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1,025 results on '"Guéant, Jean‐Louis"'

201. Production of Elastin-Derived Peptides Contributes to the Development of Nonalcoholic Steatohepatitis

Author

Romier, Béatrice, primary, Ivaldi, Corinne, additional, Sartelet, Hervé, additional, Heinz, Andrea, additional, Schmelzer, Christian E.H., additional, Garnotel, Roselyne, additional, Guillot, Alexandre, additional, Jonquet, Jessica, additional, Bertin, Eric, additional, Guéant, Jean-Louis, additional, Alberto, Jean-Marc, additional, Bronowicki, Jean-Pierre, additional, Amoyel, Johanne, additional, Hocine, Thinhinane, additional, Duca, Laurent, additional, Maurice, Pascal, additional, Bennasroune, Amar, additional, Martiny, Laurent, additional, Debelle, Laurent, additional, Durlach, Vincent, additional, and Blaise, Sébastien, additional

Published
2018
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202. Publisher Correction: A PRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients

Author

Guéant, Jean-Louis, primary, Chéry, Céline, additional, Oussalah, Abderrahim, additional, Nadaf, Javad, additional, Coelho, David, additional, Josse, Thomas, additional, Flayac, Justine, additional, Robert, Aurélie, additional, Koscinski, Isabelle, additional, Gastin, Isabelle, additional, Filhine-Tresarrieu, Pierre, additional, Pupavac, Mihaela, additional, Brebner, Alison, additional, Watkins, David, additional, Pastinen, Tomi, additional, Montpetit, Alexandre, additional, Hariri, Fadi, additional, Tregouët, David, additional, Raby, Benjamin A, additional, Chung, Wendy K., additional, Morange, Pierre-Emmanuel, additional, Froese, D. Sean, additional, Baumgartner, Matthias R., additional, Benoist, Jean-François, additional, Ficicioglu, Can, additional, Marchand, Virginie, additional, Motorin, Yuri, additional, Bonnemains, Chrystèle, additional, Feillet, François, additional, Majewski, Jacek, additional, and Rosenblatt, David S., additional

Published
2018
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205. Interaction between methionine synthase isoforms and MMACHC: characterization in cblG-variant, cblG and cblC inherited causes of megaloblastic anaemia

Author

Fofou-Caillierez, Ma'atem B., Mrabet, Nadir T., Chéry, Céline, Dreumont, Natacha, Flayac, Justine, Pupavac, Mihaela, Paoli, Justine, Alberto, Jean-Marc, Coelho, David, Camadro, Jean-Michel, Feillet, François, Watkins, David, Fowler, Brian, Rosenblatt, David S., Guéant, Jean-Louis, Fofou-Caillierez, Ma'atem B., Mrabet, Nadir T., Chéry, Céline, Dreumont, Natacha, Flayac, Justine, Pupavac, Mihaela, Paoli, Justine, Alberto, Jean-Marc, Coelho, David, Camadro, Jean-Michel, Feillet, François, Watkins, David, Fowler, Brian, Rosenblatt, David S., and Guéant, Jean-Louis

Abstract

The cblG and cblC disorders of cobalamin (Cbl) metabolism are two inherited causes of megaloblastic anaemia. In cblG, mutations in methionine synthase (MTR) decrease conversion of hydroxocobalamin (HOCbl) to methylcobalamin, while in cblC, mutations in MMACHC disrupt formation of cob(II)alamin (detected as HOCbl). Cases with undetectable methionine synthase (MS) activity are extremely rare and classified as ‘cblG-variant'. In four ‘cblG-variant' cases, we observed a decreased conversion of cyanocobalamin to HOCbl that is also seen in cblC cases. To explore this observation, we studied the gene defects, splicing products and expression of MS, as well as MS/MMACHC protein interactions in cblG-variant, cblG, cblC and control fibroblasts. We observed a full-size MS encoded by MTR-001 and a 124 kDa truncated MS encoded by MTR-201 in cblG, cblC, control fibroblasts and HEK cells, but only the MTR-201 transcript and inactive truncated MS in cblG-variant cells. Co-immunoprecipitation and proximity ligation assay showed interaction between truncated MS and MMACHC in cblG-variant cells. This interaction decreased 2.2, 1.5 and 5.0-fold in the proximity ligation assay of cblC cells with p.R161Q and p.R206W mutations, and HEK cells with knock down expression of MS by siRNA, respectively, when compared with control cells. In 3D modelling and docking analysis, both truncated and full-size MS provide a loop anchored to MMACHC, which makes contacts with R-161 and R-206 residues. Our data suggest that the interaction of MS with MMACHC may play a role in the regulation of the cellular processing of Cbls that is required for Cbl cofactor synthesis

Published
2017

206. Predictors of High Motivation Score for Performing Research Initiation Fellowship, Master 1, Research Master 2, and PhD Curricula During Medical Studies

Author

Feigerlova, Eva, Oussalah, Abderrahim, Fournier, Jean-Paul, Antonelli, Arnaud, Hadjadj, Samy, Maréchaud, Richard, Guéant, Jean-Louis, Roblot, Pascal, Braun, Marc, Service Endocrinologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA), Direction du Numérique [Lorraine] (DN), Université de Lorraine (UL), Médecine Interne et Maladies Infectieuses, CHU de Poitiers, Poitiers, France, Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), and UL, NGERE

Subjects
Adult, Male, Students, Medical, [SDV]Life Sciences [q-bio], Integration, Observational Study, Physician-Scientist, Education, Translational Research, Biomedical, Young Adult, Basic Science, Surveys and Questionnaires, Translational Research, Medical Staff, Hospital, Humans, Fellowships and Scholarships, Students, Motivation, Output, [SDV] Life Sciences [q-bio], Cross-Sectional Studies, Logistic Models, Sex-Differences, Education, Medical, Graduate, Multivariate Analysis, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Female, Clinical Medicine, Support, Research Article
Abstract

Supplemental Digital Content is available in the text, Translational research plays a crucial role in bridging the gap between fundamental and clinical research. The importance of integrating research training into medical education has been emphasized. Predictive factors that help to identify the most motivated medical students to perform academic research are unknown. In a cross-sectional study on a representative sample of 315 medical students, residents and attending physicians, using a comprehensive structured questionnaire we assessed motivations and obstacles to perform academic research curricula (ie, research initiation fellowship, Master 1, Research Master 2, and PhD). Independent predictive factors associated with high “motivation score” (top quartile on motivation score ranging from 0 to 10) to enroll in academic research curricula were derived using multivariate logistic regression analysis. Independent predictors of high motivation score for performing Master 1 curriculum were: “considering that the integration of translational research in medical curriculum is essential” (OR, 3.79; 95% CI, 1.49–9.59; P = 0.005) and “knowledge of at least 2 research units within the university” (OR, 3.60; 95% CI, 2.01–6.47; P

Published
2016
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207. BRIP1 coding variants are associated with a high risk of hepatocellular carcinoma occurrence in patients with HCV- or HBV-related liver disease

Author

Oussalah, Abderrahim, Avogbe, Patrice Hodonou, Guyot, Erwan, Chery, Céline, Guéant, Rosa-Maria, Ganne-Carrié, Nathalie, Cobat, Aurélie, Moradpour, Darius, Nalpas, Bertrand, Negro, Francesco, Poynard, Thierry, Pol, Stanislas, Bochud, Pierre, Abel, Laurent, Jeulin, Hélène, Schvoerer, Evelyne, Chabi, Nicodème, Amouzou, Emile, Sanni, Ambaliou, Barraud, Hélène, Rouyer, Pierre, Josse, Thomas, Goffinet, Laetitia, Jouve, Jean-Louis, Minello, Anne, Bonithon-Kopp, Claire, Thiefin, Gérard, Di Martino, Vincent, Doffoël, Michel, Richou, Carine, Raab, Jean-Jacques, Hillon, Patrick, Bronowicki, Jean-Pierre, Guéant, Jean-Louis, Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lorraine ( UL ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Université Paris 13 ( UP13 ), Hôpital Jean Verdier [Bondy], Assistance publique - Hôpitaux de Paris (AP-HP), Génomique Fonctionnelle des Tumeurs Solides ( U1162 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris 13 ( UP13 ), Université Paris Descartes - Faculté de Médecine ( UPD5 Médecine ), Université Paris Descartes - Paris 5 ( UPD5 ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Lausanne ( UNIL ), Département d'hépatologie [CHU Cochin], Institut Pasteur [Paris]-CHU Cochin [AP-HP]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre d'Hydrogéologie et de Géothermie [Neuchâtel] ( CHYN ), Université de Neuchâtel ( UNINE ), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition ( ICAN ), Assistance publique - Hôpitaux de Paris (AP-HP)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Pitié-Salpêtrière [APHP]-Sorbonne Université, Service d'hépatologie médicale [CHU Cochin], CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), The Rockefeller University [New-York], Université de Lorraine ( UL ), Laboratoire de Virologie [Strasbourg], Université de Kara, University of Abomey Calavi ( UAC ), Service d'Hépato-gastro-entérologie [CHRU Nancy], Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Universitaire de Reims ( CHU Reims ), Service d'hépatologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz-Université de Franche-Comté ( UFC ), CHU Strasbourg, Hôpital Jean Minjoz, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Centre hospitalier régional Metz-Thionville ( CHR Metz-Thionville ), This study was supported by a French Government grant managed by the French National Research Agency under the program 'Investissements d’Avenir', reference ANR-11-LABX-0021 and also by the Institut National du Cancer (INCA), the French regions of Lorraine and Burgundy, the Ligue Nationale contre le Cancer (CiRCE-Nutrigenex), the European Regional Development Fund, the Canceropole Grand-Est, and the Fondation de France.The ANRS Study HC EP 26 Genoscan group is supported by the National Agency for Research on AIDS and Viral Hepatitis (ANRS).The Swiss Hepatitis C Cohort Study (SCCS) is supported by grants from the Swiss National Science Foundation (3347C0-108782/1), the Swiss Federal Office for Education and Sciences (03.0599) and the European Commission (LSHM-CT-2004-503359, VIRGIL Network of Excellence on Antiviral Drug Resistance). The SCCS genetic project is supported by the Leenaards foundation, the Santos-Suarez foundation and the Swiss National Science Foundation (324730-144054), ANR-11-LABX-0021/11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du ( 2011 ), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université Paris 13 (UP13), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lausanne (UNIL), CHU Cochin [AP-HP]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Hydrogéologie et de Géothermie [Neuchâtel] (CHYN), Université de Neuchâtel (UNINE), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Rockefeller University [New York], Université de Lorraine (UL), Service de Virologie [CHRU Nancy], Stress, Immunité, Pathogènes (SIMPA), University of Abomey Calavi (UAC), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz-Université de Franche-Comté (UFC), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), ANR-11-LABX-0021/11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du(2011), CiRCE Study Group, Hôpital Jean Verdier, Université Paris 13 ( UP13 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Département d'hépathologie [CHU Cochin], Université de Neuchâtel, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Université d'Abomey Calavi, Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Cochin [AP-HP], Laboratoire de Chimie Physique et Microbiologie pour l'Environnement (LCPME), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), and ANR-11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du(2011)

Subjects
hepatitis C virus, BRIP1, DNA repair genes, hepatitis B virus, hepatocellular carcinoma, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics, Research Paper, [ SDV.CAN ] Life Sciences [q-bio]/Cancer
Abstract

IF 5.008; International audience; The molecular mechanisms of hepatocellular carcinoma (HCC) carcinogenesis are still not fully understood. DNA repair defects may influence HCC risk. The aim of the study was to look for potential genetic variants of DNA repair genes associated with HCC risk among patients with alcohol- or viral-induced liver disease. We performed four case-control studies on 2,006 European- (Derivation#1 and #2 studies) and African-ancestry (Validation#1 and #2 studies) patients originating from several cohorts in order to assess the association between genetic variants on DNA repair genes and HCC risk using a custom array encompassing 94 genes. In the Derivation#1 study, the BRIP1 locus reached array-wide significance (Chi-squared SV-Perm, P=5.00×10-4) among the 253 haplotype blocks tested for their association with HCC risk, in patients with viral cirrhosis but not among those with alcoholic cirrhosis. The BRIP1 haplotype block included three exonic variants (rs4986763, rs4986764, rs4986765). The BRIP1 'AAA' haplotype was significantly associated with an increased HCC risk [odds ratio (OR), 2.01 (1.19-3.39); false discovery rate (FDR)-P=1.31×10-2]. In the Derivation#2 study, results were confirmed for the BRIP1 'GGG' haplotype [OR, 0.53 (0.36-0.79); FDR-P=3.90×10-3]. In both Validation#1 and #2 studies, BRIP1 'AAA' haplotype was significantly associated with an increased risk of HCC [OR, 1.71 (1.09-2.68); FDR-P=7.30×10-2; and OR, 6.45 (4.17-9.99); FDR-P=2.33×10-19, respectively]. Association between the BRIP1 locus and HCC risk suggests that impaired DNA mismatch repair might play a role in liver carcinogenesis, among patients with HCV- or HBV-related liver disease.

Published
2016
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208. Minichromosome maintenance complex component 6 (MCM6) expression correlates with histological grade and survival in endometrioid endometrial adenocarcinoma

Author

Hotton, Judicaël, primary, Agopiantz, Mikaël, additional, Leroux, Agnès, additional, Charra-Brunaud, Claire, additional, Marie, Béatrice, additional, Busby-Venner, Hélène, additional, Morel, Olivier, additional, Guéant, Jean-Louis, additional, Vignaud, Jean-Michel, additional, Battaglia-Hsu, Shyue-Fang, additional, and Gauchotte, Guillaume, additional

Published
2017
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209. TREM-1 Inhibition Restores Impaired Autophagy Activity and Reduces Colitis in Mice

Author

Kökten, Tunay, primary, Gibot, Sébastien, additional, Lepage, Patricia, additional, D’Alessio, Silvia, additional, Hablot, Julie, additional, Ndiaye, Ndeye-Coumba, additional, Busby-Venner, Hélène, additional, Monot, Céline, additional, Garnier, Benjamin, additional, Moulin, David, additional, Jouzeau, Jean-Yves, additional, Hansmannel, Franck, additional, Danese, Silvio, additional, Guéant, Jean-Louis, additional, Muller, Sylviane, additional, and Peyrin-Biroulet, Laurent, additional

Published
2017
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211. Cytoplasmic overexpression of RNA-binding protein HuR is a marker of poor prognosis in meningioma, and HuR knockdown decreases meningioma cell growth and resistance to hypoxia

Author

Gauchotte, Guillaume, primary, Hergalant, Sébastien, additional, Vigouroux, Charlène, additional, Casse, Jean-Matthieu, additional, Houlgatte, Rémi, additional, Kaoma, Tony, additional, Helle, Déborah, additional, Brochin, Lydia, additional, Rech, Fabien, additional, Peyre, Matthieu, additional, Labrousse, François, additional, Vallar, Laurent, additional, Guéant, Jean-Louis, additional, Vignaud, Jean-Michel, additional, and Battaglia-Hsu, Shyue-Fang, additional

Published
2017
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212. Vitamin B12 deficiency

Author

Green, Ralph, primary, Allen, Lindsay H., additional, Bjørke-Monsen, Anne-Lise, additional, Brito, Alex, additional, Guéant, Jean-Louis, additional, Miller, Joshua W., additional, Molloy, Anne M., additional, Nexo, Ebba, additional, Stabler, Sally, additional, Toh, Ban-Hock, additional, Ueland, Per Magne, additional, and Yajnik, Chittaranjan, additional

Published
2017
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215. Diagnostic Accuracy of Procalcitonin for Predicting Blood Culture Results in Patients With Suspected Bloodstream Infection

Author

Oussalah, Abderrahim, Ferrand, Janina, Filhine-Tresarrieu, Pierre, Aissa, Nejla, Aimone-Gastin, Isabelle, Namour, Fares, Garcia, Matthieu, Lozniewski, Alain, Guéant, Jean-Louis, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), and Service de Bactériologie [CHRU Nancy]

Subjects
Community-acquired pneumonia, Antibiotic-treatment, Septic patients, Bacteremia, Metaanalysis, bacterial infections and mycoses, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Sepsis, parasitic diseases, Critically-ill patients, [SDV.IMM]Life Sciences [q-bio]/Immunology, Therapy, Emergency-department, Patterns
Abstract

International audience; Previous studies have suggested that procalcitonin is a reliable marker for predicting bacteremia. However, these studies have had relatively small sample sizes or focused on a single clinical entity. The primary endpoint of this study was to investigate the diagnostic accuracy of procalcitonin for predicting or excluding clinically relevant pathogen categories in patients with suspected bloodstream infections. The secondary endpoint was to look for organisms significantly associated with internationally validated procalcitonin intervals. We performed a cross-sectional study that included 35,343 consecutive patients who underwent concomitant procalcitonin assays and blood cultures for suspected bloodstream infections. Biochemical and microbiological data were systematically collected in an electronic database and extracted for purposes of this study. Depending on blood culture results, patients were classified into 1 of the 5 following groups: negative blood culture, Gram-positive bacteremia, Gram-negative bacteremia, fungi, and potential contaminants found in blood cultures (PCBCs). The highest procalcitonin concentration was observed in patients with blood cultures growing Gram-negative bacteria (median 2.2ng/mL [IQR 0.6-12.2]), and the lowest procalcitonin concentration was observed in patients with negative blood cultures (median 0.3ng/mL [IQR 0.1-1.1]). With optimal thresholds ranging from 0.4 to 0.75ng/mL, procalcitonin had a high diagnostic accuracy for excluding all pathogen categories with the following negative predictive values: Gram-negative bacteria (98.9%) (including enterobacteria [99.2%], nonfermenting Gram-negative bacilli [99.7%], and anaerobic bacteria [99.9%]), Gram-positive bacteria (98.4%), and fungi (99.6%). A procalcitonin concentration 10ng/mL was associated with a high risk of Gram-negative (odds ratio 5.98; 95% CI, 5.20-6.88) or Gram-positive (odds ratio 3.64; 95% CI, 3.11-4.26) bacteremia but dramatically reduced the risk of PCBCs or fungemia. In this large real-life setting experience with more than 35,000 patients, procalcitonin was highly effective at excluding bloodstream infections regardless of pathogen categories. The results from our study are limited by its cross-sectional design and deserve to be validated in prospective longitudinal studies.

Published
2015
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216. Exome-Wide Association Study Identifies New Low-Frequency and Rare UGT1A1 Coding Variants and UGT1A6 Coding Variants Influencing Serum Bilirubin in Elderly Subjects

Author

Oussalah, Abderrahim, Bosco, Paolo, Anello, Guido, Spada, Rosario, Gueant-Rodriguez, Rosa-Maria, Chery, Celine, Rouyer, Pierre, Josse, Thomas, Romano, Antonino, Elia, Maurizzio, Bronowicki, Jean-Pierre, Guéant, Jean-Louis, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Experimental and Clinical Pharmacology, Allergy Unit [Italy], Presidio Columbus [Italy]-Allergologia - Columbus - Policlinico Gemelli [Italy], Pathologie cellulaire et moléculaire en nutrition (EP616), Centre National de la Recherche Scientifique (CNRS), UL, NGERE, and Allergologia - Columbus - Policlinico Gemelli [Italy]-Presidio Columbus [Italy]

Subjects
[SDV] Life Sciences [q-bio], Genome, Common Variants, Metabolism Genes, [SDV]Life Sciences [q-bio], Populations, Prevalence, Swiss-Model, Udp-Glucuronosyltransferase, Disease, Environment, Unconjugated Bilirubin
Abstract

International audience; Genome-wide association studies (GWASs) have identified loci contributing to total serum bilirubin level. However, no exome-wide approaches have been performed to address this question. Using exome-wide approach, we assessed the influence of protein-coding variants on unconjugated, conjugated, and total serum bilirubin levels in a well-characterized cohort of 773 ambulatory elderly subjects from Italy. Coding variants were replicated in 227 elderly subjects from the same area. We identified 4 missense rare (minor allele frequency, MAF < 0.5%) and low-frequency (MAF, 0.5%–5%) coding variants located in the first exon of the UGT1A1 gene, which encodes for the substrate-binding domain (rs4148323 [MAF ¼ 0.06%; p.Gly71Arg], rs144398951 [MAF ¼ 0.06%; p.Ile215Val], rs35003977 [MAF ¼ 0.78%; p.Val2 25Gly], and rs57307513 [MAF ¼ 0.06%; p.Ser250Pro]). These variants were in strong linkage disequilibrium with 3 intronic UGT1A1 variants (rs887829, rs4148325, rs6742078), which were significantly associated with total bilirubin level (P ¼ 2.34 Â 10 À34 , P ¼ 7.02 Â 10 À34 , and P ¼ 8.27 Â 10 À34), as well as unconjugated, and conjugated bilirubin levels. We also identified UGT1A6 variants in association with total (rs6759892, p.Ser7Ala, P ¼ 1.98 Â 10 À26 ; rs2070959, p.Thr181Ala, P ¼ 2.87 Â 10 À27 ; and rs1105879, p.Arg184Ser, P ¼ 3.27 Â 10 À29), unconjugated, and conjugated bilirubin levels. All UGT1A1 intronic variants (rs887829, rs6742078, and rs4148325) and UGT1A6 coding variants (rs6759892, rs2070959, and rs1105879) were significantly associated with gallstone-related cholecystectomy risk. The UGT1A6 variant rs2070959 (p.Thr181Ala) was associated with the highest risk of gallstone–related cholecystectomy (OR, 4.58; 95% CI, 1.58–13.28; P ¼ 3.21 Â 10 À3). Using an exome-wide approach we identified coding variants on UGT1A1 and UGT1A6 genes in association with serum bilirubin level and hyperbilirubinemia risk in elderly subjects. UGT1A1 intronic single-nucleotide polymorphisms (SNPs) (rs6742078, rs887829, rs4148324) serve as proxy markers for the low-frequency and rare UGT1A1 variants, thereby providing mechanistic explanation to the relationship between UGT1A1 intronic SNPs and the UGT1A1 enzyme activity. UGT1A1 and UGT1A6 variants might be potentially associated with gallstone-related cholecystectomy risk. (Medicine 94(22):e925) Abbreviations: 3D = three-dimensional, 95% CI = 95% confidence interval, EM = expectation-maximization, GWAS = genome-wide association study, HWE = Hardy–Weinberg equilibrium, IBD = identity by descent, LD = linkage disequilibrium, MAF = minor allele frequency, MRP2 = multidrug resistance-associated protein 2, OR = odds ratio, PCA = principal-component analysis, SNP = single nucleotide polymorphism, UGT1A1 = UDP-glucuronosy-ltransferase 1 family, polypeptide A1, UGT1A6 = UDP-glucuro-nosyltransferase 1 family, polypeptide A6.

Published
2015
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217. Information-seeking Behavior During Residency Is Associated With Quality of Theoretical Learning, Academic Career Achievements, and Evidence-based Medical Practice

Author

Oussalah, Abderrahim, Fournier, Jean-Paul, Guéant, Jean-Louis, Braun, Marc, UL, NGERE, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Centre universitaire d'enseignement par simulation - Hôpital virtuel de Lorraine [Nancy] (CUESim), Faculté de Médecine [Nancy], Université de Lorraine (UL)-Université de Lorraine (UL), Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA), and Centre universitaire d'enseignement par simulation [Université de Lorraine] (CUESIM)

Subjects
[SDV] Life Sciences [q-bio], Self-Assessment, Uptodate, Knowledge, Performance, [SDV]Life Sciences [q-bio], education, Doctors, National-Survey, Faculty, Resources
Abstract

International audience; Data regarding knowledge acquisition during residency training are sparse. Predictors of theoretical learning quality, academic career achievements and evidence-based medical practice during residency are unknown. We performed a cross-sectional study on residents and attending physicians across several residency programs in 2 French faculties of medicine. We comprehensively evaluated the information-seeking behavior (I-SB) during residency using a standardized questionnaire and looked for independent predictors of theoretical learning quality, academic career achievements, and evidence-based medical practice among I-SB components using multivariate logistic regression analysis. Between February 2013 and May 2013, 338 fellows and attending physicians were included in the study. Textbooks and international medical journals were reported to be used on a regular basis by 24% and 57% of the respondents, respectively. Among the respondents, 47% refer systematically (4.4%) or frequently (42.6%) to published guidelines from scientific societies upon their publication. The median self-reported theoretical learning quality score was 5/10 (interquartile range, 3–6; range, 1–10). A high theoretical learning quality score (upper quartile) was independently and strongly associated with the following I-SB components: systematic reading of clinical guidelines upon their publication (odds ratio [OR], 5.55; 95% confidence interval [CI], 1.77–17.44); having access to a library that offers the leading textbooks of the specialty in the medical department (OR, 2.45, 95% CI, 1.33–4.52); knowledge of the specialty leading textbooks (OR, 2.12; 95% CI, 1.09–4.10); and PubMed search skill score !5/10 (OR, 1.94; 95% CI, 1.01–3.73). Research Master (M2) and/or PhD thesis enrolment were independently and strongly associated with the following predictors: PubMed search skill score !5/10 (OR, 4.10; 95% CI, 1.46– 11.53); knowledge of the leading medical journals of the specialty (OR, 3.33; 95% CI, 1.32–8.38); attending national and international academic conferences and meetings (OR, 2.43; 95% CI, 1.09–5.43); and using academic theoretical learning supports several times a week (OR, 2.23; 95% CI, 1.11– 4.49). This study showed weaknesses in the theoretical learning framework during residency. I-SB was independently associated with quality of academic theoretical learning, academic career achievements, and the use of evidence-based medicine in everyday clinical practice.

Published
2015
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218. IgE antibodies and skin tests in immediate hypersensitivity reactions to infliximab in inflammatory bowel disease

Author

Fréling, Estelle, Peyrin-Biroulet, Laurent, Poreaux, Claire, Morali, Alain, Waton, Julie, Schmutz, Jean-Luc, Guéant, Jean-Louis, Barbaud, Annick, Service de Dermatologie et Allergologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)

Subjects
induction of tolerance, Rheumatoid-Arthritis, [SDV]Life Sciences [q-bio], immediate hypersensitivity, desensitization, skin tests, anti-infliximab antibodies, Factor-Alpha Antagonists, Maintenance Infliximab, Severe Infusion Reactions, Randomized Controlled-Trial, Induced Anaphylaxis, Monoclonal-Antibodies, IgE, Crohns-Disease, Adverse Events, infliximab, acute infusion reaction, Biological Agents
Abstract

International audience; Infliximab (IFX) is used for the treatment of inflammatory bowel diseases (IBD). Immediate hypersensitivity reactions (HR) to IFX are frequently reported.ObjectivesWe investigated immunoglobulin E (IgE)-mediated mechanisms underlying immediate HR to IFX. We also evaluated the clinical utility of allergological tests as well as the tolerability of IFX retreatment in these patients.MethodsThis was a prospective single-center study including IBD patients with previous immediate HR to IFX. Skin tests to IFX, including prick tests and intradermal tests, and measurement of anti-IFX IgE antibodies were performed at least 4 weeks after HR. In case of negative skin tests and absence of IgE antibodies, readministration of IFX was performed with a twice-reduced infusion rate. In case of positive tests or recurrence of HR during readministration of IFX, a 12-step desensitization or induction of tolerance protocol was proposed.ResultsA total of 24 IBD patients were included (Crohn's disease: n=20). Prick tests to IFX were all negative. Intradermal test was positive in one patient. Anti-IFX IgE antibodies were not detected in 21 patients and were detected in three patients (significant level in one patient and intermediate level in two patients). No relationship was observed between positive skin tests and the presence of anti-IFX IgE antibodies. Switch to adalimumab was well tolerated in 10/11 patients. The readministration of IFX was well tolerated in 4/11 patients. Desensitization to IFX was successful in three out of four patients.ConclusionThe vast majority of immediate HR to IFX is not IgE-mediated. Allergological tests are of poor clinical utility. Desensitization or induction of tolerance protocol may allow continuation of IFX therapy in IBD patients with a history of immediate HR.

Published
2015
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219. Mutations in MTHFRand POLGimpaired activity of the mitochondrial respiratory chain in 46-year-old twins with spastic paraparesis

Author

Wiedemann, Arnaud, Chery, Céline, Coelho, David, Flayac, Justine, Gueguen, Naïg, Desquiret-Dumas, Valérie, Feillet, François, Lavigne, Christian, Neau, Jean-Philippe, Fowler, Brian, Baumgartner, Matthias R., Reynier, Pascal, Guéant, Jean-Louis, and Oussalah, Abderrahim

Abstract

Hereditary spastic paraplegias (HSPs) are characterized by lower extremity spasticity and weakness. HSP is often caused by mutations in SPG genes, but it may also be produced by inborn errors of metabolism. We performed next-generation sequencing of 4813 genes in one adult twin pair with HSP and severe muscular weakness occurring at the same age. We found two pathogenic compound heterozygous variants in MTHFR, including a variant not referenced in international databases, c.197C>T (p.Pro66Leu) and a known variant, c.470G>A (p.Arg157Gln), and two heterozygous pathogenic variants in POLG, c.1760C>T (p.Pro587Leu) and c.752C>T (p.Thr251Ile). MTHFRand POLGmutations were consistent with the severe muscle weakness and the metabolic changes, including hyperhomocysteinemia and decreased activity of both N(5,10)methylenetetrahydrofolate reductase (MTHFR) and complexes I and II of the mitochondrial respiratory chain. These data suggest the potential role of MTHFRand POLGmutations through consequences on mitochondrial dysfunction in the occurrence of spastic paraparesis phenotype with combined metabolic, muscular, and neurological components.

Published
2020
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220. Transcobalamin deficiency due to activation of an intra exonic cryptic splice site

Author

Anne-Catherine Helfer, Edward V. Quadros, Guéant Jean-Louis, Lars Örning, Ha M. Bibi, Jean-Marc Alberto, Farès Namour, and David S. Rosenblatt

Subjects
Genetics, Mutation, Genetic heterogeneity, Point mutation, Intron, Hematology, Biology, medicine.disease_cause, Cobalamin, Exon, chemistry.chemical_compound, chemistry, Transcobalamin, medicine, Vitamin B12
Abstract

Transcobalamin (TC), a vitamin B12 (cobalamin, Cbl) binding protein in plasma, promotes the cellular uptake of the vitamin by receptor-mediated endocytosis. Inherited TC deficiency is an autosomal recessive disorder characterized by megaloblastic anaemia caused by cellular vitamin B12 depletion. It may be accompanied by neurological complications, including a delay in psychomotor and mental development. This report describes three sisters with inherited TC deficiency resulting from a splicing defect in the TC gene. A point mutation was identified in intron 3 splice site of the TC gene that activates a cryptic splice site in exon 3. The transcript generated has an in-frame deletion of 81 nucleotides and the resulting truncated protein is unstable and not secreted by the cells. Until now, genetic studies have been reported in only five patients with TC deficiency and the molecular defect was different in each of them, which gives evidence for a genetic heterogeneity of the disease.

Published
2003
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221. Foetal programming by methyl donor deficiency produces steato-hepatitis in rats exposed to high fat diet

Author

Bison, Anaïs, primary, Marchal-Bressenot, Aude, additional, Li, Zhen, additional, Elamouri, Ilef, additional, Feigerlova, Eva, additional, Peng, Lu, additional, Houlgatte, Remi, additional, Beck, Bernard, additional, Pourié, Gregory, additional, Alberto, Jean-Marc, additional, Umoret, Remy, additional, Conroy, Guillaume, additional, Bronowicki, Jean-Pierre, additional, Guéant, Jean-Louis, additional, and Guéant-Rodriguez, Rosa-Maria, additional

Published
2016
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222. Cystathionine β-synthase genetic variant rs2124459 is associated with a reduced risk of cleft palate in French and Belgian populations

Author

Goffinet, Laetitia, primary, Oussalah, Abderrahim, additional, Guéant-Rodriguez, Rosa-Maria, additional, Chery, Céline, additional, Basha, Mirta, additional, Avogbe, Patrice Hodonou, additional, Josse, Thomas, additional, Jeannesson, Elise, additional, Rouyer, Pierre, additional, Flayac, Justine, additional, Gerard, Philippe, additional, Le Touze, Anne, additional, Bonin-Goga, Béatrice, additional, Goga, Dominique, additional, Simon, Etienne, additional, Feillet, François, additional, Vikkula, Miikka, additional, and Guéant, Jean-Louis, additional

Published
2016
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225. 7th Drug hypersensitivity meeting: part two

Author

Elera, Javier Dionicio, primary, Boteanu, Cosmin, additional, Blanco, Maria Aranzazu Jimenez, additional, Gonzalez-Mendiola, Rosario, additional, García, Irene Carrasco, additional, Alvarez, Antonio, additional, Martinez, Jose Julio Laguna, additional, Garrido, Jaume Martí, additional, Barona, Carla Torán, additional, Chorda, Carolina Perales, additional, Salgueiro, Ramón López, additional, Palacios, Miguel Díaz, additional, De Rojas, Dolores Hernández Fernández, additional, Acar, Emre Ali, additional, Aktas, Ayse, additional, Ermertcan, Aylin Türel, additional, Temiz, Peyker, additional, Lin, Chien-Yio, additional, Hui, Chung-Yee Rosaline, additional, Chang, Ya-Ching, additional, Yang, Chih-Hsun, additional, Chung, Wen-Hung, additional, Carolino, Fabrícia, additional, Silva, Diana, additional, De Castro, Eunice Dias, additional, Cernadas, Josefina R., additional, Ensina, Luis Felipe, additional, Aranda, Carolina, additional, Nunes, Ines Camelo, additional, Lacerda, Alex, additional, Martins, Ana Maria, additional, Goudouris, Ekaterini, additional, Ribeiro, Marcia, additional, Da Silva Franco, José Francisco, additional, Queiroz, Leandra, additional, Solé, Dirceu, additional, Dalgiç, Ceyda Tunakan, additional, Sin, Aytül Zerrin, additional, Günsen, Fatma Düsünür, additional, Bulut, Gökten, additional, Ardeniz, Fatma Ömür, additional, Gülbahar, Okan, additional, Gökmen, Emine Nihal Mete, additional, Kokuludag, Ali, additional, De Francisco, Ana M. Montoro, additional, De Vicente Jiménez, Talía Mª, additional, Mendoza Parra, Adriana M., additional, Burgos Pimentel, Angella M., additional, Luque, Amelia García, additional, Amaral, Luis, additional, Leão, Leonor Carneiro, additional, Pinto, Nicole, additional, Belo, Joana, additional, Marques, João, additional, Carreiro-Martins, Pedro, additional, Leiria-Pinto, Paula, additional, Chaabane, Amel, additional, Romdhane, Haifa Ben, additional, Fredj, Nadia Ben, additional, Chadly, Zohra, additional, Boughattas, Naceur A., additional, Aouam, Karim, additional, Uyttebroek, Astrid P., additional, Bridts, Chris H., additional, Romano, Antonino, additional, Ebo, Didier G., additional, Sabato, Vito, additional, Lopes, Anabela, additional, Cosme, Joana, additional, Aguiar, Rita, additional, Lourenço, Tatiana, additional, Paes, Maria-João, additional, Spínola-Santos, Amélia, additional, Pereira-Barbosa, Manuel, additional, Cruz, Cíntia Rito, additional, Dos Reis, Rute Pereira, additional, Tomaz, Elza, additional, Pires, Ana Paula, additional, Inácio, Filipe, additional, Benito-Garcia, Filipe, additional, Mota, Inês, additional, Correia, Magna, additional, Gaspar, Ângela, additional, Chambel, Marta, additional, Piedade, Susana, additional, Morais-Almeida, Mário, additional, Nakonechna, Alla, additional, Antipkin, Yurij, additional, Umanets, Tetiana, additional, Pineda, Fernando, additional, Arribas, Francisca, additional, Lapshyn, Volodymyr, additional, Miranda, Pablo Andrés, additional, De La Cruz Hoyos, Bautista, additional, Blanco, Aranzazu Jimenez, additional, Del Pozo, Marta, additional, Vultaggio, Alessandra, additional, Nencini, Francesca, additional, Pratesi, Sara, additional, Matucci, Andrea, additional, Maggi, Enrico, additional, Cegec, Ivana, additional, Nahal, Danica Juricic, additional, Turk, Viktorija Erdeljic, additional, Aumiler, Matea Radacic, additional, Ausperger, Ksenija Makar, additional, Kraljickovic, Iva, additional, Simic, Iveta, additional, Yamaguchi, Yukie, additional, Watanabe, Tomoya, additional, Satoh, Megumi, additional, Tanegashima, Tomohiko, additional, Oda, Kayoko, additional, Wada, Hidefumi, additional, Aihara, Michiko, additional, Lee, Jaechun Jason, additional, Choi, Jay Chol, additional, Lee, Hwa Young, additional, Fernandes, Rosa-Anita Rodrigues, additional, Faria, Emília, additional, Pita, Joana, additional, Sousa, Nuno, additional, Ribeiro, Carmelita, additional, Carrapatoso, Isabel, additional, Bom, Ana Todo, additional, Rodolfo, Ana, additional, Dias-Castro, Eunice, additional, Voronova, Marina, additional, Valle, Diana Kury, additional, Coronel, Verónica Pacheco, additional, Chordá, Carolina Perales, additional, Madamba, Roselle Catherine Yu, additional, Ferrer, Marta, additional, Goikoetxea, Maria Jose, additional, D’Amelio, Carmen, additional, Bernad, Amalia, additional, Vega, Olga, additional, Gastaminza, Gabriel, additional, Bibián, Beatriz Pola, additional, Salazar, Marina Lluncor, additional, Vilà-Nadal, Gemma, additional, Roman, Ana María Fiandor, additional, Ortega, Javier Dominguez, additional, Muñoz, Miguel Gonzalez, additional, Gancedo, Santiago Quirce, additional, Moreno, Maria Rosario Cabañas, additional, Hofmeier, Kathrin Scherer, additional, Barzylovych, Vladyslava, additional, Pola, Beatriz, additional, Lluncor, Marina, additional, Fiandor, Ana, additional, Bellón, Teresa, additional, Domínguez, Javier, additional, Quirce, Santiago, additional, Yang, Min-Suk, additional, Kim, Sun-Sin, additional, Kim, Sae-Hoon, additional, Kang, Hye-Ryun, additional, Park, Heung-Woo, additional, Cho, Sang-Heon, additional, Min, Kyung-Up, additional, Chang, Yoon-Seok, additional, Delahaye, Clémence, additional, Flabbee, Jenny, additional, Waton, Julie, additional, Bauvin, Olivia, additional, Barbaud, Annick, additional, Fadhel, Najah Ben, additional, Gulin, Sandra Jerkovic, additional, Chiriac, Anca, additional, Cardoso, Bárbara Kong, additional, Viseu, Regina, additional, Moreira, Ana, additional, Cadinha, Susana, additional, Neves, Ana Castro, additional, Barreira, Patrícia, additional, Malheiro, Daniela, additional, Da Silva, J. P. Moreira, additional, Jurakic-Toncic, Ružica, additional, Ljubojevic, Suzana, additional, Turcic, Petra, additional, Gilissen, Liesbeth, additional, Huygens, Sara, additional, Goossens, An, additional, Andreu, Inmaculada, additional, Romero, Alicia Martinez, additional, Cabezas, Pau Gomez, additional, Parejo, Pedro Ayuso, additional, Del Carmen Plaza-Serón, Maria, additional, Doña, Inmaculada, additional, Blanca-López, Natalia, additional, Flores, Carlos, additional, Galindo, María Luisa, additional, Molina, Ana, additional, Perkins, James Richard, additional, Cornejo-García, José Antonio, additional, García-Agúndez, José Augusto, additional, García-Martín, Elena, additional, Campo, Paloma, additional, Canto, María Gabriela, additional, Blanca, Miguel, additional, Guéant-Rodríguez, Rosa María, additional, Jurado-Escobar, Raquel, additional, Barrionuevo, Esther, additional, Salas, María, additional, Canto, Gabriela, additional, Guéant, Jean-Louis, additional, Usui, Toru, additional, Tailor, Arun, additional, Faulkner, Lee, additional, Farrell, John, additional, Alfirevic, Ana, additional, Kevin Park, B., additional, Naisbitt, Dean J., additional, Trelles, Oswaldo, additional, Guerrero, María Auxiliadora, additional, Upton, Alex, additional, Ueta, Mayumi, additional, Sawai, Hiromi, additional, Sotozono, Chie, additional, Tokunaga, Katushi, additional, Kinoshita, Shigeru, additional, Sukasem, Chonlaphat, additional, Satapornpong, Patompong, additional, Tempark, Therdpong, additional, Rerknimitr, Pawinee, additional, Pairayayutakul, Kulprapat, additional, Klaewsongkram, Jettanong, additional, Koomdee, N., additional, Jantararoungtong, T., additional, Santon, S., additional, Puangpetch, A., additional, Intusoma, U., additional, Tassaneeyakul, W., additional, Theeramoke, V., additional, Ramirez, Elena, additional, Borobia, Alberto Manuel, additional, Tong, Hoi, additional, Castañer, Jose Luis, additional, De Abajo, Francisco José, additional, Galvao, Violeta Régnier, additional, Pavlos, Rebecca, additional, Mckinnon, Elizabeth, additional, Williams, Kristina, additional, Beeghly-Fadiel, Alicia, additional, Redwood, Alec, additional, Phillips, Elizabeth, additional, Castells, Mariana, additional, Boni, Elisa, additional, Russello, Marina, additional, Mauro, Marina, additional, Ue, Kok Loong, additional, Rutkowski, Krzysztof, additional, Gomis, Victor Soriano, additional, Ferre, Jorge Frances, additional, Rodriguez, Angel Esteban, additional, Reig, Vicente Cantó, additional, Sanchez, Javier Fernandez, additional, Breynaert, Christine, additional, Van Hoeyveld, Erna, additional, Schrijvers, Rik, additional, Irigoyen, Raquel Fuentes, additional, Collado, Daniel, additional, Vida, Yolanda, additional, Najera, Francisco, additional, Perez-Inestrosa, Ezequiel, additional, Mesa-Antunez, Pablo, additional, Mayorga, Cristobalina, additional, Torres, María José, additional, Tannert, Line K., additional, Mortz, Charlotte G., additional, Skov, Per Stahl, additional, Bindslev-Jensen, Carsten, additional, Pfützner, Wolfgang, additional, Dörnbach, Hannah, additional, Visse, Johanna, additional, Rauber, Michele, additional, Möbs, Christian, additional, Elzagallaai, Abdelbaset A., additional, Chow, Lindsey, additional, Abuzgaia, Awatif M., additional, Rieder, Michael J., additional, Trubiano, Jason, additional, Woolnough, Emily, additional, Stautins, Kaija, additional, Cheng, Christina, additional, Kato, Kenichi, additional, Azukizawa, Hiroaki, additional, Hanafusa, Takaaki, additional, Katayama, Ichiro, additional, Fujiyama, Toshiharu, additional, Hashizume, Hideo, additional, Umayahara, Takatsune, additional, Ito, Taisuke, additional, Tokura, Yoshiki, additional, Silar, Mira, additional, Zidarn, Mihaela, additional, Rupnik, Helena, additional, Korosec, Peter, additional, Redwood, Alec James, additional, Strautins, Kaija, additional, White, Katie, additional, Chopra, Abha, additional, Konvinse, Katherine, additional, Leary, Shay, additional, Mallal, Simon, additional, Cabañas, Rosario, additional, Fiandor, Ana María, additional, Sullivan, Andrew, additional, Whitaker, Paul, additional, Peckham, Daniel, additional, Haw, Wei Yann, additional, Polak, Marta E., additional, Mcguire, Carolann, additional, Ardern-Jones, Michael R., additional, Aoyama, Yumi, additional, Shiohara, Tetsuo, additional, Correia, Sara, additional, Gelincik, Asli, additional, Demir, Semra, additional, Sen, Fatma, additional, Bozbey, Hamza Ugur, additional, Olgac, Muge, additional, Unal, Derya, additional, Coskun, Raif, additional, Colakoglu, Bahauddin, additional, Buyuozturk, Suna, additional, Çatin-Aktas, Esin, additional, Deniz, Gunnur, additional, Laguna, Jose Julio, additional, Dionicio, J., additional, Fernandez, Tahia, additional, Olazabal, I., additional, Ruiz, Maria Dolores, additional, Torres, Maria José, additional, Lafuente, Alberto, additional, Núñez, Jorge, additional, Fernández, Tahia Diana, additional, Palomares, Francisca, additional, Fernández, Rubén, additional, Sanchez, Maria Isabel, additional, Fernandez, Tahía, additional, Ruiz, Arturo, additional, Ariza, Adriana, additional, Alonso, Amalia Bernad, additional, Garófalo, Carmen D’Amelio, additional, Matute, Olga Vega, additional, Puga, Marta Ferrer, additional, Lapresa, María José Goikoetxea, additional, Lasarte, Gabriel Gastaminza, additional, Thinnes, Antonia, additional, Merk, Hans F., additional, Baron, Jens Malte, additional, Leverkus, Martin, additional, Balakirski, Galina, additional, Gibson, Andrew, additional, Ogese, Monday, additional, Al-Attar, Zaid, additional, Yaseen, Fiazia, additional, Meng, Xiaoli, additional, Jenkins, Rozalind, additional, Farrel, John, additional, Alhilali, Khetam, additional, Xue, Yanni, additional, Illing, Patricia, additional, Mifsud, Nicole, additional, Fettke, Heidi, additional, Lai, Jeffrey, additional, Ho, Rebecca, additional, Kwan, Patrick, additional, Purcell, Anthony, additional, Ogese, Monday O., additional, Betts, Catherine, additional, Thomson, Paul, additional, Alhaidari, Mohammad, additional, Berry, Neill, additional, O’Neill, Paul M., additional, Alzahrani, Abdulaziz, additional, Azoury, Marie Eliane, additional, Fili, Lucia, additional, Bechara, Rami, additional, Scornet, Noémie, additional, Nhim, Cathy, additional, Weaver, Richard, additional, Claude, Nancy, additional, Joseph, Delphine, additional, Maillere, Bernard, additional, Parronchi, Paola, additional, Pallardy, Marc, additional, Villani, Axel Patrice, additional, Rozières, Aurore, additional, Bensaïd, Benoît, additional, Tardieu, Mathilde, additional, Albert, Floriane, additional, Mutez, Virginie, additional, Baysal, Tugba, additional, Maryanski, Janet, additional, Nicolas, Jean-François, additional, Kanagawa, Osami, additional, Vocanson, Marc, additional, Hung, Shuen-Iu, additional, Harrison, Caroline J., additional, Jenkins, Rosalind E., additional, French, Neil S., additional, Montañez, Maria Isabel, additional, Fernandez, Tahia D., additional, Martin-Serrano, Angela, additional, Torres, Maria Jose, additional, Molina, Noemi, additional, Wood, Sally, additional, Pirmohamed, Munir, additional, Montañez, María Isabel, additional, Martín-Serrano, Ángela, additional, Pérez-Inestrosa, Ezequiel, additional, Pérez-Sala, Dolores, additional, Guzmán, Antonio E., additional, Ko, Tai-Ming, additional, Chen, Yuan-Tsong, additional, Wu, Jer-Yuarn, additional, Sánchez-Gómez, Francisco J., additional, González-Morena, Juan M., additional, Torres, María J., additional, Arreola, Alejandra Monroy, additional, Corona, Jesus Agustin Badillo, additional, Flores, Silvia Mendez, additional, Cherit, Judith Dominguez, additional, Figueroa, Noe Valentin Duran, additional, Flores, Jose Luis Castrejon, additional, Perkins, James, additional, Pérez-Alzate, Diana, additional, Bogas, Gador, additional, Torres, María J, additional, Marti, Luis Mario Tubella, additional, De La Losa, Fernando Pineda, additional, Poves, Francisca Arribas, additional, Lopez, Jaime Tubella, additional, and Santiago, Teodora Lopez, additional

Published
2016
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226. Methyl donor deficiency impairs bone developmentviaperoxisome proliferator‐activated receptor‐γ coactivator‐1α–dependent vitamin D receptor pathway

Author

Feigerlova, Eva, primary, Demarquet, Lea, additional, Melhem, Hassan, additional, Ghemrawi, Rose, additional, Battaglia‐Hsu, Shyue‐Fang, additional, Ewu, Essi, additional, Alberto, Jean‐Marc, additional, Helle, Deborah, additional, Weryha, Georges, additional, and Guéant, Jean‐Louis, additional

Published
2016
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232. Editorial

Author

Béréziat, Gilbert, primary and Guéant, Jean-Louis, additional

Published
2016
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234. MTHFR genotype modulates the effect of a 5-year supplementation with B-vitamins on homocysteine concentration: The SU.FOL.OM3 randomized controlled trial.

Author

Fezeu, Leopold K., Ducros, Veronique, Guéant, Jean-Louis, Guilland, Jean-Claude, Andreeva, Valentina A., Hercberg, Serge, and Galan, Pilar

Subjects
HOMOCYSTEINE, CARDIOVASCULAR diseases, CLINICAL trials, FATTY acids, VITAMIN B complex
Abstract

Aims: To study how MTHFR genotype modulates the effect of supplementation with B-vitamins on total homocysteine (tHcy) and B-vitamin concentrations. Methods: 2381 patients with a personal history of cardiovascular disease were randomly assigned to one of four groups: 1) B-vitamins alone (560 μg of 5-methyl-THF, 3 mg of vitamin B6 and 20 μg of vitamin B12), 2) n-3 fatty acids alone (600 mg of EPA and DHA in a 2:1 ratio), 3) B-vitamins and n-3 fatty acids, and 4) placebo. Participants were followed up for 4.7 years. At baseline and annually thereafter, biological parameters were assessed. Multivariate and linear mixed models were fit to study the interaction between B-vitamins and MTHFR genotype. Results: Among supplemented participants, concentrations of all three B-vitamins increased during the first year (all p<0.0001) across MTHFR genotype categories. tHcy decreased by 26.3% during the first year (p<0.0001), then steadily increased throughout the 5 years (ptrend<0.001). However, at the end of follow-up, that increase was smaller among than among or subjects (pinteraction<0.02). At baseline, the difference in tHcy concentrations between homozygous and homozygous subjects was 2.33 μmol/l (p<0.001). After 5 years, that difference was reduced to 1.06 μmol/l and remained statistically significant (p<0.001). Conclusion: Participants with the genotype exhibited a lower 5-year decrease in tHcy concentrations following a B-vitamin supplementation than did participants with the or genotype. Clinical trial registration: Current Controlled Trials # . [ABSTRACT FROM AUTHOR]

Published
2018
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235. Minichromosome maintenance complex component 6 (MCM6) expression correlates with histological grade and survival in endometrioid endometrial adenocarcinoma.

Author

Hotton, Judicaël, Agopiantz, Mikaël, Leroux, Agnès, Charra-Brunaud, Claire, Marie, Béatrice, Busby-Venner, Hélène, Morel, Olivier, Guéant, Jean-Louis, Vignaud, Jean-Michel, Battaglia-Hsu, Shyue-Fang, and Gauchotte, Guillaume

Abstract

Minichromosome maintenance complex component 6 (MCM6) is involved in initiating DNA replication and is upregulated during licensed G0 phase of the cell cycle. This early expression permits its labeling of more proliferating cells than those by Ki-67. Here using a cohort of 89 endometrioid adenocarcinoma, we report findings made on the prognostic value of MCM6 based on immunohistochemical labeling index (LI) of the protein in comparison with that of Ki67 as no such information is currently available. Additionally, we examined the prognostic values of these markers based on their mRNA expression using a cohort of uterine corpus endometrial carcinoma (UCEC, n = 307) taken from The Cancer Genome Atlas (TCGA) database. Our evidence indicated the presence of a positive correlation between the LI of MCM6 and the histological grade of endometrioid endometrial adenocarcinoma (grade I, 66.7%; grade II, 75.3%; grade III, 81.4%; p < 0.001) and an inverse correlation between the LI of MCM6 and the overall and progression-free survival (p = 0.02 for both). The LI of Ki-67 correlated with grade (p < 0.001), but not survival. The MCM6 and Ki-67 inter-observer intra-class correlation coefficients were excellent: 0.84 (95% confidence interval, 0.83-0.91) and 0.84 (0.77-0.90), respectively. For in silico analyses of the TCGA cohort, both univariate and multivariate Cox analyses (p = 0.003 and p = 0.03, respectively) revealed high MCM6 mRNA Z-scores associated with reduced overall survival. This association was absent for Ki-67. MCM6 is thus a highly reproducible marker of poor prognosis in endometrial cancer. Evaluation of MCM6 should thus be considered in daily practice for risk stratification. [ABSTRACT FROM AUTHOR]

Published
2018
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236. TREM-1 Inhibition Restores Impaired Autophagy Activity and Reduces Colitis in Mice.

Author

Kökten, Tunay, Gibot, Sébastien, Lepage, Patricia, D'Alessio, Silvia, Hablot, Julie, Ndiaye, Ndeye-Coumba, Busby-Venner, Hélène, Monot, Céline, Garnier, Benjamin, Moulin, David, Jouzeau, Jean-Yves, Hansmannel, Franck, Danese, Silvio, Guéant, Jean-Louis, Muller, Sylviane, and Peyrin-Biroulet, Laurent

Abstract

Background and Aims Triggering receptor expressed on myeloid cells-1 [TREM-1] is known to amplify inflammation in several diseases. Autophagy and endoplasmic reticulum [ER] stress, which activate the unfolded protein response [UPR], are closely linked and defects in these pathways contribute to the pathogenesis of inflammatory bowel disease [IBD]. Both autophagy and UPR are deeply involved in host-microbiota interactions for the clearance of intracellular pathogens, thus contributing to dysbiosis. We investigated whether inhibition of TREM-1 would prevent aberrant inflammation by modulating autophagy and ER stress and preventing dysbiosis. Methods An experimental mouse model of colitis was established by dextran sulphate sodium treatment. TREM-1 was inhibited, either pharmacologically by LR12 peptide or genetically with Trem-1 knock-out [KO] mice. Colon tissues and faecal pellets of control and colitic mice were used. Levels of macroautophagy, chaperone-mediated autophagy [CMA], and UPR proteins were evaluated by western blotting. The composition of the intestinal microbiota was assessed by MiSeq sequencing in both LR12-treated and KO animals. Results We confirmed that inhibition of TREM-1 attenuates the severity of colitis clinically, endoscopically and histologically. We observed an increase in macroautophagy [ATG1/ULK-1, ATG13, ATG5, ATG16L1, and MAP1LC3-I/II] and in CMA [HSPA8 and HSP90AA1], whereas there was a decrease in the UPR [PERK, IRE-1α, and ATF-6α] protein expression levels in TREM-1 inhibited colitic mice. TREM-1 inhibition prevented dysbiosis. Conclusions TREM-1 may represent a novel drug target for the treatment of IBD, by modulating autophagy activity and ER stress. [ABSTRACT FROM AUTHOR]

Published
2018
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237. A PRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients.

Author

Guéant, Jean-Louis, Chéry, Céline, Oussalah, Abderrahim, Nadaf, Javad, Coelho, David, Josse, Thomas, Flayac, Justine, Robert, Aurélie, Koscinski, Isabelle, Gastin, Isabelle, Filhine-Tresarrieu, Pierre, Pupavac, Mihaela, Brebner, Alison, Watkins, David, Pastinen, Tomi, Montpetit, Alexandre, Hariri, Fadi, Tregouët, David, Raby, Benjamin A, and Chung, Wendy K.

Subjects
HETEROZYGOSITY, ALLELES, FIBROBLASTS, GENETIC carriers, METABOLISM, REPRODUCTION
Abstract

To date, epimutations reported in man have been somatic and erased in germlines. Here, we identify a cause of the autosomal recessive cblC class of inborn errors of vitamin B12 metabolism that we name “epi-cblC”. The subjects are compound heterozygotes for a genetic mutation and for a promoter epimutation, detected in blood, fibroblasts, and sperm, at the MMACHC locus; 5-azacytidine restores the expression of MMACHC in fibroblasts. MMACHC is flanked by CCDC163P and PRDX1, which are in the opposite orientation. The epimutation is present in three generations and results from PRDX1 mutations that force antisense transcription of MMACHC thereby possibly generating a H3K36me3 mark. The silencing of PRDX1 transcription leads to partial hypomethylation of the epiallele and restores the expression of MMACHC. This example of epi-cblC demonstrates the need to search for compound epigenetic-genetic heterozygosity in patients with typical disease manifestation and genetic heterozygosity in disease-causing genes located in other gene trios. [ABSTRACT FROM AUTHOR]

Published
2018
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238. Extracellular vesicles as immune mediators in response to kidney injury.

Author

Feigerlová, Eva, Shyue-Fang Battaglia-Hsu, Hauet, Thierry, and Guéant, Jean-Louis

Subjects
KIDNEY injuries, VESICLES (Cytology), ANTI-inflammatory agents, THERAPEUTICS
Abstract

Important progress has been made on cytokine signaling in response to kidney injury in the past decade, especially cytokine signaling mediated by extracellular vesicles (EVs). For example, EVs released by injured renal tubular epithelial cells (TECs) can regulate intercellular communications and influence tissue recovery via both regulating the expression and transferring cytokines, growth factors, as well as other bioactive molecules at the site of injury. The effects of EVs on kidney tissue seem to vary depending on the sources of EVs; however, the literature data are often inconsistent. For example, in rodents EVs derived from mesenchymal stem cells (MSC-EVs) and endothelial progenitor cells (EPC-EVs) can have both beneficial and harmful effects on injured renal tissue. Caution is thus needed in the interpretation of these data as contradictory findings on EVs may not only be related to the origin of EVs, they can also be caused by the different methods used for EV isolation and the physiological and pathological states of the tissues/cells under which they were obtained. Here, we review and discuss our current understanding related to the immunomodulatory function of EVs in renal tubular repair in the hope of encouraging further investigations on mechanisms related to their antiinflammatory and reparative role to better define the therapeutic potential of EVs in renal diseases. [ABSTRACT FROM AUTHOR]

Published
2018
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239. Biallelic pathogenic variants in the lanosterol synthase gene LSSinvolved in the cholesterol biosynthesis cause alopecia with intellectual disability, a rare recessive neuroectodermal syndrome

Author

Besnard, Thomas, Sloboda, Natacha, Goldenberg, Alice, Küry, Sébastien, Cogné, Benjamin, Breheret, Flora, Trochu, Eva, Conrad, Solène, Vincent, Marie, Deb, Wallid, Balguerie, Xavier, Barbarot, Sébastien, Baujat, Geneviève, Ben-Omran, Tawfeg, Bursztejn, Anne-Claire, Carmignac, Virginie, Datta, Alexandre N., Delignières, Aline, Faivre, Laurence, Gardie, Betty, Guéant, Jean-Louis, Kuentz, Paul, Lenglet, Marion, Nassogne, Marie-Cécile, Ramaekers, Vincent, Schnur, Rhonda E., Si, Yue, Torti, Erin, Thevenon, Julien, Vabres, Pierre, Van Maldergem, Lionel, Wand, Dorothea, Wiedemann, Arnaud, Cariou, Bertrand, Redon, Richard, Lamazière, Antonin, Bézieau, Stéphane, Feillet, Francois, and Isidor, Bertrand

Abstract

Lanosterol synthase (LSS) gene was initially described in families with extensive congenital cataracts. Recently, a study has highlighted LSSassociated with hypotrichosis simplex. We expanded the phenotypic spectrum of LSSto a recessive neuroectodermal syndrome formerly named alopecia with mental retardation (APMR) syndrome. It is a rare autosomal recessive condition characterized by hypotrichosis and intellectual disability (ID) or developmental delay (DD), frequently associated with early-onset epilepsy and other dermatological features.

Published
2019
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240. Predictors of the utility of clinical exome sequencing as a first-tier genetic test in patients with Mendelian phenotypes: results from a referral center study on 603 consecutive cases

Author

Alix, Tom, Chéry, Céline, Josse, Thomas, Bronowicki, Jean-Pierre, Feillet, François, Guéant-Rodriguez, Rosa-Maria, Namour, Farès, Guéant, Jean-Louis, and Oussalah, Abderrahim

Abstract

Background: Clinical exome sequencing (CES) provides a comprehensive and effective analysis of relevant disease-associated genes in a cost-effective manner compared to whole exome sequencing. Although several studies have focused on the diagnostic yield of CES, no study has assessed predictors of CES utility among patients with various Mendelian phenotypes. We assessed the effectiveness of CES as a first-level genetic test for molecular diagnosis in patients with a Mendelian phenotype and explored independent predictors of the clinical utility of CES. Results: Between January 2016 and December 2019, 603 patients (426 probands and 177 siblings) underwent CES at the Department of Molecular Medicine of the University Hospital of Nancy. The median age of the probands was 34 years (IQR, 12–48), and the proportion of males was 46.9% (200/426). Adults and children represented 64.8% (276/426) and 35.2% (150/426), respectively. The median test-to-report time was 5.6 months (IQR, 4.1–7.2). CES revealed 203 pathogenic or likely pathogenic variants in 160 patients, corresponding to a diagnostic yield of 37.6% (160/426). Independent predictors of CES utility were criteria strongly suggestive of an extreme phenotype, including pediatric presentation and patient phenotypes associated with an increased risk of a priori probability of a monogenic disorder, the inclusion of at least one family member in addition to the proband, and a CES prescription performed by an expert in the field of rare genetic disorders. Conclusions: Based on a large dataset of consecutive patients with various Mendelian phenotypes referred for CES as a first-tier genetic test, we report a diagnostic yield of ~ 40% and several independent predictors of CES utility that might improve CES diagnostic efficiency.

Published
2023
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241. Methyl donor deficiency induces cardiomyopathy through altered methylation/acetylation of PGC-1α by PRMT1 and SIRT1

Author

Moreno Garcia, Maira, Gueant-Rodriguez, Rosa-Maria, Pooya, Shabnam, Brachet, Patrick, Alberto, Jean-Marc, Jeannesson, Elise, Maskali, Fathia, Gueguen, Naïg, Marie, Pierre-Yves, Lacolley, Patrick, Herrmann, Markus, Juilliere, Yves, Malthièry, Yves, Guéant, Jean-Louis, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Mitochondrie : Régulations et Pathologie, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Saarland University [Saarbrücken], and Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA)

Subjects
SIRT1, epigenetics, PRMT1, PGC-1 alpha, [SDV]Life Sciences [q-bio], PPAR alpha, vitamin B12, folate, cardiomyopathy, fatty acid oxidation
Abstract

International audience; Cardiomyopathies occur by mechanisms that involve inherited and acquired metabolic disorders. Both folate and vitamin B12 deficiencies are associated with left ventricular dysfunction, but mechanisms that underlie these associations are not known. However, folate and vitamin B12 are methyl donors needed for the synthesis of S -adenosylmethionine, the substrate required for the activation by methylation of regulators of energy metabolism. We investigated the consequences of a diet lacking methyl donors in the myocardium of weaning rats from dams subjected to deficiency during gestation and lactation. Positron emission tomography (PET), microscope and metabolic examinations evidenced a myocardium hypertrophy, with cardiomyocyte enlargement, disturbed mitochondrial alignment, lipid droplets, decreased respiratory activity of complexes I and II and decreased S -adenosylmethionine:S -adenosylhomocysteine ratio. The increased concentrations of triglycerides and acylcarnitines were consistent with a deficit in fatty acid oxidation. These changes were explained by imbalanced acetylation/methylation of PGC-1α, through decreased expression of SIRT1 and PRMT1 and decreased S -adenosylmethionine:S -adenosylhomocysteine ratio, and by decreased expression of PPARα and ERRα. The main changes of the myocardium proteomic study were observed for proteins regulated by PGC-1α, PPARs and ERRα. These proteins, namely trifunctional enzyme subunit α-complex, short chain acylCoA dehydrogenase, acylCoA thioesterase 2, fatty acid binding protein-3, NADH dehydrogenase (ubiquinone) flavoprotein 2, NADH dehydrogenase (ubiquinone) 1α-subunit 10 and Hspd1 protein, are involved in fatty acid oxidation and mitochondrial respiration. In conclusion, the methyl donor deficiency produces detrimental effects on fatty acid oxidation and energy metabolism of myocardium through imbalanced methylation/acetylation of PGC-1α and decreased expression of PPARα and ERRα. These data are of pathogenetic relevance to perinatal cardiomyopathies.

Published
2011
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242. Genotype-phenotype associations in French patients with phenylketonuria and importance of genotype for full assessment of tetrahydrobiopterin responsiveness

Author

Jeannesson-Thivisol, Elise, primary, Feillet, François, additional, Chéry, Céline, additional, Perrin, Pascal, additional, Battaglia-Hsu, Shyue-Fang, additional, Herbeth, Bernard, additional, Cano, Aline, additional, Barth, Magalie, additional, Fouilhoux, Alain, additional, Mention, Karine, additional, Labarthe, François, additional, Arnoux, Jean-Baptiste, additional, Maillot, François, additional, Lenaerts, Catherine, additional, Dumesnil, Cécile, additional, Wagner, Kathy, additional, Terral, Daniel, additional, Broué, Pierre, additional, de Parscau, Loïc, additional, Gay, Claire, additional, Kuster, Alice, additional, Bédu, Antoine, additional, Besson, Gérard, additional, Lamireau, Delphine, additional, Odent, Sylvie, additional, Masurel, Alice, additional, Guéant, Jean-Louis, additional, and Namour, Fares, additional

Published
2015
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244. Folate- and vitamin B12–deficient diet during gestation and lactation alters cerebellar synapsin expressionviaimpaired influence of estrogen nuclear receptor α

Author

Pourié, Grégory, primary, Martin, Nicolas, additional, Bossenmeyer-Pourié, Carine, additional, Akchiche, Nassila, additional, Guéant-Rodriguez, Rosa Maria, additional, Geoffroy, Andréa, additional, Jeannesson, Elise, additional, Chehadeh, Sarah El Hajj, additional, Mimoun, Khalid, additional, Brachet, Patrick, additional, Koziel, Violette, additional, Alberto, Jean-Marc, additional, Helle, Deborah, additional, Debard, Renée, additional, Leininger, Brigitte, additional, Daval, Jean-Luc, additional, and Guéant, Jean-Louis, additional

Published
2015
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246. HLA-DRA variants predict penicillin allergy in genome-wide fine-mapping genotyping

Author

Guéant, Jean-Louis, primary, Romano, Antonino, additional, Cornejo-Garcia, Jose-Antonio, additional, Oussalah, Abderrahim, additional, Chery, Celine, additional, Blanca-López, Natalia, additional, Guéant-Rodriguez, Rosa-Maria, additional, Gaeta, Francesco, additional, Rouyer, Pierre, additional, Josse, Thomas, additional, Canto, Gabriella, additional, Carmona, F. David, additional, Bossini-Castillo, Lara, additional, Martin, Javier, additional, Laguna, Jose-Julio, additional, Fernandez, Javier, additional, Feo, Francisco, additional, Ostrov, David A., additional, Plasencia, Pablo C., additional, Mayorga, Cristobalina, additional, Torres, Maria-Jose, additional, and Blanca, Miguel, additional

Published
2015
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248. Late Maternal Folate Supplementation Rescues from Methyl Donor Deficiency-Associated Brain Defects by Restoring Let-7 and miR-34 Pathways.

Author

Geoffroy, Andréa, Kerek, Racha, Pourié, Grégory, Helle, Déborah, Guéant, Jean-Louis, Daval, Jean-Luc, and Bossenmeyer-Pourié, Carine

Abstract

The micronutrients folate and vitamin B12 are essential for the proper development of the central nervous system, and their deficiency during pregnancy has been associated with a wide range of disorders. They act as methyl donors in the one-carbon metabolism which critically influences epigenetic mechanisms. In order to depict further underlying mechanisms, we investigated the role of let-7 and miR-34, two microRNAs regulated by methylation, on a rat model of maternal deficiency. In several countries, public health policies recommend periconceptional supplementation with folic acid. However, the question about the duration and periodicity of supplementation remains. We therefore tested maternal supply (3 mg/kg/day) during the last third of gestation from embryonic days (E) 13 to 20. Methyl donor deficiency-related developmental disorders at E20, including cerebellar and interhemispheric suture defects and atrophy of selective cerebral layers, were associated with increased brain expression (by 2.5-fold) of let-7a and miR-34a, with subsequent downregulation of their regulatory targets such as Trim71 and Notch signaling partners, respectively. These processes could be reversed by siRNA strategy in differentiating neuroprogenitors lacking folate, with improvement of their morphological characteristics. While folic acid supplementation helped restoring the levels of let-7a and miR-34a and their downstream targets, it led to a reduction of structural and functional defects taking place during the perinatal period. Our data outline the potential role of let-7 and miR-34 and their related signaling pathways in the developmental defects following gestational methyl donor deficiency and support the likely usefulness of late folate supplementation in at risk women. [ABSTRACT FROM AUTHOR]

Published
2017
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