J L Fauchère

Institut de France, Lutetia Parisorum, Île-de-France, France

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Publications (147)338.47 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The gastric and duodenal ulcers are indications of research and eradication of H. pylori. Eradication of H. pylori promotes healing and prevents recurrence of ulcers. Eradication of H. pylori is part of the initial management of all gastric MALT lymphoma. Eradication may be sufficient to achieve lasting remission especially if the lesion is localized (stage I of the Ann Arbor classification) and in the absence of t (11 ; 18) translocation. Search and eradication of H. pylori are justified in dyspepsia for patients having normal endoscopy. In patients issued from area with high prevalence of infection (> 50 %) the strategy of testing the presence of H. pylori and eradicate the bacterium without endoscopy remains an option if any risk factors for ulcer (history, age, NSAIDs) or gastric cancer are absent. In a country like France where the prevalence of infection is low but with high level of strains resistance to antibiotics, endoscopy should be considered first. The eradication of H. pylori is not a treatment of gastroesophageal reflux. The indications for H. pylori search and treatment are not modified by the presence of gastroesophageal reflux. Eradication should be considered for patients with long term PPI therapy in order to reduce the progression toward atrophy and intestinal metaplasia. The search and eradication of H. pylori are recommended prior treatment with NSAIDs, especially in prolonged treatment. The search and eradication of H. pylori are recommended in patient's receving NSAIDs or low-dose aspirin and who have history of complicated ulcer or not. The eradication does not exclude a PPI treatment in patients with high risks factors. Infection with H. pylori should be sought and treated in patients with iron deficiency anemia without obvious cause or with a vitamin B12 deficiency or a Idiopathic thrombocytopenic purpura. Infection with H. pylori should be sought and treated in patients with a family history of gastric cancer in the first degree, mutations in DNA mismatch repair genes (HNPCC), pre-neoplastic lesions: atrophy with or without intestinal metaplasia, previous limited resection for gastric cancer, a long-term treatment by PPI (at least 6 months) . The prevention of gastric cancer justifies endoscopy for screening and H. pylori treatment of prior a gastric bypass for bariatric purpose. In case of severe or diffuse preneoplastic lesions, a surgical procedure without isolating the gastric cavity must be preferred. The rapid urease test allows rapid diagnosis of infection with H. pylori. Its negativity does not exclude infection. The test is not recommended for the control and eradication in patients treated with PPIs or antibiotics. Histological examination assesses the mucosal lesions and detects infection by H. pylori. If a gastroscopy was performed, a minimum of five biopsies is needed for diagnosis of infection and histological lesions: one of the angle of the lesser curvature, two from the gastric body (small and large curvature), two of the antrum (small and large curvature). Culture of H. pylori with antibiotic sensitivity testing is recommended whenever possible and especially after failure of eradication therapy. Gene amplification is an alternative to culture with antibiotic susceptibility testing. This technique must be developed. Serology does not control eradication and can not be used alone for initial diagnosis. Serology is particularly recommended in situations where other tests have likewise failed: bleeding ulcer, glandular atrophy, MALT lymphoma, recent use of antibiotics or PPIs. The 13C urea breath test can be used for diagnosis and is highly recommended for validate eradication, subject to its realization at least 4 weeks after discontinuation of antibiotics and at least two weeks after discontinuation of PPI therapy. The search for bacterial antigens by monoclonal test is recommended for the diagnosis and validation of eradication, if the breath test is not feasible. When endoscopy is required, the search for H. pylori and the study of resistance to antibiotics are recommended. The infection must be proven by culture or histology associated with the rapid urease test. Based triple therapy of clarithromycin should no longer be prescribed as first-line empirical treatment in France. The sequential therapy should be recommended as first line in France. Subject to approval by the French health authorities, the empiric antibiotic quadruple therapy combining PPI, tetracycline, metronidazole and bismuth is the most interesting alternative especially in patients allergic to beta-lactams or in those having received previously macrolides. Eradication control must be systematic 4 weeks after ending antibiotic treatment and 15 days after stopping PPIs. After failure of eradication of H. pylori and in the absence of isolation of the strain, antibiotics already used in previous therapy must not be reused. In patients who have not previously received clarithromycin sequential therapy should be offered. In patients who received clarithromycin, quadruple therapy combining PPI, tetracycline, metronidazole and bismuth is an alternative, subject to approval by the French health authorities. After failure to eradicate the determination by PCR techniques of bacterial mutations associated with resistance to clarithromycin and levofloxacin is an alternative to prescribing guided combination. After two failures to eradicate the practice of endoscopy for isolation and sensitivity testing is essential to guide further treatment.
    No preview · Article · Sep 2012
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    ABSTRACT: The aim of this review is to critically assess the evidence that neuropeptide Y (NPY) plays both an important role in the control of food intake and in the peripheral metabolic processes linked to the obese state. When given into the brain, NPY stimulates food intake and a variety of metabolic processes that promote fat deposition. The stimulation of food intake and body weight observed with chronic administration of the peptide is persistent and leads to obesity. Both the acute and chronic stimulation of food intake and body weight produced by NPY can be reproduced with selective NPY Y1 and Y5agonists. Therefore, there is no doubt that exogenously administered NPY is a potent regulator of appetite and could be involved in the development and maintenance of obesity. However, questions remain as to whether the increase in food intake produced by exogenous NPY represents a true hunger state or is mediated by unrelated behavioral changes. Although brain NPY levels and food intake are temporally related, attempts to demonstrate a change in food intake after blockade of endogenous NPY have been mixed. Furthermore, although some studies have shown a change in food intake after blockade of NPY the conclusion that this peptide plays an important role in the control of food intake is difficult to fully accept because of the nonselective nature of the inhibitors used. Based on the available evidence our conclusion is that NPY probably plays a role in the day-to- day control of food intake. However, NPY is not a critical regulator of food intake. In its absence appetite can be controlled by a variety of other hormones and neurotransmitters. However, a definitive answer to the role played by NPY in the control of food intake and peripheral metabolism awaits the development of clean and selective inhibitors. KeywordsNeuropeptide Y–Food intake–Obesity–NPY receptor knockout–NPY receptor antagonists–NPY antisense oligodeoxynucleotides–NPY antibodies
    No preview · Chapter · Jul 2011

  • No preview · Article · Jan 2011 · Feuillets de biologie
  • J. L. FAUCHERE · J. M. HENLIN · J. A. BOUTIN

    No preview · Article · Dec 2010 · ChemInform
  • J. L. FAUCHERE · J. M. HENLIN · J. A. BOUTIN
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    ABSTRACT: The methods for the production of soluble peptide and non-peptide libraries are first reviewed and their use for the discovery of pharmacological leads illustrated. Special attention is drawn to the powerful deconvolution applied to the split synthesis procedure which requires only a small number of biological tests. Automation is recommended for repetitive synthesis. Ways to maximise and estimate molecular diversity are indicated in relation to the choice of the building blocks and of the scaffolds. The production of collections of individual small organic compounds via parallel synthesis is compared to the combinatorial synthesis of large libraries. The problems encountered in the coupling of mixtures, in the use of the positional scanning strategy and in the post-synthetic chemical modification of libraries are outlined. Examples of analytical evaluation of compound mixtures produced by combinatorial synthesis are given, in particular the use of high-performance capillary electrophoresis, mass spectrometry and two-dimension nuclear magnetic resonance for the analysis of tetra- and pentameric sub-libraries. Finally, the expected progress in terms of production of molecular diversity, of analytical identification of the product on a single bead and automation of screening is anticipated.
    No preview · Article · Nov 2010 · ChemInform
  • J.L. Fauchère · C. Burucoa

    No preview · Article · Nov 2010 · Feuillets de biologie
  • P.-H. Lambert · S. Bertin · J.-L. Fauchere · J.-P. Volland
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    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    No preview · Article · Apr 2010 · ChemInform
  • J. Paladino · C. Guyard · C. Thurieau · J.-L. Fauchere
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    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    No preview · Article · Mar 2010 · ChemInform

  • No preview · Article · Oct 2003 · European Neuropsychopharmacology
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    ABSTRACT: Melanin-concentrating hormone (MCH) is a cyclic peptide, mainly involved in the regulation of skin pigmentation in teleosts and feeding behavior in mammals. The human keratinocyte SVK14 cell line has been previously shown to express binding sites for the MCH analog [125I]-[Phe13,3-iodo-Tyr19]MCH. We report here that: (1) this binding site similarly recognized [125I]-[3-iodo-Tyr13]MCH; (2) its pharmacological profile clearly differed from those observed at the two human MCH receptor subtypes, MCH1-R and MCH2-R; (3) MCH did not induce any effect on second messenger systems (including cAMP, calcium, and MAP kinase signaling pathways), and (4) no mRNAs corresponding to the MCH receptors were found. In conclusion, the binding site characterized in the SVK14 cell line is distinct from the MCH1 and MCH2 receptors and deserves therefore further investigation.
    No preview · Article · Aug 2002 · Biochemical and Biophysical Research Communications
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    ABSTRACT: Helicobacter pylori resistance to macrolides is increasing, and the need for susceptibility testing has become crucial. The only standardized method is agar dilution, which is not adapted to clinical practice. The present work aimed: (1) to optimize the technical conditions and to assess the reproducibility of the E-test and disk diffusion method for macrolides susceptibility testing of H. pylori, and (2) to assess the performances of these two phenotypic methods in detecting strains harboring a resistance mechanism to macrolides. We used 191 isolates collected in nine centers of France and Belgium. Phenotypic tests were performed on Mueller-Hinton agar supplemented with 10% horse blood, inoculated with a 2-day-old H. pylori suspension (10(8) CFU/ml), and incubated for 72 hr at 37 degrees C under microaerophilic conditions. The reproducibility studied on two randomly selected strains was better for disk diffusion than for the E-test for both clarithromycin and erythromycin. For a subset of 10 strains, the MICs of erythromycin and clarithromycin did not differ from more than one two-fold dilution when determined by E-test or agar dilution method. The breakpoints were for MICs: 1 mg/L for both clarithromycin and erythromycin and for inhibition diameters, 22 mm for clarithromycin and 17 mm for erythromycin. There was a 100% concordance between susceptibility to erythromycin and clarithromycin. However, the susceptible and resistant populations were better separated by testing erythromycin. Of 34 resistant strains, two lacked the A2142G and A2143G point mutations in 23S rRNA by PCR-RFLP. None of 15 tested sensitive strains were positive for one of these two point mutations. For clinical practice, we recommend to assess macrolide susceptibility of H. pylori by using one of these two phenotypic methods under the described technical conditions.
    No preview · Article · Feb 2002 · Microbial Drug Resistance
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    ABSTRACT: Prevalence of methicillin-resistant Staphylococcus aureus is high in the Poitiers teaching hospital, particularly in the intermediate care facilities. We performed a survey of methicillin-resistant Staphylococcus aureus colonization in the intermediate care facilities and 265 patients were included. Nasal, cutaneous and wound swab cultures were done at the time of admission and at the time of the patients' departure. A decolonization procedure of methicillin-resistant Staphylococcus aureus carriers was performed using nasal application of fusidic acid and different soaps for the skin. At entry, 17.7% of patients were methicillin-resistant Staphylococcus aureus carriers (of at least one location). At departure, 30.4% were methicillin-resistant Staphylococcus aureus carriers. Among methicillin-resistant Staphylococcus aureus non-carriers at entry, 24.3% became methicillin-resistant Staphylococcus aureus carriers. The principal risk factor of carriage was the initial presence of a wound (RR = 3.6). The incidence rate of methicillin-resistant Staphylococcus aureus infection among the 265 patients included was 3%. The systematic screening of patients at the time of admission is expensive and isolation technically hard to manage in the intermediate care facilities. The risk factor we found in this study allow us to propose a 'light' screening limited to patients with wounds.
    No preview · Article · Sep 2001 · La Revue de Médecine Interne
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    ABSTRACT: Purpose. – Prevalence of methicillin-resistant Staphylococcus aureus is high in the Poitiers teaching hosiptal, particularly in the intermediate care facilities. We performed a survey of methicillin-resistant Staphylococcus aureus colonization in the intermediate care facilities and 265 patients were included.Methods. – Nasal, cutaneous and wound swab cultures were done at the time of admission and at the time of the patients’ departure. A decolonization procedure of methicillin-resistant Staphylococcus aureus carriers was performed using nasal application of fusidic acid and different soaps for the skin. At entry, 17.7% of patients were methicillin-resistant Staphylococcus aureus carriers (of at least one location). At departure, 30.4% were methicillin-resistant Staphylococcus aureus carriers. Among methicillin-resistant Staphylococcus aureus non-carriers at entry, 24.3% became methicillin-resistant Staphylococcus aureus carriers.Results. – The principal risk factor of carriage was the initial presence of a wound (RR = 3.6).The incidence rate of methicillin-resistant Staphylococcus aureus infection among the 265 patients included was 3%.Conclusion. – The systematic screening of patients at the time of admission is expensive and isolation technically hard to manage in the intermediate care facilities. The risk factor we found in this study allow us to propose a ‘light’ screening limited to patients with wounds.
    No preview · Article · Aug 2001 · La Revue de Médecine Interne
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    ABSTRACT: Shortened, more stable and weakly hydrophobic analogues of melanin-concentrating hormone (MCH) were searched as candidates for radioiodination. Starting from the dodecapeptide MCH6 – 17, we found that: (1) substitution of Tyr13 by a Phe residue; (2) addition of a 3-iodo-Tyr residue at the N-terminus; and (3) addition of a hydrophilic spacer 8-amino-3,6-dioxyoctanoyl between the 3-iodo-Tyr and MCH6 – 17 (compound S36057), led to an agonist more potent than MCH itself in stimulating [35S]-GTPγS binding at membranes from HEK293 cells stably expressing the human MCH receptor. Specific binding of [125I]-S36057 was found in HEK293 and CHO cell lines stably expressing the human MCH receptor. This radioligand recognized a similar number of binding sites (ca. 800 fmol mg−1) than [125I]-[3-iodo Tyr13]-MCH. However, the KD for [125I]-S36057 obtained from saturation studies (0.037 nM) or from binding kinetics (0.046 nM) was at least 10 fold higher to that of [125I]-[3-iodo Tyr13]-MCH (0.46 nM). Affinities determined for a series of MCH analogues were similar with both radioligands, S36057 being the most potent compound tested (Ki=0.053 nM). Finally, [125I]-S36057 also potently labelled the MCH receptor in membranes from whole rat brain (KD 0.044 nM, Bmax=11 fmol mg−1). In conclusion, [125I]-S36057 is a more potent and more stable radioligand than [125I]-[3-iodo Tyr13]-MCH that will represent a reliable tool for binding assays in the search of novel MCH ligands. It should also provide great help for autoradiographic studies of the MCH receptor distribution in the central nervous system. British Journal of Pharmacology (2001) 133, 371–378; doi:10.1038/sj.bjp.0704085
    Full-text · Article · Jul 2001 · British Journal of Pharmacology
  • P H Lambert · S Bertin · J L Fauchère · J P Volland
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    ABSTRACT: Parallel synthesis techniques aim to prepare collections of single compounds which, once tested, can easily be identified by their sole location in the synthesic array. On the other hand, true combinatorial chemistry produces libraries of compounds as mixtures of variable size which require a deconvolution procedure for identification of the active hits or leads. In the latter case, analytical methods are crucial for the success of the strategy and mass spectrometry plays a major role. If the goal is to identify all the library components, including expected products as well as by-products, various mass spectrometric techniques may be necessary. Library components can be separated according to their mass by increasing mass resolution or by their elution time by coupling liquid chromatography and mass spectrometry. The efficiency of such separation techniques are discussed as a function of the size and the degeneracy of the library. Library members possess common structural features which impart similar fragmentation patterns after ionization in the gas phase. This feature can be exploited by tandem mass spectrometry to specifically detect subfamilies of products. Examples of precursor ion scans, product ion scans and constant neutral loss scans will be shown that facilitate partial characterization of libraries. To solve the difficult problem of the quantitative analysis of libraries, i.e., to evaluate their equimolarity, the use of an evaporative light scattering detector (ELSD) or a chemiluminescent nitrogen detector (CLND) is suggested as more appropriate.
    No preview · Article · Jul 2001 · Combinatorial Chemistry & High Throughput Screening
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    ABSTRACT: Several series of low-molecular-mass ligands of the neuropeptide receptor subtype Y5 were prepared using a mixed strategy of synthesis on solid phase and in solution. Collections of single compounds were obtained by an automated parallel procedure which allowed quick variation and investigation of the central spacer moiety, as well as of the aromatic substituents on each side. The strategy of parallel synthesis and screening of partially purified analogs helped to select rapidly potent and selective leads which displayed comparable antagonistic potency against neuropeptide Y activity on the Y5 receptor and better receptor selectivity than the original reference compounds.
    No preview · Article · Jun 2001 · European Journal of Allergy and Clinical Immunology
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    ABSTRACT: Melanin-concentrating hormone (MCH) is a cyclic nonadecapeptide involved in the regulation of feeding behavior, which acts through a G protein-coupled receptor (SLC-1) inhibiting adenylcyclase activity. In this study, 57 analogues of MCH were investigated on the recently cloned human MCH receptor stably expressed in HEK293 cells, on both the inhibition of forskolin-stimulated cAMP production and guanosine-5'-O-(3-[(35)S]thiotriphosphate ([(35)S]- GTPgammaS) binding. The dodecapeptide MCH-(6-17) (MCH ring between Cys(7) and Cys(16), with a single extra amino acid at the N terminus (Arg(6)) and at the C terminus (Trp(17))) was found to be the minimal sequence required for a full and potent agonistic response on cAMP formation and [(35)S]- GTPgammaS binding. We Ala-scanned this dodecapeptide and found that only 3 of 8 amino acids of the ring, namely Met(8), Arg(11), and Tyr(13), were essential to elicit full and potent responses in both tests. Deletions inside the ring led either to inactivity or to poor antagonists with potencies in the micromolar range. Cys(7) and Cys(16) were substituted by Asp and Lys or one of their analogues, in an attempt to replace the disulfide bridge by an amide bond. However, those modifications were deleterious for agonistic activity. In [(35)S]- GTPgammaS binding, these compounds behaved as weak antagonists (K(B) 1-4 microm). Finally, substitution in MCH-(6-17) of 6 out of 12 amino acids by non-natural residues and concomitant replacement of the disulfide bond by an amide bond led to three compounds with potent antagonistic properties (K(B) = 0.1-0.2 microm). Exploitation of these structure-activity relationships should open the way to the design of short and stable MCH peptide antagonists.
    Full-text · Article · May 2001 · Journal of Biological Chemistry
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    ABSTRACT: Several series of low-molecular-mass ligands of the neuropeptide receptor subtype Y5 were prepared using a mixed strategy of synthesis on solid phase and in solution. Collections of single compounds were obtained by an automated parallel procedure which allowed quick variation and investigation of the central spacer moiety, as well as of the aromatic substituents on each side. The strategy of parallel synthesis and screening of partially purified analogs helped to select rapidly potent and selective leads which displayed comparable antagonistic potency against neuropeptide Y activity on the Y5 receptor and better receptor selectivity than the original reference compounds.
    No preview · Article · Apr 2001 · European Journal of Allergy and Clinical Immunology
  • Source
    C Audibert · C Burucoa · B Janvier · J L Fauchère
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    ABSTRACT: Helicobacter pylori virulence is associated with the presence of the cag pathogenicity island (PAI). Thecag PAI is involved in the ability to induce interleukin-8 (IL-8) secretion by human cells, which is implicated in the inflammatory response of the gastric mucosa to H. pyloriinfection. The aim of this study was to determine whether the genetic structure of the cag PAI is conserved and whether it is linked to IL-8 induction ability. Detection of specific markers (cagA, picB, cag13-cag14, virD4, and IS605) by PCR and dot blot hybridization and long-distance PCR determination of the presence of cagI, cagII, and the middle region of thecag PAI were performed on 153 strains isolated from adults suffering from ulcers (n = 79) or gastritis (n = 74). IL-8 induction ability was evaluated by coculture of the strains with HEp-2 cells. Eighty-three strains (54.3%) had an entire cag PAI, 12 strains (7.8%) had thecag PAI split in two, 49 strains (32%) had nocag PAI, and 9 strains exhibited other structural combinations. The presence of an entire cag PAI was statistically correlated with the presence of IS605(P = 0.006) and the ability to induce IL-8 secretion but not with clinical presentation of the infection. The structure of the cag PAI appears to be rather conserved and is related to the proinflammatory power of a strain. The existence of strains inducing IL-8 secretion regardless of the cag PAI structure suggests that this region is not the only requirement for IL-8 secretion.
    Full-text · Article · Apr 2001 · Infection and Immunity
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    ABSTRACT: A complete 331,776-member library of tetrapeptides made of 24 amino acid building blocks was synthesized robotically on solid phase and subjected to a deconvolution based on the inhibitory potency of the sublibraries in a HPLC assay of the S-farnesyltransferase activity in vitro. One of the non-natural peptide and noncysteine-containing leads Nip-Trp-Phe-His (Nip=p-nitrophenyl-L-alanine) was optimized chemically to give a proteolytically stable pseudopeptide with a 200-fold potency compared with the original lead. The final compound was converted to the C-terminal ethyl ester: p-F-C6H4-CO(CH2)2-CO-Bta-D-Phepsi[CH2NH]His-OEt (Bta = benzothienyl-L-alanine) and shown to behave as a prodrug which was hydrolyzed back to the C-terminal acid following cell penetration. The method confirmed that several structurally original leads can be discovered in large libraries when deconvolution relies upon a highly specific assay and that these leads can be optimized by chemical modification to impart the final compound the desired pharmacological and pharmacokinetic properties.
    No preview · Article · Mar 2001 · European Journal of Allergy and Clinical Immunology

Publication Stats

3k Citations
338.47 Total Impact Points

Institutions

  • 2001
    • Institut de France
      Lutetia Parisorum, Île-de-France, France
  • 1993-2000
    • Centre Hospitalier Universitaire de Poitiers
      Poitiers, Poitou-Charentes, France
  • 1996
    • Université de Poitiers
      Poitiers, Poitou-Charentes, France
    • Eawag: Das Wasserforschungs-Institut des ETH-Bereichs
      Duebendorf, Zurich, Switzerland