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1. Predominance of BRCA2 Mutation and Estrogen Receptor Positivity in Unselected Breast Cancer with BRCA1 or BRCA2 Mutation

Author: Pujol, Pascal, Yauy, Kevin, Coffy, Amandine, Duforet-Frebourg, Nicolas, Gabteni, Sana, Daurès, Jean-Pierre, Penault-Llorca, Frédérique, Thomas, Frédéric, Hughes, Kevin, Hughes, Kevin A., Turnbull, Clare, Galibert, Virginie, Rideau, Chloé, Corsini, Carole, Collet, Laetitia, You, Benoit, Geneviève, David, Philippe, Nicolas, Service de Biopathologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier], Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Biologie Computationnelle et Mathématique (TIMC-IMAG-BCM), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), CHU Montpellier, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Savoirs, ENvironnement et Sociétés (SENS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Paul-Valéry - Montpellier 3 (UPVM)-Institut de Recherche pour le Développement (IRD), The institute of cancer research [London], Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Service de génétique médicale [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Bureau de Recherches Géologiques et Minières (BRGM) (BRGM), REMEA, Centre de Recherches Ecologiques et Evolutives sur le Cancer (MIVEGEC-CREEC), Processus Écologiques et Évolutifs au sein des Communautés (PEEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université de Montpellier (UM), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), Harvard Medical School [Boston] (HMS), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), This work was commissioned and supported by the French Society of Predictive andPersonalized Medicine, an independent nonprofit learned society (grant SFMPP-20-C3)., SeqOne Genomics [Montpellier], Aésio Santé [Paris], and COLO, Mouniati
Subjects: Cancer Research, breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Oncology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], BRCA1, BRCA2, estrogen receptor, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.CAN]Life Sciences [q-bio]/Cancer
Abstract: Background: Poly(ADP-ribose) polymerase 1 inhibitor (PARPi) agents can improve progression-free survival of patients with breast cancer who carry a germline BRCA1 or BRCA2 pathogenic or likely pathogenic variant (gBRCA) in both the metastatic and adjuvant setting. Therefore, we need to reassess the frequency of gBRCA1 and gBRCA2 in order to redefine the criteria for women and tumor phenotype that should be tested. Objective: We studied the relative distribution of gBRCA1 and gBRCA2 in unselected populations of women with breast cancer and in unaffected individuals. We also analyzed the proportion of estrogen receptor (ER)-positive (ER+) tumors in unselected breast cancer patients with gBRCA. Design: We performed a meta-analysis of studies of unselected breast cancer that analyzed the relative contribution of gBRCA1 versus gBRCA2 among unselected breast cancer cases in gBRCA carriers. We then performed a meta-analysis of gBRCA carriage in unaffected individuals from genome-wide population studies, the gnomAD databank, and case–control studies. Results: The BRCA2 gene was involved in 54% of breast cancer cases in unselected patients with gBRCA (n = 108,699) and 60% of unaffected individuals (n = 238,973) as compared with 38% of the largest gBRCA family cohort (n = 29,700). The meta-analysis showed that 1.66% (95% CI 1.08–2.54) and 1.71% (95% CI 1.33–2.2) of unselected breast cancer patients carried gBRCA1 and gBRCA2, respectively. In a population of unaffected individuals, the frequency of heterozygosity for gBRCA1 and gBRCA2 was estimated at 1/434 and 1/288, respectively. Nearly 0.5% of unaffected individuals in the studied populations carried a gBRCA. Carriage of a gBRCA was 2.5% for patients with ER+ tumors (95% CI 1.5–4.1) and 5.7% (95% CI 5.1–6.2) for those with ER- tumors. Overall, 58% of breast tumors occurring in women carrying a gBRCA were ER+ (n = 86,870). Conclusions: This meta-analysis showed that gBRCA2 carriage is predominant in unselected breast cancer patients and unaffected individuals. ER+ tumors among women with gBRCA-related breast cancer are predominant and have been underestimated. Because PARPi agents improve progression-free survival with ER+ gBRCA breast cancer in most clinical trials, breast cancer should be considered, regardless of ER status, for BRCA1/2 screening for therapeutic purposes.
Published: 2022

2. B3GAT3-related disorder with craniosynostosis and bone fragility due to a unique mutation

Author: Marjolaine Willems, Olivier Prodhomme, Guillaume Captier, Thomas Guignard, Anne Boland, Kevin Yauy, Ikram Taleb Arrada, Vincent Meyer, Frédéric Tran Mau-Them, Jean-François Deleuze, Patricia Blanchet, Christian Herlin, Jean-Baptiste Rivière, Mouna Barat-Houari, Elodie Sanchez, Yannis Duffourd, Christine Coubes, David Geneviève, Marie-Pascale Le Gac, Jean-Michel Faure, Centre de Référence Anomalies du Développement et Syndromes Malformatifs (CHU de Montpellier), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Plastic and Craniofacial Pediatric Surgery, Hôpital Lapeyronie [Montpellier] (CHU), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Département d'imagerie pédiatrique (CHU de Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Centre pluridisciplinaire de diagnostic prénatal (CHU de Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre pluridisciplinaire de diagnostic prénatal (CHU de Nîmes), Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Montpellier 1 - UFR de Médecine ( UM1 Médecine ), Université Montpellier 1 ( UM1 ), Université de Montpellier ( UM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Lapeyronie [Montpellier] ( CHU ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Arnaud de Villeneuve, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Centre Hospitalier Régional Universitaire de Nîmes ( CHRU Nîmes ), Centre National de Génotypage ( CNG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques, Université Montpellier 1 ( UM1 ) -IFR3-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Génétique des maladies multifactorielles ( GMM ), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Université de Montpellier (UM)-Université Montpellier 1 (UM1), Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier], Département Pédiatrie [CHRU Montpellier], Pôle Femme Mère Enfant [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes)
Subjects: 0301 basic medicine, Pediatrics, medicine.medical_specialty, Antley-Bixler syndrome, Antley–Bixler syndrome, Connective tissue, Bone and Bones, Ultrasonography, Prenatal, Craniosynostosis, Diagnosis, Differential, Craniosynostoses, 03 medical and health sciences, B3GAT3, medicine, Humans, Genetic Predisposition to Disease, Joint Contracture, Glucuronosyltransferase, [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics, Foot deformity, Genetic Association Studies, Genetics (clinical), Whole Genome Sequencing, Shprintzen-Goldberg syndrome, business.industry, Skull, Shprintzen–Goldberg syndrome, Sequence Analysis, DNA, Syndrome, medicine.disease, 3. Good health, Phenotype, 030104 developmental biology, medicine.anatomical_structure, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation, Mutation (genetic algorithm), business
Abstract: International audience; PurposeBased on prenatal suspicion of the combination of radioulnar or radiohumeral synostosis and a peculiar shape of the skull suggestive of craniosynostosis, we report on six patients from four unrelated consanguineous families in whom Antley-Bixler syndrome was suspected during the prenatal period without mutation in genes known to be associated with the syndrome.MethodsMolecular diagnosis involved whole-exome and gene-panel sequencing.Results:All sequenced patients showed a unique homozygous mutation of c.667G>A, p.Gly223Ser (NM_012200) in the beta-1,3-glucuronyltransferase 3 (B3GAT3) gene known to be involved in linkeropathy syndrome. Linkeropathies correspond to a recently identified group of heterogeneous genetic syndromes along a spectrum of skeletal and connective tissue disorders. These patients featured mainly craniosynostosis, midface hypoplasia, bilateral radioulnar synostosis, multiple neonatal fractures, dislocated joints, joint contracture, long fingers, foot deformity, and cardiovascular abnormalities. All died before 1 year of age.ConclusionWe identified a novel B3GAT3-related disorder with craniosynostosis and bone fragility, due to a unique homozygous mutation in B3GAT3. This syndrome should be considered in the prenatal period in light of the severe outcome and as an alternative diagnosis to Antley-Bixler or Shprintzen-Goldberg syndrome.
Published: 2018

3. Prevalence of and Risk Factors for Extrapyramidal Side Effects of Antipsychotics

Author: Misdrahi, David, Tessier, Arnaud, Daubigney, Antoine, Meissner, Wassilios, Schurhoff, Franck, Boyer, Laurent, Godin, Ophélia, Bulzacka, Ewa, Aouizerate, Bruno, Andrianarisoa, Meja, Berna, Fabrice, Capdevielle, Delphine, Chereau-Boudet, Isabelle, D’amato, Thierry, Dubertret, Caroline, Dubreucq, Julien, Faget-Agius, Catherine, Lançon, Christophe, Mallet, Jasmina, Passerieux, Christine, Rey, Romain, Schandrin, Aurélie, Urbach, Mathieu, Vidailhet, Pierre, Llorca, Pierre, Fond, Guillaume, Fondation FondaMental [Créteil], Université Panthéon-Sorbonne - UFR Histoire (UP1 UFR09), Université Panthéon-Sorbonne (UP1), Université de Bordeaux (UB), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Hôpital Charles Perrens, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centres d'addictologies - Région Centre, CHU Clermont-Ferrand, Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes (UGA), Laboratoire de neuropsychologie cognitive et prise en charge des troubles de la communication schizophrénique, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Hôpital Mignot, Neuropsychiatrie : recherche épidémiologique et clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital Civil de Strasbourg, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Université Paris 1 Panthéon-Sorbonne - UFR Histoire (UP1 UFR09), Université Paris 1 Panthéon-Sorbonne (UP1), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire de recherches cliniques et en santé publique sur les handicaps psychique, cognitif et moteur (HANDIReSP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie (NCPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg-Université de Strasbourg (UNISTRA), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université Paris 1 Panthéon-Sorbonne - École d'Histoire (UP1 UFR09), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre hospitalier Charles Perrens [Bordeaux], Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg
Subjects: antipsychotics, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, neurology, [SCCO.NEUR]Cognitive science/Neuroscience, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, movement disorders, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, ComputingMilieux_MISCELLANEOUS, schizophrenia/schizoaffective disorders
Abstract: International audience; Background: Extrapyramidal side effects (EPS) have been identified as a complication of antipsychotic treatment. Previous meta-analyses have investigated EPS prevalence and risk factors in randomized clinical trials with highly selected patients, but studies in real-world schizophrenia are missing. Objective: To examine the prevalence and clinical correlates associated with EPS in a nonselected national multicenter sample of stabilized patients with schizophrenia. Methods: Between 2010 and 2016, patients suffering from schizophrenia (DSM-IV-TR criteria) were recruited through the FondaMental Academic Centers of Expertise for Schizophrenia (FACE-SZ) network and data were collected during a comprehensive 1-day-long standardized evaluation. The Simpson-Angus Scale and the Abnormal Involuntary Movement Scale were used to assess drug-induced parkinsonism (DIP) and tardive dyskinesia, respectively. Results: The overall prevalence of DIP and tardive dyskinesia was 13.2% and 8.3%, respectively, in this community-dwelling sample of 674 patients. DIP was associated with negative symptoms (Positive and Negative Syndrome Scale [PANSS] subscore) (adjusted odds ratio [aOR] = 1.102, P Conclusions: Our results indicate the high prevalence of EPS in a nonselected community-dwelling clinically stable sample of outpatients with schizophrenia. In the monitoring of antipsychotic treatment, EPS should be systematically evaluated, especially when negative symptoms and disorganization or cognitive alteration are present. Monotherapy with a second-generation antipsychotic should be preferentially initiated for patients with these side effects.
Published: 2019

4. Validation and refinement of the clinical staging model in a French cohort of outpatient with schizophrenia (FACE-SZ)

Author: Ophelia Godin, Guillaume Fond, Ewa Bulzacka, Frank Schürhoff, Laurent Boyer, Andre Myrtille, Meja Andrianarisoa, Bruno Aouizerate, Fabrice Berna, Delphine Capdevielle, Isabelle Chereau, Jean-Michel Dorey, Caroline Dubertret, Julien Dubreucq, Catherine Faget, Christophe Lancon, Sylvain Leignier, Jasmina Mallet, David Misdrahi, Christine Passerieux, Romain Rey, Paul Roux, Pierre Vidailhet, Dominique Costagliola, Marion Leboyer, Pierre-Michel Llorca, Méja Andrianarisoa, Olivier Blanc, Lore Brunel, Isabelle Chéreau-Boudet, Gabrielle Chesnoy-Servanin, Jean-Marie Danion, Thierry D'Amato, Arnaud Deloge, Claire Delorme, Hélène Denizot, Cécile Fluttaz, Sandrine Fonteneau, Franck Gabayet, Elisabeth Giraud-Baro, Marie-Christine Hardy-Baylé, Delphine Lacelle, Christophe Lançon, Hakim Laouamri, Tifenn Le Gloahec, Yann Le Strat, Emeline Metairie, Pauline Peri, Sylvie Pires, Céline Portalier, Céline Roman, Mathilde Sebilleau, Aurélie Schandrin, Priscille Schneider, Franck Schurhoff, Arnaud Tessier, Anne-Marie Tronche, Mathieu Urbach, Florence Vaillant, Aurélie Vehier, Estelle Vilà, Hanan Yazbek, Anna Zinetti-Bertschy, CCSD, Accord Elsevier, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Fondation FondaMental [Créteil], Sorbonne Université (SU), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Hôpital de la Colombière, Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre hospitalier Charles Perrens [Bordeaux], Nutrition et Neurobiologie intégrée (NutriNeuro), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1 (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie (NCPS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), CHU Clermont-Ferrand, Université d'Auvergne - Clermont-Ferrand I (UdA), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Référent de Réhabilitation Psychosociale [CH Alpes Isère], Centre Hospitalier Alpes Isère, Assistance Publique - Hôpitaux de Marseille (APHM), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier de Versailles André Mignot (CHV), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), FACE-SZ (FondaMental Academic Centers of Expertise for Schizophrenia) group: Méja Andrianarisoa 16 , Bruno Aouizerate 17 , Fabrice Berna 18 , Olivier Blanc 19 , Lore Brunel 16 , Ewa Bulzacka 16 , Delphine Capdevielle 20 , Isabelle Chéreau-Boudet 19 , Gabrielle Chesnoy-Servanin 21 , Jean-Marie Danion 18 , Thierry D'Amato 21 , Arnaud Deloge 22 , Claire Delorme 23 , Hélène Denizot 19 , Jean-Michel Dorey 21 , Caroline Dubertret 24 , Julien Dubreucq 23 , Catherine Faget 25 , Cécile Fluttaz 23 , Guillaume Fond 16 , Sandrine Fonteneau 26 , Franck Gabayet 23 , Elisabeth Giraud-Baro 23 , Marie-Christine Hardy-Baylé 26 , Delphine Lacelle 19 , Christophe Lançon 25 , Hakim Laouamri 27 , Marion Leboyer 16 , Tifenn Le Gloahec 16 , Yann Le Strat 24 , Pierre-Michel Llorca 19 , Jasmina Mallet 28 , Emeline Metairie 25 , David Misdrahi 22 , Christine Passerieux 26 , Pauline Peri 25 , Sylvie Pires 19 , Céline Portalier 24 , Romain Rey 21 , Céline Roman 23 , Mathilde Sebilleau 26 , Aurélie Schandrin 20 , Priscille Schneider 18 , Franck Schurhoff 16 , Arnaud Tessier 22 , Anne-Marie Tronche 19 , Mathieu Urbach 26 , Florence Vaillant 25 , Aurélie Vehier 21 , Pierre Vidailhet 18 , Estelle Vilà 22 , Hanan Yazbek 20 , Anna Zinetti-Bertschy 18, Centre de Psychiatrie et Neurosciences (U894), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes (UGA), Laboratoire de sciences cognitives et psycholinguistique (LSCP), Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS), Hôpital Charles Perrens, Centres d'addictologies - Région Centre, Physiopathologie clinique et expérimentale de la schizophrénie, Université Louis Pasteur - Strasbourg I-IFR37-Institut National de la Santé et de la Recherche Médicale (INSERM), Vulnérabilité à la schizophrénie : des bases neurobiologiques à la thérapeutique, Centre Hospitalier le Vinatier [Bron]-IFR19-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier de Bayeux, Psychiatrie, Centre Hospitalier le Vinatier [Bron], Centre Hospitalier de Saint-Egrève (CH Ste-Egrève), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Département des maladies infectieuses, Institut de Veille Sanitaire (INVS), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne (UCA), Laboratoire de neuropsychologie cognitive et prise en charge des troubles de la communication schizophrénique, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Hôpital Mignot, Université Paris Diderot - Paris 7 (UPD7), Service de pédiatrie multidisciplinaire [Hôpital de la Timone Enfants - APHM], Hôpital de la Timone [CHU - APHM] (TIMONE), Neuropsychiatrie : recherche épidémiologique et clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Université Panthéon-Sorbonne - UFR Histoire (UP1 UFR09), Université Panthéon-Sorbonne (UP1), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neuropsychologie Cognitive et Physiopathologie de la Schizophrénie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital Civil de Strasbourg, Dynamique des capacités humaines et des conduites de santé (EPSYLON), Université Montpellier 1 (UM1)-Université Paul-Valéry - Montpellier 3 (UM3)-Université de Montpellier (UM), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Civil de Strasbourg-Université de Strasbourg (UNISTRA)
Subjects: Adult, Male, Pediatrics, medicine.medical_specialty, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Comorbidity, Neuropsychological Tests, Medication Adherence, Machine Learning, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Cognition, Outpatients, medicine, Humans, Cognitive Dysfunction, Stage (cooking), Medical prescription, Major depressive episode, Biological Psychiatry, Pharmacology, Depressive Disorder, Major, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Neuropsychology, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, medicine.disease, Prognosis, 030227 psychiatry, 3. Good health, Mood, Clinical staging, Schizophrenia, Cognitive remediation therapy, Cohort, Polypharmacy, Female, Schizophrenic Psychology, France, medicine.symptom, business, [SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Algorithms
Abstract: International audience; Objective: Existing staging models have not been fully validated. Thus, after classifying patients with schizophrenia according to the staging model proposed by McGorry et al. (2010), we explored the validity of this staging model and its stability after one-year of follow-up.Method: Using unsupervised machine-learning algorithm, we classified 770 outpatients into 5 clinical stages, the highest being the most severe. Analyses of (co)variance were performed to compare each stage in regard to socio-demographics factors, clinical characteristics, co-morbidities, ongoing treatment and neuropsychological profiles.Results: The precision of clinical staging can be improved by sub-dividing intermediate stages (II and III). Clinical validators of class IV include the presence of concomitant major depressive episode (42.6% in stage IV versus 3.4% in stage IIa), more severe cognitive profile, lower adherence to medication and prescription of >3 psychotropic medications. Follow-up at one-year showed good stability of each stage.Conclusion: Clinical staging in schizophrenia could be improved by adding clinical elements such as mood symptoms and cognition to severity, relapses and global functioning. In terms of therapeutic strategies, attention needs to be paid on the factors associated with the more stages of schizophrenia such as treatment of comorbid depression, reduction of the number of concomitant psychotropic medications, improvement of treatment adherence, and prescription of cognitive remediation.
Published: 2018

5. Health professionals prepared for the future. Why Social Sciences and Humanities teaching in Medical Faculties matter

Author: Roberto Poma, Maria Teixeira, Anne Rasmussen, Gilles Moutot, Guillaume Grandazzi, Nicolas Lechopier, Céline Lefève, Sciences et Société, Historicité, Éducation et Pratiques (EA S2HEP), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Université Paris Diderot - Paris 7 (UPD7), Sciences, Philosophie, Histoire (SPHERE (UMR_7219)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Espace régional de réflexion éthique de Normandie (EREN), Université de Caen Normandie (UNICAEN), Normandie Université (NU), Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg (UNISTRA), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Faculté de Médecine Lyon-Est, parent, Sciences, Philosophie, Histoire (SPHERE UMR 7219), Département de Philosophie - Université Paris 12 Créteil, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Institut National de la Santé et de la Recherche Médicale (INSERM), and AP-HP Hôpital universitaire Robert-Debré [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Social Sciences and Humanities, curriculum development, Curriculum planning, [SHS.EDU]Humanities and Social Sciences/Education, lcsh:Medicine, Curriculum Planning, [SHS]Humanities and Social Sciences, 03 medical and health sciences, Curriculum Planning, Professionalism/Ethics, Behavioural and Social Sciences, medical education, 0302 clinical medicine, MESH: Formation académique,Rôle du médecin, Personnels médicaux, Études médicales, Behavioural and Social Sciences, Professionalism/Ethics, 030212 general & internal medicine, Sociology, critical thinking, ComputingMilieux_MISCELLANEOUS, Medical education, lcsh:LC8-6691, Health professionals, lcsh:Special aspects of education, 4. Education, Social roles, lcsh:R, [SHS.PHIL]Humanities and Social Sciences/Philosophy, reflexivity, 030206 dentistry, 3. Good health, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, medical education, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: This article was migrated. The article was marked as recommended. A public debate took place place in France in 2018 concerning ethical and social issues of biomedicine and life science and technologies. As faculty members of French medical schools and scholars in Social Sciences and Humanities, we contributed to introduce the central theme of health professionals education. What roles and what place should we assign to the social sciences and Humanities in preparing health professionals who will work in a transforming and largely unpredictable context? In this paper, we list 4 crucial issues for the present and the future of healthcare profession, concerning changes of medical roles; new biomedical concepts and innovations; long term consequences on health social contract; ethical issues in health care daily life settings. Then, we list 4 kinds of resources that are brought to students by Social Sciences and Humanities courses. They concern the connection to patients's experiences the social and cultural construction of these experiences; the social responsibility of medical doctors; and the independence of their professional judgments. This is a plea for the development of reflexivity and critical thought backed up by well identified, well integrated and sufficiently developed Social Sciences and Humanities courses in French medical schools.
Published: 2018

6. Automated and simplified identification of normal and abnormal plasma cells in Multiple Myeloma by flow cytometry

Author: Alaterre, Elina, Raimbault, Sébastien, Garcia, Jean-Michel, Rème, Thierry, Requirand, Guilhem, Klein, Bernard, Moreaux, Jerome, HORIBA Medical, Montpellier, France, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), HORIBA Medical Montpellier France, Cellules souches normales et cancéreuses, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Department of Biological Hematology, CHU Montpellier, Montpellier, France, Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), and Université de Montpellier (UM)
Subjects: [SDV.GEN]Life Sciences [q-bio]/Genetics, Neoplasm, Residual, hematology, [SDV]Life Sciences [q-bio], Plasma Cells, Reproducibility of Results, Flow Cytometry, Antibodies, Cohort Studies, Antigens, CD, Bone Marrow, multiparameter analysis, cancer, Humans, prognosis, Multiple Myeloma, health care economics and organizations
Abstract: Multiple myeloma (MM) is an incurable disease characterized by clonal plasma cell (PC) proliferation within the bone marrow (BM). Next-generation flow cytometry has become the reference tool to follow minimal residual disease (MRD). We developed a new simpler and cheaper flow cytometry method to analyze bone marrow samples in patients with MM.To identify and characterize abnormal PCs, we designed a simple panel composed of anti-CD38, antikappa, and antilambda light chain antibodies, combined with two antibody pools with the same fluorophore (anti-CD19 and anti-CD27 for the negative pool and anti-CD56, anti-CD117, and anti-CD200 antibodies for the positive pool). We also developed dedicated software for the automated identification of malignant PCs and MRD assessment. We then compared PC identification with our simple antibody panel and with the larger antibody panel routinely used at Montpellier University Hospital Center in 52 patients with MM (M-CHU cohort).Results for total PC detection (rOur simple and automated strategy for MRD assessment in MM could help increasing reproducibility and productivity without compromising sensitivity and specificity, while decreasing the test cost. © 2017 International Clinical Cytometry Society.
Published: 2017

7. Characterization of human FCRL4-positive B cells

Author: Jourdan, Michel, Robert, Nicolas, Cren, Maïlys, Thibaut, Coraline, Duperray, Christophe, Kassambara, Alboukadel, Cogné, Michel, Tarte, Karin, Klein, Bernard, Moreaux, Jérôme, Jonchère, Laurent, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules souches normales et cancéreuses, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), MRI-Cytométrie-IRB [CHU Montpellier] (Montpellier RIO Imaging), Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Microenvironnement et cancer (MiCa), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), 2012-109/087437 and PLBIO15-256, Institut National Du Cancer, R14026FF, Conseil Régional Languedoc-Roussillon, 201400047510, Fondation de France, MM&TT, ITMO Cancer, SIRIC Montpellier, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)
Subjects: B Cells, Physiology, Gene Expression, lcsh:Medicine, HIV Infections, Receptors, Fc, Immune Receptors, Biochemistry, White Blood Cells, Spectrum Analysis Techniques, Animal Cells, Immune Physiology, Medicine and Health Sciences, Cell Cycle and Cell Division, B Cell Receptors, lcsh:Science, Cells, Cultured, Innate Immune System, B-Lymphocytes, Immune System Proteins, Cell Differentiation, Flow Cytometry, Tonsils, Phenotype, Spectrophotometry, Cell Processes, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Cytophotometry, Cellular Types, Anatomy, Research Article, Signal Transduction, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immune Cells, Immunology, Down-Regulation, [SDV.CAN]Life Sciences [q-bio]/Cancer, Research and Analysis Methods, Immunophenotyping, Throat, [SDV.CAN] Life Sciences [q-bio]/Cancer, Genetics, Humans, Antibody-Producing Cells, Cell Proliferation, Blood Cells, lcsh:R, Biology and Life Sciences, Proteins, Cell Biology, Molecular Development, Antigens, CD20, ADP-ribosyl Cyclase 1, Immune System, lcsh:Q, Transcriptome, Neck, Developmental Biology
Abstract: International audience; FCRL4 is an immunoregulatory receptor that belongs to the Fc receptor-like (FCRL) family. In healthy individuals, FCRL4 is specifically expressed by memory B cells (MBCs) localized in sub-epithelial regions of lymphoid tissues. Expansion of FCRL4+ B cells has been observed in blood and other tissues in various infectious and autoimmune disorders. Currently, the mechanisms involved in pathological FCRL4+ B cell generation are actively studied, but they remain elusive. As in vivo FCRL4+ cells are difficult to access and to isolate, here we developed a culture system to generate in vitro FCRL4+ B cells from purified MBCs upon stimulation with soluble CD40 ligand and/or CpG DNA to mimic T-cell dependent and/or T-cell independent activation, respectively. After 4 days of stimulation, FCRL4+ B cells represented 17% of all generated cells. Transcriptomic and phenotypic analyses of in vitro generated FCRL4+ cells demonstrated that they were closely related to FCRL4+ tonsillar MBCs. They strongly expressed inhibitory receptor genes, as observed in exhausted FCRL4+ MBCs from blood samples of HIV-infected individuals with high viremia. In agreement, cell cycle genes were significantly downregulated and the number of cell divisions was two-fold lower in in vitro generated FCRL4+ than FCRL4- cells. Finally, due to their reduced proliferation and differentiation potential, FCRL4+ cells were less prone to differentiate into plasma cells, differently from FCRL4- cells. Our in vitro model could be of major interest for studying the biology of normal and pathological FCRL4+ cells.
Published: 2017

8. Is there a link between biological parents' insight into their offspring's schizophrenia and their cognitive functioning, expressed emotion and knowledge about disorder?

Author: Delphine Capdevielle, Alexandra Macgregor, Stéphane Raffard, Joanna Norton, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Dynamique des capacités humaines et des conduites de santé (EPSYLON), Université de Montpellier (UM)-Université Paul-Valéry - Montpellier 3 (UPVM)-Université Montpellier 1 (UM1), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Neuropsychiatrie : recherche épidémiologique et clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), and Université Montpellier 1 (UM1)-Université Paul-Valéry - Montpellier 3 (UM3)-Université de Montpellier (UM)
Subjects: Male, Adult, Parents, Health Knowledge, Attitudes, Practice, lcsh:RC435-571, Offspring, [SDV]Life Sciences [q-bio], Disease, Developmental psychology, 03 medical and health sciences, Young Adult, Executive Function, 0302 clinical medicine, Cognition, Memory, lcsh:Psychiatry, medicine, Expressed emotion, Humans, Cognitive skill, Aged, Practice, Working memory, 4. Education, Health Knowledge, Middle Aged, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Clinical Psychology, Expressed Emotion, Memory, Short-Term, Short-Term, Schizophrenia, Attitudes, Educational Status, Female, Psychology, Attribution, 030217 neurology & neurosurgery
Abstract: Background Recent studies suggest that parents' awareness of their offspring's schizophrenia could influence their offspring's insight. Low patient insight is linked to impairment of specific cognitive abilities, and biological parents of schizophrenia patients have impaired capacities in these same domains. However, little is known about what specific socio-demographic, affective or cognitive factors may influence biological parents' awareness of their offspring's disease. Method Data were drawn from 41 patient–parent dyads. Insight was assessed with a modified version of Amador's Scale to assess Unawareness of Mental Disorders, exploring dimensions of parents' awareness and attribution of their offspring's illness and symptoms. Results Higher educational levels, better working memory and executive functioning of parents were associated with better attribution of their offspring's symptoms to schizophrenia. Conclusions Parents' insight into their offspring's schizophrenia is associated with cognitive abilities. This must be taken into account when developing family interventions.
Published: 2017

9. Prevalence, risk factors for infection and subtype distribution of the intestinal parasite Blastocystis sp. from a large-scale multi-center study in France

Author: El Safadi, Dima, Cian, Amandine, Nourrisson, Céline, Pereira, Bruno, Morelle, Christelle, Bastien, Patrick, Bellanger, Anne-Pauline, Botterel, Françoise, Candolfi, Ermanno, Desoubeaux, Guillaume, Lachaud, Laurence, Morio, Florent, Pomares, Christelle, Rabodonirina, Meja, Wawrzyniak, Ivan, Delbac, Frédéric, Gantois, Nausicaa, Certad, Gabriela, Delhaes, Laurence, Poirier, Philippe, Viscogliosi, Eric, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut de Parasitologie et de Pathologie Tropicale (IPPTS), Université de Strasbourg (UNISTRA), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cibles et Médicaments des Infections et de l'Immunité (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Hospices Civils de Lyon (HCL), This work was supported by grants from the Programme Orientations Stratégiques from the University of Lille 2, the Fonds Hospitalier d’Aide à l’Emergence from the CHRU of Lille, the Centre National de la Recherche Scientifique and the Institut Pasteur of Lille. DES was supported by a PhD fellowship from the Conseil National de la Recherche Scientifique and the AZM & Saade Association and AC by a PhD fellowship from the University of Lille 2 and the Institut Pasteur of Lille., Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre d'Etude des Pathologies Respiratoires (CEPR), UMR 1100. Equipe 3 'Aérosolthérapie et biothérapies à visée respiratoire' (CEPR. Equipe 3), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Gabriel Montpied (CHU), Institut de Recherche pour le Développement (IRD [France-Sud])-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Centre d'Etude des Pathologies Respiratoires (CEPR), UMR 1100. Equipe 3 (CEPR. Equipe 3), and COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)
Subjects: Adult, Male, Blastocystis sp, Adolescent, Intestinal parasite, Blastocystis Infections, Subtyping, Feces, Young Adult, Risk Factors, Prevalence, Animals, Humans, Child, Aged, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Aged, 80 and over, Infant, Middle Aged, Infectious Diseases, PCR, Cross-Sectional Studies, Molecular epidemiology, Child, Preschool, Blastocystis, Risk factors for infection, Female, France, Research Article
Abstract: Background Blastocystis sp. is the most common intestinal parasite of humans. Despite its potential public health impact, epidemiological data regarding the prevalence and molecular subtype distribution of Blastocystis sp. in Europe are rarely reported. Therefore, the first multi-center epidemiological survey performed in Europe was conducted in France to diagnose and subtype Blastocystis sp. and to identify risk factors for infection. Methods Stool samples from 788 patients were collected either in summer or winter in 11 hospitals throughout France together with patient data. All stool samples were tested for the presence of Blastocystis sp. by quantitative PCR targeting the SSU rDNA gene. Positive samples were sequenced to determine the distribution of the subtypes in our cohort. Statistical analyses were performed to identify potential risk factors for infection. Results Using quantitative PCR, the overall prevalence of Blastocystis sp. was shown to reach 18.1 %. The prevalence was significantly higher in summer (23.2 %) than in winter (13.7 %). Travellers or subjects infected with other enteric parasites were significantly more infected by Blastocystis sp. than non-travellers or subjects free of other enteric parasites, respectively. Different age-related epidemiological patterns were also highlighted from our data. The prevalence of Blastocystis sp. was not significantly higher in patients with digestive symptoms or diagnosed with chronic bowel diseases. Among symptomatic patients, Blastocystis sp. infection was significantly associated with abdominal pain. Gender, socioeconomic status, and immune status were not identified as potential risk factors associated with infection. Among a total of 141 subtyped isolates, subtype 3 was predominant (43.3 %), followed by subtype 1 and subtype 4 (20 %), subtype 2 (12.8 %), subtype 6 and subtype 7 (2.1 %). No association between ST and clinical symptoms was statistically evidenced. Conclusions A high prevalence of Blastocystis sp. infection was found in our French patient population. Seasonal impact on the prevalence of Blastocystis sp. was highlighted and recent travels and age were identified as main risk factors for infection. Most cases were caused by subtypes 1 to 4, with a predominance of subtype 3. Large variations in both prevalence and ST distribution between hospitals were also observed, suggesting distinct reservoirs and transmission sources of the parasite. Electronic supplementary material The online version of this article (doi:10.1186/s12879-016-1776-8) contains supplementary material, which is available to authorized users.
Published: 2016

10. Encéphalite à parvovirus B19 de l’enfant

Author: G. Rondoin, Pierre Meyer, Eric Jeziorski, François Rivier, Michel Rodière, Vincent Foulongne, L. Bott-Gilton, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Pathogénèse et contrôle des infections chroniques (PCCI), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )
Subjects: Gynecology, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, 0303 health sciences, medicine.medical_specialty, biology, 030306 microbiology, Parvovirus, business.industry, Treatment outcome, medicine.disease, biology.organism_classification, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Pediatrics, Perinatology and Child Health, medicine, 030212 general & internal medicine, business, Encephalitis
Abstract: International audience; Introduction: Human parvovirus B19 (PVB19) causes erythema infectiosum or 5th disease in childhood, which mainly affects children between 3 and 15 years of age. PVB19 infections have also been described in association with a variety of neurologic manifestations including encephalitis.Case report: This 3-year 8-month-old boy developed febrile encephalitis (mental status change with seizures and left limb hypertonia) associated with a rash. The electroencephalographs revealed focal slowing with some spikes in front of the left centro-temporo-occipital areas ; bacteriological and biochemical cerebrospinal fluid (CSF) analysis were normal, brain radiologic studies (tomography and magnetic resonance imaging) were normal. The diagnosis of encephalitis associated with PVB19 primo infection was based on viral DNA detection in the serum and CSF using PCR and on the specific immunoglobulin M (without immunoglobulin G) detection in the serum.Discussion: In France, encephalitis etiology is unknown in 48% of the cases. PVB19 accounts for 4.3% of undiagnosed meningoencephalitis in children. Although there is no specific sign, seizures and rash are reported in about one-half and one-quarter of cases, respectively.Conclusion: Even if PVB19 research is not cited in the French or American infectious disease society recommendations on the diagnosis and management of infectious encephalitis, this virus may be responsible, especially in cases of child febrile rash. Therefore, PVB19 research seems reasonable if the clinical presentation is concordant in children due to its diagnostic simplicity and efficacy.; Introduction: Le parvovirus B19 (PVB19) est l’agent responsable du mégalérythème épidémique ou 5e maladie, qui touche essentiellement l’enfant entre 3 et 15 ans. Même si elles sont rares, des manifestations neurologiques ont été décrites.Cas clinique: Nous rapportons l’observation d’un patient de 3 ans et 8 mois qui avait présenté un tableau clinique d’encéphalite aiguë (troubles de la vigilance, hypertonie du membre supérieur droit, convulsions) dans un contexte d’éruption fébrile. L’électroencéphalogramme objectivait un ralentissement en regard des régions centro-temporo-occipitales gauches ; l’analyse cytobactériologique du liquide céphalorachidien (LCR) et l’imagerie cérébrale étaient normales. La sérologie pour le PVB19 était positive en immunoglobulines (Ig) M sans IgG en phase aiguë et les réactions de polymérisation en chaîne (PCR) spécifiques positives dans le sérum et le LCR avaient fait porter le diagnostic d’encéphalite à PVB19.Discussion: En France, 48 % des encéphalites sont idiopathiques (Mailles et al., 2009). Chez l’enfant, le PVB19 serait responsable de 4,3 % de ces encéphalites sans agent causal identifié (Barah et al., 2001). Il n’y a pas de signe spécifique, néanmoins des convulsions et un rash peuvent être trouvés respectivement dans la moitié et un quart des cas. (Douvoyiannis et al., 2009).Conclusion: Même si la recherche du PVB19 ne figure pas dans les recommandations de prise en charge diagnostique des encéphalites de la Société de pathologie infectieuse de langue française et de la Société nord-américaine de pathologie infectieuse, ce virus peut en être la cause notamment chez le grand enfant qui présente une éruption fébrile. Ainsi, en cas de contexte évocateur, il nous semble raisonnable d’effectuer la recherche du PVB19, agent pathogène « banal » de l’enfant, dont le diagnostic est simple et présente un bon rendement.
Published: 2011

11. Dissecting the First Transcriptional Divergence During Human Embryonic Development

Author: John De Vos, Qiang Bai, Said Assou, Sabine Gerbal-Chaloin, Samir Hamamah, Fabienne Becker, Jean-Marie Ramirez, C. Monzo, Delphine Haouzi, Cellules souches normales et cancéreuses, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Institut de recherche en biothérapie (IRB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Service de biologie de la reproduction, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve-UAM : AMP/DPI, Unité de thérapie cellulaire, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Association Française contre les Myopathies (AFM), Région Languedoc-Roussillon: Chercheur d'Avenir 09-13198-01, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Frei, Monique, Service de gynécologie-obstétrique et médecine de la reproduction, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: Cancer Research, Cellular differentiation, Embryonic Development, Biology, Article, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Antigens, Neoplasm, Ectoderm, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Humans, Human embryogenesis, Inner cell mass, Gene Regulatory Networks, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, DNA (Cytosine-5-)-Methyltransferases, Blastocyst, Induced pluripotent stem cell, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, Cells, Cultured, transcription factor, reproductive and urinary physiology, Oligonucleotide Array Sequence Analysis, 030304 developmental biology, 0303 health sciences, urogenital system, Gene Expression Profiling, Gene Expression Regulation, Developmental, Trophoblast, Cell Differentiation, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, Cell Biology, Molecular biology, Trophoblasts, medicine.anatomical_structure, 030220 oncology & carcinogenesis, embryonic structures, transcriptional network, pluripotent stem cells, trophectoderm, Stem cell, transcriptome, Developmental Biology
Abstract: The trophoblast cell lineage is specified early at the blastocyst stage, leading to the emergence of the trophectoderm and the pluripotent cells of the inner cell mass. Using a double mRNA amplification technique and a comparison with transcriptome data on pluripotent stem cells, placenta, germinal and adult tissues, we report here some essential molecular features of the human mural trophectoderm. In addition to genes known for their role in placenta (CGA, PGF, ALPPL2 and ABCG2), human trophectoderm also strongly expressed Laminins, such as LAMA1, and the GAGE Cancer/Testis genes. The very high level of ABCG2 expression in trophectoderm, 7.9-fold higher than in placenta, suggests a major role of this gene in shielding the very early embryo from xenobiotics. Several genes, including CCKBR and DNMT3L, were specifically up-regulated only in trophectoderm, indicating that the trophoblast cell lineage shares with the germinal lineage a transient burst of DNMT3L expression. A trophectoderm core transcriptional regulatory circuitry formed by 13 tightly interconnected transcription factors (CEBPA, GATA2, GATA3, GCM1, KLF5, MAFK, MSX2, MXD1, PPARD, PPARG, PPP1R13L, TFAP2C and TP63), was found to be induced in trophectoderm and maintained in placenta. The induction of this network could be recapitulated in an in vitro trophoblast differentiation model. Electronic supplementary material The online version of this article (doi:10.1007/s12015-011-9301-3) contains supplementary material, which is available to authorized users.
Published: 2011

12. Targeting NF-κB pathway with an IKK2 inhibitor induces inhibition of multiple myeloma cell growth

Author: Karène Mahtouk, Thierry Rème, Angela Romanelli, Dirk Hose, Michel Jourdan, Jean-François Rossi, Bernard Klein, Marion Baudard, Nicolas Robert, Jérôme Moreaux, Michel Dreano, Matthieu Abouladze, John De Vos, Hartmut Goldschmidt, Institut de recherche en biothérapie (IRB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Department of Internal Medicine V, Universität Heidelberg [Heidelberg], Department of Hematology and Clinical Oncology, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Serono Research Institute, Serono, Serono International SA (SERONO INTERNATIONAL SA), Serono International SA, and Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: Cell Survival, Antineoplastic Agents, Biology, Article, Bortezomib, cell cycle, 03 medical and health sciences, Paracrine signalling, chemistry.chemical_compound, 0302 clinical medicine, Multiple myeloma, Cell Line, Tumor, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Enzyme Inhibitors, Antineoplastic Agents, Alkylating, Melphalan, 030304 developmental biology, 0303 health sciences, Cell growth, NF-kappa B, apoptosis, IKK2 inhibitor, Hematology, Cell cycle, Boronic Acids, I-kappa B Kinase, Haematopoiesis, Pyrimidines, chemistry, Cell culture, Pyrazines, 030220 oncology & carcinogenesis, Cancer research, Stem cell, Growth inhibition, Cell Division, medicine.drug
Abstract: The pathophysiologic basis for multiple myeloma (MM) has been attributed to the dysregulation of various paracrine or autocrine growth factor loops and to perturbations in several signal transduction pathways including IkappaB kinase/nuclear factor-kappaB (IKK/NF-kappaB). The present study aimed at investigating the effect of a pharmaceutical IKK2 inhibitor, the anilinopyrimidine derivative AS602868, on the in vitro growth of 14 human MM cell lines (HMCL) and primary cells from 13 patients. AS602868 induced a clear dose-dependent inhibition of MM cell growth on both HMCL and primary MM cells, which was the result of a simultaneous induction of apoptosis and inhibition of the cell cycle progression. Combination of AS602868 with suboptimal doses of melphalan or Velcade showed an additive effect in growth inhibition of HMCL. AS602868 also induced apoptosis of primary myeloma cells. Importantly, AS602868 did not alter the survival of other bone marrow mononuclear cells (CD138(-)) co-cultured with primary MM (CD138(+)) cells, except for CD34(+) haematopoietic stem cells. The results demonstrate the important role of NF-kappaB in maintaining the survival of MM cells and suggest that a pharmacological inhibition of the NF-kappaB pathway by the IKK2 inhibitor AS602868 can efficiently kill HMCL and primary myeloma cells and therefore might represent an innovative approach for treating MM patients.
Published: 2007

13. Google Trends ® : Ready for real-time suicide prevention or just a Zeta-Jones effect? An exploratory study

Author: Lore Brunel, Guillaume Fond, Emmanuel Haffen, Alexandru Gaman, Pierre-Michel Llorca, Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Fondation FondaMental [Créteil], Département de psychiatrie [CHRU de Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Département de psychiatrie [CHU de Besançon], Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux - Clermont Auvergne (NPsy-Sydo), and CHU Clermont-Ferrand-Université Clermont Auvergne (UCA)
Subjects: Suicide Prevention, Bipolar Disorder, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Information Seeking Behavior, Population, Exploratory research, Suicide, Attempted, Commit, Risk Assessment, Suicide prevention, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Mass Media, 030212 general & internal medicine, Bipolar disorder, Media event, education, Biological Psychiatry, Depression (differential diagnoses), ComputingMilieux_MISCELLANEOUS, Depressive Disorder, Major, Internet, education.field_of_study, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Health Policy, [SCCO.NEUR]Cognitive science/Neuroscience, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, 16. Peace & justice, medicine.disease, Imitative Behavior, Semantics, 030227 psychiatry, Search Engine, Suicide, Psychiatry and Mental health, Cross-Sectional Studies, Search words, Psychology, Social psychology
Abstract: Two studies have shown that increasing the consultation of the word "suicide" in the Google search engine was associated with a subsequent increase in the prevalence of suicide attempts. The main goal of this article was to explore the trends generated by a key-word search associated with suicide, depression and bipolarity in an attempt to identify general trends (disorders epidemics in the population/"real events" vs newsworthy advertisement/"media event"). Based on previous studies, the frequency of the search words "how to suicide" and "commit suicide" were analyzed for suicide, as well as "depression" (for depressive disorders) and "bipolar disorder". Together, these analyses suggest that the search for the words "how to suicide" or "commit suicide" on the Google search engine may be a good indicator for suicide prevention policies. However, the tool is not developed enough to date to be used as a real time dynamic indicator of suicide epidemics. The frequency of the search for the word "suicide" was associated with those for "depression" but not for "bipolar disorder", but searches for psychiatric conditions seem to be influenced by media events more than by real events in the general population.
Published: 2015

14. GenomicScape: An Easy-to-Use Web Tool for Gene Expression Data Analysis. Application to Investigate the Molecular Events in the Differentiation of B Cells into Plasma Cells

Author: Kassambara, Alboukadel, Rème, Thierry, Jourdan, Michel, Fest, Thierry, Hose, Dirk, Tarte, Karin, Klein, Bernard, Jonchère, Laurent, Overcoming clinical relapse in multiple myeloma by understanding and targeting the molecular causes of drug resistance - OVER-MYR - - EC:FP7:HEALTH2012-01-01 - 2015-06-30 - 278706 - VALID, Cellules souches normales et cancéreuses, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Microenvironnement et cancer (MiCa), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Medizinische KlinikV, Universitätklinikum Heidelberg, Department of Internal Medicine V, Universität Heidelberg [Heidelberg]-Universität Heidelberg [Heidelberg]-National Center for Tumor Diseases (NCTD), Universität Heidelberg [Heidelberg], Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), This work was supported by grants from University Hospital of Montpellier (CEP-IRB), from ARC (SL220110603450, Paris France), and the European Community (FP7-OVERMYR). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., European Project: 278706,EC:FP7:HEALTH,FP7-HEALTH-2011-two-stage,OVER-MYR(2012), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Universität Heidelberg [Heidelberg] = Heidelberg University-Universität Heidelberg [Heidelberg] = Heidelberg University-National Center for Tumor Diseases (NCTD), Universität Heidelberg [Heidelberg] = Heidelberg University, Hematology, Basic (bio-) Medical Sciences, and European Project
Subjects: B-Lymphocytes, Internet, Principal Component Analysis, hematology, QH301-705.5, Gene Expression Profiling, [SDV]Life Sciences [q-bio], Plasma Cells, B-Lymphocytes/cytology, Cell Differentiation, Genomics, Genomics/methods, Plasma Cells/cytology, [SDV] Life Sciences [q-bio], Databases, Genetic, Cell Differentiation/physiology, Cluster Analysis, Data Mining, Humans, Biology (General), Software, Research Article
Abstract: DNA microarrays have considerably helped to improve the understanding of biological processes and diseases. Large amounts of publicly available microarray data are accumulating, but are poorly exploited due to a lack of easy-to-use bioinformatics resources. The aim of this study is to build a free and convenient data-mining web site (www.genomicscape.com). GenomicScape allows mining dataset from various microarray platforms, identifying genes differentially expressed between populations, clustering populations, visualizing expression profiles of large sets of genes, and exporting results and figures. We show how easily GenomicScape makes it possible to construct a molecular atlas of the B cell differentiation using publicly available transcriptome data of naïve B cells, centroblasts, centrocytes, memory B cells, preplasmablasts, plasmablasts, early plasma cells and bone marrow plasma cells. Genes overexpressed in each population and the pathways encoded by these genes are provided as well as how the populations cluster together. All the analyses, tables and figures can be easily done and exported using GenomicScape and this B cell to plasma cell atlas is freely available online. Beyond this B cell to plasma cell atlas, the molecular characteristics of any biological process can be easily and freely investigated by uploading the corresponding transcriptome files into GenomicScape., Author Summary The use of DNA microarrays has emerged as a powerful tool for biomedical research to understand complex biological processes and diseases, generating large amounts of publicly available data. Most of these data remain unused by scientific community due to the lack of easy-to-use bioinformatics resources to analyze them. Here we present GenomicScape (www.genomicscape.com), a free online data-mining platform to identify quickly molecular changes during any biological process. As an example, we used GenomicScape to build a comprehensive and accessible molecular atlas of human B cell differentiation, which will be of great interest for immunologists to further understand normal and malignant B cell differentiation.
Published: 2015

15. Acides nucléiques circulants et fécondation in vitro

Author: Samir Hamamah, M. Monforte, Sabine Traver, A. Ferrières, E. Scalici, E. Vintejoux, T. Mullet, Cellules souches normales et cancéreuses, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Développement embryonnaire précoce humain et pluripotence EmbryoPluripotency (UMR 1203), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-CHU Montpellier
Subjects: MESH: Ovary, medicine.medical_specialty, Embryo quality, Réserve ovarienne, Circulating nucleic acids, Biology, MESH: Prognosis, 03 medical and health sciences, Cell-free DNA, 0302 clinical medicine, In vitro fertilization, medicine, 030304 developmental biology, MESH: Treatment Outcome, Gynecology, 0303 health sciences, MicroARNs, 030219 obstetrics & reproductive medicine, MESH: Humans, Ovarian reserve, MESH: DNA, Obstetrics and Gynecology, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, General Medicine, MESH: Nucleic Acids, Acides nucléiques circulants, Implantation, MESH: Ovarian Follicle, 3. Good health, MESH: Fertilization in Vitro, MicroRNAs, Reproductive Medicine, MESH: Biomarkers, ADN libre, MESH: Female, MESH: MicroRNAs, Qualité embryonnaire, Fécondation in vitro
Abstract: Resume Au cours de ces dernieres annees, l’utilisation des acides nucleiques circulants (microARNs et ADN libre) comme outils diagnostiques et/ou pronostiques en cancerologie a ete largement documentee. De la meme maniere en gynecologie-obstetrique, le developpement du diagnostic prenatal non invasif, base sur l’etude de ces biomarqueurs, a confirme leur interet grandissant dans cette discipline. En reproduction humaine, plusieurs etudes se sont interessees aux microARNs, petites sequences d’ARN non codantes, presents dans le follicule ovarien et a leur implication dans la folliculogenese. Certains de ces microARNs, ainsi que les vesicules qui les transportent, sont facilement detectables dans la circulation sanguine et pourraient devenir de veritables biomarqueurs d’interet dans la prise en charge de l’infertilite. Le taux d’ADN libre circulant varie en fonction du contexte physiopathologique et reflete la proportion d’evenements apoptotiques et/ou necrotiques survenant dans l’organisme. De ce fait, son dosage sanguin pourrait apporter une aide complementaire aux praticiens dans l’evaluation de l’etat fonctionnel ovarien. De plus, ces acides nucleiques circulants pourraient egalement constituer de nouveaux biomarqueurs predictifs de la qualite ovocytaire et/ou embryonnaire et representer une piste prometteuse dans la prevention des echecs d’implantation. En conclusion, ces acides nucleiques circulants ouvrent la voie au developpement de nouveaux tests diagnostiques et/ou pronostiques innovants ayant pour principal objectif l’amelioration des resultats en fecondation in vitro.
Published: 2014

16. Comprehensive characterization of immunoglobulin gene rearrangements in patients with chronic lymphocytic leukaemia

Author: Jean-François Eliaou, Céline René, Odile Avinens, Mélanie Broctawik, Audrey Thuizat, Nathalie Prat, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), and Université Montpellier 1 (UM1)
Subjects: Male, [SDV]Life Sciences [q-bio], Population, Immunoglobulin Variable Region, Somatic hypermutation, Biology, medicine.disease_cause, Real-Time Polymerase Chain Reaction, 03 medical and health sciences, 0302 clinical medicine, medicine, AID, Humans, education, Gene, 030304 developmental biology, Aged, Genetics, Gene Rearrangement, 0303 health sciences, Mutation, education.field_of_study, Genes, Immunoglobulin, Cell Biology, Cytidine deaminase, Gene rearrangement, DNA, Neoplasm, Original Articles, Middle Aged, Prognosis, Leukemia, Lymphocytic, Chronic, B-Cell, 3. Good health, somatic hypermutation, ageing, Immunoglobulin J-Chains, Immunology, Molecular Medicine, Immunoglobulin heavy chain, Female, CDR3, Immunoglobulin Gene Rearrangement, Immunoglobulin Heavy Chains, immunoglobulin, CLL, 030215 immunology
Abstract: International audience; Previous studies have suggested a geographical pattern of immunoglobulin rearrangement in chronic lymphocytic leukaemia (CLL), which could be as a result of a genetic background or an environmental antigen. However, the characteristics of Ig rearrangements in the population from the South of France have not yet been established. Here, we studied CLL B-cell repertoire and mutational pattern in a Southern French cohort of patients using an in-house protocol for whole sequencing of the rearranged immunoglobulin heavy-chain genes. Described biased usage of variable, diversity and joining genes between the mutated and unmutated groups was found in our population. However, variable gene frequencies are more in accordance with those observed in the Mediterranean patients. We found that the third complementary-determining region (CDR) length was higher in unmutated sequences, because of bias in the diversity and joining genes usage and not due to the N diversity. Mutations found in CLL followed the features of canonical somatic hypermutation mechanism: preference of targeting for activation-induced cytidine deaminase and polymerase motifs, base change bias for transitions and more replacement mutations occurring in CDRs than in framework regions. Surprisingly, localization of activation-induced cytidine deaminase motifs onto the variable gene showed a preference for framework regions. The study of the characteristics at the age of diagnosis showed no difference in clinical outcome, but suggested a tendency of increased replacement and transition-over-transversion mutations and a longer third CDR length in older patients.
Published: 2014

17. Identification of a 20-gene expression-based risk score as a predictor of clinical outcome in chronic lymphocytic leukemia patients

Author: Bernard Klein, Elias Bou Samra, Thérèse Commes, Jérôme Moreaux, Cellules souches normales et cancéreuses, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Institut de Biologie Computationnelle (IBC), Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), ARC (SFI20121205949), INCA-Canceropole GSO (2012-011 et 2012-E14), ANR-12-EMMA-0028,ETTMM (Epigenetic Targeted Treatment of Multiple Myeloma),Nouvel outil diagnostic pour le traitement ciblé des modifications épigénétiques dans le myélome multiple.(2012), European Project, ANR Emergence (ETTMM),ANR Emergence (ETTMM), Frei, Monique, Emergence - Nouvel outil diagnostic pour le traitement ciblé des modifications épigénétiques dans le myélome multiple. - - ETTMM (Epigenetic Targeted Treatment of Multiple Myeloma)2012 - ANR-12-EMMA-0028 - Emergence - VALID, and FEDER (141786 and 42667) - INCOMING
Subjects: Oncology, medicine.medical_specialty, Article Subject, [SDV.IMM] Life Sciences [q-bio]/Immunology, Chronic lymphocytic leukemia, lcsh:Medicine, Disease, Bioinformatics, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Text mining, Internal medicine, medicine, T Cell Transcription Factor 1, Humans, Survival analysis, 030304 developmental biology, Adaptor Proteins, Signal Transducing, Regulation of gene expression, 0303 health sciences, Framingham Risk Score, General Immunology and Microbiology, business.industry, Microarray analysis techniques, lcsh:R, Nuclear Proteins, General Medicine, medicine.disease, Microarray Analysis, Prognosis, Leukemia, Lymphocytic, Chronic, B-Cell, Survival Analysis, Neoplasm Proteins, Nuclear Receptor Interacting Protein 1, Gene Expression Regulation, Neoplastic, Leukemia, Treatment Outcome, 030220 oncology & carcinogenesis, gene expression, chronic lymphocytic leukemia, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, Research Article
Abstract: Despite the improvement in treatment options, chronic lymphocytic leukemia (CLL) remains an incurable disease and patients show a heterogeneous clinical course requiring therapy for many of them. In the current work, we have built a 20-gene expression (GE)-based risk score predictive for patients overall survival and improving risk classification using microarray gene expression data. GE-based risk score allowed identifying a high-risk group associated with a significant shorter overall survival (OS) and time to treatment (TTT)P≤.01, comprising 19.6% and 13.6% of the patients in two independent cohorts. GE-based risk score, andNRIP1andTCF7gene expression remained independent prognostic factors using multivariate Cox analyses and combination of GE-based risk score together withNRIP1andTCF7gene expression enabled the identification of three clinically distinct groups of CLL patients. Therefore, this GE-based risk score represents a powerful tool for risk stratification and outcome prediction of CLL patients and could thus be used to guide clinical and therapeutic decisions prospectively.
Published: 2014

18. Female Aging Alters Expression of Human Cumulus Cells Genes that Are Essential for Oocyte Quality

Author: A. Ferrières, Sophie Bringer Deutsch, Said Assou, T. Al-Edani, Charles-Henri Lecellier, Ounissa Aït-Ahmed, Samir Hamamah, Anna Gala, Cellules souches normales et cancéreuses, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Biopathologie [CHRU Montpellier], Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), This work was supported by Ferring Pharmaceuticals A/S.The authors thank the direction of the Montpellier 1 Univer-sity and University Hospital of Montpellier for their support.They thank all members of ART team for their assistanceduring this study., CHU Arnaud-de-Villeneuve [Montpellier], Développement embryonnaire précoce humain et pluripotence EmbryoPluripotency (UMR 1203), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-CHU Montpellier, Institut de recherche en biothérapie (IRB), and Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: Adult, Aging, Article Subject, IGFBP3, lcsh:Medicine, Biology, Bioinformatics, General Biochemistry, Genetics and Molecular Biology, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Transforming Growth Factor beta, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], microRNA, medicine, Humans, 030304 developmental biology, Regulation of gene expression, 0303 health sciences, 030219 obstetrics & reproductive medicine, Cumulus Cells, General Immunology and Microbiology, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, lcsh:R, fungi, Gene Expression Regulation, Developmental, Reproducibility of Results, General Medicine, Activin receptor, Transforming growth factor beta, Oocyte, Gene expression profiling, MicroRNAs, medicine.anatomical_structure, biology.protein, Oocytes, Female, Signal Transduction, Research Article
Abstract: Impact of female aging is an important issue in human reproduction. There was a need for an extensive analysis of age impact on transcriptome profile of cumulus cells (CCs) to link oocyte quality and developmental potential with patient’s age. CCs from patients of three age groups were analyzed individually using microarrays. RT-qPCR validation was performed on independent CC cohorts. We focused here on pathways affected by aging in CCs that may explain the decline of oocyte quality with age. In CCs collected from patients >37 years, angiogenic genes includingANGPTL4,LEPR,TGFBR3, andFGF2were significantly overexpressed compared to patients of the two younger groups. In contrast genes implicated in TGF-βsignaling pathway such asAMH,TGFB1, inhibin, and activin receptor were underexpressed. CCs from patients whose ages are between 31 and 36 years showed an overexpression of genes related to insulin signaling pathway such asIGFBP3,PIK3R1, andIGFBP5. A bioinformatic analysis was performed to identify the microRNAs that are potential regulators of the differentially expressed genes of the study. It revealed that the pathways impacted by age were potential targets of specific miRNAs previously identified in our CCs small RNAs sequencing.
Published: 2014

19. Potential Classification Criteria for Rheumatoid Arthritis After Two Years: Results From a French Multicenter Cohort

Author: Saraux , Alain, Tobón , Gabriel J, Benhamou , Mathilde, Devauchelle-Pensec , Valérie, Dougados , Maxime, Mariette , Xavier, Berenbaum , Francis, Chiocchia , Gilles, Rat , Anne-Christine, Schaeverbeke , Thierry, Rincheval , Nathalie, Meyer , Olivier, Fautrel , Bruno, Combe , Bernard, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Cochin [AP-HP], Service de rhumatologie, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Bordeaux [Bordeaux], Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Hôpital Lapeyronie [Montpellier] (CHU), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Service de Rhumatologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Régulation de la réponse immune, infection VIH-1 et autoimmunité, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service Rhumatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Rhumatologie, Université Paris Diderot - Paris 7 (UPD7), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université de Montpellier (UM)-Université Montpellier 1 (UM1), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Cochin [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Immunologie et Pathologie ( EA2216 ), Université de Brest ( UBO ) -IFR148, Centre d'Investigation Clinique ( CIC - Brest ), Université de Brest ( UBO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHRU Brest - Service de Rhumatologie ( CHU - BREST - Rhumato ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Maladies chroniques, santé perçue, et processus d'adaptation ( APEMAC ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Université Paris Diderot - Paris 7 ( UPD7 ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Montpellier ( UM ), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 ( AIDMP ), Université Montpellier 1 ( UM1 ) -Université de Montpellier ( UM ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université de Lorraine ( UL ) -Université Paris Descartes - Paris 5 ( UPD5 ), and Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - IURC
Subjects: Adult, Male, musculoskeletal diseases, MESH : Male, [SDV]Life Sciences [q-bio], MESH : Cohort Studies, MESH: Logistic Models, Arthritis, Rheumatoid, Cohort Studies, Rheumatology, immune system diseases, MESH: Rheumatology, Humans, MESH : Female, MESH : Middle Aged, Longitudinal Studies, MESH : Rheumatology, MESH : France, MESH: Longitudinal Studies, skin and connective tissue diseases, MESH: Cohort Studies, MESH : Longitudinal Studies, MESH: Arthritis, Rheumatoid, MESH: Humans, MESH: Middle Aged, [ SDV ] Life Sciences [q-bio], MESH : Humans, MESH: Adult, MESH : Adult, Middle Aged, MESH: Male, MESH: France, Logistic Models, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, MESH : Arthritis, Rheumatoid, Female, France, MESH: Female, MESH : Logistic Models
Abstract: International audience; OBJECTIVE: To determine agreement among the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria, a diagnosis of rheumatoid arthritis (RA) by a rheumatologist, and other criteria previously used to classify arthritis. METHODS: We used a nationwide longitudinal prospective cohort of patients with recent-onset arthritis. After 2 years, the patients were classified as receiving disease-modifying antirheumatic drugs (DMARDs), having synovitis, having joint erosions typical of RA, having a rheumatologist diagnosis of RA with >50.0% certainty, having a no better alternative diagnosis with >50.0% certainty, and having a diagnosis of RA using the 1987 ACR criteria and the 2010 ACR/EULAR criteria. Agreement among these criteria was assessed based on Cohen's kappa coefficient, where ≥0.80 = excellent, 0.60-0.79 = good, 0.40-0.59 = moderate, and 50.0% certainty or a no better alternative diagnosis with >50.0% certainty (estimated κ = 0.69-0.81). The strongest associations with a rheumatologist diagnosis of RA with >50.0% certainty were the 2010 ACR/EULAR criteria and the combination of no better alternative diagnosis, persistent arthritis, 1987 ACR criteria, and positive anti-citrullinated protein antibody. CONCLUSION: Rheumatologist diagnosis of RA with >50.0% certainty after 2 years agreed well with the 2010 ACR/EULAR criteria or a combination of items including no better alternative diagnosis, confirming high value as classification criteria after 2 years of followup.
Published: 2013

20. Cognitive insight as an indicator of competence to consent to treatment in schizophrenia

Author: Catherine Bortolon, Delphine Capdevielle, Alexandra Macgregor, Marie-Christine Gély-Nargeot, Jean-Phillipe Boulenger, Guillaume Fond, Stéphane Raffard, Marie Brittner, Dynamique des capacités humaines et des conduites de santé (EPSYLON), Université Montpellier 1 (UM1)-Université Paul-Valéry - Montpellier 3 (UM3)-Université de Montpellier (UM), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Neuropsychiatrie : recherche épidémiologique et clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Montpellier (UM)-Université Paul-Valéry - Montpellier 3 (UPVM)-Université Montpellier 1 (UM1), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), and Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Male, Psychotherapist, Schizophrenia (object-oriented programming), medicine.medical_treatment, Decision Making, Self-concept, Competence (law), 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Schizophrenic Psychology, medicine, Humans, Mental Competency, Biological Psychiatry, ComputingMilieux_MISCELLANEOUS, Psychiatric Status Rating Scales, Informed Consent, Cognition, Awareness, Middle Aged, Self Concept, Cognitive bias, 030227 psychiatry, Psychiatry and Mental health, Bonferroni correction, [SCCO.PSYC]Cognitive science/Psychology, Schizophrenia, Cognitive therapy, symbols, Female, Patient Participation, Psychology, 030217 neurology & neurosurgery
Abstract: article i nfo Article history: The processes underlying the ability to make decisions about recommended treatments remain poorly understood in schizophrenia. The aim of this study was to explore the relationships between capacity to consent to medication and cognitive biases in 60 schizophrenia patients. Main measures included the MacArthur Competence Assessment tool forTreatment (MacCAT-T) and the Beck Cognitive Insight Scale(BCIS). After Bonferroni's correction for multiple correlations, the Self-Reflectiveness dimension of the BCIS was significantly associated with the dimension "Reason- ing" of the MacCAT-T. Cognitive therapy, by enhancing patients' Self-Reflectiveness and considering alternative explanations, could lead to better capacity to consent to treatment in schizophrenia.
Published: 2013

21. Anti-tumour immunotherapy with Vγ9Vδ2 T lymphocytes: from the bench to the bedside

Author: Mounia Sabrina Braza, Bernard Klein, Cellules souches normales et cancéreuses, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Institut de recherche en biothérapie (IRB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Frei, Monique
Subjects: Receptors, Antigen, T-Cell, alpha-beta, medicine.medical_treatment, Lymphocyte, MESH: Antigens, Neoplasm, MESH: Translational Medical Research, MESH: Adjuvants, Immunologic, MESH: T-Lymphocyte Subsets, Adaptive Immunity, CD8-Positive T-Lymphocytes, Immunotherapy, Adoptive, T-Lymphocytes, Regulatory, Translational Research, Biomedical, 0302 clinical medicine, Cancer immunotherapy, T-Lymphocyte Subsets, Neoplasms, MESH: Neoplasms, Immunologic Surveillance, Cells, Cultured, Clinical Trials as Topic, 0303 health sciences, MESH: Receptors, Antigen, T-Cell, alpha-beta, Diphosphonates, MESH: Dendritic Cells, Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor, Receptors, Antigen, T-Cell, gamma-delta, Hematology, Acquired immune system, MESH: Gene Rearrangement, delta-Chain T-Cell Antigen Receptor, MESH: CD8-Positive T-Lymphocytes, 3. Good health, Killer Cells, Natural, medicine.anatomical_structure, MESH: Immunotherapy, Adoptive, MESH: Tumor Escape, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Immunity, Innate, immunotherapy, monoclonal antibodies, MESH: Cells, Cultured, MESH: Killer Cells, Natural, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Clinical Trials as Topic, MESH: Diphosphonates, T cell, Gene Rearrangement, delta-Chain T-Cell Antigen Receptor, haematological oncology, 03 medical and health sciences, Adjuvants, Immunologic, Antigen, Antigens, Neoplasm, gamma delta T lymphocytes, MESH: Receptors, Antigen, T-Cell, gamma-delta, medicine, Humans, cancer, 030304 developmental biology, MESH: Immunologic Surveillance, MESH: Humans, business.industry, MESH: T-Lymphocytes, Regulatory, Mesenchymal Stem Cells, Dendritic Cells, Immunotherapy, Gene rearrangement, T lymphocyte, Immunity, Innate, MESH: Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor, Immunology, MESH: Mesenchymal Stromal Cells, Tumor Escape, business, MESH: T-Lymphocytes, Cytotoxic, MESH: Adaptive Immunity, T-Lymphocytes, Cytotoxic, 030215 immunology
Abstract: International audience; Gamma delta (γδ) Τ cells are non-conventional T lymphocyte effectors that can interact with and eradicate tumour cells. Several data demonstrate that these T cells, which are implicated in the first line of defence against pathogens, have anti-tumour activity against many cancers and suggest that γδ Τ cell-mediated immunotherapy is feasible and might induce objective tumour responses. Due to the importance of γδ Τ lymphocytes in the induction and control of immunity, a complete understanding of their biology is crucial for the development of a potent cancer immunotherapy. This review discusses recent advances in γδ Τ basic research and data from clinical trials on the use of γδ Τ cells in the treatment of different cancers. It analyses how this knowledge might be applied to develop new strategies for the clinical manipulation and the potentiation of γδ Τ lymphocyte activity in cancer immunotherapy.
Published: 2013

22. Embryonic stem cells or induced pluripotent stem cells? A DNA integrity perspective

Author: Bai, Qiang, Desprat, Romain, Klein, Bernard, Lemaitre, Jean-Marc, de Vos, John, Frei, Monique, Cellules souches normales et cancéreuses, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut de recherche en biothérapie (IRB), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Institut de Génomique Fonctionnelle - Montpellier GenomiX (IGF MGX), Institut de Génomique Fonctionnelle (IGF), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Computationnelle (IBC), Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Association Française contre les Myopathies (AFM, Paris, France), and Région Languedoc-Roussillon, France
Subjects: Induced pluripotent stem cells, genome integrity, [SDV.IMM] Life Sciences [q-bio]/Immunology, cell reprogramming, genetic abnormalities, DNA damage, [SDV.IMM]Life Sciences [q-bio]/Immunology, pluripotency
Abstract: International audience; Induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) are two types of pluripotent stem cells that hold great promise for biomedical research and medical applications. iPSCs were initially favorably compared to ESCs. This view was first based on ethical arguments (the generation of iPSCs does not require the destruction of an embryo) and on immunological reasons (it is easier to derive patient HLA-matched iPSCs than ESCs). However, several reports suggest that iPSCs might be characterized by higher occurrence of epigenetic and genetic aberrations than ESCs as a consequence of the reprogramming process. We focus here on the DNA integrity of pluripotent stem cells and examine the three main sources of genomic abnormalities in iPSCs: (1) genomic variety of the parental cells, (2) cell reprogramming, and (3) in vitro cell culture. Recent reports claim that it is possible to generate mouse or human iPSC lines with a mutation level similar to that of the parental cells, suggesting that "genome-friendly" reprogramming techniques can be developed. The issue of iPSC DNA integrity clearly highlights the crucial need of guidelines to define the acceptable level of genomic integrity of pluripotent stem cells for biomedical applications. We discuss here the main issues that such guidelines should address.
Published: 2013

23. Gene expression-based risk score in diffuse large B-cell lymphoma

Author: Caroline Bret, Jérôme Moreaux, Bernard Klein, Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Cellules souches normales et cancéreuses, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Association pourla Recherche sur le Cancer (SL220110603450, Paris, France), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Institut de recherche en biothérapie (IRB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Frei, Monique, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: Oncology, Drug resistance, nucleotide excision DNA repair, Kaplan-Meier Estimate, CHOP, Bioinformatics, Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, International Prognostic Index, Risk Factors, Prednisone, immune system diseases, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Cluster Analysis, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, Framingham Risk Score, Hematology, medicine.diagnostic_test, Research Papers, 3. Good health, Phenotype, Treatment Outcome, Vincristine, 030220 oncology & carcinogenesis, gene expression profile, [SDV.IMM]Life Sciences [q-bio]/Immunology, Lymphoma, Large B-Cell, Diffuse, Rituximab, medicine.drug, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Editorials: Cell Cycle Features, Biology, risk score, Risk Assessment, Genomic Instability, 03 medical and health sciences, Internal medicine, medicine, Biomarkers, Tumor, Humans, Genetic Predisposition to Disease, Genetic Testing, Molecular Biology, Gene, Cyclophosphamide, Genetic testing, Proportional Hazards Models, 030304 developmental biology, drug resistance, Gene Expression Profiling, fungi, Cell Biology, DNA Repair Pathway, Gene signature, medicine.disease, Lymphoma, Gene expression profiling, Doxorubicin, DLBCL, Multivariate Analysis, Immunology, prognosis, Diffuse large B-cell lymphoma, Developmental Biology
Abstract: // Caroline Bret 1,2,3 , Bernard Klein 2,3 , and Jerome Moreaux 2 1 Department of Biological Hematology, St Eloi Hospital, Montpellier, France 2 INSERM U1040, Institute of Research in Biotherapy, Montpellier, France 3 University of Montpellier 1, UFR de Medecine, Montpellier, France Correspondence: Jerome Moreaux, email: // Keywords : DLBCL, gene expression profile, risk score, prognosis Received : December 29, 2012, Accepted : December 30, 2012, Published : December 31, 2012 Abstract Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma and displays heterogeneous clinical and molecular characteristics. In this study, high throughput gene expression profiling of DLBCL tumor samples was used to design a 12-gene expression–based risk score (GERS) predictive for patient’s overall survival. GERS allowed identifying a high-risk group comprising 46,4% of the DLBCL patients in two independent cohorts (n=414 and n=69). GERS was shown to be an independent predictor of survival when compared to the previously published prognostic factors, including the International Prognostic Index (IPI). GERS displayed a prognostic value in germinal-center B-cell–like subgroup (GCB) and activated B cell–like (ABC) molecular subgroups of patients as well as in DLBCL patients treated with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) or Rituximab-CHOP (R-CHOP) regimens. Combination of GERS and IPI lead to a potent prognostic classification of DLBCL patients. Finally, a genomic instability gene signature was highlighted in gene expression profiles of patients belonging to the high-risk GERS-defined group.
Published: 2012

24. Development of gene expression-based risk score in cytogenetically normal acute myeloid leukemia patients

Author: Thérèse Commes, Bernard Klein, Jérôme Moreaux, Elias Bou Samra, Cellules souches normales et cancéreuses, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Groupe d'Etude des Transcriptomes, Université Montpellier 2 - Sciences et Techniques (UM2), CHU de Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Association pour la Recherche sur le Cancer, European Project, Frei, Monique, and European Community (FP7-OverMyr) - INCOMING
Subjects: Oncology, MESH: Neoplasm Proteins, cytogenetically normal-acute myeloid leukemia, Gene Expression, Bioinformatics, 0302 clinical medicine, Cytogenetically normal acute myeloid leukemia, Gene expression, gene expression-based risk score, prognostic gene signature, 0303 health sciences, Framingham Risk Score, MESH: Risk, Myeloid leukemia, MESH: Karyotype, Karyotype, MESH: Transcription Factors, Prognosis, Research Papers, Neoplasm Proteins, DNA-Binding Proteins, Leukemia, Myeloid, Acute, 030220 oncology & carcinogenesis, Cytogenetic Analysis, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Leukemia, Myeloid, Acute, Adult, Risk, medicine.medical_specialty, MESH: Gene Expression, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Trans-Activators, Biology, Disease-Free Survival, MESH: Prognosis, 03 medical and health sciences, MESH: Gene Expression Profiling, Text mining, Transcriptional Regulator ERG, Internal medicine, Proto-Oncogenes, Biomarkers, Tumor, medicine, Humans, MESH: Tumor Suppressor Proteins, Gene, 030304 developmental biology, MESH: Humans, business.industry, Gene Expression Profiling, Tumor Suppressor Proteins, MESH: Cytogenetic Analysis, MESH: Adult, Training cohort, MDS1 and EVI1 Complex Locus Protein, EVI1 expression, MESH: Proto-Oncogenes, MESH: Tumor Markers, Biological, MESH: Disease-Free Survival, Trans-Activators, business, MESH: DNA-Binding Proteins, Transcription Factors
Abstract: International audience; Patients with normal karyotype represent the single largest cytogenetic group of acute myeloid leukemia (AML), with highly heterogeneous clinical and molecular characteristics. In this study, we sought to determine new prognostic biomarkers in cytogenetically normal (CN)-AML patients. A gene expression (GE)-based risk score was built, summing up the prognostic value of 22 genes whose expression is associated with a bad prognosis in a training cohort of 163 patients. GE-based risk score allowed identifying a high-risk group of patients (53.4%) in two independent cohorts of CN-AML patients. GE-based risk score and EVI1 gene expression remained independent prognostic factors using multivariate Cox analyses. Combining GE-based risk score with EVI1 gene expression allowed the identification of three clinically different groups of patients in two independent cohorts of CN-AML patients. Thus, GE-based risk score is powerful to predict clinical outcome for CN-AML patients and may provide potential therapeutic advances.
Published: 2012

25. Identification of pluripotent and adult stem cell genes unrelated to cell cycle and associated with poor prognosis in multiple myeloma

Author: Hartmut Goldschmidt, Jean François Rossi, Alboukadel Kassambara, Bernard Klein, Dirk Hose, Thierry Rème, Jennifer Torrent, Jérôme Moreaux, Cellules souches normales et cancéreuses, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Department of Internal Medicine V, Universität Heidelberg [Heidelberg], Institut de recherche en biothérapie (IRB), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Association pour la Recherche sur le Cancer, ARC (SL220110603450, Paris, France), The Tumorzentrum Heidelberg/Mannheim, Germany, The Deutsche Krebshilfe, Bonn, Germany, The Deutsche Forschungsgemeinschaft (Transregio TRR79), Bonn, Germany, Frei, Monique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)
Subjects: Genetic Screens, MESH: Adult Stem Cells, Cellular differentiation, Gene Expression, MESH: Cell Cycle, MESH: Multiple Myeloma, Hematologic Cancers and Related Disorders, 0302 clinical medicine, Basic Cancer Research, Induced pluripotent stem cell, Multiple myeloma, 0303 health sciences, Induced stem cells, Multidisciplinary, Stem Cells, Cell Cycle, Genomics, Prognosis, 3. Good health, Adult Stem Cells, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, MESH: Immunologic Memory, Medicine, MESH: Pluripotent Stem Cells, [SDV.IMM]Life Sciences [q-bio]/Immunology, Stem cell, Multiple Myeloma, Research Article, Adult stem cell, Pluripotent Stem Cells, [SDV.IMM] Life Sciences [q-bio]/Immunology, Science, Biology, MESH: Prognosis, Molecular Genetics, 03 medical and health sciences, MESH: Gene Expression Profiling, Genome Analysis Tools, Cancer stem cell, Genetics, Cancer Genetics, medicine, Humans, Genetic Testing, Myelomas and Lymphoproliferative Diseases, Genetic Association Studies, 030304 developmental biology, MESH: Humans, Gene Expression Profiling, Computational Biology, Cancers and Neoplasms, Human Genetics, medicine.disease, Immunology, Bone marrow, Immunologic Memory, Developmental Biology
Abstract: International audience; Gene expression-based scores used to predict risk in cancer frequently include genes coding for DNA replication, repair or recombination. Using two independent cohorts of 206 and 345 previously-untreated patients with Multiple Myeloma (MM), we identified 50 cell cycle-unrelated genes overexpressed in multiple myeloma cells (MMCs) compared to normal human proliferating plasmablasts and non-proliferating bone marrow plasma cells and which have prognostic value for overall survival. Thirty-seven of these 50 myeloma genes (74%) were enriched in genes overexpressed in one of 3 normal human stem cell populations--pluripotent (18), hematopoietic (10) or mesenchymal stem cells (9)--and only three genes were enriched in one of 5 populations of differentiated cells (memory B lymphocytes, T lymphocytes, polymorphonuclear cells, monocytes, osteoclasts). These 37 genes shared by MMCs and adult or pluripotent stem cells were used to build a stem cell score ((SC)score), which proved to be strongly prognostic in the 2 independent cohorts of patients compared to other gene expression-based risk scores or usual clinical scores using multivariate Cox analysis. This finding highlights cell cycle-unrelated prognostic genes shared by myeloma cells and normal stem cells, whose products might be important for normal and malignant stem cell biology.
Published: 2012

26. Pure intronic rearrangements leading to aberrant pseudoexon inclusion in dystrophinopathy: a new class of mutations?

Author: Sylvie Tuffery-Giraud, Mouna Messaoud Khelifi, Serge Perelman, Philippe Khau Van Kien, Déborah Méchin, Mireille Claustres, Jean Pouget, Delphine Thorel, Aliya Ishmukhametova, Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Children's Hospital, Lenval Foundation, Service de Neurologie et maladies neuromusculaires, and Hôpital de la Timone [CHU - APHM] (TIMONE)
Subjects: Adult, Male, RNA Splicing, Biology, medicine.disease_cause, Dystrophin, 03 medical and health sciences, Exon, 0302 clinical medicine, Genetics, medicine, Humans, Genetics (clinical), 030304 developmental biology, Gene Rearrangement, 0303 health sciences, Mutation, Intron, RNA, Life Sciences, Gene rearrangement, Exons, Phenotype, Introns, Muscular Dystrophy, Duchenne, Child, Preschool, RNA splicing, 030217 neurology & neurosurgery, Comparative genomic hybridization
Abstract: International audience; We report on two unprecedented cases of pseudoexon activation in the DMD gene resulting from pure intronic double-deletion events that possibly involve microhomology-mediated mechanisms. Array comparative genomic hybridization analysis and direct genomic sequencing allowed us to elucidate the causes of the pathological pseudoexon inclusion detected in the RNA of the patients. In the first case (Duchenne phenotype), we showed that the inserted 387-bp pseudoexon was originated from an inverted ∼57kb genomic region of intron 44 flanked by two deleted ∼52kb and ∼1kb segments. In the second case (Becker phenotype), we identified in intron 56 two small deletions of 592 bp (del 1) and 29 bp (del 2) directly flanking a 166-bp pseudoexon located in a very close proximity (134 bp) to exon 57. The key role of the del 1 in pseudoexon activation was established by using splicing reporter minigenes. However the analysis of mutant constructs failed to identify cis elements that regulate the inclusion of the pseudoexon and suggested that other splicing regulatory factors may be involved such as RNA structure. Our study introduces a new class of mutations in the DMD gene that emphasizes the potential role of underdetected intronic rearrangements in human diseases.
Published: 2011

27. Encéphalite à parvovirus B19 de l'enfant

Author: Meyer, Pierre, Jeziorski, E., Bott-Gilton, L, Foulongne, V., Rivier, Francois, Rondoin, G, Rodiere, M., Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Pathogénèse et contrôle des infections chroniques (PCCI), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM)
Subjects: [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Abstract: International audience; Introduction: Human parvovirus B19 (PVB19) causes erythema infectiosum or 5th disease in childhood, which mainly affects children between 3 and 15 years of age. PVB19 infections have also been described in association with a variety of neurologic manifestations including encephalitis.Case report: This 3-year 8-month-old boy developed febrile encephalitis (mental status change with seizures and left limb hypertonia) associated with a rash. The electroencephalographs revealed focal slowing with some spikes in front of the left centro-temporo-occipital areas ; bacteriological and biochemical cerebrospinal fluid (CSF) analysis were normal, brain radiologic studies (tomography and magnetic resonance imaging) were normal. The diagnosis of encephalitis associated with PVB19 primo infection was based on viral DNA detection in the serum and CSF using PCR and on the specific immunoglobulin M (without immunoglobulin G) detection in the serum.Discussion: In France, encephalitis etiology is unknown in 48% of the cases. PVB19 accounts for 4.3% of undiagnosed meningoencephalitis in children. Although there is no specific sign, seizures and rash are reported in about one-half and one-quarter of cases, respectively.Conclusion: Even if PVB19 research is not cited in the French or American infectious disease society recommendations on the diagnosis and management of infectious encephalitis, this virus may be responsible, especially in cases of child febrile rash. Therefore, PVB19 research seems reasonable if the clinical presentation is concordant in children due to its diagnostic simplicity and efficacy.; Introduction: Le parvovirus B19 (PVB19) est l’agent responsable du mégalérythème épidémique ou 5e maladie, qui touche essentiellement l’enfant entre 3 et 15 ans. Même si elles sont rares, des manifestations neurologiques ont été décrites.Cas clinique: Nous rapportons l’observation d’un patient de 3 ans et 8 mois qui avait présenté un tableau clinique d’encéphalite aiguë (troubles de la vigilance, hypertonie du membre supérieur droit, convulsions) dans un contexte d’éruption fébrile. L’électroencéphalogramme objectivait un ralentissement en regard des régions centro-temporo-occipitales gauches ; l’analyse cytobactériologique du liquide céphalorachidien (LCR) et l’imagerie cérébrale étaient normales. La sérologie pour le PVB19 était positive en immunoglobulines (Ig) M sans IgG en phase aiguë et les réactions de polymérisation en chaîne (PCR) spécifiques positives dans le sérum et le LCR avaient fait porter le diagnostic d’encéphalite à PVB19.Discussion: En France, 48 % des encéphalites sont idiopathiques (Mailles et al., 2009). Chez l’enfant, le PVB19 serait responsable de 4,3 % de ces encéphalites sans agent causal identifié (Barah et al., 2001). Il n’y a pas de signe spécifique, néanmoins des convulsions et un rash peuvent être trouvés respectivement dans la moitié et un quart des cas. (Douvoyiannis et al., 2009).Conclusion: Même si la recherche du PVB19 ne figure pas dans les recommandations de prise en charge diagnostique des encéphalites de la Société de pathologie infectieuse de langue française et de la Société nord-américaine de pathologie infectieuse, ce virus peut en être la cause notamment chez le grand enfant qui présente une éruption fébrile. Ainsi, en cas de contexte évocateur, il nous semble raisonnable d’effectuer la recherche du PVB19, agent pathogène « banal » de l’enfant, dont le diagnostic est simple et présente un bon rendement.
Published: 2011

28. Insulin is a potent myeloma cell growth factor through insulin/IGF-1 hybrid receptor activation

Author: Jean-François Rossi, Laure Vincent, Alboukadel Kassambara, Michel Jourdan, H. Goldschmidt, Bernard Klein, Anne Catherine Sprynski, Dirk Hose, Institut de recherche en biothérapie (IRB), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), National Center for Tumor Diseases (NCTD), Universität Heidelberg [Heidelberg], Department of Internal Medicine V, Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Frei, Monique, and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)
Subjects: Cancer Research, Transcription, Genetic, medicine.medical_treatment, MESH: Insulin-Like Growth Factor I, MESH: Multiple Myeloma, MESH: Flow Cytometry, MESH: Growth Substances, Receptor, IGF Type 1, MESH: Antibodies, Monoclonal, MESH: Nucleic Acid Hybridization, MESH: Recombinant Proteins, 0302 clinical medicine, MESH: Receptor, IGF Type 1, insulin/IGF-1 hybrid receptor, Insulin receptor substrate, MESH: Reverse Transcriptase Polymerase Chain Reaction, Plasma cell differentiation, Insulin-Like Growth Factor I, Receptor, Growth Substances, Oligonucleotide Array Sequence Analysis, MESH: Kinetics, Reverse Transcriptase Polymerase Chain Reaction, Antibodies, Monoclonal, Nucleic Acid Hybridization, Hematology, MESH: Gene Expression Regulation, Neoplastic, Flow Cytometry, Recombinant Proteins, Gene Expression Regulation, Neoplastic, multiple myeloma, Oncology, MESH: Cell Survival, 030220 oncology & carcinogenesis, IGF-1, MESH: Cell Division, INSR, Cell Division, medicine.medical_specialty, insulin, MESH: Cell Line, Tumor, MESH: Receptor, Insulin, Cell Survival, MESH: Insulin, Biology, Article, 03 medical and health sciences, Internal medicine, Cell Line, Tumor, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Pancreatic hormone, MESH: Humans, Cell growth, Insulin, Growth factor, MESH: Transcription, Genetic, Receptor, Insulin, Insulin receptor, Kinetics, Endocrinology, MESH: Oligonucleotide Array Sequence Analysis, biology.protein, IGF-1R, 030215 immunology
Abstract: International audience; Insulin and insulin growth factor type 1 (IGF-1) and their receptors are closely related molecules, but both factors bind to the receptor of the other one with a weak affinity. No study has presently documented a role of insulin as a myeloma growth factor (MGF) for human multiple myeloma cells (MMCs), whereas many studies have concluded that IGF-1 is a major MGF. IGF-1 receptor (IGF-1R) is aberrantly expressed by MMCs in association with a poor prognosis. In this study we show that insulin receptor (INSR) is increased throughout normal plasma cell differentiation. INSR gene is also expressed by MMCs of 203/206 newly diagnosed patients. Insulin is an MGF as potent as IGF-1 at physiological concentrations and requires the presence of insulin/IGF-1 hybrid receptors, stimulating INSR(+)IGF-1R(+) MMCs, unlike INSR(+)IGF-1R(-) or INSR(-)IGF-1R(-) MMCs. Immunoprecipitation experiments indicate that INSR is linked with IGF-1R in MMCs and that insulin induces both IGF-1R and INSR phosphorylations and vice versa. In conclusion, we demonstrate for the first time that insulin is an MGF as potent as IGF-1 at physiological concentrations and its activity necessitates insulin/IGF-1 hybrid receptor activation. Further therapeutic strategies targeting the IGF/IGF-1R pathway have to take into account neutralizing the IGF-1R-mediated insulin MGF activity.
Published: 2010

29. La dépression majeure diminue le taux d'abstinence tabagique

Author: Fond, Guillaume, Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), and Sébastien Guillaume
Subjects: Abstinence, Dépression, Rechute, Substitution nicotinique, Sevrage tabagique, Antidépresseur, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Objectif : l'association entre le tabac et la dépression majeure a été très bien documentée dans la littérature, pourtant des études sur l'effet de la dépression sur la rechute tabagique des patients sevrés est contradictoire. Nous faisons l'hypothèse que des patients avec un épisode dépressif majeur en cours au moment du sevrage sont à plus haut risque de rechute. Méthodes : 1020 participants majeurs ont été recrutés dans une unité de tabacologie. Tous les patients ont été évalués au cours de 6 consultations dans l'année. Le statut tabagique pendant le suivi a été obtenu par interrogatoire oral à l'entretien ou par téléphone. Les participants ont été classés en « euthymiques », « déprimés mineurs » et « déprimés majeurs » selon leurs scores à l'Hospitalisation Anxiety and Depression Scale. Résultats : dans un modèle de régression de Cox ajusté sur les facteurs de confusions potentiels, il a été montré que le taux de rechute était significativement associé avec un épisode dépressif majeur à la consultation préliminaire (OR 1.2 [1.0-1.50], p=0.02). Le sexe féminin, vivre seul et le faible niveau d'éducation n'ont pas supprimé cette association, malgré leur association avec la dépression. Conclusion : nos résultats suggèrent l'importance pour le clinicien de discriminer l'épisode dépressif majeur de l'épisode dépressif mineur lors de la première consultation. Étudier et développer des supports de cessation pour les patients déprimés est un enjeu majeur pour les soignants prenant en charge le sevrage tabagique.
Published: 2010

30. The severity of phenotype linked to SUCLG1 mutations could be correlated with residual amount of SUCLG1 protein

Author: Sylvie Bannwarth, C Caruba, C. Rouzier, Véronique Paquis-Flucklinger, Elsebet Ostergaard, S Le Guédard-Méreuze, Christian Richelme, C Espil, Valérie Serre, J Miro, Brigitte Chabrol, Sylvie Tuffery-Giraud, J-F Pellissier, Annabelle Chaussenot, Konstantina Fragaki, Service de génétique médicale, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Instabilité génétique : maladies rares et cancers (IGMRC), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Biochimie, Hôpital Pasteur [Nice] (CHU)-Centre Hospitalier Universitaire de Nice (CHU Nice), Department of Clinical Genetics, National University Hospital Rigshospitalet, Service de neuropathologie, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service de pédiatrie, Service de neuropédiatrie, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), CHU Nice-Hôpital l'Archet, Instabilité génétique : maladies rares et cancers ( IGMRC ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Montpellier 1 - UFR de Médecine ( UM1 Médecine ), Université Montpellier 1 ( UM1 ), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Pasteur [Nice] ( CHU ) -CHU Nice, Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Université Nice Sophia Antipolis (1965 - 2019) (UNS), and Peer, Hal
Subjects: Male, Models, Molecular, medicine.medical_specialty, SUCLA2, Molecular Sequence Data, Mutation, Missense, methylmalonic aciduria, SUCLG1 mutation, Biology, Compound heterozygosity, medicine.disease_cause, Severity of Illness Index, 03 medical and health sciences, Exon, 0302 clinical medicine, Fatal Outcome, Western blot, respiratory chain defect, Mitochondrial Encephalomyopathies, Molecular genetics, Succinate-CoA Ligases, Genetics, medicine, Missense mutation, Humans, Amino Acid Sequence, minigene expression system, Child, Genetics (clinical), 030304 developmental biology, 0303 health sciences, Mutation, medicine.diagnostic_test, mtDNA depletion, Infant, Molecular biology, 3. Good health, Phenotype, 030217 neurology & neurosurgery, Minigene, Methylmalonic Acid
Abstract: Background Succinate-CoA ligase deficiency is responsible for encephalomyopathy with mitochondrial DNA depletion and mild methylmalonic aciduria. Mutations in SUCLA2 , the gene encoding a β subunit of succinate-CoA ligase, have been reported in 17 patients until now. Mutations in SUCLG1 , encoding the α subunit of the enzyme, have been described in two pedigrees only. Methods and findings In this study, two unrelated patients harbouring three novel pathogenic mutations in SUCLG1 were reported. The first patient had a severe disease at birth. He was compound heterozygous for a missense mutation (p.Pro170Arg) and a c.97+3G>C mutation, which leads to the complete skipping of exon 1 in a minigene expression system. The involvement of SUCLG1 was confirmed by western blot analysis, which showed absence of SUCLG1 protein in fibroblasts. The second patient has a milder phenotype, similar to that of patients with SUCLA2 mutations, and is still alive at 12 years of age. Western blot analysis showed some residual SUCLG1 protein in patient9s fibroblasts. Conclusions Our results suggest that SUCLG1 mutations that lead to complete absence of SUCLG1 protein are responsible for a very severe disorder with antenatal manifestations, whereas a SUCLA2 -like phenotype is found in patients with residual SUCLG1 protein. Furthermore, it is shown that in the absence of SUCLG1 protein, no SUCLA2 protein is found in fibroblasts by western blot analysis. This result is consistent with a degradation of SUCLA2 when its heterodimer partner, SUCLG1, is absent.
Published: 2010

31. Sodium bicarbonate ingestion prior to training improves mitochondrial adaptations in rats

Author: Bishop, David J., Thomas, Claire, Moore-Morris, Thomas, Tonkonogi, Michail, Sahlin, Kent, Mercier, Jacques, Institute of sport, exercise & active living (ISEAL), Victoria University, University of Victoria [Canada] (UVIC), Université d'Évry-Val-d'Essonne (UEVE), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Stockholm University College of Sport Science, Stockholm University College, Karolinska Institutet [Stockholm], Muscle et pathologies, Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), Stockholm University, and INSEP, documentation
Subjects: [SHS.SPORT]Humanities and Social Sciences/Sport, muscle pH, mitochondrial respiration, [SHS.SPORT.PS] Humanities and Social Sciences/Sport/Sport physiology, [SHS.SPORT] Humanities and Social Sciences/Sport, [SHS.SPORT.PS]Humanities and Social Sciences/Sport/Sport physiology, citrate synthase, state 3 respiration, muscle buffer capacity
Abstract: International audience; We tested the hypothesis that re- ducing hydrogen ion accumulation during training would result in greater improvements in muscle oxidative capacity and time to ex- haustion (TTE). Male Wistar rats were randomly assigned to one of three groups (CON, PLA, and BIC). CON served as a sedentary control, whereas PLA ingested water and BIC ingested sodium bicar- bonate 30 min prior to every training session. Training consisted of seven to twelve 2-min intervals performed five times/wk for 5 wk. Following training, TTE was significantly greater in BIC (81.2 ± 24.7 min) compared with PLA (53.5 ± 30.4 min), and TTE for both groups was greater than CON (6.5 ± 2.5 min). Fiber respiration was deter- mined in the soleus (SOL) and extensor digitorum longus (EDL), with either pyruvate (Pyr) or palmitoyl carnitine (PC) as substrates. Com- pared with CON (14.3 ± 2.6 nmol O2 • min-1 • mg dry wt-1), there was a signifi greater SOL-Pyr state 3 respiration in both PLA (19.6 ±3.0 nmol O2 • min-1 • mg dry wt-1) and BIC (24.4 ± 2.8 nmol O2 • min-1 • mg dry wt-1), with a significantly greater value in BIC. However, state 3 respiration was significantly lower in the EDL from both trained groups compared with CON. These differences remained significant in the SOL, but not the EDL, when respiration was corrected for citrate synthase activity (an indicator of mitochondrial mass). These novel findings suggest that reducing muscle hydrogen ion accumulation during running training is associated with greater improvements in both mitochondrial mass and mitochondrial respiration in the soleus.
Published: 2010

32. Early referral to the rheumatologist for early arthritis patients: evidence for suboptimal care. Results from the ESPOIR cohort

Author: Fautrel , Bruno, Benhamou , Mathilde, Foltz , Violaine, Rincheval , Nathalie, Rat , Anne-Christine, Combe , Bernard, Berenbaum , Francis, Bourgeois , Pierre, Guillemin , Francis, Saraux , Alain, Rhumatologie, Université Paris Diderot - Paris 7 ( UPD7 ), Service de Rhumatologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre de coordination, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Lapeyronie, Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Immunologie et Pathologie ( EA2216 ), Université de Brest ( UBO ) -IFR148, CHRU Brest - Service de Rhumatologie ( CHU - BREST - Rhumato ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Centre d'Investigation Clinique ( CIC - Brest ), Université de Brest ( UBO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Maladies chroniques, santé perçue, et processus d'adaptation ( APEMAC ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Montpellier ( UM ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institute of Biomedical Engineering, École Polytechnique de Montréal (EPM), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Service de Rhumatologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Sorbonne Université - Faculté de Médecine - École de sages-femmes Saint-Antoine (SU ESF), Sorbonne Université (SU), Station de Technologie des Produits Végétaux (URTPV), Institut National de la Recherche Agronomique (INRA), Université de Lorraine (UL), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Hôpital Lapeyronie [Montpellier] (CHU), Service de rhumatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and CHU Pitié-Salpêtrière [AP-HP]
Subjects: Male, Multivariate analysis, Time Factors, MESH : Aged, MESH: Epidemiologic Methods, MESH : Referral and Consultation, MESH : Early Diagnosis, MESH : Guideline Adherence, Arthritis, Rheumatoid, 0302 clinical medicine, MESH: Practice Guidelines as Topic, MESH: Early Diagnosis, Pharmacology (medical), MESH : Female, 030212 general & internal medicine, MESH: Quality of Health Care, Disease management (health), skin and connective tissue diseases, Referral and Consultation, ComputingMilieux_MISCELLANEOUS, MESH: Aged, MESH: Arthritis, Rheumatoid, MESH: Middle Aged, MESH : Quality of Health Care, Middle Aged, MESH : Adult, 3. Good health, MESH : Practice Guidelines as Topic, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, MESH: Young Adult, Rheumatoid arthritis, Cohort, MESH: Guideline Adherence, Practice Guidelines as Topic, Female, MESH: Clinical Competence, Clinical Competence, France, Guideline Adherence, Health Services Research, Family Practice, MESH: Health Services Research, MESH : Time Factors, Adult, musculoskeletal diseases, medicine.medical_specialty, Referral, Adolescent, MESH : Family Practice, MESH : Male, MESH : Health Services Research, MESH : Young Adult, MESH : Epidemiologic Methods, 03 medical and health sciences, MESH: Referral and Consultation, Young Adult, Rheumatology, Internal medicine, MESH : Adolescent, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, medicine, Humans, MESH : Middle Aged, MESH : France, MESH: Family Practice, Aged, Quality of Health Care, 030203 arthritis & rheumatology, MESH: Adolescent, MESH: Humans, business.industry, MESH: Time Factors, MESH : Humans, MESH: Adult, medicine.disease, MESH : Clinical Competence, MESH: Male, MESH: France, Early Diagnosis, MESH : Arthritis, Rheumatoid, Physical therapy, Managed care, business, Epidemiologic Methods, MESH: Female, Rheumatism, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; OBJECTIVE: To assess the time to access a rheumatologist (TTAR) by early arthritis (EA) patients participating in a nationwide incidental cohort (ESPOIR) and compare it with European League Against Rheumatism (EULAR) recommendations, which recommends rapid referral, ideally within 6 weeks, to a rheumatologist for patients presenting with EA. METHODS: Eight hundred and thirteen patients with EA were included in the cohort between 2002 and 2005. The inclusion criteria were 18-70 years old, two or more swollen joints, symptom duration from 6 weeks to 6 months and possible RA diagnosis. TTAR was defined as the time between the first synovitis and first visit to a rheumatologist. TTAR and satisfaction of the EULAR guidelines were investigated by multiple linear and logistic regressions. RESULTS: Mean TTAR was 76 days; only 46.2% of patients were seen by a rheumatologist within the EULAR-recommended time frame. Patients' patterns of accessing medical care substantially affected access to specialized care: mean TTAR was 58 days for patients who directly scheduled an appointment with the rheumatologist and 78 days for those referred by their general practitioner (P < 0.0007). Only 57.2 and 44.5%, respectively, were able to consult a rheumatologist within 6 weeks. Multivariate analysis confirmed the significant impact of indirect access on TTAR, after adjustment for EA characteristics and medical density in the region. CONCLUSIONS: Significant disparities were identified in the care of EA patients in terms of early access to a rheumatologist. More effort is needed to optimize the physicians' knowledge about EA and to improve the efficiency of medical networks.
Published: 2010

33. Topoisomerase I suppresses genomic instability by preventing interference between replication and transcription

Author: John De Vos, Laure Crabbe, Anna Jauch, Véronique Pantesco, Yves Pommier, Aubin Thomas, Heidi Holtgreve-Grez, Charles Theillet, Philippe Pasero, Sandie Tuduri, Arnaud Coquelle, Jamal Tazi, Hélène Tourrière, Chiara Conti, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), Institut de recherche en biothérapie (IRB), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Unité de thérapie cellulaire, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut de génétique humaine ( IGH ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de recherche en cancérologie de Montpellier ( IRCM ), Université Montpellier 1 ( UM1 ) -CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Institut de recherche en biothérapie ( IRB ), Université Montpellier 1 ( UM1 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Université de Montpellier ( UM ), Montpellier 1 - UFR de Médecine ( UM1 Médecine ), Université Montpellier 1 ( UM1 ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -CHU Saint-Eloi, and Institut de Génétique Moléculaire de Montpellier ( IGMM )
Subjects: DNA re-replication, DNA Replication, Chromatin Immunoprecipitation, Transcription, Genetic, Eukaryotic DNA replication, Biology, Pre-replication complex, Article, Genomic Instability, S Phase, DNA replication factor CDT1, 03 medical and health sciences, 0302 clinical medicine, Replication factor C, Minichromosome maintenance, Control of chromosome duplication, Animals, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, Cell Biology, Molecular biology, Cell biology, DNA Topoisomerases, Type I, 030220 oncology & carcinogenesis, biology.protein, Origin recognition complex, [ SDV.GEN ] Life Sciences [q-bio]/Genetics
Abstract: Topoisomerase I (Top1) is a key enzyme in functioning at the interface between DNA replication, transcription and mRNA maturation. Here, we show that Top1 suppresses genomic instability in mammalian cells by preventing a conflict between transcription and DNA replication. Using DNA combing and ChIP (chromatin immunoprecipitation)-on-chip, we found that Top1-deficient cells accumulate stalled replication forks and chromosome breaks in S phase, and that breaks occur preferentially at gene-rich regions of the genome. Notably, these phenotypes were suppressed by preventing the formation of RNA-DNA hybrids (R-loops) during transcription. Moreover, these defects could be mimicked by depletion of the splicing factor ASF/SF2 (alternative splicing factor/splicing factor 2), which interacts functionally with Top1. Taken together, these data indicate that Top1 prevents replication fork collapse by suppressing the formation of R-loops in an ASF/SF2-dependent manner. We propose that interference between replication and transcription represents a major source of spontaneous replication stress, which could drive genomic instability during the early stages of tumorigenesis.
Published: 2010

34. An in vitro model of differentiation of memory B cells into plasmablasts and plasma cells including detailed phenotypic and molecular characterization

Author: Marion Larroque, John De Vos, Michel Jourdan, Anouk Caraux, Geneviève Fiol, Dirk Hose, Christophe Duperray, Caroline Bret, Chantal Cognot, Bernard Klein, Institut de recherche en biothérapie (IRB), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Laboratoire d'immunologie, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Department of Internal Medicine V, Universität Heidelberg [Heidelberg], Nationales Centrum für Tumorerkrankungen, Grant from the Ligue Nationale Contre le Cancer (equipe labellisee 2009), INCA, MSCNET European strep (n°e06005ff), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), and Frei, Monique
Subjects: X-Box Binding Protein 1, Time Factors, MESH: Immunoglobulins, plasma cell, Cellular differentiation, Cell Culture Techniques, MESH: Flow Cytometry, Plasma cell, Biochemistry, Immunophenotyping, 0302 clinical medicine, MESH: Reverse Transcriptase Polymerase Chain Reaction, Activation-induced (cytidine) deaminase, Cells, Cultured, Oligonucleotide Array Sequence Analysis, B-Lymphocytes, 0303 health sciences, MESH: Plasma Cells, biology, Reverse Transcriptase Polymerase Chain Reaction, Stem Cells, MESH: Bone Marrow Cells, Cell Differentiation, Hematology, MESH: Transcription Factors, Flow Cytometry, humanities, 3. Good health, DNA-Binding Proteins, multiple myeloma, medicine.anatomical_structure, Interferon Regulatory Factors, Proto-Oncogene Proteins c-bcl-6, MESH: Immunologic Memory, Antibody, Stem cell, MESH: Interferon Regulatory Factors, MESH: Cells, Cultured, MESH: Cell Differentiation, MESH: Immunophenotyping, MESH: Syndecan-1, Plasma Cells, Immunology, MESH: B-Cell-Specific Activator Protein, Immunoglobulins, Bone Marrow Cells, Regulatory Factor X Transcription Factors, MESH: Stem Cells, Models, Biological, Article, 03 medical and health sciences, MESH: Gene Expression Profiling, Cytidine Deaminase, transcription factors, MESH: B-Lymphocytes, PRDM1, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, MESH: Cytidine Deaminase, MESH: Cell Culture Techniques, MESH: Humans, B lymphocyte, Gene Expression Profiling, MESH: Time Factors, PAX5 Transcription Factor, MESH: Models, Biological, Cell Biology, Molecular biology, MESH: Oligonucleotide Array Sequence Analysis, biology.protein, Syndecan-1, Bone marrow, Immunologic Memory, MESH: DNA-Binding Proteins, 030215 immunology
Abstract: Abstract 1636 Poster Board I-662 Human plasma cells (PCs) and their precursors play an essential role in humoral immune response, but are rare and difficult to harvest. We report here i) the generation of human syndecan-1+ and immunoglobulin secreting PCs starting from memory B cells (MBCs) in a 3-step- and 10-day (D) culture, including a 6-fold cell amplification. ii) We report the detailed phenotypic and Affymetrix gene expression profiles of these in vitro PCs as well as of intermediate cells - activated B cells (actBCs) and plasmablasts (PBs) - compared to MBCs and bone marrow PCs, which is accessible through an open web ATLAS (http://amazonia.transcriptome.eu/). iii) We show this B cell to PC differentiation to involve IRF4 and AICDA expression in D4 actBCs, decrease of PAX5 and BCL6 expressions and increase in PRDM1 and XBP1 expressions in D7 PBs and D10 PCs. It involves downregulation of genes controlled by Pax5, induction of genes controlled by Blimp-1 and XBP1 (unfold protein response). iv) The phenotype of D10 PCs resembles that of peripheral blood PCs detected after immunization of healthy donors. This in vitro model will facilitate further studies in PC biology. It will likewise be helpful to study plasma-cell dyscrasias, including Multiple Myeloma. Disclosures No relevant conflicts of interest to declare.
Published: 2009

35. The role of IGF-1 as a major growth factor for myeloma cell lines and the prognostic relevance of the expression of its receptor

Author: Sprynski, Anne Catherine, Hose, Dirk, Caillot, Laurent, Rème, Thierry, Shaughnessy Jr, John, Barlogie, Bart, Seckinger, Anja, Moreaux, Jérôme, Hundemer, Michael, Jourdan, Michel, Meissner, Tobias, Jauch, Anna, Mahtouk, Karene, Kassambara, Alboukadel, Bertsch, Uta, Rossi, Jean-François, Goldschmidt, Hartmut, Klein, Bernard, Institut de recherche en biothérapie (IRB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Department of Internal Medicine V, Universität Heidelberg [Heidelberg], Nationales Centrum für Tumorerkrankungen, ABCell-Bio (ABCELL-BIO), ABCell-Bio, CHU de Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences (UAMS), Dept. of Medical Physics and Clinical Engineering, University of Sheffield [Sheffield], Institut für Humangenetik, Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), and Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: IL-6, myeloma, IGF-1, growth factor, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, APRIL, HGF
Abstract: International audience; A plethora of myeloma growth factors (MGF) has been identified, but their relative importance and cooperation has not been determined. We investigated 5 well-documented MGF (IL-6, IGF-1, HGF, HB-EGF, APRIL) in serum-free cultures of human myeloma cell lines (HMCLs). In all of 3 CD45(-) HMCLs, an autocrine IGF-1 loop promoted autonomous survival. To the contrary, all 5 CD45(+) HMCLs could not survive and required addition of either IL-6 (5/5), IGF-1 (4/5), HGF (1/5), HB-EGF (1/5) or APRIL (1/5). IGF-1 was the major MGF since its activity was abrogated by an IGF-1R inhibitor only, whereas IL-6, HGF or HB-EGF activity was inhibited by both IGF-1R- and receptor-specific inhibition. APRIL activity was inhibited by its specific inhibitor only. Of the investigated MGF and their receptors, only expressions of IGF-1R and IL-6R in myeloma cells (MMC) of patients delineate a group with adverse prognosis. This is mainly explained by a strong association of IGF-1R and IL-6R expression and t(4;14) translocation, but IGF-1R expression in MMC, without t(4;14) can also have a poor prognosis. Thus, IGF-1 targeted therapy - eventually in combination with anti-IL-6 therapy - could be promising in a subset of patients with MMC expressing IGF-1R.
Published: 2009

36. APRIL and TACI interact with syndecan-1 on the surface of multiple myeloma cells to form an essential survival loop

Author: Nicolas Robert, Philippe Moine, Bernard Klein, Arnaud Ythier, Michel Jourdan, Anne-Catherine Sprynski, Jérôme Moreaux, Karène Mahtouk, Eric Jourdan, Stacey R. Dillon, Jean François Rossi, Frei, Monique, Institut de recherche en biothérapie (IRB), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), ZymoGenetics, MERCK SERONO INTERNATIONAL, Merck & Co. Inc, Service d'hématologie, Centre Hospitalier Saint Jean de Perpignan, Service d'hématologie et oncologie clinique, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Supported by grants from the Ligue Nationale Contre le Cancer (equipe labellisee 2009), Paris, France - from INCA (n°R07001FN) and from MSCNET European strep (E06005FF), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)
Subjects: MESH: Cell Line, Tumor, MESH: Heparin, MESH: Syndecan-1, Cell Survival, Transmembrane Activator and CAML Interactor Protein, Tumor Necrosis Factor Ligand Superfamily Member 13, MESH: Flow Cytometry, MESH: Multiple Myeloma, Fibroblast growth factor, Syndecan 1, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Multiple myeloma, Cell Line, Tumor, hemic and lymphatic diseases, MESH: Cell Proliferation, MESH: Reverse Transcriptase Polymerase Chain Reaction, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Transmembrane Activator and CAML Interactor Protein, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, APRIL, Receptor, B-cell activating factor, Cell Proliferation, 030304 developmental biology, 0303 health sciences, MESH: Humans, Heparin, Reverse Transcriptase Polymerase Chain Reaction, Cell growth, Cell Membrane, MESH: Tumor Necrosis Factor Ligand Superfamily Member 13, Hematology, General Medicine, Heparan sulfate, Flow Cytometry, chemistry, MESH: Cell Survival, Fibroblast growth factor receptor, Cell culture, 030220 oncology & carcinogenesis, Cancer research, BAFF, Syndecan-1, BLyS, syndecan, MESH: Cell Membrane
Abstract: International audience; BLyS and APRIL share two receptors - transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and B-cell maturation antigen (BCMA) - and BLyS binds to a third receptor, BAFF-R. We previously reported that TACI gene expression is a good indicator of a BLyS-binding receptor in human multiple myeloma cell lines (HMCLs), unlike BCMA, which is expressed by all HMCLs or BAFF-R which is typically not expressed by late-stage B cells. We hypothesised a link between APRIL and TACI through syndecan-1, similar to the situation reported for FGF and FGFR. We observed very strong binding of APRIL, but not BLyS, at the surface of all syndecan-1(+) HMCLs and primary multiple myeloma cells (MMC). All syndecan-1(+) HMCLs and MMC could also bind TACI-Fc, but not BCMA-Fc or BAFF-R-Fc molecules. Binding of APRIL or TACI-Fc was abrogated by heparin or cell pretreatment with heparitinase, which cleaves heparan sulfate chains. The growth factor activity of APRIL on MMC was also inhibited by heparin. Our data identify syndecan-1 as a co-receptor for APRIL and TACI at the cell surface of MMC, promoting the activation of an APRIL/TACI pathway that induces survival and proliferation in MMC.
Published: 2009

37. The relationship between monocarboxylate transporters 1 and 4 expression in skeletal muscle and endurance performance in athletes

Author: Grégoire P. Millet, Robert Ives, David Cameron-Smith, David J. Bentley, Jacques Mercier, Claire Thomas, Belle Roels, Université d'Évry-Val-d'Essonne (UEVE), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), University of New South Wales [Sydney] (UNSW), Euromov (EuroMov), Université de Montpellier (UM), Muscles et pathologies, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), Institut des sciences du sport et de l’éducation physique, Université de Lausanne (UNIL), School of Exercise and Nutrition Sciences, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lausanne = University of Lausanne (UNIL), and INSEP, documentation
Subjects: Physiology, 030310 physiology, Gene Expression, Muscle Proteins, [SHS.SPORT.PS]Humanities and Social Sciences/Sport/Sport physiology, Incremental exercise, 0302 clinical medicine, Time trial, Task Performance and Analysis, Citrate synthase, Orthopedics and Sports Medicine, 0303 health sciences, biology, Symporters, [SHS.SPORT] Humanities and Social Sciences/Sport, Cycling, General Medicine, Correlation, medicine.anatomical_structure, Muscle Fatigue, Regulation, Monocarboxylic Acid Transporters, medicine.medical_specialty, Vastus lateralis muscle, [SHS.SPORT.PS] Humanities and Social Sciences/Sport/Sport physiology, Athletic Performance, 03 medical and health sciences, Oxygen Consumption, Physiology (medical), Internal medicine, medicine, Humans, Power output, Muscle, Skeletal, [SHS.SPORT]Humanities and Social Sciences/Sport, Athletes, business.industry, Public Health, Environmental and Occupational Health, Skeletal muscle, Transporter, Aerobic, 030229 sport sciences, biology.organism_classification, Bicycling, Oxygen, Endocrinology, Physical Fitness, Power, biology.protein, Exercise Test, Physical Endurance, business, Energy Metabolism
Abstract: International audience; The purpose of this study was to examine the relationship between skeletal muscle monocarboxylate transporters 1 and 4 (MCT1 and MCT4) expression, skeletal muscle oxidative capacity and endurance performance in trained cyclists. Ten well-trained cyclists (mean ± SD; age 24.4 ± 2.8 years, body mass 73.2 ± 8.3 kg, VO2max 58 ± 7 ml kg−1 min−1) completed three endurance performance tasks [incremental exercise test to exhaustion, 2 and 10 min time trial (TT)]. In addition, a muscle biopsy sample from the vastus lateralis muscle was analysed for MCT1 and MCT4 expression levels together with the activity of citrate synthase (CS) and 3-hydroxyacyl-CoA dehydrogenase (HAD). There was a tendency for VO2max and peak power output obtained in the incremental exercise test to be correlated with MCT1 (r = −0.71 to −0.74; P < 0.06), but not MCT4. The average power output (Paverage) in the 2 min TT was significantly correlated with MCT4 (r = −0.74; P < 0.05) and HAD (r = −0.92; P < 0.01). The Paverage in the 10 min TT was only correlated with CS activity (r = 0.68; P < 0.05). These results indicate the relationship between MCT1 and MCT4 as well as cycle TT performance may be influenced by the length and intensity of the task.
Published: 2009

38. The role of IGF-1 as a major growth factor for myeloma cell lines and the prognostic relevance of the expression of its receptor.: IGF-1 is the major growth factor on myeloma

Author: Sprynski, Anne Catherine, Hose, Dirk, Caillot, Laurent, Rème, Thierry, Shaughnessy Jr, John, Barlogie, Bart, Seckinger, Anja, Moreaux, Jérôme, Hundemer, Michael, Jourdan, Michel, Meissner, Tobias, Jauch, Anna, Mahtouk, Karene, Kassambara, Alboukadel, Bertsch, Uta, Rossi, Jean-François, Goldschmidt, Hartmut, Klein, Bernard, Frei, Monique, Institut de recherche en biothérapie (IRB), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Department of Internal Medicine V, Universität Heidelberg [Heidelberg], Nationales Centrum für Tumorerkrankungen, ABCell-Bio (ABCELL-BIO), ABCell-Bio, CHU de Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences (UAMS), Dept. of Medical Physics and Clinical Engineering, University of Sheffield [Sheffield], Institut für Humangenetik, Université Montpellier 1 - UFR de Médecine (UM1 Médecine), and Université Montpellier 1 (UM1)
Subjects: IL-6, myeloma, IGF-1, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, growth factor, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, APRIL, HGF
Abstract: International audience; A plethora of myeloma growth factors (MGF) has been identified, but their relative importance and cooperation has not been determined. We investigated 5 well-documented MGF (IL-6, IGF-1, HGF, HB-EGF, APRIL) in serum-free cultures of human myeloma cell lines (HMCLs). In all of 3 CD45(-) HMCLs, an autocrine IGF-1 loop promoted autonomous survival. To the contrary, all 5 CD45(+) HMCLs could not survive and required addition of either IL-6 (5/5), IGF-1 (4/5), HGF (1/5), HB-EGF (1/5) or APRIL (1/5). IGF-1 was the major MGF since its activity was abrogated by an IGF-1R inhibitor only, whereas IL-6, HGF or HB-EGF activity was inhibited by both IGF-1R- and receptor-specific inhibition. APRIL activity was inhibited by its specific inhibitor only. Of the investigated MGF and their receptors, only expressions of IGF-1R and IL-6R in myeloma cells (MMC) of patients delineate a group with adverse prognosis. This is mainly explained by a strong association of IGF-1R and IL-6R expression and t(4;14) translocation, but IGF-1R expression in MMC, without t(4;14) can also have a poor prognosis. Thus, IGF-1 targeted therapy - eventually in combination with anti-IL-6 therapy - could be promising in a subset of patients with MMC expressing IGF-1R.
Published: 2009

39. Effect of intermittent hypoxic training on HIF gene expressionin human skeletal muscle and leukocytes

Author: Claire Thomas, Vincent Pialoux, Grégoire P. Millet, Nicole Fellmann, Belle Roels, Jacques Mercier, Jean Coudert, Eric Clottes, Rémi Mounier, Muscles et pathologies, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Laboratoire de Physiologie-Biologie du Sport, Université d'Auvergne - Clermont-Ferrand I (UdA), School of Sport and Education, Brunel University London [Uxbridge], Euromov (EuroMov), Université de Montpellier (UM), Academy for Sports Excellence, Doha, Qatar, Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Monocarboxylic Acid Transporters, Vascular Endothelial Growth Factor A, medicine.medical_specialty, HIF-1x, Physiology, [SDV]Life Sciences [q-bio], mRNA, Gene Expression, Muscle Proteins, [SHS.SPORT.PS]Humanities and Social Sciences/Sport/Sport physiology, Skeletal muscle, Natural antisense, Biology, Hypoxic exposure, 03 medical and health sciences, Oxygen Consumption, 0302 clinical medicine, Physiology (medical), Internal medicine, Gene expression, Leukocytes, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Orthopedics and Sports Medicine, RNA, Messenger, Hypoxia, Muscle, Skeletal, Transcription factor, ComputingMilieux_MISCELLANEOUS, Intermittent hypoxic training, 030304 developmental biology, [SHS.SPORT]Humanities and Social Sciences/Sport, 0303 health sciences, Messenger RNA, Public Health, Environmental and Occupational Health, 030229 sport sciences, General Medicine, Anatomy, Hypoxia (medical), Leukocyte, Hypoxia-Inducible Factor 1, alpha Subunit, medicine.anatomical_structure, Endocrinology, medicine.symptom, Training program
Abstract: Intermittent hypoxic exposure with exercise training is based on the assumption that brief exposure to hypoxia is sufficient to induce beneficial muscular adaptations mediated via hypoxia-inducible transcription factors (HIF). We previously demonstrated (Mounier et al. Med Sci Sports Exerc 38:1410-1417, 2006) that leukocytes respond to hypoxia with a marked inter-individual variability in HIF-1alpha mRNA. This study compared the effects of 3 weeks of intermittent hypoxic training on hif gene expression in both skeletal muscle and leukocytes. Male endurance athletes (n = 19) were divided into an Intermittent Hypoxic Exposure group (IHE) and a Normoxic Training group (NT) with each group following a similar 3-week exercise training program. After training, the amount of HIF-1alpha mRNA in muscle decreased only in IHE group (-24.7%, P0.05) whereas it remained unchanged in leukocytes in both groups. The levels of vEGF(121) and vEGF(165) mRNA in skeletal muscle increased significantly after training only in the NT group (+82.5%, P0.05 for vEGF(121); +41.2%, P0.05 for vEGF(165)). In leukocytes, only the IHE group showed a significant change in vEGF(165) (-28.2%, P0.05). The significant decrease in HIF-1alpha mRNA in skeletal muscle after hypoxic training suggests that transcriptional and post-transcriptional regulations of the hif-1alpha gene are different in muscle and leukocytes.
Published: 2009

40. Total fertilization failure and molecular abnormalities in metaphase II oocytes

Author: Thierry Rème, Samir Hamamah, Hervé Dechaud, Lionel Reyftmann, Bernard Klein, Franck Pellestor, Tal Anahory, Said Assou, John De Vos, S. Gasca, Unité biologie clinique d'AMP-DPI, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Institut de recherche en biothérapie (IRB), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service de gynécologie-obstétrique et médecine de la reproduction, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Unité d'AMP/DPI, Département de Médecine et biologie de la reproduction, Immunopathologie des maladies tumorales et autoimmunes, Université Montpellier 1 (UM1)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Maco Pharma, MacoPharma, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut Pluridisciplinaire de Recherche sur l'Environnement et les Matériaux (IPREM), Université de Pau et des Pays de l'Adour (UPPA)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Unité de Thérapie Cellulaire et Génique, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Nationaal Natuurhistorish Museum, Unité de thérapie cellulaire, Assou, Said, Institut pluridisciplinaire de recherche sur l'environnement et les matériaux (IPREM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: Adult, Male, Microarray, medicine.medical_treatment, Apoptosis, Fertilization in Vitro, Biology, Intracytoplasmic sperm injection, Male infertility, Andrology, 03 medical and health sciences, 0302 clinical medicine, Human fertilization, Meiosis, Pregnancy, Gene expression, medicine, Humans, Sperm Injections, Intracytoplasmic, Gene, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, reproductive and urinary physiology, Metaphase, 030304 developmental biology, Oligonucleotide Array Sequence Analysis, 0303 health sciences, 030219 obstetrics & reproductive medicine, urogenital system, Obstetrics and Gynecology, Oocyte activation, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, medicine.disease, Fertility, Reproductive Medicine, Gene Expression Regulation, Fertilization, Infertility, Oocytes, Female, Developmental Biology
Abstract: International audience; Total fertilization failures (TFF) are rare events of IVF by intracytoplasmic sperm injection (ICSI). When male factor is excluded, the lack of identifiable aetiological criteria raises the question of the reliable clinical management. The goal of this study was to identify molecular abnormalities in metaphase II (MII) oocytes yielding TFF. The nuclear mature MII oocytes mRNA expression profiles were compared between a 30-year-old patient who had experienced three successive TFF (egg number = 39) and control patients with fertile cohorts diagnosed with tubal or male infertility. The mRNA abundance for the 30,000 genes of the genome was evaluated by microarray and, for selected genes, by quantitative-polymerase chain reaction analysis. Transcriptional analysis of unfertilized MII oocytes revealed an altered gene expression profile associated with TFF. Meiosis, cell growth and apoptosis controlling genes were mis-expressed with important fold changes. The results reveal that, despite passing the pre-IVF morphological examination, high-grade oocytes may carry substantial molecular abnormalities at the gene expression level associated with failure of MII oocyte activation. In the absence of an identifiable defect causing TFF, this microarray approach allows improvement of clinical therapeutic management: informed counselling about alternate therapeutic solutions could be proposed.
Published: 2008

41. Effects of high-intensity training on muscle lactate transporters and postexercise recovery of muscle lactate and hydrogen ions in women

Author: David Bishop, Jacques Mercier, Johann Edge, Claire Thomas, Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Université d'Évry-Val-d'Essonne (UEVE), Università degli studi di Verona, School of Human Movement and Exercise Science, The University of Western Australia (UWA), Institute of food, Nutrition and Human health, Muscle et pathologies, Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Vérone, Università degli studi di Verona = University of Verona (UNIVR), and INSEP, documentation
Subjects: Monocarboxylic Acid Transporters, medicine.medical_specialty, Time Factors, Phosphocreatine, Physiology, [SHS.SPORT.PS] Humanities and Social Sciences/Sport/Sport physiology, [SHS.SPORT.PS]Humanities and Social Sciences/Sport/Sport physiology, Muscle Proteins, buffer capacity, 030204 cardiovascular system & hematology, Interval training, Quadriceps Muscle, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Adenosine Triphosphate, Oxygen Consumption, Physiology (medical), Internal medicine, medicine, Humans, phosphocreatine resynthesis, Lactic Acid, [SHS.SPORT]Humanities and Social Sciences/Sport, biology, Symporters, High intensity, [SHS.SPORT] Humanities and Social Sciences/Sport, monocarboxylate transporter 1, Transporter, Resistance Training, females, 030229 sport sciences, Recovery of Function, Hydrogen-Ion Concentration, monocarboxylate transporter 4, Phosphocreatine metabolism, Endocrinology, Monocarboxylate transporter 1, Biochemistry, Monocarboxylate transporter 4, biology.protein, Female, medicine.symptom, Intracellular, Muscle contraction, Muscle Contraction
Abstract: The purpose of this study was to investigate the effects of high-intensity interval training (3 days/wk for 5 wk), provoking large changes in muscle lactate and pH, on changes in intracellular buffer capacity (βmin vitro), monocarboxylate transporters (MCTs), and the decrease in muscle lactate and hydrogen ions (H+) after exercise in women. Before and after training, biopsies of the vastus lateralis were obtained at rest and immediately after and 60 s after 45 s of exercise at 190% of maximal O2 uptake. Muscle samples were analyzed for ATP, phosphocreatine (PCr), lactate, and H+; MCT1 and MCT4 relative abundance and βmin vitro were also determined in resting muscle only. Training provoked a large decrease in postexercise muscle pH (pH 6.81). After training, there was a significant decrease in βmin vitro (−11%) and no significant change in relative abundance of MCT1 (96 ± 12%) or MCT4 (120 ± 21%). During the 60-s recovery after exercise, training was associated with no change in the decrease in muscle lactate, a significantly smaller decrease in muscle H+, and increased PCr resynthesis. These results suggest that increases in βmin vitro and MCT relative abundance are not linked to the degree of muscle lactate and H+ accumulation during training. Furthermore, training that is very intense may actually lead to decreases in βmin vitro. The smaller postexercise decrease in muscle H+ after training is a further novel finding and suggests that training that results in a decrease in H+ accumulation and an increase in PCr resynthesis can actually reduce the decrease in muscle H+ during the recovery from supramaximal exercise.
Published: 2008

42. UMD-USHbases: a comprehensive set of databases to record and analyse pathogenic mutations and unclassified variants in seven Usher syndrome causing genes

Author: Mireille Claustres, David Baux, Dalil Hamroun, Valérie Faugère, Lise Larrieu, Anne-Françoise Roux, Christophe Béroud, Sandie Le Guédard-Méreuze, Sue Malcolm, Genetics, Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Clinical and Molecular Genetics, and University College of London [London] (UCL)-Institute of Child Health
Subjects: Genotype, MYO7A, Usher syndrome, Biology, computer.software_genre, medicine.disease_cause, 03 medical and health sciences, User-Computer Interface, 0302 clinical medicine, Retinitis pigmentosa, Databases, Genetic, Genetics, medicine, otorhinolaryngologic diseases, Missense mutation, Humans, Gene, Genetics (clinical), 030304 developmental biology, 0303 health sciences, Mutation, Extracellular Matrix Proteins, Polymorphism, Genetic, Database, Models, Genetic, Computational Biology, Genetic Variation, Exons, medicine.disease, Molecular diagnostics, Introns, 3. Good health, Phenotype, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], computer, Usher Syndromes, 030217 neurology & neurosurgery, PCDH15, Software
Abstract: International audience; Using the Universal Mutation Database (UMD) software, we have constructed "UMD-USHbases", a set of relational databases of nucleotide variations for seven genes involved in Usher syndrome (MYO7A, CDH23, PCDH15, USH1C, USH1G, USH3A and USH2A). Mutations in the Usher syndrome type I causing genes are also recorded in non-syndromic hearing loss cases and mutations in USH2A in non-syndromic retinitis pigmentosa. Usher syndrome provides a particular challenge for molecular diagnostics because of the clinical and molecular heterogeneity. As many mutations are missense changes, and all the genes also contain apparently non-pathogenic polymorphisms, well-curated databases are crucial for accurate interpretation of pathogenicity. Tools are provided to assess the pathogenicity of mutations, including conservation of amino acids and analysis of splice-sites. Reference amino acid alignments are provided. Apparently non-pathogenic variants in patients with Usher syndrome, at both the nucleotide and amino acid level, are included. The UMD-USHbases currently contain more than 2,830 entries including disease causing mutations, unclassified variants or non-pathogenic polymorphisms identified in over 938 patients. In addition to data collected from 89 publications, 15 novel mutations identified in our laboratory are recorded in MYO7A (6), CDH23 (8), or PCDH15 (1) genes. Information is given on the relative involvement of the seven genes, the number and distribution of variants in each gene. UMD-USHbases give access to a software package that provides specific routines and optimized multicriteria research and sorting tools. These databases should assist clinicians and geneticists seeking information about mutations responsible for Usher syndrome.
Published: 2008

43. In vitro expansion of gamma delta T cells with anti-myeloma cell activity by Phosphostim and IL-2 in patients with multiple myeloma

Author: Burjanadze, Maka, Condomines, Maud, Rème, Thierry, Quittet, Philippe, Latry, Pascal, Lugagne, Cécile, Romagne, François, Morel, Yanis, Rossi, Jean-François, Klein, Bernard, Lu, Zhao-Yang, Institut de recherche en biothérapie (IRB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Service d'hématologie et oncologie médicale, Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Unité de thérapie cellulaire, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Innate Pharma, and Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: multiple myeloma, gamma delta T cells, cytotoxicity, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, immunotherapy, cellular therapy, [SDV.BC]Life Sciences [q-bio]/Cellular Biology
Abstract: International audience; T-cell-mediated immunotherapy is a promising therapeutic option for multiple myeloma (MM). Gamma-delta T cells (gammadelta T cells) recognize phosphoantigens and display strong anti-tumour cytotoxicity. The synthetic agonist Phosphostim (bromohydrin pyrophosphate, BrHPP) has been shown to selectively activate Vgamma9Vdelta2 T cells. This study aimed to evaluate the expansion capacity and anti-myeloma cell cytotoxicity of circulating gammadelta T cells from MM patients at different time points throughout the disease, using Phosphostim and interleukin 2 (IL-2). Circulating gammadelta T cell counts in patients with newly diagnosed MM or in relapse did not differ from those in healthy donors. A 14-d culture of peripheral blood mononuclear cells with Phosphostim and IL-2 triggered a 100-fold expansion of gammadelta T cells in 78% of newly diagnosed patients. gammadelta T cells harvested at the time of haematopoietic progenitor collection or in relapsing patients expanded less efficiently. Expanded gammadelta T cells killed 13/14 myeloma cell lines as well as primary myeloma cells, but not normal CD34 cells. Their killing efficiency was not affected by 2-d IL-2 starvation. This study demonstrated the ability of Phosphostim and IL-2 to expand gammadelta T cells from MM patients, and the efficient and stable killing of human myeloma cells by gd T cells.
Published: 2007

44. Targeting NF-kappaB pathway with an IKK2 inhibitor induces inhibition of multiple myeloma cell growth

Author: Jourdan, Michel, Moreaux, Jérôme, Vos, John De, Hose, Dirk, Mahtouk, Karène, Abouladze, Matthieu, Robert, Nicolas, Baudard, Marion, Rème, Thierry, Romanelli, Angela, Goldschmidt, Hartmut, Rossi, Jean-François, Dreano, Michel, Klein, Bernard, Institut de recherche en biothérapie (IRB), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Department of Internal Medicine V, Universität Heidelberg [Heidelberg], Department of Hematology and Clinical Oncology, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Serono Research Institute, Serono, Serono International SA (SERONO INTERNATIONAL SA), Serono International SA, and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)
Subjects: cell cycle, Multiple myeloma, NF-kappa B, apoptosis, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, IKK2 inhibitor
Abstract: The pathophysiologic basis for multiple myeloma (MM) has been attributed to the dysregulation of various paracrine or autocrine growth factor loops and to perturbations in several signal transduction pathways including IkappaB kinase/nuclear factor-kappaB (IKK/NF-kappaB). The present study aimed at investigating the effect of a pharmaceutical IKK2 inhibitor, the anilinopyrimidine derivative AS602868, on the in vitro growth of 14 human MM cell lines (HMCL) and primary cells from 13 patients. AS602868 induced a clear dose-dependent inhibition of MM cell growth on both HMCL and primary MM cells, which was the result of a simultaneous induction of apoptosis and inhibition of the cell cycle progression. Combination of AS602868 with suboptimal doses of melphalan or Velcade showed an additive effect in growth inhibition of HMCL. AS602868 also induced apoptosis of primary myeloma cells. Importantly, AS602868 did not alter the survival of other bone marrow mononuclear cells (CD138(-)) co-cultured with primary MM (CD138(+)) cells, except for CD34(+) haematopoietic stem cells. The results demonstrate the important role of NF-kappaB in maintaining the survival of MM cells and suggest that a pharmacological inhibition of the NF-kappaB pathway by the IKK2 inhibitor AS602868 can efficiently kill HMCL and primary myeloma cells and therefore might represent an innovative approach for treating MM patients.
Published: 2007

45. A meta-analysis of human embryonic stem cells transcriptome integrated into a web-based expression atlas

Author: S Tondeur, Susanne Ström, Sophie Marty, Thierry Rème, Samir Hamamah, Bernard Klein, S. Gasca, Said Assou, Outi Hovatta, Tanguy Le Carrour, L Nadal, Jean-Philippe Hugnot, Véronique Pantesco, John De Vos, Audrey Gabelle, Institut de recherche en biothérapie (IRB), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Maco Pharma, MacoPharma, Department of Obstetrics and Gynecology, CLINTEC, karolinska institute, Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Physiopathologie et thérapie des déficits sensoriels et moteurs, Université Montpellier 2 - Sciences et Techniques (UM2)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité biologie clinique d'AMP-DPI, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Frei, Monique, and Institut des Neurosciences de Montpellier (INM)
Subjects: Homeobox protein NANOG, Transcription, Genetic, Cellular differentiation, Computational biology, Biology, Article, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, SOX2, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, gene expression profiling, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Growth Substances, Induced pluripotent stem cell, Embryonic Stem Cells, reproductive and urinary physiology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Genetics, Regulation of gene expression, 0303 health sciences, Microarray analysis techniques, Chromosome Mapping, Cell Differentiation, Cell Biology, equipment and supplies, Gene expression profiling, Gene Expression Regulation, 030220 oncology & carcinogenesis, embryonic structures, Molecular Medicine, microarray analysis, biological phenomena, cell phenomena, and immunity, pluripotent stem cells, Transcription Factors, Developmental Biology
Abstract: Microarray technology provides a unique opportunity to examine gene expression patterns in human embryonic stem cells (hESCs). We performed a meta-analysis of 38 original studies reporting on the transcriptome of hESCs. We determined that 1,076 genes were found to be overexpressed in hESCs by at least three studies when compared to differentiated cell types, thus composing a “consensus hESC gene list.” Only one gene was reported by all studies: the homeodomain transcription factor POU5F1/OCT3/4. The list comprised other genes critical for pluripotency such as the transcription factors NANOG and SOX2, and the growth factors TDGF1/CRIPTO and Galanin. We show that CD24 and SEMA6A, two cell surface protein-coding genes from the top of the consensus hESC gene list, display a strong and specific membrane protein expression on hESCs. Moreover, CD24 labeling permits the purification by flow cytometry of hESCs cocultured on human fibroblasts. The consensus hESC gene list also included the FZD7 WNT receptor, the G protein-coupled receptor GPR19, and the HELLS helicase, which could play an important role in hESCs biology. Conversely, we identified 783 genes downregulated in hESCs and reported in at least three studies. This “consensus differentiation gene list” included the IL6ST/GP130 LIF receptor. We created an online hESC expression atlas, http://amazonia.montp.inserm.fr, to provide an easy access to this public transcriptome dataset. Expression histograms comparing hESCs to a broad collection of fetal and adult tissues can be retrieved with this web tool for more than 15,000 genes. Disclosure of potential conflicts of interest is found at the end of this article.
Published: 2007

46. B7-1 and 4-1BB ligand expression on a myeloma cell line makes it possible to expand autologous tumor-specific cytotoxic T cells in vitro

Author: Jean François Rossi, Marie Claude Delteil, Christophe Ferrand, Karin Tarte, Zhao-Yang Lu, L Nadal, Bernard Klein, Maud Condomines, Unité de thérapie cellulaire, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Institut de recherche en biothérapie (IRB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Immunopathologie des maladies tumorales et autoimmunes, Université Montpellier 1 (UM1)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie et oncologie médicale, Hôpital Lapeyronie-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Laboratoire de biologie moléculaire, EFS, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Frei, Monique, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM)
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Cancer Research, medicine.medical_treatment, chemistry.chemical_compound, 0302 clinical medicine, Transduction, Genetic, Cytotoxic T cell, 0303 health sciences, biology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Middle Aged, medicine.anatomical_structure, 030220 oncology & carcinogenesis, B7-1 Antigen, [SDV.IMM]Life Sciences [q-bio]/Immunology, Multiple Myeloma, medicine.drug, Interleukin 2, DNA, Complementary, [SDV.IMM] Life Sciences [q-bio]/Immunology, T cell, Genetic Vectors, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Genetics, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, 030304 developmental biology, CD40, Cell Biology, Immunotherapy, Molecular biology, Coculture Techniques, CTL, 4-1BB ligand, 4-1BB Ligand, Retroviridae, chemistry, Gene Expression Regulation, biology.protein, Interleukin-2, CD8, T-Lymphocytes, Cytotoxic
Abstract: International audience; OBJECTIVE: The aim of this study was to confer an antigen-presenting cell (APC) ability on multiple myeloma cell lines (HMCLs) using B7-1 and/or 4-1BBL gene transfer. MATERIALS AND METHODS: HMCLs were retrovirally transduced with B7-1 and/or 4-1BBL cDNAs. Allogeneic or autologous T cells were stimulated by coculture with B7-1- and/or 4-1BBL-transduced HMCLs in the presence of interleukin-2. T cell clones were obtained by limiting dilution. T-cell activation was assessed by interferon-gamma Elispot assays and cytotoxicity by (51)Cr release assays. RESULTS: Neither primary multiple myeloma cells (MMCs) nor HMCLs expressed B7-1 or 4-1BBL, and these molecules could not be induced by CD40 triggering. HMCLs failed to stimulate allogeneic or autologous T cells. Transduction of HMCLs with B7-1 and/or 4-1BBL retroviruses induced a high expression of B7-1 and 4-1BBL molecules and a strong T-cell activation ability. Long-term cultured CD8(+) T-cell lines could be obtained by stimulation with the autologous B7-1/4-1BBL XG-19 HMCL. These cytotoxic T lymphocytes (CTL) efficiently killed the autologous parental XG-19 HMCL as well as autologous primary MMCs and allogeneic HMCLs. They did not kill autologous CD34 cells and autologous EBV cell line or natural killer target K562 cells. Cloned CTL could recognize allogeneic HMCLs, demonstrating that a shared anti-MMC repertoire was expanded. CONCLUSION: Transduction with B7-1 and 4-1BBL retroviruses turned HMCLs into efficient APCs. It permitted the long-term expansion of autologous anti-tumor CTL with a shared anti-MMC repertoire, for one HMCL. These data suggest developing an immunotherapy using modified tumor cells in patients with multiple myeloma.
Published: 2007

47. Identifying new human oocyte marker genes: a microarray approach

Author: V. Loup, Said Assou, John De Vos, Hervé Dechaud, Tal Anahory, Ste # phan Gasca, Samir Hamamah, Franck Pellestor, Institut de recherche en biothérapie (IRB), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Unité d'AMP/DPI, Département de Médecine et biologie de la reproduction, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service de gynécologie-obstétrique et médecine de la reproduction, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, and Frei, Monique
Subjects: Genetic Markers, Microarray, Adenomatous Polyposis Coli Protein, Cell Cycle Proteins, Protein Serine-Threonine Kinases, Biology, Retinoblastoma Protein, Article, 03 medical and health sciences, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Gene expression, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Embryo Implantation, Gene, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, Oligonucleotide Array Sequence Analysis, 030304 developmental biology, Genetics, 0303 health sciences, 030219 obstetrics & reproductive medicine, Gene Expression Profiling, Tumor Suppressor Proteins, Calcium-Binding Proteins, Obstetrics and Gynecology, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, Oocyte, Embryo transfer, Repressor Proteins, Gene expression profiling, medicine.anatomical_structure, Reproductive Medicine, Genetic marker, Mad2 Proteins, Oocytes, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], DNA microarray, Protein Kinases, Developmental Biology
Abstract: International audience; The efficacy of classical IVF techniques is still impaired by poor implantation and pregnancy rates after embryo transfer. This is mainly due to a lack of reliable criteria for the selection of embryos with sufficient development potential. Several studies have provided evidence that some gene expression levels could be used as objective markers of oocyte and embryo competence and capacity to sustain a successful pregnancy. These analyses usually use reverse transcription-polymerase chain reaction to look at small sets of pre-selected genes. However, microarray approaches allow the identification of a wider range of cellular marker genes which could include additional and perhaps more suitable genes that could serve as embryo selection markers. Microarray screenings of around 30,000 genes on U133P Affymetrix(trade mark)gene chips made it possible to establish the expression profile of these genes as well as other related genes in human oocytes and cumulus cells. This study identifies new potential regulators and marker genes such as BARD1, RBL2, RBBP7, BUB3 or BUB1B, which are involved in oocyte maturation.
Published: 2007

48. In vitro expansion of gamma delta T cells with anti-myeloma cell activity by Phosphostim and IL-2 in patients with multiple myeloma.: Anti-myeloma activity of amplified gamma delta T cells

Author: Burjanadze, Maka, Condomines, Maud, Rème, Thierry, Quittet, Philippe, Latry, Pascal, Lugagne, Cécile, Romagne, François, Morel, Yanis, Rossi, Jean-François, Klein, Bernard, Lu, Zhao-Yang, Frei, Monique, Institut de recherche en biothérapie (IRB), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Service d'hématologie et oncologie médicale, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie-Université de Montpellier (UM), Unité de thérapie cellulaire, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Innate Pharma
Subjects: multiple myeloma, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.CAN] Life Sciences [q-bio]/Cancer, gamma delta T cells, cytotoxicity, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, immunotherapy, cellular therapy, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology
Abstract: International audience; T-cell-mediated immunotherapy is a promising therapeutic option for multiple myeloma (MM). Gamma-delta T cells (gammadelta T cells) recognize phosphoantigens and display strong anti-tumour cytotoxicity. The synthetic agonist Phosphostim (bromohydrin pyrophosphate, BrHPP) has been shown to selectively activate Vgamma9Vdelta2 T cells. This study aimed to evaluate the expansion capacity and anti-myeloma cell cytotoxicity of circulating gammadelta T cells from MM patients at different time points throughout the disease, using Phosphostim and interleukin 2 (IL-2). Circulating gammadelta T cell counts in patients with newly diagnosed MM or in relapse did not differ from those in healthy donors. A 14-d culture of peripheral blood mononuclear cells with Phosphostim and IL-2 triggered a 100-fold expansion of gammadelta T cells in 78% of newly diagnosed patients. gammadelta T cells harvested at the time of haematopoietic progenitor collection or in relapsing patients expanded less efficiently. Expanded gammadelta T cells killed 13/14 myeloma cell lines as well as primary myeloma cells, but not normal CD34 cells. Their killing efficiency was not affected by 2-d IL-2 starvation. This study demonstrated the ability of Phosphostim and IL-2 to expand gammadelta T cells from MM patients, and the efficient and stable killing of human myeloma cells by gd T cells.
Published: 2007

49. Targeting NF-kappaB pathway with an IKK2 inhibitor induces inhibition of multiple myeloma cell growth

Author: Jourdan, Michel, Moreaux, Jérôme, Vos, John De, Hose, Dirk, Mahtouk, Karène, Abouladze, Matthieu, Robert, Nicolas, Baudard, Marion, Rème, Thierry, Romanelli, Angela, Goldschmidt, Hartmut, Rossi, Jean-François, Dreano, Michel, Klein, Bernard, Frei, Monique, Institut de recherche en biothérapie (IRB), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Department of Internal Medicine V, Universität Heidelberg [Heidelberg], Department of Hematology and Clinical Oncology, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Serono Research Institute, Serono, Serono International SA (SERONO INTERNATIONAL SA), and Serono International SA
Subjects: cell cycle, Multiple myeloma, NF-kappa B, apoptosis, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, IKK2 inhibitor
Abstract: The pathophysiologic basis for multiple myeloma (MM) has been attributed to the dysregulation of various paracrine or autocrine growth factor loops and to perturbations in several signal transduction pathways including IkappaB kinase/nuclear factor-kappaB (IKK/NF-kappaB). The present study aimed at investigating the effect of a pharmaceutical IKK2 inhibitor, the anilinopyrimidine derivative AS602868, on the in vitro growth of 14 human MM cell lines (HMCL) and primary cells from 13 patients. AS602868 induced a clear dose-dependent inhibition of MM cell growth on both HMCL and primary MM cells, which was the result of a simultaneous induction of apoptosis and inhibition of the cell cycle progression. Combination of AS602868 with suboptimal doses of melphalan or Velcade showed an additive effect in growth inhibition of HMCL. AS602868 also induced apoptosis of primary myeloma cells. Importantly, AS602868 did not alter the survival of other bone marrow mononuclear cells (CD138(-)) co-cultured with primary MM (CD138(+)) cells, except for CD34(+) haematopoietic stem cells. The results demonstrate the important role of NF-kappaB in maintaining the survival of MM cells and suggest that a pharmacological inhibition of the NF-kappaB pathway by the IKK2 inhibitor AS602868 can efficiently kill HMCL and primary myeloma cells and therefore might represent an innovative approach for treating MM patients.
Published: 2007

50. Effects of a Supplementation during Exercise and Recovery

Author: H. Ben Saad, Jean-Paul Cristol, M. Delage, Alain Dupuy, Jacques Mercier, Claire Thomas, Stéphane Perrey, INSEP, documentation, Laboratoire d'Etude de la PHysiologie de l'Exercice (LEPHE), Université d'Évry-Val-d'Essonne (UEVE), Université Montpellier 1 - UFR de Médecine (UM1 Médecine), Université Montpellier 1 (UM1), Laboratoire de recherche Efficience et Déficience Motrices (EDM), Laboratoire de BiochimieA des lipides et du stress oxydant, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Muscles et pathologies, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)
Subjects: Adult, Male, medicine.medical_specialty, Antioxidant, Protein Hydrolysates, medicine.medical_treatment, [SHS.SPORT.PS] Humanities and Social Sciences/Sport/Sport physiology, [SHS.SPORT.PS]Humanities and Social Sciences/Sport/Sport physiology, Physical Therapy, Sports Therapy and Rehabilitation, Physical exercise, oxidative damage, maximal blood lactate, medicine.disease_cause, Placebo, Hydrolysate, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Task Performance and Analysis, medicine, Humans, Citrate synthase, Orthopedics and Sports Medicine, Exercise, Fatigue, [SHS.SPORT]Humanities and Social Sciences/Sport, Muscle biopsy, biology, medicine.diagnostic_test, Chemistry, [SHS.SPORT] Humanities and Social Sciences/Sport, 030229 sport sciences, Adaptation, Physiological, 3. Good health, fatigue index, Oxidative Stress, Endocrinology, Biochemistry, supramaximal exercise, Dietary Supplements, biology.protein, France, Anaerobic exercise, 030217 neurology & neurosurgery, Oxidative stress
Abstract: International audience; The present study was designed to investigate whether a protein hydrolysate enriched in branched chain amino acids and antioxidants, trace and mineral elements, and vitamins would affect performance and fatigue. Eighteen sportsmen underwent testing before and after 28 days supplementation with either treatment in protein hydrolysate or placebo. Testing included exhaustive aerobic and anaerobic exercises with determination of blood lactate concentration through exercise and recovery and antioxidant status, but also measurements of maximal oxidative capacity (V·max) and citrate synthase activity (CS) from a resting muscle biopsy. Protein hydrolysate resulted in a significant decrease in fatigue indices, without affecting performances. A significant increase in enzymatic antioxidant and a decrease in oxidative damage were observed at rest after treatment but not with a placebo. Decrease in maximal blood lactate and improvement of blood lactate removal were only observed after protein hydrolysate treatment. Furthermore, CS increased significantly, whereas no change was observed in V·max. In conclusion, this protein hydrolysate treatment induced adaptations that may promote a decrease in fatigue during exercises, potentially explained by changes in parameters used to represent oxidative damage and antioxidant status at rest and changes in lactate metabolism.
Published: 2007

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