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177 results on '"Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP]"'

1. PAK3 mutations responsible for severe intellectual disability and callosal agenesis inhibit cell migration

Author: Caroline Nava, Ferechté Razavi, Kevin Duarte, Jelena Martinovic, Jacqueline Cherfils, Jean-Vianney Barnier, Christel Depienne, Delphine Héron, Cyrille Mignot, Agnès Rastetter, Solveig Heide, Marie Laure Moutard, Tania Attié-Bitach, Véronique Rousseau, Sandrine Poëa-Guyon, Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Groupe de Recherche Clinique : Déficience Intellectuelle et Autisme (GRC), Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institute of Human Genetics, University Hospital Essen, Embryology and genetics of human malformation (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de foetopathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Unité fonctionnelle de Fœtopathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Laboratoire de biologie et pharmacologie appliquée (LBPA), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay), Institut des Neurosciences de Paris-Saclay (Neuro-PSI), Department of genetics, Reference Center for Intellectual Disabilities of Rare Causes, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Department of Pediatrics Neurology, Reference Center for Intellectual Disabilities of Rare Causes, CHU Pitié-Salpêtrière [APHP], Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Barnier, Jean-Vianney, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, 0301 basic medicine, Microcephaly, Kinase, [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Intellectual disability, Medizin, medicine.disease_cause, Severity of Illness Index, Protein Structure, Secondary, 0302 clinical medicine, Neurodevelopmental disorder, Cell Movement, Chlorocebus aethiops, Missense mutation, Child, Genetics, Mutation, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Cell migration, Phenotype, Pedigree, [SDV] Life Sciences [q-bio], Neurology, COS Cells, αPIX/ARHGEF6, macromolecular substances, Biology, lcsh:RC321-571, 03 medical and health sciences, medicine, Animals, Humans, Amino Acid Sequence, Kinase activity, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Corpus Callosum Agenesis, Cell spreading, Cell adhesion, medicine.disease, Corpus callosum agenesis (CCA), HEK293 Cells, 030104 developmental biology, p21-Activated Kinases, PAK3, Agenesis of Corpus Callosum, 030217 neurology & neurosurgery
Abstract: International audience; Corpus callosum agenesis (CCA) is a brain malformation associated with a wide clinical spectrum including intellectual disability (ID) and an etiopathological complexity. We identified a novel missense G424R mutation in the X-linked p21-activated kinase 3 (PAK3) gene in a boy presenting with severe ID, microcephaly and CCA and his fetal sibling with CCA and severe hydrocephaly. PAK3 kinase is known to control synaptic plasticity and dendritic spine dynamics but its implication is less characterized in brain ontogenesis. In order to identify developmental functions of PAK3 impacted by mutations responsible for CCA, we compared the biochemical and biological effects of three PAK3 mutations localized in the catalytic domain. These mutations include two "se-vere" G424R and K389N variants (responsible for severe ID and CCA) and the "mild" A365E variant (responsible for nonsyndromic mild ID). Whereas they suppressed kinase activity, only the two severe variants displayed normal protein stability. Furthermore, they increased interactions between PAK3 and the guanine exchange factor αPIX/ARHGEF6, disturbed adhesion point dynamics and cell spreading, and severely impacted cell migration. Our findings highlight new molecular defects associated with mutations responsible for severe clinical phenotypes with developmental brain defects.
Published: 2020

2. Helicobacter bilis-Associated Suppurative Cholangitis in a Patient with X-Linked Agammaglobulinemia

Author: Agnès Ferroni, Justine Dautremer, Nicolas Degand, Julie Bruneau, Fanny Lanternier, Marc Lecuit, Olivier Hermine, Olivier Lortholary, Stéphane Blanche, Benoit Pilmis, Xavier Nassif, Laboratoire de Microbiologie [AP-HP Necker], Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des Maladies infectieuses et tropicales [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Service d'AnatomoPathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hématologie Adulte, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Paris 5 (UPD5), Service d'immuno-hématologie pédiatrique [CHU Necker], We thank Agnès Labigne, Unité de Pathogénie bactérienne des muqueuses, Institut Pasteur, Paris, France, for her help in this case report., Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP]-Institut des Maladies Génétiques Imagine [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], and Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP]
Subjects: 0301 basic medicine, Male, MESH: Helicobacter Infections/pathology, MESH: Agammaglobulinemia/pathology, [SDV]Life Sciences [q-bio], Azithromycin, Bruton’s disease, Gastroenterology, Medical microbiology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Helicobacter, Immunology and Allergy, MESH: Anti-Bacterial Agents/therapeutic use, MESH: Agammaglobulinemia/drug therapy, MESH: Genetic Diseases, X-Linked/pathology, medicine.diagnostic_test, biology, MESH: Helicobacter Infections/drug therapy, Suppurative cholangitis, Genetic Diseases, X-Linked, 3. Good health, Anti-Bacterial Agents, cholangitis, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Liver, MESH: Young Adult, Liver biopsy, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.drug, Helicobacter bilis, DNA, Bacterial, medicine.medical_specialty, 030106 microbiology, Immunology, MESH: Genetic Diseases, X-Linked/drug therapy, DNA, Ribosomal, Helicobacter Infections, MESH: Liver/pathology, 03 medical and health sciences, Young Adult, MESH: Helicobacter/genetics, Internal medicine, medicine, MESH: Helicobacter Infections/microbiology, Humans, Colitis, MESH: DNA, Ribosomal/genetics, MESH: Humans, business.industry, MESH: Agammaglobulinemia/microbiology, MESH: Genetic Diseases, X-Linked/microbiology, biology.organism_classification, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Male, MESH: DNA, Bacterial/genetics, agammaglobulinemia, Metronidazole, MESH: Cholangitis/pathology, 030104 developmental biology, MESH: Cholangitis/drug therapy, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, MESH: Cholangitis/microbiology
Abstract: International audience; Helicobacter bilis is a commensal bacterium causing chronic hepatitis and colitis in mice. In humans, enterohepatic Helicobacter spp. are associated with chronic hepatobiliary diseases. Purpose : We aimed at understanding the microbial etiology in a patient with X-linked agammaglobulinemia presenting with suppurative cholangitis. Methods : 16S rDNA PCR directly performed on a liver biopsy retrieved DNA of H. bilis. Results : Clinical outcome resulted in the normalization of clinical and biological parameters under antibiotic treatment by a combination of ceftriaxone, metronidazole, and doxycyclin followed by a 2-week treatment with moxifloxacin and a 2-month treatment with azithromycin. Conclusion : In conclusion, these data suggest a specific clinical and microbiological approach in patients with humoral deficiency in order to detect H. bilis hepatobiliary diseases.
Published: 2017

3. Contractile forces at tricellular contacts modulate epithelial organization and monolayer integrity

Author: Salomon, Julie, Gaston, Cécile, Magescas, Jérémy, Duvauchelle, Boris, Canioni, Danielle, Sengmanivong, Lucie, Mayeux, Adeline, Michaux, Grégoire, Campeotto, Florence, Lemale, Julie, Viala, Jérôme, Poirier, Françoise, Minc, Nicolas, Schmitz, Jacques, Brousse, Nicole, Ladoux, Benoit, Goulet, Olivier, Delacour, Delphine, Institut Jacques Monod (IJM (UMR_7592)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Gastroentérologie-Hépatologie et Nutrition Pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Service de pathologie [CHU Necker], BioImaging Cell and Tissue Core Facility (PICT-IBiSA), Institut Curie, Compartimentation et dynamique cellulaires (CDC), Centre National de la Recherche Scientifique (CNRS)-Institut Curie-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Ecosystème intestinal, probiotiques, antibiotiques (EA 4065), Université Paris Descartes - Paris 5 (UPD5), Gastroentérologie et Nutrition Pédiatrique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institute of Cardiometabolism and Nutrition-CHU Trousseau [APHP], Service de Gastro-entérologie Pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], CHU Necker - Enfants Malades [AP-HP], Mechanobiology Institute [Singapore] (MBI), National University of Singapore (NUS), Interactions de l'épithelium intestinal et du système immunitaire (UMR_S 793), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Recherche Agronomique (INRA), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Curie [Paris], Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-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 )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut Jacques Monod ( IJM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], BioImaging Cell and Tissue Core Facility ( PICT-IBiSA ), INSTITUT CURIE, Compartimentation et dynamique cellulaires ( CDC ), Centre National de la Recherche Scientifique ( CNRS ) -INSTITUT CURIE-Université Pierre et Marie Curie - Paris 6 ( UPMC ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Ecosystème intestinal, probiotiques, antibiotiques ( EA 4065 ), Université Paris Descartes - Paris 5 ( UPD5 ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institute of Cardiometabolism and Nutrition-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Mechanobiology Institute [Singapore] ( MBI ), National University of Singapore ( NUS ), Interactions de l'épithelium intestinal et du système immunitaire ( UMR_S 793 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Recherche Agronomique ( INRA ), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, [SDV.GEN]Life Sciences [q-bio]/Genetics, Adolescent, Science, Cell Polarity, Infant, Epithelial Cells, Actomyosin, Epithelial Cell Adhesion Molecule, Article, Epithelium, Biomechanical Phenomena, Tight Junctions, Enterocytes, Malabsorption Syndromes, Child, Preschool, Diarrhea, Infantile, Humans, Female, Caco-2 Cells, Child, [ SDV.GEN ] Life Sciences [q-bio]/Genetics
Abstract: Monolayered epithelia are composed of tight cell assemblies that ensure polarized exchanges. EpCAM, an unconventional epithelial-specific cell adhesion molecule, is assumed to modulate epithelial morphogenesis in animal models, but little is known regarding its cellular functions. Inspired by the characterization of cellular defects in a rare EpCAM-related human intestinal disease, we find that the absence of EpCAM in enterocytes results in an aberrant apical domain. In the course of this pathological state, apical translocation towards tricellular contacts (TCs) occurs with striking tight junction belt displacement. These unusual cell organization and intestinal tissue defects are driven by the loss of actomyosin network homoeostasis and contractile activity clustering at TCs, yet is reversed by myosin-II inhibitor treatment. This study reveals that adequate distribution of cortical tension is crucial for individual cell organization, but also for epithelial monolayer maintenance. Our data suggest that EpCAM modulation protects against epithelial dysplasia and stabilizes human tissue architecture., EpCAM is an unconventional epithelia-specific cell–cell adhesion molecule, that is mutated in the majority of cases of Congenital Tufting Enteropathy. Here the authors show that loss of EpCAM causes a concentration of contractile activity at tricellular junctions, leading to aberrant apical domain and tight junction displacement.
Published: 2017

4. Cyclooxygenase-2-Derived Prostaglandins Mediate Cerebral Microcirculation in a Juvenile Ischemic Rat Model

Author: Valérie C. Besson, Julien Pansiot, Pierre-Louis Leger, Bruno Palmier, Christiane Charriaut-Marlangue, Olivier Baud, Bruno Cauli, Sylvain Renolleau, Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de réanimation néonatale et pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Pharmacologie de la circulation cérébrale (EA 4475), Université Paris Descartes - Paris 5 (UPD5), Service Réanimation et surveillance continue médicochirurgicales [AP-HP Hôpital Necker-Enfants Malades], Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Neuroprotection du Cerveau en Développement ( PROTECT ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de réanimation néonatale et pédiatrique, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Pharmacologie de la circulation cérébrale ( EA 4475 ), Université Paris Descartes - Paris 5 ( UPD5 ), Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Neuroscience Paris Seine ( NPS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), and Charriaut-Marlangue, Christiane
Subjects: 0301 basic medicine, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 6-Ketoprostaglandin F1 alpha/metabolism, Prostaglandin E synthase, prostaglandins, chemistry.chemical_compound, 0302 clinical medicine, Cyclooxygenase 2/metabolism, Prostaglandin-E Synthases, ddc:618, TUNEL assay, biology, stroke, Prostaglandin-E Synthases/metabolism, [SDV] Life Sciences [q-bio], Cerebrovascular Circulation, Reperfusion Injury, Cardiology and Cardiovascular Medicine, Prostaglandin E, medicine.medical_specialty, Prostaglandin, microcirculation, 6-Ketoprostaglandin F1 alpha, ischemia–reperfusion, Microcirculation, Prostacyclin synthase, Reperfusion Injury/metabolism, 03 medical and health sciences, Internal medicine, medicine, Animals, Advanced and Specialized Nursing, Cyclooxygenase 2 Inhibitors/pharmacology, [ SDV ] Life Sciences [q-bio], Cyclooxygenase 2 Inhibitors, business.industry, COX-2, Rats, Surgery, Disease Models, Animal, 030104 developmental biology, Endocrinology, Terminal deoxynucleotidyl transferase, chemistry, Cyclooxygenase 2, biology.protein, Neurology (clinical), Cyclooxygenase, business, 030217 neurology & neurosurgery
Abstract: Background and Purpose— We previously showed that the selective neuronal nitric oxide synthase inhibitor 7-nitroindazole (7-NI) increases cerebral microcirculation in a juvenile ischemic rat model. We address the roles of cyclooxygenase (COX)-elaborated prostaglandins in collateral recruitment and blood supply. Methods— Fourteen-day-old rats were subjected to ischemia–reperfusion and treated with either PBS or 7-NI (25 mg/kg) at the reperfusion onset. Six-keto-prostaglandin F 1α was measured using ELISA. COX-1 and COX-2 and prostaglandin terminal synthesizing enzymes were evaluated using reverse-transcriptase polymerase chain reaction and immunofluorescence. Microvascular blood flow indexes (artery diameter and capillaries number) were measured using sidestream dark-field videomicroscopy in PBS- and 7-NI-treated ischemic rats in the absence or presence of the COX-2 inhibitor NS-398 (5 mg/kg). Cell death was measured with the TUNEL (terminal transferase dUTP nick end labeling) assay and cleaved-caspase-3 immunostaining. Results— Six-keto-prostaglandin F 1α and COX-2, associated with a prostaglandin E synthase, were significantly increased in PBS- and 7-NI-treated animals 15 minutes and 1 hour after ischemia–reperfusion, respectively. In contrast and as compared with PBS, 7-NI significantly decreased prostacyclin synthase and cytosolic prostaglandins E synthase mRNA. Selective COX-2 inhibition significantly decreased blood flow indexes and significantly reversed the effects of 7-NI, including the number of TUNEL + - and cleaved-caspase-3 + -nuclei. Conclusions— These results show that the juvenile rat brains mostly respond to ischemia by a COX-2-dependent prostaglandins production and suggest that the transcriptional responses observed under 7-NI facilitate and reorient COX-2-dependent prostaglandins production.
Published: 2016

5. Intérêt et utilisabilité du dossier pharmaceutique en pratique médicale. Enquête auprès de médecins et pharmaciens hospitaliers (étude MATRIX)

Author: Nicolas Griffon, M. Timsit, A. Gillibert, Stéfan Jacques Darmoni, Matthieu Schuers, Jacques Benichou, Pascal Staccini, A. Fred, Service d'informatique biomédicale [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service d'urologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Université de Rouen Normandie (UNIROUEN), Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], and Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)
Subjects: medicine.medical_specialty, Epidemiology, health care facilities, manpower, and services, education, Frequency of use, Pharmacy, 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, Intensive care, Health card, medicine, Electronic health records, 030212 general & internal medicine, Pharmacie, health care economics and organizations, business.industry, Dossiers patients informatisés, System usability scale, Information dissemination, User satisfaction, Public Health, Environmental and Occupational Health, Usability, Patient record, Hôpitaux, humanities, Hospitals, 3. Good health, Diffusion de l’information, Family medicine, [INFO.INFO-IR]Computer Science [cs]/Information Retrieval [cs.IR], Respondent, business
Abstract: Background To evaluate the impact of the pharmaceutical patient record use in emergency, geriatric and anaesthesia and intensive care departments, an experimentation was launched in 2013 in 55 hospitals. The purpose of the study was to assess the opinions of physicians and pharmacists about the benefits and usability of the patient pharmaceutical record. Methods An e-mailed self-administered questionnaire was sent to all the pharmacists, anaesthesiologists, geriatricians and emergency physicians of the 55 hospitals involved in the patient pharmaceutical record experimentation. The questionnaire assessed the usability of the patient pharmaceutical record using the “System Usability Scale”, as well as its use, its benefits and limitations perceived in clinical practice, and overall user satisfaction. Questionnaires were collected from November 2014 to January 2015. Results Ninety-six questionnaires were collected, from 47 hospitals, representing 86% of the hospitals involved in the experimentation. The patient pharmaceutical record was effectively operational in 36 hospitals. Data from 73 questionnaires filled by physicians and pharmacists with potential experience with the patient pharmaceutical record were used for evaluation. Forty-two respondents were pharmacists (57%) and 31 were physicians (43%), including 13 geriatricians, 11 emergency physicians and 7 anaesthesiologists. Patient pharmaceutical record overall usability score was 62.5 out of 100. It did not vary with the profession or seniority of the respondent. It was positively correlated with the frequency of use. More than half of respondents reported that they never or uncommonly used the patient pharmaceutical record. The length of access to data period was considered as insufficient. Main obstacles to more utilization of the patient pharmaceutical record were the lack of information about the dosage of dispensed drugs, the low number of patients in possession of their health card and the low number of patients with an activated patient pharmaceutical record. Conclusion Two years after the beginning of the experiment aiming to broaden the access to the patient pharmaceutical record to physicians, these first evaluation results are encouraging. The evaluation of the consequences of the access to the patient pharmaceutical record for physicians remains necessary.
Published: 2016

6. Formation of Nup98-containing nuclear bodies in HeLa sublines is linked to genomic rearrangements affecting chromosome 11

Author: Marie-Claude Geoffroy, Jean-Michel Lapierre, Valérie Doye, Serge Romana, Isabelle Radford-Weiss, Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service de Cytogénétique, Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Université Sorbonne Paris Cité ( USPC ), Institut Jacques Monod ( IJM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Centre national de la recherche scientifique (CNRS), Fondation ARC pour la Recherche sur le Cancer ('Programme ARC), Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Université Sorbonne Paris Cité (USPC), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, Repetitive Sequences, Amino Acid, [SDV]Life Sciences [q-bio], Chromosomal translocation, Translocation, Genetic, HeLa, 03 medical and health sciences, Rapid amplification of cDNA ends, Cell Line, Tumor, Genetics, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Nuclear pore, Nucleoporin, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Genetics (clinical), In Situ Hybridization, Fluorescence, ComputingMilieux_MISCELLANEOUS, Comparative Genomic Hybridization, [SDV.GEN]Life Sciences [q-bio]/Genetics, Leukemia, biology, Chromosomes, Human, Pair 11, Gene Amplification, Chromosome, Hep G2 Cells, Nup98 Leukaemia, biology.organism_classification, Molecular biology, Homogeneously staining region, Nuclear Pore Complex Proteins, 030104 developmental biology, Chromosome 3, Caco-2 Cells, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, Developmental biology, HeLa Cells
Abstract: Nup98 is an important component of the nuclear pore complex (NPC) and also a rare but recurrent target for chromosomal translocation in leukaemogenesis. Nup98 contains multiple cohesive Gly-Leu-Phe-Gly (GLFG) repeats that are critical notably for the formation of intranuclear GLFG bodies. Previous studies have reported the existence of GLFG bodies in cells overexpressing exogenous Nup98 or in a HeLa subline (HeLa-C) expressing an unusual elevated amount of endogenous Nup98. Here, we have analysed the presence of Nup98-containing bodies in several human cell lines. We found that HEp-2, another HeLa subline, contains GLFG bodies that are distinct from those identified in HeLa-C. Rapid amplification of cDNA ends (RACE) revealed that HEp-2 cells express additional truncated forms of Nup98 fused to a non-coding region of chromosome 11q22.1. Cytogenetic analyses using FISH and array-CGH further revealed chromosomal rearrangements that were distinct from those observed in leukaemic cells. Indeed, HEp-2 cells feature a massive amplification of juxtaposed NUP98 and 11q22.1 loci on a chromosome marker derived from chromosome 3. Unexpectedly, minor co-amplifications of NUP98 and 11q22.1 loci were also observed in other HeLa sublines, but on rearranged chromosomes 11. Altogether, this study reveals that distinct genomic rearrangements affecting NUP98 are associated with the formation of GLFG bodies in specific HeLa sublines.
Published: 2016

7. A lack of significant effect of POR*28 allelic variant on tacrolimus exposure in kidney transplant recipients

Author: Cécile Vigneau, Antoine Thierry, Isabelle Etienne, Anne-Elizabeth Heng, Xavier Vuillemin, Mathias Büchler, Bruno Moulin, Jean-Philippe Rerolle, Christophe Legendre, Gabriel Choukroun, Jean-François Subra, Philippe Beaune, Nicolas Pallet, Eric Thervet, Bruno Hurault de Ligny, Marie-Anne Loriot, Charlotte Colosio, Anne-Sophie Jannot, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Mécanismes physiologiques et conséquences des calcifications cardiovasculaires: rôle des remodelages cardiovasculaires et osseux, Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de néphrologie [Rennes], Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service de Néphrologie et Transplantation, CHU Strasbourg, Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Service de Néphrologie [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de néphrologie adultes [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de néphrologie et transplantation, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de néphrologie, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université de Picardie Jules Verne ( UPJV ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Pharmacologie des Immunosuppresseurs et de la Transplantation ( PIST ), Université de Limoges ( UNILIM ) -CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université d'Angers ( UA ) -CHU Angers, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP]
Subjects: Adult, Graft Rejection, Male, medicine.medical_specialty, Genotype, CYP3A, [SDV]Life Sciences [q-bio], Population, chemical and pharmacologic phenomena, Biology, 030226 pharmacology & pharmacy, Tacrolimus, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Cytochrome P-450 Enzyme System, Polymorphism (computer science), Internal medicine, medicine, Cytochrome P-450 CYP3A, Humans, Pharmacology (medical), Prospective Studies, CYP3A5, education, Alleles, Pharmacology, education.field_of_study, [ SDV ] Life Sciences [q-bio], Genetic Variation, Middle Aged, Kidney Transplantation, Transplant Recipients, Calcineurin, Transplantation, stomatognathic diseases, Endocrinology, 030220 oncology & carcinogenesis, Immunology, Female, Immunosuppressive Agents
Abstract: International audience; BACKGROUND: POR*28 is a recently newly described allelic variant of the cytochrome P450 oxydoreductase (POR) which might be associated with an increased metabolic activity of P450 cytochromes (CYP) 3A5 and 3A4. Consequently, carriers of at least one allele of this polymorphism could require increased calcineurin inhibitors doses to reach the target residual concentrations (Co). The objective of this study is to test whether the allelic variant of POR, which is associated with an increased metabolic activity of CYP3A, impacts Tacrolimus (Tac) pharmacokinetics. METHODS: We tested this hypothesis in a population of 229 kidney transplant recipients (KTR) from a large, multicenter, prospective and randomized study. We have analyzed the association between POR*28 genotype and the proportion of individuals reaching the target Tac residual concentration (Tac Co) 10 days after transplantation. We have also measured the association between POR*28 and the Tac Co, and adjusted Tac Co (Tac Co/Tac dose) over time using generalized mixed linear models. RESULTS: Ten days after transplantation, there was no difference of frequencies of KTR within the target range of Tac Co (Co 10-15 ng/ml) according to the POR*28 genotype (p=0.8). The mean Tac Co at day 10 in the POR*1/*1 group was 15.3±9.7 ng/ml compared with 15.7±7.8 ng/ml in the POR*1/*28 group and 14.2 ±6.8 ng/ml, in the POR*28/*28 group, p=0.8. The adjusted Tac Co was not associated with POR*28 genotype over time (random effects model, p=0.9). When restricted to KTR expressing CYP3A5, POR*28 gentoype did not impact the proportion of individuals within the Tac Co target range neither the adjusted Tac Co (random effects model, p=0.1). CONCLUSIONS: POR*28 does not significantly influence Tac pharmacokinetic parameters in a large cohort of KTR. This study does not confirm recent findings indicating that POR*28 carriers require more Tac to reach target Co
Published: 2016

8. Mosaic parental germline mutations causing recurrent forms of malformations of cortical development

Author: François Artiguenave, Jamel Chelly, Bettina Bessières, Imen Rejeb, Catherine Fallet-Bianco, Giuseppe Muraca, Catheline Vilain, Adrienne Elmorjani, Nadia Bahi-Buisson, Nicolas Lebrun, Hélène Maurey, Julia Lauer Zillhardt, Sylvie Odent, Yuri Musizzano, Karine Poirier, Nicole Philip, David Geneviève, Cécile Masson, Stanislas Lyonnet, Yoann Saillour, Robert Olaso, Jelena Martinovic, Jean-François Deleuze, Lucile Pinson, Lamia Ben Jemaa, François Rivier, Juliette Nectoux, Patrick Van Bogaert, Anne Boland, Fabienne Giuliano, Patrick Nitschke, Loic Broix, Nicolas Leboucq, Cherif Beldjord, Nicole Bigi, Olivier Dulac, 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), Service de foetopathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biochimie et biologie moléculaire, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de pathologie et biologie cellulaire, Université de Montréal (UdeM)-Hôpital Sainte-Justine, CHU Necker - Enfants Malades [AP-HP], Service de Neurologie Pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre de Reference Epilepsies Rares-CHU Necker - Enfants Malades [AP-HP], Service NEUROSPIN (NEUROSPIN), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Epilepsies de l'Enfant et Plasticité Cérébrale (U1129), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de génétique clinique [Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-hôpital Sud, CHU Pontchaillou [Rennes], 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), Service de génétique, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre de Référence Anomalies du Développement et Syndromes Malformatifs, Centre Hospitalier Régional et Universitaire, Service de génétique médicale, Hôpital l'Archet, Service de Génétique, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Génétique Médicale, Université libre de Bruxelles (ULB), Service Neuropédiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Laboratoire de biochimie et génétique moléculaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Plate Forme Paris Descartes de Bioinformatique (BIP-D), Université Paris Descartes - Paris 5 (UPD5), Service de neurologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP], CHU Cochin [AP-HP], Hôpital Sainte-Justine-Université de Montréal, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Centre de Reference Epilepsies Rares-CHU Necker - Enfants Malades [AP-HP], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-Hôpital Sud, Université Libre de Bruxelles [Bruxelles] (ULB), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], 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 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute ( ICM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -CHU Pitié-Salpêtrière [APHP], Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Centre de Reference Epilepsies Rares-CHU Necker - Enfants Malades [AP-HP], NeuroSpin, Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut d'imagerie biomédicale (I²BM), Epilepsies de l'Enfant et Plasticité Cérébrale ( U1129 ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -CHU Pontchaillou [Rennes]-Hôpital Sud, Service de Neuropédiatrie, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Gui de Chauliac, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] ( PhyMedExp ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Montpellier ( UM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Université de Montpellier ( UM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Université Libre de Bruxelles [Bruxelles] ( ULB ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 ( UPD5 ), Centre National de Génotypage ( CNG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Plate Forme Paris Descartes de Bioinformatique ( BIP-D ), Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Institut de Génétique et de Biologie Moléculaire et Cellulaire ( IGBMC ), and Université de Strasbourg ( UNISTRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: 0301 basic medicine, Adult, Male, Candidate gene, [SDV]Life Sciences [q-bio], Short Report, Biology, Bioinformatics, Germline, 03 medical and health sciences, Germline mutation, Genetics, Syntaxin, Humans, Exome, Sibling, Genetics (clinical), Germ-Line Mutation, ComputingMilieux_MISCELLANEOUS, [ SDV ] Life Sciences [q-bio], Mosaicism, Qa-SNARE Proteins, Malformation of cortical development, 3. Good health, Pedigree, Malformations of Cortical Development, 030104 developmental biology, Genetic Loci, Female
Abstract: International audience; To unravel missing genetic causes underlying monogenic disorders with recurrence in sibling, we explored the hypothesis of parental germline mosaic mutations in familial forms of malformation of cortical development (MCD). Interestingly, four families with parental germline variants, out of 18, were identified by whole-exome sequencing (WES), including a variant in a new candidate gene, syntaxin 7. In view of this high frequency, revision of diagnostic strategies and reoccurrence risk should be considered not only for the recurrent forms, but also for the sporadic cases of MCD
Published: 2016

9. A Novel Extrinsic Pathway for the Unfolded Protein Response in the Kidney

Author: Nicolas Pallet, Nicolas Bouvier, Virginie Poindessous, Eric Chevet, Rim Aboukamis, Philippe Beaune, Pierre-Louis Tharaux, Iadh Mami, Eric Thervet, Pierre Laurent-Puig, Dany Anglicheau, Geoffroy Desbuissons, Quentin Tavernier, Marion Rabant, Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Necker - Enfants Malades [AP-HP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie et transplantation, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), ANR-16-CE14-0019,TRANSLATE,L'Angiogénine, un nouveau médiateur de la réponse au Stress du Réticulum Endoplasmique dans le rein(2016), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique ( MEPPOT - U1147 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Necker Enfants-Malades (INEM) ( INEM - UM 111 (UMR 8253 / U1151) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Oncogenesis Stress Signaling ( OSS ), Université de Rennes 1 ( UR1 ), and Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -CRLCC Eugène Marquis ( CRLCC )
Subjects: 0301 basic medicine, Angiogenin, [SDV]Life Sciences [q-bio], Biology, Kidney, acute rejection, Proinflammatory cytokine, Mice, 03 medical and health sciences, Paracrine signalling, renal tubular epithelial cells, Animals, Secretion, Cells, Cultured, Tissue homeostasis, [ SDV ] Life Sciences [q-bio], Endoplasmic reticulum, Macrophages, Ribonuclease, Pancreatic, General Medicine, Endoplasmic Reticulum Stress, Cell biology, cell activation, Mice, Inbred C57BL, Basic Research, 030104 developmental biology, Nephrology, Unfolded Protein Response, Unfolded protein response, Cytokines, Signal transduction, Signal Transduction
Abstract: International audience; The ribonuclease angiogenin is a component of the mammalian stress response, and functions in both cell-autonomous and non-cell-autonomous ways to promote tissue adaptation to injury. We recently showed that angiogenin regulates tissue homeostasis during AKI associated with endoplasmic reticulum (ER) stress through the production of transfer RNA fragments that interfere with translation initiation and thereby alleviate ER stress. However, whether the paracrine signaling mediated by angiogenin secretion is a genuine component of the ER stress response to kidney injury is unknown. Here, we explored the molecular mechanisms by which angiogenin is secreted upon ER stress, and determined how it modulates the inflammatory microenvironment. In cultured renal epithelial cells, ER stress specifically induced angiogenin secretion under the selective control of inositol-requiring enzyme 1α, a key activator of the unfolded protein response. The transcription factors spliced X-box-binding protein 1 and p65, which are activated by inositol-requiring enzyme 1α upon ER stress, each bound the angiogenin promoter and controlled the amount of angiogenin secreted. Furthermore, p65 promoted angiogenin transcription in an ER stress-dependent manner. Similar to secretion of the ER stress-induced proinflammatory cytokine IL-6, secretion of angiogenin required the ER-Golgi pathway. Notably, incubation of human macrophages with angiogenin promoted macrophage reprogramming toward an activated and proinflammatory phenotype. In patients, angiogenin expression increased upon renal inflammation, and the urinary concentration of angiogenin correlated with the extent of immune-mediated kidney injury. Collectively, our data identify angiogenin as a mediator of the ER stress-dependent inflammatory response and as a potential noninvasive biomarker of AKI
Published: 2016

10. The expanding spectrum of COL2A1 gene variants IN 136 patients with a skeletal dysplasia phenotype

Author: Albert David, Chloé Quélin, Clarisse Baumann-Morel, Eric Bieth, Bruno Dumont, Judith Melki, Elise Shaeffer, Yves Alembik, Fabienne Giuliano, Christel Thauvin, Nicolas Chassaing, Sophie Julia, Anne-Lise Delezoide, Marine Lebrun, Tiffany Busa, Geneviève Baujat, David Geneviève, Séverine Audebert, Yline Capri, Patricia Blanchet, Martine Le Merrer, Sandrine Marlin, Mouna Barat-Houari, Marianne Till, Nicole Philip, Laurence Faivre, Patrick Calvas, Karine Nguyen, Alice Masurel, Vidrica Ciorca, François Cartault, Jacqueline Vigneron, Alice Goldenberg, Jelena Martinovic, Monique Mozelle-Nivoix, Renaud Touraine, Ghislaine Plessis, Marie-Line Jacquemont, Jean-Luc Alessandri, Delphine Dupin-Deguine, Valérie Cormier-Daire, Aurélie Fabre, Jeanne Amiel, Marie Brechard, Bertrand Isidor, Salima El Chehadeh, Sylvie Odent, Isabelle Touitou, Josseline Kaplan, Dominique Martin-Coignard, Lucile Pinson, Sabine Sigaudy, Christine Coubes, Didier Lacombe, Frédéric Tm Them, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital de Hautepierre [Strasbourg], Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), 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 Génétique [Purpan], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Génétique Médicale et Génomique Fonctionnelle (GMGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse, Département de génétique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service de Génétique [CHU La Réunion], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Biologie du Développement, Service de génétique médicale, Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital l'Archet, Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de génétique médicale [Toulouse], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de génétique, Centre Hospitalier Le Mans (CH Le Mans), Service de foetopathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de Génétique, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Génétique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de génétique clinique [Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-hôpital Sud, Service de cytogénétique constitutionnelle, Hospices Civils de Lyon (HCL)-CHU de Lyon-Centre Neuroscience et Recherche, Service de Génétique Clinique Chromosomique et Moléculaire, CHU Saint-Etienne-Hôpital Nord - Saint-Etienne, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Service de cytogénétique, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Service de Réanimation Néonatale et Pédiatrique, CHD Félix Guyon, 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 ), Génétique Médicale et Génomique Fonctionnelle ( GMGF ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), Service de Genetique, Service de Génétique Clinique, Centre hospitalier universitaire de Nantes ( CHU Nantes ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Université de Nantes ( UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ), Centre Hospitalier Universitaire de La Réunion ( CHU La Réunion ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), 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 de Bordeaux ( UB ) -CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, CH Le Mans, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Institut National de la Santé et de la Recherche Médicale ( INSERM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) -Aix Marseille Université ( AMU ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), CHU Caen-Hôpital Clémenceau, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -CHU Pontchaillou [Rennes]-Hôpital Sud, Hospices Civils de Lyon ( HCL ) -CHU de Lyon-Centre Neuroscience et Recherche, Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Université de Montpellier ( UM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service Génétique Médicale [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: 0301 basic medicine, Proband, Male, Candidate gene, Hearing Loss, Sensorineural, [SDV]Life Sciences [q-bio], Biology, Osteochondrodysplasias, Article, 03 medical and health sciences, symbols.namesake, Kniest dysplasia, Protein Domains, Genetics, medicine, Humans, Connective Tissue Diseases, Collagen Type II, Genetics (clinical), Sanger sequencing, [ SDV ] Life Sciences [q-bio], Arthritis, Collagen Diseases, Retinal Detachment, medicine.disease, Phenotype, Human genetics, 3. Good health, Pedigree, 030104 developmental biology, Amino Acid Substitution, Dysplasia, Spondyloepiphyseal dysplasia congenita, symbols, Female
Abstract: International audience; Heterozygous COL2A1 variants cause a wide spectrum of skeletal dysplasia termed type II collagenopathies. We assessed the impact of this gene in our French series. A decision tree was applied to select 136 probands (71 Stickler cases, 21 Spondyloepiphyseal dysplasia congenita cases, 11 Kniest dysplasia cases, and 34 other dysplasia cases) before molecular diagnosis by Sanger sequencing. We identified 66 different variants among the 71 positive patients. Among those patients, 18 belonged to multiplex families and 53 were sporadic. Most variants (38/44, 86%) were located in the triple helical domain of the collagen chain and glycine substitutions were mainly observed in severe phenotypes, whereas arginine to cysteine changes were more often encountered in moderate phenotypes. This series of skeletal dysplasia is one of the largest reported so far, adding 44 novel variants (15%) to published data. We have confirmed that about half of our Stickler patients (46%) carried a COL2A1 variant, and that the molecular spectrum was different across the phenotypes. To further address the question of genotype-phenotype correlation, we plan to screen our patients for other candidate genes using a targeted next-generation sequencing approach.European Journal of Human Genetics advance online publication, 2 December 2015; doi:10.1038/ejhg.2015.250
Published: 2016

11. Treacher Collins syndrome: a clinical and molecular study based on a large series of patients

Author: Marie, Vincent, David, Geneviève, Agnès, Ostertag, Sandrine, Marlin, Didier, Lacombe, Dominique, Martin-Coignard, Christine, Coubes, Albert, David, Stanislas, Lyonnet, Catheline, Vilain, Anne, Dieux-Coeslier, Sylvie, Manouvrier, Bertrand, Isidor, Marie-Line, Jacquemont, Sophie, Julia, Valérie, Layet, Sophie, Naudion, Sylvie, Odent, Laurent, Pasquier, Sybille, Pelras, Nicole, Philip, Geneviève, Pierquin, Fabienne, Prieur, Nisrine, Aboussair, Tania, Attie-Bitach, Geneviève, Baujat, Patricia, Blanchet, Catherine, Blanchet, Hélène, Dollfus, Bérénice, Doray, Elise, Schaefer, Patrick, Edery, Fabienne, Giuliano, Alice, Goldenberg, Cyril, Goizet, Agnès, Guichet, Christian, Herlin, Laetitia, Lambert, Bruno, Leheup, Jelena, Martinovic, Sandra, Mercier, Cyril, Mignot, Marie-Laure, Moutard, Marie-José, Perez, Lucile, Pinson, Jacques, Puechberty, Marjolaine, Willems, Hanitra, Randrianaivo, Kateline, Szakszon, Kateline, Szaskon, Annick, Toutain, Alain, Verloes, Jacqueline, Vigneron, Elodie, Sanchez, Pierre, Sarda, Jean-Louis, Laplanche, Corinne, Collet, Service de génétique médicale, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Institut National de la Santé et de la Recherche Médicale (INSERM), Clinique de Génétique médicale Guy Fontaine [CHRU LIlle], Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de génétique médicale [Toulouse], CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Unité de Cytogénétique et Génétique Médicale, Groupe Hospitalier du Havre-Hôpital Gustave Flaubert, Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service de Génétique, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Génétique Humaine, Université de Liège-CHU Liège, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Génétique Médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-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 ), Centre de Référence pour les Affections Rares en Génétique Ophtalmologique (CARGO) et Service de Génétique Médicale, Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre [Strasbourg], Centre de recherche en neurosciences de Lyon (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), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Médecine Infantile III et Génétique Clinique [CHRU Nancy], Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de foetopathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Groupe de recherche clinique 'déficience intellectuelle et autisme', Université Pierre et Marie Curie - Paris 6 (UPMC), Unité fonctionnelle de neurogénétique moléculaire et cellulaire, CHU Pitié-Salpêtrière [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), Service de génétique, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Physiopathologie et neuroprotection des atteintes du cerveau en développement, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Institut Lavoisier de Versailles (ILV), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CHU de Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service Génétique Médicale [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-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 ), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Bordeaux ( UB ) -CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Institut National de la Santé et de la Recherche Médicale, Head of the Department of Medical Genetics, Service de Génétique Clinique et Université Lille 2, Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Université de Nantes ( UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], 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 ), Institut de recherche, santé, environnement et travail ( Irset ), Université d'Angers ( UA ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -École des Hautes Études en Santé Publique [EHESP] ( EHESP ) -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 des Antilles ( UA ), Centre de recherche en neurosciences de Lyon ( 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 ), Institut Jacques Monod ( IJM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lorraine ( UL ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Université Pierre et Marie Curie - Paris 6 ( UPMC ), Service de Génétique [Pitié-Salpêtrière], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP]-Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Institut de génétique humaine ( IGH ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Bretonneau-CHRU Tours, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), Institut Lavoisier de Versailles ( ILV ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP]-Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Centre National de la Recherche Scientifique (CNRS), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA)
Subjects: Adult, Male, 0301 basic medicine, Franceschetti syndrome, medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], Molecular Sequence Data, Biology, Treacher Collins syndrome, Young Adult, 03 medical and health sciences, medicine, Humans, Base sequence, POLR1D, Amino Acid Sequence, Child, Genetic Association Studies, Ribonucleoprotein, U5 Small Nuclear, Genetics (clinical), Sequence Deletion, phenotype–genotype correlations, Base Sequence, [ SDV ] Life Sciences [q-bio], Nuclear Proteins, Large series, DNA-Directed RNA Polymerases, Mandibulofacial dysostosis, Middle Aged, Peptide Elongation Factors, Phosphoproteins, medicine.disease, Dermatology, 3. Good health, Surgery, TCOF1, 030104 developmental biology, Mutation, Microcephaly, Female, Mandibulofacial Dysostosis
Abstract: International audience; Purpose - Treacher Collins/Franceschetti syndrome (TCS; OMIM 154500) is a disorder of craniofacial development belonging to the heterogeneous group of mandibulofacial dysostoses. TCS is classically characterized by bilateral mandibular and malar hypoplasia, downward-slanting palpebral fissures, and microtia. To date, three genes have been identified in TCS:,TCOF1, POLR1D, and POLR1C. Methods - We report a clinical and extensive molecular study, including TCOF1, POLR1D, POLR1C, and EFTUD2 genes, in a series of 146 patients with TCS. Phenotype-genotype correlations were investigated for 19 clinical features, between TCOF1 and POLR1D, and the type of mutation or its localization in the TCOF1 gene. Results - We identified 92/146 patients (63%) with a molecular anomaly within TCOF1, 9/146 (6%) within POLR1D, and none within POLR1C. Among the atypical negative patients (with intellectual disability and/or microcephaly), we identified four patients carrying a mutation in EFTUD2 and two patients with 5q32 deletion encompassing TCOF1 and CAMK2A in particular. Congenital cardiac defects occurred more frequently among patients with TCOF1 mutation (7/92, 8%) than reported in the literature. Conclusion - Even though TCOF1 and POLR1D were associated with extreme clinical variability, we found no phenotype-genotype correlation. In cases with a typical phenotype of TCS, 6/146 (4%) remained with an unidentified molecular defect.
Published: 2016

12. Interfaces for noninvasive ventilation in the acute setting in children

Author: Sylvain Renolleau, Alessandro Amaddeo, Brigitte Fauroux, Sandrine Essouri, Guillaume Emeriaud, Guillaume Mortamet, Soins intensifs pédiatriques CHU Sainte -Justine Montréal, CHU Sainte Justine [Montréal], Unité de ventilation noninvasive et du sommeil de l'enfant, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biomécanique et appareil respiratoire : une approche multi-échelles (Equipe 13), 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), Soins intensifs pédiatriques [CHU Sainte -Justine Montréal], Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], Service d'assistance respiratoire et sommeil de l'enfant [CHU Necker], Département de Pédiatrie [CHU Sainte -Justine Montréal], Service Réanimation et surveillance continue médicochirurgicales [AP-HP Hôpital Necker-Enfants Malades], Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Dupuis, Christine, Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Biomécanique et appareil respiratoire : une approche multi-échelles ( Equipe 13 ), Institut Mondor de Recherche Biomédicale ( IMRB ), 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 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10, Université de Montréal ( UdeM ) -CHU Sainte Justine [Montréal], Université de Montréal-CHU Sainte Justine [Montréal], Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], and mortamet, guillaume
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, pediatrics, medicine.medical_treatment, Interface (computing), [ SDV.MHEP.PED ] Life Sciences [q-bio]/Human health and pathology/Pediatrics, mechanical ventilation, Intensive Care Units, Pediatric, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, law.invention, paediatrics, 03 medical and health sciences, Nasal mask, 0302 clinical medicine, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, children, law, medicine, Humans, Child, Intensive care medicine, Mechanical ventilation, Pediatric intensive care unit, Facial mask, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, business.industry, noninvasive ventilation, 030208 emergency & critical care medicine, Equipment Design, facial mask, 3. Good health, Treatment Outcome, 030228 respiratory system, Pediatrics, Perinatology and Child Health, Ventilation (architecture), nasal mask, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, interface, Noninvasive ventilation, Respiratory Insufficiency, business, [ SDV.MHEP.PSR ] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
Abstract: International audience; The use of noninvasive ventilation (NIV) is very specific in the acute setting as compared to its use in a chronic setting. In the Pediatric Intensive care Unit (PICU), NIV may be required around the clock and initiation has to be fast and easy. Despite the increasing use of non-invasive ventilation (NIV) and the larger choice of interfaces, data comparing the use of different interfaces for pediatric patients are scarce and recommendations for the most appropriate choice of interface are lacking. However, this choice in acute settings is crucial and a major contributor of the success of NIV. The aim of the present review was to describe the different types of interfaces available for children in the acute setting, their advantages and limitations, to highlight how to choose the optimal interface, and how to monitor the tolerance of the interface.
Published: 2016

13. Immune thrombocytopenia in adults: a prospective cohort study of clinical features and predictors of outcome

Author: Anne-Sophie Morin, Marc Michel, Daniel Adoue, Bertrand Godeau, Olivier Fain, Nathalie Costedoat-Chalumeau, Brigitte Pan-Petesch, Nadine Magy-Bertrand, Bernard Bonnotte, Clementine Nordon, Karim Sacre, François Lefrère, Mehdi Khellaf, Jean-François Viallard, Jean-Marc Durand, Lamiae Grimaldi-Bensouda, Lucien Abenhaim, Nathalie Morel, Antoinette Perlat, Philippe Quittet, LASER Paris, CHU Henri Mondor, Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Saint-Eloi, Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Morvan [Brest], Service d'Accueil des Urgences (Urgences - 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), CHU Pontchaillou [Rennes], Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Biothérapie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Service de médecine interne et maladies infectieuses [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Saint-André, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Hopital de Périgueux (CH Périgueux), Hopital de Périgueux, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Médecine Interne [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon], Service d'ORL et de chirurgie cervicale, CHU Grenoble, Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), London School of Hygiene and Tropical Medicine (LSHTM), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), HAL UPMC, Gestionnaire, Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint Eloi (CHRU Montpellier), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], CHU Henri Mondor [Créteil], Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Universitaire du Cancer de Toulouse - Oncopole ( IUCT Oncopole - UMR 1037 ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Jean Minjoz, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Hôpital de la Timone [CHU - APHM] ( TIMONE ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Médecine interne [CHU St-Antoine], CHU Saint-Antoine [APHP], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Hôpital Jean Verdier, CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Service d'Accueil des Urgences ( Urgences - Henri Mondor ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri-Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre de recherche sur l'Inflammation ( CRI ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), and Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP]
Subjects: Adult, Male, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.medical_specialty, Anti-nuclear antibody, Adolescent, [SDV]Life Sciences [q-bio], Logistic regression, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Odds Ratio, [ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology, Humans, Prospective Studies, Registries, Risk factor, Young adult, Family history, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Aged, Purpura, Thrombocytopenic, Idiopathic, business.industry, Disease Management, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Odds ratio, Articles, Middle Aged, 3. Good health, Surgery, Patient Outcome Assessment, Phenotype, 030220 oncology & carcinogenesis, Population Surveillance, Female, France, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology, Cohort study, Follow-Up Studies
Abstract: for the PGRx-ITP Study Group; International audience; This prospective observational cohort study aimed to explore the clinical features of incident immune thrombocytopenia in adults and predictors of outcome, while determining if a family history of autoimmune disorder is a risk factor for immune thrombocytopenia. All adults, 18 years of age or older, recently diagnosed with immune thrombocytopenia were consecutively recruited across 21 hospital centers in France. Data were collected at diagnosis and after 12 months. Predictors of chronicity at 12 months were explored using logistic regression models. The association between family history of autoimmune disorder and the risk of developing immune thrombocytopenia was explored using a conditional logistic regression model after matching each case to 10 controls. One hundred and forty-three patients were included: 63% female, mean age 48 years old (Standard Deviation=19), and 84% presented with bleeding symptoms. Median platelet count was 10×109/L. Initial treatment was required in 82% of patients. After 12 months, only 37% of patients not subject to disease-modifying interventions achieved cure. The sole possible predictor of chronicity at 12 months was a higher platelet count at baseline [Odds Ratio 1.03; 95%CI: 1.00, 1.06]. No association was found between outcome and any of the following features: age, sex, presence of either bleeding symptoms or antinuclear antibodies at diagnosis. Likewise, family history of autoimmune disorder was not associated with incident immune thrombocytopenia. Immune thrombocytopenia in adults has been shown to progress to a chronic form in the majority of patients. A lower platelet count could be indicative of a more favorable outcome.
Published: 2016

14. Classification of and risk factors for hematologic complications in a French national cohort of 102 patients with Shwachman-Diamond syndrome

Author: Christine Perot, Thierry Leblanc, Jean Donadieu, Odile Fenneteau, Christine Bellanné-Chantelot, Fanny Fouyssac, Anne Lambilliotte, Gérard Michel, Patrick Boutard, Catherine Paillard, Alain Morali, Nizar Mahlaoui, Florence Bellanger, Sandrine Beaufils, Valérie Mialou, Nathalie Aladjidi, Virginie Gandemer, Jacques Schmitz, Yves Bertrand, Blandine Beaupain, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hématologie Biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, AP-HP, CHU Pitié-Salpêtrière [AP-HP], IFR Necker-Enfants Malades (IRNEM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'hématologie pédiatrique-oncologie, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Hémato-oncologie Pédiatrique, CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Service de pédiatrie, Hospices Civils de Lyon (HCL)-Hôpital Debrousse, Hospices Civils de Lyon (HCL)-Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL), 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), Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'Hématologie et d'Oncologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Hémato-oncologie pédiatrique, CHU Clermont-Ferrand, Service d'hématologie-oncologie pédiatrique, CHU Pontchaillou [Rennes], Unité d'hémato-immuno-oncologie pédiatrique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Gastro-entérologie Pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Gastro-Entérologie Pédiatrique [CHRU Nancy], Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), The French registry is supported by grants from Amgen SAS, Chugai SA, GIS Maladies Rares, Institut de veille sanitaire and Inserm. This project is supported by a grant from Association Laurette Fugain and by constant and unlimited support of the Association Sportive de Saint Quentin Fallavier since 2004 with the unlimited commitment of Mr Gonnot., Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie-immunologie-oncologie pédiatrique, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré, AP-HP, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], IFR Necker-Enfants Malades ( IRNEM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Hospices Civils de Lyon ( HCL ) -Hôpital Debrousse, Hospices Civils de Lyon ( HCL ) -Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] ( IHOPe ), Hospices Civils de Lyon ( HCL ), 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 ), Hôpital de la Timone [CHU - APHM] ( TIMONE ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), and De Villemeur, Hervé
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Male, Pathology, Pediatrics, genotype, Lipomatosis, [SDV.GEN] Life Sciences [q-bio]/Genetics, secondary leukemia, 0302 clinical medicine, Risk Factors, hemic and lymphatic diseases, [ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology, cytopenia, Prospective Studies, Registries, Prospective cohort study, Bone Marrow Diseases, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Shwachman–Diamond syndrome, Shwachman-Diamond syndrome, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Prognosis, 3. Good health, Survival Rate, Leukemia, 030220 oncology & carcinogenesis, Female, France, medicine.medical_specialty, aplastic anemia, Anemia, monosomy 7, macromolecular substances, 03 medical and health sciences, [SDV.BDD] Life Sciences [q-bio]/Development Biology, medicine, Humans, [ SDV.BDD ] Life Sciences [q-bio]/Development Biology, Aplastic anemia, Survival rate, [SDV.GEN]Life Sciences [q-bio]/Genetics, Cytopenia, business.industry, Infant, medicine.disease, Hematologic Diseases, Exocrine Pancreatic Insufficiency, Original Articles and Brief Reports, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, myelodysplasia, business, Follow-Up Studies, 030215 immunology
Abstract: International audience; BACKGROUND: Patients with the Shwachman-Diamond syndrome often develop hematologic complications. No risk factors for these complications have so far been identified. The aim of this study was to classify the hematologic complications occurring in patients with Shwachman-Diamond syndrome and to investigate the risk factors for these complications. DESIGN AND METHODS: One hundred and two patients with Shwachman-Diamond syndrome, with a median follow-up of 11.6 years, were studied. Major hematologic complications were considered in the case of definitive severe cytopenia (i.e. anemia
Published: 2012

15. Case report: an unexpected link between partial deletion of the SHANK3 gene and Heller’s dementia infantilis, a rare subtype of autism spectrum disorder

Author: Nadia Bahi-Buisson, Anne Philippe, Marlène Rio, Valérie Malan, Nathalie Boddaert, Jean-Paul Bonnefont, Laurence Robel, Yann Craus, Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Psychiatrie de l'enfant et de l'adolescent [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Service de neurologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de Radiologie et imagerie médicale [CHU Necker], Laboratoire de Cytogénétique, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Génétique moléculaire, Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Santé mentale et santé publique ( SMSP - U1178 ), Université Paris-Sud - Paris 11 ( UP11 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Santé mentale et santé publique (SMSP - U1178), Université Paris-Sud - Paris 11 (UP11)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and BMC, BMC
Subjects: Pediatrics, medicine.medical_specialty, Autism Spectrum Disorder, 22q13.3 deletion syndrome, Genetic counseling, Chromosomes, Human, Pair 22, [SDV]Life Sciences [q-bio], Autism, Case Report, Nerve Tissue Proteins, ASD, Intellectual Disability, Intellectual disability, medicine, Dementia, Humans, Child, SHANK3, Heller syndrome, [ SDV ] Life Sciences [q-bio], Childhood disintegrative disorder, medicine.disease, Regression, 3. Good health, Regression, Psychology, [SDV] Life Sciences [q-bio], Developmental disorder, Psychiatry and Mental health, Phenotype, Autism spectrum disorder, Female, Haploinsufficiency, Psychology, Gene Deletion, Childhood disintegrative disorder (CDD), Clinical psychology
Abstract: International audience; AbstractBackgroundDeletions and mutations involving the SHANK3 gene lead to a nonspecific clinical presentation with moderate to profound intellectual disability, severely delayed or absent speech, and autism spectrum disorders (ASD).Better knowledge of the clinical spectrum of SHANK3 haploinsufficiency is useful to facilitate clinical care monitoring and to guide molecular diagnosis, essential for genetic counselling.Case presentationHere, we report a detailed clinical description of a 10-year-old girl carrying a pathogenic interstitial 22q13.3 deletion encompassing only the first 17 exons of SHANK3.The clinical features displayed by the girl strongly suggested the diagnosis of dementia infantilis, described by Heller in 1908, also known as childhood disintegrative disorder.ConclusionOur present case confirms several observations according to which regression may be part of the clinical phenotype of SHANK3 haploinsufficiency. Therefore, we think it is crucial to look for mutations in the gene SHANK3 in patients diagnosed for childhood disintegrative disorder or any developmental disorder with a regressive pattern involving social and communicative skills as well as cognitive and instinctual functions, with onset around 3 years.
Published: 2015

16. Burden of bacterial resistance among neonatal infections in low income countries: how convincing is the epidemiological evidence?

Author: Laurence Watier, Elisabeth Delarocque-Astagneau, Benoit Garin, Michael Padget, Elsa Kermorvant-Duchemin, Perlinot Herindrainy, Didier Guillemot, Bich-Tram Huynh, Pharmacoepidemiologie et évaluation de l'impact des produits de santé sur les populations, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Pharmacoépidémiologie et maladies infectieuses (PhEMI), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Experimental Bacteriology Laboratory [Antananarivo ], Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Epidemiology Unit, Service de Médecine Néonatale, Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was undertaken as part of the ChARLI project (http://www.charliproject.org/) which is supported by the funding of the Department of International Cooperation of the Principality of Monaco. This study has also received funding from the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant n°ANR-10-LABX-62-IBEID)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Pharmacoépidémiologie et Maladies Infectieuses ( PHEMI ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ), Experimental Bacteriology Laboratory, Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Department of Physics, Emory University [Atlanta, GA], Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ), BMC, BMC, and Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID
Subjects: Male, medicine.medical_specialty, Pediatrics, Epidemiology, [SDV]Life Sciences [q-bio], 030231 tropical medicine, HIV Infections, Drug resistance, Community, Infant, Newborn, Diseases, Developing countries, 03 medical and health sciences, 0302 clinical medicine, Medical microbiology, Antibiotic resistance, Cost of Illness, Neonatal, medicine, Humans, 030212 general & internal medicine, Poverty, Bacterial disease, Neonatal sepsis, [ SDV ] Life Sciences [q-bio], business.industry, Incidence, Antibiotic resistant bacterial infection, 1. No poverty, Infant, Newborn, Infant, Drug Resistance, Microbial, Bacterial Infections, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Community-Acquired Infections, Malnutrition, Neonatal infection, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Infectious Diseases, Child, Preschool, Female, business, Research Article
Abstract: International audience; Background: Antibiotic resistance is a threat in developing countries (DCs) because of the high burden of bacterial disease and the presence of risk factors for its emergence and spread. This threat is of particular concern for neonates in DCs where over one-third of neonatal deaths may be attributable to severe infections and factors such as malnutrition and HIV infection may increase the risk of death. Additional, undocumented deaths due to severe infection may also occur due to the high frequency of at-home births in DCs. Methods: We conducted a systematic review of studies published after 2000 on community-acquired invasive bacterial infections and antibiotic resistance among neonates in DCs. Twenty-one articles met all inclusion criteria and were included in the final analysis. Results: Ninety percent of studies recruited participants at large or university hospitals. The majority of studies were conducted in Sub-Saharan Africa (n = 10) and the Indian subcontinent (n = 8). Neonatal infection incidence ranged from 2.9 (95% CI 1.9–4.2) to 24 (95% CI 21.8–25.7) for 1000 live births. The three most common bacterial isolates in neonatal sepsis were Staphylococcus aureus, Escherichia coli, and Klebsiella. Information on antibiotic resistance was sparse and often relied on few isolates. The majority of resistance studies were conducted prior to 2008. No conclusions could be drawn on Enterobacteriaceae resistance to third generation cephalosporins or methicillin resistance among Staphylococcus aureus. Conclusions: Available data were found insufficient to draw a true, recent, and accurate picture of antibiotic resistance in DCs among severe bacterial infection in neonates, particularly at the community level. Existing neonatal sepsis treatment guidelines may no longer be appropriate, and these data are needed as the basis for updated guidelines. Reliable microbiological and epidemiological data at the community level are needed in DCs to combat the global challenge of antibiotic resistance especially among neonates among whom the burden is greatest.
Published: 2015

17. A preoperative prognostic model for patients treated with nephrectomy for renal cell carcinoma

Author: Jean Luc Descotes, Jacques Tostain, Jean Jacques Patard, Walter Artibani, Pierre I. Karakiewicz, Alexandre de la Taille, Luca Cindolo, Richard Zigeuner, Roberto Bertini, Nazareno Suardi, Antoine Valeri, Peter F.A. Mulders, Arnaud Mejean, Umberto Capitanio, Francesco Montorsi, Claudio Jeldres, Jean Jacques Rambeaud, Karim Bensalah, Laurent Salomon, Vincenzo Ficarra, Cancer Prognostics and Health Outcome Unit, Université de Montréal (UdeM), Department of urology, Università Vita-Salute San Raffaele, Department of Oncological and Surgical Sciences, Università degli Studi di Padova = University of Padua (Unipd), G Rummo Hospital, Service d'urologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'urologie-andrologie, CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Hôpital nord, Department of Urology, Radboud University Medical Center [Nijmegen], Service d'urologie [Rennes] = Urology [Rennes], Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Medical University Graz, Service d'urologie, Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Grenoble-Ministère de la santé, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Universita degli Studi di Padova, Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service d'Urologie - Andrologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Université de Montréal, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] ( UJM ) -Hôpital nord, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université de Brest ( UBO ) -Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140-Centre National de la Recherche Scientifique ( CNRS ), Université de Montréal [Montréal], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Centre National de la Recherche Scientifique (CNRS), Karakiewicz Pierre, I., Suardi, Nazareno, Capitanio, Umberto, Jeldres, Claudio, Ficarra, Vincenzo, Cindolo, Luca, de la Taille, Alexandre, Tostain, Jacque, Mulders Peter, F. A., Bensalah, Karim, Artibani, Walter, Salomon, Laurent, Zigeuner, Richard, Valeri, Antoine, Descotes Jean, Luc, Rambeaud Jean, Jacque, Mejean, Arnaud, Montorsi, Francesco, Bertini, Roberto, and Patard Jean, Jacques
Subjects: Male, Decision-making, Nomogram, Pre-treatment, Renal cell carcinoma, Urology, [ SDV.MHEP.UN ] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Time Factors, medicine.medical_treatment, 030232 urology & nephrology, Aetiology, screening and detection [ONCOL 5], urologic and male genital diseases, Nephrectomy, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Cohort Studies, 0302 clinical medicine, Cause of Death, Medicine, Prospective Studies, Survivors, Prospective cohort study, Tomography, Mortality rate, Prognosis, 3. Good health, X-Ray Computed, Survival Rate, 030220 oncology & carcinogenesis, Cohort, Regression Analysis, Female, radical nephrectomy, medicine.medical_specialty, renal cell carcinoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease-Free Survival, 03 medical and health sciences, Translational research [ONCOL 3], Humans, Survival rate, Carcinoma, Renal Cell, Neoplasm Staging, Probability, Analysis of Variance, business.industry, Proportional hazards model, Carcinoma, Renal Cell, Reproducibility of Results, Multivariate Analysis, Tomography, X-Ray Computed, medicine.disease, Surgery, business
Abstract: Background: Currently two pretreatment prognostic models with limited accuracy (65-67%) can be used to predict survival in patients with localized renal cell carcinoma (RCC). Objective: We set out to develop a more accurate pretreatment model for predicting RCC-specific mortality after nephrectomy for all stages of RCC. Design, setting, and participants: The data originated from a series of prospectively recorded contemporary cases of patients treated with radical or partial nephrectomy between 1984 and 2006. Model development was performed using data from 2474 patients from five centers and external validation was performed using data from 1972 patients from seven centers. Measurements: The probability of RCC-specific mortality was modeled using Cox regression. The significance of the predictors was confirmed using competing risks analyses, which account for mortality from other causes. Results and limitations: Median follow-up in patients who did not die of RCC-specific causes was 4.2 yr and 3.5 yr in the development and validation cohorts, respectively. The freedom from cancer-specific mortality rates in the nomogram development cohort were 75.4% at 5 yr after nephrectomy and 68.3% at 10 yr after nephrectomy. All variables except gender achieved independent predictor status. In the external validation cohort the nomogram predictions were 88.1% accurate at 1 yr, 86.8% accurate at 2 yr, 86.8% accurate at 5 yr, and 84.2% accurate at 10 yr. Conclusions: Our model substantially exceeds the accuracy of the existing pretreatment models. Consequently, the proposed nomogram-based predictions may be used as benchmark data for pretreatment decision making in patients with various stages of RCC. (c) 2008 Published by Elsevier B.V. on behalf of European Association of Urology.
Published: 2009

18. Does regular blood transfusion prevent progression of cerebrovascular lesions in children with sickle cell disease?

Author: Yann Consigny, Lucie Hertz-Pannier, Robert Girot, Gérard Lenoir, Valentine Brousse, Mariane de Montalembert, Jean-Louis Bresson, Elsa Mirre, Etablissement Français du Sang Ile de France (EFS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de pédiatrie générale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre de Référence de la Drépanocytose, Service de radiologie pédiatrique [CHU Necker], Epilepsies de l'Enfant et Plasticité Cérébrale (U1129), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Clinical Research Unit, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Centre de Référence de la Drépanocytose-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP]-Centre de Référence de la Drépanocytose, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, CHU Tenon [APHP], Etablissement Français du Sang Ile de France ( EFS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP]-Centre de Référence de la Drépanocytose, Epilepsies de l'Enfant et Plasticité Cérébrale ( U1129 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, and Haematology Laboratory
Subjects: Male, medicine.medical_specialty, Blood transfusion, Anemia, medicine.medical_treatment, Brain imaging, Anemia, Sickle Cell, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Blood Transfusion, Child, Stroke, Retrospective Studies, medicine.diagnostic_test, business.industry, Sickle cell disease, Transfusion, Angiography, Magnetic resonance imaging, Retrospective cohort study, Hematology, General Medicine, medicine.disease, Magnetic Resonance Imaging, 3. Good health, Surgery, Transcranial Doppler, Cerebrovascular Disorders, Child, Preschool, 030220 oncology & carcinogenesis, Disease Progression, Female, Transfusion therapy, business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: International audience; A retrospective study was conducted to assess changes in cerebrovascular lesions, as assessed by magnetic resonance (MR) imaging and angiography in 18 children with sickle cell disease (SCD) receiving optimised chronic transfusions for primary stroke prevention (abnormal transcranial Doppler flow, nine patients, median follow-up 14.3 months (range, 7.9–48.9)) or secondary stroke prevention (nine patients, median follow-up 59.6 months (range, 11.0–127.9)). An experienced neuroradiologist blinded to patient data reviewed the 41 MR scans (median/patient, three (2–4)). Standard scores were used to evaluate parenchymal and vascular abnormalities at baseline and last follow-up. Within-patient score changes evaluated using Wilcoxon's paired rank test indicated lesion progression in the secondary-prevention group ( = 0.027). Optimised transfusion therapy does not prevent progression of cerebral vasculopathy in SCD children with a history of stroke.
Published: 2008

19. De Novo Donor-Specific Human Leukocyte Antigen Antibodies in Nonsensitized Kidney Transplant Recipients After T Cell-Mediated Rejection

Author: Marie-Alexandra Alyanakian, Julien Zuber, Jean-Paul Duong Van Huyen, Christophe Legendre, Dominique Charron, Jonathan-Maurice Chemouny, Maryvonnick Carmagnat, Marion Rabant, Marc-Olivier Timsit, Caroline Suberbielle, Alexandre Loupy, Xavier Lebreton, Dany Anglicheau, Nathan Pinheiro, Laboratoire d'histocompatibilité [Paris], Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunology and Histocompatibility Laboratory, Service de Transplantation Rénale, Service d'urologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Hématologie -Immunologie -Cibles thérapeutiques, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie adultes [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP]
Subjects: Adult, Graft Rejection, Male, medicine.medical_specialty, Biopsy, T-Lymphocytes, 030232 urology & nephrology, Human leukocyte antigen, 030230 surgery, Kidney, Gastroenterology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Isoantibodies, 03 medical and health sciences, 0302 clinical medicine, Antigen, HLA Antigens, Internal medicine, medicine, Humans, Kidney transplantation, ComputingMilieux_MISCELLANEOUS, Aged, First episode, Transplantation, biology, business.industry, Middle Aged, medicine.disease, Kidney Transplantation, Tissue Donors, 3. Good health, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Creatinine, biology.protein, Female, Antibody, business
Abstract: BACKGROUND Local inflammation is a potential cause of humoral alloimmune responses in renal transplantation, and de novo donor-specific anti-human leucocyte antigen antibodies (dnDSAs) have been associated with a history of acute rejection. METHODS We investigated the frequencies and consequences of dnDSAs after a first episode of acute T-cell-mediated rejection (index TCMR) in previously unsensitized kidney transplant recipients. RESULTS Of the 1,054 patients who underwent kidney transplantation between September 2004 and December 2010 at our center, we identified 75 unsensitized patients with at least one TCMR. Index TCMRs were diagnosed 4.4 ± 6.8 months after transplantation. The dnDSAs were assessed using the highly sensitive single-antigen human leukocyte antigen bead assay 5.1 ± 3.9 months after the index TCMR and were detected in 16 patients (21%). Patients who developed dnDSAs were more likely to have experienced pre-transplant sensitizing events and were indistinguishable in their clinical, biologic, and histologic variables at the time of index TCMR, although the tubulitis scores tended to be higher (P = 0.079). These patients experienced a significantly higher incidence of subsequent antibody-mediated rejection episodes (P < 0.001), but reduced death-censored graft survival was not observed after a median follow-up of 5.5 years post-transplantation. Follow-up biopsies revealed increased antibody-mediated changes with significantly higher glomerulitis scores and numerically higher C4d staining scores. CONCLUSION Monitoring anti-human leukocyte antigen antibodies after cellular rejection may be useful, especially among patients with a history of pretransplant exposure to alloantigens, to predict subsequent humoral events and their consequences.
Published: 2015

20. 23andMe: a new two-sided data-banking market model

Author: Christian Hervé, Guillaume Vogt, Henri-Corto Stoeklé, Marie-France Mamzer-Bruneel, BMC, BMC, Laboratoire d'éthique médicale et de médecine légale (EA 4569), Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Cancer Research and Personalized Medicine - CARPEM [Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité fonctionnelle d'éthique Médicale [AP-HP Hôpital Necker, Paris], Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CARPEM (CAncer Research For PErsonalized Medicine)., Laboratoire d'éthique médicale et de médecine légale ( EA 4569 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université Sorbonne Paris Cité ( USPC ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Necker - Enfants Malades [AP-HP]-CHU Cochin [AP-HP], Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), and Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: 0301 basic medicine, Health (social science), Biomedical Research, Debate, [SDV]Life Sciences [q-bio], Federal law, Informed consent, Risk Factors, Medicine, Marketing, Predictive testing, Biological Specimen Banks, Informed Consent, medicine.diagnostic_test, Health Policy, 06 humanities and the arts, Biobank, 3. Good health, [SDV] Life Sciences [q-bio], Data banking, Private Sector, Personally identifiable information, Bloom Syndrome, Biobanking, Genetic genealogy, 0603 philosophy, ethics and religion, Health(social science), 03 medical and health sciences, Humans, Genetic Predisposition to Disease, Genetic Testing, Direct-to-consumer (DTC) genetic testing, Genetic testing, Service, [ SDV ] Life Sciences [q-bio], business.industry, Conflict of Interest, United States Food and Drug Administration, Research, Ethical issues, Conflict of interest, Reproducibility of Results, DNA, United States, Issues, ethics and legal aspects, 030104 developmental biology, Two-sided markets, Law, 060301 applied ethics, business
Abstract: International audience; BackgroundSince 2006, the genetic testing company 23andMe has collected biological samples, self-reported information, and consent documents for biobanking and research from more than 1,000,000 individuals (90 % participating in research), through a direct-to-consumer (DTC) online genetic-testing service providing a genetic ancestry report and a genetic health report. However, on November 22, 2013, the Food and Drug Administration (FDA) halted the sale of genetic health testing, on the grounds that 23andMe was not acting in accordance with federal law, by selling tests of undemonstrated reliability as predictive tests for medical risk factors. Consumers could still obtain the genetic ancestry report, but they no longer had access to the genetic health report in the United States (US). However, this did not prevent the company from continuing its health research, with previously obtained and future samples, provided that consent had been obtained from the consumers concerned, or with health reports for individuals from other countries. Furthermore, 23andMe was granted FDA authorization on February 19, 2015, first to provide reports about Bloom syndrome carrier status, and, more recently, to provide consumers with “carrier status” information for 35 genes known (with high levels of confidence) to cause disease.DiscussionIn this Debate, we highlight the likelihood that the primary objective of the company was probably two-fold: promoting itself within the market for predictive testing for human genetic diseases and ancestry at a low cost to consumers, and establishing a high-value database/biobank for research (one of the largest biobanks of human deoxyribonucleic acid (DNA) and personal information).SummaryBy dint of this marketing approach, a two-sided market has been established between the consumer and the research laboratories, involving the establishment of a database/DNA biobank for scientific and financial gain. We describe here the profound ethical issues raised by this setup.
Published: 2015

21. HOX11L2/TLX3 is transcriptionally activated through T-cell regulatory elements downstream of BCL11B as a result of the t(5;14)(q35;q32)

Author: Virginie Penard-Lacronique, Isabelle André-Schmutz, Xin-Ying Su, Roland Berger, Paola Ballerini, Claudie Lemercier, Véronique Della-Valle, Francine Mugneret, Serge Romana, Michel Lessard, Isabelle Radford-Weiss, Marina Lafage-Pochitaloff, Olivier Bernard, Génétique des hémopathies humaines ( EMI 210 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Developpement Normal et Pathologique du Système Immunitaire, Contrôle moléculaire de la réponse immune specifique, Université Joseph Fourier - Grenoble 1 ( UJF ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de Cytogénétique, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Service d'Hématologie Biologique, Assistance publique - Hôpitaux de Paris (AP-HP), Laboratoire d'Hématologie, CHU Strasbourg, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Laboratoire de cytogénétique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Génétique des hémopathies humaines (EMI 210), 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 Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: Oncogene Proteins, Fusion, Transcription, Genetic, T-Lymphocytes, BCL11B, Chromosomal translocation, MESH : Promoter Regions, Genetic, MESH : Oncogene Proteins, Fusion, Biochemistry, Jurkat cells, Translocation, Genetic, Jurkat Cells, MESH : Chromosomes, Human, Pair 5, 0302 clinical medicine, MESH : Translocation, Genetic, Transcription (biology), MESH: Jurkat Cells, Leukemia-Lymphoma, Adult T-Cell, MESH: Leukemia-Lymphoma, Adult T-Cell, MESH : Homeodomain Proteins, Promoter Regions, Genetic, MESH : Jurkat Cells, Oncogene Proteins, 0303 health sciences, MESH : Chromosomes, Human, Pair 14, MESH : Oncogene Proteins, MESH : Tumor Suppressor Proteins, Cell Differentiation, Hematology, Transfection, MESH: Translocation, Genetic, DNA-Binding Proteins, medicine.anatomical_structure, MESH: Repressor Proteins, 030220 oncology & carcinogenesis, Chromosomes, Human, Pair 5, MESH : DNA-Binding Proteins, MESH : Repressor Proteins, MESH : Cell Differentiation, MESH: Cell Differentiation, MESH: Chromosomes, Human, Pair 5, T cell, Immunology, Biology, 03 medical and health sciences, MESH: Oncogene Proteins, MESH: Promoter Regions, Genetic, MESH: Homeodomain Proteins, medicine, Humans, MESH: Tumor Suppressor Proteins, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Chromosomes, Human, Pair 14, Homeodomain Proteins, MESH : T-Lymphocytes, MESH: Humans, Recombinase activity, Tumor Suppressor Proteins, MESH: Transcription, Genetic, MESH : Humans, MESH : Transcription, Genetic, Cell Biology, T lymphocyte, Molecular biology, MESH : Leukemia-Lymphoma, Adult T-Cell, Repressor Proteins, MESH: T-Lymphocytes, MESH: Chromosomes, Human, Pair 14, MESH: DNA-Binding Proteins, MESH: Oncogene Proteins, Fusion
Abstract: International audience; The t(5;14)(q35;q32) chromosomal translocation is specifically observed in up to 20% of childhood T-cell acute lymphoblastic leukemia (T-ALL). It affects the BCL11B/CTIP2 locus on chromosome 14 and the RANBP17-TLX3/HOX11L2 region on chromosome 5. It leads to ectopic activation of TLX3/HOX11L2. To investigate the reasons of the association between t(5;14) and T-ALL, we isolated the translocation breakpoints in 8 t(5;14) patients. Sequence analyses did not involve recombinase activity in the genesis of the translocation. We used DNAse1 hypersensitive experiments to locate transcriptional regulatory elements downstream of BCL11B. By transient transfection experiments, 2 of the 6 regions demonstrated cis-activation properties in T cells and were also effective on the TLX3 promoter. Our data indicate that the basis of the specific association between t(5;14) and T-ALL lies on the juxtaposition of TLX3 to long-range cis-activating regions active during T-cell differentiation.
Published: 2006

22. Orthopedics management of acromicric dysplasia: follow up of nine patients

Author: Céline Klein, Christophe Glorion, Carine Le Goff, Philippe Violas, Sylvie Odent, Vicken Topouchian, Valérie Cormier-Daire, 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 chirurgie orthopédique pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de génétique clinique [Rennes], Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -CHU Pontchaillou [Rennes]-Hôpital Sud, Service de chirurgie orthopédique, réparatrice et traumatologique [Rennes], Hôpital Sud, 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-hôpital Sud, CHU Pontchaillou [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-Hôpital Sud, Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud
Subjects: Male, Fibrillin-1, 0302 clinical medicine, Acromicric dysplasia, Orthopedic Procedures, Child, [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics, Genetics (clinical), 0303 health sciences, Microfilament Proteins, Anatomy, Middle Aged, 3. Good health, REVISION, medicine.anatomical_structure, Epiphysis, Child, Preschool, Female, Adult, musculoskeletal diseases, Heterozygote, medicine.medical_specialty, Adolescent, Limb Deformities, Congenital, Fibrillins, Bone and Bones, CLASSIFICATION, Young Adult, 03 medical and health sciences, Femoral head, 030225 pediatrics, Genetics, medicine, Humans, Carpal tunnel syndrome, 030304 developmental biology, Hip dysplasia, Bone Diseases, Developmental, GENETIC SKELETAL DISORDERS, NOSOLOGY, business.industry, MUTATIONS, Bone age, CARPAL-TUNNEL-SYNDROME, medicine.disease, Acetabular dysplasia, Surgery, Radiography, Orthopedics, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Dysplasia, Mutation, business, Follow-Up Studies
Abstract: Acromicric dysplasia (AD) is an autosomal dominant disorder characterized by short stature, short extremities, stiff joint and skeleton features including brachymetacarpia, cone-shaped epiphyses, internal notch of the femoral head, and delayed bone age. Recently, we identified fibrillin 1 (FBN1) as the disease gene of AD. The aim of our study was to further describe the long-term follow up of AD patients with an emphasis on orthopedic management. Nine patients with FBN1 mutations were included in the study ranging in age from 5.5 to 64 years. For all, detailed clinical and radiological data were available. Results: Birth parameters were always normal and patients progressively developed short stature
Published: 2014

23. Pharmacokinetics, hemodynamic and metabolic effects of epinephrine to prevent post-operative low cardiac output syndrome in children

Author: Alice Bordessoule, Saik Urien, Philippe Pouard, Mehdi Oualha, Irène D’Agostino, Odile Spreux-Varoquaux, Jean-Marc Tréluyer, Réanimation Pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infections à Vih, Réservoirs, Pharmacologie des Antirétroviraux et Prévention de la Transmission Mère Enfant, Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier de Versailles André Mignot (CHV), Réanimation Chirurgicale Cardiaque Pédiatrique, The funding sources were the Programme Hospitalier de Recherche Clinique régional (PHRC) AOR 11 162, 2011, ' pharmacocinétique et pharmacodynamie de population des catécholamines chez l'enfant et le nouveau-né '., Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris Descartes - Paris 5 (UPD5) - CHU Necker - Enfants Malades [AP-HP], Unité de Pharmacologie - Toxicologie, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ) - Centre Hospitalier de Versailles (CHV) - UFR des Sciences de la Santé Ile-de-France Ouest, and BMC, Ed.
Subjects: Male, Cardiac output, Mean arterial pressure, Adolescent, Epinephrine, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Population, Cardiac Output, Low, Hemodynamics, Critical Care and Intensive Care Medicine, Models, Biological, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Heart Rate, 030225 pediatrics, Heart rate, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Postoperative Period, Prospective Studies, Cardiac Surgical Procedures, Child, education, education.field_of_study, Dose-Response Relationship, Drug, business.industry, Research, Body Weight, Age Factors, Infant, Newborn, Infant, 030208 emergency & critical care medicine, Child, Preschool, Pharmacodynamics, Anesthesia, Milrinone, Female, business, medicine.drug
Abstract: International audience; INTRODUCTION: The response to exogenous epinephrine (Ep) is difficult to predict given the multitude of factors involved such as broad pharmacokinetic and pharmacodynamic between-subject variabilities, which may be more pronounced in children. We investigated the pharmacokinetics and pharmacodynamics of Ep, co-administered with milrinone, in children who underwent open heart surgical repair for congenital defects following cardiopulmonary bypass, including associated variability factors. METHODS: Thirty-nine children with a high risk of low cardiac output syndrome were prospectively enrolled. Ep pharmacokinetics, hemodynamic and metabolic effects were analyzed using the non-linear mixed effects modeling software MONOLIX. According to the final model, an Ep dosing simulation was suggested. RESULTS: Ep dosing infusions ranged from 0.01 to 0.23 mug.kg-1.min-1 in children whose weight ranged from 2.5 to 58 kg. A one-compartment open model with linear elimination adequately described the Ep concentration-time courses. Bodyweight (BW) was the main covariate influencing clearance (CL) and endogenous Ep production rate (q0) via an allometric relationship: CL(BWi) = thetaCL x (BWi)3/4 and q0(BWi) = thetaq0 x (BWi )3/4. The increase in heart rate (HR) and mean arterial pressure (MAP) as a function of Ep concentration were well described using an Emax model. The effect of age was significant on HR and MAP basal level parameters. Assuming that Ep stimulated the production rate of plasma glucose, the increases in plasma glucose and lactate levels were well described by turnover models without any significant effect of age, BW or exogenous glucose supply. CONCLUSIONS: According to this population analysis, the developmental effects of BW and age explained a part of the pharmacokinetic and pharmacodynamics between-subject variabilities of Ep administration in critically ill children. This approach ultimately leads to a valuable Ep dosing simulation which should help clinicians to determine an appropriate a priori dosing regimen.
Published: 2014

24. Does neonatal pain management in intensive care units differ between night and day? An observational study

Author: Babak Khoshnood, Patricia Cimerman, Véronique Zupan, Patrick Daoud, Sylvain Renolleau, Romain Guedj, A Coursol, Elodie Zana, Philippe Hubert, Kanwaljeet J. S. Anand, Sophie Aizenfisz, Michèle Granier, Claude Danan, Philippe Durand, Florence Castela, Ricardo Carbajal, Alexandre Lapillonne, Laure de Saint Blanquat, Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Structure et Instabilité des Génomes (STRING), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de réanimation néonatale, CHI Créteil, Centre Hospitalier Intercommunal André Grégoire [Montreuil] (CHI André Gregoire), Service de Pédiatrie et Réanimations néonatales [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de réanimation néonatale et pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Maternité Port-Royal [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Réanimation et Surveillance Continue Pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Réanimation Néonatale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Réanimation Polyvalent Pédiatrique, Médecine néonatale, Centre Hospitalier Sud Francilien, CH Evry-Corbeil-CH Evry-Corbeil, Réanimation Néonatale et Pédiatrique, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Unité de Réanimation Néonatale, CHI Poissy-Saint-Germain, Médecine Néonatale et Réanimation Pédiatrique, CH René Dubos, University of Tennessee Health Science Center & Le Bonheur Children's Hospital, University of Tennesse Health Science, Grant funds from the Fondation CNP, and the Fondation de France, France., Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'urgences pédiatriques, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], CHI André Grégoire, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Antoine Béclère, CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Centre Nationale de Ressources de Lutte Contre la Douleur (CNRD), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Debs, Nayla, Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique ( CRESS - U1153 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Structure et Instabilité des Génomes ( STRING ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Muséum National d'Histoire Naturelle ( MNHN ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Antoine Béclère, Service de réanimation néonatale et pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Centre Nationale de Ressources de Lutte Contre la Douleur ( CNRD ), and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP]
Subjects: Male, Pediatrics, medicine.medical_specialty, Night Care, Paris, Neonatal intensive care unit, painful procedures, Analgesic, Pain, Neonatology and infant care, After-hours care, Neonate, Intensive care, Intensive Care Units, Neonatal, Epidemiology, medicine, Humans, Pain Management, Prospective Studies, Practice Patterns, Physicians', Prospective cohort study, Morning, Analgesics, business.industry, Research, Infant, Newborn, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Paediatrics, General Medicine, 3. Good health, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Observational study, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: International audience; OBJECTIVE: To determine whether analgesic use for painful procedures performed in neonates in the neonatal intensive care unit (NICU) differs during nights and days and during each of the 6 h period of the day. DESIGN: Conducted as part of the prospective observational Epidemiology of Painful Procedures in Neonates study which was designed to collect in real time and around-the-clock bedside data on all painful or stressful procedures. SETTING: 13 NICUs and paediatric intensive care units in the Paris Region, France. PARTICIPANTS: All 430 neonates admitted to the participating units during a 6-week period between September 2005 and January 2006. DATA COLLECTION: During the first 14 days of admission, data were collected on all painful procedures and analgesic therapy. The five most frequent procedures representing 38 012 of all 42 413 (90%) painful procedures were analysed. INTERVENTION: Observational study. MAIN OUTCOME ASSESSMENT: We compared the use of specific analgesic for procedures performed during each of the 6 h period of a day: morning (7:00 to 12:59), afternoon, early night and late night and during daytime (morning+afternoon) and night-time (early night+late night). RESULTS: 7724 of 38 012 (20.3%) painful procedures were carried out with a specific analgesic treatment. For morning, afternoon, early night and late night, respectively, the use of analgesic was 25.8%, 18.9%, 18.3% and 18%. The relative reduction of analgesia was 18.3%, p
Published: 2014

25. Cord serum 25-hydroxyvitamin D and risk of early childhood transient wheezing and atopic dermatitis

Author: Isabella Annesi-Maesano, Nour Baïz, Jean-Claude Souberbielle, Patricia Dargent-Molina, John D. Wark, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Recherche Epidémiologique en Santé Périnatale et Santé des Femmes et des Enfants (UMR_S 953), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris-Sud - Paris 11 (UP11), Department of Medicine, University of Melbourne-The Royal Melbourne Hospital, Laboratoire de Physiologie, Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), EDEN Mother-Child Cohort Study Group, Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), De Lauzon-Guillain, Blandine, Epidémiologie des Maladies Allergiques et Respiratoires ( EPAR ), Epidémiologie, systèmes d'information et modélisation, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -CHU Saint-Antoine [APHP]-Université Pierre et Marie Curie - Paris 6 ( UPMC ) -CHU Saint-Antoine [APHP], Recherche Epidémiologique en Santé Périnatale et Santé des Femmes et des Enfants ( UMR_S 953 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris-Sud - Paris 11 ( UP11 ), The Royal Melbourne Hospital-Université de Melbourne, and Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP]
Subjects: Male, Pediatrics, Allergy, DC, Cohort Studies, 0302 clinical medicine, Pregnancy, Surveys and Questionnaires, Etude des Déterminants pré et post natals du développement et de la santé de l′Enfant, Immunology and Allergy, 030212 general & internal medicine, Vitamin D, atopic dermatitis, 25(OH)D, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, OR, Atopic dermatitis, Odds ratio, 25-hydroxyvitamin D, 3. Good health, Cord blood, Child, Preschool, cord blood, Female, Dendritic cell, Adult, Risk, medicine.medical_specialty, allergic diseases, Cord, Rhinitis, Allergic, Perennial, Offspring, Immunology, mother-child cohort, Dermatitis, Atopic, 03 medical and health sciences, medicine, Vitamin D and neurology, Humans, Asthma, Respiratory Sounds, EDEN, business.industry, wheezing, Infant, Newborn, Infant, Immunoglobulin E, medicine.disease, Rhinitis, Allergic, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Follow-Up Studies
Abstract: BACKGROUND: There is increasing evidence of the effect of maternal vitamin D intake during pregnancy on the risk of asthma and allergic outcomes in offspring. However, studies on the relationship between cord levels of 25-hydroxyvitamin D (25[OH]D) and asthma and allergic diseases are very few. OBJECTIVE: Our aim was to investigate the associations between cord serum 25(OH)D levels and asthma, wheezing, allergic rhinitis, and atopic dermatitis in the offspring from birth to 5 years. METHODS: Cord blood samples were collected at birth and analyzed for 25(OH)D levels in 239 newborns from the Etude des Determinants pre et post natals du developpement et de la sante de l'Enfant (EDEN) birth cohort. The children were followed up until age 5 years by using International Study of Asthma and Allergies in Childhood-based symptom questionnaires. RESULTS: The median cord serum level of 25(OH)D was 17.8 ng/mL (interquartile range, 15.1 ng/mL). By using multivariable-adjusted logistic regression models, a significant inverse association was observed between cord serum 25(OH)D levels and risk of transient early wheezing and early- and late-onset atopic dermatitis, as well as atopic dermatitis, by the ages of 1, 2, 3, and 5 years. We found no association between cord serum 25(OH)D levels and asthma and allergic rhinitis at age 5 years. CONCLUSIONS: Cord serum 25(OH)D levels were inversely associated with the risk of transient early wheezing and atopic dermatitis by the age of 5 years, but no association was found with asthma and allergic rhinitis.
Published: 2014

26. Ostéopathies fragilisantes, maladie rénale chronique, malabsorptions, anomalies biologiques du métabolisme phosphocalcique : les bonnes indications pour un remboursement raisonné du dosage de vitamine D [Weakening osteopathies, chronic kidney disease, malabsorption, biological anomalies of calium/phosphorus metabolism: appropriate indications for a reasoned reimbursment of serum vitamin D measurement]

Author: Souberbielle, Jean-Claude, Benhamou, Claude-Laurent, Cortet, Bernard, Rousière, Mickael, Roux, Christian, Abitbol, Vered, Annweiler, Cédric, Audran, Maurice, Bacchetta, Justine, Bataille, Pierre, Beauchet, Olivier, Bardet, Rémi, Benachi, Alexandra, Berenbaum, Francis, Blain, Hubert, Borson-Chazot, Françoise, Breuil, Véronique, Briot, Karine, Brunet, Philippe, Carel, Jean-Claude, Caron, Philippe, Chabre, Olivier, Chanson, Philippe, Chapurlat, Roland, Cochat, Pierre, Coutant, Régis, Christin-Maitre, Sophie, Cohen-Solal, Martine, Combe, Christian, Cormier, Catherine, Courbebaisse, Marie, Debrus, Grégory, Delemer, Brigitte, Deschênes, Georges, Duquenne, Marc, Fardellone, Patrice, Fouque, Denis, Friedlander, Gérard, Gauvain, Jean-Bernard, Groussin, Lionel, Guggenbuhl, Pascal, Houillier, Pascal, Hannedouche, Thierry, Jacot, William, Javier, Rose-Marie, Jean, Guillaume, Jeandel, Claude, Joly, Dominique, Kamenicky, Peter, Knebelmann, Bertrand, Lafage-Proust, Marie-Hélène, Lebouc, Yves, Legrand, Erick, Levy-Weil, Florence, Linglart, Agnès, Machet, Laurent, Maheu, Emmanuel, Mallet, Eric, Marcelli, Christian, Mares, Pierre, Mariat, Christophe, Maruani, Gérard, Maugars, Yves, Montagnon, France, Moulin, Bruno, Orcel, Philippe, Partouche, Henri, Personne, Virginie, Pierrot-Deseilligny, Charles, Polak, Michel, Pouteil-Noble, Claire, Prié, Dominique, Raynaud-Simon, Agathe, Rolland, Yves, Sadoul, Jean-Louis, Salle, Bernard, Sault, Corinne, Schott, Anne-Marie, Sermet-Gaudelus, Isabelle, Soubrier, Martin, Tack, Ivan, Thervet, Eric, Tostivint, Isabelle, Touraine, Philippe, Trémollières, Florence, Urena-Torres, Pablo, Viard, Jean-Paul, Wemeau, Jean-Louis, Weryha, Georges, Winer, Norbert, Young, Jacques, Thomas, Thierry, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de rhumatologie[Lille], Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Cochin [AP-HP], Département de gastroentérologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine interne et gérontologie clinique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Groupe d'Études Remodelage Osseux et bioMatériaux (GEROM), Université d'Angers (UA), COREVIH Nord Pas-de-Calais, Centre Hospitalier de Tourcoing, Néphrologie Hémodialyse, Centre hospitalier de Boulogne sur mer, Département de Médecine Interne et Gérontologie clinique, Centre Hospitalier Universitaire d'Angers (CHU Angers), Service de gynécologie-obstétrique, médecine de la reproduction [Béclère], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], 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), Euromov (EuroMov), Université de Montpellier (UM), Eq 4, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Groupement Hospitalier Lyon-Est (GHE), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de médecine nucléaire, Fédération d'endocrinologie-Groupement hospitalier Lyon-Est-Fédération d'endocrinologie-Groupement hospitalier Lyon-Est, Service de rhumatologie, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Caractérisation du Tissu Osseux par Imagerie : techniques et applications, Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7), Service d'Endocrinologie Diabétologie Pédiatrique et Centre de Référence des Maladies Endocriniennes Rares de la Croissance, Hôpital Robert Debré, Service d'Endocrinologie (TOULOUSE - Endocrino), CHU Toulouse [Toulouse], Biologie du Cancer et de l'Infection (BCI ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Récepteurs stéroïdiens : physiopathologie endocrinienne et métabolique, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR93-Université Paris-Sud - Paris 11 (UP11), Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Pédiatrie, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Endocrinologie pédiatrique[CHU Angers], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Physiopathologie des maladies génétiques d'expression pédiatrique, Os et articulations, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fibrose hépatique et cancer du foie, Université Bordeaux Segalen - Bordeaux 2-IFR66-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Centre de recherche Croissance et signalisation (UMR_S 845), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Néphrologie, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service d'Endocrinologie - Diabète - Nutrition [Reims], Université de Reims Champagne-Ardenne (URCA)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Unité de Néphrologie Pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Mécanismes physiologiques et conséquences des calcifications cardiovasculaires: rôle des remodelages cardiovasculaires et osseux, Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de médecine gériatrique, Centre Hospitalier Régional d'Orléans (CHRO), Foie, métabolismes et cancer, 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 ), Service de rhumatologie [Rennes] = Rheumatology [Rennes], CHU Pontchaillou [Rennes], Service de Physiologie [Georges-Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), 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), Université Montpellier 1 (UM1), Centre de Lutte contre le Cancer, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER-UNICANCER-CHU Clermont-Ferrand, Service d'Endocrinologie et Maladies de la reproduction, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Tissu Osseux et Contraintes Mecaniques (LBTO), Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie et génétique du diabète de type 1, génétique multifactorielle en endocrinologie pédiatrique (U986), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de référence des maladies rares du calcium et du phosphore, CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Service de Rhumatologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de gynécologie obstétrique, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de Rhumatologie, Hôtel-Dieu, Service de Néphrologie et Transplantation, CHU Strasbourg, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), 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), Service de néphrologie et transplantation, Gérontopôle, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], Service d'Endocrinologie (NICE - Endocrino), Centre Hospitalier Universitaire de Nice (CHU Nice), Département d'information médicale, Hospices Civils de Lyon (HCL)-Université de Lyon, CHU Clermont-Ferrand, CHU Gabriel Montpied [Clermont-Ferrand], Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Service des explorations physiologiques, CHU Toulouse [Toulouse]-Hôpital de Rangueil, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], CHU Pitié-Salpêtrière [AP-HP], Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de ménopause, Hôpital Paule de Viguier, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Centre de Diagnost ic et de Thérapeutique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu, Service d'Endocrinologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Gynécologie Obstétrique (NANTES - Gynéco Obstétrique), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Gustave Roussy (IGR), Service d'endocrinologie, PRES Université Nantes Angers Le Mans (UNAM), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Centre Hospitalier Boulogne-sur-mer, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service Endocrinologie, maladies métaboliques et nutrition [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Nutrition [Cergy] (N - cabinet libéral ), Centre Hospitalier Le Mans (CH Le Mans), 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 ), Centre de Rein Artificiel [Tassin la demi-lune] (CRA), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Trousseau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Victor Dupouy, Normandie Université (NU), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Cabinet de Rhumatologie [Saint-Etienne] (CdR), Hôpital Lariboisière-Fernand-Widal [APHP], Département de Médecine Générale, Université Paris Cité (UPCité), CIC Hôpital Bichat, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine, Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Académie nationale de médecine, Eurofins Biomnis, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service Obstétrique [CHU Toulouse], Pôle Femme-Mère-Couple [CHU Toulouse], Clinique du Landy [Saint-Ouen] (CL), Hôpital Hôtel-Dieu [Paris], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupement Hospitalier Lyon-Est (GHE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Picardie Jules Verne (UPJV), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [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), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Roger Salengro-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), CHU Cochin [AP-HP], Université d'Angers ( UA ) -CHU Angers, Remodelage osseux et biomatériaux, Université d'Angers ( UA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Angers, Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Antoine Béclère, 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 ), Department of Geriatrics - Efficiency and Deficiency Laboratory, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Groupement Hospitalier Lyon-Est ( GHE ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ) -Centre de médecine nucléaire, CHU Nice-Hôpital l'Archet, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Hôpital de la Conception [CHU - APHM] ( LA CONCEPTION ), Promoting Research Oriented Towards Early Cns Therapies ( PROTECT ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Diderot - Paris 7 ( UPD7 ), Service d'Endocrinologie ( TOULOUSE - Endocrino ), Biologie du Cancer et de l'Infection ( BCI - UMR S1036 ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Grenoble Alpes ( UGA ), Université Paris-Sud - Paris 11 ( UP11 ) -IFR93-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases ( LYOS ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Diabétologie et Endocrinologie de la Reproduction, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Bordeaux Segalen - Bordeaux 2-IFR66-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de recherche Croissance et signalisation ( UMR_S 845 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université de Reims Champagne-Ardenne ( URCA ) -Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims ( CHU Reims ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré, Université de Picardie Jules Verne ( UPJV ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Cardiovasculaire, métabolisme, diabétologie et nutrition ( CarMeN ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hospices Civils de Lyon ( HCL ) -Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Institut National de la Recherche Agronomique ( INRA ), Centre Hospitalier Régional d'Orléans ( CHR ), 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 ), Hôpital Sud, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ), Institut de recherche en cancérologie de Montpellier ( IRCM - U896 Inserm - UM1 ), 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 ), Centre de gérontologie clinique, Université Montpellier 1 ( UM1 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), CHU Clermont-Ferrand-Centre Jean Perrin, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Tissu Osseux et Contraintes Mecaniques ( LBTO ), Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Immunologie et génétique du diabète de type 1, génétique multifactorielle en endocrinologie pédiatrique ( U986 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), AP-HP, Service de Rhumatologie, CHU Saint-Antoine [APHP], CHU Caen, Hôpital Universitaire Carémeau [Nîmes], Service de néphrologie et tranplantation, CHU Saint-Etienne-Hôpital nord, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université de Lyon-Université de Lyon-Hospices Civils de Lyon ( HCL ) -Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Gérontopôle de Toulouse, Service d'Endocrinologie ( NICE - Endocrino ), CHU Nice, Hospices Civils de Lyon ( HCL ) -Université de Lyon, CHU Gabriel Montpied ( CHU ), Institut des Maladies Métaboliques et Cardiovasculaires ( I2MC ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Department of Endocrinology and Reproductive Medicine, CHU Pitié-Salpêtrière [APHP]-Centre de Référence des Maladies Endocriniennes rares de la croissance et des maladies gynécologiques rares, Université Pierre et Marie Curie - Paris 6 ( UPMC ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôtel-Dieu, Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Service de Gynécologie Obstétrique ( NANTES - Gynéco Obstétrique ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Institut Gustave Roussy ( IGR ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Hôpital Roger Salengro-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Antoine Béclère, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Groupement Hospitalier Lyon-Est (GHE), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Centre Hospitalier Régional d'Orléans (CHR), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], CHU Gabriel Montpied (CHU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôtel-Dieu, and Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre
Subjects: MESH: Bone Diseases / blood, Calcium Metabolism Disorders / blood, Humans, Malabsorption Syndromes / blood, Phosphorus Metabolism Disorders / blood, Renal Insufficiency, Chronic / blood, Vitamin D / blood, [ SDV ] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], MathematicsofComputing_GENERAL, Phosphorus Metabolism Disorders, [SDV.CAN]Life Sciences [q-bio]/Cancer, GeneralLiterature_MISCELLANEOUS, InformationSystems_GENERAL, Malabsorption Syndromes, Calcium Metabolism Disorders, Renal Insufficiency, Chronic, Vitamin D, Bone Diseases, ComputingMilieux_MISCELLANEOUS
Abstract: National audience; No abstract available
Published: 2014

27. X-linked primary immunodeficiency associated with hemizygous mutations in the moesin (MSN) gene

Author: Jacek Majewski, Marielle E. van Gijn, Alain Fischer, Geneviève de Saint Basile, Capucine Picard, Nada Jabado, Els Verhoeyen, Sonia Luce, Tayebeh Soheili, Nathalie Lambert, Amandine Durand, Armelle Bohineust, Claire Hivroz, Virginie Gandemer, Farid Ouchani, Chantal Brouzes, Catherine Heijmans, Anne Durandy, Isabelle Pic, Myriam Chouteau, Marina Cavazzana, Virgil A. S. H. Dalm, Nizar Mahlaoui, Aude Magerus-Chatinet, François-Loïc Cosset, Isabelle André-Schmutz, Delphine Monnier, Sven Kracker, Chantal Lagresle-Peyrou, Jean-Louis Stephan, Frédéric Rieux-Laucat, Hanem Sadek, Human Lymphohematopoiesis Laboratory (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Biothérapie [CHU Necker], CHU Necker - Enfants Malades [AP-HP]-Université Paris Descartes - Paris 5 (UPD5)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), McGill University and Genome Quebec Innovation Centre, CHU Necker - Enfants Malades [AP-HP], Center for the Study of Primary Immunodeficiencies [Paris], Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Immunité et cancer (U932), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie-Université Paris Descartes - Paris 5 (UPD5), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy (Equipe EVIR), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunogenetics of pediatric autoimmune diseases (Equipe Inserm U1163), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Service d'Hématologie, Immunologie et de Thérapie Cellulaire (HITC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Hôpital Universitaire des Enfants - Reine Fabiola, Dpt of Genetics [Utrecht], University Medical Center [Utrecht], Department of Internal Medicine, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'immuno-hématologie pédiatrique [CHU Necker], CHU Saint-Etienne, the Genome Quebec Innovation Centre, McGill University, Collège de France (CdF), French National Research Agency, French National Institute of Health and Medical Research (INSERM), La Ligue contre le Cancer and La Fondation ARC pour la Recherche sur le Cancer, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy (EVIR), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-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)-École normale supérieure de Lyon (ENS de Lyon)-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), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Hôpital Universitaire des Enfants Reine Fabiola [Bruxelles, Belgique] (HUDERF), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), McGill University = Université McGill [Montréal, Canada], Collège de France - Chaire Médecine expérimentale (A. Fischer), Collège de France (CdF (institution)), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), CIC-BT 502 INSERM, Departement de Biotherapie, Laboratoire d'hématologie ( ERL 8254 ), 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 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Référence Déficits Immunitaires Héréditaires ( CEREDIH ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Immunité et cancer ( U932 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre méditérannéen de médecine moléculaire ( C3M ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ), Centre International de Recherche en Infectiologie ( CIRI ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'Hématologie, Immunologie et de Thérapie Cellulaire ( HITC ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Collège de France ( CdF ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Chaire Médecine expérimentale (A. Fischer), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Institut Curie-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunology, and Internal Medicine
Subjects: Adult, Male, 0301 basic medicine, Adolescent, Moesin, Immunology, Nonsense mutation, macromolecular substances, CD8-Positive T-Lymphocytes, Biology, Infections, primary immunodeficiency, migration, medicine.disease_cause, ezrin-radixin-moesin protein, Hypogammaglobulinemia, 03 medical and health sciences, Cell Movement, Radixin, Cell Adhesion, Journal Article, medicine, Humans, Immunology and Allergy, Missense mutation, Lymphocyte Count, Child, moesin, Genetic Association Studies, Immunodeficiency, Aged, Chromosomes, Human, X, [SDV.GEN]Life Sciences [q-bio]/Genetics, Mutation, Microfilament Proteins, Immunologic Deficiency Syndromes, Leukopenia, medicine.disease, Pedigree, 3. Good health, adhesion, 030104 developmental biology, Child, Preschool, Cancer research, Primary immunodeficiency, [ SDV.GEN ] Life Sciences [q-bio]/Genetics
Abstract: International audience; BACKGROUND: We investigated 7 male patients (from 5 different families) presenting with profound lymphopenia, hypogammaglobulinemia, fluctuating monocytopenia and neutropenia, a poor immune response to vaccine antigens, and increased susceptibility to bacterial and varicella zoster virus infections. OBJECTIVE: We sought to characterize the genetic defect involved in a new form of X-linked immunodeficiency. METHODS: We performed genetic analyses and an exhaustive phenotypic and functional characterization of the lymphocyte compartment. RESULTS: We observed hemizygous mutations in the moesin (MSN) gene (located on the X chromosome and coding for MSN) in all 7 patients. Six of the latter had the same missense mutation, which led to an amino acid substitution (R171W) in the MSN four-point-one, ezrin, radixin, moesin domain. The seventh patient had a nonsense mutation leading to a premature stop codon mutation (R533X). The naive T-cell counts were particularly low for age, and most CD8(+) T cells expressed the senescence marker CD57. This phenotype was associated with impaired T-cell proliferation, which was rescued by expression of wild-type MSN. MSN-deficient T cells also displayed poor chemokine receptor expression, increased adhesion molecule expression, and altered migration and adhesion capacities. CONCLUSION: Our observations establish a causal link between an ezrin-radixin-moesin protein mutation and a primary immunodeficiency that could be referred to as X-linked moesin-associated immunodeficiency.
Published: 2016

28. Synergy of the antibiotic colistin with echinocandin antifungals in Candida species

Author: CÃ©cile Clavaud, Christophe d'Enfert, Zacarias Garcia, Olivier Helynck, Natacha Sertour, Alexandru Lupan, Ute Zeidler, HÃ©lÃ¨ne Munier-Lehmann, Cosmin Saveanu, Marie-Elisabeth Bougnoux, Antonia Doyen, Biologie et Pathogénicité fongiques, Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris], Service de Microbiologie, Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Chimie et Biocatalyse, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Génétique des Interactions macromoléculaires, Dynamiques des Réponses Immunes, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Aspergillus, Institut Pasteur [Paris], This work was supported by a grant from the 'Conseil Régional d'Ile-de-France' (Chemical Library Project, grants I 06-222/R and I 09-1739/R) to H. M.-L., a grant (Programme Fungi) from Institut Carnot--Pasteur Maladies Infectieuses to H. M.-L. and C. d'E. and a grant from 'Agence Nationale de la Recherche' (ANR-08-JCJC-0019-01, GENO-GIM project) to C. S. U. Z. and C. C. were the recipients of postdoctoral grants in the framework of the Programme Fungi. A. L. was the recipient of a post-doctoral fellowship from the 'Conseil Régional d'Ile-de-France'., ANR-08-JCJC-0019,GENO-GIM,Obtention d'une carte d'interactions génétiques à l'échelle génomique chez la levure(2008), Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biologie et Pathogénicité fongiques (BPF), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Génétique des Interactions macromoléculaires / Genetics of Macromolecular Interactions, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), Munier-Lehmann, Hélène, Jeunes chercheuses et jeunes chercheurs - Obtention d'une carte d'interactions génétiques à l'échelle génomique chez la levure - - GENO-GIM2008 - ANR-08-JCJC-0019 - JCJC - VALID, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Institut National de la Recherche Agronomique (INRA) - Institut Pasteur [Paris], Université Paris Descartes - Paris 5 (UPD5) - CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris] - Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] - Institut National de la Santé et de la Recherche Médicale (INSERM), and ANR-08-JCJC-0019, GENO-GIM, Obtention d'une carte d'interactions génétiques à l'échelle génomique chez la levure(2008)
Subjects: Antifungal Agents, Cell Membrane Permeability, [SDV]Life Sciences [q-bio], Antibiotics, Indicator Dilution Techniques, Chitin, Pharmacology, combination therapy, Echinocandins, Mice, chemistry.chemical_compound, Cell Wall, Candida albicans, polycyclic compounds, Pharmacology (medical), caspofungin, Coloring Agents, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Candida, Mice, Inbred BALB C, 0303 health sciences, Candidiasis, Drug Synergism, Corpus albicans, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Propidium, medicine.drug, Microbiology (medical), Genotype, Echinocandin, medicine.drug_class, Microbial Sensitivity Tests, Saccharomyces cerevisiae, Biology, Microbiology, Lipopeptides, 03 medical and health sciences, medicine, Animals, Gene Library, 030304 developmental biology, sphingolipids, Colistin, 030306 microbiology, polymyxin, biology.organism_classification, bacterial infections and mycoses, [SDV.MP.MYC] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Aminocandin, chemistry, Mutation, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Genetic Fitness, Caspofungin
Abstract: International audience; OBJECTIVES: Candida albicans is the most prevalent fungal pathogen of humans, causing a wide range of infections from harmless superficial to severe systemic infections. Improvement of the antifungal arsenal is needed since existing antifungals can be associated with limited efficacy, toxicity and antifungal resistance. Here we aimed to identify compounds that act synergistically with echinocandin antifungals and that could contribute to a faster reduction of the fungal burden. METHODS: A total of 38 758 compounds were tested for their ability to act synergistically with aminocandin, a β-1,3-glucan synthase inhibitor of the echinocandin family of antifungals. The synergy between echinocandins and an identified hit was studied with chemogenomic screens and testing of individual Saccharomyces cerevisiae and C. albicans mutant strains. RESULTS: We found that colistin, an antibiotic that targets membranes in Gram-negative bacteria, is synergistic with drugs of the echinocandin family against all Candida species tested. The combination of colistin and aminocandin led to faster and increased permeabilization of C. albicans cells than either colistin or aminocandin alone. Echinocandin susceptibility was a prerequisite to be able to observe the synergy. A large-scale screen for genes involved in natural resistance of yeast cells to low doses of the drugs, alone or in combination, identified efficient sphingolipid and chitin biosynthesis as necessary to protect S. cerevisiae and C. albicans cells against the antifungal combination. CONCLUSIONS: These results suggest that echinocandin-mediated weakening of the cell wall facilitates colistin targeting of fungal membranes, which in turn reinforces the antifungal activity of echinocandins.
Published: 2013

29. Limits of patient isolation measures to control extended-spectrum beta-lactamase–producing Enterobacteriaceae: model-based analysis of clinical data in a pediatric ward

Author: Véronique Abadie, Didier Guillemot, Jean-Ralph Zahar, Matthieu Domenech de Cellès, Cellule Pasteur UPMC, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris] (IP), Pharmacoépidémiologie et maladies infectieuses, Institut Pasteur [Paris] (IP), Unité d'hygiène hospitalière, Service de microbiologie, Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité Fonctionnelle de Santé Publique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Raymond Poincaré [AP-HP], BMC, Ed., Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris], Institut Pasteur [Paris], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut Pasteur [Paris], Pharmacoépidémiologie et maladies infectieuses ( PHEMI ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ), Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP Hôpital Raymond Poincaré [Garches]
Subjects: Male, medicine.medical_specialty, Adolescent, Isolation (health care), medicine.medical_treatment, Control (management), Pediatrics, beta-Lactamases, law.invention, Patient Isolation, 03 medical and health sciences, 0302 clinical medicine, Medical microbiology, Enterobacteriaceae, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, law, Disease Transmission, Infectious, Humans, Medicine, 030212 general & internal medicine, Child, Intensive care medicine, Cross Infection, 0303 health sciences, 030306 microbiology, business.industry, Incidence (epidemiology), Enterobacteriaceae Infections, Healthcare epidemiology, Infant, Models, Theoretical, Isolation ward, 3. Good health, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Infectious Diseases, Transmission (mechanics), Child, Preschool, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Beta-lactamase, Female, Bacterial pathogens, Mathematical modeling, Observational study, business, Statistical inference, Research Article, ESBL-E
Abstract: International audience; BackgroundExtended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) are a growing concern in hospitals and the community. How to control the nosocomial ESBL-E transmission is a matter of debate. Contact isolation of patients has been recommended but evidence supporting it in non-outbreak settings has been inconclusive.MethodsWe used stochastic transmission models to analyze retrospective observational data from a two-phase intervention in a pediatric ward, successively implementing single-room isolation and patient cohorting in an isolation ward, combined with active ESBL-E screening.ResultsFor both periods, model estimates suggested reduced transmission from isolated/cohorted patients. However, most of the incidence originated from sporadic sources (i.e. independent of cross-transmission), unaffected by the isolation measures. When sporadic sources are high, our model predicted that even substantial efforts to prevent transmission from carriers would have limited impact on ESBL-E rates.ConclusionsOur results provide evidence that, considering the importance of sporadic acquisition, e.g. endogenous selection of resistant strains following antibiotic treatment, contact-isolation measures alone might not suffice to control ESBL-E. They also support the view that estimating cross-transmission extent is key to predicting the relative success of contact-isolation measures. Mathematical models could prove useful for those estimations and guide decisions concerning the most effective control strategy.
Published: 2013

30. VEGFR1 single nucleotide polymorphisms associated with outcome in patients with metastatic renal cell carcinoma treated with sunitinib - a multicentric retrospective analysis

Author: Gwenaelle Gravis, Diether Lambrechts, Bart Claes, Gael Deplanque, Virginie Verkarre, Gabrielle Couchy, Florence Joly, A. Mejean, Patrick Schöffski, Pascal Wolter, Alexandra Karadimou, Vincent Molinié, Joost Berkers, Stéphane Oudard, Nathalie Rioux Leclercq, Benoit Beuselinck, Corine Teghom, Evelyne Lerut, Aurélien Descazeaud, Thierry Lebret, Hendrik Van Poppel, Jessica Zucman-Rossi, Reza Elaidi, Jean-Jacques Patard, Robert Paridaens, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Labex Immuno-oncology, Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-PRES Sorbonne Paris Cité-Faculté de Médecine, Department of Urology, University Hospital Leuven, Multidisciplinary Breast Centre, UZLeuven, Department of Medical Oncology, Service d'urologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Anatomie et de Cytologie Pathologiques, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], PremUp Foundation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Descartes - Paris 5 (UPD5)-CHI Créteil-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7), Cancers et préventions, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'Oncologie Médicale, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Hôpital Foch [Suresnes], Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'anatomie pathologique, Hôpital Saint Joseph, Service de Génétique Moléculaire, CHU Bordeaux [Bordeaux], Service d'oncologie médicale [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Oncologie médicale [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Genomique Fonctionnelle des Tumeurs Solides, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -IFR105-Université Paris Diderot - Paris 7 ( UPD7 ), Centre de Recherche des Cordeliers ( CRC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -PRES Sorbonne Paris Cité-Faculté de Médecine, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Institut de Recherche pour le Développement ( IRD ) -Université Paris-Sud - Paris 11 ( UP11 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ) -CHI Créteil-Université Paris Descartes - Paris 5 ( UPD5 ) -Sorbonne Universités-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Centre Régional de Lutte contre le Cancer François Baclesse ( CRLC François Baclesse ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP )
Subjects: Oncology, Male, Multivariate analysis, Indoles, urologic and male genital diseases, Renal cell carcinoma, Sunitinib, Neoplasm Metastasis, Tumor Markers, Univariate analysis, Hematology, General Medicine, Single Nucleotide, Middle Aged, Prognosis, Kidney Neoplasms, 3. Good health, Survival Rate, Treatment Outcome, Female, medicine.drug, medicine.medical_specialty, Bevacizumab, Antineoplastic Agents, Polymorphism, Single Nucleotide, Internal medicine, Pancreatic cancer, medicine, Biomarkers, Tumor, Humans, Radiology, Nuclear Medicine and imaging, Pyrroles, Polymorphism, Survival rate, Carcinoma, Renal Cell, Retrospective Studies, [SDV.GEN]Life Sciences [q-bio]/Genetics, Vascular Endothelial Growth Factor Receptor-1, business.industry, Proportional hazards model, Carcinoma, Renal Cell, medicine.disease, Biological, Surgery, Neoplasm Grading, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, business, Follow-Up Studies
Abstract: International audience; BACKGROUND: There are no validated markers that predict outcome in metastatic renal cell cancer (mRCC) patients treated with sunitinib. Recently, single nucleotide polymorphism (SNP) rs9582036 in VEGFR1 has been proposed as a predictor of progression-free survival (PFS) and overall survival (OS) to bevacizumab in patients with pancreatic cancer and rs7993418 in VEGFR1 as predictor for PFS in mRCC-patients treated with bevacizumab. Here, we aim to study the impact of these SNPs in mRCC patients treated with sunitinib. METHODS: We included patients with mRCC treated in 15 institutions in France and Belgium. Patients received sunitinib as first-line targeted therapy. We assessed response, time-to-tumor progression (TTP), OS, and clinical and biochemical parameters associated with outcome. We genotyped rs9582036 and rs7993418 as well as three other surrounding SNPs in VEGFR1: rs9554320, rs9554316 and rs9513070. Association between SNPs and treatment outcome were studied by univariate analysis and by multivariate Cox regression using relevant clinical factors associated with TTP and OS as covariates. FINDINGS: Ninety-one patients were included. We found that mRCC patients with the CC-variant in rs9582036 in VEGFR1 have a poorer response rate (RR) (0% vs. 46%, p = 0.028), a poorer PFS (10 vs. 18 months, p = 0.033 on univariate and 0.06 on multivariate analysis) and a poorer OS (14 vs. 31 months, p = 0.019 on univariate and 0.008 on multivariate analysis) compared to patients with the AC- and AA-genotypes. mRCC patients with the AA-variant in rs9554320 in VEGFR1 have a poorer PFS (12 vs. 21 months, p = 0.0066 on univariate and 0.005 on multivariate analysis) and a poorer OS (22 vs. 34 months, p = 0.019 on univariate and 0.067 on multivariate analysis) compared to patients with the AC- and CC-genotypes. Interpretation. mRCC patients with the CC-genotype in VEGFR1 SNP rs9582036 have a poorer response rate, PFS and OS when treated with sunitinib. These findings are in agreement with the association of rs9582036 and outcome observed in bevacizumab treated pancreatic cancer patients. Prospective validation of this SNP is warranted.
Published: 2013

31. Natural history of Barth syndrome: a national cohort study of 22 patients

Author: Damien Bonnet, Marlène Rio, Pascale de Lonlay, Jean Donadieu, Helene Ansquer, Géraldine Viot, François Rivier, Blandine Beaupain, Philippe Charron, Charlotte Rigaud, Renaud Touraine, Sylvie Di Filippo, Chris Ottolenghi, Alice Goldenberg, Anne-Sophie Lebre, Betina Borm, Allel Chabli, Michèle Mathieu-Dramard, Hulya Ozsahin, Marie-Catherine Vaillant, Service d'Hémato-oncologie Pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], 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 Génétique Clinique Chromosomique et Moléculaire, CHU Saint-Etienne-Hôpital Nord - Saint-Etienne, Laboratoire de Biochimie, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Service de Néonatalogie, Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Service d'Onco-Hématologie Pédiatrique, Hôpitaux Universitaires de Genève ( HUG ) -Hôpital des Enfants, Service de Cardiologie Pédiatrique, Hospices Civils de Lyon ( HCL ) -Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon ( HCL ), Centre de référence des maladies métaboliques, Service de Pédiatrie, CH Béziers, Service de Neuropédiatrie, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Gui de Chauliac, Service de Médecine Pédiatrique, CHU Toulouse [Toulouse]-Centre Hospitalo-Universitaire, Service de Génétique [Amiens], CHU Amiens-Picardie, Service de génétique [Rouen], CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Service de Génétique [Cochin], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Centre de référence pour les maladies cardiaques héréditaires, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Assistance Publique-Hôpitaux de Paris, Centre de Référence M3C Malformations Cardiaques Congénitales Complexes, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], BMC, Ed., CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpitaux Universitaires de Genève (HUG), Hospices Civils de Lyon (HCL)-Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité-CHU Necker - Enfants Malades [AP-HP], Hôpitaux Universitaires de Genève (HUG)-Hôpital des Enfants, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, Pediatrics, TAZ gene, Cardiomyopathy, [SDV.GEN] Life Sciences [q-bio]/Genetics, 030204 cardiovascular system & hematology, Cohort Studies, 0302 clinical medicine, Genetics(clinical), Pharmacology (medical), Child, Genetics (clinical), Medicine(all), 0303 health sciences, Neutropenia/complications, ddc:618, Incidence (epidemiology), Cohort, Barth syndrome, General Medicine, 3. Good health, Pedigree, Natural history, Survival Rate, Child, Preschool, Cardiomyopathies/complications, Female, France, Cardiomyopathies, Cohort study, medicine.medical_specialty, Neutropenia, Adolescent, Transcription Factors/genetics, 03 medical and health sciences, medicine, Humans, Barth Syndrome/complications/genetics/mortality/physiopathology, Survival rate, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, Research, medicine.disease, Barth Syndrome, Mutation, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, business, Acyltransferases, Transcription Factors
Abstract: International audience; BACKGROUND: This study describes the natural history of Barth syndrome (BTHS). METHODS: The medical records of all patients with BTHS living in France were identified in multiple sources and reviewed. RESULTS: We identified 16 BTHS pedigrees that included 22 patients. TAZ mutations were observed in 15 pedigrees. The estimated incidence of BTHS was 1.5 cases per million births (95%CI: 0.2--2.3). The median age at presentation was 3.1 weeks (range, 0--1.4 years), and the median age at last follow-up was 4.75 years (range, 3--15 years). Eleven patients died at a median age of 5.1 months; 9 deaths were related to cardiomyopathy and 2 to sepsis. The 5-year survival rate was 51%, and no deaths were observed in patients >=3 years. Fourteen patients presented with cardiomyopathy, and cardiomyopathy was documented in 20 during follow-up. Left ventricular systolic function was very poor during the first year of life and tended to normalize over time. Nineteen patients had neutropenia. Metabolic investigations revealed inconstant moderate 3-methylglutaconic aciduria and plasma arginine levels that were reduced or in the low-normal range. Survival correlated with two prognostic factors: severe neutropenia at diagnosis (
Published: 2013

32. Toll-like receptor 3 regulates cord blood-derived endothelial cell function in vitro and in vivo

Author: Nicole Balitrand, Jérôme Larghero, Jean-Pierre Marolleau, Séverine Lecourt, Yves Lepelletier, Delphine Freida, Hélène Riesterer, Catherine Delmau, Marie-Caroline Lebousse-Kerdiles, Georges Uzan, Aurore Grelier, Wendy Cuccini, Valérie Vanneaux, Jean-Jacques Lataillade, Régis Peffault de Latour, Audrey Cras, Unité de Thérapie Cellulaire, Hopital St Louis, Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Hôpital d'instruction des Armées Percy, Service de Santé des Armées, CHU Saint Louis [APHP], Service clinique des Maladies du Sang, Hopital d'Amiens, Microenvironnement et Physiopathologie de la Differenciation, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pharmacie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Amiens-Picardie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: Cancer Research, Physiology, Angiogenesis, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Oligonucleotides, Mice, SCID, Systemic inflammation, Ligands, Mice, 0302 clinical medicine, Cell Movement, Ischemia, Mice, Inbred NOD, ComputingMilieux_MISCELLANEOUS, Cells, Cultured, 0303 health sciences, Toll-like receptor, Cell Cycle, Toll-Like Receptors, Cell cycle, Fetal Blood, 3. Good health, Cell biology, Hindlimb, Endothelial stem cell, Lipoproteins, LDL, 030220 oncology & carcinogenesis, Cord blood, Cytokines, Female, medicine.symptom, Cell Division, Neovascularization, Physiologic, Biology, Mesenchymal Stem Cell Transplantation, Real-Time Polymerase Chain Reaction, 03 medical and health sciences, medicine, Animals, Humans, Progenitor cell, 030304 developmental biology, Wound Healing, Cell growth, Tumor Necrosis Factor-alpha, Infant, Newborn, Endothelial Cells, Mesenchymal Stem Cells, Toll-Like Receptor 3, MicroRNAs, Poly I-C, Gene Expression Regulation, Endothelium, Vascular
Abstract: Circulating endothelial progenitor cells (cEPC) are capable of homing to neovascularisation sites, in which they proliferate and differentiate into endothelial cells. Transplantation of cEPC-derived cells, in particular those isolated from umbilical cord blood (UCB), has emerged as a promising approach in the treatment of cardio-vascular diseases. After in vivo transplantation, these cells may be exposed to local or systemic inflammation or pathogens, of which they are a common target. Because Toll-like receptors (TLR) are critical in detecting pathogens and in initiating inflammatory responses, we hypothesized that TLR may govern UCB cEPC-derived cells function. While these cells expressed almost all TLR, we found that only TLR3 dramatically impaired cell properties. TLR3 activation inhibited cell proliferation, modified cell cycle entry, impaired the in vitro angiogenic properties and induced pro-inflammatory cytokines production. The anti-angiogenic effect of TLR3 activation was confirmed in vivo in a hind-limb ischemic mice model. Moreover, TLR3 activation consistently leads to an upregulation of miR-29b, -146a and -155 and to a deregulation of cytoskeleton and cell cycle regulator. Hence, TLR3 activation is likely to be a key regulator of cEPC-derived cells properties.
Published: 2012

33. Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters

Author: Marion Travert, Jean-Philippe Jais, Olivier A. Bernard, Tak W. Mak, Rob A. Cairns, Laurence Lamant, Thérèse Rousset, Marie Parrens, Lucile Couronné, François Lemonnier, Bettina Fabiani, Laurence de Leval, Philippe Gaulard, Christian Bastard, Olivier Tournillac, 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), Génétique des tumeurs (U985), Institut Gustave Roussy (IGR)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service informatique médicale et biostatistique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'anatomie et cytologie pathologiques [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Thérapie ciblée combinatoire en Onco-Hématologie (EA3846), Université d'Auvergne - Clermont-Ferrand I (UdA), Centre d'Investigation Clinique [CHU Clermont-Ferrand] (CIC 1405), Institut National de la Santé et de la Recherche Médicale (INSERM)-Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Laboratoire d'anatomie cytologie pathologiques, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier], Service d'anatomie et cytologie pathologiques [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Campbell Family Institute for Breast Cancer Research, University Health Network, Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Pathologie Clinique, Université de Lausanne (UNIL)-Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV)-Institut Universitaire de Pathologie, Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), This study was supported in part by grants from INCa (Institut National du Cancer), ARC (Association pour la Recherche contre le Cancer), Ligue Nationale Contre le Cancer (équipe labelisée), PHRC (Programme Hospitalier de Recherche Clinique), FRM (Fondation pour la Recherche Médicale, équipe labellisée) and the Cancer Plan research Programme (Belgium, LdL). FL was a M2 student, granted from ARC and MT, a post-doctorant granted by FRM., 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 ), Génétique des tumeurs ( U985 ), Institut Gustave Roussy ( IGR ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Université Toulouse III - Paul Sabatier ( UPS ), Thérapie ciblée combinatoire en Onco-Hématologie ( EA3846 ), Université d'Auvergne - Clermont-Ferrand I ( UdA ), CIC - Clermont Ferrand, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Gui de Chauliac, Service d'anatomie et cytologie pathologiques, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Groupe d'étude des proliférations lymphoïdes ( GPL ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Lausanne ( UNIL ) -Centre Hospitalier Universitaire Vaudois [Lausanne] ( CHUV ) -Institut Universitaire de Pathologie, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Service Anatomie et cytologie pathologiques [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Lausanne = University of Lausanne (UNIL)-Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV)-Institut Universitaire de Pathologie, Guellaen, Georges, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]
Subjects: Male, Myeloid, MESH : Recurrence, MESH : Aged, Chromosomal translocation, MESH : T-Lymphocytes, Helper-Inducer, Biochemistry, 0302 clinical medicine, International Prognostic Index, Recurrence, MESH : Female, MESH: Aged, 0303 health sciences, Not Otherwise Specified, Hematology, T-Lymphocytes, Helper-Inducer, MESH: Lymphoma, T-Cell, Peripheral, 3. Good health, DNA-Binding Proteins, medicine.anatomical_structure, 030220 oncology & carcinogenesis, MESH : Proto-Oncogene Proteins, Female, MESH : DNA-Binding Proteins, MESH : Mutation, Angioimmunoblastic T-cell lymphoma, MESH: Mutation, T cell, MESH : Male, Immunology, Dioxygenases, 03 medical and health sciences, Proto-Oncogene Proteins, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Humans, Clinical significance, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: T-Lymphocytes, Helper-Inducer, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Aged, MESH: Humans, business.industry, MESH : Lymphoma, T-Cell, Peripheral, MESH : Humans, Lymphoma, T-Cell, Peripheral, Cell Biology, medicine.disease, MESH: Male, Lymphoma, MESH: Recurrence, MESH: Proto-Oncogene Proteins, Mutation, business, MESH: Female, MESH: DNA-Binding Proteins
Abstract: Inactivating mutations of the Ten-Eleven Translocation 2 (TET2) gene were first identified in myeloid malignancies and more recently in peripheral T-cell lymphomas (PTCLs). In the present study, we investigated the presence of TET2 coding sequence mutations and their clinical relevance in a large cohort of 190 PTCL patients. TET2 mutations were identified in 40 of 86 (47%) cases of angioimmunoblastic T-cell lymphoma (AITL) and in 22 of 58 (38%) cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), but were absent in all other PTCL entities, with the exception of 2 of 10 cases of enteropathy-associated T-cell lymphoma. Among PTCL-NOS, a heterogeneous group of lymphoma-comprising cases likely to derive from Th follicular (TFH) cells similarly to AITL, TET2 mutations were more frequent when PTCL-NOS expressed TFH markers and/or had features reminiscent of AITL (58% vs 24%, P = .01). In the AITL and PTCL-NOS subgroups, TET2 mutations were associated with advanced-stage disease, thrombocytopenia, high International Prognostic Index scores, and a shorter progression-free survival.
Published: 2012

34. In vitro combination of anidulafungin and voriconazole against intrinsically azole-susceptible and -resistant Aspergillus spp

Author: Olivier Lortholary, Sebastien Ducroz, Alexandre Alanio, Marie-Elisabeth Bougnoux, Eric Dannaoui, Virginie Planche, Unité de Parasitologie-Mycologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Mycologie moléculaire, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Service de Microbiologie, Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], This study was funded by a grant from Pfizer Inc., Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), and Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)
Subjects: Azoles, Antifungal Agents, Serial dilution, [SDV]Life Sciences [q-bio], Microbial Sensitivity Tests, Anidulafungin, Microbiology, 03 medical and health sciences, Echinocandins, 0302 clinical medicine, medicine, voriconazole, Pharmacology (medical), 030212 general & internal medicine, Agar diffusion test, [ SDV.MP.MYC ] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Pharmacology, Voriconazole, chemistry.chemical_classification, 0303 health sciences, Aspergillus, [ SDV ] Life Sciences [q-bio], biology, 030306 microbiology, Fungi imperfecti, Triazoles, biology.organism_classification, 3. Good health, Drug Combinations, Infectious Diseases, Pyrimidines, chemistry, Susceptibility, Checkerboard, Azole, medicine.drug
Abstract: In vitro interaction of anidulafungin with voriconazole was tested by a microdilution broth checkerboard technique and an agar diffusion method against 30 Aspergillus clinical isolates belonging to five different species. By using a complete inhibition endpoint, indifferent interactions were observed for 97% of the isolates by the checkerboard technique (FIC index from 0.5 to 2) and for 100% of the isolates by the agar diffusion method (variation of −2 to +1 log 2 dilutions).
Published: 2012

35. Excess primary intestinal lymphoproliferative disorders in patients with inflammatory bowel disease

Author: STEPHANE NANCEY, Francois MION, Nathalie Ganne-Carrié, Dany GARGOT, ANTOINE CORTOT, Laurent Siproudhis, Bernard FLOURIE, ROBERT BENAMOUZIG, Matthieu Allez, Tabassome SIMON, Frederic Gottrand, Guillaume Savoye, Gerard Thiefin, Fabrice Carrat, Harry Sokol, Jean-Pierre Hugot, Pierre DESREUMAUX, Laurent Peyrin-biroulet, Laurent Michaud, Christos CHRISTIDIS, Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute (RECAMO), Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Hepato-Gastroenterologie, CHU Amiens-Picardie, Hepato-Gastroenterology, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hepato Gastroenterology, Hospital and University of Rouen, Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Anatomie et Cytologie Pathologique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Masaryk Memorial Cancer Institute (MMCI), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Université Pierre et Marie Curie - Paris 6 ( UPMC ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Masaryk Memorial Cancer Institute, Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Epidémiologie des maladies infectieuses et modélisation ( ESIM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP]
Subjects: Adult, Male, medicine.medical_specialty, Population, Gastroenterology, Inflammatory bowel disease, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Interquartile range, [ CHIM.ORGA ] Chemical Sciences/Organic chemistry, Internal medicine, Azathioprine, medicine, Humans, Immunology and Allergy, Prospective Studies, Child, education, Aged, Aged, 80 and over, education.field_of_study, Crohn's disease, Thiopurine methyltransferase, biology, Mercaptopurine, business.industry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Incidence, Incidence (epidemiology), Case-control study, Odds ratio, Middle Aged, medicine.disease, Lymphoproliferative Disorders, 3. Good health, Treatment Outcome, Case-Control Studies, 030220 oncology & carcinogenesis, biology.protein, Colitis, Ulcerative, Female, 030211 gastroenterology & hepatology, France, business, Immunosuppressive Agents, Follow-Up Studies
Abstract: International audience; BACKGROUND: It remains to be shown whether inflammatory bowel disease (IBD) is associated with an increased risk of primary intestinal lymphoproliferative disorders (PILD). We assessed this risk in the CESAME French nationwide prospective observational cohort. METHODS: In all, 680 gastroenterologists enrolled 19,486 patients with IBD (Crohn's disease in 60.3%) from May 2004 to June 2005. Follow-up ended on 31 December 2007. Available biopsy samples and surgical specimens from patients with PILD (n = 14) were centralized for review. The reference incidence of PILD in the general population was obtained from the Côte d'Or registry and was used as a comparator to assess the standardized incidence ratio (SIR). The influence of thiopurine exposure was explored in a nested case-control study. RESULTS: In the CESAME population the crude incidence of PILD was 0.12/1000 patient-years, with a corresponding SIR of 17.51 (95% confidence interval [CI], 6.43-38.11; P < 0.0001). The risk was highest in patients exposed to thiopurines (SIR 49.52, 95% CI 13.49-126.8; P < 0.0001), while it did not reach statistical significance in patients naïve to thiopurines (SIR 4.83, 95% CI, 0.12-26.91; P = 0.37). The odds ratio associated with ongoing thiopurine exposure (vs. naïve) was 2.97 (95% CI, 0.30-infinity; P = 0.38). All 14 cases of PILD were non-Hodgkin's B-cell LD, 78.6% occurred in males, 85.7% arose in IBD lesions, and 45.5% were Epstein-Barr virus-positive. Eleven cases occurred in patients with Crohn's disease. Mean (SD) age at PILD diagnosis was 55.1 (5.6) years and the median time since IBD onset was 8.0 years (interquartile range, 3.0-15.8). CONCLUSIONS: Patients with IBD have an increased risk of developing PILD. (Inflamm Bowel Dis 2012;).
Published: 2012

36. The French Gaucher's disease registry: clinical characteristics, complications and treatment of 562 patients

Author: Christine de Roux-Serratrice, Jérôme Stirnemann, Dries Dobbelaere, Bernard Grosbois, Olivier Fain, Fabrice Camou, Thierry Levade, Agathe Masseau, Vassili Valayanopoulos, Djazia Heraoui, Marc G. Berger, Bruno Fantin, Marie T. Vanier, Cyril Mignot, Linda Rossi-Semerano, Catherine Caillaud, Christian Rose, Nadia Belmatoug, Alain Robert, Frédéric Sedel, Marie Vigan, P. Kaminsky, Thierry Billette de Villemeur, Dalil Hamroun, Roselyne Froissart, Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Laboratoire de biostatistiques, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Pathology Department, VU University Medical Center [Amsterdam], Service de médecine interne, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine interne générale, Hôpitaux Universitaires de Genève (HUG), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Service de Pédiatrie et Pédiatrie Rhumatologique, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital de Bicêtre, Centre de référence des maladies auto-inflammatoires, Service d'Hématologie Biologique-Immunologie, CHU Clermont-Ferrand, Service d'hématologie, Hôpital Saint-Vincent-de-Paul, Service de réanimation médicale, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Médecine Interne [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Service de Médecine interne et immunologie clinique [Rennes] = internal medicine and clinical immunology [Rennes], CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de pédiatrie, Hôpital des Enfants, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Laboratoire de Génétique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Centre de Biologie Est, Hospices Civils de Lyon (HCL), Laboratoire de biochimie métabolique, CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Trousseau [APHP], Centre de référence des maladies héréditaires du métabolisme de l'enfant et de l'adulte, Hôpital Jeanne de Flandre [Lille], Métabolomique et maladies métaboliques, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Référence Maladies Métaboliques de l'Enfant et de Adulte (MaMEA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], The salaries of a statistician and a clinical research associate who participated in this study were funded, in part, by a grant from Genzyme France.The development of the original software for the French Gaucher Disease Registry (FGDR) was funded by a grant from the association VML (Vaincre les Maladies Lysosomales). J. Stirnemann's work was funded, in part, by a grant from INSERM (Institut National de la Santé et de la Recherche Médicale). The FGDR was funded, in part, by INSERM and InVS (Institut national de Veille Sanitaire)., Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), BMC, Ed., Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques, Université Paris Diderot - Paris 7 ( UPD7 ) -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 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Jean Verdier, Hôpitaux Universitaires de Genève ( HUG ), 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 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Beaujon, Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital de Bicêtre, Assistance publique - Hôpitaux de Paris (AP-HP), Aix Marseille Université ( AMU ) -Hôpital Saint-Joseph [Marseille], CHU Pontchaillou [Rennes]-Hôpital Sud, Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Hospices Civils de Lyon ( HCL ), Hôtel-Dieu-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Unité fonctionnelle de génétique clinique, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Service de neuropédiatrie [Trousseau], Fédération de Neurologie [Salpétrière], Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP]
Subjects: Male, medicine.medical_treatment, lcsh:Medicine, Avascular necrosis, [SDV.GEN] Life Sciences [q-bio]/Genetics, France/epidemiology, 0302 clinical medicine, Epidemiology, Miglustat, Genetics(clinical), Pharmacology (medical), Child, Genetics (clinical), Medicine(all), 0303 health sciences, Incidence (epidemiology), Incidence, General Medicine, Enzyme replacement therapy, Middle Aged, 3. Good health, Gaucher's disease, Child, Preschool, Splenectomy, Female, France, Enzyme-replacement therapy, medicine.drug, Adult, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Imiglucerase, Adolescent, French Gaucher’s Disease Registry, Gaucher Disease/complications/epidemiology/pathology/therapy, French Gaucher's Disease Registry, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, 030304 developmental biology, Aged, [SDV.GEN]Life Sciences [q-bio]/Genetics, Gaucher Disease, business.industry, Research, lcsh:R, Infant, Newborn, nutritional and metabolic diseases, Infant, medicine.disease, ddc:618.97, business, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, 030217 neurology & neurosurgery, Bone events
Abstract: Background Clinical features, complications and treatments of Gaucher’s disease (GD), a rare autosomal–recessive disorder due to a confirmed lysosomal enzyme (glucocerebrosidase) deficiency, are described. Methods All patients with known GD, living in France, with ≥1 consultations (1980–2010), were included in the French GD registry, yielding the following 4 groups: the entire cohort, with clinical description; and its subgroups: patients with ≥1 follow-up visits, to investigate complications; recently followed (2009–2010) patients; and patients treated during 2009–2010, to examine complications before and during treatment. Data are expressed as medians (range) for continuous variables and numbers (%) for categorical variables. Results Among the 562 registry patients, 265 (49.6%) were females; 454 (85.0%) had type 1, 22 (4.1%) type 2, 37 (6.9%) perinatal–lethal type and 21 (3.9%) type 3. Median ages at first GD symptoms and diagnosis, respectively, were 15 (0–77) and 22 (0–84) years for all types. The first symptom diagnosing GD was splenomegaly and/or thrombocytopenia (37.6% and 26.3%, respectively). Bone-marrow aspiration and/or biopsy yielded the diagnosis for 54.7% of the patients, with enzyme deficiency confirming GD for all patients. Birth incidence rate was estimated at 1/50,000 and prevalence at 1/136,000. For the 378 followed patients, median follow-up was 16.2 (0.1–67.6) years. Major clinical complications were bone events (BE; avascular necrosis, bone infarct or pathological fracture) for 109 patients, splenectomy for 104, and Parkinson’s disease for 14; 38 patients died (neurological complications for 15 type-2 and 3 type-3 patients, GD complications for 11 type-1 and another disease for 9 type-1 patients). Forty-six had monoclonal gammopathy. Among 283 recently followed patients, 36 were untreated and 247 had been treated during 2009–2010; 216 patients received treatment in December 2010 (126 with imiglucerase, 45 velaglucerase, 24 taliglucerase, 21 miglustat). BE occurred before (130 in 67 patients) and under treatment (60 in 41 patients) with respective estimated frequencies (95% CI) of first BE at 10 years of 20.3% (14.1%–26.5%) and 19.8% (13.5%–26.1%). Conclusion This registry enabled the epidemiological description of GD in France and showed that BE occur even during treatment.
Published: 2012

37. IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma. : IDH2 mutations in AITL

Author: Tak W. Mak, Luc Xerri, Jean-Philippe Jais, Li Chong Chan, Javeed Iqbal, Marie Parrens, Laurence de Leval, Antoine Martin, Wing C. Chan, François Lemonnier, Philippe Gaulard, Can Küçük, Pierre Brousset, Rob A. Cairns, Campbell Family Institute for Breast Cancer Research, University Health Network, Department of Pathology and Microbiology, University of Nebraska Medical Center, University of Nebraska System-University of Nebraska System, 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), Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Pathologie Clinique, Université de Lausanne = University of Lausanne (UNIL)-Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV)-Institut Universitaire de Pathologie, Service informatique médicale et biostatistique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de pathologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service d'Anatomie et de Cytologie Pathologiques [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Département de biopathologie, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'anatomie pathologique et histologie-cytologie [Rangueil], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], Department of Pathology, The University of Hong Kong (HKU), This work is supported by the CIHR, The Canadian Cancer Society, The Terry Fox Foundation, and the Leukemia and Lymphoma Society (TWM), INCa (Institut National du Cancer), PHRC (Programme Hospitalier de Recherche Clinique) and FRM (Fondation pour la Recherche Médicale) (PG), The Institut Universitaire de France and the CITTIL program (PB), the Cancer Plan research Programme (Belgium) (LdL), NCI grant (5U01/CA114778), NIH grant (U01/CA84967), lymphoma SPORE grant P50CA13641-02, and Eppley Core Grant (W-CC and JI)., 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 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Université de Lausanne ( UNIL ) -Centre Hospitalier Universitaire Vaudois [Lausanne] ( CHUV ) -Institut Universitaire de Pathologie, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Centre de Recherche en Cancérologie de Toulouse ( CRCT ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], The University of Hong Kong ( HKU ), Université de Lausanne (UNIL)-Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV)-Institut Universitaire de Pathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne-Université Paris 13 (UP13)
Subjects: Male, Mutation rate, Angioimmunoblastic T-cell lymphoma, IDH1, Genotype, Immunology, Kaplan-Meier Estimate, Biology, medicine.disease_cause, Lymphoma, T-Cell, Biochemistry, IDH2, 03 medical and health sciences, 0302 clinical medicine, Lymphoma, T-Cell, Peripheral - enzymology - genetics - pathology, Gene Frequency, Mutation Rate, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Isocitrate Dehydrogenase - genetics, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Aged, 0303 health sciences, Mutation, Lymphoid Neoplasia, Lymphoma, T-Cell, Peripheral, Cell Biology, Hematology, medicine.disease, Prognosis, Isocitrate Dehydrogenase, 3. Good health, Lymphoma, Lymphoma, T-Cell - enzymology - genetics - pathology, Isocitrate dehydrogenase, 030220 oncology & carcinogenesis, Immunoblastic Lymphadenopathy, Cancer research, Female, Immunoblastic Lymphadenopathy - enzymology - genetics - pathology
Abstract: Mutations in isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) occur in most grade 2 and 3 gliomas, secondary glioblastomas, and a subset of acute myelogenous leukemias but have not been detected in other tumor types. The mutations occur at specific arginine residues and result in the acquisition of a novel enzymatic activity that converts 2-oxoglutarate to D-2-hydroxyglutarate. This study reports IDH1 and IDH2 genotyping results from a set of lymphomas, which included a large set of peripheral T-cell lymphomas. IDH2 mutations were identified in approximately 20% of angioimmunoblastic T-cell lymphomas (AITLs), but not in other peripheral T-cell lymphoma entities. These results were confirmed in an independent set of AITL patients, where the IDH2 mutation rate was approximately 45%. This is the second common genetic lesion identified in AITL after TET2 and extends the number of neoplastic diseases where IDH1 and IDH2 mutations may play a role., link_to_OA_fulltext
Published: 2012

38. Screening for primary creatine deficiencies in French patients with unexplained neurological symptoms

Author: L. Lion-François, Delphine Héron, François Cartault, Soumeya Bekri, Gaelle Pitelet, Olivier Douay, Karine Mention-Mulliez, Brigitte Chabrol, Vincent des Portes, David Cheillan, Richard Delorme, Jean-Marie Cuisset, Dries Dobbelaere, Kumaran Deiva, Gajja S. Salomons, Allel Chabli, JM Pinard, Jean-François Benoist, Gilbert Briand, Vassili Valayannopoulos, Alice Goldenberg, Marc Tardieu, Nicole Porchet, Marion Gérard, Christine Vianey-Saban, François Rivier, Alexandra Afenjar, Gilles Simard, Marie Joncquel-Chevalier Curt, Fabienne Prieur, Joseph Vamecq, Service Maladies Héréditaires du Métabolisme et Dépistage Néonatal, Hospices Civils de Lyon (HCL)-Groupement Hospitalier Est, Laboratoire d'Hormonologie, Métabolisme-Nutrition & Oncologie (HMNO), Département de Biochimie et Biologie Moléculaire-Centre de Biologie et Pathologie (CBP) Pierre-Marie Degand-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Mass Spectrometry Application Laboratory, Université de Lille, Droit et Santé, Metabolic Unit, Department of Clinical Chemistry-VU University Medical Center [Amsterdam], Centre de Référence des Maladies Héréditaires du Métabolisme, Hôpital Jeanne de Flandres-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Neurologie Infantile, Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de neurologie pédiatrique, Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Biochimie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Biochimie-Hormonologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Unité de Neurologie Pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Raymond Poincaré [AP-HP]-Département de Pédiatrie, Laboratoire de Biochimie et Biologie moléculaire, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de Neuropédiatrie, Hôpital Bicêtre, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), 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), Service Neuropédiatrie, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Génétique, CHU Saint-Etienne-Hôpital nord, Service de génétique, Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Hôpital l'Archet, Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Laboratoire de biochimie générale [Rouen], Normandie Université (NU)-Centre hospitalier universitaire de Rouen, Service de Génétique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Pédopsychiatrie, This work was supported by grants from the French Ministère de la Santé (PHRC 2003R/1903) and FMO (Fédération des Maladies Orphelines)., Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Clinical chemistry, Human genetics, NCA - Childhood White Matter Diseases, BMC, Ed., Hospices Civils de Lyon ( HCL ) -Groupement Hospitalier Est, Laboratoire d'Hormonologie, Métabolisme-Nutrition & Oncologie ( HMNO ), Département de Biochimie et Biologie Moléculaire-Centre de Biologie et Pathologie (CBP) Pierre-Marie Degand-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Hôpital Jeanne de Flandres-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Hôpital Roger Salengro-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Hôpital Femme Mère Enfant [CHU - HCL] ( HFME ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré, Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP Hôpital Raymond Poincaré [Garches]-Département de Pédiatrie, CHU Angers, Service de neuropédiatrie [Trousseau], Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière ( CRICM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), 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 ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Centre hospitalier Felix Guyon (Saint-Denis), CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Normandie Université ( NU ) -Normandie Université ( NU ) -Centre hospitalier universitaire de Rouen, and Hôpital Clémenceau
Subjects: Male, medicine.medical_specialty, Population, Glycine, lcsh:Medicine, Nerve Tissue Proteins, [SDV.GEN] Life Sciences [q-bio]/Genetics, Creatine, Plasma Membrane Neurotransmitter Transport Proteins, Frameshift mutation, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Humans, Missense mutation, Genetics(clinical), Pharmacology (medical), education, Gene, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, Retrospective Studies, 030304 developmental biology, Medicine(all), 0303 health sciences, Creatinine, education.field_of_study, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, Research, lcsh:R, Retrospective cohort study, General Medicine, 3. Good health, Guanidinoacetate N-methyltransferase, Endocrinology, chemistry, Female, Nervous System Diseases, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, business, 030217 neurology & neurosurgery
Abstract: A population of patients with unexplained neurological symptoms from six major French university hospitals was screened over a 28-month period for primary creatine disorder (PCD). Urine guanidinoacetate (GAA) and creatine:creatinine ratios were measured in a cohort of 6,353 subjects to identify PCD patients and compile their clinical, 1H-MRS, biochemical and molecular data. Six GAMT [N-guanidinoacetatemethyltransferase (EC 2.1.1.2)] and 10 X-linked creatine transporter (SLC6A8) but no AGAT (GATM) [L-arginine/glycine amidinotransferase (EC 2.1.4.1)] deficient patients were identified in this manner. Three additional affected sibs were further identified after familial inquiry (1 brother with GAMT deficiency and 2 brothers with SLC6A8 deficiency in two different families). The prevalence of PCD in this population was 0.25% (0.09% and 0.16% for GAMT and SLC6A8 deficiencies, respectively). Seven new PCD-causing mutations were discovered (2 nonsense [c.577C > T and c.289C > T] and 1 splicing [c.391 + 15G > T] mutations for the GAMT gene and, 2 missense [c.1208C > A and c.926C > A], 1 frameshift [c.930delG] and 1 splicing [c.1393-1G > A] mutations for the SLC6A8 gene). No hot spot mutations were observed in these genes, as all the mutations were distributed throughout the entire gene sequences and were essentially patient/family specific. Approximately one fifth of the mutations of SLC6A8, but not GAMT, were attributed to neo-mutation, germinal or somatic mosaicism events. The only SLC6A8-deficient female patient in our series presented with the severe phenotype usually characterizing affected male patients, an observation in agreement with recent evidence that is in support of the fact that this X-linked disorder might be more frequent than expected in the female population with intellectual disability.
Published: 2012

39. INF2 mutations in Charcot-Marie-Tooth disease with glomerulopathy

Author: Christophe Charasse, Miguel A. Alonso, Rodrick Montjean, Dominique Pouthier, Leila Balafrej, Pierre Ronco, Jacques Dantal, Georges Deschênes, Jean-Michel Vallat, Eric LeGuern, Guillaume Canaud, Alain Bonnardeaux, Anne Guiochon-Mantel, Marie-Josèphe Tête, Olivier Gribouval, Olivia Boyer, Laurence Richard, Christelle Arrondel, Philippe Petiot, Geneviève Benoit, Odile Dubourg, Alexandre Karras, Evelyne Huynh Cong, Isabelle Broutin, Emmanuelle Plaisier, Corinne Antignac, Géraldine Mollet, Claire Pouteil-Noble, Marie-Claire Gubler, Sophie Saunier, Benoît Funalot, Patrice Deteix, Fabien Nevo, Néphropathies héréditaires et rein en développement (UMR_S 983), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de néphrologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Biochimie et Génétique Moléculaire [CHU Limoges], CHU Limoges, Centre de référence national neuropathies périphériques rares [CHU Limoges], Service de Neurologie [CHU Limoges], Service de néphrologie pédiatrique, Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], SARS International Centre for Marine Molecular Biology, Neuropathies héréditaires et rein en développement, Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe Avenir Tour Lavoisier, Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Service de néphrologie et transplantation, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de Recherche Guy- Bernier, Hôpital Maisonneuve-Rosemont, Service de transplantation et soins intensifs, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], CH de Saint-Brieuc, Service de Néphrologie et Immunologie Clinique, Hôtel Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Université Paris Diderot - Paris 7 (UPD7), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de neurologie, Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Service de Néphrologie, Centre Hospitalier de Luxembourg [Luxembourg] (CHL), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de génétique moléculaire, pharmacogénétique et hormonologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Laboratoire de cristallographie et RMN biologiques (LCRB - UMR 8015), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Paris Descartes - Paris 5 (UPD5), Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centro de Biología Molecular Severo Ochoa [Madrid] (CBMSO), Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Service de Génétique Médicale [CHU Necker], Néphropathies héréditaires et rein en développement ( UMR_S 983 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Necker - Enfants Malades [AP-HP], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Université Paris Descartes - Paris 5 ( UPD5 ), Service de néphrologie et dialyses, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Université Pierre et Marie Curie - Paris 6 ( UPMC ), Université de Montréal-CHU Sainte Justine [Montréal], Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Hospices Civils de Lyon ( HCL ) -Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Hôtel Dieu-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré, Université Paris Diderot - Paris 7 ( UPD7 ), CHU Gabriel Montpied ( CHU ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Association française contre les myopathies ( AFM-Téléthon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hospices Civils de Lyon ( HCL ) -Hôpital de la Croix-Rousse [CHU - HCL], Centre Hospitalier de Luxembourg, Centre de Référence pour les Epilepsies Rares, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP]-Centre de Référence pour les Epilepsies Rares, Service de Génétique [Pitié-Salpêtrière], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière ( CRICM ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Laboratoire de cristallographie et RMN biologiques ( LCRB - UMR 8015 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centro de Biología Molecular Severo Ochoa ( CBMSO ), Universidad Autonoma de Madrid ( UAM ) -Consejo Superior de Investigaciones Científicas [Spain] ( CSIC ), RONCO, Pierre, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Universidad Autónoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), CHU de Saint-Brieuc, Agence Nationale de la Recherche (France), Association Française contre les Myopathies, Fondation pour la Recherche Médicale, Fonds de la Recherche en Sante du Québec, and Ministerio de Ciencia e Innovación (España)
Subjects: Male, Charcot–Marie–Tooth neuropathy, Pathology, MESH : Actins, MESH : Charcot-Marie-Tooth Disease, urologic and male genital diseases, Mice, Myelin, 0302 clinical medicine, MESH : Child, Charcot-Marie-Tooth Disease, MESH: Child, MESH: Charcot-Marie-Tooth Disease, Medicine, MESH: Animals, Age of Onset, Child, 0303 health sciences, MESH: Middle Aged, Glomerulosclerosis, Focal Segmental, General Medicine, female genital diseases and pregnancy complications, MESH : Age of Onset, 3. Good health, MESH : Phenotype, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Myelin maintenance, MESH: Young Adult, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH: Myelin and Lymphocyte-Associated Proteolipid Proteins, MESH: Proteolipids, MESH : Heterozygote, medicine.medical_specialty, Proteolipids, MESH: Age of Onset, MESH : Young Adult, Formins, MESH: Phenotype, MESH: Actins, 03 medical and health sciences, MESH : Adolescent, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Humans, MESH: Myelin Proteins, MESH : Middle Aged, MESH: Adolescent, MESH: Humans, MESH : Humans, Membrane Transport Proteins, Kidney metabolism, MESH: Adult, medicine.disease, MESH : Glomerulosclerosis, Focal Segmental, INF2, Endocrinology, Mutation, MESH: Schwann Cells, MESH: Female, 030217 neurology & neurosurgery, Kidney, MESH: Membrane Transport Proteins, Glomerulosclerosis, Focal segmental glomerulosclerosis, MESH : Membrane Transport Proteins, Peripheral myelin protein 22, MESH : Myelin and Lymphocyte-Associated Proteolipid Proteins, MESH : Female, MESH: Heterozygote, Myelin and Lymphocyte-Associated Proteolipid Proteins, Microfilament Proteins, Middle Aged, MESH : Adult, MESH : Kidney, Phenotype, medicine.anatomical_structure, Female, MESH : Mutation, Myelin Proteins, Adult, Heterozygote, MESH: Mutation, Adolescent, MESH : Microfilament Proteins, MESH: Glomerulosclerosis, Focal Segmental, MESH : Male, MESH : Schwann Cells, MESH : Myelin Proteins, Young Adult, MESH: Microfilament Proteins, Glomerulopathy, Internal medicine, MESH : Mice, Animals, MESH: Mice, 030304 developmental biology, urogenital system, business.industry, Myelin protein zero, MESH: Kidney, Actins, MESH: Male, MESH : Proteolipids, Schwann Cells, MESH : Animals, business
Abstract: Backgrounds: Charcot–Marie–Tooth neuropathy has been reported to be associated with renal diseases, mostly focal segmental glomerulosclerosis (FSGS). However, the common mechanisms underlying the neuropathy and FSGS remain unknown. Mutations in INF2 were recently identified in patients with autosomal dominant FSGS. INF2 encodes a formin protein that interacts with the Rho-GTPase CDC42 and myelin and lymphocyte protein (MAL) that are implicated in essential steps of myelination and myelin maintenance. We therefore hypothesized that INF2 may be responsible for cases of Charcot–Marie–Tooth neuropathy associated with FSGS., Methods: We performed direct genotyping of INF2 in 16 index patients with Charcot–Marie–Tooth neuropathy and FSGS who did not have a mutation in PMP22 or MPZ, encoding peripheral myelin protein 22 and myelin protein zero, respectively. Histologic and functional studies were also conducted., Methods: We identified nine new heterozygous mutations in 12 of the 16 index patients (75%), all located in exons 2 and 3, encoding the diaphanous-inhibitory domain of INF2. Patients presented with an intermediate form of Charcot–Marie–Tooth neuropathy as well as a glomerulopathy with FSGS on kidney biopsy. Immunohistochemical analysis revealed strong INF2 expression in Schwann-cell cytoplasm and podocytes. Moreover, we demonstrated that INF2 colocalizes and interacts with MAL in Schwann cells. The INF2 mutants perturbed the INF2–MAL–CDC42 pathway, resulting in cytoskeleton disorganization, enhanced INF2 binding to CDC42 and mislocalization of INF2, MAL, and CDC42., Conclusions: INF2 mutations appear to cause many cases of FSGS-associated Charcot–Marie–Tooth neuropathy, showing that INF2 is involved in a disease affecting both the kidney glomerulus and the peripheral nervous system. These findings provide new insights into the pathophysiological mechanisms linking formin proteins to podocyte and Schwann-cell function., Funded by the Agence Nationale de la Recherche and others.Supported by grants from the Association pour l'Utilisation du Rein Artificiel (to Dr. Antignac), Association Française contre les Myopathies (ANR-08-GENOPAT-017-01, to Dr. Antignac), Agence Nationale de la Recherche (PodoNet project number ANR-07-E-RARE-011-01 in the ERA-Net Consortium [JTC2007], to Dr. Antignac, and ANR-06-MRAR-024-01, to Dr. Leguern), Fondation pour la Recherche Médicale (project number DMP 2010-11-20-386, to Dr. Antignac, and doctoral funding, to Dr. Boyer), Association des Malades du Syndrome Néphrotique (to Dr. Mollet), Fonds de la Recherche en Santé du Québec (Fellowship Training Award to Dr. Benoit), and Ministerio de Ciencia e Innovación (BFU2009-07886 and CONSOLIDER COAT CSD2009-00016, to Dr. Alonso).
Published: 2011

40. Mycobacterium genavense as a cause of subacute pneumonia in patients with severe cellular immunodeficiency

Author: Blandine Rammaert, Olivier Lortholary, Pierre Cahen, Marc Lecuit, Louis-Jean Couderc, Emmanuel Bille, Emilie Catherinot, Elisabeth Rivaud, Marie-France Mamzer, Patrick Honderlick, David Zucman, Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de pneumologie [Hôpital Foch], Hôpital Foch [Suresnes], Service de microbiologie, Service de médecine interne, Service de transplantation rénale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Microorganismes et Barrières de l'Hôte (Equipe avenir), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mycologie moléculaire, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), BMC, Ed., Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de pneumologie, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Hôpital Foch [Suresnes], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Equipe avenir Microorganismes et Barrières de l'Hôte, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, medicine.medical_specialty, Tuberculosis, Rifabutin, Mycobacterium genavense, Mycobacterium Infections, Nontuberculous, Case Report, HIV Infections, lcsh:Infectious and parasitic diseases, Immunocompromised Host, 03 medical and health sciences, 0302 clinical medicine, Medical microbiology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Clarithromycin, Pneumonia, Bacterial, medicine, Humans, lcsh:RC109-216, 030212 general & internal medicine, 0303 health sciences, biology, 030306 microbiology, Immunologic Deficiency Syndromes, Nontuberculous Mycobacteria, biology.organism_classification, medicine.disease, Kidney Transplantation, Anti-Bacterial Agents, 3. Good health, Pneumonia, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Infectious Diseases, Immunology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Sputum, Female, Nontuberculous mycobacteria, medicine.symptom, medicine.drug
Abstract: Background Mycobacterium genavense is a rare nontuberculous mycobacteria (NTM). Human infections are mostly disseminated in the setting of the AIDS epidemic or the use of aggressive immunosuppressive treatments. M. genavense culture is fastidious, requiring supplemented media. Pulmonary involvement rarely occurs as a primary localization. Cases presentation We report here two patients with pneumonia as the predominant manifestation of M. genavense infection: one kidney transplanted patient and one HIV-infected patient. Both patients were initially treated with anti-tuberculous drugs before the identification of M. genavense on sputum or broncho-alveolar lavage fluid culture. A four-drug regimen including clarithromycin and rifabutin was started. Gamma interferon has been helpful in addition to antimycobacterial treatment for one patient. Conclusion Clinicians should be aware that M. genavense could be the etiologic agent of sub-acute pneumonia mimicking tuberculosis in patients with cellular immunodeficiency status.
Published: 2011

41. [Renal biopsy practice: results of a French study and recommendations]

Author: Bollée , Guillaume, Moulin , Bruno, Martinez , Frank, Meulders , Quentin, Rougier , Jean-Philippe, Baumelou , Alain, Glotz , Denis, Subra , Jean-François, Ulinski , Tim, Vrigneaud , Laurence, Brasseur , José, Alhenc-Gelas , Martine, Martin , Laurent, DANIEL , Laurent, Kourilsky , Olivier, Deteix , Patrice, Sie , Pierre, Ronco , Pierre, Houillier , Pascal, Laboratoire de Recherche en Imagerie : Méthodes d'imagerie des Échanges transcapillaires (LRI - EA4062), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie et Transplantation, CHU Strasbourg, Service de Transplantation Rénale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie [Avignon], Centre Hospitalier Henri Duffaut (Avignon), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Service de Néphrologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service de Néphrologie [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), CHU Trousseau [APHP], Service de Néphrologie [Valenciennes], Centre Hospitalier de Valenciennes, Service de Néphrologie [Bois-Bernard], Hôpital privé Bois-Bernard, Service d'Hématologie [Georges-Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Service de Pathologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire d'Anatomopathologie [Aix-Marseille], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Néphrologie [Evry], Centre Hospitalier Sud Francilien, Service de Néphrologie [Clermont-Ferrand], CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I (UdA), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Physiologie [Georges-Pompidou], Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Néphrologie [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CH Evry-Corbeil-CH Evry-Corbeil, Laboratoire d'Hématologie [Rangueil], Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], RONCO, Pierre, Service de Département de Néphrologie = Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de néphrologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Laboratoire de Recherche en Imagerie : Méthodes d'imagerie des Échanges transcapillaires ( LRI - EA4062 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université d'Angers ( UA ) -CHU Angers, Service de Néphrologie Pédiatrique [Trousseau], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I ( UdA ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital de Rangueil, and CHU Toulouse [Toulouse]
Subjects: MESH: Kidney Diseases, MESH: Humans, Biopsy, MESH : Humans, MESH: Kidney, Kidney, MESH : Kidney, MESH: France, MESH: Biopsy, MESH : Physician's Practice Patterns, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH : Biopsy, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH : Kidney Diseases, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Humans, Kidney Diseases, France, Practice Patterns, Physicians', MESH : France, MESH: Physician's Practice Patterns
Abstract: International audience; BACKGROUND: Although several risk factors associated with complications after renal biopsy (RB) have been identified, recommendations for RB procedures are still lacking. Our working group, appointed by the scientific commission of the Société de néphrologie in France, aimed to depict the main aspects of the practice of RB in adults in France, before establishing some guidelines. METHODS: Members of the Société de néphrologie in France were asked to participate to a questionnaire survey on RB procedures. RESULTS: Eighty-eight nephrologists from 74 units (27 in teaching hospitals, 35 in public general hospitals, and 12 in private centers) participated in our study. Native kidney and graft biopsies were performed in 73 and 35 units, respectively. RB activity was highly variable among units, ranging from several hundred to less than ten per year. Transjugular RB was judged to be smoothly accessible in 28 out of 73 units (38.4%). Significant variations in practices were observed regarding patient information before RB, assessment of hemorrhagic risk factors, care of patients with antiplatelet agents and hemorrhagic risk factors, and radiological guidance. Early discharge (
Published: 2011

42. Long-term Impact of Subclinical Inflammation Diagnosed by Protocol Biopsy One Year After Renal Transplantation

Author: Jean-Michel Goujon, Luc Marcellin, Sandrine Girardot-Seguin, Guy Touchard, Arnaud François, Antoine Thierry, François Comoz, Marie-Christine Machet, Laure-Hélène Noël, Nathalie Rioux-Leclercq, Carole Cordonnier, Eric Thervet, Vincent Vuiblet, Ischémie - Reperfusion en transplatation rénale, Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de néphrologie et transplantation, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Laboratoire d'anatomopathologie, Service d'Anatomopathologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP], Service d'anatomie pathologique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Service d'anatomie et cytologie pathologiques [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Laboratoire d'Anatomie Pathologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'anatomie et cytopathologie, CHU Amiens-Picardie, Service d'Anatomie et Cytologie Pathologique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Département de Pathologie, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Laboratoire Roche, Laboratoire Roche SAS, Roche SAS, France, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes], CHU Pontchaillou [Rennes], 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), Service d'Anatomie et Cytologie Pathologique [CHU Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Université de Poitiers-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier Universitaire de Reims ( CHU Reims ), Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), CHRU Tours-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Laboratoire d'anatomie pathologique, CHU Caen-Hôpital côte de nacre, CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), and De Villemeur, Hervé
Subjects: [ SDV.MHEP.UN ] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Protocol biopsy, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, Biopsy, 030232 urology & nephrology, Renal function, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, 030230 surgery, Kidney, Gastroenterology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 03 medical and health sciences, 0302 clinical medicine, subclinical inflammation, Internal medicine, medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, Humans, Pharmacology (medical), [ SDV.MHEP.CHI ] Life Sciences [q-bio]/Human health and pathology/Surgery, Kidney transplantation, Survival analysis, Subclinical infection, Inflammation, Transplantation, medicine.diagnostic_test, business.industry, Incidence (epidemiology), Graft Survival, renal function, renal transplantation, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Kidney Transplantation, Survival Analysis, 3. Good health, Surgery, Sirolimus, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, Immunosuppressive Agents, medicine.drug
Abstract: International audience; The long-term impact of subclinical acute rejection (SCAR) on renal graft function remains poorly understood. Furthermore, the interpretation of borderline lesions is difficult and their incidence is variable. The aim of this study was to analyze the characteristics of subclinical inflammation (SCI) in protocol biopsies performed 1-year after renal transplantation. SCI was defined as the presence of borderline lesions or SCAR according to the Banff 2005 classification. The patients included were a subpopulation of the CONCEPT study in which patients were randomized 3 months after transplantation to receive either sirolimus (SRL) or cyclosporine A (CsA) in combination with mycophenolate mofetil. At 1 year, we observed SCI in 37 of the 121 patients observed with an evaluable biopsy. The incidence was more frequent in the SRL group (SRL 45.2% vs. CsA 15.3%). At 30 months , SCI was associated with a significantly lower level of estimated glomerular filtration rate (mean MDRD 50.8 [±13.3] vs. 57.7 [±16.3] mL/min/1.73 m(2) , p = 0.035). In conclusion, SCI at 1-year posttransplantation is associated with worsening renal function and is more frequent in SRL-treated patients. Therefore, evaluation of SCI may be a valuable tool to allow the optimization of immunosuppressive regimens.
Published: 2011

43. Renal cell carcinoma (RCC) in patients with end-stage renal disease exhibits many favourable clinical, pathologic, and outcome features compared with RCC in the general population

Author: Laurent Salomon, Lionel Badet, Georges Karam, Jacques Tostain, Pierre Bigot, Nathalie Rioux-Leclercq, Sébastien Barbet, Jean-Etienne Terrier, Bernard Escudier, Michel Soulié, Hicham Elkentaoui, Abdel-Rahmène Azzouzi, Fabrice Dugardin, Yann Neuzillet, Jean-Christophe Bernhard, Jacques Hubert, Aurélien Descazeaux, Karim Fehri, Nicolas Brichart, Philippe Paparel, J.M. Boutin, Laurent Guy, Baptiste Tisserand, Arnaud Mejean, Ismaël Galliot, Marc-Olivier Timsit, Laurence Bastien, Jérôme Rigaud, Antoine Valeri, Jacques Petit, Laurent Zini, Benoit Barrou, Christian Pfister, Xavier Tillou, Franck Bruyère, Fabien Saint, Herve Lang, Jean-Jacques Patard, Marie-Dominique Azemar, Denis Chautard, Julien Branchereau, Hervé Wallerand, Pascal Rischmann, Laura Poissonnier, Charles Deruelle, Lucille Martin, Laurence Albiges, Jacques Irani, Arnauld Villers, Thierry Lebret, Hervé Baumert, François Kleinclauss, Nicolas Terrier, Jean-Alexandre Long, Pierre-Etienne Theveniaud, M. Gigante, Frédéric Staerman, Jean-Marie Ferriere, Romain Mathieu, Morgan Rouprêt, F. Sallusto, Benoit Feuillu, Service d'urologie, Hôpital Foch [Suresnes], CHU Amiens-Picardie, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], CHU Grenoble-Hôpital Michallon, Service d'urologie-andrologie, CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] ( UJM ) -Hôpital nord, Service d'urologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Hôpital Saint-Joseph, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy ( IGR ), CHU Strasbourg, Service d'anatomie et cytologie pathologiques [Rennes], Université d'Angers ( UA ) -CHU Angers, Service d'urologie, andrologie et transplantation rénale, Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Institut Mondor de recherche biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Service d'urologie [Tours], Hôpital Bretonneau-CHRU Tours, Hôtel-Dieu, Service d'Urologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Hôpital Huriez-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Service de Chirurgie urologique et andrologie [CHU Limoges], CHU Limoges, Service d'urologie et transplantation rénales [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Service de Néphrologie et Urologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques, Service d'urologie [Rouen], CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Université de Reims Champagne-Ardenne ( URCA ), Centre hospitalier universitaire de Poitiers ( CHU Poitiers ) -Hôpital La Milétrie, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Service d'Urologie - Transplantation Rénale - Andrologie, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], CHU Clermont-Ferrand-Hôpital Gabriel Montpied, Université de Brest ( UBO ) -Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Service d'urologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, members of the Comité de Transplantation de l'Association Française d'Urologie, the Comité de Cancérologie de l'Association Française d'Urologie, Service d'urologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Hôpital nord, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut Gustave Roussy (IGR), Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Institut Mondor de recherche biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Huriez-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'urologie et transplantation rénales [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Saint-Jacques, CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Université de Reims Champagne-Ardenne (URCA), Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Hôpital La Milétrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Brest (UBO)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Service d'urologie [Rennes] = Urology [Rennes], Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes], CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service d'Urologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, De Villemeur, Hervé, CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Hôpital nord, Département d'Urologie-Andrologie et Transplantation Rénale [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)
Subjects: Male, [ SDV.MHEP.UN ] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, MESH: Chi-Square Distribution, Time Factors, MESH : Retrospective Studies, 030232 urology & nephrology, MESH : Aged, Kaplan-Meier Estimate, MESH: Risk Assessment, urologic and male genital diseases, Gastroenterology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Proportional Hazards Models, MESH : Carcinoma, Renal Cell, 0302 clinical medicine, Renal cell carcinoma, MESH: Risk Factors, Risk Factors, MESH : Female, MESH : Neoplasm Staging, MESH : Risk Assessment, MESH: Treatment Outcome, MESH: Aged, education.field_of_study, Univariate analysis, MESH: Middle Aged, MESH: Carcinoma, Renal Cell, MESH: Neoplasm Staging, Middle Aged, MESH : Adult, MESH : Survival Rate, MESH : Risk Factors, Kidney Neoplasms, 3. Good health, Survival Rate, Treatment Outcome, MESH: Kidney Failure, Chronic, 030220 oncology & carcinogenesis, Female, France, MESH : Time Factors, Adult, medicine.medical_specialty, MESH: Survival Rate, Urology, MESH : Male, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH : Treatment Outcome, Risk Assessment, MESH : Kidney Failure, Chronic, End stage renal disease, MESH : Kaplan-Meier Estimate, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Humans, MESH : Middle Aged, education, MESH : France, Survival rate, Carcinoma, Renal Cell, MESH: Kaplan-Meier Estimate, Aged, Neoplasm Staging, Proportional Hazards Models, Retrospective Studies, MESH: Humans, Chi-Square Distribution, MESH : Chi-Square Distribution, business.industry, MESH: Time Factors, MESH : Humans, MESH: Adult, MESH: Retrospective Studies, medicine.disease, MESH : Proportional Hazards Models, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, MESH: Male, MESH : Kidney Neoplasms, Surgery, Transplantation, MESH: France, Kidney Failure, Chronic, MESH: Kidney Neoplasms, business, Kidney cancer, MESH: Female, Kidney disease
Abstract: International audience; BACKGROUND: Patients with end-stage renal disease (ESRD) are at risk of developing renal tumours. OBJECTIVE: Compare clinical, pathologic, and outcome features of renal cell carcinomas (RCCs) in ESRD patients and in patients from the general population. DESIGN, SETTING, AND PARTICIPANTS: Twenty-four French university departments of urology participated in this retrospective study. INTERVENTION: All patients were treated according to current European Association of Urology guidelines. MEASUREMENTS: Age, sex, symptoms, tumour staging and grading, histologic subtype, and outcome were recorded in a unique database. Categoric and continuous variables were compared by using chi-square and student statistical analyses. Cancer-specific survival (CSS) was assessed by Kaplan-Meier and Cox methods. RESULTS AND LIMITATIONS: The study included 1250 RCC patients: 303 with ESRD and 947 from the general population. In the ESRD patients, age at diagnosis was younger (55 ± 12 yr vs 62 ± 12 yr); mean tumour size was smaller (3.7 ± 2.6 cm vs 7.3 ± 3.8 cm); asymptomatic (87% vs 44%), low-grade (68% vs 42%), and papillary tumours were more frequent (37% vs 7%); and poor performance status (PS; 24% vs 37%) and advanced T categories (≥ 3) were more rare (10% vs 42%). Consistently, nodal invasion (3% vs 12%) and distant metastases (2% vs 15%) occurred less frequently in ESRD patients. After a median follow-up of 33 mo (range: 1-299 mo), 13 ESRD patients (4.3%), and 261 general population patients (27.6%) had died from cancer. In univariate analysis, histologic subtype, symptoms at diagnosis, poor PS, advanced TNM stage, high Fuhrman grade, large tumour size, and non-ESRD diagnosis context were adverse predictors for survival. However, only PS, TNM stage, and Fuhrman grade remained independent CSS predictors in multivariate analysis. The limitation of this study is related to the retrospective design. CONCLUSIONS: RCC arising in native kidneys of ESRD patients seems to exhibit many favourable clinical, pathologic, and outcome features compared with those diagnosed in patients from the general population.
Published: 2011

44. Mutations in the TGFβ binding-protein-like domain 5 of FBN1 are responsible for acromicric and geleophysic dysplasias

Author: Angela F. Brady, Louise Zylberberg, Yasemin Alanay, Gwenaëlle Collod-Béroud, Andrea Superti-Furga, Sally Ann Lynch, Michel Polak, Avinash Abhyankar, André Mégarbané, Martine Le Merrer, Suneel S. Apte, Marie-Pierre Cordier, Carine Le Goff, Arnold Munnich, Clémentine Mahaut, David Sillence, Sacha A. Jensen, Pelin Özlem Şimşek Kiper, Christine Bole-Feysot, Lauren W. Wang, David L. Rimoin, Vicken Topouchian, Patrick Nitschke, Slimane Allali, Koenraad Devriendt, Penny A. Handford, Catherine Boileau, Sylvie Odent, Deborah Krakow, Irene Stolte-Dijkstra, Damien Bonnet, Geert Mortier, Valérie Cormier-Daire, Sheila Unger, Jean-Laurent Casanova, Bernhard Zabel, Marianne Rohrbach, Hiroshi Kitoh, David Geneviève, Çocuk Sağlığı ve Hastalıkları, 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 Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University [New York], Department of Biochemistry [Oxford], University of Oxford, 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), 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), Service de cardiologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Department of Pediatrics, Hacettepe University = Hacettepe Üniversitesi, Service de cytogénétique constitutionnelle, Hospices Civils de Lyon (HCL)-CHU de Lyon-Centre Neuroscience et Recherche, Institute of Child Health, Service de génétique médicale [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Department of Orthopaedic Surgery, Nagoya University, Department of Molecular Cellular and Developmental Biology, University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC)-Howard Hughes Medical Institute (HHMI), Our Lady's hospital for Sick Children, Our Lady's Hospital for Sick Children, Unité de génétique médicale, Université Saint-Joseph de Beyrouth (USJ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Medical Genetics, Universiteit Gent = Ghent University (UGENT), hôpital Sud, Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Clinical Genetics, Academic Department of Medical Genetics, Westmead Hospital [Sydney], Department of Clinical Genetics, Service de Pédiatrie, Université de Lausanne = University of Lausanne (UNIL), Service de chirurgie orthopédique pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Service de Génétique humaine, Centre for Pediatrics and Adolescent Medicine, University of Freiburg [Freiburg]-University Hospital Freiburg, Endocrinologie moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM), Plate Forme Paris Descartes de Bioinformatique (BIP-D), Université Paris Descartes - Paris 5 (UPD5), Génétique Humaine des Maladies Infectieuses (Inserm U980), Service de cardiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), COLLOD-BEROUD, Gwenaëlle, Department of Biomedical Engineering, Cleveland Clinic-Lerner Research Institute, University of Oxford [Oxford], Institut des Sciences de la Terre de Paris (iSTeP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre de Référence Malformations Cardiaques Congénitales Complexes, North West Thames Regional Genetics, Northwick Park Hospital, Service de Génétique, Hospices Civils de Lyon (HCL), Center for Human Genetics, Université Catholique de Louvain (UCL)-Cliniques Universitaires Saint-Luc [Bruxelles], Cellules souches mésenchymateuses, environnement articulaire et immunothérapies de la polyarthrite rhumatoide, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), Departments of Orthopedic Surgery and Human Genetics, University of California-University of California, National Centre for Medical Genetics, Antwerp University Hospital [Edegem] (UZA), Service de Génétique Clinique, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Sud, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Centre National de la Recherche Scientifique (CNRS), service d'endocrinologie, gynécologie, diabétologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Division of Metabolism, University Children's Hospital, Clinical genetics, University Medical Center Groningen [Groningen] (UMCG), Université de Lausanne (UNIL), Medical Genetics Institute, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Bioinformatique, Service de biochimie, d'hormonologie et de génétique moléculaire [CHU Amrboise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré [AP-HP], Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de recherche génomique et physiologie de la lactation (GPL), Institut National de la Recherche Agronomique (INRA), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of California-University of California-Howard Hughes Medical Institute (HHMI), Universiteit Gent = Ghent University [Belgium] (UGENT), Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Génomique et Physiologie de la Lactation (GPL), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, rockefeller university, Ghent University [Belgium] (UGENT), Hôpital Sud, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), 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 ), Cleveland Clinic Foundation-Lerner Research Institute, St Giles laboratory of Human Genetics and Infectious Diseases, Institut des Sciences de la Terre de Paris ( iSTeP ), Centre National de la Recherche Scientifique ( CNRS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), 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 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Hospices Civils de Lyon ( HCL ), Université Catholique de Louvain ( UCL ) -Cliniques Universitaires Saint-Luc [Bruxelles], Université Montpellier 1 ( UM1 ) -IFR3-Institut National de la Santé et de la Recherche Médicale ( INSERM ), University of California at Los Angeles [Los Angeles] ( UCLA ), Université Saint-Joseph de Beyrouth ( USJ ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), University Hospital Antwerp, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Sud, Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140-Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], The Children's Hospital at Westmead, University Medical Center Groningen, Université de Lausanne ( UNIL ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Université Paris Descartes - Paris 5 ( UPD5 ), Génétique Humaine des Maladies Infectieuses ( Inserm U980 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Service de biochimie, d'hormonologie et de génétique moléculaire, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Hémostase, bio-ingénierie et remodelage cardiovasculaires ( LBPC ), Université Paris 13 ( UP13 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Galilée, University of Zurich, and Cormier-Daire, V
Subjects: MESH: Extracellular Matrix Proteins, DNA Mutational Analysis, Fluorescent Antibody Technique, Marfan Syndrome, MESH : Dwarfism, MESH: Protein Structure, Tertiary, Arachnodactyly, 0302 clinical medicine, MESH : Child, MESH: Child, Acromicric dysplasia, Genetics(clinical), Eye Abnormalities, MESH: DNA Mutational Analysis, MESH: Dwarfism, Child, MESH: Fluorescent Antibody Technique, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Exome sequencing, Genetics & Heredity, Inclusion Bodies, 0303 health sciences, Mutation, Extracellular Matrix Proteins, MESH: Middle Aged, 3. Good health, MESH : Connective Tissue, MESH : Phenotype, MESH: Young Adult, Child, Preschool, MESH : Protein Structure, Tertiary, musculoskeletal diseases, MESH : Heterozygote, MESH: Connective Tissue, MESH : Young Adult, Limb Deformities, Congenital, Dwarfism, MESH : DNA Mutational Analysis, MESH: Phenotype, Fibrillins, Article, 03 medical and health sciences, 1311 Genetics, MESH : Adolescent, Genetics, Humans, MESH : Middle Aged, MESH: Adolescent, MESH: Bone Diseases, Developmental, [SDV.GEN]Life Sciences [q-bio]/Genetics, Bone Diseases, Developmental, MESH : Bone Diseases, Developmental, MESH: Humans, MESH : Humans, MESH: Child, Preschool, MESH: Adult, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, Protein Structure, Tertiary, MESH : Microfibrils, MESH : Fluorescent Antibody Technique, Human medicine, MESH : Transforming Growth Factor beta1, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, 030217 neurology & neurosurgery, MESH: Signal Transduction, Candidate gene, Fibrillin-1, MESH : Child, Preschool, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease_cause, MESH: Transforming Growth Factor beta1, MESH : Exons, Genetics (clinical), MESH: Heterozygote, Microfilament Proteins, Exons, MESH : Adult, Middle Aged, MESH: Eye Abnormalities, Weill–Marchesani syndrome, MESH: Microfibrils, Phenotype, Connective Tissue, MESH : Mutation, medicine.symptom, Fibrillin, Signal Transduction, MESH : Limb Deformities, Congenital, Adult, 2716 Genetics (clinical), congenital, hereditary, and neonatal diseases and abnormalities, Heterozygote, MESH: Limb Deformities, Congenital, MESH: Mutation, MESH : Microfilament Proteins, Adolescent, 610 Medicine & health, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Biology, Short stature, MESH: Marfan Syndrome, Transforming Growth Factor beta1, MESH: Microfilament Proteins, Young Adult, MESH : Extracellular Matrix Proteins, MESH : Eye Abnormalities, medicine, [ SDV.BDD ] Life Sciences [q-bio]/Development Biology, 030304 developmental biology, MESH : Signal Transduction, MESH : Marfan Syndrome, MESH: Inclusion Bodies, GENE, MESH : Inclusion Bodies, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, 10036 Medical Clinic, Microfibrils, MESH: Exons, MATRIX
Abstract: International audience; Geleophysic (GD) and acromicric dysplasia (AD) belong to the acromelic dysplasia group and are both characterized by severe short stature, short extremities, and stiff joints. Although AD has an unknown molecular basis, we have previously identified ADAMTSL2 mutations in a subset of GD patients. After exome sequencing in GD and AD cases, we selected fibrillin 1 (FBN1) as a candidate gene, even though mutations in this gene have been described in Marfan syndrome, which is characterized by tall stature and arachnodactyly. We identified 16 heterozygous FBN1 mutations that are all located in exons 41 and 42 and encode TGFb-binding protein-like domain 5 (TB5) of FBN1 in 29 GD and AD cases. Microfibrillar network disorganization and enhanced TGFb signaling were consistent features in GD and AD fibro-blasts. Importantly, a direct interaction between ADAMTSL2 and FBN1 was demonstrated, suggesting a disruption of this interaction as the underlying mechanism of GD and AD phenotypes. Although enhanced TGFb signaling caused by FBN1 mutations can trigger either Marfan syndrome or GD and AD, our findings support the fact that TB5 mutations in FBN1 are responsible for short stature phenotypes.
Published: 2011

45. Plexiform fibrohistiocytic tumor with molecular and cytogenetic analysis

Author: Stéphanie, Leclerc-Mercier, Florence, Pedeutour, Thibault, Fabas, Christophe, Glorion, Nicole, Brousse, Sylvie, Fraitag, Institute of Developmental Biology and Cancer (IBDC), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Service d'Anatomie et Cytologie Pathologique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Service d'anatomie pathologique [CHU Necker], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), 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)-Université Côte d'Azur (UCA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Institute of Developmental Biology and Cancer ( IBDC ), Centre National de la Recherche Scientifique ( CNRS ) -Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP]
Subjects: Granuloma, Skin Neoplasms, Adolescent, Antigens, Differentiation, Myelomonocytic, Sex Chromosome Disorders, Histiocytoma, Malignant Fibrous, Sensitivity and Specificity, Treatment Outcome, Antigens, CD, Cytogenetic Analysis, Humans, Female, [ SDV.BDD ] Life Sciences [q-bio]/Development Biology, Chromosome Deletion, Diagnostic Errors, [SDV.BDD]Life Sciences [q-bio]/Development Biology
Abstract: International audience; A child with plexiform fibrohistiocytic tumor is presented, in whom a superficial biopsy was misdiagnosed as an inflammatory granuloma. Cytogenetic analysis revealed a 46,X,del(X)(q13)[3]/46,XX[23] karyotype. However, fluorescence in situ hybridization (FISH) and array-comparative genomic hybridization (CGH) analysis failed to detect any numerical or quantitative genomic anomaly. Because of lack of specific chromosomal hallmarks, a molecular diagnosis of plexiform fibrohistiocytic tumor with the currently available tools is not reliable.
Published: 2011

46. Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Author: Bastard, Paul, Vazquez, Sara, Liu, Jamin, Laurie, Matthew, Wang, Chung, Gervais, Adrian, Le Voyer, Tom, Bizien, Lucy, Zamecnik, Colin, Philippot, Quentin, Rosain, Jérémie, Catherinot, Emilie, Willmore, Andrew, Mitchell, Anthea, Bair, Rebecca, Garçon, Pierre, Kenney, Heather, Fekkar, Arnaud, Salagianni, Maria, Poulakou, Garyphallia, Siouti, Eleni, Sahanic, Sabina, Tancevski, Ivan, Weiss, Günter, Nagl, Laurenz, Manry, Jérémy, Duvlis, Sotirija, Arroyo-Sánchez, Daniel, Paz Artal, Estela, Rubio, Luis, Perani, Cristiano, Bezzi, Michela, Sottini, Alessandra, Quaresima, Virginia, Roussel, Lucie, Vinh, Donald, Reyes, Luis, Garzaro, Margaux, Hatipoglu, Nevin, Boutboul, David, Tandjaoui-Lambiotte, Yacine, Borghesi, Alessandro, Aliberti, Anna, Cassaniti, Irene, Venet, Fabienne, Monneret, Guillaume, Halwani, Rabih, Sharif-Askari, Narjes, Danielson, Jeffrey, Burrel, Sonia, Morbieu, Caroline, Stepanovskyy, Yurii, Bondarenko, Anastasia, Volokha, Alla, Boyarchuk, Oksana, Gagro, Alenka, Neuville, Mathilde, Neven, Bénédicte, Keles, Sevgi, Hernu, Romain, Bal, Antonin, Novelli, Antonio, Novelli, Giuseppe, Saker, Kahina, Ailioaie, Oana, Antolí, Arnau, Jeziorski, Eric, Rocamora-Blanch, Gemma, Teixeira, Carla, Delaunay, Clarisse, Lhuillier, Marine, Le Turnier, Paul, Zhang, Yu, Mahevas, Matthieu, Pan-Hammarström, Qiang, Abolhassani, Hassan, Bompoil, Thierry, Dorgham, Karim, Gorochov, Guy, Laouenan, Cédric, Rodríguez-Gallego, Carlos, Ng, Lisa, Renia, Laurent, Pujol, Aurora, Belot, Alexandre, Raffi, François, Allende, Luis, Martinez-Picado, Javier, Ozcelik, Tayfun, Imberti, Luisa, Notarangelo, Luigi, Troya, Jesus, Solanich, Xavier, Zhang, Shen-Ying, Puel, Anne, Wilson, Michael, Trouillet-Assant, Sophie, Abel, Laurent, Jouanguy, Emmanuelle, Ye, Chun, Cobat, Aurélie, Thompson, Leslie, Andreakos, Evangelos, Zhang, Qian, Anderson, Mark, Casanova, Jean-Laurent, Derisi, Joseph, Achille, Cristian, Aiuti, Alessandro, Al-Muhsen, Saleh, Al-Mulla, Fahd, Angelini, Micol, Arias, Andrés, Aytekin, Gokhan, Baldanti, Fausto, Feldman, Hagit, Bergami, Federica, Biggs, Catherine, Bogunovic, Dusan, Bolze, Alexandre, Bondarenko, Anastasiia, Bousfiha, Ahmed, Brodin, Petter, Bryceson, Yenan, Bustamante, Carlos, Butte, Manish, Casari, Giorgio, Christodoulou, John, Condino-Neto, Antonio, Constantinescu, Stefan, Conti, Francesca, Cooper, Megan, Dalgard, Clifton, Desai, Murkesh, Drolet, Beth, El Baghdadi, Jamila, Ergun, Recai, Ergun, Dilek, Espinosa-Padilla, Sara, Fellay, Jacques, Flores, Carlos, Franco, José, Froidure, Antoine, Ghirardello, Stefano, Gregersen, Peter, Grimbacher, Bodo, Haerynck, Filomeen, Hagin, David, Hammarström, Lennart, Heath, James, Henrickson, Sarah, Hsieh, Elena, Husebye, Eystein, Imai, Kohsuke, Itan, Yuval, Jarvis, Erich, Kanat, Fikret, Karamitros, Timokratis, Kisand, Kai, Kopcha, Vasyl, Korda, Mykhaylo, Ku, Cheng-Lung, Lau, Yu-Lung, Ling, Yun, Lucas, Carrie, Maniatis, Tom, Mansouri, Davood, Maródi, László, Meyts, Isabelle, Milner, Joshua, Mironska, Kristina, Mogensen, Trine, Mojoli, Francesco, Morandeira, Francisco, Morio, Tomohiro, O'Farrelly, Cliona, Okada, Satoshi, Okamoto, Keisuke, Pagani, Michele, Pape, Jean, de Diego, Rebeca, Perlin, David, Pesole, Graziano, Pession, Andrea, Piralla, Antonio, Planas, Anna, Prando, Carolina, Quintana-Murci, Lluis, Ramaswamy, Sathishkumar, Resnick, Igor, Rigo-Bonnin, Raúl, Sancho-Shimizu, Vanessa, Sediva, Anna, Seppänen, Mikko, Shahrooei, Mohammed, Shcherbina, Anna, Slaby, Ondrej, Snow, Andrew, Soler-Palacín, Pere, Spaan, András, Tangye, Stuart, Abou Tayoun, Ahmad, Tulek, Baykal, Turvey, Stuart, Uddin, K, Uddin, Mohammed, Clément, Bénédicte, Abe-Jones, Yumiko, Asthana, Saurabh, Bhide, Sharvari, Calfee, Carolyn, Carrillo, Sidney, Chak, Suzanna, Collins, Zachary, Erle, David, Fragiadakis, Gabriela, Ghale, Rajani, Hendrickson, Carolyn, Jauregui, Alejandra, Kangelaris, Kirsten, Krummel, Matthew, Langelier, Charles, Lea, Tasha, Lee, Deanna, Leligdowicz, Aleksandra, Leroux, Carolyn, Lota, Raphael, Matthay, Michael, Nguyen, Viet, Patel, Ravi, Pierce, Logan, Prasad, Priya, Rao, Arjun, Rashid, Ahmad, Rodriguez, Nicklaus, Samad, Bushra, Shaw, Cole, Sigman, Austin, Tang, Kevin, Altamirano, Luz, Ward, Alyssa, Woodruff, Prescott, Allavena, Clotilde, Andrejak, Claire, Angoulvant, François, Azoulay, Cecile, Bachelet, Delphine, Bartoli, Marie, Basmaci, Romain, Behilill, Sylvie, Beluze, Marine, Benech, Nicolas, Benkerrou, Dehbia, Bhavsar, Krishna, Bitker, Laurent, Bouadma, Lila, Bouscambert, Maude, Paz, Pauline, Cervantes-Gonzalez, Minerva, Chair, Anissa, Chirouze, Catherine, Coelho, Alexandra, Cordel, Hugues, Couffignal, Camille, Couffin-Cadiergues, Sandrine, D’ortenzio, Eric, de Montmollin, Etienne, Debard, Alexa, Debray, Marie-Pierre, Deplanque, Dominique, Descamps, Diane, Desvallée, Mathilde, Diallo, Alpha, Diehl, Jean-Luc, Diouf, Alphonsine, Dorival, Céline, Dubos, François, Duval, Xavier, Eloy, Philippine, Enouf, Vincent, Epaulard, Olivier, Esperou, Hélène, Esposito-Farese, Marina, Etienne, Manuel, Garot, Denis, Gault, Nathalie, Gaymard, Alexandre, Ghosn, Jade, Gigante, Tristan, Gilg, Morgane, Goehringer, François, Guedj, Jérémie, Hoctin, Alexandre, Hoffmann, Isabelle, Houas, Ikram, Hulot, Jean-Sébastien, Jaafoura, Salma, Kafif, Ouifiya, Kaguelidou, Florentia, Kali, Sabrina, Kerroumi, Younes, Khalil, Antoine, Khan, Coralie, Kimmoun, Antoine, Laine, Fabrice, Laouénan, Cédric, Laribi, Samira, Le, Minh, Le Bris, Cyril, Le Gac, Sylvie, Le Hingrat, Quentin, Le Mestre, Soizic, Le Nagard, Hervé, Lemaignen, Adrien, Lemee, Véronique, Lescure, François-Xavier, Letrou, Sophie, Levy, Yves, Lina, Bruno, Lingas, Guillaume, Lucet, Jean, Machado, Moïse, Malvy, Denis, Mambert, Marina, Manuel, Aldric, Mentré, France, Meziane, Amina, Mouquet, Hugo, Mullaert, Jimmy, Neant, Nadège, Nguyen, Duc, Noret, Marion, Papadopoulos, Aurélie, Paul, Christelle, Peiffer-Smadja, Nathan, Peigne, Vincent, Petrov-Sanchez, Ventzislava, Peytavin, Gilles, Pham, Huong, Picone, Olivier, Piquard, Valentine, Poissy, Julien, Puéchal, Oriane, Rosa-Calatrava, Manuel, Rossignol, Bénédicte, Rossignol, Patrick, Roy, Carine, Schneider, Marion, Su, Richa, Tardivon, Coralie, Tellier, Marie-Capucine, Téoulé, François, Terrier, Olivier, Timsit, Jean-François, Tual, Christelle, Tubiana, Sarah, van der Werf, Sylvie, Vanel, Noémie, Veislinger, Aurélie, Visseaux, Benoit, Wiedemann, Aurélie, Yazdanpanah, Yazdan, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Rockefeller University [New York], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Center for the Study of Primary Immunodeficiencies [Paris], Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Foch [Suresnes], Grand Hôpital de l'Est Francilien (GHEF), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 4th Department of Internal Medicine, ATTIKON University General Hospital, Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Imagine Institute, Goce Delchev University (UGD), Génétique Evolutive Humaine - Human Evolutionary Genetics, and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Subjects: Basic medicine, Settore MED/03, [SDV]Life Sciences [q-bio], Immunology, COVID-19, Pneumònia, Pneumonia, General Medicine
Abstract: International audience; Life-threatening ‘breakthrough’ cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS-CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals (age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto-Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-α2 and IFN-ω, while two neutralized IFN-ω only. No patient neutralized IFN-β. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population.
Published: 2022

47. Effectiveness of chest physiotherapy in infants hospitalized with acute bronchiolitis: a multicenter, randomized, controlled trial

Author: Véronique Abadie, Nicole Beydon, Sylvie Chevret, Jean Bouyer, Philippe Labrune, Loïc de Pontual, Sophie Larrar, Alix Mollet-Boudjemline, Sandrine Katsahian, Vincent Gajdos, Sylvain Bailleux, Bertrand Chevallier, Ralph Epaud, Service de pédiatrie [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biostatistiques et information médicale [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pneumologie [Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de Pédiatrie [Jean Verdier], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], Service d'urgences pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], 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), Service de pédiatrie, urgences enfants [CHU Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], This work was supported by a grant from French Health Ministry (PHRC AOM 03/123) and by a grant from the Association des Réseaux Bronchiolites (ARB)., Autard, Delphine, AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Antoine Béclère, Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris 13 ( UP13 ) -Hôpital Jean Verdier, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de pédiatrie, urgences enfants, and Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré
Subjects: Pediatrics, MESH: Bronchiolitis, MESH: Hospitalization, Respiratory Medicine/Respiratory Infections, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, law.invention, 0302 clinical medicine, Randomized controlled trial, law, 030212 general & internal medicine, MESH: Treatment Outcome, First episode, Human studies, MESH: Respiratory Therapy, MESH : Infant, General Medicine, MESH : Bronchiolitis, MESH: Infant, 3. Good health, Hospitalization, Treatment Outcome, Acute Bronchiolitis, MESH : Hospitalization, Medicine, Bronchiolitis, France, Research Article, Respiratory Therapy, medicine.medical_specialty, MESH : Respiratory Therapy, MESH : Treatment Outcome, Chest physiotherapy, Pediatrics and Child Health/Respiratory Pediatrics, 03 medical and health sciences, 030225 pediatrics, Infectious Diseases/Viral Infections, medicine, Humans, MESH : France, MESH: Humans, business.industry, MESH : Humans, Infant, medicine.disease, Clinical trial, MESH: France, Clinical research, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, business, [ SDV.MHEP.PSR ] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
Abstract: Vincent Gajdos and colleagues report results of a randomized trial conducted among hospitalized infants with bronchiolitis. They show that a physiotherapy technique (increased exhalation and assisted cough) commonly used in France does not reduce time to recovery in this population., Background Acute bronchiolitis treatment in children and infants is largely supportive, but chest physiotherapy is routinely performed in some countries. In France, national guidelines recommend a specific type of physiotherapy combining the increased exhalation technique (IET) and assisted cough (AC). Our objective was to evaluate the efficacy of chest physiotherapy (IET + AC) in previously healthy infants hospitalized for a first episode of acute bronchiolitis. Methods and Findings We conducted a multicenter, randomized, outcome assessor-blind and parent-blind trial in seven French pediatric departments. We recruited 496 infants hospitalized for first-episode acute bronchiolitis between October 2004 and January 2008. Patients were randomly allocated to receive from physiotherapists three times a day, either IET + AC (intervention group, n = 246) or nasal suction (NS, control group, n = 250). Only physiotherapists were aware of the allocation group of the infant. The primary outcome was time to recovery, defined as 8 hours without oxygen supplementation associated with minimal or no chest recession, and ingesting more than two-thirds of daily food requirements. Secondary outcomes were intensive care unit admissions, artificial ventilation, antibiotic treatment, description of side effects during procedures, and parental perception of comfort. Statistical analysis was performed on an intent-to-treat basis. Median time to recovery was 2.31 days, (95% confidence interval [CI] 1.97–2.73) for the control group and 2.02 days (95% CI 1.96–2.34) for the intervention group, indicating no significant effect of physiotherapy (hazard ratio [HR] = 1.09, 95% CI 0.91–1.31, p = 0.33). No treatment by age interaction was found (p = 0.97). Frequency of vomiting and transient respiratory destabilization was higher in the IET + AC group during the procedure (relative risk [RR] = 10.2, 95% CI 1.3–78.8, p = 0.005 and RR = 5.4, 95% CI 1.6–18.4, p = 0.002, respectively). No difference between groups in bradycardia with or without desaturation (RR = 1.0, 95% CI 0.2–5.0, p = 1.00 and RR = 3.6, 95% CI 0.7–16.9, p = 0.10, respectively) was found during the procedure. Parents reported that the procedure was more arduous in the group treated with IET (mean difference = 0.88, 95% CI 0.33–1.44, p = 0.002), whereas there was no difference regarding the assessment of the child's comfort between both groups (mean difference = −0.07, 95% CI −0.53 to 0.38, p = 0.40). No evidence of differences between groups in intensive care admission (RR = 0.7, 95% CI 0.3–1.8, p = 0.62), ventilatory support (RR = 2.5, 95% CI 0.5–13.0, p = 0.29), and antibiotic treatment (RR = 1.0, 95% CI 0.7–1.3, p = 1.00) was observed. Conclusions IET + AC had no significant effect on time to recovery in this group of hospitalized infants with bronchiolitis. Additional studies are required to explore the effect of chest physiotherapy on ambulatory populations and for infants without a history of atopy. Trial registration ClinicalTrials.gov NCT00125450 Please see later in the article for the Editors' Summary, Editors' Summary Background Bronchiolitis, which is usually caused by the respiratory syncytial virus (RSV), is the commonest infection of the lower respiratory tract (the lungs and the passages through which air enters the lungs) in infants. A third of all children have bronchiolitis during their first year of life. The illness begins with stuffiness, a runny nose, a mild cough, and mild fever. Then, as the smallest airways in the lung (the bronchioles) become inflamed (swell) and blocked with mucus, the cough worsens, and the infant may develop a wheeze, shallow breathing, and a rapid heartbeat. Most cases of bronchiolitis are mild and clear up within two weeks without any treatment but some infants develop severe disease. Such infants struggle to get enough air into their lungs, drawing in their chest with each breath (chest recession). They have trouble eating and drinking, and the oxygen level in their blood can drop dangerously low. About 1% of previously healthy infants need hospitalization because of severe bronchiolitis. These severely affected infants are not normally given any medications but, where necessary, they are given oxygen therapy, fed through a tube into their stomach, and given fluids through a vein. Why Was This Study Done? In some countries, chest physiotherapy is routinely given to infants with bronchiolitis even though this is not a recommended treatment internationally. In France, for example, virtually all outpatients with bronchiolitis receive a form of chest physiotherapy known as increased exhalation technique with assisted cough (IET + AC). IET—manual chest compression—is designed to clear mucus from the bronchioles whereas AC—coughing triggered by applying pressure to the top of the breastbone—facilitates clearance of the large airways. But is IET + AC an effective treatment for bronchiolitis? In this study, the researchers undertook a multicenter, randomized, controlled trial to answer this question. A randomized trial is a study in which patients are randomly allocated to receive either the treatment under study or a control treatment. Usually in such trials, noone is aware of the treatment allocations until the trial has been completed. This is called blinding and avoids unconscious biases being introduced into the results. In this trial, although the parents, caregivers, and outcome assessors were blinded, the physiotherapists and the infants were aware of treatment allocations. The physiotherapists were not involved in patient assessment, however, and the infants were sufficiently young that their knowledge of their treatment was unlikely to bias the results. What Did the Researchers Do and Find? The researchers enrolled nearly 500 children aged 15 days to 2 years who were admitted to seven French hospitals for a first episode of acute bronchiolitis. They randomly allocated the patients to receive IET + AC (intervention group) or nasal suction (control group) three times a day from a physiotherapist working alone in a room with blacked-out windows. The primary outcome of the trial was the patients' time to recovery. Infants were judged to have recovered if they had not had oxygen therapy or showed signs of chest recession for 8 hours and had ingested more than two-thirds of their daily food requirement. Infants in the control group took an average of 2.31 days to recover whereas those in the intervention group took 2.02 days. However, this difference in recovery time was not statistically significant. That is, it could have happened by chance. The researchers also recorded several secondary outcomes such as admission to an intensive care unit, help with breathing, antibiotic treatment, and parental perceptions of their child's comfort. There were no significant differences between the two treatment groups for any of these secondary outcomes, although the parents did report that the IET + AC treatment was harder on their children than nasal suction while not reducing their overall comfort. What Do These Findings Mean? These findings show that IET + AC had no significant effect on the time to recovery of a large population of French infants admitted to hospital with severe bronchiolitis. These results cannot be extrapolated, however, to infants with mild or moderate bronchiolitis, and further studies are needed to assess whether chest physiotherapy is of any benefit in an outpatient setting. Three small trials of a different form of chest physiotherapy have also previously failed to find any effect of chest physiotherapy on recovery time. Thus, none of the currently available results support the routine use of chest physiotherapy in infants admitted to a hospital for severe bronchiolitis. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000345 The UK National Health Service Choices Web site provides detailed information on all aspects of bronchiolitis Kidshealth, a resource maintained by the Nemours Foundation (a not-for-profit organization for children's health) provides information for parents on bronchiolitis schizophrenia and on respiratory syncytial virus (in English and Spanish) The British Lung Foundation also provides information on bronchiolitis schizophrenia and on respiratory syncytial virus The MedlinePlus encyclopedia has a page on bronchiolitis schizophrenia (in English and Spanish) The US Centers for Disease Control and Prevention has detailed information on respiratory syncytial virus
Published: 2010

48. Diffuse large B-cell lymphomas with CDKN2A deletion have a distinct gene expression signature and a poor prognosis under R-CHOP treatment: a GELA study

Author: Jardin, Fabrice, Jais, Jean-Philippe, Molina, Thierry-Jo, Parmentier, Françoise, Picquenot, Jean-Michel, Ruminy, Philippe, Tilly, Hervé, Bastard, Christian, Salles, Gilles-André, Feugier, Pierre, Thieblemont, Catherine, Gisselbrecht, Christian, De Reyniès, Aurélien, Coiffier, Bertrand, Haioun, Corinne, Leroy, Karen, Groupe d'étude des proliférations lymphoïdes ( GPL ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Département d'Hématologie, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen ( CLCC Henri Becquerel ), Service informatique médicale et biostatistique, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Département de Pathologie, Hôpital Hôtel-Dieu [Paris], Service d'Hématologie, Hospices Civils de Lyon ( HCL ), Laboratoire de Biologie Moléculaire de la Cellule ( LBMC ), École normale supérieure - Lyon ( ENS Lyon ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Service d'hématologie-oncologie adultes, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], 'Cartes d'Identité des Tumeurs ' program ( CIT ), Ligue Nationale Contre le Cancer, Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), 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 ), Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hospices Civils de Lyon (HCL), Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], 'Cartes d'Identité des Tumeurs ' program (CIT), Ligue Nationale Contre le Cancer (LNCC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), 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)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Ganivet, Agnès, École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, hemic and lymphatic diseases, [ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, neoplasms
Abstract: Genomic alterations play a crucial role in the development and progression of diffuse large B-cell lymphomas (DLBCLs). We determined gene copy number alterations (GCNAs) of TP53, CDKN2A, CDKN1B, BCL2, MYC, REL, and RB1 with a single polymerase chain reaction (PCR) assay (quantitative multiplex PCR of short fragments [QMPSF]) in a cohort of 114 patients with DLBCL to assess their prognostic value and relationship with the gene expression profile. Losses of TP53 and CDKN2A, observed in 8% and 35% of patients, respectively, were significantly associated with a shorter survival after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) treatment, independently of the International Prognostic Index and of the cell of origin. Analysis of the 9p21 genomic region indicated that transcripts encoding p14ARF and p16INK4A were both disrupted in most patients with CDKN2A deletion. These patients predominantly had an activated B-cell profile and showed a specific gene expression signature, characterized by dysregulation of the RB/E2F pathway, activation of cellular metabolism, and decreased immune and inflammatory responses. These features may constitute the molecular basis sustaining the unfavorable outcome and chemoresistance of this DLBCL subgroup. Detection of TP53 and CDKN2A loss by QMPSF is a powerful tool that could be used for patient stratification in future clinical trials.
Published: 2010

49. Defective angiogenesis in hypoplastic human fetal lungs correlates with nitric oxide synthase deficiency that occurs despite enhanced angiopoietin-2 and VEGF

Author: Jacques R. Bourbon, Virginie Masse, Jelena Martinovic, Bernard Thébaud, Caroline Elie, Olivier Boucherat, Alexandra Benachi, Christophe Delacourt, Marie-Laure Franco-Montoya, Centre de Recherche en Cancérologie, Université Laval, 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 ), PremUp Foundation, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Sorbonne Universités-Université Paris Descartes - Paris 5 ( UPD5 ) -CHI Créteil-Institut de Recherche pour le Développement ( IRD ) -Université Paris-Sud - Paris 11 ( UP11 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ), Service de foetopathologie, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Department of Pediatrics-Division of Neonatology, University of Alberta [Edmonton], Service d'Obstétrique et Gynécologie, Université Laval [Québec] (ULaval), 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 de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], University of Alberta, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Descartes - Paris 5 (UPD5)-CHI Créteil-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Guellaen, Georges
Subjects: Vascular Endothelial Growth Factor A, MESH : Hypertension, Pulmonary, Physiology, Angiogenesis, Neovascularization, 0302 clinical medicine, MESH: Pregnancy, Pregnancy, MESH : Angiopoietin-2, MESH : Angiopoietin-1, MESH : Female, Lung, 0303 health sciences, biology, Neovascularization, Pathologic, Nitric Oxide Synthase Type III, Receptor, TIE-2, MESH: Receptor, TIE-2, 3. Good health, Nitric oxide synthase, Vascular endothelial growth factor A, medicine.anatomical_structure, 030220 oncology & carcinogenesis, MESH : Vascular Endothelial Growth Factor A, Female, medicine.symptom, MESH: Nitric Oxide Synthase Type III, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Hypertension, Pulmonary, MESH : Lung, MESH : Nitric Oxide Synthase Type III, Article, Angiopoietin-2, 03 medical and health sciences, MESH: Angiopoietin-1, MESH: Angiopoietin-2, Physiology (medical), Internal medicine, medicine, Angiopoietin-1, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Receptor, TIE-2, Humans, MESH: Lung, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, MESH: Humans, MESH: Hypertension, Pulmonary, business.industry, MESH: Vascular Endothelial Growth Factor A, MESH : Humans, Congenital diaphragmatic hernia, MESH : Neovascularization, Pathologic, Cell Biology, medicine.disease, Pulmonary hypertension, MESH : Pregnancy, Endocrinology, biology.protein, business, MESH: Neovascularization, Pathologic, MESH: Female
Abstract: International audience; Lung hypoplasia (LH) is a life-threatening congenital abnormality with various causes. It involves vascular bed underdevelopment with abnormal arterial muscularization leading to pulmonary hypertension. Because underlying molecular changes are imperfectly known and sometimes controversial, we determined key factors of angiogenesis along intrauterine development, focusing at the angiopoietin (ANG)/Tie-2 system. Lung specimens from medical terminations of pregnancy (9-37 wk) were used, including LH due to congenital diaphragmatic hernia (CDH) or other causes, and nonpulmonary disease samples were used as controls. ELISA determination indicated little ANG-1 change during pregnancy and no effect of LH, whereas Tie-2 declined similarly between 9 and 37 wk in LH and controls. By contrast, ANG-2 markedly increased in LH from 24 wk, whereas it remained stable in controls. Because VEGF increased also, this was interpreted as an attempt to overcome vascular underdevelopment. Hypothesizing that its inefficiency might be due to impaired downstream mechanism, endothelial nitric oxide synthase (eNOS) was determined by semiquantitative Western blot and found to be reduced by approximately 75%, mostly in the instance of CDH. In conclusion, angiogenesis remains defective in hypoplastic lungs despite reactive enhancement of VEGF and ANG-2 production, which could be due, at least in part, to insufficient eNOS expression.
Published: 2010

50. Retrospective French nationwide survey of childhood aggressive vascular anomalies of bone, 1988-2009

Author: Jean-Claude Léonard, Pierre Mary, Michèle Bigorre, Jacques de Blic, Ralph Epaud, Makram Ziade, Marion Gillibert-Yvert, Isabelle Pin, Martine Le Merrer, Sébastien Héritier, Benoit de Courtivron, Marie Ouache, Véronique Houdoin, Brigitte Fauroux, Jeanne Wagnon, Pascal Chastagner, Francis Jaubert, Daniel Wendling, Christian Carrie, Liliane Boccon-Gibod, Jean Donadieu, J. Languepin, Véronique Forin, Yann Revillon, Yves Bertrand, Cécile Bost-Bru, Hubert Ducou Lepointe, Service de Génétique Médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Service d'AnatomoPathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Conception et Test de Systèmes MICroélectroniques (SysMIC), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Necker - Enfants Malades [AP-HP], Département de Pédiatrie - CHRU de Grenoble, CHU Grenoble, Agents pathogènes et inflammation - UFC (EA 4266) (API), Université de Franche-Comté (UFC), Physiologie, biologie des organismes, populations, interactions, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pneumologie [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Centre de référence des Histiocytoses, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire [Grenoble] (CHU), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (UMRS893), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Conception et Test de Systèmes MICroélectroniques ( SysMIC ), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier ( LIRMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Agents pathogènes et inflammation - UFC (EA 4266) ( API ), Université de Franche-Comté ( UFC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de pneumologie, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Service d'hématologie-immunologie-oncologie pédiatrique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: Male, medicine.medical_specialty, Pediatrics, Pleural effusion, Vascular Malformations, medicine.medical_treatment, Alpha interferon, lcsh:Medicine, Kaplan-Meier Estimate, 030218 nuclear medicine & medical imaging, [ SDV.MHEP.RSOA ] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, 03 medical and health sciences, 0302 clinical medicine, Epidemiology, medicine, Humans, Genetics(clinical), Pharmacology (medical), Child, Genetics (clinical), Retrospective Studies, Medicine(all), Respiratory distress, Diphosphonates, business.industry, Mortality rate, Research, lcsh:R, Interferon-alpha, General Medicine, Bone fracture, medicine.disease, 3. Good health, Radiation therapy, Thalidomide, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, 030220 oncology & carcinogenesis, Female, France, Bone Diseases, business, medicine.drug
Abstract: Objective To document the epidemiological, clinical, histological and radiological characteristics of aggressive vascular abnormalities of bone in children. Study design Correspondents of the French Society of Childhood Malignancies were asked to notify all cases of aggressive vascular abnormalities of bone diagnosed between January 1988 and September 2009. Results 21 cases were identified; 62% of the patients were boys. No familial cases were observed, and the disease appeared to be sporadic. Mean age at diagnosis was 8.0 years [0.8-16.9 years]. Median follow-up was 3 years [0.3-17 years]. The main presenting signs were bone fracture (n = 4) and respiratory distress (n = 7), but more indolent onset was observed in 8 cases. Lung involvement, with lymphangiectasies and pleural effusion, was the most frequent form of extraosseous involvement (10/21). Bisphosphonates, alpha interferon and radiotherapy were used as potentially curative treatments. High-dose radiotherapy appeared to be effective on pleural effusion but caused major late sequelae, whereas antiangiogenic drugs like alpha interferon and zoledrenate have had a limited impact on the course of pulmonary complications. The impact of bisphosphonates and alpha interferon on bone lesions was also difficult to assess, owing to insufficient follow-up in most cases, but it was occasionally positive. Six deaths were observed and the overall 10-year mortality rate was about 30%. The prognosis depended mainly on pulmonary and spinal complications. Conclusion Aggressive vascular abnormalities of bone are extremely rare in childhood but are lifethreatening. The impact of anti-angiogenic drugs on pulmonary complications seems to be limited, but they may improve bone lesions.
Published: 2010

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