. 1 BP 113 EP 123 UT ISI:000166958800013 ER PT J AU Hadjadj, S Gallois, Y Simard, G Bouhanick, B Passa, P Grimaldi, A Drouin, P Tichet, J Marre, M CA GENEDIAB Study Grp; DESIR Study Grp TI Lack of relationship in long-term type 1 diabetic patients between diabetic nephropathy and polymorphisms in apolipoprotein epsilon, lipoprotein lipase and cholesteryl ester transfer protein SO NEPHROLOGY DIALYSIS TRANSPLANTATION DE apolipoprotein E; cholesteryl ester transfer protein; diabetic nephropathy; genetics; lipoprotein lipase; type 1 diabetes ID PLASMA TRIGLYCERIDE; IDDM PATIENTS; MICROALBUMINURIA; ATHEROSCLEROSIS; METAANALYSIS; PROGRESSION; DISEASE; LOCUS; CETP; GENE AB Background. Genetic susceptibility contributes to the risk of diabetic nephropathy. Lipid disorders may favour diabetic nephropathy. Thus polymorphisms in lipid metabolism are candidates for the genetic component of risk for diabetic nephropathy. Methods. We searched for a contribution of the genetic polymorphisms of lipoprotein lipase (LPL), cholesteryl ester transfer protein (CETP) and apolipoprotein epsilon (Apo E) to the development of diabetic nephropathy by studying 494 type 1 diabetic patients with proliferative retinopathy and various stages of diabetic nephropathy (GENEDIAB Study). The selection process ensured that all patients had expressed their risk of chronic complications due to uncontrolled diabetes. Thus the nephropathy stages were largely influenced by genetic background. The lipid profile included fasting plasma total cholesterol (TC), triglycerides (TG), apolipoprotein Al (Apo Al) and B (Apo B), and lipoprotein (a) (Lp(a)). Genetic polymorphisms were determined by PCR-based detection of Apo E (e2/e3/e4), LPL (mutation Asn 291 Ser) and CETP (TaqIB B1/B2). Results. One hundred and fifty-seven patients (32%) had no nephropathy, 104 (21%) incipient nephropathy, 126 (25%) established nephropathy and 107 (22%) advanced nephropathy. There was a significant relationship between the stages of diabetic nephropathy and TC (P = 0.002), TG (P < 0.0001), Apo B (P = 0.0007) or Lp(a) (P = 0.038), but not Apo Al. However the genetic polymorphism distributions of LPL, CETP and Apo did not differ in terms of renal complications. The study power to reject the null hypothesis was 58% for the Apo epsilon genotypes. Conclusion. These results support no or only marginal effects of a genetic basis for lipid disturbances encountered in diabetic nephropathy. C1 Univ Hosp, Angers, France. St Louis Hosp, Paris, France. Pitie Hosp, Paris, France. Jeanne DArc Hosp, Dommartin Les Toul, France. Inst Reg Sante, La Riche, France. RP Marre, M, Hop Bichat, 46 Rue Henri Huchard, F-75018 Paris, France. TC 17 PD DEC PY 2000 VL 15 IS 12 BP 1971 EP 1976 UT ISI:000165657900018 ER PT J AU Fromy, B Merzeau, S Abraham, P Saumet, JL TI Mechanisms of the cutaneous vasodilator response to local external pressure application in rats: involvement of CGRP, neurokinins, prostaglandins and NO SO BRITISH JOURNAL OF PHARMACOLOGY DE capsaicin; CGRP; laser Doppler; neurokinins; NO; pressure; prostaglandins; skin blood flow ID GENE-RELATED PEPTIDE; NK1 RECEPTOR ANTAGONIST; NITRIC-OXIDE SYNTHASE; MUCOSAL BLOOD-FLOW; SENSORY NEURONS; NEUROGENIC INFLAMMATION; SKIN MICROCIRCULATION; L-ARGININE; ANTIDROMIC VASODILATATION; NONPEPTIDE ANTAGONIST AB 1 Local pressure-induced vasodilation (PIV) is a neural vasodilator response to non-nociceptive externally applied pressure in the skin, previously described in humans. We first determined whether PIV exists ill rats and depends on capsaicin-sensitive fibres as it does in humans. We then examined the mediators involved in the efferent pathway of PTV. 2 Cutaneous blood flow was measured by laser Doppler flowmetry during 11.1 Pa s(-1) increases in local applied pressure in anaesthetized rats. The involvement of capsaicin-sensitive fibres in PTV was tested in rats treated neonatally with capsaicin. To antagonize CORP, neurokinin-l, -2, or -3 receptors, different groups of rats were treated with CGRP(8-37), SR140333, SR48968 or SR142801, respectively. Prostaglandins involvement was tested with indomethacin treatment. To inhibit nitric oxide synthase (NOS) activity or specific neuronal NOS, rats were treated with N-G-nitro-L-arginine or 7-nitroindazole, respectively. 3 PIV was found in rats, as in humans. PIV was abolished by neonatal treatment with capsaicin and by administration of CGRP(8-37) but remained unchanged with SR140333, SR48968 and SR142801 treatments. Prostaglandin inhibition resulted in a significant decrease in PIV. Inhibition of NOS abolished PIV, whereas inhibition of neuronal NOS caused a diminution of PN. 4 These data suggest that PIV depends on capsaicin-sensitive fibres in rats, as in humans. II appears that CGRP plays a major role in the PTV, whereas neurokinins have no role. Furthermore, PIV involves a contribution from prostaglandins and depends on endothelial NO, whereas neuronal NO has a smaller role. C1 Fac Med, Physiol Lab, F-49045 Angers, France. RP Saumet, JL, Fac Med, Physiol Lab, F-49045 Angers, France. TC 17 PD NOV PY 2000 VL 131 IS 6 BP 1161 EP 1171 UT ISI:000165377400017 ER PT J AU Kraimps, JL Bouin-Pineau, MH Mathonnet, M De Calan, L Ronceray, J Visset, J Marechaud, R Barbier, J TI Multicentre study of thyroid nodules in patients with Graves' disease SO BRITISH JOURNAL OF SURGERY ID CANCER; CARCINOMA AB Background: The association of Graves' disease with thyroid nodules and thyroid carcinoma is rarely reported. The incidence seems to be increasing according to recent literature. The aim of this multicentre study was to review patients who had surgery for Graves' disease associated with thyroid nodules, and to evaluate the risk of thyroid carcinoma. Methods: A retrospective study was made of 557 consecutive patients who underwent operation for Graves' disease between 1991 and 1997 in five endocrine surgery departments, Each patient underwent clinical, biochemical, ultrasonographic and scintigraphic evaluation. None of the patients had had previous radioactive iodine therapy or external irradiation. Surgery consisted of either a subtotal or total thyroidectomy. Results: Nodules were observed before operation in 140 patients (25.1 per cent). Thyroid carcinoma was diagnosed in 21 patients (15.0 per cent), always inside a nodule. The incidence of thyroid carcinoma associated with Graves' disease was 3.8 per cent (21 of 557 patients): 20 papillary and one follicular carcinoma. The carcinoma was multifocal in two patients. Tumour diameter ranged from 2 to 25 mm. A nodule was palpable in four patients. Conclusion: This multicentre study of patients having thyroidectomy for Graves' disease showed that 3.8 per cent had a carcinoma; the rate of carcinoma in cold nodules was 15.0 per cent. Surgery should be advised in any patient with Graves' disease and a thyroid nodule; the operation should be total thyroidectomy. C1 Jean Bernard Hosp, Dept Endocrine Surg, F-86021 Poitiers, France. Jean Bernard Hosp, Dept Nucl Med, F-86021 Poitiers, France. Jean Bernard Hosp, Dept Endocrinol, F-86021 Poitiers, France. Dupuytren Hosp, Dept Endocrine Surg, Limoges, France. Bretonneau Hosp, Dept Endocrine Surg, Tours, France. Univ Hosp Angers, Dept Endocrine Surg, Angers, France. Laennec Hosp, Dept Endocrine Surg, Nantes, France. RP Kraimps, JL, Jean Bernard Hosp, Dept Endocrine Surg, F-86021 Poitiers, France. TC 17 PD AUG PY 2000 VL 87 IS 8 BP 1111 EP 1113 UT ISI:000088939800023 ER PT J AU Allam, B Paillard, C Auffret, M TI Alterations in hemolymph and extrapallial fluid parameters in the Manila clam, Ruditapes philippinarum, challenged with the pathogen Vibrio tapetis SO JOURNAL OF INVERTEBRATE PATHOLOGY DE shell disease; bivalve; immune defense; lysozyme; hemocyte; bacteria ID BROWN-RING-DISEASE; OYSTERS CRASSOSTREA-VIRGINICA; CAUSATIVE AGENT; HAPLOSPORIDIUM-NELSONI; BACTERIAL CHALLENGE; EASTERN OYSTERS; BIVALVIA; HEMOCYTES; SHELL; RESPONSES AB In a recent study, we demonstrated the presence of defense factors, competent hemocytes and high enzymatic activities (peptidases, hydrolases, lytic, etc.), in the extrapallial fluid, located between the mantle and the shell, of the Manila clam, Ruditapes philippinarum. In Europe, this species is affected by brown ring disease, an epizootic disease caused by the bacterium Vibrio tapetis. The present work focused on the effect of the development of the disease on cellular and humoral defense parameters in the hemolymph and the extrapallial fluid of experimentally infected clams. Results indicate significant changes in total and dead hemocyte counts, as well as modifications in lysozyme activity and protein content, in the hemolymph and extrapallial fluid of challenged animals. Hemocyte counts and lysozyme activity increased significantly in the hemolymph, but particularly in the extrapallial fluid, where the highest values were observed. A healing (recalcification) process was observed 7 weeks following challenge, suggesting defense system efficiency at neutralizing the pathogen. These results are discussed with emphasis on the role of extrapallial fluids in the defense process against invading microorganisms, (C) 2000 Academic Press. C1 Univ Bretagne Occidentale, Inst Univ Europeen de la Mer, UMR 6539, Technopole Brest Iroise, F-29280 Plouzane, France. RP Allam, B, Univ Angers, Lab Ecol Anim, 2 Blvd Lavoisier, F-49045 Angers 01, France. TC 17 PD JUL PY 2000 VL 76 IS 1 BP 63 EP 69 UT ISI:000088586500010 ER PT J AU Allam, B Paillard, C Howard, A Le Pennec, M TI Isolation of the pathogen Vibrio tapetis and defense parameters in brown ring diseased Manila clams Ruditapes philippinarum cultivated in England SO DISEASES OF AQUATIC ORGANISMS DE shell disease; bivalve; bacteria; immune defense; lysozyme; hemocyte ID CRASSOSTREA-VIRGINICA; HAPLOSPORIDIUM-NELSONI; PERKINSUS-MARINUS; CAUSATIVE AGENT; EASTERN OYSTERS; BIVALVIA; MOLLUSCA; CHALLENGE; BACTERIA; GIGAS AB The Manila clam Ruditapes philippinarum was introduced for aquacultural purposes to Europe in the 1970s. In 1987, brown ring disease (BRD), caused by Vibrio tapetis, appeared in clams cultivated in Brouenou (Finistere, France) and later became increasingly widespread and was reported in cultivated and wild clams existing on the Atlantic coasts of France and Spain. The present study reports, for the first time, the presence of BRD in clams cultivated in England. The etiologic bacterium was isolated and identified using bacteriological and serological techniques. The defence response of affected clams was also studied and significant changes in the hematological and biochemical characteristics of hemolymph and extrapallial fluids were demonstrated. Significant mobilization of hemocytes toward the extrapallial fluids, in contact with the main site of infection (mantle-periostracal lamina area), was observed, suggesting a role for these pseudo-internal compartments in the preservation of clam health. C1 Univ Bretagne Occidentale, Inst Univ Europeen Mer, UMR 6539, Technopole Brest Iroise, F-29280 Plouzane, France. CEFAS, Weymouth Lab, Weymouth DT4 8UB, Dorset, England. RP Allam, B, Univ Angers, Lab Ecol Anim, 2 Blvd Lavoisier, F-49045 Angers, France. TC 17 PD JUN 19 PY 2000 VL 41 IS 2 BP 105 EP 113 UT ISI:000088642600003 ER PT J AU Streubel, A Siepmann, J Peppas, NA Bodmeier, R TI Bimodal drug release achieved with multi-layer matrix tablets: transport mechanisms and device design SO JOURNAL OF CONTROLLED RELEASE DE bimodal drug release; multi-layer tablet; release mechanism; modeling; HPMCAS ID POLYMER DISENTANGLEMENT CONCENTRATION; ORDER SUSTAINED-RELEASE; HYDROPHILIC MATRICES; HYDROXYPROPYLMETHYL CELLULOSE; DIFFUSIONAL MATRICES; DISSOLUTION; DELIVERY; BIOAVAILABILITY; VISCOSITY; REPTATION AB The aim of this study was to develop new multi-layer matrix tablets to achieve bimodal drug release profiles (fast release/slow release/fast release). Hydroxypropyl methylcellulose acetate succinate (HPMCAS, type MF) was chosen as a matrix former, because it is water-insoluble at low, and water-soluble at high pH values. Studies focused on the elucidation of the drug release mechanisms from HPMCAS-MF:drug tablets. In 0.1 N HCl the resulting release kinetics can be described using Fick's second law of diffusion, taking into account axial and radial mass transfer in cylindrical geometry. As the diffusion coefficients are found to be constant and the boundary conditions to be stationary, these systems are purely drug diffusion-controlled In contrast, the dominating mass transport phenomena in phosphate buffer pH 7.4 are more complex. Due to polymer dissolution the resulting matrix structure is time-variant, leading to increasing drug diffusion coefficients and decreasing tablet dimensions, and thus moving boundary conditions. Drug release is affected by water imbibition, drug diffusion and polymer dissolution and is faster compared to 0.1 N HCl. With knowledge of these underlying release mechanisms, multi-layer matrix tablets were developed to achieve bimodal drug release. HPMCAS-MF:drug mixtures were used as tablet cores. As expected, changing the release medium from 0.1 N HCl to phosphate buffer pH 7.4 after 2 h, lead to a significant increase in drug release. The abruptness of this rate change could be enhanced by adding two drug-free HPMCAS-MF barrier layers tone on each side) to the system. The addition of a fourth, drug-containing and fast disintegrating initial dose layer yielded the desired bimodal drug release patterns. Tie process and formulation parameters affecting the resulting release rates were investigated using theophylline and acetaminophen as model drugs. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ Angers, Coll Pharm, F-49100 Angers, France. Free Univ Berlin, Coll Pharm, D-12169 Berlin, Germany. Purdue Univ, Sch Chem Engn, W Lafayette, IN 47907 USA. RP Bodmeier, R, Univ Angers, Coll Pharm, 16 Blvd Daviers, F-49100 Angers, France. TC 16 PD DEC 3 PY 2000 VL 69 IS 3 BP 455 EP 468 UT ISI:000166067200013 ER PT J AU Moran, C Azziz, R Carmina, E Dewailly, D Fruzzetti, F Ibanez, L Knochenhauer, ES Marcondes, JAM Mendonca, BB Pignatelli, D Pugeat, M Rohmer, V Speiser, PW Witchel, SF TI 21-Hydroxylase-deficient nonclassic adrenal hyperplasia is a progressive disorder: A multicenter study SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY DE acne; adrenal hyperplasia; clitoromegaly; 21-hydroxylase; hirsutism ID ACNE-VULGARIS; DEFICIENCY; WOMEN; HIRSUTISM; HYPERANDROGENISM; STIMULATION; PUBERTY AB OBJECTIVE: Our aim was to determine whether the clinical features of 21-hydroxylase-deficient nonclassic adrenal hyperplasia are correlated with either age at symptom onset or age at presentation, or both, and with the degree of adrenocortical abnormality. STUDY DESIGN: In a multicenter cohort design 220 women with nonclassic adrenal hyperplasia, with a basal or adrenocorticotropic hormone-stimulated 17-hydroxyprogesterone level >30.3 nmol/L, were studied, either prospectively (n = 39) or retrospectively (n = 181). Patients were stratified by age of presentation into 5 groups: (1) <10 years (n = 25), (2) 10 to 19 years (n = 64), (3) 20 to 29 years (n = 83), (4) 30 to 39 years (n = 30), and (5) 40 to 49 years (n = 16). Two patients >50 years old were excluded from the analysis because of age. RESULTS: Ninety-two percent of patients <10 years old had premature pubarche at presentation, whereas clitoromegaly and acne were each present in only 20% of these younger subjects. With only patients 10 years old considered, presenting clinical features included hirsutism (59%), oligomenorrhea (54%), acne (33%); infertility (13%), clitoromegaly (10%), alopecia (8%), primary amenorrhea (4%), and premature pubarche (4%). Among the patients greater than or equal to 10 years old, the prevalence but not the degree of hirsutism increased significantly with age. Basal levels of 17-hydroxyprogesterone in adolescents were significantly higher than the levels found either in children (<10 years old) or women 40 to 49 years old (P <.01 and P <.03, respectively), although no difference was noted in the stimulated 17-hydroxyprogesterone levels between age groups: The adrenocorticotropic hormone-stimulated levels but not the basal levels of 17-hydroxyprogesterone were significantly higher in patients with clitoromegaly than in women without clitoromegaly. Alternatively, there were no differences in either basal or stimulated 17-hydroxyprogesterone levels between patients with and those without hirsutism, acne, or alopecia. CONCLUSION: In children 10 years old the most common presenting complaint was premature pubarche, whereas hirsutism and oligomenorrhea were more common in older patients. The prevalence of hirsutism increased with age, suggesting the progressive nature of nonclassic adrenal hyperplasia. Furthermore, the adrenocorticotropic hormone-stimulated levels of 17-hydroxyprogesterone were higher in patients with clitoromegaly, which suggests that the degree of adrenocortical dysfunction in nonclassic adrenal hyperplasia determines, at least in part, the clinical presentation. C1 Univ Alabama, Dept Obstet & Gynecol, Div Reprod Biol & Endocrinol, Birmingham, AL 35249 USA. Univ Alabama, Dept Med, Birmingham, AL 35249 USA. Inst Mexicano Seguro Social, Res Unit Reprod Med, Mexico City, DF, Mexico. Univ Palermo, Palermo, Italy. CHU Lille, F-59037 Lille, France. Univ Pisa, Pisa, Italy. Univ Barcelona, Hosp Sant Joan de Deu, Barcelona, Spain. Hosp Clin, Sao Paulo, Brazil. Fac Med Porto, Porto, Portugal. Hospices Civils Lyon, Lyon, France. CHU Angers, Angers, France. N Shore Univ Hosp, Manhasset, NY USA. Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. RP Azziz, R, Univ Alabama, Dept Obstet & Gynecol, Div Reprod Biol & Endocrinol, 618 S 20th St,549 OHB, Birmingham, AL 35249 USA. TC 16 PD DEC PY 2000 VL 183 IS 6 BP 1468 EP 1474 UT ISI:000165952000034 ER PT J AU Briard, M Le Clerc, V Grzebelus, D Senalik, D Simon, PW TI Modified protocols for rapid carrot genomic DNA extraction and AFLP (TM) analysis using silver stain or radioisotopes SO PLANT MOLECULAR BIOLOGY REPORTER DE AFLP; DNA extraction; electrophoresis; molecular markers; polyacrylamide; radioactivity; silver staining ID POLYACRYLAMIDE GELS AB AFLP(TM) is one of the most frequently used techniques for identification of molecular markers. We have modified the procedures for genomic DNA extraction, AFLP product generation and silver staining in order to speed up analyses and screen large numbers of plant samples. Using this protocol, we were able to achieve an 82% reduction of costs without compromising the reliability and quality of data gathered. C1 Inst Natl Hort, Angers, France. Krakow Agr Univ, Krakow, Poland. Univ Wisconsin, USDA ARS, Madison, WI 53706 USA. TC 16 PY 2000 VL 18 IS 3 BP 235 EP 241 UT ISI:000165703900003 ER PT J AU Triki, S Berezovsky, F Pala, JS Coronado, E Gomez-Garcia, CJ Clemente, JM Riou, A Molinie, P TI Oxalato-bridged dinuclear complexes of Cr(III) and Fe(III): Synthesis, structure, and magnetism of [(C2H5)(4)N](4)[MM '(ox)(NCS)(8)] with MM ' = CrCr, FeFe, and CrFe SO INORGANIC CHEMISTRY ID X-RAY; NETWORKS; FIELD; CLUSTERS; EXCHANGE; LAYERS; COPPER; DESIGN; LIGAND AB A new series of homo- and heterometallic oxalato-bridged dinuclear compounds of formulas [Et4N](4)[MM'(ox)(NCS)(8)] ([Et4N](+) = [(C2H5)(4)N](+); ox = C2O42-) with MM' = Cr(III)-Cr(III) (1), Fe(III)-Fe(III) (2), and Cr(III)-Fe(III) (3) is reported. They have been structurally characterized by infrared spectra and single-crystal X-ray diffraction. The three compounds are isostructural and crystallize in the orthorhombic space group Cmca with Z = 8, a = 16.561(8) Angstrom, b = 13.481(7) Angstrom, and c = 28.168(8) Angstrom for 1, a = 16.515(2) Angstrom, b = 13.531(1) Angstrom, and c = 28.289(4) Angstrom for 2, a = 16.664(7) Angstrom, b = 13.575(6) Angstrom, and c = 28.386(8) Angstrom for 3. The structure of 3 is made up of a discrete dinuclear anion [CrFe(ox)(NCS)(8)](4-) and four disordered [Et4N](+) cations, each of them located on special positions. The anion, in a crystallographically imposed C-2h symmetry, contains metal cations in distorted octahedral sites. The Cr(ox)Fe group, which is planar within 0.02 Angstrom, presents an intramolecular metal-metal distance of 5.43 Angstrom. Magnetic susceptibility measurements indicate antiferromagnetic pairwise interactions for 1 and 2 with J = -3.23 and -3.84 cm(-1), respectively, and ferromagnetic Cr-Fe coupling with J = 1.10 cm(-1) for 3 (J being the parameter of the exchange Hamiltonian H = -2JS(1)S(2)). The ESR spectra at different temperatures confirm the magnetic susceptibility data. C1 Univ Bretagne Occidentale, CNRS, UMR 6521, F-29285 Brest, France. Univ Valencia, Dept Quim Inorgan, E-46100 Burjassot, Spain. Univ Angers, CNRS, UMR 6501, F-49045 Angers, France. Univ Nantes, CNRS, UMR 6502, F-44072 Nantes, France. RP Triki, S, Univ Bretagne Occidentale, CNRS, UMR 6521, F-29285 Brest, France. TC 16 PD AUG 21 PY 2000 VL 39 IS 17 BP 3771 EP 3776 UT ISI:000088959100008 ER PT J AU Apperloo, JJ Raimundo, JM Frere, P Roncali, J Janssen, RAJ TI Redox states and associated interchain processes of thienylenevinylene oligomers SO CHEMISTRY-A EUROPEAN JOURNAL DE conducting materials; oligomers; pi interactions; radical ions; redox chemistry ID MODEL THIOPHENE OLIGOMERS; CHAIN-LENGTH DEPENDENCE; CONDUCTING POLYMERS; CATION RADICALS; PI-DIMERS; CONJUGATED OLIGOMERS; REVERSIBLE DIMERIZATION; ELECTRONIC-PROPERTIES; POLYTHIOPHENE MODELS; OPTICAL-TRANSITIONS AB The electronic structure of successive redox states of two series of thienylenevinylene oligomers (nTVs, n=4, 5, 6, 8, and 12) that carry hexyl substituents at the alpha- or beta-positions in order to increase the solubility was investigated in detail by means of UV/Vis/near-IR and ESR spectroscopy in solution. The nTV redox states have been fully characterized up to the dication for the shorter oligomers (n less than or equal to 6) and up to the tetracation for the longer oligomers (n greater than or equal to 8). While the monocation radicals of the nTVs exhibit two dipole-allowed electronic transitions in the Vis/near-IR region, all the higher oxidized states invariably show a single strong absorption in the near-IR region. The electronic transitions of the various oxidized states and those of their vibronic replicas shift to lower energies with increasing conjugation length. The ESR spectra, recorded as a function of the degree of oxidation, provide evidence for the presence of electron spin in the odd-charged and the absence of spin in even-charged cations. Variable-temperature UV/Vis/near-IR and ESR spectroscopy establish that the tendency of the nTV monocation radicals to form spin-less pi dimers in solution strongly depends on the number of solubilizing hexyl groups. While the oligomers that carry two hexyl chains at the alpha-positions of the terminal thiophenes (alpha-nTVs) readily form pi dimers at low temperature, the oligomers that carry hexyl groups on the beta- and beta'-positions of every thiophene ring (beta-nTVs) do not form pi dimers. Low-temperature UV/Vis/near-IR and ESR experiments on solutions in which neutral and singly oxidized nTVs are simultaneously present, reveal the occurrence of interchain interactions between these two species, accompanied by a pronounced change in the existing disproportionation equilibrium. C1 Eindhoven Univ Technol, Lab Macromol & Organ Chem, NL-5600 MB Eindhoven, Netherlands. Univ Angers, CNRS UMR 6501, F-49045 Angers, France. RP Roncali, J, Eindhoven Univ Technol, Lab Macromol & Organ Chem, POB 513, NL-5600 MB Eindhoven, Netherlands. TC 16 PD MAY 2 PY 2000 VL 6 IS 9 BP 1698 EP 1707 UT ISI:000086967800021 ER PT J AU Fromy, B Abraham, P Saumet, JL TI Progressive calibrated pressure device to measure cutaneous blood flow changes to external pressure strain SO BRAIN RESEARCH PROTOCOLS DE C fiber; neural control of skin blood flow; pressure strain; laser Doppler; human ID HUMAN-SKIN; HUMAN HAND; DOPPLER; PLETHYSMOGRAPHY AB The present methodological paper describes a simple and useful device for local, external pressure application, The mechanical devices, the difficulties, the time required, the possibilities and limitations of the technique to apply a progressive calibrated pressure and to measure cutaneous blood flow with a laser Doppler probe at the same site are discussed. This technique was used to study the effects of local pressure on the cutaneous blood flow with laser Doppler technique. Use of this protocol has provided evidence for a transient cutaneous vasodilation in the human hand during progressive externally applied pressure strain. Results from our laboratory thus far suggest that this vasodilator response is mediated by small sensory nerve fibres in the skin. (C) 2000 Elsevier Science B.V. All rights reserved. C1 CHU Angers, Lab Physiol & Explorat Vasc, F-49033 Angers 01, France. RP Saumet, JL, CHU Angers, Lab Physiol & Explorat Vasc, F-49033 Angers 01, France. TC 16 PD APR PY 2000 VL 5 IS 2 BP 198 EP 203 UT ISI:000086907300012 ER PT J AU Akoudad, S Roncali, J TI Modification of the electrochemical and electronic properties of electrogenerated poly(3,4-ethylenedioxythiophene) by hydroxymethyl and oligo(oxyethylene)substituents SO ELECTROCHEMISTRY COMMUNICATIONS DE polythiophene; polyether; electropolymerization; 3,4-ethylenedioxythiophene; low bandgap ID CONJUGATED POLYMERS; CONDUCTING POLYMERS; 3,4-ETHYLENEDIOXYTHIOPHENE; POLY(THIOPHENES); BANDGAP; OXYGEN AB Ethylenedioxythiophene (EDOT) derivatives with hydroxymethyl and oligo(oxyethylene) groups covalently attached at the ethylenedioxy bridge have been synthesized. The hydroxymethyl group considerably increases the ability of EDOT to electropolymerize in water and the electroactivity of the polymer in aqueous media. The electrochemical and optical properties of the oligo(oxyethylene)-substituted polymer reveal a negative shift of the oxidation potential and a significant enhancement of the effective conjugation length with a 0.10 eV decrease of the bandgap. The optical spectra of the polymer undoped in the presence and absence of oxygen indicate a high sensitivity of the polymer towards molecular oxygen, suggesting possible spontaneous doping by molecular oxygen. (C) 2000 Elsevier Science S.A. All rights reserved. C1 Univ Angers, CNRS, UMR 6501, F-49045 Angers, France. RP Roncali, J, Univ Angers, CNRS, UMR 6501, 2 Blvd Lavoisier, F-49045 Angers, France. TC 16 PD JAN PY 2000 VL 2 IS 1 BP 72 EP 76 UT ISI:000084783500017 ER PT J AU Wrynn, AS Mac Sweeney, CP Franconi, F Lemaire, L Pouliquen, D Herlidou, S Leonard, BE Gandon, JM de Certaines, JD TI An in-vivo magnetic resonance imaging study of the olfactory bulbectomized rat model of depression SO BRAIN RESEARCH DE olfactory bulbectomy; animal model of depression; degeneration; MRI; ventricular enlargement ID ANATOMY; CORTEX; STRESS AB The olfactory bulbectomized (OB) rat is a well-accepted animal model of depression. The present magnetic resonance imaging (MRI) investigation demonstrates alterations in signal intensities in cortical, hippocampal, caudate and amygdaloid regions in OB animals, but not in sham operated controls. Ventricular enlargement was also evident in OB animals. These alterations have implications with regard to the face and construct validity of this model. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Biotrial, Preclin Pharmacol Unit, Rennes, France. Natl Univ Ireland Univ Coll Galway, Dept Pharmacol, Galway, Ireland. Fac Sci Angers, Serv Commun RMN, Angers, France. Fac Med, Biophys Lab, F-49045 Angers, France. Fac Med, LRMBM, Rennes, France. RP Wrynn, AS, Novartis Pharma AG, Mental Hlth Unit, WSJ 386-3-26, CH-4002 Basel, Switzerland. TC 15 PD OCT 6 PY 2000 VL 879 IS 1-2 BP 193 EP 199 UT ISI:000089762900025 ER PT J AU Damgaard, D Nielsen, MB Lau, J Jensen, KB Zubarev, R Levillain, E Becher, J TI Synthesis of linear oligo-TTFs and their [2]rotaxanes with cyclobis(paraquat-p-phenylene) SO JOURNAL OF MATERIALS CHEMISTRY ID TETRATHIAFULVALENE; ROTAXANES; <3>ROTAXANE; CATENANES AB Two linear oligo-TTFs were synthesised employing a stepwise strategy involving two different thiolate protecting groups. These linear TTFs were incorporated into donor-acceptor rotaxanes with the cyclic acceptor, cyclobis(paraquat-p-phenylene). Moreover, a prototype rotaxane based on a bis(pyrrolo)-TTF was prepared and studied. C1 Odense Univ, Dept Chem, Univ So Denmark, DK-5230 Odense M, Denmark. IMMO, CNRS, UMR 6501, F-49045 Angers, France. RP Damgaard, D, Odense Univ, Dept Chem, Univ So Denmark, Campusvej 55, DK-5230 Odense M, Denmark. TC 15 PY 2000 VL 10 IS 10 BP 2249 EP 2258 UT ISI:000089359800008 ER PT S AU Ritz, P CA Investigators TI Body water spaces and cellular hydration during healthy aging SO IN VIVO BODY COMPOSITION STUDIES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES ID FAT-FREE BODY; NEUTRON-ACTIVATION ANALYSIS; FREE MASS; ELDERLY WOMEN; OLDER ADULTS; MODEL; DENSITY; YOUNG; AGE; ABSORPTIOMETRY AB Age-related changes in the proportions of intracellular or extracellular water to total body water and in the ratio of total body water to fat-free mass are debatable. These are important issues both fur medical reasons (dehydration is a threat in the diseased elderly) and for methodological reasons (most techniques for assessing of body composition assume constant hydration of the fat-free mass), This study compared hydration in young and elderly (60 years) people, In the first part of the study, we analyzed the literature and computed the ratio of total body water over fat-free mass, Hf. Eligible studies involved independent measurements of fat-free mass and total body water. Hf did not appear to change with age. The second part of this study computed Hf in 103 individuals studied in our laboratory, The mean values were not different in young (73.2 +/- 2.4%) and elderly people (73.4 +/- 2.4%). At all ages, the proportion of intracellular or extracellular water las measured by bromide dilution) to total body water las measured by oxygen 18 dilution) was similar The same finding holds for the proportion of intracellular water to fat-free mass. We conclude that hydration of fat-free mass and cellular hydration are not affected in healthy aging. C1 CHU Angers, Serv Med B, F-49033 Angers 1, France. RP Ritz, P, CHU Angers, Serv Med B, F-49033 Angers 1, France. TC 15 PY 2000 VL 904 BP 474 EP 483 UT ISI:000088775500089 ER PT J AU Tuveri, R Jaffredo, F Lunel, F Nalpas, B Pol, S Feray, C Marcellin, P Thibault, V Delagneau, JF Opolon, P Scarpa, B Brechot, C Thiers, V TI Impact of TT virus infection in acute and chronic, viral- and non viral-related liver diseases SO JOURNAL OF HEPATOLOGY DE non A-non G virus; polymerase chain reaction; TT virus ID HEPATITIS-G VIRUS; NON-A-HEPATITIS; NON-B-HEPATITIS; BLOOD-DONORS; POSTTRANSFUSION HEPATITIS; MOLECULAR-CLONING; UNKNOWN ETIOLOGY; TRANSFUSION; PREVALENCE; EXCRETION AB Background/Aims: The prevalence and pathogenicity of TT virus, recently identified in patients with non A-non G post-transfusional hepatitis, are questioned. Methods: We investigated the impact of this new viral infection in a large series of patients with non A-non G, cryptogenic, non-viral and viral-related, acute and chronic liver diseases (n=577) and blood donors (n=300). TTV DNA was detected in serum by hemi-nested polymerase chain reaction, Phylogenetic analysis was performed in 13 isolates. Results: TTV DNA was detected in 6/25 and 15/127 patients with cryptogenic non A-non G acute and chronic liver disease, respectively. TTV DNA positive subjects with post-transfusional acute hepatitis scored negative before transfusion. TTV prevalence was increased in patients with cryptogenic non A-non G acute and chronic liver disease compared to blood donors (6/300; p<0.001) and non-viral-related chronic liver diseases (6/137; p<0.05), TTV/HBV coinfection was frequently identified (35/147), but this was not the case for HCV-infected subjects (4/77), Transaminase activity or liver histological score was not significantly increased among TTV positive, HBV infected or non A-non G patients. The HBV infection and Mediterranean origin were the risk factors associated with TTV infection. The majority of analysed sequences clustered in genotype 1 (8=1b; 3=1a). Two isolates showed homology do genotype 2. Conclusions: These results support the view that TTV is a widely spread infectious agent with a weak pathogenicity, It raises the possibility, however, that TTV might be implicated in a few cases of acute and chronic non A-non G hepatitis. TTV-DNA-analysed sequences are related to genotypes 1 and 2 described in Europe. C1 Necker Inst, INSERM, U370, F-75730 Paris 15, France. Necker Univ, Necker Inst, CNR Viral Hepatitis, Paris, France. Necker Univ, Inst Pasteur, CNR Viral Hepatitis, Paris, France. Univ Cagliari, Dept Publ Hlth, I-09124 Cagliari, Italy. Necker Hosp, Liver Unit, Paris, France. Sanofi Diagnost Pasteur, Marnes La Coquette, France. Hop Paul Brousse, Hepatobiliary Ctr, Villejuif, France. CHU Angers, Microbiol & Virol Lab, Angers, France. Beaujon Hosp, Liver Unit, Clichy, France. Hop La Pitie Salpetriere, Dept Virol, Paris, France. Hop La Pitie Salpetriere, Liver Unit, Paris, France. RP Brechot, C, Necker Inst, INSERM, U370, 156 Rue Vaugirard, F-75730 Paris 15, France. TC 15 PD JUL PY 2000 VL 33 IS 1 BP 121 EP 127 UT ISI:000087896400018 ER PT J AU Lefrere, F Hermine, O Belanger, C Francois, S Tilly, H de La Cour, JCL Valensi, F Varet, B Troussard, X TI Fludarabine: an effective treatment in patients with splenic lymphoma with villous lymphocytes SO LEUKEMIA DE splenic lymphoma with villous lymphocytes; purine analogue; fludarabine ID DIFFERENTIAL-DIAGNOSIS; DISORDERS AB Splenic lymphoma with villous lymphocytes (SLVL) is a B cell chronic lymphoproliferative disorder. Splenectomy and/or chlorambucil are usually regarded as the most effective treatment in SLVL patients. However, a few patients relapse and the second-line treatment remains questionable. In a retrospective study, we evaluated the efficacy and toxicity of fludarabine (FDR) in 10 SLVL patients. The median duration between diagnosis and treatment was 17 months (range, 1-30). Two patients were previously untreated. The patients received FDR 25 mg/m(2)/day by venous infusion for 5 days with a median of four cycles of chemotherapy (range, 2-6). All patients were assessable: five patients achieved a good and persistent response after a median follow-up of 14 months (5-31), two achieved a good response but relapsed after a follow-up of 15 and 36 months. One out of the three partial responders have a persistent response. The treatment was well tolerated. FDR appears to be an efficient therapy with a favorable toxicity profile for patients in relapse after splenectomy or resistant to CLB. Furthermore it could constitute an alternative to splenectomy in older patients. A longer follow-up and the study of a larger group of patients are warranted to confirm our findings. C1 Grp Hosp Necker Enfants Malad, Serv Hematol Adultes, F-75743 Paris 15, France. CHU Angers, Serv Malad Sang, Angers, France. Ctr Henri Becquerel, Dept Hematol, F-76038 Rouen, France. Ctr Hosp Nevers, Nevers, France. Hop Necker Enfants Malad, Hematol Lab, Paris, France. CHU Caen, Hematol Lab, F-14000 Caen, France. RP Lefrere, F, Grp Hosp Necker Enfants Malad, Serv Hematol Adultes, 149-161 Rue Sevres, F-75743 Paris 15, France. TC 15 PD APR PY 2000 VL 14 IS 4 BP 573 EP 575 UT ISI:000086406200003 ER PT J AU Rachet, F Chrysos, M Guillot-Noel, C Le Duff, Y TI Unique case of highly polarized collision-induced light scattering: The very far spectral wing by the helium pair SO PHYSICAL REVIEW LETTERS ID RAMAN-SPECTRA; POLARIZABILITY; DIATOM AB Contrary to what has been observed thus far collision-induced light scattering (CILS) can be completely polarized. This exceptional behavior characterizes the very far wing of the binary CILS spectrum by gaseous helium. This conclusion is drawn from an experimental study of the depolarization ratio of He-2 in a much extended, previously unexplored, spectral domain. Our analysis shows that this property, unique thus far, is mainly due to an almost perfect cancellation between polarization and exchange pair polarizability contributions to the depolarized spectrum, taking place at internuclear distances shorter than the atomic diameter. C1 Univ Angers, CNRS, EP 130, Lab Proprietes Opt Mat & Applicat, F-49045 Angers, France. RP Rachet, F, Univ Angers, CNRS, EP 130, Lab Proprietes Opt Mat & Applicat, 2 Blvd Lavoisier, F-49045 Angers, France. TC 15 PD MAR 6 PY 2000 VL 84 IS 10 BP 2120 EP 2123 UT ISI:000085650100018 ER PT J AU Gillet, P Barrat, JA Heulin, T Achouak, W Lesourd, M Guyot, F Benzerara, K TI Bacteria in the Tatahouine meteorite: nanometric-scale life in rocks SO EARTH AND PLANETARY SCIENCE LETTERS DE meteorites; bacteria; alteration; carbonates; exobiology ID MARTIAN METEORITE; ALH84001; AQUIFERS; MARS AB We present a study of the textural signature of terrestrial weathering and related biological activity in the Tatahouine meteorite. Scanning and transmission electron microscopy images obtained on the weathered samples of the Tatahouine meteorite and surrounding soil show two types of bacteria-like forms lying on mineral surfaces: (1) rod-shaped forms (RSF) about 70-80 nm wide and ranging from 100 nm to 600 nm in length; (2) ovoid forms (OVF) with diameters between 70 and 300 nm, They look like single cells surrounded by a cell wall. Only Na, K, C, O and N with traces of P and S are observed in the bulk of these objects. The chemical analyses and electron diffraction patterns confirm that the RSF and OVF cannot be magnetite or other iron oxides, iron hydroxides, silicates or carbonates. The rites of the RSF and OVF are below those commonly observed for bacteria but are very similar to some bacteria-like forms described in the Martian meteorite ALH84001. All the previous observations strongly suggest that they are bacteria or their remnants. This conclusion is further supported by microbiological experiments in which pleomorphic bacteria with morphology similar to the OVF and RSF objects are obtained from biological culture of the soil surrounding the meteorite pieces. The present results show that bacteriomorphs of diameter less' than 100 nm may in fact represent real bacteria or their remnants. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Ecole Normale Super Lyon, Lab Sci Terre, CNRS, UMR 5570, F-69364 Lyon 07, France. Univ Angers, Fac Sci, F-49045 Angers, France. CNRS, CEA Cardarache, DSV, DEVM,Lab Ecol Microbienne Rhizosphere,UMR 163, F-13108 St Paul Durance, France. CNRS, F-49045 Angers, France. Fac Med, Serv Commun Microscopie Elect, F-49045 Angers, France. Inst Univ France, Lab Min Cristallog, F-75252 Paris, France. Inst Phys Globe, F-75252 Paris, France. RP Gillet, P, Ecole Normale Super Lyon, Lab Sci Terre, CNRS, UMR 5570, 46 Allee Italie, F-69364 Lyon 07, France. TC 15 PD FEB 15 PY 2000 VL 175 IS 3-4 BP 161 EP 167 UT ISI:000085407100001 ER PT J AU Blanchard, P Huchet, L Levillain, E Roncali, J TI Cation template assisted electrosynthesis of a highly pi-conjugated polythiophene containing oligooxyethylene segments SO ELECTROCHEMISTRY COMMUNICATIONS DE polythiophene; polyether; electropolymerization; template effect; spectroelectrochemistry ID CROWN-ETHER; POLY(THIOPHENES); THIOPHENES AB A polythiophene precursor involving two bithiophene groups linked by an oligooxyethylene chain has been synthesized. Electropolymerizations performed in the presence of tetrabutylammonium, lithium, sodium and barium perchlorate show that the nature of the electrolyte cation strongly affects the polymerization process. The electrochemical and spectroelectrochemical properties of the resulting polymers show that the presence of barium cation in the electrosynthesis medium leads to a 300 mV decrease in the oxidation potential of the polymer, together with a significant red shift in the absorption maximum providing conclusive evidence for a metal template effect during electropolymerization. (C) 2000 Elsevier Science S.A. All rights reserved. C1 Univ Angers, CNRS, UMR 6501, F-49045 Angers, France. RP Roncali, J, Univ Angers, CNRS, UMR 6501, 2 Blvd Lavoisier, F-49045 Angers, France. TC 15 PD JAN PY 2000 VL 2 IS 1 BP 1 EP 5 UT ISI:000084783500001 ER PT J AU Dumarcher, V Rocha, L Denis, C Fiorini, C Nunzi, JM Sobel, F Sahraoui, B Gindre, D TI Polymer thin-film distributed feedback tunable lasers SO JOURNAL OF OPTICS A-PURE AND APPLIED OPTICS DE luminescent polymer; organic laser; distributed feedback; thin-film waveguide ID MICROCAVITY STRUCTURE; STIMULATED-EMISSION; DYE-LASER; ELECTROLUMINESCENCE; GRATINGS AB We report on measurements of laser emission from poly-methylmethacrylate and poly-vinyl carbazole polymer films doped with rhodamine-6G, DCM and coumarin laser dyes in an optically pumped distributed feedback scheme. We obtain tunability on a broad spectral range for all samples. We show the impact of waveguiding in the polymer film on reducing the laser threshold. We also show that the number of laser modes increases with the polymer film thickness, following the guided mode dispersion. C1 CEA Saclay, Grp Composants Organ, DEIN SPE, LETI CEA Technol Avancees, F-91191 Gif Sur Yvette, France. Univ Angers, Lab Proprietes Opt Mat & Applicat, F-49045 Angers, France. RP Nunzi, JM, CEA Saclay, Grp Composants Organ, DEIN SPE, LETI CEA Technol Avancees, F-91191 Gif Sur Yvette, France. TC 14 PD JUL PY 2000 VL 2 IS 4 BP 279 EP 283 UT ISI:000089910100008 ER PT J AU Becher, SA Steinmetz, K Weising, K Boury, S Peltier, D Renou, JP Kahl, G Wolff, K TI Microsatellites for cultivar identification in Pelargonium SO THEORETICAL AND APPLIED GENETICS DE cultivar identification; geranium; Pelargonium; simple sequence repeats; protected varieties ID ACTINIDIA-CHINENSIS; GENETIC DIVERSITY; BREAD WHEAT; DNA; MARKERS; AMPLIFICATION; POLYMORPHISMS; ENRICHMENT; ABUNDANCE; REPEATS AB We have isolated and characterised microsatellite loci from Pelargonium sp. to explore the potential of these markers for cultivar identification. Small-insert libraries from a zonal (Pelargonium x hortorum cv. Isabell) and an ivy-leaved variety (P. peltatum cv. Guenievre gergue) were enriched for d(AG), d(AC), d(CAA), d(GAA) and d(GATA) repeats. Of 141 positive clones sequenced, 133 contained a microsatellite. Primers for PCR amplification were designed to the flanking regions of 57 microsatellites, resulting in interpretable amplification products of the expected size for 29 loci. Seventeen primer pairs amplifying 18 loci were used to fingerprint 44 di- and tetra-ploid Pelargonium accessions representative of commercially available varieties. Multilocus genotypes obtained at 3 loci distinguished among all accessions, except for three known flower colour sports and a fourth, phenotypically very similar, variety. Allelic composition was also identical within two other sport 'families' typed at the same 18 loci. UPGMA and principal co-ordinate analysis of pairwise distance matrices derived from PCR amplification patterns revealed four distinct assemblages. The first group consisted of tetraploid P. x hortorum varieties, a second group contained diploid P. x hortorum, a third, tetraploid P. peltatum accessions, while a fourth, very distinct, group consisted solely of diploid P. peltatum varieties. Polymorphism in P. peltatum was equal or greater than in P. x hortorum at 17 of the 18 loci, indicating that the analysed P. peltatum varieties form a genetically more variable array. C1 Univ St Andrews, Sch Evolut & Environm Biol, St Andrews KY16 9TH, Fife, Scotland. Univ Frankfurt, Biozentrum, D-60439 Frankfurt, Germany. Bretagne Biotechnol Vegetale, F-29250 St Pol De Leon, France. Univ Angers, UFR Sci, Genet Lab, F-49045 Angers, France. INRA Angers, F-49045 Angers, France. RP Becher, SA, Univ St Andrews, Sch Evolut & Environm Biol, Sir Harold Mitchell Bldg, St Andrews KY16 9TH, Fife, Scotland. TC 14 PD SEP PY 2000 VL 101 IS 4 BP 643 EP 651 UT ISI:000089517200018 ER PT J AU Raymond, V Sattelle, DB Lapied, B TI Co-existence in DUM neurones of two GluCl channels that differ in their picrotoxin sensitivity SO NEUROREPORT DE BIDN; fipronil; L-glutamate-gated chloride channels; insect neurones; picrotoxin ID GATED CHLORIDE CHANNELS; METABOTROPIC GLUTAMATE RECEPTORS; COCKROACH PERIPLANETA-AMERICANA; DROSOPHILA GABA RECEPTOR; CENTRAL-NERVOUS-SYSTEM; NEUROTRANSMITTERS; CURRENTS; GANGLION; CELLS; BIDN AB Whole cell patch-clamp electrophysiology was used to study the effects of L-glutamate on dissociated cockroach (Periplaneto americana) dorsal unpaired median (DUM) neurones. Application of L-glutamate via pressure-ejection pipette resulted in a two-component hyperpolarization, consisting of an initial transient and a second, prolonged phase. Under voltage-clamp, using isotonic chloride in the saline and intrapipette solutions, two L-glutamate-gated inward currents were characterized. Their reversal potentials were close to the equilibrium potential for chloride ions. One component was selectively activated by ibotenate and was sensitive to picrotoxin (100 mu M), BIDN (10 mu M) and the phenylpyrazole insecticide fipronil (10 mu M), known to be potent blockers of insect GABA-gated chloride channels. The second component was insensitive to picrotoxin (100 mu M) and BIDN (10 mu M). These findings demonstrated, for the first time, the co-existence of two pharmacologically distinct native insect neuronal L-glutamategated chloride channels. (C) 2000 Lippincott Williams & Wilkins. C1 Univ Angers, UFR Sci, Neurophysiol Lab, UPRES EA 2647, F-49045 Angers, France. Univ Oxford, Dept Human Anat & Genet, Oxford OX1 3QX, England. RP Lapied, B, Univ Angers, UFR Sci, Neurophysiol Lab, UPRES EA 2647, 2 Bd Lavoisier, F-49045 Angers, France. TC 14 PD AUG 21 PY 2000 VL 11 IS 12 BP 2695 EP 2701 UT ISI:000089003300026 ER PT J AU Reginster, JY Bruyere, O Audran, M Avouac, B Body, JJ Bouvenot, G Brandi, ML Gennari, C Kaufman, JM Lemmel, EM Vanhaelst, L Weryha, G Devogelaer, JP CA Grp Respect Ethics Excellence Sci TI Do estrogens effectively prevent osteoporosis-related fractures? SO CALCIFIED TISSUE INTERNATIONAL ID HORMONE REPLACEMENT THERAPY; PERCUTANEOUS ESTRADIOL IMPLANTS; POSTMENOPAUSAL WOMEN; HIP FRACTURE; RANDOMIZED TRIAL; BONE MASS; EFFICACY; DENSITY; RISK; HRT C1 Univ Liege, Dept Epidemiol & Publ Hlth, WHO, Collaborating Ctr Publ Hlth Aspects Osteoarticula, Liege, Belgium. Univ Liege, Bone & Cartilage Metab Unit, Liege, Belgium. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. CHU Angers, Angers, France. Hop Henri Mondor, F-94010 Creteil, France. Inst Jules Bordet, B-1000 Brussels, Belgium. Ctr Hosp Reg & Univ Marseille, Marseille, France. Univ Florence, Florence, Italy. Univ Siena, I-53100 Siena, Italy. Univ Ziekenhuis Gent, Ghent, Belgium. Max Grunding Klin, Buhl, Germany. Free Univ Brussels, Brussels, Belgium. Ctr Hosp Univ, Nancy, France. Hop Univ St Luc, Brussels, Belgium. RP Reginster, JY, CHU Sart Tilman, Batiment B23, B-4000 Liege, Belgium. TC 14 PD SEP PY 2000 VL 67 IS 3 BP 191 EP 194 UT ISI:000088781400001 ER PT J AU Lievre, M Marre, M Chatellier, G Plouin, PF Reglier, JC Richardson, L Bugnard, F Vasmant, D CA DIABHYCAR Study Grp TI The non-insulin-dependent diabetes, hypertension, microalbuminuria or proteinuria, cardiovascular events, and Ramipril (DIABHYCAR) study: Design, organization, and patient recruitment SO CONTROLLED CLINICAL TRIALS DE Ramipril; diabetes mellitus; randomized controlled trial; cardiovascular diseases ID LEFT-VENTRICULAR HYPERTROPHY; ALBUMIN EXCRETION; RISK-FACTORS; MORTALITY; NIDDM; PREDICTOR AB The non-insulin-dependent DIABetes, HYpertension, microalbuminuria or proteinuria, CARdiovascular events, and Ramipril (DIABHYCAR) study is a randomized, prospective, double-blind, placebo-controlled, multicenter international trial of the ACE inhibitor ramipril (1.25 mg/day) in patients with type II diabetes and micro- or macroalbuminuria. The main outcome of the study is the time to first occurrence of either death from a cardiovascular origin, including sudden death, nonfatal myocardial infarction, stroke, or congestive heart failure, or requirement of hemodialysis or renal transplantation. The study was launched in France in early 1995 with the participation of general practitioners only, but had to be extended to 15 other countries in 1997 due to difficulties in recruitment. Since 2.5 years after the beginning of the trial the observed event rate was much less than anticipated, it was decided to increase recruitment and follow-up duration and to include congestive heart failure in the definition of the main outcome to keep the study power at a satisfactory level. Recruitment ended on April 1, 1998 with 4937 randomized patients. Following the early discontinuation for efficacy of another study of ramipril in high cardiovascular risk patients, the Heart Outcomes Prevention Evaluation study (HOPE), the second interim analysis of DIABHYCAR was performed early (when 406 instead of 500 patients presented a main outcome) and the Data Safety and Monitoring Board recommended that the study continue. Follow-up is planned to end on March 31, 2001. (C) Elsevier Science Inc. 2000. C1 Dept Clin Pharmacol, Lyon, France. CHU Angers, Dept Med B, Angers, France. Hop Broussais, Dept Med Comp Sci, F-75674 Paris, France. Hop Broussais, Dept Hypertens, F-75674 Paris, France. Hoechst Marion Roussel, Paris, France. DIABHYCAR Subcoordinating Ctr Europe, London, England. RP Lievre, M, Fac Med Laennec, Serv Pharmacol Clin, BP 8071, F-69376 Lyon 08, France. TC 14 PD AUG PY 2000 VL 21 IS 4 BP 383 EP 396 UT ISI:000088415600009 ER PT J AU Rachet, F Le Duff, Y Guillot-Noel, C Chrysos, M TI Absolute isotropic spectral intensities in collision-induced light scattering by helium pairs over a large frequency domain SO PHYSICAL REVIEW A ID POTENTIAL-ENERGY CURVE; AB-INITIO CALCULATIONS; DIATOM POLARIZABILITIES; DIELECTRIC PROPERTIES; RAMAN-SPECTROSCOPY; MOLECULES; GASES; ATOMS AB We measured the polarized binary collision-induced light scattering spectrum from room-temperature gaseous helium over the greatly extended spectral domain nu = 5-1200 cm(-1), and then deduced the isotropic spectrum that we report in the interval nu = 100-1200 cm(-1). Our experimental results were calibrated on an absolute scale. These data were compared to those from quantum-mechanical computations, where use of advanced induced-polarizability incremental traces was made. This comparison enabled us to check several trace models and to show that for certain ab initio ones the computed spectra agree well with our measurements. As was borne out from our computations the main contributions to the spectral intensities come from the exchange component of the incremental trace and its negative mixing with the rest of the trace components. C1 Univ Angers, Lab Proprietes Opt Mat & Applicat, EP CNRS 130, F-49045 Angers, France. RP Rachet, F, Univ Angers, Lab Proprietes Opt Mat & Applicat, EP CNRS 130, 2 Blvd Lavoisier, F-49045 Angers, France. TC 14 PD JUN PY 2000 VL 6106 IS 6 AR 062501 DI ARTN 062501 UT ISI:000087567900034 ER PT J AU Lode, T TI Effect of a motorway on mortality and isolation of wildlife populations SO AMBIO ID SMALL MAMMALS; HABITAT ISOLATION; ROADS; COMMUNITIES; DISPERSAL; MOVEMENTS; HIGHWAYS; BARRIERS; ARVALIS; DENSITY AB Although motorways could affect wildlife species, only few studies have been documented on their effects on mortality and isolation. With 2266 road-killed animals representing 97 species, the results of a study on a motorway section emphasized that traffic considerably affected vertebrate populations (14.5 animals day(-1) 100 km(-1)). Road-killed animals were mainly mammals (43.2%), with predators also suffering critical impacts (21.7% vertebrates). Rare or endangered species such as the Midwife toad, the Blue throat, the little Horseshoe bat, or the European otter were among the victims. Animal mortality exponentially increased with traffic volume. Mortality reached almost 100% of migrants when no passage existed, and this barrier effect was only reduced when underground passages crossed the road restraining the mortality to 31% of migrants in Field mice and 23% in Common toads, while mortality always exceeded 74% in a road section with fauna ducts. It is reasonable to conclude that traffic severely influenced both wildlife species demography and population exchanges resulting in effective population isolation. C1 UFR Sci, Lab Ecol Anim, F-49045 Angers Belle Beille, France. RP Lode, T, UFR Sci, Lab Ecol Anim, 2Bd Lavoisier, F-49045 Angers Belle Beille, France. TC 14 PD MAY PY 2000 VL 29 IS 3 BP 163 EP 166 UT ISI:000087670400008 ER PT J AU Symoens, F Bouchara, JP Heinemann, S Nolard, N TI Molecular typing of Aspergillus terreus isolates by random amplification of polymorphic DNA SO JOURNAL OF HOSPITAL INFECTION DE Aspergillus terreus; RAPD; nosocomial infections ID RESTRICTION ENDONUCLEASE ANALYSIS; POLYMERASE CHAIN-REACTION; INVASIVE ASPERGILLOSIS; CYSTIC-FIBROSIS; IMMUNOCOMPROMISED HOSTS; GENETIC DIVERSITY; FUMIGATUS; INFECTION; ENDOPHTHALMITIS; OSTEOMYELITIS AB Forty three isolates of Aspergillus terreus of environmental or clinical origin were typed by random amplification of polymorphic DNA (RAPD) with two different primers NS3 and NS7 from the fungal ribosomal 18S subunit gene. Fur the 31 epidemiologically unrelated isolates tested, the primers NS3 and NS7 gave rise to 23 and 24 different genotypes, respectively, and combining the: results obtained with the two primers allowed the differentiation of all these isolates. No clustering was found in relation to pathogenicity clinical signs, or geographic origin of the isolates. Five groups of related isolates of A. terreus were also typed. Analysis of sequential isolates from patients with cystic fibrosis or with invasive aspergillosis showed the clonality of the colonization or infection by ii. terreus. Likewise, this straightforward typing method demonstrated the clonal origin of a massive contamination of the environment in a haematology unit. Therefore this RAPD typing method may constitute a valuable tool for the epidemiological follow-up of airway colonization in patients with cystic fibrosis or investigations of links between nosocomial outbreaks of invasive aspergillosis and environmental contamination. (C) 2000 The Hospital infection Society. C1 Sci Inst Publ Hlth, Mycol Sect, B-1050 Brussels, Belgium. Ctr Hosp Univ, Grp Etud Interact Hote Parasite, Angers, France. RP Symoens, F, Sci Inst Publ Hlth, Mycol Sect, 14 Juliette Wytsman St, B-1050 Brussels, Belgium. TC 14 PD APR PY 2000 VL 44 IS 4 BP 273 EP 280 UT ISI:000086904800005 ER PT J AU Delumeau, O Morere-Le Paven, MC Montrichard, F Laval-Martin, DL TI Effects of short-term NaCl stress on calmodulin transcript levels and calmodulin-dependent NAD kinase activity in two species of tomato SO PLANT CELL AND ENVIRONMENT DE Lycopersicon esculentum; Lycopersicon pimpinellifolium; calcium; calmodulin; NAD kinase; salt stress; tomato ID INDUCED OXIDATIVE STRESS; CORN ROOT PROTOPLASTS; SALT STRESS; LYCOPERSICON-PIMPINELLIFOLIUM; INTRACELLULAR CALCIUM; BINDING PROTEINS; WATER-DEFICIT; PLANTS; SALINITY; RESPONSES AB NAD kinase is thought to play an important role in the plant cellular responses to biotic and abiotic stress as one of the isoforms of the enzyme is activated by the Ca2+-calmodulin (CaM) complex. NAD kinase activity was measured after short-term NaCl stress applied to isolated cells from Lycopersicon esculentum, var. Volgogradskij (NaCl-sensitive tomato) and L. pimpinellifolium, acc. PE2 (NaCl-tolerant species). NAD kinase activity remained constant in the sensitive species, whereas a sharp decrease was observed in the tolerant one. After salt treatment, an induction of the calmodulin gene(s) was observed in the two species, together with a 30-50% decrease in 'active' CaM content, i.e. CaM able to activate purified NAD kinase, in L. pimpinellifolium. The decrease in NAD kinase activity could not, however, be fully explained by this decrease in active CaM content. A similar decrease in NAD kinase activity was also recorded with other ionic stresses and exposure to high temperatures, but not in the case of drought, exposure to low temperatures, hormonal (indole-3-acetic acid and abscisic acid) or H2O2 treatments. External Ca2+ certainly plays a role in the biochemical mechanism(s) leading to NAD kinase inhibition, while no role could be shown for intracellular Ca2+. In addition, after salt stress, a modification of the redox state of NAD kinase seems to be responsible for the inhibition of the enzyme. C1 Univ Angers, UFR Sci, EA 917, Grp Biochim & Biol Mol Vegetales, F-49045 Angers 01, France. RP Laval-Martin, DL, Univ Angers, UFR Sci, EA 917, Grp Biochim & Biol Mol Vegetales, 2 Blvd Lavoisier, F-49045 Angers 01, France. TC 14 PD MAR PY 2000 VL 23 IS 3 BP 329 EP 336 UT ISI:000086254900009 ER PT J AU Legras, S Mouneyrac, C Amiard, JC Amiard-Triquet, C Rainbow, PS TI Changes in metallothionein concentrations in response to variation in natural factors (salinity, sex, weight) and metal contamination in crabs from a metal-rich estuary SO JOURNAL OF EXPERIMENTAL MARINE BIOLOGY AND ECOLOGY DE crab; heavy metals; salinity; metallothionein ID CARCINUS-MAENAS L; CALLINECTES-SAPIDUS; BLUE-CRAB; PALAEMON-ELEGANS; TRACE-METALS; ZINC UPTAKE; CADMIUM; COPPER; ACCUMULATION; CD AB Intermoult male and female crabs Pachygrapsus marmoratus and Carcinus maenas were sampled from three sites between the mouth and 25 km upstream in the Gironde, the most Cd-contaminated estuary in France, in order to study the relative importance of natural factors (salinity, sex, weight) and accumulated metal concentrations on metallothionein (MT) concentrations. In the two species studied, higher metal, total protein and MT concentrations were observed in the hepatopancreas than in the gills. In P. marmoratus, MT concentrations were mainly related to changes in the natural factors even if MT and Zn concentrations were positively correlated in the hepatopancreas whereas in C. maenas, the main relationships were with accumulated metal levels. In the case of the natural factors, the most important ones were weight in gills of both crab species, and salinity changes in both hepatopancreas and gills of P. marmoratus. Cd and Cu concentrations in both organs of the two species were inversely related to salinity. The same observation was found for Zn concentrations in C. maenas but not in P. marmoratus. In the hepatopancreas of both species, the highest total protein concentrations were found in crabs from the site with the highest salinity, whereas there were no such differences in the gills. It seems that changes in MT concentrations are linked more to changes in general protein metabolism than to changes in metal accumulation. Thus it was important to examine the storage of metals in other tissue compartments, particularly the insoluble fraction which includes mineral granules which is known to also contribute to trace metal detoxification in invertebrates. In the gills of the crabs, Zn was present mainly in the insoluble fraction, whereas Cd was nearly equally distributed between soluble and insoluble fractions. In contrast, Cu in the gills and all three metals in the hepatopancreas of both species were mainly cytosolic, but. this does not necessarily imply a predominant role for MT since the cytosolic fraction also includes other macramolecules which may be the target binding site for accumulated trace metals. (C) 2000 Elsevier Science B.V. All rights reserved. C1 IRFA, Dept Sci Vie & Terre, Lab Ecol Anim, F-49100 Angers, France. GDR 1117 CNRS, F-44322 Nantes 3, France. Fac Pharm, ISOMER, Serv Ecotoxicol, F-44322 Nantes 3, France. Nat Hist Museum, Dept Zool, London SW7 5BD, England. RP Mouneyrac, C, IRFA, Dept Sci Vie & Terre, Lab Ecol Anim, 44 Rue Rabelais, F-49100 Angers, France. TC 14 PD APR 5 PY 2000 VL 246 IS 2 BP 259 EP 279 UT ISI:000086000000006 ER PT J AU Barrat, JA Boulegue, J Tiercelin, JJ Lesourd, M TI Strontium isotopes and rare-earth element geochemistry of hydrothermal carbonate deposits from Lake Tanganyika, East Africa SO GEOCHIMICA ET COSMOCHIMICA ACTA ID RIFT SYSTEM; COMPLEXATION; 25-DEGREES-C; CALCITE; IONS AB At Cape Banza (North Tanganyika Lake), fluids and aragonite chimneys have been collected many times since the discovery of this sublacustrine field in 1987. This sampling has been investigated here for the Sr isotopic compositions and the rare-earth element features of the carbonates and a few fluid samples. The Sr-87/Sr-86 ratios Of the chimneys indicate that they have precipitated from a mixture of lake water (more than 95%) and hydrothermal fluids. No zoning in the chimneys was detected with our Sr data. For the rare-earth elements, the situation is more complex. The external walls of the chimneys are rare-earth-element-poor (La approximate to 500 ppb, Yb approximate to 200 ppb, La/Yb = 2 to 3.4). Their shale normalised rare-earth element patterns suggest that they are in equilibrium with the inferred carbonate-depositing fluids. The rare-earth element concentrations of the internal walls of the chimneys are significantly light rare earth elements (LREE)-enriched with La contents sometimes up to 5 ppm. We suggest that they contain more vent-fluid rare-earth elements than the external wall samples, possibly adsorbed on the surface of growing crystals or simply hosted by impurities. It was not possible to constrain the nature of these phases, but the variations of the compositions of the internal wall materials of the active chimneys with time, as well as data obtained on an inactive chimney indicate that this rare-earth element excess is mobile. Partition coefficients were calculated between the external wall aragonite and carbonate-depositing fluid. The results are strikingly similar to the values obtained by Sholkovitz and Shen (1995) on coral aragonite, and suggest that there is no significant biologic effect on the incorporation of rare-earth elements into coral aragonite and that the various carbonate complexes involved Me(CO3+) complexes are the main LREE carriers in seawater (Cantrell and Byrne, 1987) instead of Me(CO3)(2)(-) in Banza fluids) have the same behaviour during aragonite precipitation. Copyright (C) 2000 Elsevier Science Ltd. C1 Univ Angers, Fac Sci, CNRS UMR 5025, LGCA, F-69065 Angers, France. Univ Paris 11, Lab Geochim & Metallogenie, F-75252 Paris 05, France. Inst Univ Europeen Mer, CNRS UMR 6538, F-29280 Plouzane, France. Fac Med, CNRS, F-49045 Angers, France. Fac Med, SCME, F-49045 Angers, France. RP Barrat, JA, Univ Angers, Fac Sci, CNRS UMR 5025, LGCA, 2 Bd Lavoisier, F-69065 Angers, France. TC 14 PD JAN PY 2000 VL 64 IS 2 BP 287 EP 298 UT ISI:000085089600012 ER PT J AU Hall, IH Lackey, CB Kistler, TD Durham, RW Jouad, EM Khan, M Thanh, XD Djebbar-Sid, S Benali-Baitich, O Bouet, GM TI Cytotoxicity of copper and cobalt complexes of furfural semicarbazone and thiosemicarbazone derivatives in murine and human tumor cell lines SO PHARMAZIE ID METALLIC COMPLEXES; FURAN OXIMES; INHIBITORS AB The 2-furfural semicarbazone and thiosemicarbazone copper and cobalt complexes demonstrated potent cytotoxicity against the growth of suspended leukemias and lymphomas as well as human lung MB9812, colon SW480, ovary 1-A9 and HeLa-S-3 uterine carcinoma. In L1210 lymphoid leukemia cell the complexes inhibited preferentially DNA synthesis over 60 min at 25 to 100 muM. The copper and cobalt complexes functioned by multiple mechanisms to suppress synthetic steps in nucleic acid metabolism to reduce deoxynucleotide pools for incorporation into DNA. At high concentrations the complexes suppressed human DNA topoisomerase II activity with DNA nicks and DNA fragmentation but they did not alkylate the bases of DNA, cause intercalation between base pairs or cause cross-linking of DNA strands. C1 Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA. Fac Pharm Angers, Chim Coordinat Lab, Angers, France. Inst Chim, USTHB, Chim Coordinat Lab, Alger, Algeria. RP Hall, IH, Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, CB 7360, Chapel Hill, NC 27599 USA. TC 13 PD DEC PY 2000 VL 55 IS 12 BP 937 EP 941 UT ISI:000165934700012 ER PT J AU Morel, C Seraphin, D Oger, JM Litaudon, M Sevenet, T Richomme, P Bruneton, J TI New xanthones from Calophyllum caledonicum SO JOURNAL OF NATURAL PRODUCTS ID MESUA-RACEMOSA; 2 XANTHONES; ROOT BARK; INOPHYLLUM; CONSTITUENTS; DERIVATIVES; COUMARINS; APETALUM; TREE AB Four new xanthones, caledonixanthones A-D (1-4), were isolated from the tr;ni; bark of Caolphyllum caledonicum, in addition to 17 known compounds. The structures of 1-4 were determined by means of spectroscopic analysis and chemical derivatization. C1 SONAS, UFR Sci Pharmaceut & Ingn Sante, F-49100 Angers, France. ICSN, CNRS, F-91191 Gif Sur Yvette, France. RP Richomme, P, SONAS, UFR Sci Pharmaceut & Ingn Sante, 16 Bd Daviers, F-49100 Angers, France. TC 13 PD NOV PY 2000 VL 63 IS 11 BP 1471 EP 1474 UT ISI:000165548000003 ER PT J AU Lortholary, A Maillard, P Delva, R Boisdron-Celle, M Perard, D Vernillet, L Besenval, M Gamelin, E TI Docetaxel in combination with 5-fluorouracil in patients with metastatic breast cancer previously treated with anthracycline-based chemotherapy: a phase I, dose-finding study SO EUROPEAN JOURNAL OF CANCER DE anthracycline; docetaxel; 5-fluorouracill; pharmacokinetics; metastatic breast cancer ID CONTINUOUS-INFUSION; RANDOMIZED TRIAL; PLASMA; CYCLOPHOSPHAMIDE; TAXOTERE(R); DOXORUBICIN; CLEARANCE; 5-DAY; 5-FU AB This phase I study evaluated the maximum tolerated dose. dose-limiting toxicity and recommended dose of docetaxel in combination with 5-fluorouracil (5-FU) in patients with metastatic breast cancer previously treated with anthracycline-based chemotherapy. 32 patients received docetaxel at 60, 75, 85 or 100 mg/m(2) by 1-h intravenous (i.v.) infusion, followed, after a 1-h interval, by 5-FU at 250, 350, 500 or 750 mg/m(2)/day by continuous infusion over 5 days every 3 weeks. Dose-limiting stomatitis defined the maximum tolerated dose at a docetaxel dose of 100 mg/m(2) with 5-FU 750 mg/m(2)/day. None of 5 patients treated at the previous dose level (docetaxel 85 mg/m(2) with 5-FU 750 mg/m(2)/day) had a dose-limiting toxicity in the first cycle, and this was, therefore, considered the recommended dose. The combination was generally well tolerated. Grade 4 neutropenia was common (29 patients; 91%), but no patient experienced febrile neutropenia of duration > 3 days requiring i.v. antibiotics. An objective response was achieved by 18 patients overall (56%), and in 4 out of 5 patients treated with the determined recommended dose. No pharmacokinetic interaction between docetaxel and 5-fluorouracil was apparent. The activity of docetaxel 85 mg/m(2) with 5-fluorouracil 750 mg/m(2)/day will be explored more extensively in phase II studies of patients with metastatic breast cancer previously treated with anthracycline-based chemotherapy. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Ctr Paul Papin, F-49033 Angers, France. Rhone Poulenc, Antony, France. RP Lortholary, A, Ctr Paul Papin, 2 Rue Moll, F-49033 Angers, France. TC 13 PD SEP PY 2000 VL 36 IS 14 BP 1773 EP 1780 UT ISI:000089434700014 ER PT J AU Deconinck, E Lamy, T Foussard, C Gaillard, F Delwail, V Colombat, P Casassus, P Lemevel, A Brion, A Milpied, N CA Grp Ouest-Est Etude Leucemies Autr TI Autologous stem cell transplantation for anaplastic large-cell lymphomas: results of a prospective trial SO BRITISH JOURNAL OF HAEMATOLOGY DE anaplastic; diffuse large-cell lymphoma; CD30; autologous stem cell transplantation; prognostic factor ID BONE-MARROW TRANSPLANTATION; NON-HODGKINS-LYMPHOMAS; REED-STERNBERG CELLS; SEQUENTIAL CHEMOTHERAPY; ADULT PATIENTS; KI-1 LYMPHOMA; DISEASE; CLASSIFICATION; THERAPY; T(2-5)(P23-Q35) AB Autologous stem cell transplantation (ASCT) in the front line treatment of non-Hodgkin's lymphoma (NHL) remains controversial. Anaplastic large-cell lymphoma (ALCL) is known to have its own clinical and biological features. The outcome of ALCL patients treated with high-dose chemotherapy and ASCT as part of their first-line therapy was analysed in 202 intermediate or high-grade NHL patients in a prospective randomized trial. First-line chemotherapy comprised two alternating anthracycline-containing regimens. Responding patients were autografted after a BEAM (BCNU, cytarabine, etoposide and melphalan) regimen. Patients with bulky or residual masses were irradiated. Fifteen patients with ALCL were identified by morphological and immunological features (CD30 was expressed in 14 out of 15 patients, three patients expressed B-cell markers, five patients expressed T-cell markers and seven patients did not express cell markers). Anaplastic lymphoma kinase (ALK) expression was confirmed in seven cases. The median age was 39 years with a predominant male sex ratio (2.75). Thirteen patients were stage greater than or equal to III and six presented with two or more adverse prognostic factors. According to the international age-adjusted prognostic index, the expected complete remission (CR), event-free survival (EFS) and overall survival (OS) rates were 69%, 71% and 69%. Two deaths were observed (one due to interstitial pneumonitis, one due to pulmonary carcinoma). All patients entered CR, no relapse occurred and EFS and survival reached 87% with a follow-up of more than 5 years. These results differ significantly from those observed in the other 176 lymphoma patients: event-free survival was only 53 +/- 5% and OS reached 60 +/- 4% with a median follow-up of 56 months (P = 0.006). Intensified chemotherapy with autologous stem cell support appeared effective in the treatment of ALCL, offering patients the real chance of a cure. C1 CHU Besancon, Hop Jean Minjoz, Serv Hematol, F-25030 Besancon, France. Ponchailloux Univ Hosp, Rennes, France. Univ Hosp, Angers, France. Hotel Dieu Univ Hosp, Nantes, France. Univ Hosp, Poitiers, France. Bretonneau Univ Hosp, Tours, France. Avicenne Hosp, Bobigny, France. Gauducheau Anticanc Ctr, Rennes, France. RP Deconinck, E, CHU Besancon, Hop Jean Minjoz, Serv Hematol, F-25030 Besancon, France. TC 13 PD JUN PY 2000 VL 109 IS 4 BP 736 EP 742 UT ISI:000088482900009 ER PT J AU Fraysse, B Guillet, C Huchet-Candiou, C Camerino, DC Gascan, H Leoty, C TI Ciliary neurotrophic factor prevents unweighting-induced functional changes in rat soleus muscle SO JOURNAL OF APPLIED PHYSIOLOGY DE ciliary neurotrophic factor receptor-alpha; mammalian skeletal muscle; hindlimb unweighting ID HINDLIMB SUSPENSION; SKELETAL-MUSCLE; CONTRACTILE PROPERTIES; SARCOPLASMIC-RETICULUM; GENE-EXPRESSION; CNTF RECEPTOR; FIBERS; SPACEFLIGHT; CYTOKINES; RESPONSES AB The purpose of the present work was to see whether changes in rat soleus characteristics due to 3 wk of hindlimb suspension could be modified by ciliary neurotrophic factor (CNTF) treatment. Throughout the tail suspension period, the cytokine was delivered by means of an osmotic pump (flow rate 16 pg kg(-1) h(-1)) implanted under the hindlimb skin. In contrast to extensor digitorum longus, CNTF treatment was able to reduce unweighting-induced atrophy in the soleus. Twitch and 146 mM potassium (K) tensions, measured in small bundles of unloaded soleus, decreased by 48 and 40%, respectively. Moreover, the time to peak tension and the time constant of relaxation of the twitch were 48 and 54% faster, respectively, in unloaded soleus than in normal muscle. On the contrary, twitch and 146 mM K contracture generated in CNTF-treated unloaded and normal soleus were not different. CNTF receptor-alpha mRNA expression increased in extensor digitorum longus and soleus unloaded nontreated muscles but was similar in CNTF-treated unloaded muscles. The present results demonstrate that exogenously provided CNTF could prevent functional changes occurring in soleus innervated muscle subject to unweighting. C1 Fac Sci Nantes, Lab Physiol Gen, F-4322 Nantes 3, France. CHU Angers, INSERM, U298, F-49033 Angers, France. Univ Bari, Dipartimento Farmacobil, Unita Farmacol, I-70125 Bari, Italy. RP Fraysse, B, Fac Sci Nantes, CNRS, Lab Physiol Gen, EP 1593, 2 Rue Houssiniere,BP 92208, F-44322 Nantes 3, France. TC 13 PD MAY PY 2000 VL 88 IS 5 BP 1623 EP 1630 UT ISI:000086985000018 ER PT J AU Terkia-Derdra, N Andreu, R Salle, M Levillain, E Orduna, J Garin, J Orti, E Viruela, R Pou-Amerigo, R Sahraoui, B Gorgues, A Favard, JF Riou, A TI pi conjugation across the tetrathiafulvalene core: Synthesis of extended tetrathiafulvalene derivatives and theoretical analysis of their unusual electrochemical properties SO CHEMISTRY-A EUROPEAN JOURNAL DE ab initio calculations; cyclic voltammetry; nonlinear optics; tetravalent sulfur; tetrathiafulvalene ID NONLINEAR-OPTICAL PROPERTIES; NONCLASSICAL CONDENSED THIOPHENES; SUBSTITUTED TETRATHIAFULVALENES; INTRAMOLECULAR CYCLIZATION; INCREASED DIMENSIONALITY; REVERSIBLE DIMERIZATION; CRYSTAL-STRUCTURES; DONOR MOLECULES; ELECTRON-DONORS; ORGANIC METALS AB A series of extended tetrathiafulvalene (TTF) derivatives bearing one or two 1,4-dithiafulven-6-yl substituents has been prepared. The new compounds present remarkable electrochemical singularities compared with other TTF derivatives, which are strongly affected by the nature of the substitution on the lateral heterocycle(s). This unusual electrochemical behaviour follows a square-scheme sequence and is attributed to structural changes upon oxidation of the pi-donating molecules. Digital simulations of the electrochemical data have been used to reach the values of the kinetic and thermodynamic constants involved in the square scheme. Theoretical calculations establish an important contribution of a highly delocalised resonant form involving a tetravalent sulphur in oxidised species, which could justify the occurrence of an electrochemical behaviour distinct from that of TTF. Finally, third-order susceptibilities chi(3) of two of these systems, for which electron-donating and electron-withdrawing substituents coexist and are conjugated through the TTF pi system, are given. C1 Univ Angers, Lab Ingn Mol & Mat Organ, CNRS, UMR 6501, F-49045 Angers, France. Univ Zaragoza, Fac Ciencias, CSIC, Unidad Nuevos Mat Organ,Inst Ciencia Mat Aragon, E-50009 Zaragoza, Spain. Univ Valencia, Dept Quim Fis, E-46100 Valencia, Spain. Univ Angers, Lab Proprietes Opt Mat & Applicat, F-49045 Angers, France. Univ Oran, Lab Synth Organ Appl, Oran, Algeria. RP Salle, M, Univ Angers, Lab Ingn Mol & Mat Organ, CNRS, UMR 6501, 2 Bd Lavoisier, F-49045 Angers, France. TC 13 PD APR 3 PY 2000 VL 6 IS 7 BP 1199 EP 1213 UT ISI:000086437900013 ER PT J AU Marot-Leblond, A Grimaud, L Nail, S Bouterige, S Apaire-Marchais, V Sullivan, DJ Robert, R TI New monoclonal antibody specific for Candida albicans germ tube SO JOURNAL OF CLINICAL MICROBIOLOGY ID CELL-SURFACE HYDROPHOBICITY; PUTATIVE VIRULENCE FACTORS; RAPID IDENTIFICATION; DUBLINIENSIS; ANTIGEN; ADHERENCE; BINDING; MANNOPROTEIN; PURIFICATION; EXPRESSION AB Hydrophobic components of the germ tube of the dimorphic pathogenic fungus Candida albicans were used as immunogens to prepare monoclonal antibodies (MAbs). Among the resulting MAbs, one (MAb 16B1-F10) was shown by indirect immunofluorescence to be specific to the surface of the mycelium phase of the C. albicans and C. stellatoidea species. No labeling of any other genera and Candida species tested was observed, including C. dubliniensis, a newly described species which has many phenotypic similarities to C. albicans. This phase-specific epitope resides on a protein moiety. The molecular mass of the antigen released by Zymolyase digestion was determined by gel filtration and ranges from 25 to 166 kDa. The antigen was also shown to be highly hydrophobic. This anti-C. albicans cell wall surface-specific MAb may be a good candidate for use in tests for the rapid differentiation of the two closely related species C. albicans and C. dubliniensis. C1 UFR Sci Pharmaceut & Ingn Sante, Grp Etud Interact Hote Parasite, F-49100 Angers, France. Univ Dublin Trinity Coll, Sch Dent Sci, Dept Oral Surg Oral Med & Oral Pathol, Dublin 2, Ireland. RP Marot-Leblond, A, Fac Pharm Angers, Lab Mycol, 16 Blvd Daviers, F-49100 Angers, France. TC 13 PD JAN PY 2000 VL 38 IS 1 BP 61 EP 67 UT ISI:000084689800012 ER PT J AU Chapeau-Blondeau, F Rojas-Varela, J TI Nonlinear signal propagation enhanced by noise via stochastic resonance SO INTERNATIONAL JOURNAL OF BIFURCATION AND CHAOS ID CRAYFISH MECHANORECEPTORS; BISTABLE SYSTEM; NEURON MODEL; TRANSMISSION; INFORMATION; ELEMENTS; CAPACITY AB A model is developed for a nonlinear line of coupled noisy threshold elements. The propagation on the line of various information-carrying signals, periodic, aperiodic or random, is analyzed. Different measures quantifying the efficacy of the propagation are calculated, including signal-to-noise ratio, cross-correlation measures, information-theoretic measures and propagation length. These measures are shown to be improvable by the addition of noise. These results establish a new instance of the nonlinear phenomenon of stochastic resonance under the form of a noise-enhanced propagation applying to a broad variety of signals and noises. The results also contain significance for the propagation of neuronal signals. C1 Univ Angers, Lab Ingn Syst Automatises, F-49000 Angers, France. RP Chapeau-Blondeau, F, Univ Angers, Lab Ingn Syst Automatises, 62 Ave Notre Dame du Lac, F-49000 Angers, France. TC 12 PD AUG PY 2000 VL 10 IS 8 BP 1951 EP 1959 UT ISI:000089932000010 ER PT J AU Stone, JD Peterson, AP Eyer, J Sickles, DW TI Neurofilaments are non-essential elements of toxicant-induced reductions in fast axonal transport: Pulse labeling in CNS neurons SO NEUROTOXICOLOGY DE acrylamide; 2,5-hexanedione; fast anterograde axonal transport; neurofilaments; central nervous system ID ACRYLAMIDE-INDUCED NEUROPATHY; FAST AXOPLASMIC-TRANSPORT; PERIPHERAL NERVOUS-SYSTEM; RAT OPTIC-SYSTEM; SCIATIC-NERVE; BIDIRECTIONAL TRANSPORT; MOLECULAR PATHOGENESIS; MICROTUBULE MOTILITY; HEXANE NEUROPATHY; JAPANESE-QUAILS AB Acrylamide (ACR) and g-diketones (g-DK) produce distal sensory-motor neuropathy in a variety of species, including humans. The specific molecular site and mechanism of toxicant action leading to specific morphological and behavioral abnormalities requires definition. The relative roles of fast anterograde axonal transport and neurofilaments (NF) are investigated using optic nerves of mice, with and without axonal neurofilaments. Segmental analysis, following pulse labeling with H-3-leucine into the vitreous body, was used to detect changes in fast anterograde transport in the optic nerve and tract. Single injections of ACR significantly reduced the quantity of radiolabeled proteins transported in both transgenic (lacking NF) and non-transgenic (containing NF] mice by 68.4% and 46.2%, respectively. Similarly, single injections of a,5-hexanedione (2,5-HD) reduced the quantity of radiolabeled transport in transgenic and non-transgenic mice by 55.2% and 47.1%, respectively. Equimolar doses of propionamide and 3,4-hexanedione (non-neurotoxic analogues of ACR and 2,5-HD, respectively) produced no changes in the quantity or apparent rate of optic nerve transport Additionally, no differences in quantity or apparent rate of transport between transgenic and non-transgenic animals were observed under control or experimental conditions. Therefore, ACR and 2,5- HD reduce the quantity of fast anterograde axonal transport in mouse CNS axons in a comparable amount to previously reported reductions in rat PNS axons. The absence of axonal neurofilaments had no effect on normal fast transport. Furthermore, the presence or absence of neurofilaments did not alter the effect of these toxicants on fast axonal transport. We conclude that toxicant-induced reductions in fast axonal transport are unrelated to ACR and g-diketone effects on NF or their accumulation. (C) 2000 Inter Press, Inc. C1 Med Coll Georgia, Dept Cellular Biol & Anat, Augusta, GA 30912 USA. McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ H3A 2T5, Canada. McGill Univ, Mol Oncol Grp, Montreal, PQ H3A 2T5, Canada. CHU Angers, INSERM, F-49033 Angers, France. RP Sickles, DW, Med Coll Georgia, Dept Cellular Biol & Anat, Augusta, GA 30912 USA. TC 12 PD AUG PY 2000 VL 21 IS 4 BP 447 EP 457 UT ISI:000089582900003 ER PT J AU Terret, C Erdociain, E Guimbaud, R Boisdron-Celle, M McLeod, HL Fety-Deporte, R Lafont, T Gamelin, E Bugat, R Canal, P Chatelut, E TI Dose and time dependencies of 5-fluorouracil pharmacokinetics SO CLINICAL PHARMACOLOGY & THERAPEUTICS ID DIHYDROPYRIMIDINE DEHYDROGENASE-ACTIVITY; ADVANCED COLORECTAL-CANCER; POSITRON-EMISSION-TOMOGRAPHY; CONTINUOUS VENOUS INFUSION; MONONUCLEAR-CELLS; SPECTROSCOPY DATA; CIRCADIAN-RHYTHM; RANDOMIZED TRIAL; FLUOROURACIL; PLASMA AB Objectives: The purpose of this study was to examine the interpatient and intrapatient variability of the Michaelis-Menten plasma parameters of 5-fluorouracil administered according to a schedule combining a bolus of 400 mg/m(2) followed by 22-hour infusion of 600 mg/m(2) for 2 consecutive days. Patients. A pharmacokinetic population approach was used to analyze the data from 21 patients with colorectal cancer. Results: The 5-fluorouracil plasma concentrations versus time were best described by a two-compartment model with nonlinear elimination from the central compartment. The relationships between the pharmacokinetic parameters and patient characteristics were tested. On day 1 the mean values (with interindividual variability as expressed by the coefficient of variation) were 1390 mg . h(-1) (20%), and 5.57 mg . L-1 (22%) for the maximum rate of elimination, and the half-saturating plasma concentration. The maximum rate of elimination was positively correlated to the body surface area and the percentage of liver involvement by metastatic disease determined by tomodensitometric examination. The model was successfully tested with independent data sets corresponding to other schedules. The analysis of this intrapatient variability showed that the half-saturating plasma concentration increased from day 1 to day 2, especially in the patients with low lymphocyte cell dihydropyrimidine dehydrogenase activity. Conclusion: The pharmacokinetic parameters obtained in this study would be useful to predict the 5-fluorouracil plasma concentrations following other schedules of administration of 5-fluorouracil and to study the possible pharmacokinetic interactions between 5-fluorouracil and other drugs. C1 Ctr Paul Papin, Angers, France. Univ Aberdeen, Aberdeen, Scotland. Ctr Rene Gauducheau, Nantes, France. Inst Claudius Regaud, Toulouse, France. Univ Toulouse 3, F-31062 Toulouse, France. RP Chatelut, E, 20-24 Rue Pont-St-Pierre, F-31052 Toulouse, France. TC 12 PD SEP PY 2000 VL 68 IS 3 BP 270 EP 279 UT ISI:000089560000006 ER PT J AU Vergani, B Kintrup, M Hillen, W Lami, H Piemont, E Bombarda, E Alberti, P Doglia, SM Chabbert, M TI Backbone dynamics of Tet repressor alpha 8 boolean AND alpha 9 loop SO BIOCHEMISTRY ID N-15 NMR RELAXATION; NUCLEAR MAGNETIC-RESONANCE; TIME-RESOLVED FLUORESCENCE; FK506 BINDING-PROTEIN; SIDE-CHAIN DYNAMICS; MOLECULAR-DYNAMICS; CONFORMATIONAL-CHANGES; TRYPTOPHAN RESIDUES; STRUCTURAL BASIS; STAPHYLOCOCCAL NUCLEASE AB A set of single Trp mutants of class B Tet repressor (TetR), in which Trp residues are located from positions 159 to 167, has been engineered to investigate the dynamics of the loop joining the alpha-helices 8 and 9. The fluorescence anisotropy decay of most mutants can be described by the sum of three exponential components. The longest rotational correlation time, 30 ns at 10 degrees C, corresponds to the overall rotation of the protein. The shortest two components, on the subnanosecond and nanosecond time scale, are related to internal motions of the protein. The initial anisotropy, in the 0.16-0.22 range, indicates the existence of an additional ultrafast motion on the picosecond time scale. Examination of physical models for underlying motions indicates that librational motions of the Trp side chain within the rotameric chi(1) x chi(2) potential wells contribute to the picosecond depolarization process, whereas the subnanosecond and nanosecond depolarization processes are related to backbone dynamics. In the absence of inducer, the order parameters of these motions, about 0.90 and 0.80 for most positions, indicate limited flexibility of the loop backbone. Anhydrotetracycline binding to TetR induces an increased mobility of the loop on the nanosecond time scale. This suggests that entropic factors might play a role in the mechanism of allosteric transition. C1 Univ Strasbourg 1, Fac Pharm, Lab Pharmacol & Physicochim, CNRS,UMR 7034, F-67401 Illkirch, France. Univ Milan, Dipartimento Fis, I-20133 Milan, Italy. Univ Erlangen Nurnberg, Inst Mikrobiol Biochem & Genet, Lehrstuhl Mikrobiol, D-91058 Erlangen, Germany. RP Chabbert, M, CHU Angers, INSERM E 9928, 4 Rue Larrey, F-49033 Angers, France. TC 12 PD MAR 14 PY 2000 VL 39 IS 10 BP 2759 EP 2768 UT ISI:000085905300037 ER PT J AU Sebastian, RM Caminade, AM Majoral, JP Levillain, E Huchet, L Roncali, J TI Electrogenerated poly(dendrimers) containing conjugated poly(thiophene) chains SO CHEMICAL COMMUNICATIONS ID DENDRIMERS; REACTIVITY; SHAPE AB Electroactive conjugated polymers have been synthesized by electropolymerisation of increasing generations of dendrimers derivatized by peripheral bithiophene groups. C1 Chim Coordinat Lab, CNRS, UPR 8241, F-31077 Toulouse, France. Univ Angers, CNRS, UMR 6501, F-49045 Angers, France. RP Roncali, J, Univ Angers, CNRS, UMR 6501, 2 Bd Lavoisier, F-49045 Angers, France. TC 12 PY 2000 IS 6 BP 507 EP 508 UT ISI:000085822200039 ER PT J AU Audran, M Legrand, E TI Hypercalciuria SO JOINT BONE SPINE DE hypercalciuria ID BONE-MINERAL CONTENT; CALCIUM STONE FORMERS; IDIOPATHIC HYPERCALCIURIA; URINARY CALCIUM; VITAMIN-D; NEPHROLITHIASIS; DENSITY; PATHOGENESIS; DIET; UROLITHIASIS AB Hypercalciuria is a biological syndrome defined as excretion in the urine of more than 0.1 mmol/kg/24 hours of calcium in the absence of dietary manipulation. A number of endocrine, renal, and bone diseases can cause hypercalciuria. Urinary calcium excretion is substantially influenced by dietary intakes of calcium, sodium, protein, carbohydrates, alcohol, and potassium: a poorly balanced diet can result in hypercalciuria. Recently, there has been a burst of interest in the molecular underpinnings of rare nephrolithiasis syndromes, which have been shown to result from mutations in the CLCN5 chloride channel gene. Mutations affecting the calcium-sensing receptor (CaSR) have been identified in other forms of hypercalciuria. Idiopathic hypercalciuria is defined as hypercalciuria that persists after correction of dietary imbalances and has no detectable cause. The classification suggested by Pak ("absorptive" hypercalciuria [with three types] and "renal" hypercalciuria) is controversial and of little assistance in clinical practice. Three mechanisms can be incriminated in idiopathic hypercalciuria: increased intestinal absorption of calcium, defective reabsorption of calcium by the renal tubule, and increased bone resorption. Overexpression of the vitamin D receptor (VDR) and deficiencies in renal tubule enzymes may also be involved. Bone mineral density is moderately decreased in idiopathic hypercalciuria, particularly in the renal type. The risk of vertebral fracture seems increased, however. Overproduction of calcitriol and cytokines that stimulate bone resorption have been incriminated in the bone loss. Treatment of the cause is essential in secondary hypercalciuria (dietary advice, treatment of an underlying disease, etc.). A diet low in sodium and meat and containing no more than 800 mg of calcium per day is advocated in idiopathic hypercalciuria. Hydrochlorothiazide therapy is warranted in patients with osteopenia and an inadequate response to dietary therapy. (C) 2000 Editions scientifiques et medicales Elsevier SAS. C1 CHU Angers, Serv Rhumatol, F-49033 Angers 01, France. RP Audran, M, CHU Angers, Serv Rhumatol, 4 Rue Larrey, F-49033 Angers 01, France. TC 11 PY 2000 VL 67 IS 6 BP 509 EP 515 UT ISI:000166012900004 ER PT J AU Colombat, P Cornillet, P Deconinck, E Tourani, JM Gardembas, M Delain, M Abgrall, JF Kootz, C Milpied, N TI Value of autologous stem cell transplantation with purged bone marrow as first-line therapy for follicular lymphoma with high tumor burden: a GOELAMS phase II study SO BONE MARROW TRANSPLANTATION DE autologous stem cell transplantation; chemotherapy; follicular lymphoma; minimal residual disease; purging ID NON-HODGKINS-LYMPHOMA; POLYMERASE-CHAIN-REACTION; HIGH-DOSE THERAPY; MYELOABLATIVE THERAPY; BCL-2 TRANSLOCATION; POSITIVE CELLS; CHEMOTHERAPY; CONSOLIDATION; ENGRAFTMENT; SURVIVAL AB This prospective phase II study was undertaken to evaluate the efficacy and toxicity of early intensive therapy followed by purged autologous bone marrow transplantation (ABMT) in patients with follicular lymphoma with high tumor burden, All patients received the VCAP regimen (vindesine, cyclophosphamide, doxorubicin and prednisone) as conventional chemotherapy and DHAP as second-line therapy. Twenty-nine consecutive patients were included in the study. Twenty-seven patients were grafted, seven in first complete remission (CR) and 20 in first partial remission (PR), Preparative therapy consisted of cyclophosphamide and total body irradiation (TBI) in all the patients. With a median follow-up of 6 years, the actuarial overall survival is 64% and the actuarial event-free survival is 55%, Two treatment-related early deaths were observed. Eleven patients were informative for serial PCR analysis of minimal residual disease after ABMT: two relapsed, four remained disease-free with PCR positivity and five were disease-free with PCR negativity. These encouraging results lay the basis of future prospective randomized trials comparing autologous stem cell transplantation as front-line treatment with conventional chemotherapy for patients with bad prognostic factors. C1 CHU Bretonneau, Dept Hematol, F-37044 Tours, France. CHU Reims, Hop Robert Debre, Reims, France. CHU Besancon, Hop J Minjoz, F-25030 Besancon, France. Hop Laennec, F-75340 Paris, France. CHU Angers, Angers, France. CHU Brest, Hop Morvan, F-29285 Brest, France. CHU Nantes, Hotel Dieu, F-44035 Nantes 01, France. RP Colombat, P, CHU Bretonneau, Dept Haematol, 2 Bd Tonnelle, F-37044 Tours, France. TC 11 PD NOV PY 2000 VL 26 IS 9 BP 971 EP 977 UT ISI:000165098900006 ER PT J AU Hensen, SM Pavicic, MJAM Lohuis, JACM de Hoog, JAM Poutrel, B TI Location of Staphylococcus aureus within the experimentally infected bovine udder and the expression of capsular polysaccharide type 5 in situ SO JOURNAL OF DAIRY SCIENCE DE Staphylococcus aureus; mastitis; capsular polysaccharide ID MAMMARY EPITHELIAL-CELLS; MICROCAPSULE EXPRESSION; BACTERIAL VIRULENCE; MASTITIS; GROWTH; GLAND; MILK; PATHOGENESIS; ADHERENCE; INVASION AB The objective of this study was to locate Staphylococcus aureus in the bovine udder and to investigate the expression of capsular polysaccharide type 5 (CP5) in situ in both the early and chronic stages of experimental intramammary S. aureus infections. Bovine udder tissue was obtained in early and chronic stages of intramammary infection; i.e., 24 to 96 h and 122 d after experimental intramammary infection with S. aureus Newbould 305. The presence and location of S. aureus was investigated by Gram staining of tissue sections. The expression of CP5 by S. aureus in situ was investigated by immunochemical staining of tissue sections with specific antibodies against CP5. Both in the early and chronic stages of infection, S. aureus was located within the lumen of alveoli or lactiferous ducts, in association with the epithelium, and within phagocytic cells. The staphylococci were mainly observed in clusters and often in the presence of polymorphonuclear neutrophils. Expression of CP5 by S. aureus was observed both in the early and chronic stages of infection. In general, CP5-positive S. aureus were located in alveoli and in association with the mammary epithelium. In the chronic infection, CP5-positive S. aureus were also located deep in the interstitial tissue. These results indicate that-both in early and chronic stages of experimental S. aureus mastitis-colonization of the mammary epithelia and invasion into the interstitial tissue occurs and that CP5 is expressed by S. aureus Newbould 305 in situ. The invasion of S. aureus in the interstitial tissue and the expression of CP5 probably help the bacteria to withstand the host defense mechanisms. C1 Intervet Int BV, Dept Bacteriol R&D, Boxmeer, Netherlands. Intervet Pharma Res & Dev, Angers, France. Inst Natl Rech Agron, Lab Pathol Infect & Immunol, Nouzilly, France. RP Hensen, SM, Intervet Int BV, Dept Bacteriol R&D, Boxmeer, Netherlands. TC 11 PD SEP PY 2000 VL 83 IS 9 BP 1966 EP 1975 UT ISI:000089295200010 ER PT J AU Robert, J Trystram, D Truffot-Pernot, C Carbonnelle, B Grosset, J CA AZAY Mycobacteria Study Grp TI Surveillance of Mycobacterium tuberculosis drug resistance France, 1995-1997 SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE DE M. tuberculosis; resistance; epidemiology ID RISK-FACTORS; NETHERLANDS; ORIGIN; TRENDS; RATES AB OBJECTIVE: To measure the rate of primary and secondary drug resistance of Mycobacterium tuberculosis on an ongoing basis. DESIGN: Data on all culture-positive tuberculosis were collected prospectively from 1995 through 1997 from a microbiological laboratory network of 19 university hospitals throughout France, and submitted quarterly to the National Reference Centre for Surveillance of Mycobacterial Diseases. RESULTS: A total of 2998 patients were included in the study. Among the 2333 (78%) previously untreated patients, 8.6% had isolates resistant to any drug, 4.8% to streptomycin (SM) alone, 1.2% to isoniazid (INH) alone, 1.8% to SM + INH, and 0.3% to INH + rifampicin (RMP) or multidrug resistance (MDR). Foreign birth was independently associated with a higher risk of primary resistance to any drug (odds ratio [OR] 1.5). Among the 268 (9%) previously treated patients, 20.9% had isolates resistant to any drug, 6.3% to SM alone, 3.4% to INH alone, 4.1% to SM + INH, and 3.7% to INH + RMP. Foreign birth (OR = 2.3), and human immunodeficiency virus positive status (OR = 4.4) were independently associated with a higher risk of secondary resistance to any drug. CONCLUSION: During the last 30 years there has been no increase in resistance to any drug among previously untreated patients. As expected, secondary resistance was highly associated with foreign birth. MDR-TB remains a rare event in France. C1 Grp Hosp Pitie Salpetriere, Lab Bacteriol Hyg, Ctr Natl Reference Surveillance Infect Mycobacter, F-75651 Paris 13, France. CHU Angers, AZAY, Mycobacteria Study Grp, Angers, France. CHU Angers, Lab Bacteriol Virol, Angers, France. RP Grosset, J, Grp Hosp Pitie Salpetriere, Lab Bacteriol Hyg, Ctr Natl Reference Surveillance Infect Mycobacter, 47-83 Blvd Hop, F-75651 Paris 13, France. TC 11 PD JUL PY 2000 VL 4 IS 7 BP 665 EP 672 UT ISI:000088752600012 ER PT J AU Rahali, V Chobert, JM Haertle, T Gueguen, J TI Emulsification of chemical and enzymatic hydrolysates of beta-lactoglobulin: characterization of the peptides adsorbed at the interface SO NAHRUNG-FOOD ID EMULSIFYING PROPERTIES; LIQUID INTERFACES; MILK-PROTEINS; FUNCTIONAL-PROPERTIES; TRYPTIC PEPTIDES; FOOD PROTEINS; WHEY PROTEINS; CASEIN; PROTEOLYSIS; SOLUBILITY AB Bovine beta-Lactoglobulin (BLG) was cleaved by BNPS-skatole (2-(2'-nitrophenylsulfenyl)-3-methyl-3'-bromoindolenine), trypsin, or pepsin in 40% ethanol before emulsification with hexadecane in order to characterize the peptides active at the interfaces. The total digests and the different phases obtained after emulsification were analyzed by RP-HPLC to separate the peptides according to their gradual order on a hydrophilicity-to-hydrophobicity scale. In each case, hydrophobic peptides were recovered in the creamed phase and characterized by mass spectrometry and sequencing. After tryptic hydrolysis, short peptides were identified at the interfacial layer as fragments S-21-L-32, V-41-L-57, V-41-K-60, and W-61-K-70 linked to L-149-I-162 by a C-66-C-160 bond. It indicates that the hydrophilic/hydrophobic distribution of the amino acids in the sequence of the fragments is more relevant to adsorption than the length of the peptide. BNPS-skatole and peptic hydrolysis produced larger hydrophobic peptides which were also recovered in the creamed phase of the emulsion and characterized. C1 Inst Natl Rech Agron, Unite Biochim & Technol Prot, F-44316 Nantes 3, France. Ecole Super Agr, Angers, France. Inst Natl Rech Agron, Lab Etud & Interact Mol Alimentaires, F-44316 Nantes, France. RP Gueguen, J, Inst Natl Rech Agron, Unite Biochim & Technol Prot, BP 71627, F-44316 Nantes 3, France. TC 11 PD APR PY 2000 VL 44 IS 2 BP 89 EP 95 UT ISI:000086539900004 ER PT J AU Chabasse, D Baran, R De Chauvin, MF TI Onychomycosis I: epidemiology and etiology SO JOURNAL DE MYCOLOGIE MEDICALE ID QUALITY-OF-LIFE; HENDERSONULA-TORULOIDEA; SCYTALIDIUM-HYALINUM; TINEA-PEDIS; DERMATOPHYTE ONYCHOMYCOSIS; SUBUNGUAL ONYCHOMYCOSIS; ONYCHOCOLA-CANADENSIS; CHAETOMIUM-GLOBOSUM; FUNGAL-INFECTIONS; CLINICAL-FEATURES AB A common disease. Onychomycosis is one of the most common nail diseases. Difficult to bear by some patients, onychomycosis is one of the most frequent reasons for consulting a mycological center. However, the estimated frequency of onychomycosis varies depending on whether the studies of prevalence concern the general population (2 to 13 % according to different authors) or target individuals consulting a primary care physician. Recent large scale surveys in Europe indicate a high prevalence in adults: 20 to 30 %, depending on whether the instigator is a general practitioner or a dermatologist. Epidemiological features. All studies concur that onychomycosis has been in constant progression over the last twenty years. Rarely observed in children, frequent in adults, onychomycosis principally affects the elderly. In Western Europe and in North America, onychomycosis involves principally the feet, especially in men. By contrast, in Southern Europe, in the Middle and Far East, the prevalence is highest in women's fingernails (often associated with paronychia). Favoring factors. Among the factors promoting fungal nail invasion, some are local patient-dependent factors (trophic disorders and circulatory impairment, overlapping of digits, etc.) and others are more general factors such as immunosuppression, diabetes mellitus or psoriasis. There are also behavioral factors (occupation, lifestyle, sports) which favor encounter with the pathogenic fungi. Causal species. Among the numerous species (nearly one hundred) responsible for onychomycosis, emphasis should be given to those which are keratinophilic, i.e., dermatophytes (mainly the antropophilic types) such as Trichophyton rubrum, and Trichophyton mentagrophytes, var. interdigitale, pseudo-dermatophytes such as Scytalidium spp. and Onychocola canadensis, or geophilic saprophytes (molds) requiring stringent criteria (direct mycological or histological examination) to establish their; pathogenicity. A mold (Aspergillus sp., Fusarium sp.) in a nail can be a dangerous portal of entry in immunocompromised subjects. Among the yeasts that invade mainly the fingernails, besides commensal species (such as Candida albicans), other species behave as predictive parasites of the nail (Candida ciferrii, Candida haemulonii). C1 CHU Angers, Lab Parasitol Mycol, F-49033 Angers, France. RP Chabasse, D, CHU Angers, Lab Parasitol Mycol, 4 Rue Larrey, F-49033 Angers, France. TC 10 PD DEC PY 2000 VL 10 IS 4 BP 177 EP 190 UT ISI:000166938200002 ER PT J AU Marques, ASD Corbiere, R Gardan, L Tourte, C Manceau, C Taylor, JD Samson, R TI Multiphasic approach for the identification of the different classification levels of Pseudomonas savastanoi pv.phaseolicola SO EUROPEAN JOURNAL OF PLANT PATHOLOGY DE PCR; Phaseolus vulgaris; phenotypic characters; RAPD; rep-PCR; serology ID SYRINGAE PV PHASEOLICOLA; POLYMERASE CHAIN-REACTION; BACTERIAL SYSTEMATICS; POLYPHASIC TAXONOMY; ARBITRARY PRIMERS; BEAN SEED; REP-PCR; DNA; PATHOVARS; STRAINS AB The relationships between strains of Pseudomonas savastanoi pv. phaseolicola (P. sav. phaseolicola), P. syringae pv. tabaci (P. syr. tabaci) and P. syr. syringae which all cause disease on bean; the related species P. sav. glycinea and P. syr. actinidiae, and reference bacteria, were evaluated by studying the phenotypic and genetic diversity of a collection of 62 strains. All the P. sav. phaseolicola strains tested produced characteristic watersoaked lesions on bean pods. Other pathovars produced varying combinations of symptoms including necrotic lesions, with or without watersoaked centres and sunken tissue collapse of the lesion (P. syr. tabaci) and necrotic lesions with or without sunken collapse (P. syr. syringae). At the genomospecies level, all the strains of P. sav. phaseolicola, P. sav. glycinea and P. syr. tabaci, belonging to genomospecies 2, could be separated from P. syr. syringae strains (genomospecies 1) and P. syr. actinidiae strains (unknown genomospecies) by BOX-PCR and DNA/DNA hybridisation. To distinguish P. sav. phaseolicola, within genomospecies 2, from P. sav. glycinea and P. syr. tabaci, it was necessary to perform nutritional characterisations (myo-inositol negative and p-hydroxy benzoate positive for P. sav. phaseolicola strains), PCR with specific primers designed from the tox region (positive for all of the P. sav. phaseolicola strains) and serotyping, as 71% of the P. sav. phaseolicola strains reacted as O-serogroup PHA1. Important intrapathovar variation was seen by genomic fingerprinting with REP and ERIC primers, as well as with RAPD primers (AE7 and AE10) and esterase profilings. While RAPD fingerprinting detected variability correlated with two race-associated evolutionary lines, REP, ERIC and esterase profiles revealed intrapathovar variation linked to some host origins, that separated the kudzu isolates, and the mungbean isolates, from the other P. sav. phaseolicola strains. C1 INRA, Pathol Vegetale Stn, Ctr Angers, F-49071 Beaucouze, France. EMBRAPA, BR-70870900 Brasilia, DF, Brazil. Hort Res Int, Warwick CV35 9EF, England. RP Samson, R, INRA, Pathol Vegetale Stn, Ctr Angers, 42 Rue Georges Morel,BP 57, F-49071 Beaucouze, France. TC 10 PD OCT PY 2000 VL 106 IS 8 BP 715 EP 734 UT ISI:000165474600002 ER PT J AU Buitink, J Leprince, O Hoekstra, FA TI Dehydration-induced redistribution of amphiphilic molecules between cytoplasm and lipids is associated with desiccation tolerance in seeds SO PLANT PHYSIOLOGY ID ELECTRON-PARAMAGNETIC-RESONANCE; PATHOGEN BACILLUS-CEREUS; MEMBRANE-PERMEABILITY; BILAYER-MEMBRANES; WATER-CONTENT; SPIN-PROBE; FLAVONOIDS; FOOD; THERMODYNAMICS; TEMPERATURE AB This study establishes a relationship between desiccation tolerance and the transfer of amphiphilic molecules from the cytoplasm into lipids during drying, using electron paramagnetic resonance spectroscopy of amphiphilic spin probes introduced into imbibed radicles of pea (Pisum sativum) and cucumber (Cucumis sativa) seeds. Survival following drying and a membrane integrity assay indicated that desiccation tolerance was present during early imbibition and lost in germinated radicles. In germinated cucumber radicles, desiccation tolerance could be re-induced by an incubation in polyethylene glycol (PEG) before drying. In desiccation-intolerant radicles, partitioning of spin probes into lipids during dehydration occurred at higher water contents compared with tolerant and PEG-induced tolerant radicles. The difference in partitioning behavior between desiccation-tolerant and -intolerant tissues could not be explained by the loss of water. Consequently, using a two-phase model system composed of sunflower or cucumber oil and water, physical properties of the aqueous solvent that may affect the partitioning of amphiphilic spin probes were investigated. A significant relationship was found between the partitioning of spin probes and the viscosity of the aqueous solvent. Moreover, in desiccation-sensitive radicles, the rise in cellular microviscosity during drying commenced at higher water contents compared with tolerant or PEG-induced tolerant radicles, suggesting that the microviscosity of the cytoplasm may control the partitioning behavior in dehydrating seeds. C1 Agr Univ Wageningen, Dept Plant Sci, Lab Plant Physiol, NL-6703 BD Wageningen, Netherlands. RP Leprince, O, Inst Natl Hort, Grp Physiol mol Sci, UMR, 2 Rue Notre, F-49045 Angers, France. TC 10 PD NOV PY 2000 VL 124 IS 3 BP 1413 EP 1425 UT ISI:000165365800048 ER PT J AU Grolleau, F Sattelle, DB TI Single channel analysis of the blocking actions of BIDN and fipronil on a Drosophila melanogaster GABA receptor (RDL) stably expressed in a Drosophila cell line SO BRITISH JOURNAL OF PHARMACOLOGY DE GABA receptor; BIDN; fipronil; Drosophila melanogaster; stable cell line; single channel ID GATED CHLORIDE CHANNEL; BICYCLIC DINITRILE CONVULSANT; XENOPUS OOCYTES; HOMO-OLIGOMERS; ION CHANNELS; AMINO-ACID; WILD-TYPE; INSECTICIDE; DIELDRIN; NEURONS AB 1 Single channel recordings were obtained from a Drosophila S2 cell line stably expressing the wildtype RDLac Drosophila melanogaster homomer-forming ionotropic GABA receptor subunit, a product of the resistance to dieldrin gene, Rdl. GABA (50 mu M) was applied by pressure ejection to outside-out patches from S2-RDL cells at a holding potential of -60 mV. The resulting inward current was completely blocked by 100 mu M picrotoxin (PTX). The unitary current-voltage relationship was linear at negative potentials but showed slight inward rectification at potentials more positive than 0 mV. The reversal potential of the current (E-GABA = - 1.4 mV) was close to the calculated chloride equilibrium potential. 2 The single channel conductance elicited by GABA was 36 pS. A 71 pS conductance channel was also observed when the duration of the pulse, used to eject GABA, was longer than SO ms. The mean open time distribution of the unitary events was fitted best by two exponential functions suggesting two open channel states. 3 When either 1 mu M fipronil or 1 mu M BIDN was present in the external saline, the GABA-gated channels were completely blocked. When BIDN or fipronil was applied at a concentration close to the IC50 value for suppression of open probability (281 nM, BIDN; 240 nM, fipronil), the duration of channel openings was shortened. In addition, the blocking action of BIDN resulted in the appearance of a novel channel conductance (17 pS). 4 The effects of co-application of BIDN and fipronil were examined. Go-application of BIDN (300 nM) with various concentrations (100-1000 nM) of fipronil resulted in an additional BIDN-induced dose-dependent reduction of the maximum P-o value. 5 Thus both BIDN and fipronil shorten the duration of wild-type RDLac GABA receptor channel openings but appear to act at distinct sites. C1 Univ Angers, UFR Sci, Neurophysiol Lab, RCIM,UPRES EA 2647, F-49045 Angers, France. Univ Oxford, Dept Human Anat & Genet, MRC, Funct Genet Unit, Oxford OX1 3QX, England. RP Grolleau, F, Univ Angers, UFR Sci, Neurophysiol Lab, RCIM,UPRES EA 2647, 2 Blvd Lacoisier, F-49045 Angers, France. TC 10 PD AUG PY 2000 VL 130 IS 8 BP 1833 EP 1842 UT ISI:000088880100014 ER PT J AU Hambli, R Badie-Levet, D TI Damage and fracture simulation during the extrusion processes SO COMPUTER METHODS IN APPLIED MECHANICS AND ENGINEERING DE fracture; damage; extrusion; finite element; experiment AB In order to accurately predict the damage and failure evolution in the case of metal forming processes, such as stamping and extrusion, a finite element model valid for numerically describing of such processes has been developed. Damage and crack propagation have been taken into account by means of continuum damage mechanics concepts. To study the effects of variation of processes parameters on the geometry of the workpiece, we have implemented a calculation algorithm by means of the user routine (UMAT) of ABAQUS/Standard finite element code. This model enables deformation and fracture initiation to be examined under several different loading conditions. An example is also given to illustrate the potential applicability of the model. The numerical results obtained by the simulation were compared with experimental ones in order to verify the validity of th proposed finite element model. (C) 2000 Elsevier Science S.A. All rights reserved. C1 ENSAM, Lab Genie Mecan, F-49035 Angers, France. CAO, F-49035 Angers, France. RP Hambli, R, ENSAM, Lab Genie Mecan, 2 Blvd Ronceray,BP 3525, F-49035 Angers, France. TC 10 PY 2000 VL 186 IS 1 BP 109 EP 120 UT ISI:000087521100007 ER PT J AU Bailly, C Benamar, A Corbineau, F Come, D TI Antioxidant systems in sunflower (Helianthus annuus L.) seeds as affected by priming SO SEED SCIENCE RESEARCH DE catalase; germination; glutathione reductase; Helianthus annuus; lipid peroxidation; osmopriming; sunflower seed; superoxide dismutase ID GLUTATHIONE-REDUCTASE; SUPEROXIDE-DISMUTASE; TOMATO SEEDS; STRESS; PLANTS; GERMINATION; OXYGEN; EXPRESSION; RESPONSES; CATALASE AB Priming treatment of sunflower (Helianthus annuus L., cv Briosol) seeds for 7 days at 15 degrees C with a polyethylene glycol solution at -2.0 MPa strongly improved their subsequent germination at 15 degrees C on water. This stimulatory effect of priming remained after drying back the seeds at 20 degrees C for 3 days. Malondialdehyde (MDA) and activities of superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) were measured in control unprimed seeds, primed seeds, seeds primed then dried, and after 3 and 6 hours of imbibition of control and dried primed seeds in order to determine whether the cell antioxidant systems were involved in the beneficial effect of priming. The osmotreatment resulted in a strong increase in SOD and CAT activities but did not markedly affect MDA and GR activity. Following the 3 days of drying, MDA increased and the enzyme activities became similar to those measured in dry unprimed seeds, although the stimulatory effect of priming on germination remained. Imbibition of control dry seeds was associated with an increase in MDA and a decrease in CAT and GR activities, whereas reimbibition of dried primed seeds resulted in a decrease in MDA and an increase in SOD, CAT and GR activities. Isoform patterns on native gels showed no difference between treated (priming with or without subsequent drying) and control seeds for SOD (7 isoforms) and GR (5 isoforms), but the osmotreatment did induce a second isoform of CAT. The results obtained indicate that the CAT isoform pattern might be used as an indicator of the priming treatment that promotes germination. Involvement of the antioxidant systems in seed vigour is discussed. C1 Univ Paris 06, F-75252 Paris 05, France. LRPV, F-49045 Angers, France. RP Corbineau, F, Univ Paris 06, Tour 53,1er Etage,4 Pl Jussieu, F-75252 Paris 05, France. TC 10 PD MAR PY 2000 VL 10 IS 1 BP 35 EP 42 UT ISI:000087063100003 ER PT J AU Banine, F Gangneux, C Mercier, L Le Cam, A Salier, LP TI Positive and negative elements modulate the promoter of the human liver-specific alpha 2-HS-glycoprotein gene SO EUROPEAN JOURNAL OF BIOCHEMISTRY DE alpha 2-HS-glycoprotein; hepatic transcription; NF-1; promoter; silencer ID RECEPTOR TYROSINE KINASE; MAMMALIAN FETUIN FAMILY; HUMAN ALPHA-2-HS GLYCOPROTEIN; INSULIN-RECEPTOR; RAT FETUIN; TRANSCRIPTIONAL REGULATION; MOUSE COUNTERTRYPIN; NATURAL INHIBITOR; BOVINE FETUIN; GROWTH-FACTOR AB The human alpha 2-HS-glycoprotein (AHSG) and the 63-kDa rat phosphoprotein (pp63) are homologous plasma proteins that belong to the fetuin family. AHSG and pp63 are involved in important functions such as inhibition of insulin receptor tyrosine kinase activity, inhibition of protease activities, and regulation of calcium metabolism and osteogenesis. Studies of the AHSG proximal promoter performed in vitro, in rat and human cells indicate that several NF-1 and C/EBP binding sites exert a positive effect on its transcriptional activity. However, until now, no distal elements have been examined in this gene, in either species. We report that the human AHSG gene promoter acts in a liver-specific manner and is further controlled by three distal, 5'-flanking elements. The negative elements III and I are, respectively, located 5' and 3' of the positive element II. All three elements require the natural context of the human AHSG gene to fully exert their negative or positive effect. Element I harbours a single binding site for NF-1. This nuclear factor thus appears to be able to up- or downregulate the AHSG gene depending on the site it binds to. Elements I, II and possibly III are absent in the rodent Ahsg gene encoding pp63. C1 Fac Med Pharm, INSERM, U519, F-76183 Rouen, France. Inst Federatif Rech Multidisciplinaires Peptides, Rouen, France. Fac Med Pharm, Lab Histol Embryol, Angers, France. INSERM, U376, Montpellier, France. RP Salier, LP, Fac Med Pharm, INSERM, U519, 22 Bvd Gambetta, F-76183 Rouen, France. TC 10 PD FEB PY 2000 VL 267 IS 4 BP 1214 EP 1222 UT ISI:000085738300036 ER PT J AU Lepinard, C Descamps, P Meneguzzi, G Blanchet-Bardon, C Germain, DP Larget-Piet, L Beringue, F Berchel, C Muller, F Dumez, Y TI Prenatal diagnosis of pyloric atresia-junctional epidermolysis bullosa syndrome in a fetus not known to be at risk SO PRENATAL DIAGNOSIS DE prenatal diagnosis; ultrasonography; pyloric atresia-junctional epidermolysis bullosa syndrome; amniotic acetylcholinesterase; alpha 6-beta 4 integrin mutation ID GASTRIC OUTLET OBSTRUCTION; APLASIA-CUTIS-CONGENITA; ELEVATED ALPHA-FETOPROTEIN; INTEGRIN BETA-4; CLASSIFICATION; SKIN; ULTRASONOGRAPHY; ASSOCIATION; EXPRESSION; MUTATION AB Junctional epidermolysis bullosa with pyloric atresia (PA-JEB) is a highly lethal, inherited, autosomal recessive disease. Thus far, prenatal diagnosis of this syndrome was only realized on pregnancies at risk for recurrence. We report the case of a 26-year-old woman, first cousin to her husband, who had undergone amniocentesis for polyhydramnios. The karyotype was normal but the amniotic fluid contained acetylcholinesterase. A targeted scan at 25 weeks' gestation did not find spina bifida, but polyhydramnios with a dilated stomach, and several other anomalies: echogenic particles in the amniotic fluid, a thin skin which closely adhered to the nasal bones, narrow nostrils, abnormal ears, fisted hands, malposition of both first toes, and kidney malformation. Despite no previous case in the family, it was thought that sonographic findings were suggestive of the PA-JEB syndrome. A fetal skin biopsy was carried out at 28 weeks' gestation. The ultrastructural examination of fetal skin displayed JEB. Genetic analysis detected a homozygous mutation in the gene encoding integrin alpha 6. Termination of pregnancy was carried out at 29 weeks' gestation. These results illustrate that in the case of a fetus not known to be at risk, diagnosis of PA-JEB can be achieved by ultrasound findings leading to fetal skin biopsy and ultrastructural examination of blistered epidermis. Some new sonographic signs should raise the possibility of significant cutaneous desquamation and blister formation in a fetus, especially when there is positive amniotic acetylcholinesterase coupled with elevated alpha-fetoprotein or suspected pyloric atresia. Copyright (C) 2000 John Wiley & Sons, Ltd. C1 Ctr Hosp Reg Angers, Serv Gynecol Obstet, Angers, France. Fac Med Nice, INSERM, U385, F-06034 Nice, France. Hop St Louis, Serv Dermatol, F-75475 Paris, France. CHU Cochin, Genet Lab, Paris, France. Ctr Hosp Reg Angers, Serv Genet, Angers, France. Ctr Hosp Reg Angers, Ctr Neonatal, Angers, France. Hop Ambroise Pare, Boulogne Sur Seine, France. Hop Necker Enfants Malad, Paris, France. RP Lepinard, C, 20 D Rue Dupetit Thouars, F-49000 Angers, France. TC 10 PD JAN PY 2000 VL 20 IS 1 BP 70 EP 75 UT ISI:000085087100016 ER PT J AU Schlegel, L Coudray-Lucas, C Barbut, F Le Boucher, J Jardel, A Zarrabian, S Cynober, L TI Bacterial dissemination and metabolic changes in rats induced by endotoxemia following intestinal E-coli overgrowth are reduced by ornithine alpha-ketoglutarate administration SO JOURNAL OF NUTRITION DE ornithine alpha-ketoglutarate; endotoxemia; bacterial translocation; protein catabolism rats ID ENTERAL NUTRITION; HYPERMETABOLIC RESPONSE; BURNED MICE; TRANSLOCATION; GUT; GLUTAMINE; ARGININE; MALNUTRITION; SUPPLEMENTATION; ADAPTATION AB The efficacy of ornithine alpha -ketoglutarare (OKG) in preventing bacterial translocation and dissemination, metabolic disorders and changes in mucosal enzyme activities was assessed in a model of bacterial translocation in rats. Antibiotic decontamination was performed 4 d before intragastric inoculation with an Escherichia coil strain (10(10) bacteria/kg body). Two days later, the rats were given either a lipopolysaccharide (LPS) 0127:B8 or a saline injection and were deprived of food for 24 h. Enteral nutrition, [Osmolite, 880 kJ/(kg d)] supplemented with either OKG (LPS + OKG) or glycine (Saline + Gly or LPS + Gly), was then given for 2 d. Urinary total nitrogen losses and 3-methylhistidine excretion were determined daily. On killing at d 3, bacterial translocation to the mesenteric lymph nodes (MLN) and dissemination to the spleen and liver were evaluated, jejunal mucosa enzyme activities were assayed and tissue free amino acids in muscles were measured. Endotoxin induced translocation from the gut lumen to the MLN in all groups, whereas dissemination occurred only in LPS-treated rats. OKG significantly reduced dissemination of the bacteria in the spleen. 3-Methylhistidine excretion was greater in the LPS + Gly group (+25%, P < 0.05) than in either the LPS + OKG or Saline + Gly group. The group fed the OKG-enriched diet had higher muscular glutamine, ornithine and arginine concentrations than did the Gly-supplemented groups (P < 0.05). Intestinal sucrase and aminopeptidase activities were higher in the LPS + OKG group than in the LPS + Gly group (-30%, P < 0.05). OKG supplementation limits bacterial dissemination and metabolic changes after injury in rats and thus may be useful in the prevention of gut-derived sepsis in critically ill patients. C1 Fac Pharm, Lab Biol Nutr, EA 2498, F-75270 Paris 06, France. Fac Med St Antoine, INSERM, U402, F-75012 Paris, France. Hop St Antoine, Assistance Publ Hop Paris, Bacteriol Lab, F-75012 Paris, France. UFR Pharm, Lab Physiol Humaine, F-49000 Angers, France. Hop Robert Debre, Assistance Publ Hop Paris, INSERM, U458, F-75019 Paris, France. Hotel Dieu, INSERM, U341, F-75181 Paris 04, France. RP Cynober, L, Fac Pharm, Lab Biol Nutr, EA 2498, F-75270 Paris 06, France. TC 9 PD DEC PY 2000 VL 130 IS 12 BP 2897 EP 2902 UT ISI:000165866200006 ER PT J AU Saint-Martin, JP Neraudeau, D Lauriat-Rage, A Goubert, E Secretan, S Babinot, JF Boukli-Hacene, S Pouyet, S Lacour, D Pestrea, S Conesa, G TI Interbedded faunas in the Messinian gypsum of Los Yeses (Sorbas Basin, SE Spain): consequences SO GEOBIOS DE Messinian; gypsum; faunal content; salinity crisis; Spain; Andalusia ID SALINITY CRISIS; BENTHIC FORAMINIFERA; ASSEMBLAGES; DEPOSITS AB Marine faunas have been recently found interbedded in the Messinian gypsum of Los Yeses, in the Sorbas Basin (SE Spain). More than 80 species have been identified, including molluscs, echinoids, foraminifers, ostracods, crustaceans and bryozoans. Several specimens from these exceptional marine fossils are figured for the first time. The palaeoecological analysis of these fossils show that their environment of deposit was located between the deep part of the inner shelf with photophile seagrass and the upper part of the outer shelf with sciaphile seagrass. Biostratigraphically, the association of species is typically Messinian in age, but include taxa that survive during the Pliocene and even to the Recent inside of the Mediterranean basin. These results ask again the question of the real impact the 'Messinian crisis' on the shelf Mediterranean faunas. C1 Univ Aix Marseille 1, UPRESA 6019 CNRS, F-13331 Marseille 3, France. Univ Rennes 1, UPR 4661, Lab Paleontol & Geosci, F-35042 Rennes, France. Museum Natl Hist Nat, Lab Paleontol, F-75005 Paris, France. Univ Angers, Geol Lab, F-49045 Angers, France. RP Saint-Martin, JP, Univ Aix Marseille 1, UPRESA 6019 CNRS, Case 67,3 Pl Victor Hugo, F-13331 Marseille 3, France. TC 9 PY 2000 VL 33 IS 5 BP 637 EP 649 UT ISI:000165819900008 ER PT J AU Asfar, P Kerkeni, N Labadie, F Gouello, JP Brenet, O Alquier, P TI Assessment of hemodynamic and gastric mucosal acidosis with modified fluid gelatin versus 6% hydroxyethyl starch: a prospective, randomized study SO INTENSIVE CARE MEDICINE DE gastric mucosal acidosis; hemodynamics; colloid; modified fluid gelatin; hydroxyethyl starch; sepsis ID CRITICALLY ILL PATIENTS; DIFFERENT VOLUME THERAPIES; INTRAMUCOSAL PH; BLOOD-FLOW; PENTOXIFYLLINE INFUSION; ADHESION MOLECULES; TISSUE OXYGENATION; CARDIAC-SURGERY; SEPTIC PATIENTS; INTRAMURAL PH AB Objective:To investigate the effect of 4% succinylated modified fluid gelatin (MFG) versus mean weight, highly substituted 6% hydroxyethyl starch (HES) on hemodynamic and gastric mucosal acidosis variables, in septic hypovolemic patients. Design: Prospective, randomized, clinical investigation. Setting: University hospital intensive care unit. Patients: Thirty-four septic hypovolemic ventilated and hemodynamically controlled patients. Interventions: Invasive hemodynamic and gastric tonometric measurements. Measurements and results: Hemodynamic and tonometric parameters were recorded at baseline and 60 min after infusion of 500 ml of each colloid. In all patients central venous pressure, pulmonary artery occlusion pressure, cardiac index and mean arterial pressure increased significantly with both colloids, and hemoglobin concentration decreased by the same amount while oxygen delivery remained stable. Gastric intramucosal pH increased from 7.27 +/- 0.08 to 7.31 +/- 0.07 (p < 0.001) with MFG and decreased non-significantly from 7.26 +/- 0.11 to 7.22 +/- 0.08 (ns) with HES. Carbon dioxide gastric mucosal arterial gradient decreased from 18 +/- 9 to 13 +/- 9 mmHg (p < 0.0005) in the MFG group and rose non-significantly from 18 +/- 11 to 21 +/- 11 mmHg with HES. Conclusions: Although MFG and 6% HES have the same hemodynamic effects, their physicochemical properties induce different responses on gastric mucosal acidosis in septic, hypovolemic and ventilated patients. These effects of MFG and HES on gastric mucosa need to be considered in patient management. C1 CHU Angers, Serv Reanimat Med, F-49033 Angers 01, France. RP Asfar, P, CHU Angers, Serv Reanimat Med, 4 Rue Larrey, F-49033 Angers 01, France. TC 9 PD SEP PY 2000 VL 26 IS 9 BP 1282 EP 1287 UT ISI:000089616700020 ER PT J AU Le Corff, J Marquis, RJ Whitfield, JB TI Temporal and spatial variation in a parasitoid community associated with the herbivores that feed on Missouri Quercus SO ENVIRONMENTAL ENTOMOLOGY DE Quercus; insect herbivores; Lepidoptera; parasitoids; community ID 3 TROPHIC LEVELS; POPULATION-DYNAMICS; WHITEFLY HOMOPTERA; INSECT HERBIVORES; SPECIES RICHNESS; LEAF QUALITY; ENEMY IMPACT; HOST PLANT; TOP-DOWN; HYMENOPTERA AB To determine whether the probability of parasitoid attack differed across years, seasons, sites, host plant species, and herbivore feeding modes, leaf-chewing insects (Lepidoptera) that feed on Quercus alba L. and Q. velutina Lam. were collected four times in the Missouri Ozarks (May, June. July, and August-September) in each of the years 1993-1995 and reared in the laboratory. Parasitism rates at a given census were relatively constant from year to year and decreased as the season progressed from May to September: 30% of the herbivores collected in May were parasitized, whereas <15% were attacked in the summer and fall. Similarly, parasitism rates were predictable based on host plant (higher on Q, velutina than on Q, alba) and feeding guild (higher for leaf miners than for external feeders, leaf tiers and leaf webbers, in the summer and fall). Leaf rollers encountered in May had the highest probability of being parasitized. There was also significant variation in parasitism rates among sites. Community composition during the spring was very similar among spring censuses across years and different from all other censuses. In contrast, in the summer and fall, the species assemblage of the parasitoid community remained relatively constant within a year despite the fact that the herbivore community composition changed across censuses. C1 Univ Missouri, Dept Biol, St Louis, MO 63121 USA. Univ Arkansas, Dept Entomol, Fayetteville, AR 72701 USA. RP Le Corff, J, Inst Natl Hort, F-49045 Angers, France. TC 9 PD APR PY 2000 VL 29 IS 2 BP 181 EP 194 UT ISI:000089623200007 ER PT J AU Jaspard, E TI Role of protein-solvent interactions in refolding: Effects of cosolvent additives on the renaturation of porcine pancreatic elastase at various pHs SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS ID ALPHA-CHYMOTRYPSIN; SERINE PROTEASES; MECHANISM; WATER; STABILIZATION; SUBSTRATE; DYNAMICS; LYSOZYME; GLYCEROL; PATHWAYS AB The effects of cosolvent additives on the refolding of porcine pancreatic elastase were studied by comparing the enzymatic activity and the conformation of the enzyme renatured at various pHs with those of the native elastase under the same cosolvent and pH conditions. A lag period was observed before reaching the steady state of the hydrolysis of an amide substrate, and the lag period measured with the refolding enzyme was longer than that measured with the native elastase. Depending on the cosolvent studied (acetonitrile, dimethylsulfoxide, glycerol, methanol) there was or was not a dramatic increase in the duration of the lag period measured with the refolding enzyme, but not in the case of the native elastase. These results and additional kinetic data on inactivation of the enzyme demonstrated that dimethylsulfoxide, glycerol, and methanol enhance the stability of the intermediates able to refold into the native form, contrary to acetonitrile. In neither the case of the native enzyme nor that of the renatured enzyme, did the cosolvents modify the pK(app) of ionization of the amino acids that control enzymatic activity, indicating that they did not penetrate the core of the refolded elastase. Conversely, they shifted toward a more alkaline pH the structural transition of the native elastase, and the amplitude of the shift was comparable to that observed in bulk water with elastase whose Ser 195 has been acylated, suggesting that cosolvents stabilized the structure of the folded molecule by increasing its packing. (C) 2000 Academic Press. C1 Univ Paris Sud, CNRS, Lab Physicochim Prot, URA 1131, Paris, France. RP Jaspard, E, Univ Angers, EA 917, UFR Sci, Grp Biochim & Biol Mol Vegetables, 2 Blvd Lavoisier, F-49045 Angers 01, France. TC 9 PD MAR 15 PY 2000 VL 375 IS 2 BP 220 EP 228 UT ISI:000086018900002 ER PT J AU Raimundo, JM Levillain, E Gallego-Planas, N Roncali, J TI Steric effects on the reversible dimerization of short-chain oligothiophene cation radicals SO ELECTROCHEMISTRY COMMUNICATIONS DE cation radicals; oligomerization; dimerization; substituted thiophenes; 2,5 ''-dihexylterthiophenes ID THIOPHENE OLIGOMERS; PI-STACKS; DIMERS; MODEL; REACTIVITY; BIPOLARONS; POLARONS; FORMS AB The reversible dimerization of cation radicals of a series of end-capped 2,5"-dihexylterthiophenes with the median thiophene ring either unsubstituted (1) or mono- and di-substituted by methyl and hexyl groups (2-5) has been investigated. Concentration-dependent cyclic voltammetry UV-Vis-NIR spectroelectrochemistry and temperature-dependent ESR spectroscopy lead to consistent results showing that, whereas the cation radical of compound 1 already dimerizes at room temperature, substitution of the median thiophene ring leads to a dramatic decrease in the propensity of the corresponding cation radical to dimerize. These results provide conclusive evidence for a steric control of the reversible dimerization of short-chain oligothiophene cation radicals. (C) 2000 Elsevier Science S.A. All rights reserved. C1 Univ Angers, CNRS UMR 6501, F-49045 Angers, France. RP Roncali, J, Univ Angers, CNRS UMR 6501, 2 Blvd Lavoisier, F-49045 Angers, France. TC 9 PD MAR PY 2000 VL 2 IS 3 BP 211 EP 215 UT ISI:000085666700015 ER PT J AU Malzert, A Boury, F Saulnier, P Benoit, JP Proust, JE TI Interfacial properties of mixed polyethylene glycol/poly(D,L-lactide-co-glycolide) films spread at the air/water interface SO LANGMUIR ID AIR-WATER-INTERFACE; POLY(ETHYLENE OXIDE); MONOLAYERS SPREAD; BIODEGRADABLE MICROSPHERES; CONTROLLED DELIVERY; POLYMER MONOLAYERS; LIGHT-SCATTERING; RELEASE; FORMULATIONS; COPOLYMERS AB The interfacial behavior and conformation of mixed films composed of poly(ethylene glycol) (PEG4000) and poly(D,L-lactide-co-glycolide) (PLGA) were studied. This was achieved by analyzing the isotherms and the dilatational rheological properties of the polymer films spread at the air/water interface and by performing atomic force microscopy (AFM) on the films after sampling on mica. The classical representation of molar fraction of mixtures against surface pressure deduced from the isotherms led us to conclude that PEG and PLGA were miscible in the mixed film at least in the range of pressure 0-7 mN/m. The viscoelastic properties of PEG were recovered in the mixed film with, however, a decrease of the relaxation time indicating the slower expulsion of PEG segments into the aqueous subphase. This was attributed to interpenetration of polymer segments in the plane of the interface. At higher surface coverage (12-15 mN/m), we demonstrated that PEG strongly influenced the behavior and the conformation of the PLGA. This was well supported by AFM images that indicated the presence of PEG segments between the PLGA ones. This led, for the mixed films, to large modification of the condensation properties of PLGA and gave rise to characteristic condensed patterns different from those observed in PLGA films. From the characterization of this simplified model, the anchoring of PEG in the PLGA film may constitute a suitable feature for the prevention of protein adsorption in the drug delivery systems formulated with those polymers. C1 Fac Pharm Angers, UPRES EA 2169, Unite Vectorisat Particulaire, F-49100 Angers, France. RP Proust, JE, Fac Pharm Angers, UPRES EA 2169, Unite Vectorisat Particulaire, 16 Blvd Daviers, F-49100 Angers, France. TC 9 PD FEB 22 PY 2000 VL 16 IS 4 BP 1861 EP 1867 UT ISI:000085412600054 ER PT J AU Kurdyka, K Mostowski, T Parusinski, A TI Proof of the gradient conjecture of R. Thom SO ANNALS OF MATHEMATICS ID STRATIFICATION; SETS AB Let x(t) be a trajectory of the gradient of a real analytic function and suppose that to is a limit point of x(t). We prove the gradient conjecture of R. Them which states that the secants of x(t) at to have a limit. Actually we show a stronger statement: the radial projection of x(t) from to onto the unit sphere has finite length. C1 Jagiellonian Univ, PL-31007 Krakow, Poland. Univ Warsaw, PL-00325 Warsaw, Poland. Univ Angers, Angers, France. RP Kurdyka, K, Jagiellonian Univ, PL-31007 Krakow, Poland. TC 8 PD NOV PY 2000 VL 152 IS 3 BP 763 EP 792 UT ISI:000167476400004 ER PT J AU Gallais, S de Crescenzo, MAP Laval-Martin, DL TI Evidence of active NADP(+) phosphatase in dormant seeds of Avena sativa L. SO JOURNAL OF EXPERIMENTAL BOTANY DE Avena sativa; dormancy; germination; NADP(+) phosphatase ID ACHLOROPHYLLOUS ZC MUTANT; KLEBS STRAIN-Z; HYDROGEN-PEROXIDE; GIBBERELLIC-ACID; NAD KINASE; PURIFICATION; CARYOPSES; EMBRYOS; CELLS AB Freshly-harvested seeds of Avena sativa L. do not germinate when imbibed at temperatures higher than 25 degreesC, This high temperature dormancy is due to the seed coats, and to the low activities of glycolysis and the oxidative pentose phosphate pathway (OPP) in the embryo. The analysis by exclusion chromatography of soluble NADP(+) phosphatase activities of embryos revealed two isoforms: a 37 kDa isoform present in both dormant and after-ripened caryopses, and a second isoform, with an apparent molecular weight of 160 kDa, five times more active in embryos of dormant seeds than in the after-ripened ones, after 6 h of imbibition at 30 degreesC. Moreover, the activity of this 160 kDa isoform was three times less in embryos from dormant caryopses when they were grown at 10 degreesC, a permissive temperature for radicle protrusion. These results suggest a correlation between the activity of the 160 kDa NADP(+) phosphatase and the dormancy state of the caryopsis. The two isoforms differed in the pH required for optimal activity: pH 5.7 and 6.5 for the 37 kDa and the 160 kDa phosphatases, respectively. Furthermore, the 160 kDa NADP(+) phosphatase displayed a strong specificity for NADP(+), whereas the 37 kDa isoform was able to hydrolyse numerous other phosphorylated compounds. C1 Univ Angers, Grp Biochim & Biol Mol Vegetales, EA 917, UFR Sci, F-49045 Angers 01, France. RP Laval-Martin, DL, Univ Angers, Grp Biochim & Biol Mol Vegetales, EA 917, UFR Sci, 2 Blvd Lavoisier, F-49045 Angers 01, France. TC 8 PD AUG PY 2000 VL 51 IS 349 BP 1389 EP 1394 UT ISI:000165779900008 ER PT J AU Cales, P Lacave, N Silvain, C Vinel, JP Besseghir, K Lebrec, D TI Prospective study on the application of the Baveno II Consensus Conference criteria in patients with cirrhosis and gastrointestinal bleeding SO JOURNAL OF HEPATOLOGY DE Baveno II criteria; cirrhosis; clinical trial; definitions; methodology; variceal bleeding ID VARICEAL HEMORRHAGE; PORTAL-HYPERTENSION AB Background/Aims: This study aimed to evaluate the Baveno II criteria defining key events in variceal bleeding. Methods: These criteria were applied to 196 patients with cirrhosis admitted for upper gastrointestinal bleeding due to portal hypertension and enrolled in a trial. Blood pressure, heart rate, hematocrit and clinical signs of upper digestive tract hemorrhage were recorded for 5 days. The blind overall clinical judgment of hemodynamic stability was recorded separately by the Steering Committee. Results: The evaluation of several hemodynamic criteria was left to the judgment of the clinician, The first time point for the control of bleeding, fixed at 6 h after admission, was impractical since 13% of the patients had not yet received specific treatment. The independent judgment did not agree in 38% of 82 cases without control of bleeding. In 15% of cases this was due to tachycardia, Calculation of several judgment criteria was not defined in the Baveno II criteria: survival without bleeding at 5 days, transfusion rate, and length of hospital stay. Conclusions: Although the Baveno II criteria have improved the definitions of key events, the criteria are hampered by limits such as false positive criteria of failure to control bleeding. We make several proposals for improvement. C1 CHU Angers, Serv Hepatogastroenterol, F-49033 Angers 01, France. French Club Study Portal Hypertens, Angers, France. Univ Angers, Lab Hemodynam Splanchn, Angers, France. Debiopharm, Lausanne, Switzerland. RP Cales, P, CHU Angers, Serv Hepatogastroenterol, F-49033 Angers 01, France. TC 8 PD NOV PY 2000 VL 33 IS 5 BP 738 EP 741 UT ISI:000090112100008 ER PT J AU Escoubas, P Stankiewicz, M Takaoka, T Pelhate, M Romi-Lebrun, R Wu, FQ Nakajima, T TI Sequence and electrophysiological characterization of two insect-selective excitatory toxins from the venom of the Chinese scorpion Buthus martensi SO FEBS LETTERS DE scorpion; insecticidal toxin; sequence; pharmacology; insect sodium channel ID K+ CHANNELS; NEUROTOXIN; KARSCH; POLYPEPTIDE; ACT AB The two insecticidal peptides Bm32-VI and Bm33-I, isolated from the venom of the Chinese scorpion Buthus martensi induce paralytical symptoms typical of insect contractive toxins. They show, respectively, 74% and 77% homology with AaIT from Androctonus australis, comparable insecticidal activity and no vertebrate toxicity. Under voltage-clamp conditions, both toxins induced (1) an increased fast Na+ current, (2) a shift in voltage dependence of Na+ current activation, (3) the occurrence of a delayed current, and (4) a slow development of a holding current. Increased Na+ conductance at negative potential values is responsible for axonal hyperexcitabilty and the contractive paralysis of insect prey. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved. C1 Suntory Inst Bioorgan Res, Osaka, Japan. N Copernicus Univ, Inst Gen & Mol Biol, Biophys Lab, Torun, Poland. Univ Angers, Fac Med, UPRES EA 2647, Neurophysiol Lab, Angers, France. Sichuan Province Inst Antibiot, Chengdu, Peoples R China. RP Escoubas, P, Univ Paris 06, ENS, Lab Signaux Endocrines, 46 Rue Ulm, F-75230 Paris 05, France. TC 8 PD OCT 20 PY 2000 VL 483 IS 2-3 BP 175 EP 180 UT ISI:000090090200018 ER PT J AU Ursino, M Ter Minassian, A Lodi, CA Beydon, L TI Cerebral hemodynamics during arterial and CO2 pressure changes: in vivo prediction by a mathematical model SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY DE carbon dioxide reactivity; intracranial pressure; cerebral autoregulation; severe brain damage; transcranial Doppler ID SEVERE HEAD-INJURY; ACUTE BRAIN-DAMAGE; BLOOD-FLOW; INTRACRANIAL-PRESSURE; PERFUSION-PRESSURE; CEREBROSPINAL-FLUID; OUTFLOW RESISTANCE; CARBON-DIOXIDE; PLATEAU WAVES; VOLUME INDEX AB The aim of this work was to analyze changes in cerebral hemodynamics and intracranial pressure (ICP) evoked by mean systemic arterial pressure (SAP) and arterial CO2 pressure (Pa-CO2) challenges in patients with acute brain damage. The study was performed by means of a new simple mathematical model of intracranial hemodynamics, particularly aimed at routine clinical investigation. The model was validated by comparing its results with data from transcranial Doppler velocity in the middle cerebral artery (V-MCA) and ICP measured in 44 tracings on 13 different patients during mean SAP and Pa-CO2 challenges. The validation consisted of individual identification of 6 parameters in all 44 tracings by means of a best fitting algorithm. The parameters chosen for the identification summarize the main aspects of intracranial dynamics, i.e., cerebrospinal fluid circulation, intracranial elastance, and cerebrovascular control. The results suggest that the model is able to reproduce the measured time patterns of V-MCA and ICP in all 44 tracings by using values for the parameters that lie within the ranges reported in the pathophysiological literature. The meaning of parameter estimates is discussed, and comments on the main virtues and limitations of the present approach are offered. C1 Univ Bologna, Dept Elect Comp Sci & Syst, I-40136 Bologna, Italy. CHU Angers, Dept Anesthesie, F-49033 Angers, France. RP Ursino, M, Univ Bologna, Dipartimento Elettron Informat & Sistemist, Viale Risorgimento 2, I-40136 Bologna, Italy. TC 8 PD NOV PY 2000 VL 279 IS 5 BP H2439 EP H2455 UT ISI:000090012600048 ER PT J AU Pellicer, V Guehl, JM Daudet, FA Cazet, M Riviere, LM Maillard, P TI Carbon and nitrogen mobilization in Larix x eurolepis leafy stem cuttings assessed by dual C-13 and N-15 labeling: relationships with rooting SO TREE PHYSIOLOGY DE allocation; C : N ratio; isotopic abundance; reserve; vegetative propagation ID VEGETATIVE PROPAGATION; SEEDLING CUTTINGS; AUXIN APPLICATION; ENDOGENOUS AUXIN; CARBOHYDRATE; WATER; INITIATION; MORPHOLOGY AB Changes in use of both stored and newly synthesized sources of carbon (C) and nitrogen (N) were investigated during rooting of leafy cuttings of Larix x eurolepis A. Henry. We used dual C-13 and N-15 long-term labeling of reserves of stock plants and followed isotope dilution of the labels in the cuttings to determine the respective proportions of C and N derived from stock plant reserves (Q(C,old). Q(N,old)) and from newly synthesized sources (Q(C,new), Q(N,new)). We also assessed their partitioning into the growing needles and roots. Because rooting development occurred over several months, destructive harvests were made during three periods (t(0): April 9; t(1): May 15 to June 5; t(2): June 12 to June 26). Total C content (Q(C)) of cuttings did not change with time, whereas total N content (Q(N)) decreased significantly between t(0) and t(2). In rooted cuttings, unlike unrooted cuttings, total N concentration decreased less markedly in needles and in the lower stem component between t(1) and t(2) than between t(0) and t(2). The lower stem of rooted cuttings contained more Q(N,old) than that of unrooted cuttings and showed lower C:N and C-13:N-15 ratios. The increase in Q(N,new) in the lower stem was positively correlated with rooting status. At t(1), new roots appeared and grew mainly at the expense of Q(C,new) and Q(N,old). By t(2), root growth was mainly dependent on new assimilates. We conclude that in leafy cuttings the initial amount of N reserves, rather than C reserves, may constitute a limiting factor for rooting. C1 INRA Nancy, Unite Ecophysiol Forestiere, F-54280 Champenoux, France. Cemagref, Div Ressources Genet & Plants Forestiers, F-45290 Nogent Sur Vernisson, France. INRA Clermont Theix, Unite Associee PIAF Bioclimatol, F-63039 Clermont Ferrand, France. INRA Angers, Stn Agron, F-49071 Beaucouze, France. RP Maillard, P, INRA Nancy, Unite Ecophysiol Forestiere, F-54280 Champenoux, France. TC 8 PD JUN PY 2000 VL 20 IS 12 BP 807 EP 814 UT ISI:000088200500004 ER PT J AU Gouhier, C Chalon, S Venier-Julienne, MC Bodard, S Benoit, JP Besnard, JC Guilloteau, D TI Neuroprotection of nerve growth factor-loaded microspheres on the D2 dopaminergic receptor positive-striatal neurones in quinolinic acid-lesioned rats: a quantitative autoradiographic assessment with iodobenzamide SO NEUROSCIENCE LETTERS DE poly-D,L-lactide-co-glycolide microspheres; nerve growth factor; Huntington's disease; dopaminergic D2 receptor; [I-125]-iodobenzamide; [H-3]-PK 11195 ID HUNTINGTONS-DISEASE; CHOLINE-ACETYLTRANSFERASE; GENE-EXPRESSION; IMMUNOREACTIVITY; CNTF AB Huntington's disease (HD) results from the degeneration of striatal neurones, mainly gamma-aminobutyric acid (GABA)ergic projection neurones and lately cholinergic interneurones. The use of trophic factors as agents able to prevent such neural degeneration is a promising strategy. The aim of this study was to validate nerve growth factor-loaded (NGF-loaded) poly-D,L-lactide-co-glycolide (PLGA) microspheres for treatment of HD in a rat model with quinolinic acid lesion using autoradiographic study of D2 dopaminergic receptors (D2R). This target is expressed by about half of striatal neurones and its scintigraphic exploration has already been performed for the follow-up of this degenerative process. Ex vivo autoradiography of D2R performed with iodobenzamide, the widely used ligand for single photo emission computerized tomography, reveal ed slight neuroprotection. Moreover, tolerance of microspheres was demonstrated by in vitro autoradiography with the marker of gliosis, [H-3]-PK 11195. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Tours, UFR Sci, Lab Biophys Med & Pharmaceut, INSERM U316, F-37200 Tours, France. UFR Sci Pharmaceut, UPRES EA 2169, F-49100 Angers, France. RP Gouhier, C, Univ Tours, UFR Sci, Lab Biophys Med & Pharmaceut, INSERM U316, 31 Ave Monge, F-37200 Tours, France. TC 8 PD JUL 7 PY 2000 VL 288 IS 1 BP 71 EP 75 UT ISI:000087916600018 ER PT J AU Chapeau-Blondeau, F TI Nonlinear test statistic to improve signal detection in non-Gaussian noise SO IEEE SIGNAL PROCESSING LETTERS DE detection; non-Gaussian noise; nonlinear statistic; threshold nonlinearity AB We compare two simple test statistics that a detector can compute from multiple noisy data in a binary decision problem based on a maximum a posteriori probability (MAP) criterion. One of these statistics is the standard sample mean of the data (linear detector), which allows one to minimize the probability of detection error when the noise is Gaussian. The other statistic is even simpler and consists of a sample mean of a two-state quantized version of the data (nonlinear detector). Although simpler to compute, we show that this nonlinear detector can achieve smaller probability of error compared to the linear detector. This especially occurs for non-Gaussian noises with heavy tails or a leptokurtic character. C1 Univ Angers, Lab Ingn Syst Automatises, Angers, France. RP Chapeau-Blondeau, F, Univ Angers, Lab Ingn Syst Automatises, Angers, France. TC 8 PD JUL PY 2000 VL 7 IS 7 BP 205 EP 207 UT ISI:000087899200010 ER PT J AU Lacquemant, C Gaucher, C Delorme, C Chatellier, G Gallois, Y Rodier, M Passa, P Balkau, B Mazurier, C Marre, M Froguel, P CA GENEDIAB Study Grp; DESIR Study Grp TI Association between high von Willebrand factor levels and the Thr789Ala VWF gene polymorphism but not with nephropathy in type 1 diabetes SO KIDNEY INTERNATIONAL DE genetics; diabetic renal disease; CHD; von Willebrand factor ID VONWILLEBRAND-FACTOR GENE; CONVERTING-ENZYME GENE; MYOCARDIAL-INFARCTION; MELLITUS; DISEASE; COMPLICATIONS; PLASMA; RISK; IDDM; RETINOPATHY AB Background. A genetic susceptibility for diabetic kidney disease is suspected since diabetic nephropathy occurs in only 30 to 40% of type I diabetic patients. As elevated von Willebrand factor (VWF) plasma concentrations have been reported to precede the development of microalbuminuria in type I diabetes, we addressed a possible implication of VWF as a genetic determinant for diabetic nephropathy. Methods. Three known VWF gene polymorphisms were genotyped in a group of 493 type I diabetic subjects, all showing proliferative retinopathy, but with various stages of renal involvement, which ranged from no microalbuminuria, despite a mean duration of diabetes of 31 years, to advanced nephropathy (GENEDIAB Study): Thr789Ala (Rsa I), M-/M+ (Msp I) (intron 19), and Ala1381Thr (Hph I). Plasma VWF and factor VIII (F VIII) levels were also measured in this population. Results. Plasma vWF and F VIII levels were increased in diabetic subjects with nephropathy (P < 0.001) or with coronary heart disease (CHD; P < 0.001), but there was no interaction of both conditions on plasma levels. The Map I polymorphism (M-/M+) was weakly associated with nephropathy (P = 0.04), but this association was not more significant when other risk factors were used in a logistic regression analysis. The VWF Ths789Ala polymorphism was associated with CHD (P = 0.002) and with plasma VWF levels. Logistic regression analysis indicated an independent and codominant, effect of the Thr789Ala polymorphism on CHD, but not on nephropathy, with a maximal risk for Ala/Ala homozygotes (OR = 4.2, 95% CI, 1.8 to 9.9, P = 0.0008). Conclusion. It is unlikely that polymorphisms in the VWF gene contribute to the risk for nephropathy in type I diabetic patients. However, the Thr7898Ala polymorphism might affect the risk for CHD in this population through modulation of plasma VWF levels. C1 Inst Biol Lille, Lab Genet Malad Multifactorielles, CNRS, UPRES A 8090, Lille, France. Lab Francais Fractionnement & Biotechnol, Lille, France. Broussais Hosp, Paris, France. Arras Hosp, Paris, France. Univ Hosp, Angers, France. Univ Hosp, Nimes, France. St Louis Hosp, Paris, France. INSERM, U258, Villejuif, France. RP Marre, M, CHU Angers, F-49033 Angers, France. TC 8 PD APR PY 2000 VL 57 IS 4 BP 1437 EP 1443 UT ISI:000086269300032 ER PT J AU Marre, M Lievre, M Vasmant, D Gallois, Y Hadjadj, S Reglier, JC Chatellier, G Mann, J Viberti, GC Passa, P CA The DIABHYCAR Study Grp TI Determinants of elevated urinary albumin in the 4,937 type 2 diabetic subjects recruited for the DIABHYCAR Study in Western Europe and North Africa SO DIABETES CARE ID ALCOHOL-CONSUMPTION; RANDOMIZED TRIAL; RISK-FACTORS; MICROALBUMINURIA; HYPERTENSION; DISEASE; NEPHROPATHY; PREVALENCE; MORTALITY; NIDDM AB OBJECTIVE - Whether ACE inhibition is useful for type 2 diabetic patients with micro- and macroalbuminuria remains unknown. The Non-Insulin-Dependent Diabetes, Hypertension, Microalbuminuria, Cardiovascular Events and Ramipril (DIABHYCAR) Study was set up to address this issue through a multicenter double-blind parallel placebo-controlled greater than or equal to 3-year trial in Europe and North Africa. In this article, we report the characteristics of the randomized patients. RESEARCH DESIGN AND METHODS - The main selection criteria were as follows: men or women aged greater than or equal to 50 years with type 2 diabetes treated with oral antidiabetic drugs, with or without hypertension, with a plasma creatinine level <150 mu mol/l, and with persistent micro- or macroalbuminuria, as assessed centrally by two successive urine samples containing a urinary albumin concentration greater than or equal to 20 mg/l. Patient characteristics were studied by comparing patients who were randomized to those who were not, taking their geographical origin into account. RESULTS - There were 25,455 patients screened for urinary albumin (20,296 from France, 918 from Germany, 1,019 from Northwest Europe, 969 from Central Europe, 959 from Mediterranean Europe, and 1,294 from North Africa). Of these patients, 4,937 were randomized. Compared with the nonrandomized patients, the randomized patients were older, more often men, more obese, had higher systolic/diastolic blood pressure and plasma glucose, smoked more tobacco, drank more alcohol, and had complications more frequently. Using a logistic regression analysis, all the above-mentioned items appeared as independent determinants for randomization into the study, with the exception of alcohol intake. The contribution of each item varied slightly from one geographical origin to another. CONCLUSIONS - The physical, biological, and behavioral characteristics create a poor renal and cardiovascular prognosis for the type 2 diabetic patients randomized to the DIABHYCAR Study because of micro- and macroalbuminuria. Testing the usefulness of ACE inhibition for the type 2 diabetic patients with microalbuminuria seems feasible through the DIABHYCAR Study. C1 Ctr Hosp Univ, Angers, France. Fac Med, Lab Biochim B, Angers, France. Serv Pharmacol Clin, Lyon, France. Hoechst Marion Roussel, Paris la Defense, France. Hop Broussais, Serv Informat Med, F-75674 Paris, France. Hop St Louis, Serv Diabetol, Paris, France. Stadt Krankenhaus Munchen Schwabing, Munich, Germany. Guys Hosp, Unit Metab Med, London SE1 9RT, England. RP Marre, M, Hop Bichat, Serv Endocrinol Diabetol Malad Metab, 46 Rue Henri Huchard, F-75877 Paris 18, France. TC 8 PD APR PY 2000 VL 23 SU Suppl. 2 BP B40 EP B48 UT ISI:000086273600008 ER PT J AU Guillot-Noel, C Chrysos, M Le Duff, Y Rachet, F TI Depolarized collision-induced light scattering by gaseous helium SO JOURNAL OF PHYSICS B-ATOMIC MOLECULAR AND OPTICAL PHYSICS ID FREQUENCY RAMAN-SCATTERING; POTENTIAL-ENERGY CURVE; DIATOM POLARIZABILITIES; SPECTRA; SPECTROSCOPY; GAS AB We have carried out a joint study, experimental and theoretical, of the binary depolarized collision-induced light scattering spectrum by gaseous helium at room temperature. The intensities from helium pairs, calibrated on an absolute scale, have been measured in the much extended, previously unexplored, 5-680 cm(-1) spectral domain. A critical analysis of the spectrum has been made by using ab initio anisotropy models available in the literature. Quantum-mechanical computations have enabled us to determine the spectral response of the pair polarizability terms which compose the most up-to-date anisotropy data (Moszynski et at 1996 J. Chem. Phys. 104 6997). The conclusion has been drawn that internuclear distances shorter than the helium atomic diameter are probed via the very far wing of our spectrum. C1 Univ Angers, Lab Proprietes Opt Mat & Appl, EP CNRS 130, F-49045 Angers, France. RP Guillot-Noel, C, Univ Angers, Lab Proprietes Opt Mat & Appl, EP CNRS 130, 2 Bd Lavoisier, F-49045 Angers, France. TC 8 PD FEB 14 PY 2000 VL 33 IS 3 BP 569 EP 580 UT ISI:000085480600025 ER PT J AU Chapeau-Blondeau, F TI Stochastic resonance at phase noise in signal transmission SO PHYSICAL REVIEW E ID BISTABLE SYSTEM; INFORMATION AB A model is developed for a periodic signal corrupted by an arbitrarily distributed phase noise and transmitted by an arbitrary memoryless system. The model establishes a new form of the phenomenon of stochastic resonance, whereby signal transmission can be enhanced by addition of noise. This is revealed by tbe standard signal-to-noise ratio of stochastic resonance, which here receives an explicit theoretical expression, and which is shown improvable via noise addition. This model is the first to propose a theory of stochastic resonance with phase noise. It represents a unique framework for further investigations on stochastic:resonance and its applications. C1 Univ Angers, Lab Ingenierie Syst Automatises, LISA, F-49000 Angers, France. RP Chapeau-Blondeau, F, Univ Angers, Lab Ingenierie Syst Automatises, LISA, 62 Ave Norte Dame du Lac, F-49000 Angers, France. TC 8 PD JAN PY 2000 VL 61 IS 1 BP 940 EP 943 UT ISI:000084935200123 ER PT J AU Fournet, A de Arias, AR Ferreira, ME Nakayama, H de Ortiz, ST Schinini, A Samudio, M de Bilbao, NV Lavault, M Bonte, F TI Efficacy of the bisbenzylisoquinoline alkaloids in acute and chronic Trypanosoma cruzi murine model SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS DE Chagas' disease; Trypanosoma cruzi; bisbenzylisoquinoline; daphnoline; cepharanthine; experimental treatment ID NECROSIS-FACTOR-ALPHA; CHAGAS-DISEASE; NITRIC-OXIDE; IN-VITRO; TETRANDRINE; MICE; CA2+; SERODIAGNOSIS; MACROPHAGES; INFECTIONS AB We have shown previously that daphnoline and cepharanthine are active against Trypanosoma cruzi and inhibited trypanothione reductase. The effects of oral treatments with daphnoline, cepharanthine and benznidazole were examined in Balb/c mice infected with T. cruzi acutely and chronically. In acute infections, parasitaemia was significantly reduced in the daphnoline-treated mice compared with controls and benznidazole-treated mice. The parasitological cure rate was increased in mice treated with daphnoline. Fifty days after infection, the negative serological response in both models was significantly different for the three tested drugs. Daphnoline showed the highest negative serological rate (48%). In chronically infected mice treated with daphnoline, we were unable to detect parasites in 70% of mice. The results obtained of oral treatment of daphnoline suggest that this bisbenzylisoquinoline may be useful in the treatment of acute and chronic Chagas' disease. This was not seen with cepharanthine, an excellent trypanothione reductase inhibitor. (C) 2000 Elsevier Science B.V. and International Society of Chemotherapy. All rights reserved. C1 UR Sante, Ex ORSTOM, Inst Rech Dev, F-75480 Paris 10, France. Inst Invest Ciencias Salud, Dept Trop Med, Asuncion, Paraguay. Fac Pharm Angers, Lab Pharmacognosie, F-49045 Angers, France. LVMH Rech, F-92752 Nanterre, France. RP Fournet, A, UR Sante, Ex ORSTOM, Inst Rech Dev, 213 Rue Fayette, F-75480 Paris 10, France. TC 8 PY 2000 VL 13 IS 3 BP 189 EP 195 UT ISI:000084157600006 ER PT J AU Filmon, R Basle, MF Barbier, A Chappard, D TI Poly(2-hydroxy ethyl methacrylate)-alkaline phosphatase: A composite biomaterial allowing in vitro studies of bisphosphonates on the mineralization process SO JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION DE alkaline phosphatase; poly(2-hydroxy ethyl methacrylate); pHEMA; methacrylate; mineralization; bone biology; biomaterials; bone substitute; polymer; bisphosphonate; etidronate; alendronate; tiludronate ID ALKALINE-PHOSPHATASE; LOW-TEMPERATURE; IN-VITRO; BETA-GLYCEROPHOSPHATE; CALCIFICATION; POLYMERIZATION; MECHANISMS; DEPOSITION; RESORPTION; IMPLANTS AB We have immobilized the mineralizing agent alkaline phosphatase (AlkP) in a hydrophilic polymer: poly(2-hydroxy ethyl methacrylate) - (pHEMA)- in a copolymerization technique. Histochemical study on polymer sections revealed that AlkP has retained its enzymic activity. The image analysis of sections using a tessellation method showed a lognormal distribution of the area of the tiles surrounding AlkP particles, thus confirming a homogeneous distribution of the enzyme in the polymer. Pellets of pHEMA-AlkP were incubated with a synthetic body fluid containing organic phosphates (beta -glycerophosphate). Mineral deposits with a rounded shape (calcospherites) were obtained in about 17 days. We have investigated the effects of three bisphosphonic pharmacological compounds (etidronate, alendronate and tiludronate) on this system which mimics the mineralization process of cartilage and woven bone. Bisphosphonates at a concentration of 10(-2) M totally inhibited AlkP in solution at a concentration of 10(-4) mg/ml. Inhibition has been reported being due to the chelation of a metal cofactor (Zn2+). Etidronate and alendronate appeared to similarly inhibit the calcospherite deposition onto the pHEMA-AlkP material. Both bisphosphonates possess three sites for the mineral complexion by Ca chemisorbtion. On the other hand, tiludronate having only two sites, was associated with a reduced inhibitory effect on mineralization but larger crystals were obtained. The pHEMA-AlkP material contains an immobilized enzyme in a hydrogel and mimics the physiological conditions of matrix vesicles entrapped within the cartilage (or bone) matrix. It provides an interesting method to study the effects of pharmacological compounds on the mineralization process in bone and cartilage in a non cellular and protein-free model. C1 Fac Med & CHU Angers, LHEA, Lab Histol Embryol, F-49045 Angers, France. Fac Med, Serv Commun Microscopie Elect, F-49045 Angers, France. Sanofi Rech, F-34082 Montpellier, France. RP Chappard, D, Fac Med & CHU Angers, LHEA, Lab Histol Embryol, F-49045 Angers, France. TC 7 PY 2000 VL 11 IS 8 BP 849 EP 868 UT ISI:000166490300005 ER PT J AU Menguy, E Boimond, JL Hardouin, L Ferrier, JL TI Just-in-time control of timed event graphs: Update of reference input, presence of uncontrollable input SO IEEE TRANSACTIONS ON AUTOMATIC CONTROL DE dioid; discrete event systems; just-in-time control; residuation; timed event graphs AB A linear system theory has been dei;eloped for the class of discrete-event systems subject to synchronization. This paper presents the just-in-time control of such systems when reference input is updated and/or in the presence of uncontrollable input(s). The proposed controls are the solutions to an optimization problem under equality constraint. C1 Lab Ingn Syst Automatises, F-49000 Angers, France. RP Menguy, E, Lab Ingn Syst Automatises, F-49000 Angers, France. TC 7 PD NOV PY 2000 VL 45 IS 11 BP 2155 EP 2159 UT ISI:000165579300025 ER PT J AU Delumeau, O Renard, M Montrichard, F TI Characterization and possible redox regulation of the purified calmodulin-dependent NAD(+) kinase from Lycopersicon pimpinellifolium SO PLANT CELL AND ENVIRONMENT DE Lycopersicon pimpinellifolium; CaM-dependent NAD(+) kinase; characterization; purification; redox regulation ID DISULFIDE BOND FORMATION; OXIDATIVE STRESS; ROOT PROTOPLASTS; SALINITY; PROTEIN; ACTIVATOR; RESPONSES; GROWTH; NACL AB The soluble and calmodulin (CaM)-dependent NAD(+) kinase from Lycopersicon pimpinellifolium was previously shown to be largely inactivated in isolated cells exposed to a short-term NaCl stress (Delumeau, Morere-Le Paven, Montrichard, Laval-Martin (2000) Plant Cell & Environment 23, 329-336). Nevertheless, the activity could be restored by adding a high dithiothreitol concentration to the protein extract, suggesting that the salt stress triggers an oxidation of the enzyme which leads to its inactivation. It was then interesting to investigate the effect of thiol-modifying reagents and disulphide reductants on the activity of L. pimpinellifolium NAD(+) kinase. A three-step purification procedure was then established and allowed isolation of the enzyme which exists under two forms: a monomer and a dimer of a 56 kDa subunit, characterized, respectively, by pIs of 6.8 and 7.1. Isolated NAD(+) kinase had a high affinity for CaM, half saturation being obtained for 7 ng mL(-1) bovine CaM. The activity of NAD(+) kinase was strongly inhibited by thiol-modifying reagents and oxidized glutathione. NAD(+) kinase was also found to be air-inactivated, the residual activity being stimulated by disulphide reductants. The most efficient of them is reduced thioredoxin from Escherichia coli which induced a five-fold increase in activity and restored 80% of the initial activity. These results which can be related to those previously observed in vivo suggest that the activity of the L. pimpinellifolium NAD(+) kinase, besides its dependence on CaM, is also dependent on the reduction state of the protein which could be regulated by the thioredoxin h/NADP-thioredoxin reductase system. C1 LRPV, GIS Semences, F-49045 Angers 01, France. RP Montrichard, F, LRPV, GIS Semences, 16 Bd Lavoisier, F-49045 Angers 01, France. TC 7 PD NOV PY 2000 VL 23 IS 11 BP 1267 EP 1273 UT ISI:000165460900012 ER PT J AU Bergamaschi, R Tuetch, JJ Pessaux, P Arnaud, JP TI Intracorporeal vs laparoscopic-assisted resection for uncomplicated diverticulitis of the sigmoid SO SURGICAL ENDOSCOPY-ULTRASOUND AND INTERVENTIONAL TECHNIQUES DE anastomosis; diverticulitis; laparoscopic sigmoid resection; sigmoid ID DISEASE; COLECTOMY; ANASTOMOSIS; SURGERY AB Background: Minimally invasive surgery for uncomplicated diverticulitis of the sigmoid (UDS) may be performed either as an intracorporeal procedure (LICR) or as laparoscopically assisted colon resection (LACR). Methods: Prospectively collected data of 40 selected patients who had undergone LICR for UDS between 1992 and 1994 were compared retrospectively with those of 34 diagnosis-matched LACR controls operated on at the same hospital between 1995 and 1996 to assess the short-term outcome. Results: There were no mortalities. LICR and LACR patients were well matched for age, gender, weight, American Society of Anesthesiologists (ASA) grade, duration of symptoms, and number of previous admissions. There were no significant differences in conversions (one vs three), mobilization of splenic flexure (11:29 vs 9:25), anastomotic distance from anal verge (12 vs 13 cm), estimated blood loss (270 vs 285 ml), passage of flatus (3.1 vs 3.8 days), operating room (OR) costs ($3,040 vs $2,820), and total hospital costs ($9,250 vs $10,050) in LICR and LACR patients, respectively. Suprapubic skin-incision length (36 vs 60 mm, p << 0.01), size of circular stapler 28:31 mm (1:39 vs 6:28, p = 0.03), specimen length (21 vs 11 cm, p << 0.01), complication rates (6 vs 5, p = 0.02), OR time (180 vs 244 min, p < 0.001), resumption of oral solid food intake (3.2 vs 5.8 days, p < 0.001), hospital stay (4.6 vs 9.9 days, p < 0.001), and ward costs ($2,360 vs $4,950, p < 0.001) were significantly different in LICR and LACR patients, respectively. Conclusion: The immediately recognizable advantages of LICR over LACR surmised from this study need further evaluation in a prospective randomized setting. LICR remains a procedure of considerable technical complexity requiring high surgical skills. C1 CHU Angers, Dept Visceral Surg, F-49033 Angers, France. RP Bergamaschi, R, Univ Trondheim Hosp, Natl Ctr Adv Laparoscop Surg, Olav Kyrres Gate 17, N-7006 Trondheim, Norway. TC 7 PD JUN PY 2000 VL 14 IS 6 BP 520 EP 523 UT ISI:000088064300002 ER PT J AU Ageorges, H Fauchais, P TI Plasma spraying of stainless-steel particles coated with an alumina shell SO THIN SOLID FILMS DE aluminium oxide; coatings; plasma processing and deposition; steel AB The effect of an alumina coating, obtained by mechanofusion, on stainless-steel particles used in plasma spraying has been studied by examining sprayed particles in mid-flight and their resulting splats and coatings. The mean size of the injected powders is about 65 mu m and the thickness of the alumina shell 4 mu m. The results show that without preheating the substrate the splats of both types of powder are extensively fingered and become circular when the substrate surface is preheated over 200 degrees C. For the case of the stainless steel/alumina composite splats, Energy dispersive spectroscopy (EDS) analysis of the distribution of the various elements shows that the alumina is either spread exactly on the stainless-steel splat or is dispersed in pieces and frozen over the surface of the stainless-steel splat. The first case corresponds to well molten particles where, after their flight in the plasma jet, all the alumina shell has flowed to the tail of the particle; the second case is related to particles which have still an alumina shell uniformly distributed around the stainless-steel core. Finally, a composite stainless steel/alumina coating sprayed on a rough (R-a similar to 6.7 +/- 0.3 mu m) stainless-steel substrate preheated to 400 degrees C is compared with a pure stainless-steel coating. Both hardness and cohesion are found to improve for the alumina-coated particles. (C) 2000 Elsevier Science S.A. All rights reserved. C1 Univ Limoges, Fac Sci, SPCTS, Equipe PLM, F-87060 Limoges, France. Univ Angers, LETP, F-49045 Angers, France. RP Ageorges, H, Univ Limoges, Fac Sci, SPCTS, Equipe PLM, 123 Ave Albert Thomas, F-87060 Limoges, France. TC 7 PD JUL 17 PY 2000 VL 370 IS 1-2 BP 213 EP 222 UT ISI:000087942200033 ER PT J AU Assi, A Castro-Jimenez, FJ Granger, M TI The Grobner fan of an A(n)-module SO JOURNAL OF PURE AND APPLIED ALGEBRA ID D-MODULE AB Let I be a non-zero left ideal of the Weyl algebra A(n) of order n over a field k and let L : R-2n --> R be a linear form defined by L(alpha, beta) = Sigma(i-l)(n) e(i)alpha(i) + Sigma(i=l)(n) f(i)beta(i). If e(i) + f(i) greater than or equal to 0, then L defines a filtration F.(L) on A(n). Let gr(L)(I) be the graded ideal associated with the filtration induced by F.(L) on I. Let finally U denote the set of all linear form L for which e(i) + f(i) greater than or equal to 0 for all 1 less than or equal to i less than or equal to n. The aim of this paper is to study, by using the theory of Grobner bases, the stability of grL(I) when L varies in U, In a previous paper, we obtained finiteness results for some particular linear forms (used in order to study the regularity of a D-module along a smooth hypersurface). Here we generalize these results by adapting the theory of Grobner fall of Mora-Robbiano to the D-module case. Our main tool is the homogenization technique initiated in our previous paper, and recently clarified in a work by F. Castro-Jimenez and L, Narvaez-Macarro. (C) 2000 Elsevier Science B.V. All rights reserved. MSC. Primary 35A27; secondary 13P10; 68Q40. C1 Univ Angers, Dept Math, F-49045 Angers 01, France. Univ Sevilla, Fac Math, Dept Algebra Computat Geometria Topol, E-41012 Seville, Spain. RP Granger, M, Univ Angers, Dept Math, 2 Bd Lavoisier, F-49045 Angers 01, France. TC 7 PD JUN 23 PY 2000 VL 150 IS 1 BP 27 EP 39 UT ISI:000087818600002 ER PT J AU Helesbeux, JJ Guilet, D Seraphin, D Duval, O Richomme, P Bruneton, J TI ortho-prenylphenol photooxygenation as a straightforward access to ortho-(2-hydroxy-3-methylbut-3-enyl)phenols SO TETRAHEDRON LETTERS ID MESUA-RACEMOSA; COUMARINS; FLAVONOIDS; PLANTS AB Photooxygenation (O-1(2)) Of ortho-prenylphenols followed by a reduction (PPh3) at low temperature (-30 degrees C) yields a mixture of ortho-(2-hydroxy-3-methylbut-3-enyl)phenols and ortho-(3-hydroxy-3-methyl-but-1-enyl)phenols. However, by running the two-step sequence at a higher temperature (15 degrees C), the secondary allylic alcohol could be selectively recovered. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Sci Pharmaceut & Ingn Sante, UFR, SONAS, F-49100 Angers, France. RP Seraphin, D, Sci Pharmaceut & Ingn Sante, UFR, SONAS, 16 Bd Daviers, F-49100 Angers, France. TC 7 PD JUN 12 PY 2000 VL 41 IS 23 BP 4559 EP 4562 UT ISI:000087639500010 ER PT J AU Lemaire, L Franconi, F Saint-Andre, JP Roullin, VG Jallet, P Le Jeune, JJ TI High-field quantitative transverse relaxation time, magnetization transfer and apparent water diffusion in experimental rat brain tumour SO NMR IN BIOMEDICINE DE quantitative MRI; rat-brain tumours; relaxometry; apparent diffusion coefficient; magnetization transfer ID IN-VIVO; TRANSFER CONTRAST; MRI; TESLA AB The potential of quantitative parameter images of transverse relaxation time T-2, apparent diffusion coefficient (ADC) and magnetization transfer ratio (MTR) to characterize experimental brain tumours was studied. Necrosis or haemorrhage can be detected using either MTR, ADC or T-2 (necrosis-MTR reduced by 35%, ADC and T-2 increased respectively by 170% and 100% compared with normal brain tissue; haemorrhage-MTR increased by 60%, ADC and T-2 decreased by 40% and 20%, respectively). Normal brain tissue can only be distinguished from tumour on T-2 and MTR parameter images. However, for small tumours (10 mu l), the best contrast is observed with MTR, ca. 30%, whereas for T-2 the contrast is ca. 10%. Copyright (C) 2000 John Wiley & Sons, Ltd. C1 Univ Angers, UPRESA EA 2169 Vectorisat Particulaire, Angers, France. Univ Angers, Serv Commun RMN, Angers, France. CHU Angers, Anat Pathol Lab, Angers, France. RP Lemaire, L, Fac Med, Lab Biophys Med, 2 Rue Haute Reculee,Pavillon Ollivier, F-49045 Angers, France. EM laurent.lemaire@univ-angers.fr TC 7 PD MAY PY 2000 VL 13 IS 3 BP 116 EP 123 UT ISI:000087669300002 ER PT J AU Barrat, JA Taylor, RN Andre, JP Nesbitt, RW Lecuyer, C TI Strontium isotopes in biogenic phosphates from a neogene marine formation: implications for palaeoseawater studies SO CHEMICAL GEOLOGY DE neogene; Sr isotope; biogenic phosphate ID PHANEROZOIC TIME; SR-87 SR-86; SEAWATER; SR; DIAGENESIS; BONE; ND; STRATIGRAPHY; SYSTEMATICS; APATITES AB Neogene marine deposits of NW France ("Faluns") are rich in a variable array of well preserved phosphatic vertebrate fragments. Many of these are of the same age as the host sediments and consist of the remains of fish, mammals and reptiles whilst others are clearly Mesozoic (Turonian) in age, We have determined the Sr isotopic composition of 24 phosphatic samples in order to study the efficacy of using the method to date the Neogene materials and to investigate the effects of diagenesis and seawater alteration on the terrestrial material. The Sr isotope results obtained on the ichthyoliths and the other Neogene marine vertebrates suggest an age of 11 Ma for the base of the host sediments (Tortonian), which corresponds precisely with the palaeontological data. In contrast, the initial isotopic composition of the contemporaneous terrestrial mammals and reptiles, which should record higher (continental) Sr ratios are close to the value of their marine counterparts. The same trend is observed for a sample of shark's tooth of Mesozoic age where the Sr isotopic composition approaches a Neogene value. The results demonstrate that alteration by seawater or interstitial waters is able to introduce significant quantities of Sr into the phosphate. Leaching experiments carried out on the materials does not remove this secondary strontium and we were unable to establish the original values of the terrestrial material. Our conclusion is that the use of Sr isotopes to characterise phosphatic materials must be viewed with caution particularly if the materials are reworked. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ Angers, Fac Sci, F-49045 Angers, France. Univ Southampton, Southampton Oceanog Ctr, Southampton SO14 3ZH, Hants, England. Ecole Normale Super Lyon, CNRS UMR 5570, Lab Sci Terre, F-69364 Lyon, France. RP Barrat, JA, Univ Angers, Fac Sci, 2 Bd Lavoisier, F-49045 Angers, France. TC 7 PD AUG 1 PY 2000 VL 168 IS 3-4 BP 325 EP 332 UT ISI:000087608000012 ER PT J AU Cacoub, P Ohayon, V Sekkat, S Dumont, B Sbai, A Lunel, F Benslimane, A Godeau, P Archane, MI TI Epidemiologic and virologic study of hepatitis C virus infection in Morocco SO GASTROENTEROLOGIE CLINIQUE ET BIOLOGIQUE DE hepatitis C virus; hepatitis G virus; epidemiology; Morocco ID LINE PROBE ASSAY; NON-B-HEPATITIS; BLOOD-DONORS; RISK-FACTORS; UNITED-STATES; NON-A; GENOTYPES; AGENT; ASSOCIATION; PARTNERS AB Objectives - We prospectively studied 783 consecutive Moroccan patients to define: 1) the prevalence of anti-hepatitis C virus (HCV) antibody (Ab), 2) the prevalence of other viral infections: HBs Aa, anti-HAV IgM, anti-HGV HGV RNA, 3) the risk factors of spreading spread HCV infection, and 4) the distribution of HCV genotypes. Results - 60/783 (7.7%) patients had anti-HCV Ab (48 H/12 Fl, 26 (3.3%) HBs Ag, and 3 (0.3%) IgM anti-HAV. Anti-HGV Ab was found in 11/60 (18.3%) anti-HCV positive patients, and 6/38 (15.8%) anti-HCV negative patients. 2/22 (9%) serum anti-HCV positive and anti-HGV negative patients were positive for HGV RNA. The 60 HCV positive patients rarely had other viral infections: 3 (5%) HBs Ag, 11 (18.3%) anti-HGV positive, 2 (9%) HGV RNA positive, and none had anti-HBc, IgM anti-HAV, or anti-HIV. HCV positive patients had more often undergone transfusion of blood products (21.7 vs 5.5% P < 0.0001), and dental treatment (55% vs 8.3% p < 0.0001). Patients with anti-HCV Ab frequently had hepatitis lesions on liver biopsy, i.e. chronic active hepatitis (n=44) or cirrhosis (n = 16). HCV RNA was positive in 45/60 (75%) anti-HCV positive patients. HCV genotypes were: 1b (n = 21, 47%), 2a/2c in = 13, 29%), 1a (n = 6, 13%), et 3 (n = 1, 2%). Conclusions - In our Moroccan population, the prevalence of HCV was high (7.7%). Other viral infections (HBV, HAV, HGV) were rare. C1 Hop La Pitie Salpetriere, Serv Med Interne, F-75651 Paris 13, France. Hop Mohammed V, Serv Med Interne, Rabat, Morocco. Inst Pasteur, Unite Immunol Virol, Casablanca, Morocco. CHU Angers, Virol Lab, Angers, France. RP Cacoub, P, Hop La Pitie Salpetriere, Serv Med Interne, 47 Blvd Hop, F-75651 Paris 13, France. TC 7 PD FEB PY 2000 VL 24 IS 2 BP 169 EP 173 UT ISI:000086229500003 ER PT J AU Lipiec, R Graja, A Hudhomme, P Liu, SG Gorgues, A TI Spectral studies of the molecular dynamics of some adducts of C-60 to TTF SO SYNTHETIC METALS DE fullerene, C-60; tetrathiafulvalene, TTF; C-60 adducts; IR spectra ID BIS-LINKING; TETRATHIAFULVALENE TTF; ELECTRON-TRANSFER; PI-DONORS AB Synthesis and some properties of two monoadducts of C-60 to TTF (EDT-TTF-C-60 dyad for the ethylenedithio- and DMDT-TTF-C-60 dyad for both methylthio-TTF substituents) and a third compound, in which TTF is linked to two C-60 (C-60-TTF-C), are presented. Infrared spectra of the investigated compounds show that the chemical bonding of C-60 to TTF involves the latter in vibrations of the C-60 part, mainly in its tangential vibrations. Some typical bands of the TTF core present distinct temperature anomalies suggesting an inclination of C-60 group(s) in relation to the plane of TTF core, and/or changes in dynamics of molecular groups. (C) 2000 Elsevier Science S.A. All rights reserved. C1 Polish Acad Sci, Inst Mol Phys, PL-60179 Poznan, Poland. Univ Angers, Lab Ingn Mol & Mat Organ, F-49045 Angers, France. RP Graja, A, Polish Acad Sci, Inst Mol Phys, Smoluchowskiego 17-19, PL-60179 Poznan, Poland. TC 7 PD MAR 1 PY 2000 VL 109 IS 1-3 BP 67 EP 72 UT ISI:000085941500013 ER PT J AU Winkfield, B Lunel, F Beurrier, P Cales, P TI Eradication of hepatitis C virus after 3 months of interferon treatment in a patient with chronic C hepatitis SO GASTROENTEROLOGIE CLINIQUE ET BIOLOGIQUE ID SUSTAINED RESPONSE; ALPHA C1 Ctr Hosp Univ, Serv Hepatogastroenterol, F-49000 Angers, France. CHU Angers, Reseau Hepatites 49, F-49000 Angers, France. CHU Angers, Virol Lab, F-49000 Angers, France. Ctr Traitement Hemophilie, Angers, France. RP Winkfield, B, Ctr Hosp Univ, Serv Hepatogastroenterol, F-49000 Angers, France. TC 7 PD JAN PY 2000 VL 24 IS 1 BP 136 EP 137 UT ISI:000085710000025 ER PT J AU De Ledinghen, V Person, B Legoux, JL Le Sidaner, A Desaint, B Greff, M Moesch, C Grollier, G Ingrand, P Sautereau, D Beauchant, M TI Prevention of biliary stent occlusion by ursodeoxycholic acid plus norfloxacin - A multicenter randomized trial SO DIGESTIVE DISEASES AND SCIENCES DE polyethylene stents; malignant biliary stricture; norfloxacin; ursodeoxycholic acid ID ENDOPROSTHESES; OBSTRUCTION; BILIRUBIN; BLOCKAGE AB We report a prospective randomized multicenter trial that tested the efficacy of combining ursodeoxycholic acid and norfloxacin in the prevention of polyethylene stent clogging in patients with obstructive jaundice due to an unresectable malignancy at the level of the common bile duct. After insertion of a 10-Fr straight polyethylene stent, patients were allocated to receive oral treatment with ursodeoxycholic acid and norfloxacin, or conservative treatment. The primary outcome measure was stent blockage within six months. Thirty-three patients (group I) received ursodeoxycholic acid and norfloxacin, and 29 received conservative treatment (group II). At six months, cumulative stent patency rate did not differ significantly between group I (47 +/- 11%, mean +/- SE, median 149 days) and group II patients (24 +/- 10%, mean +/- SE, median 100 days, P = 0.23, log-rank test). Four stents were clogged by ursodeoxycholic acid. Survival did not differ between the two groups. Combined therapy with ursodeoxycholic acid and norfloxacin failed to improve stent patency. Moreover, ursodeoxycholic acid can cause stent obstruction. C1 Ctr Hosp Poitiers, Poitiers, France. CHU Angers, Angers, France. Ctr Hosp Reg, Orleans, France. Ctr Hosp Univ, Paris, France. Inst Arnault Tzanck, Nice, France. RP Beauchant, M, Univ Hosp, Serv Hepatogastroenterol, BP 577, F-86021 Poitiers, France. TC 7 PD JAN PY 2000 VL 45 IS 1 BP 145 EP 150 UT ISI:000085471400023 ER PT S AU Demoen, B Nguyen, PL TI So many WAM variations, so little time SO COMPUTATIONAL LOGIC - CL 2000 SE LECTURE NOTES IN ARTIFICIAL INTELLIGENCE AB The WAM allows within its framework many variations e.g. regarding the term representation, the instruction set and the memory organization. Consequently several Prolog systems have implemented successful variants of the WAM. While these variants are effective within their own context, it is difficult to assess the merit of their particular variation. In this work, four term representations that were used by at least one successful system are compared empirically within dProlog, one basic implementation which keeps all other things equal. We also report on different implementation choices in the dProlog emulator itself, dProlog is reasonably efficient, so it makes sense to use it for these experiments. C1 Katholieke Univ Leuven, Dept Comp Sci, B-3001 Louvain, Belgium. Univ Catholique Ouest, Inst Appl Math, F-49008 Angers, France. RP Demoen, B, Katholieke Univ Leuven, Dept Comp Sci, Celestijnenlaan 200A, B-3001 Louvain, Belgium. TC 6 PY 2000 VL 1861 BP 1240 EP 1254 UT ISI:000165607800083 ER PT J AU Basuyau, JP Blanc-Vincent, MP Bidart, JM Daver, A Deneux, L Eche, N Gory-Delabaere, G Pichon, MF Riedinger, JM CA Grp travail SOR TI Standards, Options and Recommendations (SOR) for tumor markers in breast cancer SO BULLETIN DU CANCER DE guidelines; breast-neoplasms; CA 15.3 antigen; tumor markers; carcinoembryonic-antigen ID CARCINOMA-ASSOCIATED ANTIGEN; POSTOPERATIVE FOLLOW-UP; CARCINOEMBRYONIC ANTIGEN; CA 15-3; CLINICAL-VALUE; SERUM LEVELS; POLYPEPTIDE ANTIGEN; MALIGNANT DISEASES; CA-15-3; CEA AB Context: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC) the 20 French Cancer Centres and specialists from French Public Universities, General Hospital; and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. Objectives: To define, according to the definitions of the Standards, Options and Recommendations project, the characteristics of various tumour markers in breast cancer and the potential role of these markers in the management of patients with this malignancy Methods: Data were identified by searching Medline and the personal reference lists of members of the expert groups. Once the guidelines were defined, the document tons submitted for review to 43 independent reviewers, and to the medical committees of the 20 French Cancer Centres. Results: The main recommendations are: 1) CA 153 and CEA are the serum tumour markers most often used in breast cancer (standard). 2) if the CA 15.3 is raised at presentation, there is no place for the measurement of other tumour markers (standard, expert agreement). 3) All analyses for each patient must be performed in the same laboratory using the same technique (standard expert agreement). 4) CA 15.3 should not be used for screening or diagnosis. 5) The level of CIA 15.3 before treatment is a recognised prognostic factor, the independent value of which has not been proven (standard, level of evidence C). 6) If the initial value of CA 15.3 is greater than 50 kU.L-1 disseminated disease should be actively sought before any treatment decisions are made (standard, expert agreement). 7) An initial elevation of CIA 15.3 that does not return to normal reflects a lack of response to treatment and is a strong adverse prognostic factor (standard, level of evidence C). 8) The accuracy of tumours markers (especially CA 15.3) as early indicators of metastatic disease is well recognised (standard) but the clinical benefit has not been established. 9) There is a correlation between tumour markers and clinical response in the treatment of metastatic disease (level of evidence C). The level of CA 15.3 in metastatic disease does not predict response to treatment. C1 Ctr Henri Becquerel, F-76038 Rouen, France. Inst Bergonie, Bordeaux, France. Inst Gustave Roussy, Villejuif, France. Ctr Paul Papin, Angers, France. Inst Curie, Paris, France. Inst Claudius Regaud, Toulouse, France. FNCLCC, Operat Stand Opt Recommandat, F-75654 Paris 13, France. Ctr Rene Huguenin, St Cloud, France. Ctr Georges Francois Leclerc, Dijon, France. RP Basuyau, JP, FNCLCC, Operat Stand Opt Recommandat, 101 Rue Tolbiac, F-75654 Paris 13, France. TC 6 PD OCT PY 2000 VL 87 IS 10 BP 723 EP 737 UT ISI:000165412500005 ER PT J AU Gerland, K Bataille-Simoneau, N Basle, M Fourcin, M Gascan, H Mercier, L TI Activation of the Jak/Stat signal transduction pathway in GH-treated rat osteoblast-like cells in culture SO MOLECULAR AND CELLULAR ENDOCRINOLOGY DE growth hormone; Jak2; Stat5; osteoblasts ID GROWTH-HORMONE RECEPTOR; TYROSINE PHOSPHORYLATION; NUCLEAR TRANSLOCATION; TRANSCRIPTION FACTOR; OSTEOSARCOMA CELLS; BINDING; PROLACTIN; STAT5B; PROTEINS; DESENSITIZATION AB In this study, activation of the Jak/Stat signaling pathway was followed upon growth hormone (GH) stimulation, using the rat osteosarcoma cell-line UMR-106.01 that expresses high affinity GH receptors. The results show a GH-induced and sustained phosphorylation of Jak2 and Stat5 on tyrosine residues. The tyrosine phosphorylation status of Jak2 was increased in a dose-dependent manner. In contrast to Jak2, tyrosine phosphorylation of Stat5 also elicited at 42 ng/ml GH, remained unchanged when GH concentration was raised up to 4200 ng/ml. DNA binding activity of StatS was also observed in response to GH. However, GH was unable to cause transactivation of reporter gene constructs harboring StatS binding sites (the GHREII from the rat spi 2.1 gene promoter, and the LHRE from the rat beta -casein gene promoter), except in cells transiently transfected with either StatS cDNAs or the rat GHR cDNA. Altogether the results suggest that UMR-106.01 cells exhibit original features of the GH-dependent Jak/Stat signaling pathway. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 UFR Sci Med, Lab Histol Embryol, F-49045 Angers, France. CHU Angers, INSERM, E9928, F-49033 Angers, France. RP Mercier, L, UFR Sci Med, Lab Histol Embryol, 1 Rue Haute de Reculee, F-49045 Angers, France. TC 6 PD OCT 25 PY 2000 VL 168 IS 1-2 BP 1 EP 9 UT ISI:000165062000001 ER PT J AU Ageorges, H Fauchais, P TI Oxidation of stainless steel particles with and without an alumina shell during their flight in a plasma jet SO HIGH TEMPERATURE MATERIAL PROCESSES DE aluminium oxide; steel; plasma processing and deposition; oxidation AB Investigations are carried out to study the oxidation of stainless steel particles collected after their flight in a plasma jet. In some tests, the injected particles are coated with an alumina shell. Particles are sprayed in Atmospheric Plasma Spraying (APS) and then collected in a concentric cylinder where they are quenched by argon jets. SEM observations of sprayed stainless steel particles show the formation of dark spots within their clear cross section, which displays the chromium and oxygen elements prominently. X-ray diffraction shows a chromium oxide phase which seems to be CrO. This is due to the convective movements within the particle renewing continuously fresh chromium at the surface and entraining the formed CrO inside the particle. It seems that, as for FeO, CrO is immiscible with liquid steel. On the other hand, alumina coated particles are less oxidized : cross sections present less oxide inclusions. Two types of particles were observed : some are still fully coated but the shell is broken due to the higher expansion of the stainless steel core. They probably result from particles where alumina has not been fully melted. Others have their alumina fused and entrained by liquid flow to the back of the moving droplet. Fused alumina droplets at the particles surface have coalesced creating a melted alumina cap. The two types of particles are probably due to the wide distribution trajectories within the spray cone which result in temperature differences. The particles with the alumina at the tail have probably traveled in the core of the plasma jet where temperatures are higher and then both materials have been melted, whereas the others have traveled in the jet fringes where the temperatures are lower. C1 Univ Angers, LETP, F-49045 Angers, France. Univ Limoges, SPCTS, F-87060 Limoges, France. RP Ageorges, H, Univ Angers, LETP, 2 Blvd Lavoisier, F-49045 Angers, France. TC 6 PY 2000 VL 4 IS 3 BP 323 EP 337 UT ISI:000089288400002 ER PT J AU Antic-Fidancev, E Corbel, G Mercier, N Leblanc, M TI Evidence of anionic disorder in fluoride borate Eu-3(BO3)(2)F-3 from Eu2+ luminescence: Comparison with fluoride carbonate Ba2Eu(CO3)(2)F-3 SO JOURNAL OF SOLID STATE CHEMISTRY DE fluoride borate; fluoride carbonate; europium luminescence; crystal field analysis ID CRYSTAL-STRUCTURE; GD AB The optical behavior of europium fluoride borate Eu-3(BO3)(2)F-3 and barium fluoride carbonates Ba2Eu(CO3)(2)F-3 is investigated with Eu3+ as local structural probe. Tentative correlation between the optical and structural data are discussed. Unexpected broad emission lines are observed for Eu3+ in fluoride borate and the separation of two crystallographic sites, predicted from the structure determination, is impossible. It is assumed that deviation from the ideal stoichiometry Eu-3(BO3)(2)F-3 occurs and is due to the substitution BO33- -3F(-), leading to the formulation Eu-3(BO3)(2+x)F3-3x. Crystal field analysis is performed on the F-7(J) basis of the 4f(6) configuration of Eu3+. The crystal field parameters (cfp) and crystal field strength parameter N-V are similar for both compounds though slightly larger for Eu-3(BO3)(2)F-3 This difference is especially significant for two rank (cfp), indicative of a larger electrostatic field in Eu-3(BO3)(2)F-3. (C) 2000 Academic Press. C1 ENSCP, CNRS, UMR 7574, Lab Chim Appl Etat Solide, F-75231 Paris 05, France. Fac Sci, Lab Fluorures UPRES A 6010, F-72085 Le Mans, France. Fac Sci, Lab IMMO, UMR 6501, F-49045 Angers, France. RP Antic-Fidancev, E, ENSCP, CNRS, UMR 7574, Lab Chim Appl Etat Solide, 11 Rue Pierre & Marie Curie, F-75231 Paris 05, France. TC 6 PD SEP PY 2000 VL 153 IS 2 BP 270 EP 274 UT ISI:000089082800010 ER PT J AU Debenay, JP Guillou, JJ Geslin, E Lesourd, M TI Crystallization of calcite in foraminiferal tests SO MICROPALEONTOLOGY ID ORGANIC MATRIX; SHELL; BIOMINERALIZATION C1 Fac Sci, Geol Lab, F-49045 Angers, France. Fac Sci, UPRESA EA 2644, F-49045 Angers, France. EBO, F-85350 Ile Dyeu, France. Fac Sci, Geol Lab, F-44072 Nantes 3, France. Fac Sci, UPRESA EA 2644, F-44072 Nantes 3, France. Univ Angers, Fac Med, CNRS, Serv Commun Microscopie Elect, F-49045 Angers, France. RP Debenay, JP, Fac Sci, Geol Lab, 2 Bd Lavoisier, F-49045 Angers, France. TC 6 PY 2000 VL 46 SU Suppl. 1 BP 87 EP 94 UT ISI:000088250500008 ER PT J AU Krempf, M Rohmer, V Farnier, M Issa-Sayegh, M Corda, C Sirugue, I Gerlinger, C Masseyeff-Elbaz, MF TI Efficacy and safety of micronised fenofibrate in a randomised double-blind study comparing four doses from 200 mg to 400 mg daily with placebo in patients with hypercholesterolemia SO DIABETES & METABOLISM DE fenofibrate; dyslipidaemia; LDL-cholesterol ID DENSITY-LIPOPROTEIN CHOLESTEROL; PRIMARY TYPE IIA; SIMVASTATIN; ATORVASTATIN; HYPERLIPIDEMIA; LOVASTATIN; GOALS AB The aim of this study was to evaluate the efficacy on LDL-cholesterol (LD L-C) of micronised fenofibrate given for three months at doses ranging from 200 to 400 mg once daily, compared with placebo. A double-blind, randomised, parallel-group, multi-centre trial was performed in four centers of France in 340 hypercholesterolemic patients (163M, 177F) aged 18-75 years. After a 2-3 month single-blind run-in period on placebo and diet, patients with LDL-C greater than or equal to 4.65 mmol/l (180 mg/dl) maintained on the same diet throughout the study were randomly allocated to placebo or to 200, 267, 340 or 400 mg micronised fenofibrate, given once daily with the evening meal for 3 months. LDL-C, total cholesterol (TC), total triglycerides (TG) and apolipoprotein B (Apo B) significantly decreased compared with placebo in all four fenofibrate groups. For all randomised patients, the decrease in the fenofibrate groups ranged from 31.6-38.8% for LDL-C, 24.5-31.9% for TC, 26.7-40.8% for TG, and 27.3-35.0% for Apo B. An increase in HDL-cholesterol of 4.1-8.2% was observed in the fenofibrate groups, but did not reach statistical significance. Lipid values in the placebo group remained unchanged. The therapeutic goal of LDL-C < 3.36 mmol/l (130 mg/dl)was reached in 27% in the 200 mg group and increased to 56% in the 300 mg group. There were no major clinical or biological adverse events in the dose interval from 200 mg to 400 mg of micronised fenofibrate per day. This study showed treatment for 3 months with micronised fenofibrate at doses up to 400 mg per day is effective and can reduce LDL-cholesterol up to 30% allowing further evaluation of these doses on longer trials. C1 Hotel Dieu, Clin Endocrinol & Nutr, F-44093 Nantes 1, France. CHRU Angers Med C, F-49000 Angers, France. Point Med, F-21000 Dijon, France. Clin St Basile, Grp Tzanck, F-06250 Maugins, France. Labs Fournier SA, F-21000 Dijon, France. Inst A Tzanck, F-06721 St Laurent du Var, France. RP Krempf, M, Hotel Dieu, Clin Endocrinol & Nutr, F-44093 Nantes 1, France. TC 6 PD MAY PY 2000 VL 26 IS 3 BP 184 EP 191 UT ISI:000088018500003 ER PT J AU Lode, T TI Functional response and area-restricted search in a predator: seasonal exploitation of anurans by the European polecat, Mustela putorius SO AUSTRAL ECOLOGY DE anuran; area-restricted search; carnivores; functional response; polecat; predation ID BIALOWIEZA NATIONAL-PARK; WESTERN FRANCE; RODENT POPULATIONS; DECIDUOUS FOREST; FEEDING-HABITS; PREY; MICROTINE; POLAND; CYCLE; STABILITY AB A study of the feeding habits and movements of 11 radiotracked polecats Mustela putorius in western France revealed that seasonal predation upon agile frogs, Rana dalmatina, was directly influenced by prey abundance and distribution. Although dietary structure showed the importance of mammalian prey (71.5%), polecats exploited nocturnal, terrestrial anurans in spring (31.6%). The periodic activity of anurans at spawning sites led both to a maximum density in spring and to a patchy distribution. The monthly variations in anuran dietary occurrences were associated with changes in frog availability. The functional response of polecats to frog density was sigmoidal shared (type 3 response). Frog consumption rate increased more slowly than prey density but frogs were actively removed at higher density. It is therefore suggested that frog populations were moderately affected by the predator and this density dependent effect tends to stabilise anuran populations. Predation upon anurans was also correlated with a prey dispersion index as revealed by a polynomial regression. Polecats concentrated their predation on spawning congregations of the breeding adult frogs. Movements were smallest in spring and polecats changed their track length by increasing the difference between a succession of small movements and of longer journeys towards profitable sites. Changes in movements correlated with the anuran dispersion index and the response was sigmoidal (polynomial regression) revealing an area-restricted search. This response may be regarded as an 'aggregative response' according to the first part of the definition of Begon et al. (1996). Functional and area-restricted search responses to the frog abundance and dispersion constitute an original example of predator-prey coexistence strategies among vertebrates. I suggest that such predation could be favoured by the individualistic habits of the mustelid. C1 Univ Angers, UFR Sci, F-49045 Angers, France. RP Lode, T, Univ Angers, UFR Sci, 2 Blvd Lavoisier, F-49045 Angers, France. TC 6 PD JUN PY 2000 VL 25 IS 3 BP 223 EP 231 UT ISI:000087878400002 ER PT J AU Gautier, N Cariou, M Gorgues, A Hudhome, P TI A novel array in extended tetrathiafulvalenes (TTF): the 'H' shape SO TETRAHEDRON LETTERS ID ELECTRON-DONORS; DERIVATIVES AB The highly extended, cro;ss-conjugated and sulfur rich rr-electron donor 2a was synthesized and characterized introducing the 'H' shape as a new approach in the tetrathiafulvalene (TTF) array. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 UMR CNRS 6501, F-49045 Angers, France. UMR CNRS 6513, Organ Synth Lab, F-44322 Nantes 03, France. RP Hudhome, P, UMR CNRS 6501, 2 Blvd Lavoisier, F-49045 Angers, France. TC 6 PD MAR 27 PY 2000 VL 41 IS 13 BP 2091 EP 2095 UT ISI:000086358400015 ER PT J AU Lunel, F Cacoub, P TI Treatment of autoimmune and extra-hepatic manifestations of HCV infection SO ANNALES DE MEDECINE INTERNE DE hepatitis C virus; autoimmune hepatitis; autoantibodies; sicca syndrome; vasculitis; glomerulonephritis; lichen planus; thyroid diseases; mixed cryoglobulinemia; treatment; interferon; ribavirin ID CHRONIC ACTIVE HEPATITIS; C VIRUS-INFECTION; CHRONIC VIRAL-HEPATITIS; ESSENTIAL MIXED CRYOGLOBULINEMIA; ORGAN-SPECIFIC AUTOANTIBODIES; INTERFERON ALFA-2A THERAPY; ALPHA-INTERFERON; LICHEN-PLANUS; LONG-TERM; IMMUNOLOGICAL DISORDERS AB Hepatitis C virus (HCV) infects mononuclear cells and may, like other viruses, cause immunological disorders, Immunological abnormalities observed in HCV infections are usually nonspecific (e.g. cryoglobulinemia, immune complex deposits, autoantibodies). There is a clear association between cryglobulinemia and hepatitis C and cryoglobulinemia related symptoms are usually improved by treatment with interferon alfa, although patients usually relapse after treatment end. The relationships between hepatitis C and other immunological abnormalities are unclear. The association between chronic hepatitis C and anti-smooth muscle or anti-nuclear antibodies does not appear to be significantly different from that in other hepatic disorders, particularly hepatitis B. Conversely, patients with hepatitis C have significantly more often anti-liver kidney microsomal (LKM1) antibodies than patients with other causes of liver diseases. When clinical, histological and biological findings are indicative of HCV infection with chronic hepatitis, interferon alfa or combination therapy with ribavirin are treatments options, Conversely, when clinical context and results of laboratory tests are in favor of an autoimmune disorder or of overlap-syndromes (i.e. both autoimmune and viral hepatitis), interferon should not be given in first intention, since revelation or exacerbation of autoimmune hepatitis have been reported under interferon. An important prevalence of anti-HCV antibodies has also been reported in patients with sialadenitis, lichen planus and thyroiditis, It has been clearly demonstrated that interferon may in;luce or worsen such immunological diseases, but there are very few studies shoeing improvement of these manifestations under interferon In conclusion, interferon mag be appropriate in patients with HCV infection and extrahepatic manifestations linked to immune complex deposition, whereas, in other cases, careful assessement of patients with autoimmune processes is necessary before choosing any treatment strategy. C1 CHU Angers, Serv Bacteriovirol, F-49033 Angers, France. Hop La Pitie Salpetriere, Serv Med Interne, F-75651 Paris 13, France. RP Lunel, F, CHU Angers, Serv Bacteriovirol, 4 Rue Larrey, F-49033 Angers, France. TC 6 PD FEB PY 2000 VL 151 IS 1 BP 58 EP 64 UT ISI:000086325200009 ER PT J AU Bourienne, A Pagenault, M Heresbach, D Jacquelinet, C Faroux, R Lejean-Colin, I Person, B Masliah, C Nouel, O Seyrig, JA Gosselin, M Bretagne, JF TI Prospective multicenter study of prognostic factors in peptic ulcer bleeding. Reassessment of clinical and endoscopic data at the era of endoscopic hemostasis SO GASTROENTEROLOGIE CLINIQUE ET BIOLOGIQUE DE gastrointestinal bleeding; peptic ulcer bleeding; prognostic factors; Helicobacter pylori ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; UPPER GASTROINTESTINAL HEMORRHAGE; INJECTION THERAPY; INTEROBSERVER AGREEMENT; CONTROLLED TRIAL; DUODENAL-ULCERS; RISK-FACTORS; FAILURE; EPIDEMIOLOGY; SCLEROSIS AB Aim - To evaluate in a prospective study the prognostic factors of recurrent bleeding and mortality in patients presenting with high risk peptic ulcer bleeding routinely treated by endoscopic hemostasis. Patients and methods - A multicenter study was carried out in 8 Western French hospitals in 144 patients with gastrointestinal bleeding peptic from ulcer type I or IIa, b as defined by Forrest classification. Thirty four and 38 parameters were studied respectively in order to predict recurrent bleeding and death. Significant predictive factors (P < 0.1) in univariate analysis were entered in a multivariate logistic regression analysis. Results - Endoscopic hemostasis was performed in 108 of 144 cases (75%) Recurrent bleeding and death occurred in 39 (28%) and 22 cases (15%) respectively. By multivariate analysis, the only predictor of rebleeding was hypovolemia at admission. Predictors of death were ASA score, cardiovascular Goldman score and recurrent bleeding. In this study, prevalence of Helicobacter pylori infection was low (41%) but was not a predictive factor Conclusions - In a selected population of peptic ulcer bleeding patients with high risk of rebleeding, prevalence of recurrent bleeding and dec;th remains rather high; despite routine endoscopic hemostasis. In the era of endoscopic hemostasis, clinical parameters remain the best prognostic factors of peptic ulcer bleeding outcome. C1 CHRU Pontchaillou, Serv Hepatogastroenterol, Rennes, France. Fac Med, Dept Sante Publ, Rennes, France. CHD, Serv Hepatogastroenterol, La Roche Sur Yon, France. CHG, Serv Hepatogastroenterol, Niort, France. CHU Angers, Serv Hepatogastroenterol, Angers, France. CHU Nantes, Serv Hepatogastroenterol, F-44035 Nantes 01, France. CHG, Serv Hepatogastroenterol, St Brieuc, France. CH, Serv Hepatogastroenterol, Pontivy, France. RP Bretagne, JF, CHU Pontchaillou, Clin Malad Appareil Digest, F-35033 Rennes, France. TC 6 PD FEB PY 2000 VL 24 IS 2 BP 193 EP 200 UT ISI:000086229500007 ER PT J AU Martin, S Lisbona, A Richard, J Morteau, S Denizot, B Bardies, M TI Production of new thermoluminescent mini-dosimeters SO PHYSICS IN MEDICINE AND BIOLOGY ID LIF-MG,CU,P TL DETECTORS; QUANTITATIVE AUTORADIOGRAPHY; DOSE MEASUREMENTS; IN-VIVO; RADIOIMMUNOTHERAPY; ANTIBODY AB A method of producing CaSO4:Dy thermoluminescent mini-dosimeters was reported in 1986 by B W Wessels for determination of the in vivo absorbed dose in radioimmunotherapy, a field in which absorbed dose gradients are important. These dosimeters, which undergo dissolution when used in a liquid environment, showed a sensitivity loss of up to 30% after 4 days of immersion in our tests. Moreover, several studies have shown that biocompatibility problems can occur during in vive studies in animals. This paper describes the production and testing of a new type of thermoluminescent mini-dosimeter obtained by microextrusion of a mixture of LiF:Mg,Cu,P polypropylene and plastic adjuvants. These dosimeters, in the form of long 400 mu m diameter filaments, can be cut to the desired length. The production process allows an LiF:Mg,Cu,P load of up to 50%. Results obtained in external irradiation indicate that these new miniature LiF:Mg,Cu,P dosimeters have good sensitivity (about 1.6 times that of CaSO4:Dy mini-TLDs), homogeneous response within a production batch (mean +/-4%), response stability in water (0.7% of variation in sensitivity after 2 weeks of immersion) and stability in aqueous solutions at different pH. LiF:Mg,Cu,P mini-dosimeters appear to be highly promising for internal dosimetry, and evaluation is in progress in animals. C1 INSERM, U463, F-44000 Nantes, France. Ctr Rene Gauducheau, F-44805 St Herblain, France. Ctr Microencapsulat, F-49100 Angers, France. Univ Angers, UPRESEA 2169, F-49045 Angers, France. RP Bardies, M, INSERM, U463, 9 Quai Moncousu, F-44000 Nantes, France. TC 6 PD FEB PY 2000 VL 45 IS 2 BP 479 EP 494 UT ISI:000085410400017 ER PT J AU Robert, R Nail, S Marot-Leblond, A Cottin, J Miegeville, M Quenouillere, S Mahaza, C Senet, JM TI Adherence of platelets to Candida species in vivo SO INFECTION AND IMMUNITY ID ALBICANS GERM TUBES; EXTRACELLULAR-MATRIX; FORMED INVITRO; IN-VITRO; BINDING; PATHOGENESIS; ENDOCARDITIS; FIBRONECTIN; RECEPTORS; PROTEINS AB The in vivo interactions of platelets with Candida species yeast cells were investigated in a murine model. Mice were injected intravenously via the lateral caudal vein, and blood drawn by periorbital puncture was collected in phosphate-buffered saline-formaldehyde to avoid in vitro platelet activation. The study of the clearance of blastoconidia of Candida albicans and Candida glabrata showed that these cells disappeared quickly from the bloodstream. Microscopic observation of blood samples, stained by Calcofluor white or May Grunwald Giemsa, demonstrated the rapid attachment of platelets to fungal elements of all the Candida spp, tested, The attachment of murine platelets to C, albicans cells, observed by scanning electron microscopy, revealed morphological changes. The platelets lost their discoid shape, generated pseudopodia, and flattened against the yeast cells, The reversibility of platelet binding to C, albicans by chelating agents suggests a cation-dependent link. In contrast, the fixation of C, glabrata and Candida tropicalis was not modified by chelating agents. The mechanisms involved in the in vivo adherence of platelets to Candida cells may therefore differ according to the species of Candida. C1 Fac Pharm Angers, Lab Parasitol Mycol, Grp Etude Interact Hote Parasite, F-49000 Angers, France. UFR Sci Med, Lab Parasitol Mycol, Nantes, France. RP Robert, R, Fac Pharm Angers, Lab Parasitol Mycol, Grp Etude Interact Hote Parasite, 16 Blvd Daviers, F-49000 Angers, France. TC 6 PD FEB PY 2000 VL 68 IS 2 BP 570 EP 576 UT ISI:000084842000020 ER PT J AU Devuyst, G de Bray, JM Despland, PA Maeder, P Meuli, R Uske, A Alecu, C Dubas, F Bogousslavsky, J TI Focal adherent thrombus in the common carotid artery: Clinical, ultrasonographic, and pathogenic aspects in two cases SO JOURNAL OF ULTRASOUND IN MEDICINE ID VALVE STRANDS; CEREBRAL-ISCHEMIA; DISSECTION; THROMBOCYTOSIS C1 CHU Vaudois, Dept Neurol, CH-1011 Lausanne, Switzerland. CHU Vaudois, Dept Diagnost Radiol Neuroradiol, CH-1011 Lausanne, Switzerland. CHU Angers, Hop Larrey, Dept Neurol, Vasc Lab, Angers, France. RP Devuyst, G, CHU Vaudois, Dept Neurol, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland. TC 5 PD OCT PY 2000 VL 19 IS 10 BP 707 EP 711 UT ISI:000167754800012 ER PT J AU Gillet, P Dauvin, JC TI Polychaetes from the Atlantic seamounts of the southern Azores: biogeographical distribution and reproductive patterns SO JOURNAL OF THE MARINE BIOLOGICAL ASSOCIATION OF THE UNITED KINGDOM ID DIVERSITY; ROCKALL AB A study of the polychaetes living on isolated seamounts was undertaken to give data on marine biogeography and the dispersal of marine invertebrates. The data from the Meteor and Josephine seamounts came from Hartmann-Schroder and Rosenfeldt's work in the 1980s. Data from Hyeres came from Bellan's work in the 1960s, and data from the Atlantis and Hyeres seamounts were obtained during the Seamount 2 French expedition on board the 'Suroit' in 1993. Thirty-five sites from 280 to 2205 m were sampled: 16 on Atlantis (13 with polychaetes), and 19 on Hyeres (16 with polychaetes). In all 84 polychaete taxa from four seamounts were studied: Atlantis, 36; Hyeres, 33; Josephine, 34; and Meteor 50, but data analysis was based on the following number of taxa: Atlantis, 31; Hyeres, 29; Josephine, 34, and Meteor 48. Two groups of sites were identified by cluster analysis: I, Atlantis and Hyeres; and II, Josephine and Meteor. Only seven species were present at all sites. Nine families were present only in group I and six other families only in group II. Hesionidae (three species) occurred in group I, conversely Syllidae (16 species) were sampled only in group II. Some of the species were cosmopolitan (31%), 49% had a large distribution in the Atlantic, 11% were lusitano-mauretanian species, and only 6% were endemic; 51% of the species have direct development against 46% of the species which had a planktotrophic development and 3% a lecithotrophic development. Results of the biogeographical distribution and reproductive patterns of the polychaetes collected on these four sites were compared. C1 Univ Catholique Ouest, Inst Ecol Appliquee, Dept Sci Vie & Terre, F-49008 Angers 01, France. Univ Lille 1, Stn Marine Wimereux, UPRESA 8013, ELICO, F-620930 Wimereux, France. RP Gillet, P, Univ Catholique Ouest, Inst Ecol Appliquee, Dept Sci Vie & Terre, 3 Pl Andre Leroy,BP 808, F-49008 Angers 01, France. TC 5 PD DEC PY 2000 VL 80 IS 6 BP 1019 EP 1029 UT ISI:000167458800007 ER PT J AU Viturro, CI Molina, A Guy, I Charles, B Guinaudeau, H Fournet, A TI Essential oils of Satureja boliviana and S-parvifolia growing in the region of Jujuy, Argentina SO FLAVOUR AND FRAGRANCE JOURNAL DE Satureja parvifolia (Phil.) Epl.; Satureja boliviana Briq.; Lamiaceae; essential oil composition; piperitenone oxide; gamma-terpinene; beta-caryophyllene; bicyclogermacrene; germacrene-D; linalool ID MEDICINAL-PLANTS AB Essential oils of aerial parts of Satureja parvifolia and S. boliviana of Argentina were analysed by CC-MS and GC-FID. Fifty-six components were identified. The main compound of S. parvifolia essential oil is piperitenone oxide. The most abundant constituents identified in S. holiviana essential oil were gamma -terpinene, beta -caryophyllene, germacrene-D, bicyclogermacrene, 1,8-cineol and linalool. Copyright (C) 2000 John Wiley & Sons, Ltd. C1 Inst Rech Dev, Dept Soc & Sante, F-75480 Paris 10, France. Univ Nacl Jujuy, Fac Ingn, RA-4600 San Salvador De Jujuy, Argentina. Univ Angers, Fac Pharm, F-49000 Angers, France. RP Fournet, A, Inst Rech Dev, Dept Soc & Sante, 213 Rue La Fayette, F-75480 Paris 10, France. TC 5 PD NOV-DEC PY 2000 VL 15 IS 6 BP 377 EP 382 UT ISI:000166761300003 ER PT J AU Ferrari, M Armellini, C Ronchin, S Rolli, R Duverger, C Monteil, A Balu, N Innocenzi, P TI Influence of the Er3+ content on the luminescence properties and on the structure of Er2O3-SiO2 xerogels SO JOURNAL OF SOL-GEL SCIENCE AND TECHNOLOGY DE silica sol-gel; erbium; OH content; densification; upconversion ID SILICA XEROGELS; GLASSES; RAMAN AB Er2O3-SiO2 xerogels doped with different Er/Si concentrations were annealed at 950 degreesC for 120 h. The Er3+ doping level varied from 0 to 40000 Er/Si ppm. The effect of Er2O3 content on the sintering behavior of silica gels and on the luminescence properties was studied by Vis-NIR absorption, Raman and luminescence spectroscopies. C1 CNR CeFSA, Ctr Fis Stati Aggregati, I-38050 Trent, Italy. Univ Trent, Dipartimento Fis, Ist Nazl Fis Mat, I-38050 Trent, Italy. Univ Angers, Lab POMA, CNRS, EP 130, F-49045 Angers, France. Univ Padua, Dipartimento Ingn Meccan, Set Mat, I-35131 Padua, Italy. RP Ferrari, M, CNR CeFSA, Ctr Fis Stati Aggregati, Via Sommarive 14, I-38050 Trent, Italy. TC 5 PD DEC PY 2000 VL 19 IS 1-3 BP 569 EP 572 UT ISI:000166544900107 ER PT J AU Dapoigny, L de Tourdonnet, S Roger-Estrade, J Jeuffroy, MH Fleury, A TI Effect of nitrogen nutrition on growth and nitrate accumulation in lettuce (Lactuca sativa L.), under various conditions of radiation and temperature SO AGRONOMIE DE radiation use efficiency; RUE; nitrate; water; shading; sand culture; drip irrigation; greenhouse ID LIGHT INTERCEPTION; MAIZE SEEDLINGS; WINTER LETTUCE; USE EFFICIENCY; PLANTS; PHOTOSYNTHESIS; NUTRIENT; WATER; INTENSITIES; VEGETABLES AB A better understanding of the effect of environmental factors on growth and nitrate accumulation in plants is necessary to develop cultivation practices, and in particular for providing lettuces with a low nitrate content. This study was conducted to analyse the effect of nitrogen supply on the interception and conversion of the PAR in dry matter, and on the nitrate and water accumulations in fresh tissues of the lettuce, for various conditions of temperature and radiation. The growth, and water and nitrate concentrations of two soilless cultures of lettuce (summer and autumn) were measured for two levels of radiation and two levels of nitrogen supply. RUE ranged from 2.12 to 3.50 g.MJ(-1), being higher for a low radiation level and for a high nitrogen supply. There was a positive correlation between the lettuce nitrate and water contents. The slope of this relationship was not affected by environmental conditions, indicating a strong interdependance between nitrate and water accumulation in lettuce. C1 INRA, INAPG, Agron Lab, F-78850 Thiverval Grignon, France. ENSH, Chaire Sci & Tech Prod Legumieres, F-49005 Angers, France. ENSP, Lab Agr Periurbaine, F-78009 Versailles, France. RP de Tourdonnet, S, INRA, INAPG, Agron Lab, BP 01, F-78850 Thiverval Grignon, France. TC 5 PD DEC PY 2000 VL 20 IS 8 BP 843 EP 855 UT ISI:000166409700002 ER PT J AU Chautard, D Daver, A Bocquillon, V Verriele, V Colls, P Bertrand, G Soret, JY TI Comparison of the bard Trak (TM) test with voided urine cytology in the diagnosis and follow-up of bladder tumors SO EUROPEAN UROLOGY DE bladder cancer; bladder neoplasm; BTA Track (TM); cytology ID BTA TEST; CANCER AB Objectives: To compare the results of the BTA Trak(TM) test with voided urine cytology (VUC) in the diagnosis and follow-up of bladder tumors. Patients and Methods: Urine samples were obtained from 53 patients with bladder tumor (77 samples) and 53 patients treated for bladder tumor with no evidence of disease on the basis of cystoscopic evaluation (88 samples). Urine samples were collected prior to cystoscopy. The BTA assay was performed by the BTA Trak(TM) test according to the manufacturer's recommendations. A value >14 U/ml was considered abnormal. Results: There was a statistically significant increase in median BTA value with increasing stage of tumor: 11.9, 57.9 and 391.0 U/ml respectively for stages pTa, pT1 and pT2/3 (p<0.0001, Kruskal-Wallis test). There was also a correlation between increasing grade and median BTA values measured at 6.9, 13.1 and 235.0 U/ml in grades 1, 2 and 3 tumors respectively (p<0.0001, Kruskall-Wallis test). The overall sensitivity of the BTA Trak(TM) test was 58.4% compared to 46.7% for VUC, a difference of 11.7%, which was statistically significant (McNemar test, p<0.005). The sensitivity of both tests combined was 63.6%. The specificity of the VUC (94.3%) was significantly higher than that of the BTA Trak(TM) (75.0%) (p<0.005, McNemar test). The accuracy of the Bard Trak(TM) test (67.3%) was similar to that of VUC (66.9%). Conclusion: The BTA Trak(TM) test is more sensitive than urinary cytology in the detection of bladder tumors but the improvement involved is insufficient to consider decreasing the frequency of endoscopic examinations in the follow-up of superficial bladder tumor. Copyright (C) 2000 S. Karger AG, Basel. C1 CHU Angers, Urol Serv, F-49033 Angers 01, France. Ctr Paul Papin, Lab Radio Analyse, Angers, France. Ctr Paul Papin, Anat Pathol Lab, Angers, France. RP Chautard, D, CHU Angers, Urol Serv, F-49033 Angers 01, France. TC 5 PD DEC PY 2000 VL 38 IS 6 BP 686 EP 690 UT ISI:000165692800009 ER PT J AU Limat, S Woronoff-Lemsi, MC Milpied, N Chartrin, I Ifrah, N Deconinck, E Gressin, R Colombat, P Cahn, JY Arveux, P CA Grp Ouest Etude Leucemies Autres TI Effect of cell determinant (CD)34(+) cell dose on the cost and consequences of peripheral blood stem cell transplantation for non-Hodgkin's lymphoma patients in front-line therapy SO EUROPEAN JOURNAL OF CANCER DE cost; autologous stem cell transplantation; CD34; lymphoma; granulocyte macrophage-colony stimulating factor (GM-CSF) ID ACCELERATES HEMATOPOIETIC RECOVERY; PROGENITOR CELLS; BONE-MARROW; CD34(+) CELLS; MYELOABLATIVE CHEMOTHERAPY; ENGRAFTMENT KINETICS; RESOURCE UTILIZATION; MOBILIZATION; GRANULOCYTE; TRIAL AB The aim of this study was to assess the effect of cell determinant (CD)34-+ cell dose on the cost and consequences of peripheral blood stem cell transplantation for non-Hodgkin's lymphoma (NHL) patients in front-line therapy. Resource utilisation, length of aplasia, overall (OS) and event-free survival (EFS) were assessed for 63 patients. Economic data were calculated taking into account harvest, hospitalisation, blood product requirements and drugs required until discharge. The point of view of the Hospital Institution was chosen. A significantly earlier haematopoietic engraftment was achieved in patients with a count of more than 5x10(6) CD34 + /kg. There were no differences for OS and EFS. A high CD34 + cell content resulted in a total cost saving of $4210. This was principally related to a significant reduction in the length of hospitalisation (-$3010) and platelet and red blood cell transfusions (-$815), although the latter was not significant. Several sensitivity analyses showed the robustness of our results. A CD34 + cell dose higher than 5x10(6)/kg appeared to be optimal for clinical and economic considerations in NHL patients undergoing transplantation in front-line therapy. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Besancon Univ Hosp, Doubs Canc Registry, F-25030 Besancon, France. Besancon Univ Hosp, Dept Pharm, F-25030 Besancon, France. Nantes Univ Hosp, Dept Haematol, F-44035 Nantes, France. Tours Univ Hosp, Dept Pharm, F-37100 Tours, France. Angers Univ Hosp, Dept Haematol, F-49033 Angers, France. Besancon Univ Hosp, Dept Haematol, F-25030 Besancon, France. Grenoble Univ Hosp, Dept Haematol, F-38000 Grenoble, France. Tours Univ Hosp, Dept Haematol, F-37100 Tours, France. RP Arveux, P, Besancon Univ Hosp, Doubs Canc Registry, F-25030 Besancon, France. TC 5 PD DEC PY 2000 VL 36 IS 18 BP 2360 EP 2367 UT ISI:000165724700023 ER PT J AU Rohmer, V Freneau, E Morange, I Simonetta, C CA Clud Hypophyse TI Efficacy of quinagolide in resistance to ergot dopamine agonists: results of a multicenter study SO ANNALES D ENDOCRINOLOGIE DE quinagolide; prolactin adenoma; anti-tumoral effect; resistant prolactinomas ID PROLACTINOMAS RESISTANT; HYPERPROLACTINEMIC PATIENTS; CV 205-502; BROMOCRIPTINE; INTOLERANT; MACROADENOMAS; CV-205-502 AB Objective: A retrospective French multicenter analysis was carried out to assess changes in tumor volume and plasma prolactin concentration in order to evaluate the efficacy of quinagolide (Norprolac(R)) in patients with prolactinoma resistant to ergot dopamine agonists. Patients and methods : One hundred seven patients (46 men and 61 women) from 27 centers were included in the statistical analysis. All had previously been treated with a dopamine agonist (bromocriptine). Fifty-five patients had undergone surgery before being administered quinagolide: 17 of the patients had also received radiotherapy (before and after the initiation of treatment with quinagolide in 14 and 3 cases respectively). Quinagolide was given at doses ranging from 75 to 750 mug daily and continued for more than one year for 84 patients. Results:The prolactin level returned to normal after a mean interval of 9.8 +/- 1.6 months (1-48) in 47 of the 107 patients (44 %) using a mean dose of quinagolide of 259 +/- 32.7 mug/d (75-750). The plasma prolactin concentration had already been normalized using bromocriptine in three patients. The variation in tumor volume was assessed in 82 patients since 8 had no residual tumor post-operatively and 17 had received radiotherapy: at least partial regression of the tumor was noted in 25 (30.8 %), including 16 (19.5 %) with a more than 50 % decrease in the remaining tumor. The mean time taken to observe the anti-tumoral effect was 16.8 +/- 3.1 months (3-78) using a mean dose of quinagolide of 255.4 +/- 37.8 mug/d d (75-750). The following predictive indicators were identified concerning the efficacy of quinagolide: a pre-quinagolide prolactin level of < 300 ng/ml in the group of patients whose plasma prolactin concentration was normalized, and a mean decrease in prolactin of 619 ng/ml in the group of patients showing a reduction in tumor Volume treated with quinagolide for 3 months. Side effects (nausea, vomiting, hypotension) were generally mild and were observed in 51 patients (47.6 %). Only 11 (10.2 %) of patients had to discontinue treatment because of adverse reactions. Conclusion : An anti-tumoral effect was noted in 30.8 % of patients and occurred within an interval of less than 2 years in 80 % of cases at a dose of 300 mug/d. Normalization of the plasma prolactin concentration was obtained in 44 % of cases and occurred in less than one year in 80 % of patients at a dose of 300 mug/d. Quinagolide is a useful drug and from now on should be prescribed as first-line treatment for patients presenting with bromocriptine-resistant prolactinoma. C1 CHU Angers, Serv Endocrinol, Angers, France. Hop Nord, Serv Endocrinol, Marseille, France. Lab Novartis, Rueil Malmaison, France. RP Rohmer, V, Serv Med C, 4 Rue Larrey, F-49100 Angers, France. TC 5 PD NOV PY 2000 VL 61 IS 5 BP 411 EP 417 UT ISI:000165527200001 ER PT J AU Villers, A Chautard, D TI It is too early to routinely use free PSA for prostate cancer screening SO PROGRES EN UROLOGIE DE prostate cancer; PSA; free PSA; screening; diagnosis ID RATIO IMPROVES; ANTIGEN RATIO; SERUM; HYPERPLASIA; POPULATION; PERCENTAGE; NG/ML AB The free form of PSA represents an average of 30% of total PSA. The free PSA level, in relation to total PSA, is expressed as a percentage (of free PSA). The percentage of free PSA appears to be relatively independent of benign prostatic hypertrophy, but it is markedly and significantly decreased in the case of prostate cancer and acute prostatitis. A cut-off value for the percentage of free PSA combined with a cut-off value for total PSA can decrease the number of biopsies indicated for the detection of prostate cancer. This approach avoids 20 to 30% of useless biopsies (specificity), but is accompanied by a 5 to 10% reduction of the number of cancers detected (sensitivity of 90 to 95%) compared to the use of total PSA alone. This 5 to 10% risk of missing a cancer of significant volume in a man under the age of 65 years explains why the use of free PSA to guide prostatic biopsies is not routinely recommended. Despite the promising performance of the percentage of free PSA to improve the indication for prostatic biopsies, the methodology of the studies performed to evaluate this test is not sufficient to validate their conclusions. The percentage of free PSA can be prescribed as a second-line test by the urologist, following a first series of negative biopsies in a man with a high clinical and laboratory suspicion of prostatic cancer, in order to propose a second series of biopsies after three months or to define the frequency of clinical and laboratory surveillance. While waiting for the results of prospective studies in the screening setting, recommendations concerning the use of PSA by general practitioners, who are the first to order this test in the context of screening, can be formulated as follows: The value of free PSA assay for first-line cancer screening has not been validated. A consensus has not been reached concerning the use of free PSA as nit indication for biopsies and the frequency of assays. Total PSA assay (cut-off value: 4 ng/ml) remains the reference laboratory test for screening and indication of biopsies. A lower normal cut-off value (between 2 and 4 ng/ml) is currently under evaluation. C1 CHU Toulouse, Hop Rangueil, Serv Urol, F-31043 Toulouse 4, France. CHU Angers, Serv Urol, Angers, France. RP Villers, A, CHU Toulouse, Hop Rangueil, Serv Urol, F-31043 Toulouse 4, France. TC 5 PD SEP PY 2000 VL 10 IS 4 BP 618 EP 621 UT ISI:000089788800024 ER PT J AU Desport, JC Preux, PM Guinvarc'h, S Rousset, P Salle, JY Daviet, JC Dudognon, P Munoz, M Ritz, P TI Total body water and percentage fat mass measurements using bioelectrical impedance analysis and anthropometry in spinal cord-injured patients SO CLINICAL NUTRITION DE body composition; spinal cord-injury; total body water; fat mass; BIA; anthropometry ID DAILY ENERGY-EXPENDITURE; PRESSURE SORES; RISK-FACTORS; INDIVIDUALS; PARAPLEGIA; NUTRITION; ULCERS; O-18; MEN AB Background and aims: Spinal cord injured patients may be adversely affected by disturbances of nutritional status, particularly malnutrition and fat mass overload. Malnutrition increases the risk for development of pressure sores, and fat mass excess increases the cardiovascular and respiratory risks of these patients, as well as predisposing to the development of diabetes mellitus, pressures sores and bony fractures. Body impedance analysis and anthopometry are easy bedside methods for body composition assessment. The aims of the study were to validate, in 20 spinal cord injured patients, body impedance analysis as a means to estimate total body water, and to validate a skinfold measurement of percentage fat independent of hydration of fat-free mass in the same population. Methods: Total body water was measured by O-18 dilution as a reference method. Impedance and anthropometric measurements (four different skinfolds) were obtained. The results of total body water given by impedance analysis and calculated with three formulas were compared to the reference method. The fat mass percentage obtained with each of the skinfolds using the 3-compartment Siri's formula was compared to a reference value using the sum of the skinfolds. Results and conclusion: The formula using 100 kHz resistance, height, weight and gender overestimated total body water by only 0.76 +/- 1.85 L, with an acceptable concordance with labeled water results. The formula with 50 kHz resistance was less accurate and concordant. Each skinfold may be used for assessing percentage fat mass. Based on these findings, we feel that the triceps skinfold, whose the variability is the lowest compared to the reference values, can be used alone in clinical practice. (C) 2000 Harcourt Publishers Ltd. C1 State Univ Limburg Hosp, Serv Gastroenterol, Limoges, France. Fac Med, Biostat Lab, Limoges, France. State Univ Limburg Hosp, Phys Med & Readaptat Dept, Limoges, France. Human Nutr Lab, Clermont Ferrand, France. Univ Hosp Angers, Med Serv B, Angers, France. RP Desport, JC, CHU Dupuytren, Serv Hepatogastroenterol, UF Nutr, F-87042 Limoges, France. TC 5 PD JUN PY 2000 VL 19 IS 3 BP 185 EP 190 UT ISI:000088719700007 ER PT J AU Marre, M Hadjadj, S Bouhanick, B TI Hereditary factors in the development of diabetic renal disease SO DIABETES & METABOLISM DE genetics; follow-up studies; family studies; candidate genes; diabetic nephropathy; angiotensin-I-converting enzyme (ACE); polymorphism ID ANGIOTENSIN-CONVERTING ENZYME; ALBUMIN EXCRETION RATE; ALDOSE REDUCTASE GENE; INSERTION DELETION POLYMORPHISM; INSULIN-DEPENDENT DIABETICS; POOR GLYCEMIC CONTROL; MICROVASCULAR COMPLICATIONS; MYOCARDIAL-INFARCTION; JAPANESE PATIENTS; KIDNEY-FUNCTION AB The role of genetics in diabetic renal disease has been suspected on the basis of follow-up and familial studies. Barely half of Type I patients who develop a diabetic retinopathy also develop nephropathy, and the relative risk of nephropathy for a diabetic proband is around 3 ii a sib is affected. Candidate genes for diabetic nephropathy can be divided into two categories: those affecting glucose metabolism in target organs of diabetic microangiopathy, and those affecting renal changes in response to hyperglycaemia. The role of angiotensin-I-converting enzyme (ACE) insertion/deletion (I/D) polymorphism has been suspected for several years. Evidence of its possible role in the development and progression of diabetic renal disease is presented here. C1 Hop Bichat, Dept Diabet, Serv Diabetol Endocrinol Metab, F-75877 Paris 18, France. Ctr Hosp Univ, Dept Diabet, Poitiers, France. Ctr Hosp Univ, Dept Diabet, Angers, France. RP Marre, M, Hop Bichat, Dept Diabet, Serv Diabetol Endocrinol Metab, 46 Rue Henri Huchard, F-75877 Paris 18, France. TC 5 PD JUL PY 2000 VL 26 SU Suppl. 4 BP 30 EP 36 UT ISI:000088633600006 ER PT J AU Cales, P Oberti, F Delmotte, JS Basle, M Casa, C Arnaud, JP TI Gastric mucosal surface in cirrhosis evaluated by magnifying endoscopy and scanning electronic microscopy SO ENDOSCOPY ID ANTRAL VASCULAR ECTASIA; PORTAL-HYPERTENSION; HEPATIC-DYSFUNCTION; LESIONS; CHROMOSCOPY; GASTROPATHY; FEATURES AB Background and Study Aims: Gastric mucosa may have several tiny patterns in portal hypertension. In this prospective study we used magnifying endoscopy and scanning electron microscopy (SEM) to better characterize the morphology of gastric mucosa in patients with cirrhosis, and we evaluated the diagnostic accuracy of magnifying endoscopy. Patients and Methods: Videotapes of gastric mucosal patterns from 39 cirrhotic patients and 20 control patients were blindly evaluated by the same observer using magnifying endoscopy (magnification x15) and conventional endoscopy. SEM was performed in 12 other patients. The basic anatomical entities of the gastric architecture on conventional endoscopy were the gastric area in control patients and the mosaic pattern in patients with cirrhosis. Results: With regard to the prevalence of endoscopic patterns in the antrum, the mosaic pattern was more frequent in cirrhotic patients. Tn the body, the mosaic pattern, white spots, and red marks were significantly more frequent in cirrhotic patients, whereas gastric areas were more frequent in control patients. Concerning the contributions of the techniques, significantly more gastric areas were identified by magnifying endoscopy than by conventional endoscopy: However, in multivariate analysis, only conventional endoscopy with esophageal varices had significant independent diagnostic accuracy for cirrhosis, and magnifying endoscopy of mucosal signs did not add any significant information. SEM did not improve discrimination between control and cirrhotic patients. Conclusions: Magnifying endoscopy provides more details of the mucosa, thus improving the delineation of gastric mucosal morphology However, magnifying endoscopy has little clinical value in cirrhosis since it does not improve an the accuracy of conventional endoscopy for the diagnosis of cirrhosis. C1 CHU Angers, Serv Hepatogastroenterol, F-49033 Angers 01, France. CHU Lille, Serv Hepatogastroenterol, F-59037 Lille, France. CHU Angers, Histol Lab, Angers, France. Univ Angers, Angers, France. CHU Angers, Serv Chirurg Digest, Angers, France. RP Cales, P, CHU Angers, Serv Hepatogastroenterol, F-49033 Angers 01, France. TC 5 PD AUG PY 2000 VL 32 IS 8 BP 614 EP 623 UT ISI:000088329200005 ER PT J AU Gallais, S de Crescenzo, MAP Laval-Martin, DL TI Changes in soluble and membrane-bound isoforms of calcium-calmodulin-dependent and -independent NAD(+) kinase, during the culture of after-ripened and dormant seeds of Avena sativa SO AUSTRALIAN JOURNAL OF PLANT PHYSIOLOGY DE Avena sativa L.; calcium; calmodulin; dormancy; germination; membrane-bound and soluble enzyme; NAD(+) kinase ID ACHLOROPHYLLOUS ZC MUTANT; KLEBS STRAIN-Z; GIBBERELLIC-ACID; EUGLENA-GRACILIS; CYTOSOLIC CALCIUM; HYDROGEN-PEROXIDE; ENHANCED ACTIVITY; NADP PHOSPHATASE; BARLEY ALEURONE; RED-LIGHT AB Activities of the soluble and membrane-bound isoforms of Ca2+ calmodulin (CaCam)-dependent and -independent NAD(+) kinases, were followed in the embryos during the culture of dormant (D) and after-ripened (AR) seeds of Avena sativa L. Embryos of D and AR seeds differ mainly in the evolution of membrane-bound activities, the majority of which are CaCam-dependent and linked to mitochondria. The in vivo application of gibberellic acid, CaCl2 and H2O2, which enhanced germination, induced an enhancement of all CaCam-dependent isoforms. Trifluoperazine (TFP), a calmodulin antagonist, greatly enhanced all CaCam-dependent isoforms and abolished the differences between the NAD(+) kinase activities of the two kinds of embryo. In addition, TFP rendered embryos unable to resume axis growth, probably due to pleiotropic effects. In contrast to H2O2, the reducing agent dithiothreitol diminished the soluble CaCam-dependent enzyme and blocked the germination of both types of seed, whereas it increased the dependent membrane-bound activities. The results demonstrate (1) that the CaCam-dependent NAD(+) kinase isoforms - amongst which is the isoform bound to mitochondrial membranes - play an important role at the end of sensu stricto germination and during the following growth of Avena sativa; and (2) that an excess of activity of these isoforms could be markers of stress or lethal conditions. C1 Univ Angers, UFR Sci, Grp Biochim & Biol Mol Vegetales, EA 917, F-49045 Angers 01, France. RP de Crescenzo, MAP, Univ Angers, UFR Sci, Grp Biochim & Biol Mol Vegetales, EA 917, 2 Blvd Lavoisier, F-49045 Angers 01, France. TC 5 PY 2000 VL 27 IS 7 BP 649 EP 658 UT ISI:000088166400003 ER PT J AU Jousselme, B Blanchard, P Frere, P Roncali, J TI Enhancement of the pi-electron delocalization and fluorescence efficiency of 1,6-diphenyl-1,3,5-hexatriene by covalent rigidification SO TETRAHEDRON LETTERS DE annulation; electrochemistry; fluorescence; optical properties ID CONJUGATED SYSTEMS; BANDGAP CONTROL; POLYMERS AB Bridged 1,6-diphenyl-1,3,5-hexatrienes were prepared from 1-indanone by successive Robinson annulation and McMurry coupling reaction. Rigidification produces a decrease in oxidation potential and HOMO-LUMO gap, and a considerable enhancement of fluorescence quantum yield compared to the open-chain analog. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 CNRS, UMR 6501, F-49045 Angers, France. RP Blanchard, P, CNRS, UMR 6501, 2 Blvd Lavoisier, F-49045 Angers, France. TC 5 PD JUN 24 PY 2000 VL 41 IS 26 BP 5057 EP 5061 UT ISI:000087942400014 ER PT J AU Vialettes, B Reynier, P Atlan-Gepner, C Mekki, N Lesluyes-Mazzochi, L Luc, G Lairon, D Malthiery, Y TI Dietary fat clearance in type V hyperlipoproteinaemia secondary to a rare variant of human apolipoprotein E: the apolipoprotein E3 (Arg 136 -> Ser) SO BRITISH JOURNAL OF NUTRITION DE apolipoprotein E; hypertriacylglycerolaemia; hyperlipoproteinaemia; triacylglycerol-rich lipoprotein ID CORONARY-ARTERY DISEASE; POSTPRANDIAL LIPOPROTEIN METABOLISM; TRIGLYCERIDE-RICH LIPOPROTEINS; RECEPTOR-BINDING ACTIVITY; III HYPERLIPOPROTEINEMIA; E POLYMORPHISM; CHYLOMICRON REMNANTS; E PHENOTYPE; E GENE; IDENTIFICATION AB This present case report describes two siblings with severe type V hyperlipoproteinaemia, diagnosed very early in life and due to the combination of the common apolipoprotein (Apo) E2 allele and a rare mutant variant of ApoE, ApoE3 (Arg 136 --> Ser). Phenotyping of ApoE falsely identified E2/E2 phenotype. The presence of mutated ApoE was suspected on an unusual restriction polymorphism of a Hha 1 restriction site and confirmed by sequence analysis of the cloned polymerase chain reaction fragment of exon 4 and familial segregation study. The severity of the hypertriacylglycerolaemia was modulated by the lipid content of the diet. A low-fat diet enriched in medium-chain triacylglycerol (TAG) decreased but did not normalize plasma TAG levels in both affected patients of the pedigree. A standardized lipid-enriched test meal showed a marked impairment of TAG-rich lipoprotein (TRL) clearance, especially the exogeneous TRL bearing ApoB-48 which still represented 79% of total TRL 7 h after the fat load. Finally, differences between the male and female siblings with the existence of a consanguine relationship in their parents suggested the involvement of other genetic factors in modulating the severity of phenotypic expression. This observation reinforces the usefulness of genotyping of ApoE for the characterization of genetic hypertriacylglycerolaemia and selection of the appropriate diet and treatment. C1 Univ Mediterranee, Hop St Marguerite, Serv Nutr Malad Metab Endocrinol, UPRES EA 2193, Marseille, France. Univ Angers, Biochim Lab, Angers, France. INSERM, U476, F-13258 Marseille, France. Inst Pasteur, F-59019 Lille, France. RP Vialettes, B, Univ Mediterranee, Hop St Marguerite, Serv Nutr Malad Metab Endocrinol, UPRES EA 2193, Marseille, France. TC 5 PD JUN PY 2000 VL 83 IS 6 BP 615 EP 622 UT ISI:000087771500006 ER PT J AU Bergamaschi, R Tuech, JJ Cervi, C Arnaud, JP TI Re-establish pneumoperitoneum in laparoscopic-assisted sigmoid resection? Randomized trial SO DISEASES OF THE COLON & RECTUM DE anastomosis; colectomy; diverticulitis; laparoscopic sigmoid resection ID COLORECTAL SURGERY; COLON RESECTION; LEARNING-CURVE; COLECTOMY AB PURPOSE: Operating room time and anastomosis-related morbidity of laparoscopic-assisted sigmoid resection with anastomosis performed in an open fashion through a horizontal suprapubic incision or laparoscopically after re-establishing pneumoperitoneum were compared. METHODS: A randomized trial was performed on patients with recurrent uncomplicated diverticulitis of the sigmoid colon during a 14-month period. Inclusion criteria were persistence of symptoms despite medical treatment and two previous admissions. Exclusion criteria included complicated diverticulitis, suspected cancer, and previous extensive abdominal surgery. Because skin incisions were similar and patients were randomly assigned in the operating room, the trial was performed as double blind. RESULTS: There were no deaths. Two patients were excluded before randomization. Three patients were not treated as allocated because of conversion to open surgery. Aside from previous abdominal-surgery rates, 16 patients with laparoscopic-assisted sigmoid resections after re-establishing pneumoperitoneum and 15 patients with laparoscopic-assisted sigmoid resections with anastomosis performed in an open fashion through a horizontal suprapubic incision were well-matched for age, gender, weight, American Society of Anesthesiology class, previous admissions, skin-incision length, size of circular stapler, and mobilization of splenic flexure. There were no significant differences in morbidity fates (3/16 vs. 3/15), complete doughnuts (16/16 vs. 15/ 15), blood loss (300 vs. 200 ml), natus (4 vs. 4 days), solid-food resumption (5 vs. 6 days), stay (8.5 vs. 9 days) in laparoscopic-assisted sigmoid resection after re-establishing pneumoperitoneum and laparoscopic-assisted sigmoid resection with anastomosis performed in an open fashion through a horizontal suprapubic incision groups, respectively. Patients with laparoscopic-assisted sigmoid resection after re-establishing pneumoperitoneum had statistically longer operating room time (295 vs. 190 minutes; P < 0.01). Median follow-up was 12 and 10 months in 10 patients with laparoscopic-assisted sigmoid resection after reestablishing pneumoperitoneum and 11 patients with laparoscopic-assisted sigmoid resection with anastomosis performed in an open fashion through a horizontal suprapubic incision, respectively. One patient with laparoscopic-assisted sigmoid resection with anastomosis performed in an open fashion through a horizontal suprapubic incision had an anastomotic stenosis endoscopically dilated. CONCLUSIONS: Nonrestoration of pneumoperitoneum after laparoscopic-assisted sigmoid resection allows a decrease in operating room time and a similar outcome. C1 Angers Univ Hosp, Dept Visceral Surg, Angers, France. RP Bergamaschi, R, Univ Trondheim Hosp, Natl Ctr Adv Laparoscop Surg, Olav Kyrres Gate 17, N-7006 Trondheim, Norway. TC 5 PD JUN PY 2000 VL 43 IS 6 BP 771 EP 774 UT ISI:000087531700006 ER PT J AU Croquet, V Pilette, C Aube, C Bouju, B Oberti, F Cervi, C Arnaud, JP Rousselet, MC Boyer, J Cales, P TI Late recurrence of a hepatic angiomyolipoma SO EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY DE benign liver tumour; hepatic angiomyolipoma; HMB-45 antibody; mesenchymal tumour; renal angiomyolipoma ID TUBEROUS SCLEROSIS; LIVER; HMB-45 AB Angiomyolipomas are benign mesenchymal tumours, mostly of renal origin. Hepatic angiomyolipomas are rare, and radiological and pathological diagnoses may be difficult, We report on the first case of hepatic angiomyolipoma recurrence known to us, 6 years after surgical treatment of the initial tumour. Morever, this hepatic recurrence was associated with renal angiomyolipoma without any stigmata of tuberous sclerosis. (C) 2000 Lippincott Williams & Wilkins. C1 CHU Angers, Serv Hepatogastroenterol, F-49033 Angers 01, France. RP Cales, P, CHU Angers, Serv Hepatogastroenterol, F-49033 Angers 01, France. TC 5 PD MAY PY 2000 VL 12 IS 5 BP 579 EP 582 UT ISI:000086944900018 ER PT J AU Olivier, C Auguste, P Chabbert, M Lelievre, E Chevalier, S Gascan, H TI Identification of a gp130 cytokine receptor critical site involved in oncostatin M response SO JOURNAL OF BIOLOGICAL CHEMISTRY ID LEUKEMIA-INHIBITORY FACTOR; COLONY-STIMULATING FACTOR; CILIARY NEUROTROPHIC FACTOR; IL-6 SIGNAL TRANSDUCER; HIGH-AFFINITY BINDING; SEVERE COMBINED IMMUNODEFICIENCY; COMMON BETA-CHAIN; MOLECULAR-CLONING; LIGAND-BINDING; MONOCLONAL-ANTIBODIES AB Gp130 cytokine receptor is involved in the formation of multimeric functional receptors for interleukin-6 (IL-6), IL-11, leukemia inhibitory factor (LIF), oncostatin Rf (OSM), ciliary neurotrophic factor, and cardiotrophin-1. Cloning of the epitope recognized by an OSM-neutralizing anti-gp130 monoclonal antibody identified a portion of gp130 receptor localized in the EF loop of the cytokine binding domain. Site-directed mutagenesis of the corresponding region was carried out by alanine substitution of residues 186-198. To generate type 1 or type 2 OSM receptors, gp130 mutants were expressed together with either LIF receptor beta or OSM receptor beta. When positions Val-189/Tyr-190 and Phe-191/Val-192 were alanine-substituted, Scatchard analyses indicated a complete abrogation of OSM binding to both type receptors. Interestingly, binding of LIF to type 1 receptor was not affected, corroborating the notion that in this case gp130 mostly behaves as a converter protein rather than a binding receptor. The present study demonstrates that positions 189-192 of gp130 cytokine binding domain are essential for OSM binding to both gp130/LIF receptor beta and gp130/OSM receptor beta heterocomplexes. C1 CHU Angers, INSERM E 9928, F-49033 Angers, France. RP Gascan, H, CHU Angers, INSERM 9928, 4 Rue Larrey, F-49033 Angers, France. TC 5 PD FEB 25 PY 2000 VL 275 IS 8 BP 5648 EP 5656 UT ISI:000085474500055 ER PT J AU Uhrhammer, N Bay, JO Gosse-Brun, S Kwiatkowski, F Rio, P Daver, A Bignon, YJ TI Allelic imbalance at NBS1 is frequent in both proximal and distal colorectal carcinoma SO ONCOLOGY REPORTS DE colorectal cancer; chromosomal instability; Nijmegen breakage syndrome; ataxia-telangiectasia; allelic imbalance; loss of heterozygosity ID NIJMEGEN-BREAKAGE-SYNDROME; DOUBLE-STRAND BREAKS; HEPATOCELLULAR-CARCINOMA; DNA-DAMAGE; CANCER; DELINEATION; INSTABILITY; ALLELOTYPE; RESPONSES; PROTEIN AB Nijmegen breakage syndrome (NBS) is a hereditary disorder involving chromosomal instability, cancer risk and radiosensitivity. NBS carriers have an increased risk of cancer, though the significance of mutations in the NBS1 gene in sporadic cancer has not yet been investigated. Because the loss of NBS1 is associated with increased chromosomal rearrangements, and tumors of the colon are particularly prone to chromosomal anomalies, we have begun to study the NBS1 locus in colorectal cancer (CRC). DNA was isolated from 99 microdissected colorectal tumors, and micro-satellite markers flanking the NBS1 locus at 8q21.3 as well as elsewhere on 8q were analyzed. Normal lymphocyte DNA from each patient served to normalize the amplification of each allele, and a reduction of at least 35% in the intensity of one allele was taken as evidence of allelic imbalance (AI). In proximal and distal CRCs we found 25.9 and 36.2% with AI at 8q21.3, respectively. AI in proximal CRC tended not to extend to marker D8S555 at 8q24.1, whereas in distal CRC the region of AI frequently included all the informative markers. AI of 8q21.3 was not associated with any clinical variable. These results suggest that 8q21.3 contains a tumor suppressor gene involved in proximal CRC, possibly NBS1. The large regions of AI make it difficult to determine the importance of AI at the NBSI locus in distal CRC. C1 Ctr Jean Perrin, Mol Oncol Lab, INSERM CRI 9502, F-63011 Clermont Ferrand, France. Ctr Jean Perrin, EA 2145, F-63011 Clermont Ferrand, France. Ctr Paul Papin, Serv Radiotherapie, F-49033 Angers, France. Ctr Jean Perrin, F-63011 Clermont Ferrand, France. INSERM U484, Clermont Ferrand, France. RP Uhrhammer, N, Ctr Jean Perrin, Mol Oncol Lab, INSERM CRI 9502, 58 Rue Montalembert, F-63011 Clermont Ferrand, France. TC 5 PD MAR-APR PY 2000 VL 7 IS 2 BP 427 EP 431 UT ISI:000085194400037 ER PT J AU Genet, S Costalat, R Burger, J TI A few comments on electrostatic interactions in cell physiology SO ACTA BIOTHEORETICA ID BULLFROG SYMPATHETIC NEURONS; ENZYME ORGANIZATION; SURFACE-CHARGES; MEMBRANE; CHANNEL; FLOW AB The role of fixed charges present at the surface of biological membranes is usually described by the Gouy-Chapman-Grahame theory of the electric double-layer where the Grahame equation is applied independently on each side of the membrane and where the capacitive charges (linked to the transmembrane ionic currents) are disregarded. In this article, we generalize the Gouy-Chapman-Grahame theory by taking into account both intrinsic charges (resulting from the dissociation of membrane constituents) and capacitive charges, in the density value of the membrane surface charges. In the first part, we show that capacitive charges couple electrostatic potentials present on both sides of the membrane. The intensity of this coupling depends both on the value of the membrane specific capacitance and the transmembrane electric potential difference. In the second part, we suggest some physiological implications of membrane electric double-layers. C1 Univ Paris 06, INSERM, U483, F-75252 Paris 05, France. Univ Angers, LISA, F-49045 Angers, France. RP Costalat, R, Univ Paris 06, INSERM, U483, Boite 23,9 Quai St Bernard, F-75252 Paris 05, France. TC 4 PY 2000 VL 48 IS 3-4 BP 273 EP 287 UT ISI:000167685400008 ER PT J AU Roquelaure, Y Raimbeau, G Dano, C Martin, YH Pelier-Cady, MC Mechali, S Benetti, F Mariel, J Fanello, S Penneau-Fontbonne, D TI Occupational risk factors for radial tunnel syndrome in industrial workers SO SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH DE force; musculoskeletal disorders; nerve entrapment; posture; radial nerve; work-related ID DISORDERS AB Objectives The aim of the study was to evaluate both nonoccupational and occupational factors associated with radial tunnel syndrome (RTS) among industrial workers in 3 large plants. Methods Twenty-one cases of RTS were compared with 21 referents matched for gender, age, and plant. RTS was associated with carpal tunnel syndrome (CTS) in 9 cases. Past medical history, household activities, and ergonomic and organizational characteristics of the job were analyzed. Results The study found 3 occupational risk factors for RTS. Exertion of force of over 1 kg [odds ratio (OR) 9.1, 95% confidence interval (95% CI) 1.4-56.9] more than 10 times per hour was the main biomechanical risk factor. Prolonged static load applied to the hand during work was strongly associated with RTS (OR 5.9, 95% CI 1.2-29.9). Work posture with the elbow fully extended (0-45 degrees) was associated with RTS (OR 4.9, 95% CI 1.0-25.0). Full extension of the elbow, associated with a twisted posture of the forearm, stressed the radial nerve at the elbow. However, personal activities, household chores, and sport and leisure activities were not associated with RTS. Conclusions The study confirms that RTS occurs in workers performing hard manual labor that requires forceful and repetitive movements involving elbow extension and forearm prosupination. C1 Ctr Main, Hand Surg Ctr, Angers, France. Serv Med Interenterprise Anjou, Occupat Hlth Serv Anjou, Angers, France. CHU Angers, Ctr Consultat Pathol Profess, Occupat Hlth Ctr, Univ Hosp, Angers, France. RP Roquelaure, Y, CHU Angers, Ctr Consultat Pathol Profess, Occupat Hlth Ctr, F-49033 Angers, France. TC 4 PD DEC PY 2000 VL 26 IS 6 BP 507 EP 513 UT ISI:000166404800008 ER PT J AU Zandecki, M Genevieve, F Jego, P Grosbois, B TI Monoclonal gammopathy of undetermined significance SO REVUE DE MEDECINE INTERNE DE monoclonal gammopathy; MGUS; multiple myeloma; plasma cell ID PLASMA-CELL DYSCRASIAS; HEPATITIS-C VIRUS; IN-SITU HYBRIDIZATION; SMOLDERING MULTIPLE-MYELOMA; POPULATION-BASED REGISTRY; MALIGNANT TRANSFORMATION; FOLLOW-UP; DIFFERENTIAL-DIAGNOSIS; BONE-RESORPTION; CD56 EXPRESSION AB Introduction.-Monoclonal gammopathy of undetermined significance is an asymptomatic disorder associated with serum monoclonal immunoglobulin spike. Its incidence is about 1% in patients of 50 years of age, and rapidly increases in elderly patients. Current knowledge and key points. - Within the 20 years following diagnosis, about 25% of patients will evolve towards either multiple myeloma (for patients with IgG or Ig A) or malignant lymphoproliferative disorder (for patients with IgM). Definition, circumstances associated with a transient monoclonal spike, and currently available parameters used for differential diagnosis with either multiple myeloma or malignant lymphoproliferative disorder are successively discussed. One part of the most usual biological parameters is of prognostic value, and is reviewed in more detail. Recent data concerning immunophenotype, cytogenetics and molecular biology of plasma cells reinforce the link between the asymptomatic condition and multiple myeloma. In monoclonal gammopathy of undetermined significance, some plasma cells resemble normal or reactive plasma cells, whereas others mimic those found in multiple myeloma. Future prospects and projects.-The most recent biological data are also discussed in order to evaluate whether some would help to discriminate those patients who will remain asymptomatic lifelong from those who will evolve towards multiple myeloma. (C) 2000 Editions scientifiques et medicales Elsevier SAS. C1 CHU Angers, Hematol Lab, F-49033 Angers, France. RP Zandecki, M, CHU Angers, Hematol Lab, 4 Rue Larrey, F-49033 Angers, France. TC 4 PD DEC PY 2000 VL 21 IS 12 BP 1060 EP 1074 UT ISI:000166374700005 ER PT J AU Coutand, C Julien, JL Moulia, B Mauget, JC Guitard, D TI Biomechanical study of the effect of a controlled bending on tomato stem elongation: global mechanical analysis SO JOURNAL OF EXPERIMENTAL BOTANY DE bending; biomechanics; growth; thigmomorphogenesis; tomato ID INDUCED HYDRAULIC SIGNALS; MAIZE LEAF; RESPONSES; GROWTH; PLANTS; STRESS; SEEDLINGS; STIMULATION; SUNFLOWER; THIGMOMORPHOGENESIS AB An experiment was designed to apply a controlled bending to a tomato stem and simultaneously to measure its effect on stem elongation. Stem elongation was measured over 2 d until steady and equal rates were obtained for the control and the treated plants. Thereafter, the basal part of the stem was submitted to a transient controlled bending at constant displacement rate using a motorized dynamo; meter. After load removal, stem elongation was again measured for 2 d. The tested plants were mature (height visible internodes) and only the basal part of the stem, which had already finished elongation, was loaded (hypocotyl and the first three internodes). A few minutes after the application of bending, elongation stopped completely for 60 min. Thereafter it took 120-1000 min to recover a rate of elongation similar to the control. The growth response was exclusively due to the bending of the basal part of the stem. It was shown that the side mechanical perturbations on the roots and on the stem tissues interacting directly with the clamp were not significantly involved on the elongation response. These results give evidence for mechanical perception and plant signalling from the basal stem to the upper elongating zone. However, none of the variables characterizing the global mechanical state of the bent part of the stem (i.e. the maximal force, bending moment, inclination, mean curvature of the stem, stored mechanical energy) could quantitatively explain the variability of the growth response. A more local mechanical analysis is therefore needed to elucidate how the mechanical stimulus is perceived. C1 INRA, Stn Ecophysiol Plantes Fourrageres, F-86600 Lusignan, France. INRA, Unite Bioclimatol PIAF, F-63039 Clermont Ferrand 2, France. Univ Blaise Pascal, Unite Bioclimatol PIAF, F-63177 Clermont Ferrand, France. Ecole Natl Super Hort, F-49000 Angers, France. Ecole Natl Super Arts & Metiers, Lab Energet & Phenomenes Transfert, F-33405 Talence, France. RP Moulia, B, INRA, Stn Ecophysiol Plantes Fourrageres, F-86600 Lusignan, France. TC 4 PD NOV PY 2000 VL 51 IS 352 BP 1813 EP 1824 UT ISI:000165981900005 ER PT J AU Bensmaine, MA de Gramont, A Brienza, S Marty, M Levi, F Ducreux, M Francois, E Gamelin, E Bleiberg, H Bleuzen, P Simon, J Cvitkovic, E TI Factors predicting for efficacy of oxaliplatin in combination with 5-fluorouracil (5-FU)+/- folinic acid (FA) in a compassionate-use cohort of 370 5-FU-resistant advanced colorectal cancer (CRC) patients SO EUROPEAN JOURNAL OF CANCER DE clinical resistance; multivariate analysis; salvage chemotherapy ID CONTINUOUS-INFUSION 5-FLUOROURACIL; PHASE-II; FOLINIC ACID; CHEMOTHERAPY; FLUOROURACIL; TRIAL; LEUCOVORIN; CARCINOMA; IRINOTECAN; CISPLATIN AB Univariate and multivariate analyses were performed on data from 370 5-fluorouracil (5-FU)-resistant advanced colorectal cancer patients treated with oxaliplatin (Eloxatin(R))/5-FU+/-folinic acid (FA) to identify prognostic factors for oxaliplatin-based treatment. The response rate was 14.6% (95% confidence interval (CT): 11.0-18.2%), median time to progression was 4.3 months (95% CI, 3.9-4.7), and median overall survival 9.7 months (95% CT: 8.5-10.8). Multivariate analysis indicated <2 prior chemotherapy regimens, bi-weekly treatment administration schedule (versus tri-weekly) and continuous chronomodulated delivery (CCM) as significantly associated (P < 0.05) with a higher overall response rate. Performance status (PS) <2, having only one involved organ, biweekly schedule and CCM were associated (P<0.05) with a longer time to progression. Good PS, one involved organ, low alkaline phosphatase (AP) serum levels, bi-weekly schedule and CGM were significantly correlated with longer overall survival, while confirming the efficacy of oxaliplatin/5-FU+/-FA in this indication. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Cvitkov & Associates, Le Kremlin Bicetre, France. Hop St Antoine, Serv Med Interne Oncol, F-75571 Paris, France. Debiopharm, Charenton Le Pont, France. Hop St Louis, Med Oncol Serv, Paris, France. Hop Paul Brousse, Serv Cancerol, Villejuif, France. Inst Gustave Roussy, Dept Med, Villejuif, France. Ctr Antoine Lacassagne, Oncopharmacol Unit, F-06054 Nice, France. Ctr Paul Papin, Dept Oncol Med & Oncopharmacol, Angers, France. Inst Jules Bordet, Dept Gastroenterol, B-1000 Brussels, Belgium. RP Cvitkovic, E, Cvitkov & Associates, Le Kremlin Bicetre, France. TC 4 PD DEC PY 2000 VL 36 IS 18 BP 2335 EP 2343 UT ISI:000165724700020 ER PT J AU Riou, M Renier, G Mattman, S Fialaire, P Loison, J Chennebault, JM Payan, C TI Dynamic study of anti-VIH antibodies avidity with cellular immune restoration under Haart SO ANNALES DE BIOLOGIE CLINIQUE DE HIV; antibodies; immunity ID HUMAN-IMMUNODEFICIENCY-VIRUS; DISTINGUISHES PRIMARY; IGG ANTIBODIES; PREGNANT-WOMEN; INFECTION; DIAGNOSIS; RESPONSES; AFFINITY; MATURATION; HIV-1 AB We have studied the evolution of the avidity of anti-HIV antibodies, in 14 infected patients with Aids, including 11 patients with severe immunodeficiency at Aids stage and under active antiretroviral therapy (HAART), and 3 non-treated patients with moderate immunodeficiency. These patients have been followed up to 4 years, every 4 months the first year and every 6 months the three others, with HIV1 RNA viral load, CD4 and CD8 cells dosages and anti-HIV avidity measurements (Axsym HIV-1/2), using 1 M guanidine denaturation. A rapid decrease of the viral load was observed under Haart, inducing immune restoration with CD4 and CD8 cells increases (10 and 2-fold respectively). The decrease of anti-HIV avidity (- 20%) has been observed after 5 to 8 months under Haart, with a return to baseline value (84%). The quick restoration of CD4 cells with a persistance of viral antigens at the begining of treatment has facilitated the selection of novel naive B lymphocytes producing low-affinity antibodies, measured by the decrease of global anti-HIV avidity. The reduction or even clearance of viral antigens under Haart could secondarly induce the selection of B lymphocytes with higher antibody affinity and therefore higher anti-HIV avidity. Thus, this avidity measurement could be used to assess the functional activity of CD4 cells restoration in HIV infected patients under Haart. C1 CHU Angers, Serv Malad Infect, Lab Bacteriol Virol, F-49033 Angers, France. CHU Angers, Immunol Lab, F-49033 Angers, France. RP Payan, C, CHU Angers, Serv Malad Infect, Lab Bacteriol Virol, 4 Rue Larrey, F-49033 Angers, France. TC 4 PD NOV-DEC PY 2000 VL 58 IS 6 BP 715 EP 720 UT ISI:000165642600007 ER PT J AU Grolier, P Boirie, Y Levadoux, E Brandolini, M Borel, P Azais-Braesco, V Beaufrere, B Ritz, P TI Age-related changes in plasma lycopene concentrations, but not in vitamin E, are associated with fat mass SO BRITISH JOURNAL OF NUTRITION DE age; carotenoids; vitamin E; body composition ID ALPHA-TOCOPHEROL LEVELS; HUMAN ADIPOSE-TISSUE; BETA-CAROTENE; ENERGY-EXPENDITURE; NUTRITIONAL-STATUS; BODY-COMPOSITION; MEN; LIPOPROTEIN; RETINOL; ADULTS AB The aim of the present study was to assess the influence of age on plasma concentration of alpha -tocopherol, retinol and carotenoids with a special attention paid to natural differences in body composition. Forty healthy subjects were recruited: twenty were less than 35 years old and twenty above 60 years old. Males and females were equally represented in each age group. Subjects were kept in energy balance and received controlled diets for 36 h. Fat mass and fat-free mass were determined with the (18)0-enriched water dilution technique. Plasma vitamins A and E, and carotenoid levels were determined after 12 h fasting and were shown to be similar in women and men. Plasma alpha -tocopherol concentration increased with age (+44 % elderly v. young), and correlated with % fat mass and plasma cholesterol. After adjustment for plasma cholesterol, the effect of age and % fat mass disappeared. In contrast, plasma lycopene level was 2-fold lower in the elderly than in the young group, and was inversely correlated with fat mass. When lycopene values were adjusted for fat mass, the effect of age disappeared. These results suggest that plasma levels of vitamin E and lycopene differed in the two age groups and that differences in plasma cholesterol and fat mass might participate in such an effect. Short-term vitamin intake did not appear to influence plasma vitamin concentrations. C1 INRA, Unite Malad Metab & Micronutriments, Grp Vitamines, F-63122 St Genes Champanelle, France. Univ Auvergne, Lab Nutr Humaine, F-63009 Clermont Ferrand, France. RP Ritz, P, CHU Angers, Serv Med B, F-49033 Angers 01, France. TC 4 PD NOV PY 2000 VL 84 IS 5 BP 711 EP 716 UT ISI:000165553000016 ER PT J AU Bourasseau, I Savagner, F Rodien, P Duquenne, M Reynier, P Guyetant, S Bigorgne, JC Malthiery, Y Rohmer, V TI No evidence of thyrotropin receptor and G(S alpha) gene mutation in high iodine uptake thyroid carcinoma SO THYROID ID AUTONOMOUSLY FUNCTIONING NODULE; GRAVES-DISEASE; TSH RECEPTOR; ACTIVATING MUTATION; HOT NODULE; CANCER; TUMORS; HYPERTHYROIDISM; MIMICKING; ADENOMAS AB Usually, thyroid carcinoma presents as a cold nodule on radioiodine scintigraphy. High-uptake nodules on iodine thyroid scans are associated with an exceedingly low incidence of malignancy. Only 29 cases of carcinomas appearing as hot or warm nodules have as yet been reported. From 1993 to 1999, we have observed eight similar cases (4 hot and 4 warm thyroid nodules) suggesting that thyroid carcinomas may not be as rare as usually considered in these circumstances. Four tumors were available for molecular analysis on paraffin-embedded sections. Because no mutations were found in the whole coding portions of thyrotropin-receptor (TSH-R) gene and fragments encompassing the mutational hot spots of the Gs alpha gene, it is unlikely that activating mutations of the TSH-R or G(s alpha) genes were involved in these carcinomas. C1 CHU Angers, Lab Biochim & Biol Mol, Angers, France. CHU Angers, Serv Endocrinol Nutr Med Interne, Angers, France. CHU Angers, Anat Pathol Lab, Angers, France. Fac Med, Inserm EMI U 00 18, Angers, France. RP Savagner, F, Ctr Hosp Angers, Lab Biochem & Biol Mol, 4 Rue Larrey, F-49033 Angers 01, France. TC 4 PD SEP PY 2000 VL 10 IS 9 BP 761 EP 765 UT ISI:000089745700005 ER PT J AU Feldman, GM Graczyk, P TI On the Skitovich-Darmois theorem for compact Abelian groups SO JOURNAL OF THEORETICAL PROBABILITY DE characterization of probability distributions; independence of linear statistics; compact Abelian group AB Let X be a separable compact Abelian group, Aut(X) the group of topological automorphisms of X, f(n): X --> X a homomorphism f(n)(x) = nx, and X-(n) = Im f(n). Denote by I(X) the set of idempotent distributions on X and by Gamma(X) the set of Gaussian distributions on X. Consider linear statistics L-1 =alpha(1)(xi(1)) + alpha(2)(xi(2)) and L-2 = beta(1)(xi(1))+ beta(2)(xi(2)), where xi(j) are independent random variables taking on values in X and with distributions mu(j), and alpha(j), beta(j) is an element of Aut(X). The following results are obtained. Let X be a totally disconnected group. Then the independence of L-1 and L-2 implies that mu(1), mu(2) is an element of I(X) if and only if X possesses the property: for each prime p the factor-group X/X-(p) is finite. If X is connected, then there exist independent random Variables xi(j) taking on values in X and with distributions mu(j), and alpha(j), beta(j) is an element of Aut(X) such that L-1 and L-2 are independent, whereas mu(1), mu(2) is not an element of Gamma(X)*I(X). C1 Inst Low Temp Phys & Engn, UA-310164 Kharkov, Ukraine. Univ Angers, F-49045 Angers, France. RP Feldman, GM, Inst Low Temp Phys & Engn, 47 Lenin Ave, UA-310164 Kharkov, Ukraine. TC 4 PD JUL PY 2000 VL 13 IS 3 BP 859 EP 869 UT ISI:000089780000012 ER PT J AU Ibrahim, G Bouet, GM Hall, IH Khan, MA TI Stability constants of potent cytotoxic copper(II) complexes with furan semicarbazones in ethanolic solutions SO JOURNAL OF INORGANIC BIOCHEMISTRY DE copper; cytotoxic complexes; furan; semicarbazones; stability constants; ethanolic solutions ID 3D ELEMENT DIHALIDES; CULTURED CELL-LINES; METALLIC COMPLEXES; DERIVATIVES; THIOSEMICARBAZONES; OXIMES; 2-ACETYLPYRIDINE; HALIDES; MURINE AB Potent cytotoxic copper(II) complexes of furannic semicarbazones were studied in ethanolic solutions at 25 degrees C. The four ligands used were synthesized in our laboratory, i.e. 2-furfural semicarbazone (FSC), 5-methyl 2-furfural semicarbazone: (MFSC), 2-furfural 4-phenyl semicarbazone (FPSC) and 3-(2-furyl) prop-2-enal semicarbazone (FASC). The mathematical analysis was carried out with a recent computer program smite which indicated the formation of one: metal-ligand complex in each case and the logarithm of their stability constants are: log beta = 2.02, 3.84, 4.58 and 4.52 for ligands FSC, MFSC, FASC and FPSC, respectively. A relation between stability and molecular weight of the ligands is proposed which may prove to be interesting as these complexes are being investigated for their cytotoxic activities. (C) 2000 Elsevier Science S.A. All rights reserved. C1 Univ Angers, Fac Pharm, Chim Coordinat Lab, F-49100 Angers, France. Univ Libanaise, Ramle El Baida, Beyrouth, Lebanon. Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA. RP Khan, MA, Univ Angers, Fac Pharm, Chim Coordinat Lab, 16 Blvd Daviers, F-49100 Angers, France. TC 4 PD JUL 15 PY 2000 VL 81 IS 1-2 BP 29 EP 34 UT ISI:000089337800004 ER PT J AU Ligot, J Benayoun, S Hantzpergue, JJ TI Analysis of cracking induced by scratching of tungsten coatings on polyimide substrate SO WEAR DE scratch test; tungsten; coating; polyimide; fracture ID THIN-FILMS; ADHESION AB Tungsten films were deposited on Upilex S polyimide substrates using a triode discharge system. Films 200, 400 and 600 nm thick were produced at three different argon deposition pressures (0.2, 0.7 and 1.2 Pa). The behaviour of the metallic coating-polymeric substrate composite was studied by sliding indentation. Three different scratching tests were carried out: in increasing load mode (ILM), in increasing load mode with multipass (ILM-M), and in constant load mode (CLM). These scratchings induced transversal crack formation but no coating delamination in the range of the studied parameters (applied load L less than or equal to 30 N, load gradient less than or equal to 15 N mm(-1)). The critical load, L-c(i) was defined as the load at which cracks occurred in the coating homogeneously throughout the scratch. The superscript i denotes the number of scratches in multipass mode. Intrinsic parameters such as scratching speed (dx/dt) or loading rate (dL/dt) were considered in order to facilitate the interpretation of the critical load results. It was shown that L-c(1) (in ILM) increased with deformation rate of the polyimide substrate. Qualitative assessments of the coating toughness under sliding indentation were proposed by the comparison of L-c(1) and L-c(10) (in ILM-M). Comparative information about the size and the length distribution of pre-existing cracks within the tungsten coatings were obtained by interpreting the CLM results. (C) 2000 Elsevier Science S.A. All rights reserved. C1 ENSAM, Lab Procedes Mat Instrumentat, CER Angers, F-49035 Angers, France. RP Benayoun, S, ENSAM, Lab Procedes Mat Instrumentat, CER Angers, 2 Bd Ronceray,BP 3525, F-49035 Angers, France. TC 4 PD AUG PY 2000 VL 243 IS 1-2 BP 85 EP 91 UT ISI:000089129400011 ER PT J AU Grandiere-Perez, L Asfar, P Foussard, C Chennebault, JM Penn, P Degasne, I TI Spondylodiscitis due to Aspergillus terreus during an efficient treatment against invasive pulmonary aspergillosis SO INTENSIVE CARE MEDICINE C1 CHU Angers, Dept Intens Care, F-49033 Angers, France. CHU Angers, Dept Hematol, F-49033 Angers, France. CHU Angers, Dept Mycol, F-49033 Angers, France. CHU Angers, Dept Rheumatol, F-49033 Angers, France. RP Asfar, P, CHU Angers, Dept Intens Care, F-49033 Angers, France. TC 4 PD JUL PY 2000 VL 26 IS 7 BP 1010 EP 1011 UT ISI:000088623500030 ER PT J AU Burtin, P Kaassis, M Aube, C Giovannini, M Di Stefano, D Arnaud, JP Cellier, P Boyer, J TI Asa classification and lymph node extent at endosonography are independent predictive factors of survival of patients with esophageal cancer. SO GASTROINTESTINAL ENDOSCOPY C1 Univ Hosp, Angers, France. Inst J Paoli I Calmettes, F-13009 Marseille, France. Ctr Paul Papin, Angers, France. TC 4 PD APR PY 2000 VL 51 IS 4 PN Part 2 BP AB119 EP AB119 UT ISI:000087007300229 ER PT J AU Tcherniega, N Sokolovskaia, A Kudriavtseva, AD Barille, R Rivoire, G TI Backward stimulated Raman scattering in water SO OPTICS COMMUNICATIONS ID PICOSECOND RANGE; RECONSTRUCTION AB The backward Stimulated Raman scattering (BSRS) is studied in Liquid water. We show that BSRS can be produced by small volumes of active materials. Our experimental results and calculations with different geometries and intensities of excitation allow us to choose the best experimental set-up for BSRS efficiencies. The competition with librational scattering is also observed. (C) 2000 Published by Elsevier Science B.V. C1 Univ Angers, Lab Proprietes Opt Mat & Applicat, F-49016 Angers, France. Russian Acad Sci, PN Lebedev Inst, Moscow 117924, Russia. RP Barille, R, Univ Angers, Lab Proprietes Opt Mat & Applicat, 4 Blvd Lavoisier,BP 2018, F-49016 Angers, France. TC 4 PD JUL 1 PY 2000 VL 181 IS 1-3 BP 197 EP 205 UT ISI:000088039400024 ER PT J AU Pessaux, P Tuech, JJ Regenet, N Fauvet, R Boyer, J Arnaud, JP TI Laparoscopic cholecystectomy in acute cholecystitis. A prospective non-randomized study SO GASTROENTEROLOGIE CLINIQUE ET BIOLOGIQUE DE laparoscopic cholecystectomy; acute cholecystitis; optimal timing ID TRIAL; CHOLELITHIASIS AB Objectives - To evaluate the results of laparoscopic cholecystectomy in patients with acute cholecystitis and to determine the optimal timing. Patients and methods - From January 1993 to December 1999, 168 patients (91 women and 77 men with a mean age of 57.3 years) underwent laparoscopic cholecystectomy for acute cholecystitis confirmed by histopathological examination. Patients were divided into 2 groups (similar in age and ASA classification) : group 1 (106 patients) underwent laparascopic cholecystectomy within 3 days after the onset of symptoms of acute cholecystitis and group 2 (62 patients) underwent laparoscopic cholecystectomy after 3 days. Results-There was no death. Conversion rates were 30.9%. Surgery lasted 141.3 min, postoperative morbidity was 12.5%, and the postoperative length of hospital stay was 6.9 days. The conversion rates in patients who underwent surgery before and 3 days after the onset of symptoms were respectively 21.7% and 46.7% (P=0.0007). There was no statistical difference between early and delayed surgery For time to surgery and postoperative complications. On the of her hand the total hospital stay was significantly shorter in group 1. Conclusion - laparoscopic cholecystectomy for acute cholecystitis is safe and associated with a shorter postoperative stay, a lesser morbidity and a lesser mortality compared to "open surgery. Laparoscopic cholecystectomy should be carried out soon as the diagnostic of acute cholecystitis established and preferably before 3 days after the onset of the symptoms. Early laparoscopic cholecystectomy allows a reduction of the conversion rate and a reduction of total hospital stay that are medical and economic benefits. C1 CHU Angers, Dept Chirurg Viscerale, F-49033 Angers 01, France. CHU Angers, Dept Gastroenterol, F-49033 Angers, France. RP Pessaux, P, CHU Angers, Dept Chirurg Viscerale, 4 Rue Larrey, F-49033 Angers 01, France. TC 4 PD APR PY 2000 VL 24 IS 4 BP 400 EP 403 UT ISI:000087885800002 ER PT J AU Descamps, P Marret, H Binelli, C Chaplot, S Gillard, P TI Modifications of the maternal organism during pregnancy. SO NEUROCHIRURGIE DE physiology; pregnancy; post-partum; Cardiovascular system; hemostasis; hormones ID PULSED DOPPLER VELOCIMETRY; CEREBRAL BLOOD-FLOW; NONPREGNANT WOMEN; VELOCITY; OUTPUT AB Pregnancy induces numerous changes in the physiology of the woman. Those changes are necessary for the embryo and fetus to have a normal growth, and for the woman to adapt to that physiologic event A 50% raised cardiac flow is the consequence of increased systolic flow and cardiac frequency. Blood volume is about 40 % larger than in non-pregnant woman. It is the consequence of enlargement of the plasmatic volume (50 %), and the red cells mass (30 %). Those different changes explain the physiologic anemia of pregnancy. The main part of the blood volume increase corresponds to an enlargement of the venous system, but without any change of the central venous pressure. Arterial pressure remains unchanged throught the pregnancy, or sometimes gently decreases (10 %). Those changes are more important during an effort, particularly during the labor Increase of cerebral blood flow (as a consequence of a raised cardiac flow) is limited by the cerebral autoregulation. As a consequence. there is no evidence for dramatic cerebral hemodynamic changes during pregnancy. Nevertheless, autoregulation is less effective for arterial pressure over than 150 mmNg, what can induce an hemorrhagic stroke. Blood levels of steroid (progesterone, oestrogens) and peptidic (HCG, NPL) hormones are increased. Oestrogens are said to make capillary fragile, and progesterone is responsible for the enlargement of the venous system. In order to prevent an hemorrhagic accident, pregnancy induces a lack of fibrinolysis, and an Excess in coagulation. The consequence is the ability of the pregnant and post-partum woman to develop venous thrombosis. C1 CHU Angers, Serv Gynecol Obstet, F-49033 Angers, France. CHU Tours, Serv Gynecol Obstet, F-37044 Tours 01, France. RP Descamps, P, CHU Angers, Serv Gynecol Obstet, F-49033 Angers, France. TC 4 PD APR PY 2000 VL 46 IS 2 BP 68 EP 75 UT ISI:000087621100002 ER PT J AU Monteil, A Bernard, C Chaussedent, S Ferrari, M Balu, N Obriot, J TI Pressure effect on the structure and the luminescence of rare-earth ions doped glasses: an investigation by molecular dynamics simulation SO JOURNAL OF LUMINESCENCE DE rare earth; glasses; pressure; simulation ID SODIUM DISILICATE GLASS AB Molecular dynamics simulation has been used to study the effect of hydrostatic pressure on the structural and spectroscopic properties of Eu3+-doped Na2O . 2SiO(2) glass. The short- and medium-range order has been investigated. The evolution of angular and radial distribution has shown the dependence of the structure with pressure. It was found that pressure induces an increase of the coordination number of the Eu3+ ion and a shortening in the Eu-O bond distance. The pressure effects on the crystal-field parameters and on the luminescent spectra are computed and discussed in comparison with experimental data. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ Angers, EP CNRS 130, Lab POMA, F-49045 Angers, France. Ctr Fis Stati Aggregati, CNR, CeFSA, I-38050 Trent, Italy. RP Monteil, A, Univ Angers, EP CNRS 130, Lab POMA, 2 Bd Lavoisier, F-49045 Angers, France. TC 4 PD MAY PY 2000 VL 87-9 BP 691 EP 693 UT ISI:000086818000201 ER PT J AU Roy, E Abraham, P Montresor, S Saumett, JL TI Comparison of time-frequency estimators for peripheral embolus detection SO ULTRASOUND IN MEDICINE AND BIOLOGY DE time-frequency distribution; detection; emboli ID SIGNALS; REPRESENTATION; KERNELS AB Recently, a time-frequency processing of peripheral arterial Doppler signals, based on the spectrogram, was proposed to detect automatically high-intensity transient signal. Three time-frequency representations, the smooth-pseudo-Wigner-Ville, the Cloi-Williams and the cone-kernel distributions were compared with the spectrogram, following the detection scheme previously reported. The results showed that the spectrogram provided the best compromises between false-detection and no-detection compared with the other time-frequency representations. (C) 2000 World Federation for Ultrasound in Medicine & Biology. C1 CHU Angers, Lab Physiol & Explorat Fonctionnelles Vasc, F-49033 Angers 01, France. Univ Maine, Lab Informat, F-72017 Le Mans, France. RP Saumett, JL, CHU Angers, Lab Physiol & Explorat Fonctionnelles Vasc, F-49033 Angers 01, France. TC 4 PD MAR PY 2000 VL 26 IS 3 BP 419 EP 423 UT ISI:000086614900008 ER PT J AU McCrory, C Parusinski, A TI Topology of real algebraic sets of dimension 4: necessary conditions SO TOPOLOGY DE real algebraic sets; algebraically constructible functions; links; Euler characteristic ID CONSTRUCTIBLE FUNCTIONS AB Operators on the ring of algebraically constructible functions are used to compute local obstructions for a four-dimensional semialgebraic set to be homeomorphic to a real algebraic set. The link operator and arithmetic operators yield 2(43) - 43 independent characteristic numbers mod 2, which generalize the Akbulut-King numbers in dimension three. (C) 2000 Elsevier Science Ltd. All rights reserved. MSG: primary: 14P25; secondary: 14B05, 14P10. C1 Univ Angers, Dept Math, F-49045 Angers 01, France. Univ Georgia, Dept Math, Athens, GA 30602 USA. RP Parusinski, A, Univ Angers, Dept Math, 2 Bd Lavoisier, F-49045 Angers 01, France. TC 4 PD MAY PY 2000 VL 39 IS 3 BP 495 EP 523 UT ISI:000086005700004 ER PT J AU Sylla, M Manaila-Maximean, D Albu, AM Delaunay, A TI Synthesis, characterization and nonlinear optical properties study of polymers based on coloured monomers SO POLYMER DE nonlinear optics; polymeric materials; third-order susceptibility ID TETRATHIAFULVALENE AB We have synthesized coloured monomer structures characterized by the simultaneous existence of a polarizable double bond and an extended chromophore. The polymerization and copolymerization of these monomers have been tested with styrene and methyl methacrylate. The third-order nonlinear optical (NLO) properties of different samples have been studied from their solutions using chloroform as solvent. The third-order hyperpolarizability gamma(xxxx) of the better materials can reach 10(-29) esu at 532 nm and their response time is faster than 35 ps. The corresponding third-order NLO susceptibility X-xxxx((3)) is estimated to be 6 x 10(-11) esu and the figure of merit X-(3)/alpha = 7.510(-2) esu cm is larger than that of most currently known nonlinear optical polymers. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Univ Angers, Lab POMA, CNRS, EP 130, F-49045 Angers, France. Univ Politehn Bucaresti, Dept Phys, Bucharest 77206, Romania. Univ Politehn Bucaresti, Dept Macromol Chem, Bucharest, Romania. Univ Angers, Serv Commun RMN, F-49045 Angers, France. RP Manaila-Maximean, D, Univ Angers, Lab POMA, CNRS, EP 130, 2 Blvd Lavoisier, F-49045 Angers, France. TC 4 PD MAY PY 2000 VL 41 IS 10 BP 3507 EP 3511 UT ISI:000085388300002 ER PT J AU Cutuli, B Janvier, M de la Rochefordiere, A Julien, JP Isambert, N Alzieu, C Kerbrat, P de Lafontan, B van Lemmens, L Cure, H Ganem, G Baume, D Le Mevel, A Lorthoraly, A de Gislain, C Marchal, C Chevelle, C Lauche, H Serin, D TI Leukemias and preleukemic states developing after treatment of breast cancer SO PRESSE MEDICALE ID ACUTE MYELOID-LEUKEMIA; ADJUVANT CHEMOTHERAPY; SECONDARY LEUKEMIAS; CYCLOPHOSPHAMIDE; MYELODYSPLASIA; TRANSLOCATIONS; RADIOTHERAPY; METHOTREXATE; FLUOROURACIL; EXPERIENCE AB OBJECTIVE: The purpose of this study was to determine the clinical and prognostic features of leukemias and preleukemic states, whatever the mode of development, observed in patients after treatment of breast cancer. PATIENTS AND METHODS: A retrospective multicentric analysis was made of 121 patients treated for breast cancer and who later developed leukemia or a preleuke- mic state. Initially, 44 patients had undergone mastectomy, 72 had conservative surgery and 119 had locoregional irradiation. At least one chemotherapy session was performed in 90 patients and 48 had received tamoxifen. The risk of relapse of breast cancer was high, moderate or low for 44, 46 and 24 patients respectively (data not available for 7 patients). RESULTS: By class, the hematology diseases found were: myelodysplasia (n = 9), refractory anemia with blast excess (n = 7), acute lymphoblastic leukemia (n = 6), acute myoblastic leukemia (n = 93 including a majority of type 2 and type 4). For acute myeloblastic leukemia, mean delay to onset was 65 and 37 months respectively without and after chemotherapy. The prognosis of these cases of leukemia and preleukemic states was poor with an overall death rate of 86%. CONCLUSION: In light of the recent development of indications for adjuvant chemotherapy even for subgroups of patients at moderate risk, it is important to more precisely assess the absolute benefit in terms of survival compared with the risk of severe complications, particular secondary leukemia. In the future, a systematic registry and a case-control study are required. C1 CRLCC, Strasbourg, France. CRLCC, St Cloud, France. CRLCC, Paris, France. CRLCC, Rouen, France. CRLCC, Dijon, France. CRLCC, Marseille, France. CRLCC, Rennes, France. CRLCC, Toulouse, France. CRLCC, Lille, France. CRLCC, Clermont Ferrand, France. CRLCC, Nantes, France. CRLCC, Angers, France. CRLCC, Vandoeuvre Nancy, France. Ctr Jean Bernard, Le Mans, France. CHG Toulon, Toulon, France. Clin Pasteur, Toulouse, France. Clin Clementville, Montpellier, France. Clin St Catherine, Avignon, France. RP Cutuli, B, Ctr Radiotherapie & Oncol Med, Clin Courlancy, 38 Rue Courlancy, F-51100 Reims, France. TC 4 PD JAN 29 PY 2000 VL 29 IS 3 BP 135 EP 138 UT ISI:000085145100002 ER PT J AU Arnaud, JP Tuech, JJ Pessaux, P TI Management of presacral venous bleeding with the use of thumbtacks SO DIGESTIVE SURGERY DE presacral venous bleeding, management occlusion of bleeding sites with thumbtacks ID HEMORRHAGE AB Massive bleeding from the sacral basivertebral vein is uncommon and can be fatal because conventional methods to control the bleeding are often futile. The authors report an effective technique of the occlusion of the bleeding site with a thumbtack. Copyright (C) 2000 S. Karger AG, Basel. C1 CHU Angers, Dept Visceral Surg, F-49033 Angers, France. RP Arnaud, JP, CHU Angers, Dept Visceral Surg, 4 Rue Larrey, F-49033 Angers, France. TC 3 PY 2000 VL 17 IS 6 BP 651 EP 652 UT ISI:000166681500020 ER PT S AU Vostrikova, L Yor, M TI Some invariance properties (of the laws) of Ocone's martingales SO SEMINARIE DE PROBABILITES XXXIV SE LECTURE NOTES IN MATHEMATICS C1 Univ Angers, Fac Sci, Dept Math, F-49045 Angers 01, France. Univ Paris 06, Lab Probabilites & Modeles Aleatoires, F-75252 Paris, France. RP Vostrikova, L, Univ Angers, Fac Sci, Dept Math, 2 Blvd Lavoisier, F-49045 Angers 01, France. TC 3 PY 2000 VL 1729 BP 417 EP 431 UT ISI:000166278800020 ER PT J AU Vielle, B TI A new explicit stability criterion for human periodic breathing SO JOURNAL OF MATHEMATICAL BIOLOGY DE stability criterion; delay differential equation; dynamic characteristics of ventilatory control; periodic breathing ID RESPIRATORY SYSTEM STABILITY; VENTILATORY STABILITY; CO2 DISTURBANCES; INSTABILITY; SLEEP AB The aim of this paper is to carry out a stability analysis for periodic breathing in humans that incorporates the dynamic characteristics of ventilation control. A simple CO2 model that takes into account the main elements of the respiratory system, i.e. the lungs and the ventilatory controller with its dynamic properties, is presented. This model results in a three-dimensional non-linear delay differential system for which there exists a unique equilibrium point. Our stability analysis of this equilibrium point lends to the definition of a new explicit stability criterion and to the demonstration of the existence of a Hopf bifurcation. Numerical simulations illustrate the influence of physiological parameters on the stability of ventilation, and particularly the major role of the dynamic characteristics of the respiratory controller. C1 Univ Angers, Inst Theoret Biol, F-49100 Angers, France. RP Vielle, B, Univ Angers, Inst Theoret Biol, 10 Rue Boquel, F-49100 Angers, France. TC 3 PD DEC PY 2000 VL 41 IS 6 BP 546 EP 558 UT ISI:000166066200004 ER PT J AU Lode, T Pagano, A TI Variations in call and morphology in male water frogs: taxonomic and evolutionary implications SO COMPTES RENDUS DE L ACADEMIE DES SCIENCES SERIE III-SCIENCES DE LA VIE-LIFE SCIENCES DE specific recognition; hybridization; prezygotic isolation; postzygotic isolation ID RANA-TEMPORARIA L; REPRODUCTIVE SUCCESS; ADVERTISEMENT CALL; MATE SELECTION; POPULATIONS; TOADS; BUFO AB In Anurans, the specific mate recognition system (SMRS), which contributes to prezygotic isolation, is mainly based on morphological and call features. This is why such criteria are used by zoologists for taxonomic identification. In hybridogenetic water frogs (Rana ridibunda, R. lessonae, R. perezi, R. kl. grafi and R. kl. esculenta), hybridization opens up the question of the efficiency of these criteria for taxon identification and of the specific recognition system in this context. Variation in both morphological and call features revealed both significant mean differences among taxa but also large overlapping among individuals belonging to different taxa. Thus, using call or morphometrical features in order to identify water frogs may be hazardous. Moreover, species differ poorly in their specific mate recognition system, facilitating hybridization events, and therefore suggesting that postzygotic mechanisms may be prevalent over prezygotic mechanisms. (C) 2000 Academie des sciences/Editions scientifiques et medicales Elsevier SAS. C1 Univ Angers, Lab Ecol Anim, F-49045 Angers, France. RP Pagano, A, Univ Angers, Lab Ecol Anim, 2 Bd Laboisier, F-49045 Angers, France. TC 3 PD NOV PY 2000 VL 323 IS 11 BP 995 EP 1001 UT ISI:000165818900007 ER PT J AU Leblond, H TI Transverse stability of solitons and moving domain walls SO JOURNAL OF PHYSICS A-MATHEMATICAL AND GENERAL ID ELECTROMAGNETIC-WAVES; FERROMAGNET AB The effect of transverse perturbations on the domain walls and Nakata's solitons is studied. The integro-differential equation giving an account of this problem is derived using a multiscale expansion. The line-soliton solutions are shown analytically to be unstable with regard to transverse perturbations. Oblique line-soliton interactions, and eventual localized solutions are studied numerically: wave breaking always occurs. This instability gives rise to the emission of a new type of solitary wave. C1 Univ Angers, Lab POMA, CNRS, UMR 6136, F-49045 Angers 01, France. RP Leblond, H, Univ Angers, Lab POMA, CNRS, UMR 6136, 2 Bd Lavoisier, F-49045 Angers 01, France. TC 3 PD NOV 17 PY 2000 VL 33 IS 45 BP 8105 EP 8126 UT ISI:000165753400011 ER PT J AU Marot-Leblond, A Robert, R Loiseau, O Apaire-Marchais, V Senet, JM TI Hydrophobic and hydrophilic cell surface (glyco)proteinic components of Candida albicans SO JOURNAL DE MYCOLOGIE MEDICALE ID BUCCAL EPITHELIAL-CELLS; TUBE SPECIFIC ANTIGEN; GERM-TUBES; EXTRACELLULAR-MATRIX; ADHERENCE; PROTEINS; ADHESION; BINDING; GROWTH; PURIFICATION AB Objective. Cell surface hydrophobicity (CSH) has been shown to influence adhesion and virulence of the opportunistic fungal pathogen Candida albicans. The aim of this work was to identify the potential cell surface (glyco)proteins supporting the relative CSH according to the morphological phase and culture conditions of Candida albicans. Material and methods. To characterize cell surface hydrophobic and hydrophilic components, Candida albicans Zymolyase crude soluble extracts of germ tubes and blastoconidia were fractionated by hydrophobic interaction chromatography. Prior to extraction, Candida cells were biotinylated in order to label cell surface proteins and glycoproteins. Proteinic and glycosylated compounds of the fractionated extracts were then tested by SDS-PAGE and concanavalin A staining, and probed with streptavidin peroxidase conjugate. Results and conclusion. For both morphological phases, cell surface hydrophilic fractions corresponded to highly glycosylated components of high molecular masses (over 94-kDa) and to a 34-kDa glycoprotein, whereas hydrophobic material was mainly represented by proteins with molecular masses between 10- to 94-kDa. Cell surface glycosylated high molecular mass components were more slightly hydrophobic for blastoconidia grown at 22 degreesC than for yeasts grown at 37 degreesC. Chromatography allowed identification of two peculiar cell surface germ tube specific components: a glycosylated polydispersed material of 110- to 220-kDa, and a 30-kDa proteinic components. These two hyphal phase specific components were characterized as being very hydrophobic. C1 Fac Pharm Angers, UFR Sci Pharmaceut & Ingn Sante, Lab Immunol Parasitol, F-49100 Angers, France. RP Marot-Leblond, A, Fac Pharm Angers, UFR Sci Pharmaceut & Ingn Sante, Lab Immunol Parasitol, 16 Bd Daviers, F-49100 Angers, France. TC 3 PD SEP PY 2000 VL 10 IS 3 BP 115 EP 122 UT ISI:000165530400001 ER PT J AU Khassouani, CE Soulaymani, R Mauras, Y Allain, P TI Blood cadmium concentration in the population of the Rabat area, Morocco SO CLINICA CHIMICA ACTA DE cadmium; blood; concentration; population; Morocco ID GENERAL-POPULATION; URINE; WORKERS; HEALTH; BELGIUM; SMOKING; KIDNEY; LEAD AB Blood cadmium concentrations were determined in 377 adults, 297 men and 80 women, randomly selected from the Rabat Transfusion Center, Morocco. The mean blood cadmium level was 1.1+/-0.7 mug/l, which was higher than in French subjects, with an average of 0.7+/-0.6 mug/l. In Moroccan people, the mean blood cadmium concentration of men, 1.1+/-0.8 mug/l, was significantly higher than that of women, 0.8+/-0.4 mug/l, whereas in the French people tested, there was no statistically significant difference between men and women. In Morocco, employment of men and the smoking habits of men and women were linked to an increase of blood cadmium levels. The significantly higher level observed in men could be due to a higher percentage of men who were smokers and to professional activity leading to increased exposure to cadmium. (C) 2000 Elsevier Science B.V. All rights reserved. C1 CHU Angers, Lab Pharmacol & Toxicol, F-49033 Angers, France. Ctr Antipoisons Maroc & Pharmacovigilance, Rabat, Morocco. RP Allain, P, CHU Angers, Lab Pharmacol & Toxicol, 4 Rue Larrey, F-49033 Angers, France. TC 3 PD DEC PY 2000 VL 302 IS 1-2 BP 155 EP 160 UT ISI:000165637800014 ER PT J AU Bonnard, I TI A criterion for recognizing algebraically constructible functions SO JOURNAL FUR DIE REINE UND ANGEWANDTE MATHEMATIK ID SEMIALGEBRAIC SETS; BASICNESS AB Algebraically constructible functions on a real algebraic set are sums of signs of polynomials on this set. The representation theorem gives an effective criterion to characterize these functions. On the other hand results on spaces of orderings can be used to bound the minimal number of polynomials needed to describe a given algebraically constructible function. C1 Univ Angers, Dept Math, F-49045 Angers 01, France. RP Bonnard, I, Univ Angers, Dept Math, 2 Bd Lavoisier, F-49045 Angers 01, France. TC 3 PD SEP 29 PY 2000 VL 526 BP 61 EP 88 UT ISI:000089876700003 ER PT J AU Pessaux, P Lebigot, J Tuech, JJ Regenet, N Aube, C Ridereau, C Arnaud, JP TI Percutaneous cholecystostomy for acute cholecystitis in high-risk patients SO ANNALES DE CHIRURGIE DE acute cholecystitis; elderly; high-risk patients; percutaneous cholecystostomy ID ACUTE CALCULOUS CHOLECYSTITIS; CRITICALLY ILL PATIENTS; DRAINAGE; LIMITATIONS; MANAGEMENT; PUNCTURE AB Aim of the study: The aim of this retrospective study was to report the results of percutaneous cholecystostomy in a selected group of high-risk patients with contraindications of general anesthesia. Patients and methods: From October 1995 to December 1999, a percutaneous cholecystostomy was performed in 29 patients with acute cholecystitis, There were 20 women and nine men with a mean age of 80.6 years (range: 59 to 95 years). All the patients were ASA III (N = 23) or ASA IV (N = 6). Ultrasound-guided percutaneous cholecystostomy was performed in 24 cases and computed tomography-guided cholecystostomy in five cases. Results: Percutaneous cholecystostomy was easily performed in 28 cases; there was one failed procedure. The drainage was not efficient in three patients who were operated on with one postoperative death of a patient who had a necrotic cholecystitis. There was no mortality in relation with cholecystostomy. One patient died at day 15 from myocardic infarction. The morbidity rate was 3.4% (one case). Postoperative length of hospital stay was 13 days (range: 7-30 days). The duration of the entire procedure ranged from 9 to 60 days (mean: 20 days). The mean follow-up of patients was 17 months (range: 4-40 months). One patient had recurrent acute cholecystitis and another one had angiocholitis; two patients underwent delayed elective laparoscopic cholecystectomy; 20 patients remained asymptomatic and 16 were still alive at the time of this study (13 with biliary stones and three without). Conclusion: Percutaneous cholecystostomy is a Valuable alternative procedure for high-risk patients with acute cholecystitis. It's a safe and usually effective procedure without mortality and with a low morbidity. Whenever possible, percutaneous cholecystostomy should be followed by laparoscopic cholecystectomy. (C) 2000 Editions scientifiques et medicales Elsevier SAS. C1 CHU Angers, Serv Chirurg Viscerale, F-49033 Angers, France. CHU Angers, Serv Radiol, F-49033 Angers, France. RP Arnaud, JP, CHU Angers, Serv Chirurg Viscerale, 4 Rue Larrey, F-49033 Angers, France. TC 3 PD OCT PY 2000 VL 125 IS 8 BP 738 EP 743 UT ISI:000089924400005 ER PT J AU Portier, B Oulidi, A TI Nonparametric estimation and adaptive control of functional autoregressive models SO SIAM JOURNAL ON CONTROL AND OPTIMIZATION DE adaptive control; discrete-time stochastic nonlinear system; nonparametric estimation; optimal adaptive tracking ID SELF-TUNING REGULATORS; LEAST-SQUARES; HAMMERSTEIN SYSTEMS; NEURAL NETWORKS; TRACKING AB This paper deals with nonparametric estimation and adaptive control of nonlinear systems of the form Xn+1 = f (X-n) + U-n + xi(n+1) (n is an element of N) where the state X-n is observed, f is an unknown function, and the control U-n is chosen in order to track a given reference trajectory. We estimate the function f using a nonparametric estimator and study two adaptive control laws built from this nonparametric estimator and derived from the self-tuning control. The rst one can be used for open-loop stable systems and requires an additional exciting noise. The second one needs some a priori knowledge on function f but allows us to control open-loop unstable systems. We establish some general results on the nonparametric estimator of f like the uniform almost sure convergence over dilating sets and then prove that both adaptive control laws are asymptotically optimal in quadratic mean. In addition, we give a strongly consistent estimator of the covariance matrix of the unobservable white noise xi(n). C1 Univ Paris 11, Math Lab, UMR Probabil Stat & Modelisat C 8628, F-91405 Orsay, France. Univ Catholique Ouest, IMA, F-49008 Angers 01, France. RP Portier, B, Univ Paris 11, Math Lab, UMR Probabil Stat & Modelisat C 8628, Bat 425, F-91405 Orsay, France. TC 3 PD SEP 27 PY 2000 VL 39 IS 2 BP 411 EP 432 UT ISI:000089648700004 ER PT J AU Menguy, E Boimond, JL Hardouin, L Ferrier, JL TI A first step towards adaptive control for linear systems in Max algebra SO DISCRETE EVENT DYNAMIC SYSTEMS-THEORY AND APPLICATIONS DE discrete event systems; timed event graphs; max-algebra; identification; adaptive control AB A linear system theory has been developed for discrete event systems subject to synchronization. We are interested in the just in time control of such systems in presence of a possible mismatch between the system and its model. Taking such mismatch into account in controller synthesis prevents us from using the usual open loop control structure. The approach we propose to synthesize the controller is inspired by the principle of the indirect adaptive control well known in conventional system theory. Its design leads to solve an optimal tracking problem under an equality constraint. Preliminary results about the estimation of models are presented. C1 LISA, F-49000 Angers, France. RP Menguy, E, LISA, 62 Ave Notre Dame Lac, F-49000 Angers, France. TC 3 PD OCT PY 2000 VL 10 IS 4 BP 347 EP 367 UT ISI:000089610100003 ER PT J AU Pottecher, B Herbrecht, R Blanc-Vincent, MP Malgrange, VB Escande, MC Fuhrmann, C Crokaert, F Gory-Delabaere, G Senet, JM Lesimple, T Raveneau, J Beal, J Biron, P Viot, M TI Standards, Options and Recommendations (SOR) for the surveillance and the prevention of cross infections in oncology SO BULLETIN DU CANCER DE cross infection; prevention; surveillance; protective isolation; septic isolation; guidelines; cancer ID MARROW TRANSPLANT RECIPIENTS; NOSOCOMIAL INVASIVE ASPERGILLOSIS; PRIMARY CUTANEOUS ASPERGILLOSIS; SURGICAL-WOUND INFECTIONS; AIR-FLOW ROOM; BONE-MARROW; ACUTE-LEUKEMIA; CANCER-PATIENTS; PULMONARY ASPERGILLOSIS; PROTECTED ENVIRONMENTS AB Context. The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French Cancer Centres and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of expert, with feedback from specialists in cancer cae delivery. Objectives. To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the prevention and the surveillance of cross infection in oncology. Methods. Data were identified by searching Medline(R) and the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 106 independent reviewers, and to the medical committees of the 20 French Cancer Centres Results. 1) Criteria of infection status and nosocomiality defined by the Centers for Infectious Diseases (CDC) and Prevention and the Superior Counsil of Public Hygiene (CSHPF) are not adapted and have to be redefined in oncology. 2) The epidemiology of nosocomial infections in oncology is not well known but their incidence seems to be higher. Numerous risk factors of cross infections coexist in cancer patients, among which the duration adn depth of neutropenia. 3) Surveillance and prevention of cross infection are compulsory and were taken into account in the accreditation of hospitals. Obligation is expressed in terms of means and results. 4) The objectives of the cross infection surveillance are to detect major problems and critic situations, to guide probabilistic antibiotic therapy and to assess the effectiveness of the infections control. The surveillance means consist in prevalence and incidence survey, punctually and continuously conducted. 5) The three specific behaviors to be adopted to prevent cross infections are to control; all the patients, infected patients carrying multiresistant bacteria, immunodepressed patients. 6) Standards of care have to be applied to all patients with cancer. 7) It is necessary to add particular septic cares for the patients infected with micro-organisms indicated on reference lists or carrying multiresistant bacteria. 8) The only objective of the protective isolation of immunodepressed cancer patients is to reduce thr cross infection. There is not standard behavior for the indications and the modalities of protective isolation. The prevention behaviors to be taken are defined by expert agreements. C1 FNCLCC, SOR, F-75654 Paris 13, France. Ctr Paul Strauss, Strasbourg, France. CHU Strasbourg, F-67000 Strasbourg, France. Inst Jean Godinoi, F-51056 Reims, France. Inst Curie, Paris, France. Ctr Reg Leon Berard, Lyon, France. Inst Jules Bordet, B-1000 Brussels, Belgium. Ctr Paul Papin, Angers, France. Ctr Eugene Marquis, Rennes, France. Ctr Rene Huguenin, St Cloud, France. Ctr Oscar Lambret, F-59020 Lille, France. Ctr Antoine Lacassagne, F-06054 Nice, France. RP Pottecher, B, FNCLCC, SOR, 101 Rue Tolbiac, F-75654 Paris 13, France. TC 3 PD JUL-AUG PY 2000 VL 87 IS 7-8 BP 557 EP 591 UT ISI:000089256700007 ER PT J AU Volle, R Boucher, V Dorkenoo, KD Chevalier, R Phu, XN TI Local polarization state observation and third-order nonlinear susceptibility measurements by self-induced polarization state changes method SO OPTICS COMMUNICATIONS ID RAYLEIGH-WING SCATTERING; KERR MEDIA; INSTABILITIES; LIQUIDS; FIBERS; WAVES AB We report on a new method appropriate to the study of the polarization states of the electromagnetic field at the output of nonlinear medium. The novelty here is the measurement of the elliptical parameters of the polarization state field function of the input laser intensity. New relations were found to estimate the local ellipticity e(r) and the local polarization ellipse rotation theta(r) at the output of the medium. In order to check the reliability of the proposed method, we have confronted this one to determine the third-order nonlinear susceptibility tensor components chi(xyyx)([3]). The comparison between the values obtained by this approach and some previous values from the literature was entirely satisfying. For instance, we have obtained the chi(xyyx)([3]) (CS2) = 6.5 x 10(-20) m(2)V(-2) with a 10% relative error. (C) 2000 Published by Elsevier Science B.V. C1 Univ Angers, Lab Proprietes Opt Mat & Applicat, F-49045 Angers 01, France. RP Dorkenoo, KD, Univ Angers, Lab Proprietes Opt Mat & Applicat, 2 Blvd Lavoisier, F-49045 Angers 01, France. TC 3 PD AUG 15 PY 2000 VL 182 IS 4-6 BP 443 EP 451 UT ISI:000088891500023 ER PT J AU Leftheriotis, G Dupuis, JM Victor, J TI Cerebral hemodynamics in carotid sinus syndrome and atrioventricular block SO AMERICAN JOURNAL OF CARDIOLOGY ID TRANSCRANIAL DOPPLER; LOWER LIMIT; AUTOREGULATION; HYPERSENSITIVITY; FLOW; VASOCONSTRICTION; HYPERTENSION; HYPOTENSION; RESPONSES; VELOCITY AB Carotid sinus syndrome (CSS) is a cause of syncope due to exaggerated baroreceptor-mediated cardioinhibiiory/vasodepressive reflexes. We sought to determine if cerebral hemodynamics and regulation were specifically altered in these patients by comparison with pure asystole without vasodepression in patients with atrioventricular block (AVB), Mean blood flow velocity (transcranial Doppler sonography) and mean arterial blood pressure (Finapres) were recorded during cardioinhibition induced by carotid massage in patients with CSS (n = 14, 75 +/- SD 8 years) and asystole induced by temporary pacemaker inhibition in patients with complete AVE (n = 10, 69 +/- 11 years), Cerebrovascular resistance was estimated by the arterial pressure/cerebral flow velocity ratio, and dynamic cerebral autoregulatory responses were determined by the rate of regulation and autoregulatory index. Asystole and cardioinhibition each induced a decrease in arterial pressure (CSS 55 +/- 9% vs AVE 40 +/- 14%, p <0.05) and cerebral flow velocity (CSS 66 +/- 19% vs AVE 69 +/- 14%, p = NS), with an initial transient increase in cerebrovascular resistance (CSS 102 +/- 136% vs AVE 128 +/- 92%, p = NS) followed by a decrease (CSS 38 +/- 12%, AVB 29 +/- 13%, p = NS), The rate of regulation and autoregulatory index were higher with AVE (0.43 +/- 0.20 and 8.5 +/- 1.1 second(-1)) than CSS (0.20 +/- 0.12 and 4.8 +/- 1.3 second(-1), respectively, p <0.01 and p <0.001 vs AVE). During asystole and vasodepression, cerebral hypoperfusion in CSS is normally compensated for by cerebral autoregulation. The lower rate of regulation in CSS compared with AVE likely results from persistent peripheral vasodepression triggered by carotid massage. (C) 2000 by Excerpta Medico, Inc. C1 Med Sch & Teching Hosp Angers, Physiol Lab, Angers, France. Med Sch & Teching Hosp Angers, Dept Cardiol, Angers, France. RP Leftheriotis, G, Fac Med Angers, Physiol Lab, Rue Haute de Reculee, F-49033 Angers, France. TC 3 PD SEP 1 PY 2000 VL 86 IS 5 BP 504 EP 508 UT ISI:000088926800005 ER PT J AU Leitao, M Leglize, L TI Long-term variations of epilimnetic phytoplankton in an artificial reservoir during a 10-year survey SO HYDROBIOLOGIA DE reservoir; phytoplankton; population dynamics; long-term variation; biomass; species succession ID SEASONAL SUCCESSION AB Vieux-Pre' is an artificial reservoir in the north-east part of France (61 Mm(3)), created in 1986 for hydraulic management. The phytoplankton and several environmental parameters in the upper part of the lake were monitored at a mid-lake station, from 1988 to 1997. The specific composition of the community changed during this period, from a predominantly pennate-diatom phytoplankton (Asterionella formosa, Fragilaria crotonensis), the lake passed to dominance by a sparse, motile nanoplankton (Mallomonas akrokomos, M. caudata, Cryptomonas erosa, Chroomonas/Rhodomonas, a.o.) and then by large colonies of small-celled species (Uroglena americana, Dinobryon spp., Radiocystis geminata, Aphanothece clathrata, Coelosphaerium kuetzingianum a.o.). This paper describes the algal successions involved and shows the decisive effects of the decrease of trophic level from an eutrophic stage to an oligo-mesotrophic condition. In the beginning, externally imposed disturbances (flooding and dewatering) were frequent, while now the lake has stabilised as a deep, stratified pelagic system. Under these conditions, autogenic phytoplankton appear to dominate. C1 BI EAU, F-49000 Angers, France. Univ Metz, CREUM, F-57040 Metz, France. RP Leitao, M, BI EAU, 14 Rue Volney, F-49000 Angers, France. TC 3 PD APR 15 PY 2000 VL 424 BP 39 EP 49 UT ISI:000088483000005 ER PT J AU Hofrichter, A Constantinescu, A Benayoun, S Bulkin, P Drevillon, B TI Study of the mechanical behavior of plasma-deposited silica films on polycarbonate and steel SO JOURNAL OF VACUUM SCIENCE & TECHNOLOGY A ID CYCLOTRON-RESONANCE REACTOR; CHEMICAL-VAPOR-DEPOSITION; THIN-FILMS; DEFORMATION; COATINGS AB In the present study, we deposited amorphous hydrogenated silicon oxide films on polycarbonate, stainless steel, and silicon by plasma enhanced chemical vapor deposition using a low pressure, high density integrated distributed electron cyclotron resonance plasma reactor. Substrate curvature, vibrating slab, and Vickers indentation experiments were used to evaluate the intrinsic stress, the Young modulus of the films, and the composite hardness of the film-substrate system. The indentation experiments were modeled by finite element analysis and the calculated values were compared to experimentally measured hardness values. A reasonable accordance with the experiment was found both for stainless-steel and polycarbonate substrates, indicating that the modeling is valid and may be used to enhance the interpretation of the indentation experiments. The calculations show an important bending of the film in the noncontact region in the case of a Vickers indentation on a coated polycarbonate sample. The analysis of the thus-induced strain distribution in the coating indicates that the measured diagonal might be overestimated and not representative of the real contact area. The calculations indicate that the yield limit of the plasma-deposited silica films is of about 4 GPa. (C) 2000 American Vacllnm Society. [S0734-2101(00)06604-5]. C1 Ecole Polytech, CNRS, LPICM, F-91128 Palaiseau, France. Ecole Polytech, CNRS, LMS, F-91128 Palaiseau, France. ENSAM, Angers, France. RP Hofrichter, A, Ecole Polytech, CNRS, LPICM, F-91128 Palaiseau, France. TC 3 PD JUL-AUG PY 2000 VL 18 IS 4 PN Part 2 BP 2012 EP 2016 UT ISI:000088277000089 ER PT J AU Debenay, JP TI Foraminifers of paralic tropical environments SO MICROPALEONTOLOGY ID ESTUARY; SENEGAL C1 Fac Sci, Geol Lab, F-49045 Angers, France. Fac Sci, UPRESA EA 2644, F-49045 Angers, France. LEBIM, F-85350 Ile Dyeu, France. RP Debenay, JP, Fac Sci, Geol Lab, 2 Bd Lavoisier, F-49045 Angers, France. TC 3 PY 2000 VL 46 SU Suppl. 1 BP 153 EP 160 UT ISI:000088250500012 ER PT J AU de Baynast, H Bouteville, A Remy, JC TI Optimization of titanium nitride rapid thermal CVD process SO CHEMICAL VAPOR DEPOSITION DE CVD; TiN; film growth; microelectronics; mechanical applications ID CHEMICAL-VAPOR-DEPOSITION; TIN THIN-FILMS; TICL4-NH3-H-2; ADHESION; LAYERS AB Anomalous behavior during TiN growth through rapid thermal low-pressure chemical vapor deposition (RTLPCVD) from gas phase TiCl4-NH3-H-2 has been observed. Two deposition temperatures are used (500 degrees C and 800 degrees C) and two types of deposition process are defined (a long one-step process, and a multiple-step process). Resistivity, structure, composition, and growth behavior are examined and discussed in terms of oxygen contamination and classical nucleation theory. The long one step process is better for mechanical applications, whereas the multiple-step process is more suitable for microelectronics. C1 CER Angers, ENSAM, Equipe Genie Procedes, Lab Procedes Mat Instrumentat, F-49035 Angers, France. RP de Baynast, H, CER Angers, ENSAM, Equipe Genie Procedes, Lab Procedes Mat Instrumentat, 2 Bd Ronceray,BP 3525, F-49035 Angers, France. TC 3 PD JUN PY 2000 VL 6 IS 3 BP 115 EP 119 UT ISI:000087580700003 ER PT J AU Le Fur, E Riou, A Pena, O Pivan, JY TI Crystal structure of (V0.94Co0.46)[PO4(OH)(0.74)(OH2)(0.26)]: a mixed-valence phosphate related to the mineral caminite and the synthetic lipscombite SO SOLID STATE SCIENCES DE synthesis; crystal structure; mixed-valence; magnetism ID HYDROTHERMAL SYNTHESIS; VANADIUM PHOSPHATES; MAGNETIC-PROPERTIES; VANADYL(IV) ORTHOPHOSPHATE; HYDRATE; CA; SR AB The new compound Vsimilar to 0.94Cosimilar to 0.46[PO4(OH)(similar to 0.74)(H2O)(similar to 0.26)] has been isolated from soft hydrothermal treatment. X-ray single crystal diffraction data gave a tetragonal cell (space group I41/amd, Z = 4) with a = 5.2130(5) and c = 12.959(1). It is isostructural with the caminite Mg-1.33[SO4(OH)(0.66)(H2O)(0.33)] and is closely related to the mixed-valence iron phosphate Lipscombite Fe(2-3x)2+Fe2x3+ [PO4OH] with x varying in the range 0 less than or equal to x less than or equal to 2/3, Vsimilar to 0.94Cosimilar to 0.46[PO4(OH)(similar to 0.74)(H2O)(similar to 0.26)] orders antiferromagnetically below 7 K (theta = -18.7 K) as suggested by the broad maximum observed from susceptibility measurements. The magnetic data are discussed together with the susceptibility data of the tetragonal and monoclinic forms of the trivalent vanadium orthophosphate VPO4(H2O). (C) 2000 Editions scientifiques et medicales Elsevier SAS, All rights reserved. C1 Ecole Natl Super Chim Rennes, Lab Physicochim, F-35700 Rennes, France. UMR CNRS 6501, Lab Ingn Mol & Mat Organ, F-49045 Angers, France. Chim Solide & Inorgan Mol Lab, F-35700 Rennes, France. RP Le Fur, E, Ecole Natl Super Chim Rennes, Lab Physicochim, Campus Beaulieu,Ave Gen Leclerc, F-35700 Rennes, France. TC 3 PD JAN-FEB PY 2000 VL 2 IS 1 BP 135 EP 141 UT ISI:000087149500016 ER PT J AU Cudennec, Y Riou, A Gerault, Y Lecerf, A TI Synthesis and crystal structures of Cd(OH)Cl and Cu(OH)Cl and relationship to brucite type SO JOURNAL OF SOLID STATE CHEMISTRY DE crystal structure; cadmium; copper; hydroxychloride AB Synthesis of single crystals of Cd(OH)CI and Cu(OH)CI allowed us to revise the structure of these hydroxychlorides and confirm their space group: P6(3)mc (R = 0.041; R-w = 0.050) for Cd(OH)CI and P2(1)/c (R = 0.051; R-w = 0.069) for Cu(OH)CI. Positions of hydrogen atoms mere determined and an hypothesis of hydrogen bonds is discussed in relation to the infrared spectra, A comparison of the structures shows that an isomorphism is not possible between the two compounds, due to the important Jahn-Teller effect of divalent copper. On the other hand, a structural relationship exists between Cd(OH)CI and beta-Cd(OH)(2), which belongs to the brucite-type family. (C) 2000 Academic Press. C1 Inst Natl Sci Appl Rennes, Grp Rech Chim & Met, F-35043 Rennes, France. Univ Angers, Fac Sci, Lab IMMO, F-49045 Angers, France. RP Cudennec, Y, Inst Natl Sci Appl Rennes, Grp Rech Chim & Met, 20 Ave Buttes Coesmes, F-35043 Rennes, France. TC 3 PD MAY PY 2000 VL 151 IS 2 BP 308 EP 312 UT ISI:000087054800020 ER PT J AU Humeau, A Saumet, JL L'Huillier, JP TI Simplified model of laser Doppler signals during reactive hyperaemia SO MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING DE laser Doppler flowmetry; model; reactive hyperaemia ID CUTANEOUS BLOOD-FLOW; BIOLOGICAL ZERO; FLUX MOTION; HUMAN SKIN; HYPEREMIA; TISSUE; LIGHT; INSTRUMENT; FLOWMETER; INVIVO AB Laser Doppler flowmetry (LDF) is a non-invasive method to measure tissue blood flow. During reactive hyperaemia, the LDF signal increases to a peak and then returns to a resting value. A simplified model is developed to explain these variations. The emphasis is on simulating the effects occurring rather than on trying to mimic the anatomical structure of the microcirculation. A single blood vessel is therefore analysed. The increasing value of blood velocity is studied, and vasodilatation as well as vasoconstriction are taken into account. The model parameters are calculated using wavelets. For a 2-min occlusion on a healthy subject, the radius of the vessel is initially 15 mu m, increasing to 24.6 mu m at the peak, reached 14s after the release of the occlusion. The model shows that the high value of the LDF signal during the initial phase of reactive hyperaemia is produced by an increasing number of erythrocytes in a cross-section, due to vasodilatation rather than an increase in moving blood cell velocities. Moreover, the rapidity of the vasodilatation and vasoconstriction effects determine the rapidity of the signal variations. The paper aims to give a basic solution to develop a numerical model. C1 ESAIP, Grp ISAIP, St Barthelemy, France. CHU Angers, Serv Explorat Vasc, Angers, France. Ecole Natl Super Arts & Metiers, Lab Adv Instrumentat & Robot, Angers, France. RP Humeau, A, ESAIP, Grp ISAIP, St Barthelemy, France. TC 3 PD JAN PY 2000 VL 38 IS 1 BP 80 EP 87 UT ISI:000086521600014 ER PT J AU Sahraoui, B Kityk, IV Kasperczyk, J Salle, M Nguyen, TT TI Photoinduced anisotropy of push-pull chromophores incorporating 5-(1,3-benzodithiol-2-ylidene)-1-(4-nitrophenyl) penta-1,3-diene embedded into photopolymer oligoetheracrylate matrices SO OPTICS COMMUNICATIONS DE photoinduced optical anisotropy; optical chromophore organic molecule ID TETRATHIAFULVALENE DERIVATIVES; POLYMERS AB Photoinduced (PI) birefringence (Delta n) and phototransparency (T) have been studied for a wavelength of 633 nm (He-Ne laser) under photoillumination by doubled-frequency YAG:Nd pulse laser polarized beam (lambda = 0.53 mu m; pulse duration tau = 10-50 ps). The push-pull chromophore 5-(1,3-benzodithiol-2-ylidene)-1-(4-nitrophenyl) penta-1,3-diene was incorporated into an oligoetheracrylate photopolymer matrix in a concentration of about 2.5 wt.%. Special properties of the molecule are connected with substantial role played by electron-vibration interactions in the observed PI effects. The Delta n decreases with decreasing temperature. Optical density D depends non-linearly on the PI beam power. With increasing photoinducing power (up to 0.41 GW/cm(2)), the PI birefringence Delta n and the optical density D approaches (1.4-1.7) x 10(-3) and 1.5%, respectively. The intensity dependence of intramolecular (669 cm(-1)) and intermolecular (89.5 cm(-1)) vibration mode has a maximum and a broad minimum (at a PI power of about 0.45 GW/cm(2)), respectively. Such behavior correlates well with the PI dependencies of the Delta n and the optical density D. Description of the obtained results is based on quantum chemical calculations with taking into account an electron-vibration anharmonicity of the chromophore. Essential role of the PI electrostatic potential redistribution under influence of the PI polarized light beam has been demonstrated. Possible mechanisms of the observed phenomena are discussed within a phenomenological as well as microscopic approach. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Zawiercie Univ, PL-42400 Zawiercie, Poland. Univ Angers, Lab Poma, F-49040 Angers, France. Univ Angers, Lab Ingn Mol & Mat Organ, UMR CNRS 6501, F-49045 Angers, France. RP Kityk, IV, Zawiercie Univ, Ul Sadowa 8, PL-42400 Zawiercie, Poland. TC 3 PD APR 1 PY 2000 VL 176 IS 4-6 BP 503 EP 511 UT ISI:000086357200026 ER PT J AU Conreux, F Beydon, L Safran, D Cazalaa, JB CA Membres Sous Commissions 4 4b Mat TI Incidents involving implantable catheter ports, in 1996/1998: analysis of the data base of the French Health Ministry. SO ANNALES FRANCAISES D ANESTHESIE ET DE REANIMATION DE catheter; port; venous access; perfusion; complication; adverse effects ID VENOUS ACCESS DEVICES; RARE COMPLICATION; FRACTURE; SYSTEM; EXPERIENCE AB We analyse all incident reports to the French Health Ministry over the 1996-1998 period, concerning implantable catheter ports. They represent 7% of all reports in the field of anaesthesia and intensive care. Two hundred eleven reports have been analysed. There were 93 catheter ruptures with 77 intravascular migrations. In more than 50% of cases, a pinch-off syndrome mechanism was responsible of these ruptures and a displacement of the O'ring was involved in 25%. Additional minor complications were reported and discussed in regard to literature. We conclude that implantable catheter ports may lead to serious incidents which are preventable in most cases. (C) 2000 Editions scientifiques et medicales Elsevier SAS. C1 CHU Angers, Dept Anesthesia, F-49033 Angers 01, France. RP Conreux, F, CHU Angers, Dept Anesthesia, F-49033 Angers 01, France. TC 3 PD MAR PY 2000 VL 19 IS 3 BP 171 EP 176 UT ISI:000086340400005 ER PT J AU Turcant, A Cailleux, A Le Bouil, A Allain, P Harry, P Renault, A TI Acute metobromuron poisoning with severe associated methemoglobinemia. Identification of four metabolites in plasma and urine by LC-DAD, LC-ESI-MS, and LC-ESI-MS-MS SO JOURNAL OF ANALYTICAL TOXICOLOGY ID PERFORMANCE LIQUID-CHROMATOGRAPHY; INTOXICATION; INGESTION; DIURON C1 CHU Angers, Lab Pharmacol Toxicol, F-49033 Angers, France. CHU Angers, Ctr Anti Poison, F-49033 Angers, France. RP Turcant, A, CHU Angers, Lab Pharmacol Toxicol, 4 Rue Larrey, F-49033 Angers, France. TC 3 PD APR PY 2000 VL 24 IS 3 BP 157 EP 164 UT ISI:000086123600001 ER PT J AU Le Moustarder, S Hudhomme, P Durand, C Mercier, N Azcondo, MT Delhaes, P Riou, A Gorgues, A TI First radical cation salts from the symmetrical outer S-position isomer of BEDT-TTF SO JOURNAL OF MATERIALS CHEMISTRY AB The X-ray crystal structures and physical characterizations of the first radical cation salts obtained from the symmetrical S-position isomer of bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF), are presented in this work. The unusual feature of this new pi-donor D1, involved in the described salts (D1)(3).(ClO4)(2), (D1)(3).(BF4)(2) and D1 . Cu(SCN)(2), is the presence of two disulfide bridges, allowing weak intermolecular S ... S interactions. The influence of these outer sulfur atoms on the network of related materials is also discussed in relation to the first physical characterizations which have been carried out. C1 Univ Angers, Lab Ingn Mol & Mat Organ, CNRS, UMR 6501, F-49045 Angers, France. CNRS, Ctr Rech Paul Pascal, F-33600 Pessac, France. RP Hudhomme, P, Univ Angers, Lab Ingn Mol & Mat Organ, CNRS, UMR 6501, 2 Bd Lavoisier, F-49045 Angers, France. TC 3 PY 2000 VL 10 IS 3 BP 617 EP 623 UT ISI:000085886200008 ER PT J AU Croquet, V Pilette, C Lespine, A Vuillemin, E Rousselet, MC Oberti, F Andre, JPS Periquet, B Francois, S Ifrah, N Cales, P TI Hepatic hyper-vitaminosis A: importance of retinyl ester level determination SO EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY DE chronic hyper-vitaminosis A; hepatic stellate cell; perisinusoidal fibrosis; portal hypertension; retinyl ester ID HYPERVITAMINOSIS-A; LIVER FIBROSIS; PORTAL-HYPERTENSION; HEPATOTOXICITY; PATIENT; INTOXICATION; CIRRHOSIS; PROTEIN; DAMAGE; CELLS AB We report the case of a 32-year-old man with portal hypertension without cirrhosis due to chronic vitamin A intoxication, Portal hypertension revealed by oesophageal varice rupture progressively worsened and ascites occurred 5 years after the patient stopped vitamin A intake. Initially, serum retinyl palmitate concentration was increased whereas serum retinol concentration was normal. There was no hepatic fibrosis on light microscopic examination of liver biopsy specimens. Five years after the patient stopped excessive vitamin A intake, serum retinol and retinol-binding protein concentrations were below the normal range even though there was an increased hepatic retinyl ester content. This was attributed to the late development of peri-sinusoidal fibrosis, This case mainly shows the importance of retinyl ester level determination: serum retinyl palmitate should be measured immediately after intoxication and hepatic retinyl esters should be measured initially and particularly later. Indeed, later serum and hepatic retinol levels in chronic hyper-vitaminosis A may be normal and lead to under-estimation of liver vitamin A overload. fur J Gastroenterol Hepatol 12:361-364 (C) 2000 Lippincott Williams & Wilkins. C1 CHU Angers, Serv Hepatogastroenterol, F-49033 Angers 01, France. RP Cales, P, CHU Angers, Serv Hepatogastroenterol, F-49033 Angers 01, France. TC 3 PD MAR PY 2000 VL 12 IS 3 BP 361 EP 364 UT ISI:000085942500016 ER PT J AU Ivanova, T Panaiotov, I Boury, F Saulnier, P Proust, JE Verger, R TI Role of the electrostatic interactions on the basic or acidic hydrolysis kinetics of poly-(D,L-lactide) monolayers SO COLLOIDS AND SURFACES B-BIOINTERFACES DE hydrolysis; monolayer; poly-(D,L-lactide); electrostatic interactions ID INVITRO DEGRADATION; ABSORBABLE SUTURES; AQUEOUS-MEDIA; POLY(D,L-LACTIDE); MICROSPHERES; GLYCOLIDE); BEHAVIOR; EROSION; MODEL AB The hydrolysis kinetics of insoluble poly-(D,L-lactide) monolayers spread on basic or acidic aqueous subphase were followed by measuring simultaneously the decrease in the surface area at constant surface pressure and the evolution of the surface potential. An approach to analyse the role of the electrostatic interactions during the hydrolysis at alkaline pH, interpreting the surface potential data was developed. The theoretical predictions based on the idea of a random fragmentation of polymer molecules leading to the interfacial accumulation of charged insoluble products and solubilisation of small fragments describes well the experimental results. The reversibility of the hydrolysis/esterification reaction at acidic pH is taken into account. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ Sofia, Biophys Chem Lab, BU-1126 Sofia, Bulgaria. Fac Pharm Angers, F-49100 Angers, France. CNRS, ERS Lypolyse Enzymat 26, F-13402 Marseille, France. TC 3 PD APR 15 PY 2000 VL 17 IS 4 BP 241 EP 254 UT ISI:000085909800004 ER PT J AU Valo, I Rohmer, V Guyetant, S Martin, JF Venault, S Saint-Andre, JP TI Cushing's syndrome caused by a well-differentiated ileal neuroendocrine carcinoma SO ENDOCRINE PATHOLOGY DE carcinoid; small bowel; Cushing's syndrome; ectopic ACTH secretion ID TUMORS; MIDGUT; SCINTIGRAPHY; DIAGNOSIS AB We report a very rare case of Cushing's syndrome caused by an ileal adrenocorticotrophin-secreting well-differentiated endocrine carcinoma with liver metastases. A 62-yr-old woman presented with clinical and biological signs suggestive of paraneoplastic Cushing's syndrome. Radiological investigations, including magnetic resonance imaging of the pituitary gland, chest and abdominal computerized tomography scan, small bowel barium study and pancreatic endoscopic scan, 111-pentetreotide scintigraphy (octreoscan), esogastroduodenoscopy, and colonoscopy did not detect the source of the ectopic adrenocorticotropic hormone (ACTH) secretion but showed a few liver nodules. Because a 10-mo-long ketoconazole treatment was not effective, a bilateral adrenalectomy was performed in order to control the Cushing's syndrome, and a liver nodule biopsy diagnosed a metastatic neuroendocrine tumor. Subsequently, a second laparotomy disclosed a 1.8 cm ileal neuroendocrine tumor, cosecreting ACTH and serotonin on immunohistochemistry with many liver metastases. ACTH secretion by intestinal neuroendocrine tumors is rare, and the secretion is almost always clinically silent. Cushing's syndrome caused by an intestinal low-grade neuroendocrine tumor is even rarer, with only two previous cases reported in the literature. Our observation underlines the difficulty of localizing the source of ectopic ACTH secretion in paraneoplastic Cushing's syndrome. C1 CHU Angers, Anat Pathol Lab, Dept Pathol, F-49033 Angers 01, France. CHU Angers, Dept Endocrinol, F-49033 Angers, France. Ctr Hosp, Dept Internal Med, Le Mans, France. RP Saint-Andre, JP, CHU Angers, Anat Pathol Lab, Dept Pathol, F-49033 Angers 01, France. TC 2 PD WIN PY 2000 VL 11 IS 4 BP 359 EP 364 UT ISI:000168653800007 ER PT J AU Hamrit, H Djebbar-Sid, S Benali-Baitich, O Khan, MA Bouet, G TI Potentiometric studies, synthesis and characterization of mixed-ligand complexes of copper(II), nickel(II), cobalt(II) and manganese(II) with N-(2-acetamidoiminodiacetic) acid as the primary ligand and histidine as the secondary one SO SYNTHESIS AND REACTIVITY IN INORGANIC AND METAL-ORGANIC CHEMISTRY ID N-(2-ACETAMIDO)IMINODIACETIC ACID; METAL-IONS AB The formation equilibria of new ternary mixed-ligand complexes of copper(II), nickel(II), cobalt(II), and manganese(II) with N-(2-acetamidoiminodiacetic) acid (H(2)ADA) as the primary ligand and histidine (His) as the secondary one were investigated. The formation constants of these complexes have been determined at 25.0 degreesC in 0.3 M aqueous Na2SO4 solution. They show that the ternary complexes are more stable than the corresponding binary ones. The ternary complexes have been synthesized and were characterized using elemental analyses, molar conductance, IR spectra, magnetic measurements as well as electronic and ESR spectra. The spectral results support the binding of H(2)ADA and histidine with, respectively, the NOO and NO sites, to copper(II), cobalt(II), and manganese(II) providing an octahedral geometry, while nickel(II) is bonded to the same ligands in a bidentate manner by the OO and NO donor groups giving a square-pyramidal complex. The other axial sites are occupied by OH- or H2O groups. Magnetic and ESR data indicate that cobalt(II) and manganese(II) adopt a high-spin configuration in the complexes and also show that the metal ions do not undergo any change in the oxidation state. C1 USTHB, Inst Chim, Chim Coordinat Lab, El Alia, Alger, Algeria. Fac Pharm, Chim Coordinat Lab, F-49100 Angers, France. RP Benali-Baitich, O, USTHB, Inst Chim, Chim Coordinat Lab, BP32, El Alia, Alger, Algeria. TC 2 PY 2000 VL 30 IS 10 BP 1835 EP 1848 UT ISI:000166507700001 ER PT J AU Clavreul, A Fisson, S D'hellencourt, CL Couez, D TI Interelationship between CD3 and CD28 pathways in a murine T cell thymoma SO MOLECULAR IMMUNOLOGY DE CD3; CD28; T cell receptor; P13-kinase; T lymphocyte activation ID PHOSPHATIDYLINOSITOL 3-KINASE ASSOCIATION; INTERLEUKIN-2 GENE-EXPRESSION; RECEPTOR ZETA-CHAIN; SIGNAL-TRANSDUCTION; CYTOPLASMIC DOMAIN; TYROSINE KINASES; SH3 DOMAIN; ACTIVATION; COSTIMULATION; BINDING AB It is well known that the CD28 costimulatory signal is important to complement T cell receptor (TCR)/CD3-initiated T cell activation, but the mechanism by which these two distinct signaling pathways are integrated is not clearly understood. In our laboratory. we dispose of a murine T cell hybridoma transfected with human CD28 molecule which is able to produce IL-2 in response to stimulation, suggesting that the signal transduction machinery coupled to the CD28 molecule is capable of triggering effector functions. Nevertheless, the action of three immunosuppressive agents previously shown in our model, suggested an interaction between the CD3 and CD28 pathways. We confirmed here this hypothesis by transfecting the cDNA of the human CD28 molecule in the BW5147 thymoma which lacks CD3 surface expression. Stimulation of the human CD28 did not lead to IL-2 secretion while the restoration of the TCR/CD3 complex re-established the functionality of this costimulatory molecule. These data demonstrate that the IL-2 production induced by the CD28 activation pathway is dependent of the TCR/CD3 complex cell surface expression and suggest the formation of a functional membrane complex between the CD3 and CD28 molecules. The molecular basis of the functional dependence of CD28 signaling on the TCR/CD3 complex is presently unknown. Nonetheless, we showed that some early events induced by CD28 stimulation, such as PI3-kinase association, are independent of the TCR/CD3 complex expression. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 CHU Angers, Lab Biol Mol Immunol & Therapeut Canc, BMITC, UPRES EA 3140, F-49033 Angers 01, France. RP Couez, D, CHU Angers, Lab Biol Mol Immunol & Therapeut Canc, BMITC, UPRES EA 3140, Batiment Monteclair,4 Rue Larrey, F-49033 Angers 01, France. TC 2 PD AUG PY 2000 VL 37 IS 10 BP 571 EP 577 UT ISI:000166338500003 ER PT J AU Lefrere, F Delmer, A Suzan, F Levy, V Belanger, C Djabarri, M Arnulf, B Damaj, G Ribrag, V Janvier, M Sebban, C Casasnovas, RO Bouabdallah, R Dreyfus, F Verkarre, V Delabesse, E Valensi, F McIntyre, E Brousse, N Varet, B Hermine, O TI Further evaluation of a sequential chemotherapy by CHOP and DHAP regimens followed by high-dose therapy with stem cell transplantation in mantle cell lymphoma. SO BLOOD C1 Hop Necker Enfants Malad, Paris, France. Hop Hotel Dieu, F-75181 Paris, France. Hop Andre Mignot, Versailles, France. Hop St Louis, Dept Biostat, Paris, France. Hop Cochin, Villejuif, France. IGR, Villejuif, France. Ctr Rene Huguenin, St Cloud, France. Hop Edouard Herriot, Lyon, France. Ctr Hosp Dijon, Dijon, France. Inst J Paoli I Calmettes, F-13009 Marseille, France. Serv Anatomopathol, Paris, France. Hematol Lab, Angers, France. TC 2 PD NOV 16 PY 2000 VL 96 IS 11 PN Part 1 BP 792A EP 792A UT ISI:000165256103420 ER PT J AU Cudennec, Y Riou, A Gerault, Y Lecerf, A TI Crystallographical and chemical hypothesis for the formation process of CuO(s) and Cu(OH)(2(s)) from Na2Cu(OH)4((s)). SO COMPTES RENDUS DE L ACADEMIE DES SCIENCES SERIE II FASCICULE C-CHIMIE DE synthesis; topotactic reaction; divalent copper; hydroxide; oxide ID OXIDATION AB Addition of water into systems containing the solid Na2Cu(OH)(4(s)), and its saturated solution allows the formation of two different solids: CuO(s) and Cu(OH)(4(s)). Cooper oxide is obtained by a slow addition and corrresponds to the equilibrium state: copper hydroxide is obtained by the fast addition of a large amount of water and is a metastable phase. In order to explain these different behaviours we propose a hypothesis involving two different reaction mechanisms. When systems containing Na2Cu(OH)(4(s)) are softly diluted, Na+ ions leave the crystal structure towards the solution. In parallel, the two longest Cu-O bonds of the octahedral surrounding of copper break down to give rise to free Cu(OH)(4)(2-) comples ions, stable in solution, which constitute elementary bricks for the formation of CuO4(s). Synthesis of Cu(OH)(2(s)) is only possible when dilution of systems containing Na2Cu(OH)(4(s)) is carried out in a large amount of water to make OH- ion concentration quickly decrease in order to avoid the formation of Cu(OH)(42-(aq)) complex ions, precursors of CuO(s). In these conditions, Na2Cu(OH)(4(s)) gives rise to Cu(OH)(2(s)) by a topotactic reaction. (C) 2000 academie des sciences/Editions scientifiques et medicales Elsevier SAS. C1 Insa Rennes, Grp Rech Chim & Met, F-35043 Rennes, France. Univ Angers, Fac Sci, UMR 6501, Lab Immo, F-49045 Angers, France. RP Cudennec, Y, Insa Rennes, Grp Rech Chim & Met, 20 Av Buttes Coesmes, F-35043 Rennes, France. TC 2 PD AUG PY 2000 VL 3 IS 8 BP 661 EP 666 UT ISI:000165923000005 ER PT J AU Buitink, J Hoekstra, FA Hemminga, MA TI Molecular mobility in the cytoplasm of lettuce radicles correlates with longevity SO SEED SCIENCE RESEARCH DE EPR spectroscopy; Lactuca sativa; lettuce; molecular mobility; seed longevity ID ELECTRON-SPIN-RESONANCE; SEED STORAGE STABILITY; MOISTURE-CONTENT LIMIT; GLASSY STATE; PARAMAGNETIC-RESONANCE; LOGARITHMIC RELATION; THEORETICAL BASIS; PROBE ESR; TEMPERATURE; WATER C1 Univ Wageningen & Res Ctr, Lab Plant Physiol, NL-6703 BD Wageningen, Netherlands. Mol Phys Lab, NL-6703 HA Wageningen, Netherlands. RP Buitink, J, LRPV, INH GIS Semences, 16 Bd Lavoisier, F-49045 Angers 01, France. TC 2 PD SEP PY 2000 VL 10 IS 3 BP 285 EP 292 UT ISI:000165586100010 ER PT J AU Oberti, F Vuillemin, E Fort, J Cales, P TI Experimental models of portal hypertension SO GASTROENTEROLOGIE CLINIQUE ET BIOLOGIQUE ID SECONDARY BILIARY-CIRRHOSIS; VEIN STENOSED RATS; BILE-DUCT LIGATION; CARBON-TETRACHLORIDE; LONG-TERM; HEMODYNAMIC CHARACTERIZATION; HEPATIC-FIBROSIS; NITRIC-OXIDE; MICRONODULAR CIRRHOSIS; LIVER-CIRRHOSIS C1 CHU Angers, Serv Hepatogastroenterol, F-49033 Angers 01, France. RP Cales, P, CHU Angers, Serv Hepatogastroenterol, F-49033 Angers 01, France. TC 2 PD OCT PY 2000 VL 24 IS 10 BP 896 EP 901 UT ISI:000165597300005 ER PT J AU Chachoua, M Pacholczyk, D TI A symbolic approach to uncertainty management SO APPLIED INTELLIGENCE DE artificial intelligence; uncertainty representation; qualitative reasoning; uncertainty management; ignorance; belief; entropy; many-valued logic ID ENTROPY; SETS AB In this paper, we present a new symbolic approach to deal with the uncertainty encountered in common-sense reasoning. This approach enables us to represent the uncertainty by using linguistic expressions of the interval [Certain, Totally uncertain]. The original uncertainty scale that we use here, presents some advantages over other scales in the representation and in the management of the uncertainty. The axioms of our theory are inspired by Shannon's entropy theory and built on the substrate of a symbolic many-valued logic. So, the uncertainty management in the symbolic logic framework leads to new generalizations of classical inference rules. C1 Univ Angers, Lab Informat LERIA, UFR Sci, F-49045 Angers 01, France. RP Chachoua, M, Univ Angers, Lab Informat LERIA, UFR Sci, 2 Blvd Lavoisier, F-49045 Angers 01, France. TC 2 PD NOV PY 2000 VL 13 IS 3 BP 265 EP 283 UT ISI:000165639100007 ER PT J AU Royer, A Beguin, S Sochor, H Communal, PY TI Determination of glufosinate ammonium and its metabolite (AE F064619 and AE F061517) residues in water by gas chromatography with tandem mass spectrometry after ion exchange cleanup and derivatization SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY DE glufosinate ammonium; GC/CI/MS/MS; ion-exchange resins; derivatization; water ID COLUMN LIQUID-CHROMATOGRAPHY; (AMINOMETHYL)PHOSPHONIC ACID; AMINOMETHYLPHOSPHONIC ACID; FLUORESCENCE DETECTION; RAPID-DETERMINATION; HERBICIDES GLYPHOSATE; PESTICIDES; SAMPLES; SOIL AB An analytical method for the determination of glufosinate ammonium and its principal metabolites, AE F064619 and AE F061517, in water of two different hardnesses (5 and 30 DH, French hardness) has been developed and validated. Samples were spiked at different levels (0.05 and 0.5 mug/L) and were purified by column chromatography on ion-exchange resins. After derivatization with glacial acetic acid and trimethylarthoacetate mixture, the derivatives were quantified by using capillary gas chromatography with an ion-trap tandem mass spectrometric detector. Analytical conditions for MS/MS detection were optimized, and the quantification was carried out on the areas of the most representative ions. The limit of quantification was validated at 0.05 mug/L for each compound. The mean recovery value and the relative standard deviation (n = 20) were 92.0% and 17.8% for glufosinate ammonium, 90.2% and 15.8% for AE F064619, and 89.7% and 12.7% for AE F061517. C1 Angers Technol, Groupement Interreg Rech Prod Agropharmaceut, F-49070 Beaucouze, France. AgrEvo GMBH, D-65926 Frankfurt, Germany. RP Communal, PY, Angers Technol, Groupement Interreg Rech Prod Agropharmaceut, 8 Rue H Becquerel, F-49070 Beaucouze, France. TC 2 PD NOV PY 2000 VL 48 IS 11 BP 5184 EP 5189 UT ISI:000165490000014 ER PT J AU Alix, P Grolleau, F Hue, B TI Modulation by intracellular calcium of a GABA receptor-mediated chloride current via a calcium/calmodulin-dependent protein kinase in insect neurosecretory cells SO EUROPEAN JOURNAL OF NEUROSCIENCE C1 Univ Angers, UPRES EA 2647, Angers, France. TC 2 PY 2000 VL 12 SU Suppl. S BP 43 EP 43 UT ISI:000088236600247 ER PT J AU Sutra, L Risede, JM Gardan, L TI Isolation of fluorescent pseudomonads from the rhizosphere of banana plants antagonistic towards root necrosing fungi SO LETTERS IN APPLIED MICROBIOLOGY ID PATHOGENS AB Total aerobic bacteria and fluorescent pseudomonads were counted in bulk and rhizospheric soils of banana plants of 14 plantations in Martinique (French West Indies). Fluorescent Pseudomonas isolates were then identified and investigated for in vitro antagonism towards Cylindrocladium sp., a fungal pathogen of banana roots. Total aerobic bacteria and fluorescent pseudomonads were significantly more abundant in rhizospheric soils than in bulk soils. Among 58 fluorescent Pseudomonas isolates, 41 were identified as Pseudomonas fluorescens biovar V and 17 as Ps. putida biovar A. Six strains exhibited an antagonism towards Cylindrocladium isolates. Among them, Ps. putida strain 93.1 totally blocked fungal growth. No relationship was established between the antifungal effect and enzyme or hydrogen cyanide production by bacteria, suggesting that siderophores and other compounds were involved in fungal inhibition. Antagonistic fluorescent pseudomonads represent a potential for the biological control of banana root infections by Cylindrocladium sp. C1 Univ Angers, INH, INRA, UMR Pathol Vegetale, F-49071 Beaucouze, France. CIRAD, FLHOR, Stn Neufchateau, Capesterre Belle Eau, Guadeloupe. RP Sutra, L, Univ Angers, INH, INRA, UMR Pathol Vegetale, 42 Rue Georges Morel,BP57, F-49071 Beaucouze, France. TC 2 PD OCT PY 2000 VL 31 IS 4 BP 289 EP 293 UT ISI:000165069800006 ER PT J AU Rahali, V Gueguen, J TI Foaming characteristics of chemical and enzymatic hydrolysates of bovine beta-lactoglobulin SO NAHRUNG-FOOD ID VIDEO IMAGE-ANALYSIS; LIQUID INTERFACES; FUNCTIONAL-PROPERTIES; PROTEINS; PROTEOLYSIS; ADSORPTION; STABILITY; EMULSIONS; CASEIN AB The foaming properties of bovine beta -lactoglobulin (BLG), BNPS-skatole (2-(2'-nitrophenylsulfenyl)-3-methyl-3'-bromoindolenine) (BNPS), trypsin (T) and pepsin in 25, 30 and 40% ethanol (P25, P30, P40) hydrolysates were investigated in the 0.2 to 1 mg/ml range. Foaming capacity and foam stability were assessed in terms of drained liquid volume and foam volume. Foam texture was analyzed from video images obtained during foam decay. The foaming capacity of BNPS, P30 and P40 was similar to that of BLG and greater than that of T or P25. All hydrolysates except BNPS were less stable than BLG at all concentrations tested. This result was insured by texture analysis. Principal component analysis confirmed the distribution of the samples into three groups based on their increasing stability: (i): P25, (ii): P30 and P40, and (iii): BLG and BNPS. Tryptic hydrolysate had the poorest foaming properties. The results are considered in relation to the molecular characteristics of the peptides, particularly their size and hydrophobicity. C1 INRA, Unite Biochim & Technol Prot, F-44316 Nantes 3, France. Ecole Super Agr, Angers, France. RP Gueguen, J, INRA, Unite Biochim & Technol Prot, Rue Geraudiere, F-44316 Nantes 3, France. TC 2 PD OCT PY 2000 VL 44 IS 5 BP 309 EP 317 UT ISI:000089988900003 ER PT J AU Binuani, P Baufreton, C Subayi, JB de Brux, JL TI The CarboMedics 'Top-Hat' aortic valve prosthesis: Short-term results SO JOURNAL OF HEART VALVE DISEASE ID JUDE MEDICAL PROSTHESIS; SUPRAANNULAR PROSTHESIS; REPLACEMENT AB Background and aim of the study: The CarboMedics 'Top-Hat' aortic valve prosthesis has been specifically designed for supra-annular implantation. The aim of this study was to assess the safety of implantation of this prosthesis by reporting the short-term results of follow up. Methods: Between May 1993 and May 1998, 128 patients (mean age 62.5 +/- 9.8 years; range: 22-76 years) received a CarboMedics 'Top-Hat' prosthesis at our institution. Among patients, 55% were in NYHA functional classes III or IV, and 54.7% had an isolated aortic valve replacement. Associated procedures were: coronary artery bypass grafting (25.7%), double valve replacement (17.1%), treatment of ascending aortic aneurysm (4.7%) and miscellaneous (5.5%). Follow up was 100% complete; total cumulative follow up was 265 patient-years (pt-yr) (range: 2-60 months). Results: The overall mortality rate was 1.5% (two deaths). The operative mortality rate was 0.8% tone death); this patient died from neurological complications after operation for aortic dissection. The other patient died on postoperative day 40 from a massive cerebral hemorrhage. Four patients presented thromboembolic events; in all cases these were reversible ischemic neurologic deficits. One patient had a nonstructural deterioration (endocarditis) and required reoperation. Freedom from mortality was 98.3% at five years (linearized rate of 0.75%/pt-yr). Freedom from thromboembolism was 63.1% at five years (linearized rate 1.5%/pt-yr). Conclusion: Short-term results with the CarboMedics 'Top-Hat' prosthesis were satisfactory, with low rates of morbidity and mortality. As this prosthesis has demonstrated a good reliability to date, we have continued its implantation in our institution, and longterm follow up will be necessary to confirm these good early results. C1 CHU Angers, Dept Cardiovasc & Thorac Surg, F-49033 Angers, France. RP de Brux, JL, CHU Angers, Dept Cardiovasc & Thorac Surg, 4 Rue Larrey, F-49033 Angers, France. TC 2 PD SEP PY 2000 VL 9 IS 5 BP 693 EP 696 UT ISI:000089560900016 ER PT J AU Avenel-Audran, M Hausen, BM le Sellin, J Ledieu, G Verret, JL TI Allergic contact dermatitis from hydrangea - is it so rare? SO CONTACT DERMATITIS DE Hydrangea macrophylla; cultivars; hydrangenol; occupational allergic contact dermatitis; plants; nursery workers AB 8 cases of allergic contact dermatitis from hydrangea seen in Angers, France, during the last 15 years are reported and compared to other cases found in the literature. In this review, allergic contact dermatitis from hydrangeas appears to be an occupational dermatosis among nursery workers, presenting as an eczema involving the hands and especially the first 3 fingers, with chronic features of fissuring and scaling and with a chronic course. Differential diagnosis from irritant contact dermatitis may be difficult. Patch tests with the stem as well as the leaf of hydrangeas gave strong positive reactions in all patients, and hydrangenol, the allergen of hydrangea, when tested, always also gave a positive reaction. Sensitization seems to occur after close and prolonged contact with the plant, which could explain the relative frequency in Angers because it provides almost 90% of hydrangea seedling production in France. C1 CHU Angers, Serv Dermatol, F-49033 Angers 01, France. Kreiskrankenhaus Buxtehude, Dermatol Zentrum, Buxtehude, Germany. CHU Angers, Lab Explorat Fonct Allergol, Angers, France. RP Avenel-Audran, M, CHU Angers, Serv Dermatol, F-49033 Angers 01, France. TC 2 PD OCT PY 2000 VL 43 IS 4 BP 189 EP 191 UT ISI:000089366500001 ER PT J AU Boisdron-Celle, M Gamelin, E TI Platinum compounds-taxanes pharmacologic interactions SO BULLETIN DU CANCER DE platinum derivatives; taxoids; interactions ID PHASE-I; SOLID TUMORS; PACLITAXEL; CARBOPLATIN; CANCER; CISPLATIN; PHARMACOKINETICS; DOCETAXEL; ACCUMULATION; METABOLISM AB Taxoids and platinum derivatives display a true activity against many types of solid tumors. Their relatively non overlapping toxicity profiles and their different mechanisms of action made their combination attractive. Actually, the frequence and the severity of the toxicity appeared schedule-dependent. Thus, cisplatin-paclitaxel combination generates more neutropenia, when cisplatin is delivered before paclitaxel. Cisplatin reduces paclitaxel plasma clearance, bat the interference appears more due to pharmacodynamic interaction. Cisplatin-induced DNA adducts are more limited when paclitaxel is administered before cisplatin. Tolerance is better but we cannot conclude in term of efficacy. Cisplatin and docetaxel interaction and schedule-dependence appear much less obvious in term of toxicity. On the other hand, thrombopenia carboplatin-induced is significatively decreased when combined to paclitaxel. In that case, the interaction is clearly pharmacodynamic. The correlation curve of thrombopenia and platinum in plasma area under the curve is modified and shows an increased tolerance of platelets to carboplatin. The cause remains unknown, to our knowledge. The interaction protects only the platelets. No data is available for docetaxel and carboplatin combination. A better knowledge of the metabolism and the interactions of these two drug families is quite necessary for better using them in combination, both in term of efficacy and tolerance. C1 CRLCC Paul Papin, Lab Oncopharmacol, F-49000 Angers, France. RP Boisdron-Celle, M, CRLCC Paul Papin, Lab Oncopharmacol, 2 Rue Moll, F-49000 Angers, France. TC 2 PD AUG PY 2000 VL 87 SI Sp. Iss. SI BP 30 EP 33 UT ISI:000089347500005 ER PT J AU Humeau, A Saumet, JL L'Huillier, AP TI Use of wavelets to accurately determine parameters of laser Doppler reactive hyperemia SO MICROVASCULAR RESEARCH DE laser Doppler flowmetry; reactive hyperemia; wavelets ID CUTANEOUS BLOOD-FLOW; HUMAN-SKIN; LIGHT; OSCILLATIONS; INSTRUMENT; DISEASE; SIGNAL AB Laser Doppler flowmetry (LDF) is a noninvasive method to monitor skin perfusion and is very useful in studying reactive hyperemia signals. For this latter case, the determination of peak flow (pLDF) and time to peak flow (tpLDF) is of great interest in discriminating between subjects with peripheral arterial obliterative diseases and those who are healthy. However, the myogenic mechanism provokes marked oscillations on all LDF signals. Therefore, an accurate detection of the parameters is very difficult. The present study shows that wavelets are a powerful tool to overcome this drawback. Six different processes using several wavelets are tested on 44 signals recorded on 11 healthy volunteers. The results prove that thresholding coefficients of a multilevel wavelet decomposition does not allow a valuable computation of the parameters but that the reconstruction of the approximation branch is an efficient method to accurately determine pLDF and tpLDF. Using this latter method, mt:an results for a 3-min occlusion give pLDF = 46.80 a.u. and tpLDF = 17.08 s. For a 2-min occlusion, pLDF and tpLDF are 39.19 a.u. and 11.63 s, respectively. For a 1-min occlusion, the results give pLDF = 36.01 a.u., tpLDF = 8.48 s. Eventually, for a 30-s occlusion they give pLDF = 33.86 a.u. and tpLDF = 5.60 s. These results can now be compared with those obtained on pathological subjects. (C) 2000 Academic Press. C1 Grp ISAIP ESAIP, F-49180 St Barthelemy 01, France. CHU Angers, Serv Explorat Vasc, F-49033 Angers, France. ENSAM, LIRA, F-49035 Angers 01, France. RP Humeau, A, Grp ISAIP ESAIP, 18 Rue 8 Mai 1945,BP 22, F-49180 St Barthelemy 01, France. TC 2 PD SEP PY 2000 VL 60 IS 2 BP 141 EP 148 UT ISI:000089324400007 ER PT J AU Le Moustarder, S Hudhomme, P Illien, B Halet, JF Gorgues, A Riou, A TI Synthesis, X-ray structure and molecular orbital study of a radical cation salt of a S-position isomer of an EDT-TTF derivative: C.I-3 where C=6,7-dimethylsulfanyl-2,3-(dithiabutane-1,4-diyl)tetrathiafulvalene SO MOLECULAR CRYSTALS AND LIQUID CRYSTALS DE tetrathiafulvalene; radical cation salts; X-ray structure; molecular orbital calculations ID ORGANIC SUPERCONDUCTORS; CRYSTAL-STRUCTURES; ELECTRONIC-STRUCTURES; BEDT-TTF AB The X-ray crystalline structure at 293 K and 150 K of the radical cation salt (C10H10S8I3) obtained from a disulfide tetrathiafulvalene (TTF) derivative, is described. The title compound crystallizes in the P1 space group with the lattice constants at 293 K: a = 9.7634(12) Angstrom, b = 9.9311(13) Angstrom, c = 12.780(2) Angstrom, alpha = 72.94(1)degrees, beta = 74.51(1)degrees, gamma = 63.08(3)degrees, V = 1043.1(6) Angstrom(3), Z = 2. The structural study at low temperature indicates a similar crystal structure without any apparent symmetry and structural modifications. Donors are stacked in a zig-zag mode along a-axis with a strong dimerization, confirmed by the molecular orbital calculations, The structural particularity of the new pi-donor C engaged in the described salt bring the terminal disulfide bridge, we discuss here the influence of outer sulfur atoms on the structural organization. C1 Univ Angers, UMR CNRS 6501, Lab Ingn Mol & Mat Organ, F-49045 Angers, France. Univ Rennes 1, UMR CNRS 6511, Chim Solide & Inorgan Mol Lab, F-35042 Rennes, France. RP Illien, B, Univ Nantes, Fac Sci & Tech, Lab Spectrochim, 2 Rue Houssiniere,BP 92208, F-44322 Nantes 03, France. TC 2 PY 2000 VL 338 BP 61 EP 74 UT ISI:000089192400006 ER PT J AU Hadjadj, S Guilloteau, G Weekers, L Bouhanick, B Fressinaud, P Marre, M TI Changes in glycaemic control (but not in body weight control) are positively correlated with changes in coronary risk profile in diabetic patients. SO ARCHIVES DES MALADIES DU COEUR ET DES VAISSEAUX ID DISEASE AB Coronary Risk Profile (CRP), assessed according to the Framingham equation takes the presence of diabetes into account, but not the glycemic control or the body overweight. We have performed an observational survey to study the respective roles of changes in body weight or glycaemic control on calculated CRP, in a given subject, by an effect on several items of the CRP equation (systolic blood pressure, total and HDL cholesterol) which can be modified by blood glucose or weight. We have studied the CRP of 179 type 1 and 208 type 2 diabetes patients, admitted in the department of diabetology of the Angers Hospital, twice (interval<3 years: 1.6+/-0.8 yr). The patients yielded no coronary heart disease, their age ranged from 30 to 74 yr (mean+/-SD : 53+/-13), they were not on antihypertensive or lipid lowering medication. Glycemic control was assessed by glyco-hamoglobin (HbA1c), systolic blood pressure (SBP) was measured with an automatic device (Dinamap). Total and HDL cholesterol were determined by an enzymatic method, in fasting patients. Only age at first examination was taken into account to compute CRP. Initially, SEP was 131+/-17 mmHg, total and HDL cholesterol were 2.20+/-0.47 et 0.56+/-0.20 g/L, respectively. SEP was positively correlated with body weight (Rho=0.310; p<0.0001), but not with HbA1c. Median 5 yr CRP was 5% (range: <1% - 25%), Between both admissions, mean change in body weight, HbA1c and 5 yr CRP was +1.0 kg (range: -27 a +29), -0.2% (range: -4.5 a +7.6) et -0.01% (range : -10 a +13) respectively. Change in CRP between both admissions was associated with change in HbA1c (Rho=0,109; p=0.0315) but not in body weight (Rho=0.072: p=0.1588), This result was explained by the effect of the change in HbA1c on total cholesterol (Rho=0.151: p=0.003), (no effect on SEP or HDL cholesterol: Rho=0.008 and Rho=0.019: NS, respectively). These results suggest that, in diabetic patients, changes in glycaemic control affect their CRP by an effect on total cholesterol, but the changes in body weight do not affect their CRP. C1 CHU Angers, Serv Med B, F-49033 Angers, France. RP Hadjadj, S, CHU Poitiers, Serv Med Interne Diabetol, BP 577, F-86021 Poitiers, France. TC 2 PD AUG PY 2000 VL 93 IS 8 BP 1033 EP 1036 UT ISI:000089059200027 ER PT J AU Conreux, F Guilleux, AM Beydon, L Cazalaa, JB Fougere, S CA Sous Commission 4b Materiovigilanc TI Infusion devices postmarketing survey: analysis of the reports made in 1998 to the French agency for medical devices. SO ANNALES FRANCAISES D ANESTHESIE ET DE REANIMATION DE equipment; incident reporting; vigilance; perfusion; pumps; catheters ID SURVEILLANCE AB Objectives: To analyze retrospectively the data base of the French national vigilance reporting system concerning infusion devices during the year 1998. Methods: Each report has been reviewed and classified, except implantable catheter ports. Results: The study included 309 reports. Among them, 28% concerned infusion pumps and 72% single use devices, i.e. catheters, infusion lines, taps, connectors, etc. We observed six deaths and 23 severe incidents. Only 25% of devices could be formally investigated by manufacturers. The origins of incidents were very different between infusion pumps and single use devices. The first showed simple failures, software errors, maintenance omissions or errors, and problems related to obsolescence of the device. The second revealed manufacturer quality insurance failures, design and utilization errors, and problems related to the technique itself rather than device. Discussion: Our findings are similar to the few data available in international literature,. They address the need to obtain an adequacy between the performances of devices which vary with generations of devices and the clinical risks: newest and safest devices should be preferred for the infusion of the most critical drugs. (C) 2000 Editions scientifiques et medicates Elsevier SAS. C1 CHU Angers, Dept Anesthesie, F-49033 Angers 01, France. RP Beydon, L, CHU Angers, Dept Anesthesie, F-49033 Angers 01, France. TC 2 PD AUG PY 2000 VL 19 IS 7 BP 523 EP 529 UT ISI:000089002900004 ER PT J AU Stephan, C Renard, M Montrichard, F TI Evidence for the existence of two soluble NAD(+) kinase isoenzymes is Euglena gracilis Z SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY DE NAD(+) kinase; soluble isoenzymes; specificity; catalytic mechanism; Euglena gracilis ID NAD+ KINASE; PLANTS AB Two soluble NAD(+) kinase isoenzymes (isoenzymes 1 and 2) from Euglena gracilis were separated by preparative electrophoresis and characterized. They display several similar properties: both have an identical apparent molecular weight of 68 kDa and their activities are independent on calmodulin, insensitive to 2-mercaptoethanol but inhibited by p-chloromercurybenzoate, 5,5'-dithiobis(2-nitrobenzoate) and, surprisingly, by low dithiothreitol concentrations, the inhibition by dithiothreitol being irreversible for isoenzyme 1 but reversible for isoenzyme 2. Nevertheless, the two isoenzymes mainly differ by their specificities towards triphosphate nucleotides and their catalytic mechanisms. Isoenzyme 1 is as active in the presence of ATP as of GTP and acts by a ping-pong mechanism with a k(M) for NAD(+) of 0.26 mM and a k(M) for low MgATP(2)-concentrations of 0.03 mM. Isoenzyme 2 is three-fold more active in the presence of CTP than of ATP and operates by a sequential mechanism with k(M)s for NAD(+) and MgGTP(2-) of 1.03 and 0.20 mM, respectively. This study shows the evidence for the existence of two structurally similar but catalytically different NAD(+) kinase isoenzymes in E. gracilis. One resembles the enzyme previously described in bacteria. The other displays a catalytic mechanism identical to that of NAD(+) kinase from other organisms but remains unique among all the NAD(+) kinases studied to-date regarding its specificity towards GTP. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 UFR Sci, GBBMV EA917, F-49045 Angers, France. RP Montrichard, F, UFR Sci, GBBMV EA917, 2 Blvd Lavoisier, F-49045 Angers, France. TC 2 PD AUG PY 2000 VL 32 IS 8 BP 855 EP 863 UT ISI:000088850900005 ER PT J AU Gardais, J TI Dyshaemopoiesis in adults: a pr