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1. Cancer stem cells: beyond Koch's postulates

Author: Philippe Naveilhan, Emmanuel Garcion, Didier Wion, François Berger, Ingénierie de la vectorisation particulaire, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de recherche sur l'immunointervention dans les allo et xénotransplantations, Hôtel-Dieu de Nantes-INSERM-Institut de Transplantation Urologie-Néphrologie (ITUN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Nanomédecine et Cerveau, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), and wion, didier
Subjects: MESH: Cell Differentiation, Cancer Research, medicine.medical_specialty, cancer stem cell, Cellular differentiation, [SDV]Life Sciences [q-bio], targeted therapies 2, Biology, Infections, Models, Biological, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Medical microbiology, Cancer stem cell, Koch's postulates, Neoplasms, medicine, Humans, cancer, MESH: Neoplasms, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH: Humans, MESH: Models, Biological, Cancer, Medical reasoning, Cell Differentiation, Neoplasms surgery, medicine.disease, MESH: Neoplastic Stem Cells, 3. Good health, Germ theory of disease, [SDV] Life Sciences [q-bio], Oncology, 030220 oncology & carcinogenesis, Immunology, symbols, Neoplastic Stem Cells, MESH: Cell Division, Neuroscience, MESH: Infection, Cell Division, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Until the last century, infectious diseases were the leading cause of human mortality. Therefore, our current medical reasoning is profoundly influenced by views that originated from medical microbiology. The notion that cancer growth is sustained by a sub-population of particular cells, the cancer stem cells, is highly reminiscent of the germ theory of disease as exemplified by Koch's postulates in the XIX th century. However, accumulating data underscore the importance of cell-cell interactions and tumor environment. Hence it is essential to critically review the basic tenets of the cancer stem cell concept on the light of their relationships with Koch's postulates. Shifting the pathogenic element from a special cellular entity (cancer stem cell or microorganism) to a " pathogenic field " could be critical for curing both cancer and drug-resistant infectious diseases.
Published: 2009
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2. Unique and specific Agrobacterium diversity in urinary microbiota of tolerant kidney transplanted recipients

Author: Colas, Luc, Mongodin, Emmanuel, Montassier, Emmanuel, Chesneau, Mélanie, Guérif, Pierrick, Hittle, Lauren, Giral, Magali, Bromberg, Jonathan, Brouard, Sophie, Blancho, Gilles, Branchereau, Julien, Cantarovich, Diego, Cesbron, Anne, Chapelet, Agnès, Dantal, Jacques, Delbos, Florent, Deltombe, Clement, Devis, Anne, Figueres, Lucile, Garandeau, Claire, Gourraud‐Vercel, Caroline, Hourmant, Maryvonne, Kandell, Christine, Karam, Georges, Kerleau, Clarisse, Meurette, Aurelie, Moreau, Anne, Renaudin, Karine, Ville, Simon, Walencik, Alexandre, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Dynamique cellulaire et moléculaire de la muqueuse respiratoire, Université de Reims Champagne-Ardenne (URCA)-IFR53-Institut National de la Santé et de la Recherche Médicale (INSERM), Thérapeutiques cliniques et expérimentales des infections (EA 3826) (EA 3826), Université de Nantes (UN)-Université de Nantes (UN), Institute of Transplantation Urology and Nephrology [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Etablissement Français du Sang [Nantes], Service de Néphrologie et Immunologie Clinique, Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôtel Dieu, Développement du Systeme Immunitaire, 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'urologie, Hôtel-Dieu, Institut de Mathématiques de Jussieu (IMJ), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), This work was carried out with the support of CENTAURE foundation grants, a Roche Organ Transplantation Research Foundation and European Society for Organ Transplantation grant, and under the auspices of the IHU‐Cesti project, which received French government financial support managed by the National Research Agency via the 'Investment Into The Future' program (ANR‐10‐IBHU‐005). The IHU‐Cesti project is also supported by Nantes Metropole and the Pays de la Loire Region. This work was also supported by the Labex IGO project (ANR‐11‐LABX‐0016‐01) funded by the Investissements d'Avenir French Government program, managed by the French National Research Agency., Le Bihan, Sylvie, Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Hôtel Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: Adult, Graft Rejection, Male, medicine.medical_specialty, translational research/science, Urinary system, kidney transplantation/nephrology, immunosuppression/immune modulation, 030230 surgery, clinical research/practice, Organ transplantation, 03 medical and health sciences, 0302 clinical medicine, Immune system, Risk Factors, RNA, Ribosomal, 16S, Proteobacteria, Immune Tolerance, medicine, Humans, Immunology and Allergy, Pharmacology (medical), Microbiome, Kidney transplantation, Transplantation, Kidney, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, tolerance, biology, business.industry, Graft Survival, Biodiversity, Middle Aged, Prognosis, medicine.disease, biology.organism_classification, Kidney Transplantation, 3. Good health, Calcineurin, medicine.anatomical_structure, Case-Control Studies, Immunology, Female, business, microbiomics, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies
Abstract: International audience; Host‐microbiota interactions can modulate the immune system both at local and systemic levels, with potential consequences for organ transplantation outcomes. In this study, we hypothesized that differences in the urinary microbiome following kidney transplantation would be associated with posttransplantation status: stable, minimally immunosuppressed, or tolerant. One hundred thirteen urine samples from stable (n = 51), minimally immunosuppressed (n = 19), and spontaneously tolerant (n = 16) patients, paired with age‐matched controls (n = 27) were profiled and compared to each other at a taxonomic level with special interest in the immunosuppressive regimen. All comparisons and correlations were adjusted on sex and time posttransplantation. Our results highlighted a unique and specific urinary microbiota associated with spontaneous tolerance characterized by a high diversity and a clear Proteobacteria profile. Finally, we report that this profile is (1) impacted by gender, (2) inversely correlated with immunosuppressive drugs (calcineurin inhibitors and mammalian target of rapamycin inhibitors), and (3) stable in time.
Published: 2019
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3. High-flow Nasal Cannulae Versus Non-invasive Ventilation for Preoxygenation of Obese Patients: The PREOPTIPOP Randomized Trial

Author: Eric Mirallié, Fanny Feuillet, Claire Blanchard, Mickael Vourc'h, Samir Jaber, Karim Asehnoune, Christophe Guitton, Gabrielle Baud, MORNET, Dominique, Centre hospitalier universitaire de Nantes (CHU Nantes), Biostatistique, Recherche Clinique et Mesures Subjectives en Santé, Université de Nantes (UN), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), General and Digestive Surgery Department, Clinique de chirurgie digestive et endocrinienne, IMAD, Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Centre Hospitalier Le Mans (CH Le Mans), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Apnoeic oxygenation, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Laryngoscopy, 01 natural sciences, law.invention, Morbid obesity, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Preoxygenation, medicine, Intubation, 030212 general & internal medicine, 0101 mathematics, lcsh:R5-920, medicine.diagnostic_test, business.industry, 010102 general mathematics, Apnea, General Medicine, Institutional review board, High-flow oxygen therapy by nasal cannulae, 3. Good health, Clinical trial, [SDV] Life Sciences [q-bio], Pulse oximetry, Anesthesia, Breathing, Non-invasive ventilation, medicine.symptom, lcsh:Medicine (General), business, Research Paper
Abstract: Background: In obese patients, preoxygenation with non-invasive ventilation (NIV) was reported to improve outcomes compared with facemask. In this setting, high-flow nasal cannulae (HFNC) used before and during intubation has never been studied against NIV. Methods: The PREOPTIPOP study is a randomised, single-centre, open-labelled, controlled trial including obese patients requiring intubation before scheduled surgery. Patients were randomised to receive preoxygenation by HFNC or NIV. HFNC was maintained throughout intubation whereas NIV was removed when apnea occurred to perform laryngoscopy. The study was designed to assess the superiority of HNFC. The primary outcome was the lowest level of end-tidal oxygen concentration (EtO2) within 2 min after intubation. Secondary outcomes included drop in pulse oximetry and complications related to intubation. Main findings: A total of 100 patients were randomised. The intent-to-treat analysis found median [IQR] lowest EtO2 of 76% [66–82] for HFNC and 88% [82–90] for NIV (mean difference − 12·1 [−15·1 to −8·5], p
Published: 2019
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4. Clinical and genetic heterogeneity in familial steroid-sensitive nephrotic syndrome

Author: Imen Chabchoub, Didier Lacombe, Marion Sallée, Phillippe Dolhem, Dominique Durand, Karin Dahan, Pierre Ronco, Eric Rondeau, Sylvie Cloarec, Julien Hogan, Gérard Champion, David Ribes, Hubert Nivet, Laurent Mesnard, Georges Deschênes, Thierry Krummel, Khalil El Karoui, Claire Pouteil Noble, Christine Pietrement, Yahsou Delmas, Olivier Gribouval, Olivia Boyer, Tim Ulinski, N. Mohsin, Patrick Niaudet, Guillaume Dorval, Aurélie Hummel, Vanesa Martinez-Barquero, Mongia Hachicha, Véronique Baudouin, Corinne Antignac, Marie-Josèphe Tête, Michel Fischbach, Paloma Maria Parvex, Hassib Chehade, Rémi Salomon, Brigitte Llanas, Dominique Chauveau, Jacques Dantal, Jean-Pierre Grünfeld, S. Benoit, Nassim Kamar, Loïc de Pontual, Eduardo Machuca, Pierre Cochat, Vincent Guigonis, Maryvonne Hourmant, Zelal Ekinci, Chokri Chouchane, Michel Tsimaratos, Laboratoire des Maladies Rénales Héréditaires, 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 Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Molecular bases of hereditary kidney diseases: nephronophthisis and hypodysplasia (Equipe Inserm U1163), Néphropathies héréditaires et rein en développement (UMR_S 983), CHU Necker - Enfants Malades [AP-HP]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service de neuropédiatrie et maladies métaboliques [CHU Robert-Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hedi Chaker Hospital [Sfax], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Département de Néphrologie et Transplantation d'organes, Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Université de Monastir - University of Monastir (UM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Département de Pédiatrie, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institute of Pathology and Genetics, Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Service de néphrologie et pédiatrie générale [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Centre hospitalier de Saint-Quentin, Unité Mixte de Recherches sur les Herbivores - UMR 1213 (UMRH), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA), Kocaeli Academy for Solidarity, Centre d'infectiologie Necker-Pasteur [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Service de Pédiatrie, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Service de néphrologie pédiatrique [CHU Necker], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Department of Pediatrics, Service de Néphrologie pédiatrique [Hôpital Robert Debré, Paris], Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Service de néphrologie et hémodialyse [CHU de Strasbourg], CHU Strasbourg, Service de génétique médicale, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre de Référence du Sud Ouest des Maladies Rénales Rares, CHU Toulouse [Toulouse]-Hôpital des Enfants, 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), Sultan Qaboos University (SQU), Service de Néphrologie, Hôpital de Clocheville, Geneva University Hospital (HUG), Centre Hospitalier Universitaire de Reims (CHU Reims)-American Memorial Hospital (Reims), Hôpital Jean Verdier [Bondy], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Tenon [APHP], Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Centre recherche en CardioVasculaire et Nutrition (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Néphrologie Pédiatrique [Trousseau], 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)-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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Département de Néphrologie et Transplantation d'organes [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [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), Hôpital Jean Verdier [AP-HP], CHU Tenon [AP-HP], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), 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), Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris], Hôpital Robert Debré-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)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, Glucocorticoids/therapeutic use, Adult, Male, Nephrotic Syndrome, Adolescent, Nephrotic Syndrome/drug therapy/genetics, 030232 urology & nephrology, Disease, Biology, medicine.disease_cause, HLA-DQ alpha-Chains, 03 medical and health sciences, Genetic Heterogeneity, Young Adult, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], HLA-DQ alpha-Chains/genetics, medicine, Humans, Genetic Predisposition to Disease, Young adult, Preschool, Child, Gene, Glucocorticoids, Exome sequencing, ComputingMilieux_MISCELLANEOUS, Genetics, Mutation, ddc:618, Membrane Glycoproteins, Genetic heterogeneity, Infant, Sequence Analysis, DNA, Membrane Glycoproteins/genetics, Middle Aged, medicine.disease, 3. Good health, DNA/methods, 030104 developmental biology, Nephrology, Child, Preschool, Pediatrics, Perinatology and Child Health, Cohort, Female, Nephrotic syndrome, Sequence Analysis
Abstract: Familial steroid-sensitive nephrotic syndrome (SSNS) is a rare condition. The disease pathophysiology remains elusive. However, bi-allelic mutations in the EMP2 gene were identified, and specific variations in HLA-DQA1 were linked to a high risk of developing the disease. Clinical data were analyzed in 59 SSNS families. EMP2 gene was sequenced in families with a potential autosomal recessive (AR) inheritance. Exome sequencing was performed in a subset of 13 families with potential AR inheritance. Two variations in HLA-DQA1 were genotyped in the whole cohort. Transmission was compatible with an AR (n = 33) or autosomal dominant (AD, n = 26) inheritance, assuming that familial SSNS is a monogenic trait. Clinical features did not differ between AR and AD groups. All patients, including primary (n = 7) and secondary steroid resistant nephrotic syndrone (SRNS), (n = 13) were sensitive to additional immunosuppressive therapy. Both HLA-DQA1 variations were found to be highly linked to the disease (OR = 4.34 and OR = 4.89; p
Published: 2018
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5. Risk factors and outcomes for airway failure versus non-airway failure in the intensive care unit: a multicenter observational study of 1514 extubation procedures

Author: Julien Pottecher, Elie Azoulay, C. Ichai, Gerald Chanques, Raphaël Cinotti, Bernard Claud, Nicolas Molinari, Christophe Guitton, Karim Asehnoune, Jean-Michel Arnal, Hervé Quintard, Gaëtan Plantefève, Zied Hajjej, Samir Jaber, Audrey De Jong, Philippe Corne, Sigismond Lasocki, Laurent Papazian, Paer Abback, Catherine Paugam-Burtz, Armand Mekontso Dessap, Karim Lakhal, MORNET, Dominique, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), Institut de pharmacologie moléculaire et cellulaire (IPMC), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Réanimation polyvalente, Hopital Font-Pre, Sainte Musse Hospital, Toulon, Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Beaujon [AP-HP], INSERM U955, équipe 13, Service d'anesthésie-réanimation SAMU94-SMUR94 [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-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)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CH Argenteuil, General Hospital Centre, Mitochondries, stress oxydant et protection musculaire (Strasbourg), Mitochondrie, stress oxydant et protection musculaire (MSP), Université de Strasbourg (UNISTRA)-Université de Strasbourg (UNISTRA), Université de Strasbourg (UNISTRA), Département d'anesthésie-réanimation[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier], Centre Hospitalier Universitaire de Nice (CHU Nice), Mathématiques, Informatique et STatistique pour l'Environnement et l'Agronomie (MISTEA), Institut National de la Recherche Agronomique (INRA)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Unité de Recherche sur les Maladies Infectieuses Tropicales Emergentes (URMITE), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Service de réanimation médicale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], 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 ), Institut de pharmacologie moléculaire et cellulaire ( IPMC ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Assistance publique - Hôpitaux de Paris (AP-HP) ( APHP ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) ( APHP ) -Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre Hospitalier Universitaire d'Angers ( CHU Angers ), PRES Université Nantes Angers Le Mans ( UNAM ), Centre Hospitalier Victor Dupouy, Mitochondrie, stress oxydant et protection musculaire ( MSP ), Université de Strasbourg ( UNISTRA ) -Université de Strasbourg ( UNISTRA ), Université Montpellier 1 ( UM1 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Gui de Chauliac [Montpellier], Service de réanimation, Centre Hospitalier Universitaire de Nice ( CHU Nice ) -Hôpital St Roch, Optimal and secure management of manufacturing systems ( COSTEAM ), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Université Paul Verlaine - Metz ( UPVM ), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes ( URMITE ), Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR48, INSB-INSB-Centre National de la Recherche Scientifique ( CNRS ), Medical ICU, Assistance publique - Hôpitaux de Paris (AP-HP) ( APHP ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, 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)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut Mondor de Recherche Biomédicale (IMRB), INSB-INSB-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Université de Montpellier (UM)-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)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)
Subjects: Male, Time Factors, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Critical Care and Intensive Care Medicine, law.invention, 0302 clinical medicine, Risk Factors, law, Extubation, Outcome Assessment, Health Care, Clinical endpoint, Intubation, Prospective Studies, Airway Management, ComputingMilieux_MISCELLANEOUS, Non-airway, weaning, weaning, lcsh:Medical emergencies. Critical care. Intensive care. First aid, Middle Aged, respiratory system, Intensive care unit, 3. Good health, [SDV] Life Sciences [q-bio], Intensive Care Units, Anesthesia, Female, medicine.symptom, Non-airway, Tracheal tube, 03 medical and health sciences, Intensive care, medicine, Humans, Aged, Mechanical ventilation, Coma, [ SDV ] Life Sciences [q-bio], business.industry, 030208 emergency & critical care medicine, lcsh:RC86-88.9, Length of Stay, Respiration, Artificial, respiratory tract diseases, Airway, Logistic Models, 030228 respiratory system, Multivariate Analysis, Airway Extubation, business
Abstract: Background Patients liberated from invasive mechanical ventilation are at risk of extubation failure, including inability to breathe without a tracheal tube (airway failure) or without mechanical ventilation (non-airway failure). We sought to identify respective risk factors for airway failure and non-airway failure following extubation. Methods The primary endpoint of this prospective, observational, multicenter study in 26 intensive care units was extubation failure, defined as need for reintubation within 48 h following extubation. A multinomial logistic regression model was used to identify risk factors for airway failure and non-airway failure. Results Between 1 December 2013 and 1 May 2015, 1514 patients undergoing extubation were enrolled. The extubation-failure rate was 10.4% (157/1514), including 70/157 (45%) airway failures, 78/157 (50%) non-airway failures, and 9/157 (5%) mixed airway and non-airway failures. By multivariable analysis, risk factors for extubation failure were either common to airway failure and non-airway failure: intubation for coma (OR 4.979 (2.797–8.864), P 8 days (OR 1.956 (1.087–3.518), P = 0.025), copious secretions (OR 4.066 (2.268–7.292), P
Published: 2018
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6. Interleukin-22 level is negatively correlated with neutrophil recruitment in the lungs in a Pseudomonas aeruginosa pneumonia model

Author: Broquet, Alexis, Jacqueline, Cédric, Davieau, Marion, Besbes, Anissa, Roquilly, Antoine, Martin, Jérôme, Caillon, Jocelyne, Dumoutier, Laure, Renauld, Jean-Christophe, Heslan, Michèle, Josien, Régis, Asehnoune, Karim, Cédric, Jacqueline, Thérapeutiques cliniques et expérimentales des infections (EA 3826) (EA 3826), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de Soins Intensifs et Anesthésie-Réanimation, Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Fluides, automatique, systèmes thermiques (FAST), Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Ludwig Institute for Cancer Research, Experimental Medicine Unit, Université Catholique de Louvain = Catholic University of Louvain (UCL), Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Laboratoire d’Immunologie, Centre d’Immunomonitorage Nantes Atlantique (CIMNA), Centre hospitalier universitaire de Nantes (CHU Nantes), and Service d'anesthésie et réanimation chirurgicale [Nantes]
Subjects: [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, actue respiratory distress syndrome, interleukin-22, Pseudomonas aeruginosa, Neutrophil, Host response, Pneumonia
Abstract: International audience; Pseudomonas aeruginosa is a major threat for immune-compromised patients. Bacterial pneumonia can induce uncontrolled and massive neutrophil recruitment ultimately leading to acute respiratory distress syndrome and epithelium damage. Interleukin-22 plays a central role in the protection of the epithelium. In this study, we aimed to evaluate the role of interleukin-22 and its soluble receptor IL-22BP in an acute Pseudomonas aeruginosa pneumonia model in mice. In this model, we noted a transient increase of IL-22 during Pseudomonas aeruginosa challenge. Using an antibody-based approach, we demonstrated that IL-22 neutralisation led to increased susceptibility to infection and to lung damage correlated with an increase in neutrophil accumulation in the lungs. On the contrary, rIL-22 administration or IL-22BP neutralisation led to a decrease in mouse susceptibility and lung damage associated with a decrease in neutrophil accumulation. This study demonstrated that the IL-22/IL-22BP system plays a major role during Pseudomonas aeruginosa pneumonia by moderating neutrophil accumulation in the lungs that ultimately leads to epithelium protection. Pneumonia induced by Pseudomonas aeruginosa (PA), a Gram-negative opportunistic bacteria, is a major threat for immune-compromised patients 1. During infection, the host must activate a robust but adapted immune response against the pathogen while protecting the integrity and the functionality of the lungs. In the early period of pulmonary infection, there is massive polymorphonuclear neutrophil (PMN) recruitment generating oedema and tissue damage through the generation of an oxidative burst and pro-inflammatory microenvironment. Deregulated and overwhelming activation of PMN can lead to destruction of the alveolar-capillary barrier and to acute respiratory distress syndrome (ARDS) 2. Interleukin (IL)-22 is a member of the IL-10 superfamily and is currently described as the cytokine of epithelium protection.
Published: 2017
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7. Low-Dose Pesticide Mixture Induces Senescence in Normal Mesenchymal Stem Cells (MSC) and Promotes Tumorigenic Phenotype in Premalignant MSC

Author: Dominique Heymann, Jérôme Alexandre Denis, Jérôme Amiaud, Christophe Olivier, Lisa Oliver, Pierre Avril, François M. Vallette, Mazène Hochane, Valérie Trichet, Philippe Naveilhan, Alain Pineau, Claire Pecqueur, Régis Brion, Apoptosis and Tumor Progression (CRCINA-ÉQUIPE 9), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Physiopathologie des Adaptations Nutritionnelles (PhAN), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Interfaces, Confinement, Matériaux et Nanostructures ( ICMN), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Laboratoire de Biologie des Cancers et de Théranostic [St Herblain, Nantes] (LabCT), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN), Vallette, Francois, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bernardo, Elizabeth, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Service de pharmacologie et de Toxicologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Neuropathies du système nerveux entérique et pathologies digestives, implication des cellules gliales entériques, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Laboratoire de Biologie des Cancers et de Théranostic (LabCT)
Subjects: 0301 basic medicine, Senescence, Stromal cell, senescence, Carcinogenesis, Cellular differentiation, Cell, Cell Respiration, Mice, Nude, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, medicine.disease_cause, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Stress, Physiological, medicine, Animals, Humans, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Cellular Senescence, Genetics, mesenchymal stem cells, Adipogenesis, Mesenchymal stem cell, Endothelial Cells, Cell Differentiation, Cell Biology, pesticides, Fibroblasts, Phenotype, 3. Good health, tumorigenesis, 030104 developmental biology, medicine.anatomical_structure, 13. Climate action, Cancer research, pesticide mixture, Molecular Medicine, Female, Tumor Suppressor Protein p53, Reactive Oxygen Species, Precancerous Conditions, Developmental Biology
Abstract: International audience; Humans are chronically exposed to multiple environmental pollutants such as pesticides with no significant evidence about the safety of such poly-exposures. We exposed mesenchymal stem cells (MSC) to very low doses of mixture of seven pesticides frequently detected in food samples for 21 days in vitro. We observed a permanent phenotype modification with a specific induction of an oxidative stress-related senescence. Pesticide mixture also induced a shift in MSC differentiation towards adipogenesis but did not initiate a tumorigenic transformation. In modified MSC in which a premalignant phenotype was induced, the exposure to pesticide mixture promoted tumorigenic phenotype both in vitro and in vivo after cell implantation, in all nude mice. Our results suggest that a common combination of pesticides can induce a premature ageing of adult MSC, and as such could accelerate age-related diseases. Exposure to pesticide mixture may also promote the tumorigenic transformation in a predisposed stromal environment. STEM CELLS 2017;35:800-811 SIGNIFICANCE STATEMENT The environmental exposure to pesticides is recognized as a potential threat to human health. However, little is known on the effect of pesticides on stem cells. Here we show that a pesticide mixture, at doses commonly found in western diet, promotes stress-related senescence in normal MSC and tumorigenesis in premalignant MSC. Our results provide a new insight in the effect of pesticides on the acceleration of stem cell ageing and possibly on cancer.
Published: 2017
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8. Ex Vivo Expanded Human Non-Cytotoxic CD8+CD45RClow/-Tregs Efficiently Delay Skin Graft Rejection and GVHD in Humanized Mice

Author: Bézie, Séverine, Meistermann, Dimitri, Boucault, Laetitia, Kilens, Stéphanie, Zoppi, Johanna, Autrusseau, Elodie, Donnart, Audrey, Nerrière-Daguin, Véronique, Bellier-Waast, Frédérique, Charpentier, Eric, Duteille, Franck, David, Laurent, Anegon, Ignacio, Guillonneau, Carole, Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Genetic and Cellular Engineering in Immunology and Regenerative Medicine (Team 2 - U1064 Inserm - CRTI), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), LabEx IGO 'Immunotherapy, Graft, Oncology' [Nantes], Service de Biologie de la Reproduction [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Equipe labellisée Ligue contre le Cancer, Service de Chirurgie Plastique et des Brulés [CHU Nantes], Ingénierie des Matériaux Polymères (IMP), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-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, and LabEX IGO Immunothérapie Grand Ouest
Subjects: Treg, tolerance, NSG mice, graft, [SDV]Life Sciences [q-bio], Immunology, gVhD, hemic and immune systems, chemical and pharmacologic phenomena, cell therapy, Original Research, transplantation
Abstract: International audience; Both CD4+and CD8+Tregs play a critical role in the control of immune responses and immune tolerance; however, our understanding of CD8+Tregs is limited while they are particularly promising for therapeutic application. We report here existence of highly suppressive human CD8+CD45RClow/-Tregs expressing Foxp3 and producing IFNγ, IL-10, IL-34, and TGFβ to mediate their suppressive activity. We demonstrate that total CD8+CD45RClow/-Tregs can be efficiently expanded in the presence of anti-CD3/28 mAbs, high-dose IL-2 and IL-15 and that such expanded Tregs efficiently delay GVHD and human skin transplantation rejection in immune humanized mice. Robustly expanded CD8+Tregs displayed a specific gene signature, upregulated cytokines and expansion in the presence of rapamycin greatly improved proliferation and suppression. We show that CD8+CD45RClow/-Tregs are equivalent to canonical CD4+CD25highCD127low/-Tregs for suppression of allogeneic immune responsesin vitro. Altogether, our results open new perspectives to tolerogenic strategies in human solid organ transplantation and GVHD.
Published: 2017
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9. Risk of Aggressive Skin Cancers After Kidney Retransplantation in Patients With Previous Posttransplant Cutaneous Squamous Cell Carcinomas

Author: Ducroux, Emilie, Martin, Clemmie, Bouwes Bavinck, Jan Nico, Decullier, Evelyne, Brocard, Anabelle, Westhuis-van Elsäcker, Marlies, Lebbé, Céleste, Frances, Camille, Morelon, Emmanuel, Legendre, Christophe, Joly, Pascal, Kanitakis, Jean, Jullien, Denis, Euvrard, Sylvie, Dantal, Jacques, Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Immunologie, dermatologie, oncologie, Oncodermatologie, immunologie et cellules souches cutanées (IDO (U976 / UMR_S 976)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de dermatologie et allergologie [CHU Tenon], CHU Tenon [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), Service de néphrologie, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, France (Service de néphrologie, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, France), Service de néphrologie adultes [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), Service de dermatologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Clinique Dermatologique, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Club Rhumatismes et Inflammation, Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: integumentary system, [SDV]Life Sciences [q-bio], education, health care economics and organizations, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: International audience; The course of skin cancer after retransplantation in organ-transplant recipients who have already developed posttransplant skin cancer has not been assessed.
Published: 2017
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10. Advanced glycation inhibition and protection against endothelial dysfunction induced by coumarins and procyanidins from Mammea neurophylla

Author: Gilbertine Rakolomalala, Séverine Derbré, Denis Séraphin, Marc Litaudon, Pierre Tonnerre, Patricia Blanchard, Charlotte Gény, Caroline Rouger, Joseph Iharinjaka Randriamboavonjy, Bach Tai Dang, Gervaise Loirand, Pascal Richomme, Béatrice Charreau, Pierre Pacaud, Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Physiopathologie et pharmacologie cellulaires et moléculaires, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut du thorax, Substances d'Origine Naturelle et Analogues Structuraux (SONAS), Université d'Angers (UA), Molécules bioactives, conception, isolement et synthèse (MBCIS), and Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Glycation End Products, Advanced, Male, Cell Survival, Stereochemistry, Xanthones, Friedelin, Pharmacology, Catechin, Terpene, chemistry.chemical_compound, Coumarins, Glycation, Betulinic acid, Drug Discovery, Animals, Biflavonoids, Proanthocyanidins, Rats, Wistar, Betulinic Acid, Molecular Structure, biology, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Plant Extracts, Endothelial Cells, Mammea, Clusiaceae, General Medicine, biology.organism_classification, Calophyllaceae, Antineoplastic Agents, Phytogenic, Triterpenes, Rats, 3. Good health, Plant Leaves, chemistry, Phytochemical, Fruit, Plant Bark, Pentacyclic Triterpenes
Abstract: International audience; Advanced glycation end-products (AGEs) are associated with many pathogenic disorders such as pathogenesis of diabetes or endothelial dysfunction leading to cardiovascular events. Therefore, the identification of new anti-AGE molecules or extracts aims at preventing such pathologies. Many Clusiaceae and Calophyllaceae species are used in traditional medicines to treat arterial hypertension as well as diabetes. Focusing on these plant families, an anti-AGE plant screening allowed us to select Mammea neurophylla for further phytochemical and biological studies. Indeed, both DCM and MeOH stem bark extracts demonstrated in vitro their ability to prevent inflammation in endothelial cells and to reduce vasoconstriction. A bioguided fractionation of these extracts allowed us to point out 4-phenyl- and 4-(1-acetoxypropyl)coumarins and procyanidins as potent inhibitors of AGE formation, potentially preventing endothelial dysfunction. The fractionation steps also led to the isolation of two new compounds, namely neurophyllols A and B from the DCM bark extract together with thirteen known mammea A and E coumarins (mammea A/AA, mammea A/AB, mammea A/BA, mammea A/BB, mammea A/AA cycloD, mammea A/AB cycloD, disparinol B, mammea A/AB cycloE, ochrocarpin A, mammea A/AA cycloF, mammea A/AB cycloF, mammea E/BA, mammea E/BB) as well as δ-tocotrienol, xanthones (1-hydroxy-7-methoxyxanthone, 2-hydroxyxanthone) and triterpenes (friedelin and betulinic acid). During this study, R,S-asperphenamate, previously described from fungal origin was also purified.
Published: 2014
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11. Anticorps monoclonaux en transplantation

Author: Bernard Vanhove, Immunointervention dans les allo et xénotransplantations, and Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN
Subjects: medicine.medical_specialty, anticorps monoclonaux, medicine.drug_class, medicine.medical_treatment, 030230 surgery, Monoclonal antibody, General Biochemistry, Genetics and Molecular Biology, Organ transplantation, Muromonab-CD3, 03 medical and health sciences, 0302 clinical medicine, Immune system, Antigen, Medicine, CD20, Transplantation, biology, business.industry, Immunosuppression, General Medicine, 3. Good health, Immunology, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, 030215 immunology, medicine.drug
Abstract: Polyclonal anti-lymphoyctes antibodies were first successfully used in the 1970 in organ transplantation, but ten years later, monoclonal antibodies (mAb) emerged as a new class of immunosuppressive agents in transplantation with the potential to target highly specifically immune cells responsible for acute rejection. Some have proved their efficacy, such as mAb recognizing CD3- and CD25-positive T cells and have been extensively studied in clinical trials. Others such as mAb against CD52 and CD20, are still under investigation; finally, the next challenge is, based on our improved understanding of the mechanisms of immune recognition and allograft rejection, to use these mAb either alone or in combination with standard immunosuppressive regimens to manipulate the allogenic response to reach antigen-specific tolerance desired in solid-organ transplantation.
Published: 2009
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12. Expanded CD8 T-cell sharing between periphery and CNS in multiple sclerosis

Author: Marion Salou, Alexandra Garcia, David Laplaud, Philippe Hulin, Anne Gainche-Salmon, Gérard Ramstein, Delphine Loussouarn, Jean-Paul Soulillou, Flora Guillot, Nicolas Degauque, Steven Nedellec, Arnaud Nicot, Sophie Brouard, Daniel Baron, Bryan Nicol, Laure Michel, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Génétique Animale et Biologie Intégrative (GABI), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Institut Fédératif de Recherche 26 (IFR26), Université de Nantes (UN), Plateforme MicroPicel, Laboratoire d'Informatique de Nantes Atlantique (LINA), Mines Nantes (Mines Nantes)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, and Centre National de la Recherche Scientifique (CNRS)-Mines Nantes (Mines Nantes)-Université de Nantes (UN)
Subjects: General Neuroscience, Multiple sclerosis, Central nervous system, T-cell receptor, Biology, medicine.disease, Phenotype, Granzyme B, medicine.anatomical_structure, Cerebrospinal fluid, Immunology, medicine, Cytotoxic T cell, Neurology (clinical), [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Research Articles, CD8
Abstract: Objective In multiple sclerosis (MS), central nervous system (CNS), cerebrospinal fluid (CSF), and blood display TCR clonal expansions of CD8+ T cells. These clones have been assumed – but never demonstrated – to be similar in the three compartments. Addressing this key question is essential to infer the implication of peripheral clonally expanded CD8+ T cells in the disease. Methods For the first time, TCR Vβ repertoire from paired blood (purified CD8+ and CD4+ T cells), CSF and CNS (22 lesions, various inflammatory and demyelination statuses) samples from three MS patients was studied using complementary determining region 3 (CDR3) spectratyping and high-throughput sequencing. In parallel, blood and CNS clonally expanded CD8+ T cells were characterized by fluorescent staining. Results TCR Vβ repertoire analysis revealed strong sharing of predominant T-cell clones between CNS lesions, CSF, and blood CD8+ T cells. In parallel, we showed that blood oligoclonal CD8+ T cells exhibit characteristics of pathogenic cells, as they displayed a bias toward a memory phenotype in MS patients, with increased expression of CCR5, CD11a and Granzyme B (GZM-B) compared to non oligoclonal counterparts. CNS-infiltrating T cells were mainly CD8 expressing CD11a and GZM-B. Interpretation This study highlights the predominant implication of CD8+ T cells in MS pathophysiology and demonstrates that potentially aggressive CD8+ T cells can be easily identified and characterized from blood and CSF samples.
Published: 2015
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13. Development of a Cyclosporin-A-Induced Immune Tolerant Rat Model to Test Marrow Allograft Cell Type Effects on Bone Repair

Author: Espitalier, Florent, Durand, Nicolas, Rémy, Séverine, Corre, Pierre, Sourice, Sophie, Pilet, Paul, Weiss, Pierre, Guicheux, Jérôme, Malard, Olivier, Université de Nantes - UFR Odontologie, Université de Nantes (UN), Service d'Oto-Rhino-Laryngologie et de Chirurgie Cervico-Faciale [CHU Nantes] (PHU4 - OTONN), Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire d'ingénierie osteo-articulaire et dentaire (LIOAD), Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Service de Chirurgie maxillo-faciale et stomatologie, and Jehan, Frederic
Subjects: [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Cell tracking, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Bone repair, Cyclosporin-A, Bone marrow allograft, Immunotolerance
Abstract: International audience; Bone repair is an important concept in tissue engineering, and the ability to repair bone in hypotrophic conditions such as that of irradiated bone, represents a challenge for this field. Previous studies have shown that a combination of bone marrow and (BCP) was effective to repair irradiated bone. However, the origin and role played by each cell type in bone healing still remains unclear. In order to track the grafted cells, the development of an animal model that is immunotolerant to an allograft of bone marrow would be useful. Furthermore, because the immune system interacts with bone turnover, it is of critical importance to demonstrate that immunosuppressive drugs do not interfere with bone repair. After a preliminary study of immunotolerance, cyclosporin-A was chosen to be used in immunosuppressive therapy. Ten rats were included toobserve qualitative and quantitative bone repair 8 days and 6 weeks after the creation of bone defects. The defects werefilled with an allograft of bone marrow alone or in association with BCP under immunosuppressive treatment (cyclosporin-A). The results showed that there was no significant interaction of cyclosporin-A with osseous regeneration. The use of this new immunotolerant rat model of bone marrow allograft in future studies will provide insight on how the cells within the bone marrow graft contribute to bone healing, especially in irradiated conditions.
Published: 2015

14. Phenotypic analysis of immunocompetent cells in healthy human dental pulp

Author: Jean-Christophe Farges, Maria-Cristina Cuturi, Marcello Hill, Brigitte Alliot-Licht, Laurence Bouchet-Delbos, Géraldine Bienvenu-Louvet, Alexis Gaudin, Emmanuelle Renard, Institut National de la Santé et de la Recherche Médicale (INSERM), Cytokines, chimiokines et immunopathologie, Université Paris-Sud - Paris 11 (UP11)-IFR13-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunointervention dans les allo et xénotransplantations, and Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN
Subjects: Adult, Adolescent, CD14, CD3, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], CD16, CD19, Flow cytometry, Immunophenotyping, Young Adult, Immune system, stomatognathic system, medicine, Leukocytes, Humans, Child, General Dentistry, Tissue homeostasis, ComputingMilieux_MISCELLANEOUS, Dental Pulp, biology, medicine.diagnostic_test, FOXP3, Flow Cytometry, Molecular biology, stomatognathic diseases, Immunology, biology.protein, Leukocyte Common Antigens
Abstract: Introduction Like other tissues in the body, the human dental pulp is equipped with a network of immune cells that can be mobilized against pathogens when they invade the tooth. Very little data, mostly obtained with classic histologic methods, have reported their quantities and relative percentages. The objective of this study was to characterize and precisely quantify immunocompetent cells in healthy human dental pulp by using fluorescence-activated cell sorting, together with identifying specific cell subsets in the leukocyte (CD45 + ) cells. Methods Healthy human third molars were collected from 42 young patients. Dental pulps were separated from the hard tissues and prepared for flow cytometry or immunostaining analyses. Results CD45 + cells represented 0.94% ± 0.65% of cells obtained from the enzymatic digestion of whole dental pulps ( n = 34). CD16 + CD14 + granulocytes/neutrophils (50.01% ± 9.08%, n = 7) were found to represent the major subpopulation in CD45 + cells followed by CD3 + T lymphocytes (32.58% ± 11%, n = 17), CD14 + monocytes (8.93% ± 5.8%, n = 7), and HLA-DR high Lin1 - dendritic cells (4.51% ± 1.12%, n = 7). Minor subpopulations included CD3 − CD56 + natural killer cells (2.63% ± 1.15%, n = 7) and CD19 + B lymphocytes (1.65% ± 0.89%, n = 17). We further identified cells harboring a phenotype compatible with Foxp3/CD25-expressing regulatory T lymphocytes (CD45 + CD3 + CD4 + CD127 low ). Fluorescence-activated cell sorting analysis and confocal microscopy also revealed expression of HO-1 in HLA-DR + cells. Conclusions For the first time, this study identifies and precisely quantifies the relative proportion of immunocompetent cells potentially involved in tissue homeostasis of healthy human dental pulp.
Published: 2014
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15. Survival and Differentiation of Adenovirus-Generated Induced Pluripotent Stem Cells Transplanted into the Rat Striatum

Author: Robert D. Wyse, Ming Lu, Matthew T. Schloop, Ludovic Vallier, Travis D. Hulse, Xavier Lévêque, Julien Rossignol, Kyle D. Fink, Dylan J. Dues, Véronique Nerrière-Daguin, Phillip A. Starski, Andrew T. Crane, Philippe Naveilhan, Tuan H. Nguyen, Laurent Lescaudron, Ignacio Anegon, Steve J. Witte, Gary L. Dunbar, Cheng Song, Le Bihan, Sylvie, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Field Neurosciences Laboratory for Restorative Neurology [Mount Pleasant, MI, USA] (Program in Neuroscience ), Central Michigan University (CMU), Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN), Laboratoire d'ingénierie osteo-articulaire et dentaire (LIOAD), Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Faculté de Médecine - Université de Nantes, College of Medicine [Mount Pleasant, MI, USA], Field Neurosciences Institute, St. Mary's of Michigan, Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge [UK] (CAM), Biothérapies Hépatiques, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropathies du système nerveux entérique et pathologies digestives, implication des cellules gliales entériques, Université de Nantes - UFR Odontologie, A Partner University Fund grant (Chateaubriand fellowship from the Embassy of France in the US)., INSERM U643., and Funding from the John G. Kulhavi Professorship and Field Neurosciences Institute.
Subjects: Male, Somatic cell, Cell Survival, Induced Pluripotent Stem Cells, Biomedical Engineering, lcsh:Medicine, Biology, Transfection, Induced pluripotent stem cells (iPSCs), Adenoviridae, Rats, Sprague-Dawley, Animals, Adenovirus, Induced pluripotent stem cell, Transplantation, Stem cell, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, lcsh:R, Mesenchymal stem cell, Cell Differentiation, Cell Biology, Cellular Reprogramming, Embryonic stem cell, Corpus Striatum, 3. Good health, Cell biology, Rats, Neuronal differentiation, Reprogramming, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Stem Cell Transplantation
Abstract: International audience; Induced pluripotent stem cells (iPSCs) offer certain advantages over embryonic stem cells in cell replacement therapy for a variety of neurological disorders. However, reliable procedures, whereby transplanted iPSCs can survive and differentiate into functional neurons, without forming tumors, have yet to be devised. Currently, retroviral or lentiviral reprogramming methods are often used to reprogram somatic cells. Although the use of these viruses has proven to be effective, formation of tumors often results following in vivo transplantation, possibly due to the integration of the reprogramming genes. The goal of the current study was to develop a new approach, using an adenovirus for reprogramming cells, characterize the iPSCs in vitro, and test their safety, survivability, and ability to differentiate into region-appropriate neurons following transplantation into the rat brain. To this end, iPSCs were derived from bone marrow-derived mesenchymal stem cells and tail-tip fibro-blasts using a single cassette lentivirus or a combination of adenoviruses. The reprogramming efficiency and levels of pluripotency were compared using immunocytochemistry, flow cytometry, and real-time polymerase chain reaction. Our data indicate that adenovirus-generated iPSCs from tail-tip fibroblasts are as efficient as the method we used for lentiviral reprogramming. All generated iPSCs were also capable of differentiating into neuronal-like cells in vitro. To test the in vivo survivability and the ability to differentiate into region-specific neurons in the absence of tumor formation, 400,000 of the iPSCs derived from tail-tip fibroblasts that were transfected with the adenovirus pair were transplanted into the striatum of adult, immune-competent rats. We observed that these iPSCs produced region-specific neuronal phenotypes, in the absence of tumor formation, at 90 days posttransplantation. These results suggest that adenovirus-generated iPSCs may provide a safe and viable means for neuronal replacement therapies.
Published: 2014
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16. Intrastriatal Transplantation of Adenovirus-Generated Induced Pluripotent Stem Cells for Treating Neuropathological and Functional Deficits in a Rodent Model of Huntington's Disease

Author: Rachel E. DeJonge, Laurent Lescaudron, Gary L. Dunbar, Ming Lu, Aaron Antcliff, Allison C. Moore, Xavier Lévêque, Lucas D. Huffman, Andrew T. Crane, Darren Story, Dylan J. Dues, Julien Rossignol, Phillip A. Starski, Kyle D. Fink, Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Field Neurosciences Laboratory for Restorative Neurology [Mount Pleasant, MI, USA] (Program in Neuroscience ), Central Michigan University (CMU), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire d'ingénierie osteo-articulaire et dentaire (LIOAD), Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Field Neurosciences Institute, St. Mary's of Michigan, Regenerative Medicine and Skeleton research lab (RMeS), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Nantes - UFR Odontologie, Centre Hospitalier Universitaire Hôtel-Dieu de Nantes (CHU Hôtel-Dieu), Regenerative Medicine and Skeleton (RMeS), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Jehan, Frederic
Subjects: Male, Huntington's Disease, Pathology, Striosome, Medical Biotechnology, Convulsants, Striatum, Neurodegenerative, medicine.disease_cause, Regenerative Medicine, Rats, Sprague-Dawley, 0302 clinical medicine, Transduction, Genetic, Adenovirus, Induced pluripotent stem cell, 0303 health sciences, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, iPSC, Stem cell, Behavior, Animal, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, 3-Nitropropionic acid, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, General Medicine, Anatomy, Nitro Compounds, 3. Good health, Huntington Disease, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Neurological, Female, Development of treatments and therapeutic interventions, Huntington’s disease, medicine.medical_specialty, Induced Pluripotent Stem Cells, Clinical Sciences, Neuropathology, Biology, Adenoviridae, 03 medical and health sciences, Transduction, Rare Diseases, Huntington's disease, Genetic, medicine, Animals, Embryonic Stem Cells/Induced Pluripotent Stem (iPS) Cells, 030304 developmental biology, Behavior, Transplantation, Stem Cell Research - Induced Pluripotent Stem Cell, 5.2 Cellular and gene therapies, Animal, Neurosciences, Cell Biology, medicine.disease, Stem Cell Research, Corpus Striatum, Rats, Brain Disorders, Disease Models, Animal, Disease Models, Sprague-Dawley, Biochemistry and Cell Biology, Propionates, 030217 neurology & neurosurgery, Developmental Biology, Stem Cell Transplantation
Abstract: Induced pluripotent stem cells (iPSCs) show considerable promise for cell replacement therapies for Huntington's disease (HD). Our laboratory has demonstrated that tail-tip fibroblasts, reprogrammed into iPSCs via two adenoviruses, can survive and differentiate into neuronal lineages following transplantation into healthy adult rats. However, the ability of these cells to survive, differentiate, and restore function in a damaged brain is unknown. To this end, adult rats received a regimen of 3-nitropropionic acid (3-NP) to induce behavioral and neuropathological deficits that resemble HD. At 7, 21, and 42 days after the initiation of 3-NP or vehicle, the rats received intrastriatal bilateral transplantation of iPSCs. All rats that received 3-NP and vehicle treatment displayed significant motor impairment, whereas those that received iPSC transplantation after 3-NP treatment had preserved motor function. Histological analysis of the brains of these rats revealed significant decreases in optical densitometric measures in the striatum, lateral ventricle enlargement, as well as an increase in striosome size in all rats receiving 3-NP when compared with sham rats. The 3-NP-treated rats given transplants of iPSCs in the 7- or 21-day groups did not exhibit these deficits. Transplantation of iPSCs at the late-stage (42-day) time point did not protect against the 3-NP-induced neuropathology, despite preserving motor function. Transplanted iPSCs were found to survive and differentiate into region-specific neurons in the striatum of 3-NP rats, at all transplantation time points. Taken together, these results suggest that transplantation of adenovirus-generated iPSCs may provide a potential avenue for therapeutic treatment of HD.
Published: 2014
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17. Systemic immunosuppression plus local production of CTLA4-Ig to control rejection of transgenic pig neuroblasts in non-human primates

Author: Romina Aron Badin, Bernard Vanhove, Marta Vadori, Fabio Fante, Massimo Boldrin, Giulia Maria Debenedictis, Laura Cavicchioli, Dino Sgarabotto, Caroline Jan, Véronique Daguin, Philippe Naveilhan, Jean-Paul Soulillou, Luca Denaro, Renzo Manara, Paolo Zampieri, Avella, Domenico D., Martin Plat, Eric Venturi, Françoise Botté, Domenico Rubello, Philippe HANTRAYE, Emanuele Cozzi, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Nantes (CHU Nantes), Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Consorzio per la Ricerca sul Trapianto di Organi, Partenaires INRAE, Universita di Padova, University Hospital of Padua, Institut National de la Recherche Agronomique (INRA), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Ospedale 'Santa Maria della Misericordia' = University Hospital 'Santa Maria della Misericordia', Università degli Studi di Padova = University of Padua (Unipd), Azienda Ospedale Università di Padova = Hospital-University of Padua (AOUP), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), ProdInra, Migration, and Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], [INFO]Computer Science [cs], [INFO] Computer Science [cs], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2013

18. 'It is not superstition that worries me, Herr Doctor, but genes and chromosomes' Inspector Kemp, from the movie Young Frankenstein, 1974

Author: Anegon, Ignacio, Anegon, Ignacio, Immunointervention dans les allo et xénotransplantations, and Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN
Subjects: InformationSystems_GENERAL, [SDV.GEN]Life Sciences [q-bio]/Genetics, MathematicsofComputing_GENERAL, [SDV.GEN] Life Sciences [q-bio]/Genetics, ComputingMilieux_MISCELLANEOUS, GeneralLiterature_MISCELLANEOUS
Abstract: Editorial; International audience
Published: 2013

19. Control of transplant tolerance and intragraft regulatory T cell localization by CCL5

Author: Claire Usal, Bernard Vanhove, Bernard Martinet, Gilles Blancho, Nahzli Dilek, Nicolas Poirier, BMC, Ed., Immunointervention dans les allo et xénotransplantations, and Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN
Subjects: Cell type, Pathology, medicine.medical_specialty, Regulatory T cell, lcsh:Medicine, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, General Biochemistry, Genetics and Molecular Biology, CCL5, Andrology, chemistry.chemical_compound, medicine, ComputingMilieux_MISCELLANEOUS, Medicine(all), Creatinine, Messenger RNA, Kidney, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Biochemistry, Genetics and Molecular Biology(all), business.industry, lcsh:R, FOXP3, hemic and immune systems, General Medicine, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, medicine.anatomical_structure, chemistry, Poster Presentation, Urea, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Material, methods and results In rat recipients of kidney allografts where tolerance was induced by costimulation blockade, we observed a 2-fold decrease of plasma CCL5 levels as compared to control syngeneic grafted animals (0.60 ± 0.17 vs. 1.17 ± 0.48 ng/ml; p
Published: 2012

20. Evaluation of FR104, a Treg sparing antagonist anti-CD28 monovalent Fab’ antibody in kidney transplantation in non-human primates

Author: Nahzli Dilek, Xavier Tillou, David Minault, Nicolas Poirier, Caroline Mary, Gilles Blancho, Stéphanie Le Bas-Bernardet, Jeremy Hervouet, Julien Branchereau, Bernard Vanhove, Effimune, Faculté de Médecine de Nantes, Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, and BMC, Ed.
Subjects: Pathology, medicine.medical_specialty, lcsh:Medicine, Pharmacology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, General Biochemistry, Genetics and Molecular Biology, biology.animal, Medicine, ComputingMilieux_MISCELLANEOUS, Kidney transplantation, Medicine(all), Kidney, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, Biochemistry, Genetics and Molecular Biology(all), business.industry, lcsh:R, Antagonist, CD28, Histology, General Medicine, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Tacrolimus, medicine.anatomical_structure, Poster Presentation, biology.protein, Antibody, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Baboon
Abstract: Methods and results Here we evaluated in a non-human primates this “Treg sparing strategy” with FR104, a novel monovalent humanized and pegylated Fab’ anti-CD28 antibody fragment. PK/PD studies in monkeys revealed that FR104 presented an elimination half-life of 8 days and 100% target saturation over at least a month after a single iv injection of 5 mg/kg. FR104 was next evaluated in a baboon kidney allograft model at the dose of 5 mg/kg at day 0, 4, 14 and then every two-week until 3 months. Monotherapy modestly but significantly prolonged allograft survival (MST: 18.5 days for monotherapy vs 6 days for untreated recipients). FR104 synergized with low doses tacrolimus (lowTac, trough: 5-10 ng/ml; MST >100 days for FR104/ lowTac vs. 15 days for lowTac alone) as well as with calcineurin-free regimens: therapeutic doses of MMF or rapamycin (day 0-90) with 1 mg/kg of corticosteroids from day 0-14 (MST >100 days for FR104 + MMF/Rapa vs. 18/15 days for MMF/Rapa alone). Flow cytometry analyses indicated that blood Treg cells of the natural and inducible types were preserved in FR104/MMF or FR104/lowTAC bitherapies and accumulated in FR104 monotherapy and in FR104/Rapa bitherapy, whereas Treg cells were lowered by MMF and lowTac monotherapies. Histology also revealed that CTLA4+ and Foxp3+ T lymphocytes were accumulated into the graft of FR104 treated recipients.
Published: 2012

21. Absence of Galectin-1 accelerates CD8⁺ T cell-mediated graft rejection

Author: Aurélie, Moreau, Alistair, Noble, Kulachelvy, Ratnasothy, Jian-Guo, Chai, Louise, Deltour, Maria-Cristina, Cuturi, Elizabeth, Simpson, Robert, Lechler, Giovanna, Lombardi, Centre for Transplantation, King's College London (MRC), Guy's Hospital [London], Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, (MRC), Transplantation Biology Group, Imperial College London, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, and British Heart Foundation, MRC Centre for Transplantation, National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS, Foundation Trust, King's College London
Subjects: Graft Rejection, Male, Galectin 1, MESH: Spleen, MESH: Interferon-gamma, MESH: Interleukin-17, MESH: Flow Cytometry, MESH: Graft Rejection, MESH: Lymph Nodes, CD8-Positive T-Lymphocytes, MESH: Mice, Knockout, Interferon-gamma, Mice, Transplant immunology, MESH: Mice, Inbred C57BL, Galectin-1, Animals, MESH: Animals, MESH: Mice, Mice, Knockout, MESH: Galectin 1, Interleukin-17, Skin Transplantation, Flow Cytometry, MESH: CD8-Positive T-Lymphocytes, MESH: Male, Specific Pathogen-Free Organisms, Mice, Inbred C57BL, MESH: Specific Pathogen-Free Organisms, MESH: Skin Transplantation, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Lymph Nodes, Tc1 CD8+ T cells, MESH: Female, Spleen, Knockout mice
Abstract: International audience; Galectin-1 (Gal-1) is a member of a family of endogenous β-galactose-binding proteins with a role in preventing autoimmune diseases and chronic inflammation. In this study, the involvement of Gal-1 in graft rejection was investigated by using Gal-1-deficient mice (Gal-1⁻/⁻). We demonstrate that in the absence of Gal-1, skin grafts are rejected earlier compared with those of WT mice, and that this is due to the role played by CD8⁺ T cells in graft rejection. The difference in graft survival observed between Gal-1⁻/⁻ and WT mice was explained by both an increase in the percentage of antigen-specific CD8+ T cells and by preferential secretion of IFN-γ and IL-17 by CD8⁺ T cells in Gal-1⁻/⁻ mice compared with WT mice. This study suggests that endogenous expression of Gal-1 contributes to graft survival. The results obtained from the use of mice deficient in Gal-1 also confirm a key role for CD8⁺ T cells in graft rejection.
Published: 2012
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22. Comparison of spheroids formed by rat glioma stem cells and neural stem cells reveals differences in glucose metabolism and promising therapeutic applications

Author: Naïg Gueguen, François M. Vallette, Catherine Guette, Philippe Naveilhan, Muriel Bahut, Virginie Bonnamain, Lisenn Lalier, Marie Morfouace, Pascal Reynier, Lisa Oliver, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Université d'Angers (UA), Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de Biologie Neurovasculaire Intégrée [Angers] (CNRS UMR6214 - INSERM U771), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers, Département de Biochimie et Génétique [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), and Lalier, Lisenn
Subjects: Proteomics, Pyruvate dehydrogenase kinase, [SDV.CAN]Life Sciences [q-bio]/Cancer, Apoptosis, Biology, Biochemistry, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Adenosine Triphosphate, [SDV.CAN] Life Sciences [q-bio]/Cancer, Neural Stem Cells, Cancer stem cell, Spheroids, Cellular, Tumor Cells, Cultured, Animals, Glycolysis, Phosphorylation, Molecular Biology, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, Reactive oxygen species, Dichloroacetic Acid, Glioma, Cell Biology, Neural stem cell, 3. Good health, Cell biology, Rats, Gene Expression Regulation, Neoplastic, Glucose, chemistry, Proto-Oncogene Proteins c-bcl-2, 030220 oncology & carcinogenesis, Drug Design, FOXO3, Neoplastic Stem Cells, Stem cell, Glioblastoma, Reactive Oxygen Species
Abstract: International audience; Cancer stem cells (CSCs) are thought to be partially responsible for cancer resistance to current therapies and tumor recurrence. Dichloroacetate (DCA), a compound capable of shifting metabolism from glycolysis to glucose oxidation, via an inhibition of pyruvate dehydrogenase kinase was used. We show that DCA is able to shift the pyruvate metabolism in rat glioma CSCs but has no effect in rat neural stem cells. DCA forces CSCs into oxidative phosphorylation but does not trigger the production of reactive oxygen species and consecutive anti-cancer apoptosis. However, DCA, associated with etoposide or irradiation, induced a Bax-dependent apoptosis in CSCs in vitro and decreased their proliferation in vivo. The former phenomenon is related to DCA-induced Foxo3 and p53 expression, resulting in the overexpression of BH3-only proteins (Bad, Noxa, and Puma), which in turn facilitates Bax-dependent apoptosis. Our results demonstrate that a small drug available for clinical studies potentiates the induction of apoptosis in glioma CSCs.
Published: 2012
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23. A subset of dendritic cells as a major and constitutive source of IL-22BP

Author: Gaelle Beriou, Michèle Heslan, Anne-Chantal Knol, Céline Bossard, Régis Josien, Brigitte Dréno, Miriam Merad, Jerome Martin, Simon Milling, Laboratoire d'immunologie, Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Service d'anatomo-pathologie, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), University of Glasgow, Mount Sinai School of Medicine, Icahn School of Medicine at Mount Sinai [New York] (MSSM), and BMC, Ed.
Subjects: [SDV.IMM] Life Sciences [q-bio]/Immunology, medicine.medical_treatment, Retinoic acid, lcsh:Medicine, 02 engineering and technology, Inhibitory postsynaptic potential, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Psoriasis, medicine, Receptor, ComputingMilieux_MISCELLANEOUS, Medicine(all), [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Biochemistry, Genetics and Molecular Biology(all), lcsh:R, General Medicine, 021001 nanoscience & nanotechnology, medicine.disease, 3. Good health, Haematopoiesis, Retinoic acid receptor, Cytokine, chemistry, 030220 oncology & carcinogenesis, Rheumatoid arthritis, Immunology, Poster Presentation, Cancer research, [SDV.IMM]Life Sciences [q-bio]/Immunology, ComputingMethodologies_GENERAL, 0210 nano-technology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: IL-22 is a cytokine produced by T cells and innate lymphocytes. Its receptor is exclusively expressed by non hematopoietic cells mostly epithelial cells and hepatocytes. IL-22 has pathogenic or protective effects depending on the model. A role for IL-22 is suggested in IMID such as psoriasis, rheumatoid arthritis and Crohn disease. IL-22BP is a soluble inhibitory receptor specific for IL-22 whose cellular source and physiological role are mainly unknown.
Published: 2011

24. Alloantigenic recognition properties of CD8+ regulatory T cells

Author: Carole Guillonneau, I. Anegon, Elodie Picarda, BMC, Ed., Immunointervention dans les allo et xénotransplantations, and Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN
Subjects: [SDV.IMM] Life Sciences [q-bio]/Immunology, lcsh:Medicine, chemical and pharmacologic phenomena, Peptide, Major histocompatibility complex, General Biochemistry, Genetics and Molecular Biology, Allograft survival, Medicine, ComputingMilieux_MISCELLANEOUS, Medicine(all), chemistry.chemical_classification, Transplantation, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, CD40, biology, Biochemistry, Genetics and Molecular Biology(all), business.industry, lcsh:R, T-cell receptor, hemic and immune systems, General Medicine, Cell biology, chemistry, Poster Presentation, Immunology, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, CD8, Heart allograft
Abstract: Background We recently reported that in a rat major histocompatibility complex (MHC) mismatched heart allograft model, treatment with CD40Ig, a chimeric molecule that blocks CD40L, leads to indefinite allograft survival mediated by CD8CD45RC Tregs [1]. Although essential, the exact role of TCR/MHC/peptide interaction in Treg activity is still unknown. We therefore characterize the allogeneic peptide(s) recognized and the TCR usage of the CD8 CD45RC Tregs.
Published: 2011
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25. Immunosuppressive role of fibrinogen-like protein 2 (FGL2) in CD8+regulatory T cells-mediated long-term graft survival

Author: Laurent Tesson, Claire Usal, Séverine Bézie, Ignacio Anegon, Séverine Ménoret, Lise Caron, Xian-Liang Li, Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Plateforme de rats trangéniques, IBISA CNRS, and BMC, Ed.
Subjects: [SDV.IMM] Life Sciences [q-bio]/Immunology, lcsh:Medicine, Spleen, General Biochemistry, Genetics and Molecular Biology, Virus, law.invention, In vivo, law, Splenocyte, medicine, ComputingMilieux_MISCELLANEOUS, Medicine(all), [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Biochemistry, Genetics and Molecular Biology(all), business.industry, lcsh:R, General Medicine, Molecular biology, In vitro, FGL2, medicine.anatomical_structure, Recombinant DNA, [SDV.IMM]Life Sciences [q-bio]/Immunology, Oral Presentation, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, CD8
Abstract: Material and methods A lewis 1W rat heart is grafted in a MHC-mismatched Lewis 1A rat and infected with 2.10pi of adenovirus recombinant for CD40Ig molecule (AdCD40Ig) the day of the graft. Tregs, effector CD4CD25 T lymphocytes (TL), and plasmacytoide dendritic cells (pDC) from spleen are sorted by FACS Aria for in vitro tests. For in vivo studies, 4,5.10vg of FGL2-recombinant adenovirus associated virus (AAVFGL2) are intramuscularly or intravenously injected in recipients 30 days before the graft. Splenocytes are transferred to sublethaly irradiated rats by i.v injection the day before the graft.
Published: 2011
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26. Kidney and liver transplantation in patients with autosomal recessive polycystic kidney disease: a multicentric study

Author: Chantal Loirat, Gwenaelle Roussey, Marion Chapal, Fadi Fakhouri, Gilles Blancho, Rémi Salomon, Alexandre Dufay, Cécile Vigneau, Maryvonne Hourmant, Emma Allain Launay, Agnes Debout, Stéphane Burtey, Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Référence des Maladies Rénales Héréditaires de l'enfant et de l'adulte, 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 de néphrologie et transplantation rénale [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Service de néphrologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], 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), Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Service de néphrologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service de Néphrologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], and 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 )
Subjects: Nephrology, Adult, Male, medicine.medical_specialty, Pathology, Caroli disease, Adolescent, medicine.medical_treatment, 030232 urology & nephrology, Liver transplantation, urologic and male genital diseases, Gastroenterology, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, autosomal recessive polycystic kidney disease, medicine, Humans, Longitudinal Studies, Child, Kidney transplantation, Polycystic Kidney, Autosomal Recessive, Retrospective Studies, Transplantation, Kidney, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, Caroli's disease, Disease Management, medicine.disease, Kidney Transplantation, Autosomal Recessive Polycystic Kidney Disease, female genital diseases and pregnancy complications, Caroli Disease, 3. Good health, Liver Transplantation, Survival Rate, medicine.anatomical_structure, Treatment Outcome, Child, Preschool, 030211 gastroenterology & hepatology, Female, France, business, Kidney disease
Abstract: International audience; Background and objectives. In contrast to the improvement in our understanding of the pathogenesis and presentation of autosomal recessive polycystic kidney disease (ARPKD), data regarding the issue of kidney and liver transplantation in patients with ARPKD remain particularly scarce. Here, we report the results and outcome of renal and/or liver transplantation in a series of patients with ARPKD. Methods. Fourteen ARPKD patients (age: 3-25 years) who underwent renal transplantation with or without liver transplantation were retrospectively identified in five French nephrology departments. The patients' medical charts were reviewed and relevant data were collected. Results. The clinical and radiological presentation of the 14 patients was highly variable illustrating the heterogeneity of ARPKD. Six patients underwent kidney and/or liver transplantation in adulthood. First renal graft survival was 92, 78 and 14% at 1, 5 and 10 years after renal transplantation, respectively. Mortality rate was relatively high (3/14; 21%) in these young patients and was directly related to infectious complications (recurrent angiocholitis) of severe Caroli's disease (dilatation of intra- and/or extra-hepatic bile ducts), a typical feature of ARPKD. Conclusions. Our data suggest that ARPKD patients evaluated for renal transplantation should be carefully screened for severe Caroli's disease. Even though the limited number of patients included in our study precludes any definite recommendation, pre-emptive liver transplantation may be a therapeutic option in ARPKD patients with severe Caroli's disease evaluated for renal transplantation.
Published: 2011
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27. Xenotransplantation of porcine CTLA4-Ig+/+ neural precursors enables recovery of the locomotor activity in parkinsonian primates

Author: Badin, A.R., Denaro, L., Vadori, M., Boldrin, M., Cavicchioli, Lionel, De Benedictis, G.M., Fante, F., Sgarabotto, D., Jan, Charlie, Daguin, V., Naveilhan, P., Vanhove, B., Blancho, G., Soulillou, J.P., Plat, Martine, Venturi, Eric, Botté, Françoise, Padoan, A., Manara, R., Zampieri, P., D'avella, D., Rubello, D., Gianello, P., Hantraye, P., Cozzi, Elena, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre National de la Recherche Scientifique (CNRS), Universita di Padova, Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Unité Expérimentale de Physiologie Animale de l‘Orfrasiére (UE PAO), Institut National de la Recherche Agronomique (INRA), Ospedale 'Santa Maria della Misericordia' = University Hospital 'Santa Maria della Misericordia', Université Catholique de Louvain = Catholic University of Louvain (UCL), ProdInra, Migration, Università degli Studi di Padova = University of Padua (Unipd), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV] Life Sciences [q-bio], XENOGREFFE, [SDV]Life Sciences [q-bio], [INFO]Computer Science [cs], HISTOLOGIE, [INFO] Computer Science [cs], ComputingMilieux_MISCELLANEOUS, activité leucomotrice
Abstract: 331; International audience
Published: 2011

28. Early rise in circulating endothelial protein C receptor correlates with poor outcome in severe sepsis

Author: Guitton, Christophe, Gérard, Nathalie, Sébille, Véronique, Bretonnière, Cédric, Zambon, Olivier, Villers, Daniel, Charreau, Béatrice, Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Service de Réanimation Médicale Polyvalente, Biostatistique, Recherche Clinique et Mesures Subjectives en Santé, Université de Nantes (UN), Plateforme de Biométrie, Cellule de promotion de la recherche clinique, This work was supported by grants from l'Agence de Biomédecine, La Société de Néphrologie, l'Association pour le Développement de la Réanimation (ADR, Nantes), Lilly-France. This work was also in part supported by XENOME a EU-funded Integrated Project in Life Sciences, Genomics and Biotechnology for Health (LSHBCT-2006-037377) and by a grant from la Fondation de l'Avenir (contrat ET8-498)., and Guitton, Christophe
Subjects: MESH: Aged, MESH: Humans, MESH: Middle Aged, MESH: Vasculitis, MESH: Adult, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, infection, MESH: Male, severe sepsis, survival analysis, MESH: France, soluble EPCR, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Severity of Illness Index, gender, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Intensive Care Units, MESH: Sepsis, MESH: Antigens, CD, MESH: Female, MESH: Outcome Assessment (Health Care), [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Receptors, Cell Surface
Abstract: International audience; PURPOSE: The endothelial protein C receptor (EPCR) negatively regulates the coagulopathy and inflammatory response in sepsis. Mechanisms controlling the expression of cell-bound and circulating soluble EPCR (sEPCR) are still unclear. Moreover, the clinical impact of EPCR shedding and its potential value to predict sepsis progression and outcome remain to be established. METHODS: We investigated the time course of plasma sEPCR over the 5 first days (D) of severe sepsis in 40 patients. RESULTS: No significant difference was observed when comparing sEPCR at admission (D1) to healthy volunteers and to patients with vasculitis. We report that the kinetics profile of plasma sEPCR in patients was almost stable at the onset of sepsis with no change from D1 to D4 and then a significant decrease at D5. This pattern of release was consistently observed whatever the level of sEPCR at D1. Characteristics of patients or of infections (except Gram negative) had no or little critical influence on the sEPCR profile. However, we found that sEPCR kinetics was clearly associated with patient's outcome (D28 survival). We demonstrate that a significant but moderate (
Published: 2011
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29. LONG TERM CLINICAL RECOVERY OF PARKINSON'S DISEASE FOLLOWING TRANSPLANTATION OF CTLA4-IG(+) PORCINE EMBRYONIC NEURONAL CELLS IN NON HUMAN PRIMATE

Author: Badin, Ra, Padoan, A, Vadori, M, Boldrin, M, Cavicchioli, Laura, DE BENEDICTIS, GIULIA MARIA, Fante, F, Seveso, M, Sgarabotto, D, Jan, C, Daguin, V, Naveilhan, P, Neveu, I, Soulillou, Jp, Giannello, P, Vanhove, B, Plat, M, Botte, F, Venturi, E, Denaro, Luca, Manara, R, Zampieri, P, D'Avella, Domenico, Rubello, D, Ancona, Ermanno, Hantraye, P, Cozzi, E., Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre National de la Recherche Scientifique (CNRS), Universita di Padova, Consorzio per la Ricerca sul Trapianto di Organi, Partenaires INRAE, Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Université Catholique de Louvain = Catholic University of Louvain (UCL), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Unité Expérimentale de Physiologie Animale de l‘Orfrasiére (UE PAO), Institut National de la Recherche Agronomique (INRA), Ospedale 'Santa Maria della Misericordia' = University Hospital 'Santa Maria della Misericordia', Azienda Ospedaliera di Padova, Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Padova = University of Padua (Unipd), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), and ProdInra, Migration
Subjects: [SDV] Life Sciences [q-bio], XENOGREFFE, [SDV]Life Sciences [q-bio], [INFO]Computer Science [cs], [INFO] Computer Science [cs], porc transgénique, ComputingMilieux_MISCELLANEOUS
Abstract: Communication orale O-330; International audience
Published: 2011

30. Natalizumab alters the TCR repertoire after one year of treatment in four MS patients

Author: Anne Salmon, Arnaud Nicot, David Laplaud, Marion Salou, Annie Elong Ngono, Nicolas Degauque, Sophie Brouard, Alexandra Garcia, Jean-Paul Soulillou, Laure Michel, Sandrine Wiertlewski, BMC, Ed., Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Service de neurologie [Nantes], Hôpital Guillaume-et-René-Laennec [Saint-Herblain]-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes (UN), and Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Hôpital Guillaume-et-René-Laennec [Saint-Herblain]
Subjects: [SDV.IMM] Life Sciences [q-bio]/Immunology, lcsh:Medicine, Bioinformatics, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Immune system, Natalizumab, Parenchyma, Medicine, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Medicine(all), 0303 health sciences, biology, Biochemistry, Genetics and Molecular Biology(all), business.industry, Multiple sclerosis, lcsh:R, General Medicine, medicine.disease, Tcr repertoire, 3. Good health, 030220 oncology & carcinogenesis, Poster Presentation, Immunology, Monoclonal, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Antibody, business, Infiltration (medical), medicine.drug
Abstract: Background Natalizumab is an approved drug used in relapsing and aggressive Multiple Sclerosis (MS). This is a monoclonal anti-integrin antibody that decreases the transmigration of immune cells through the blood-brain-barrier in animal models of MS. In human, the number of T cells in the CSF is dramatically decreased while the number of circulating lymphocytes usually increases. We hypothesized that in patients treated with natalizumab, the infiltration of T cells in the brain parenchyma decreases. These cells may accumulate in the blood of the patients and thus alter the T cell repertoire.
Published: 2011

31. Expression of CTLA4-Ig Is Indispensable To Enable Clinical Recovery in Parkinsonian Primate Recipients of Porcine Neural Xenografts

Author: Badin, R.A., Padoan, A., Vadori, M., Boldrin, M., Cavicchioli, Lionel, De Benedictis, G.M., Fante, F., Sgarabotto, D., Jan, Charlie, Daguin, V., Naveilhan, P., Soulillou, J.P., Vanhove, B., Plat, Martine, Venturi, Eric, Botté, Françoise, Denaro, L., Manara, R., Zampieri, P., D'avella, D., Rubello, D., Hantraye, P., Cozzi, Elena, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), ura2210, Centre National de la Recherche Scientifique (CNRS), Neurosciences, Universita degli Studi di Padova, Consorzio per la Ricerca sul Trapianto di Organi, Partenaires INRAE, Universita di Padova, Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Centre hospitalier universitaire de Nantes (CHU Nantes), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Unité Expérimentale de Physiologie Animale de l‘Orfrasiére (UE PAO), Institut National de la Recherche Agronomique (INRA), Ospedale 'Santa Maria della Misericordia' = University Hospital 'Santa Maria della Misericordia', Azienda Ospedaliera di Padova, Università degli Studi di Padova = University of Padua (Unipd), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)
Subjects: XENOGREFFE, [SDV]Life Sciences [q-bio], [INFO]Computer Science [cs], ComputingMilieux_MISCELLANEOUS
Abstract: Poster Board #-Session: P89-III Abstract# 1236; International audience
Published: 2011
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32. Heme oxygenase and carbon monoxide as an immunotherapeutic approach in transplantation and cancer

Author: Ignacio Anegon, Thomas Simon, Philippe Blancou, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), ONTRIS, Partenaires INRAE, LUNAM Université [Nantes Angers Le Mans], Immunointervention dans les allo et xénotransplantations, and Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN
Subjects: medicine.medical_treatment, [SDV]Life Sciences [q-bio], MOUSE, 0302 clinical medicine, TUMOR, Neoplasms, Immunology and Allergy, 0303 health sciences, Immunosuppression, heme oxygenase, 3. Good health, Oncology, 030220 oncology & carcinogenesis, SURVIVAL, Immunotherapy, medicine.symptom, EXPRESSION, Immunology, INHIBITION, Inflammation, GENE-TRANSFER, carbon monoxide, Autoimmune Diseases, Proinflammatory cytokine, 03 medical and health sciences, Cross-Priming, Immune system, INFLAMMATION, medicine, Animals, Humans, cancer, dendritic cells, Immune Evasion, 030304 developmental biology, Immunosuppression Therapy, Innate immune system, business.industry, Organ Transplantation, Transplantation, Heme oxygenase, Oxidative Stress, MICE, Cytoprotection, T-CELLS, OVEREXPRESSION, business, Heme Oxygenase-1, transplantation
Abstract: International audience; Heme oxygenases (HOs) are the rate-limiting intracellular enzymes that degrade heme into carbon monoxide (CO), biliverdin and free divalent iron. Among HOs, HO-1 is the only isoform that is highly inducible in response to numerous stress factors and proinflammatory cytokines. This enzyme has shown cytoprotective, antioxidant and anti-inflammatory properties. Moreover, HO-1 and, in particular, CO also have tolerogenic actions in adaptive immune responses. HO-1 can provide immunosuppression through its expression by regulatory T cells or antigen-presenting cells. The physiological importance of HO-1 has been demonstrated in both mice and humans, and modulation of HO-1 expression has therapeutic effects in a variety of disorders involving inflammation and immune responses, including organ transplantation and cancer. Consistently, upregulation of the HO-1 pathway has a significant protective effect against spontaneous or induced autoimmune diseases, allergy and can be beneficial to graft survival. However, HO-1 may also play a role in tumorigenesis by lowering antitumor innate immune responses that control tumor growth or reduce tumor expansion. Thus, controlling HO-1 expression may be of great interest in immune intervention protocols where tolerance is desirable, such as in transplantation, or where enhanced immunogenicity is needed in the case of cancer.
Published: 2011
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33. Differential regulation of IL-22BP in Crohn's disease versus ulcerative colitis

Author: Martin, Jérôme, Bossard, Céline, Boureille, Arnaud, Josien, Régis, BMC, Ed., Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Laboratoire d'immunologie, Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'anatomo-pathologie, Neuropathies du système nerveux entérique et pathologies digestives, implication des cellules gliales entériques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes (UN), and Service d'hépato-gastroentérologie
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2011

34. Elevated soluble Flt1 mediates an anti-angiogenic state in patients with ANCA-associated vasculitis

Author: Maryvonne Hourmant, Ruth J. Pepper, M Néel, Marie Rimbert, S. Le Roux, Alan D. Salama, Fadi Fakhouri, E Larger, Régis Josien, H.-T. Cook, Béatrice Charreau, Mohamed Hamidou, Noël Lamandé, Alexandre Dufay, Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre for Nephrology, University College of London [London] (UCL), Angiogénèse embryonnaire et pathologique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Labex MemoLife, Université Paris sciences et lettres (PSL)-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), Laboratoire d'immunologie, Service de médecine interne [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre for Complement and Inflammation Research, Imperial College London, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), and BMC, Ed.
Subjects: medicine.medical_specialty, lcsh:Medicine, General Biochemistry, Genetics and Molecular Biology, chemistry.chemical_compound, Internal medicine, Blocking antibody, medicine, Anaphylatoxin, Receptor, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, business.industry, lcsh:R, General Medicine, Blood flow, In vitro, 3. Good health, Complement system, Vascular endothelial growth factor, Chorioallantoic membrane, Endocrinology, chemistry, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Immunology, Poster Presentation, business
Abstract: Serum levels of soluble Flt1 (sFlt1), a potent inhibitor of VEGF, are significantly increased during the acute phase of PR3-AAV (2592 ± 11347 pg/ml) and MPO-AAV (476 ± 4258 pg/ml) compared to controls (118 ± 269 pg/ml). sFlt1 levels decreased during disease remission but remained increased compared to controls in patients with PR3-AAV. sFlt1 serum levels correlated with serum levels of C5a, an anaphylatoxin released following complement activation. Serum from patients with acute PR3-AAV induced the release of sFlt1 by human monocytes in vitro, but failed to induce a similar effect on endothelial cells. Pre-treatment of monocytes with an anti-C5a receptor blocking antibody attenuated sFlt1 release. Serum from patients with acute AAV induced a disruption of blood flow in the chicken chorioallantoic membrane assay and this effect was prevented by incubating patients’ serum with an excess of human VEGF.
Published: 2010
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35. T cell repertoire analysis and comparison between different compartments in two MS patients

Author: David-Axel Laplaud, Alexandra Garcia, Laure Michel, A Elong-Ngono, Sandrine Wiertlewski, Sophie Brouard, Marion Salou, Jean-Paul Soulillou, Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Service de neurologie [Nantes], Hôpital Guillaume-et-René-Laennec [Saint-Herblain]-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes (UN), and BMC, Ed.
Subjects: Medicine(all), [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Biochemistry, Genetics and Molecular Biology(all), business.industry, Repertoire, T cell, Multiple sclerosis, Central nervous system, T-cell receptor, lcsh:R, lcsh:Medicine, General Medicine, Bioinformatics, medicine.disease, General Biochemistry, Genetics and Molecular Biology, Hypervariable region, medicine.anatomical_structure, Cerebrospinal fluid, Antigen, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Poster Presentation, Immunology, medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract: Background/objectives T cells play probably a major role in the physiopathology of Multiple Sclerosis (MS). One way to study T cell responses in MS is to investigate the T cell receptor (TCR) structure in patients. This method is based on the analysis of the hypervariable region of the TCR named CDR3, responsible of the specific recognition of the antigen. To date, we know that the alterations of T cell repertoire in circulating lymphocytes are more pronounced in MS patients than in healthy controls. Moreover, several teams showed that the infiltrating T cells of the Central Nervous System (CNS) of MS patients present an oligoclonal repartition. So, it would be essential to know if correspondence exists between the alterations of the repertoire in the blood or Cerebrospinal Fluid (CSF) and in the CNS.
Published: 2010
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36. Porcine embryonic xenografts transgenic for CTLA4-Ig enable longterm recovery in parkinsonian macaques

Author: Badin, Ra, Padoan, A., Vadori, M., Boldrin, M., Giulia Maria De Benedictis, Fante, F., Sgarabotto, D., Jan, C., Daguin, V., Naveilhan, P., Neveu, I., Soullilou, Jp, Vanhove, B., Plat, M., Botte, F., Venturi, F., LUCA DENARO, Seveso, M., Manara, R., Zampieri, P., Avella, Domenico D., Rubello, D., Ancona, E., Hantraye, P., Cozzi, E., Commissariat à l'énergie atomique et aux énergies alternatives (CEA), ura2210, Centre National de la Recherche Scientifique (CNRS), Universita di Padova, Consorzio per la Ricerca sul Trapianto di Organi, Partenaires INRAE, Azienda Ospedaliera di Padova, Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Unité Expérimentale de Physiologie Animale de l‘Orfrasiére (UE PAO), Institut National de la Recherche Agronomique (INRA), Ospedale 'Santa Maria della Misericordia' = University Hospital 'Santa Maria della Misericordia', Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), ProdInra, Migration, Università degli Studi di Padova = University of Padua (Unipd), and Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV] Life Sciences [q-bio], XENOGREFFE, [SDV]Life Sciences [q-bio], [INFO]Computer Science [cs], HISTOLOGIE, [INFO] Computer Science [cs], EMBRYON TRANSGENIQUE, MACAQUE, ComputingMilieux_MISCELLANEOUS
Abstract: LB01; International audience
Published: 2010

37. Lentiviral Vectors That Express UGT1A1 in Liver and Contain Mir-142 Target Sequences Normalize Hyperbilirubinemia in Gunn Rats

Author: Anne Dariel, Séverine Remy, Tuan Huy Nguyen, Nicolas Ferry, Ignacio Anegon, Sébastien Boni, Guillaume Podevin, Claire Usal, Sophie Laplanche, Françoise Schmitt, Virginie Pichard, Anne Myara, Maude Flageul, Philippe Labrune, Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), Faculté de Médecine, Université Francois Rabelais [Tours], Laboratoire de Thérapie Génique Translationnelle des Maladies Génétiques (Inserm UMR 1089), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Faculté de Médecine - Université de Nantes, Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Plateforme d’Analyses Cellulaires et Moléculaires - PACeM [Angers], Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Service de Biologie [GH Saint-Joseph - APHP], Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), UMR643, 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), UMR S948 Biothérapies hépatiques, and Neurology
Subjects: Male, Time Factors, Crigler–Najjar syndrome, RNA Stability, Genetic enhancement, [SDV]Life Sciences [q-bio], Genetic Vectors, Rats, Gunn, Gene Transfer, Antigen-Presenting Cells, Biology, digestive system, Antibodies, 03 medical and health sciences, 0302 clinical medicine, Multiplicity of infection, Immune system, Transduction, Genetic, medicine, Animals, Humans, Prealbumin, RNA, Messenger, Vector (molecular biology), Crigler–Najjar Syndrome, Glucuronosyltransferase, Promoter Regions, Genetic, Antigen-presenting cell, Crigler-Najjar Syndrome, 030304 developmental biology, 0303 health sciences, Hepatology, Lentivirus, Gastroenterology, Bilirubin, MicroRNA, Genetic Therapy, medicine.disease, Molecular biology, Rats, 3. Good health, Disease Models, Animal, MicroRNAs, Haematopoiesis, Real-time polymerase chain reaction, Liver, 030220 oncology & carcinogenesis, Biomarkers, HeLa Cells
Abstract: International audience; Background & AimsCrigler–Najjar type 1 (CN-I) is an inherited liver disease caused by an absence of bilirubin–uridine 5′-diphosphate–glucuronosyltransferase (UGT1A1) activity. It results in life-threatening levels of unconjugated bilirubin, and therapeutic options are limited. We used adult Gunn rats (an animal model of the disease) to evaluate the efficiency of lentiviral-based gene therapy to express UGT1A1 in liver. Methods Gunn rats were given intraportal injections of VSVG-pseudotyped lentiviral vectors that encode UGT1A1 under the control of a liver-specific transthyretin promoter (mTTR.hUGT1A1); this vector does not contain target sequences for miR-142, a microRNA that is expressed specifically in hematopoietic cells. Rats were also injected with the vector mTTR.hUGT1A1.142T, which contains 4 copies of the miR-142 target sequences; its messenger RNA should be degraded in antigen-presenting cells. Bilirubinemia was monitored, and the presence of transduced hepatocytes was analyzed by quantitative polymerase chain reaction. Vector expression was tested in vitro in rat hematopoietic cells. Results In Gunn rats, bilirubin levels normalized 2 weeks after administration of mTTR.hUGT1A1. However, hyperbilirubinemia resumed 8 weeks after vector administration, concomitant with the induction of an immune response. In contrast, in rats injected with mTTR-UGT1A1.142T, bilirubin levels normalized for up to 6 months and transduced cells were not eliminated. Conclusions Lentiviral vectors that express UGT1A1 reduce hyperbilirubinemia in immunocompetent Gunn rats for at least 6 months. The immune response against virally expressed UGT1A1 can be circumvented by inclusion of miR-142 target sequences, which reduce vector expression in antigen-presenting cells. This lentiviral-based gene therapy approach might be developed to treat patients with CN-I.
Published: 2010
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38. White matter reactive astrocytes express nuclear estrogen receptor alpha (ESR1) in experimentalautoimmune encephalomyelitis and multiple sclerosis

Author: GIRAUD, Sébastien, Seilhean, Danielle, Pham-Dinh, Danielle, Nicot, Arnaud, Nicot, Arnaud, Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), 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), 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), Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, and Inserm, Université Pierre et Marie Curie (BQR), Région Pays de Loire
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; The mechanism of action of estrogens as modulators of inflammation and neuroprotection in neurodegenerative disorders is a matter of great debate. Whereas an active astrocytic involvement in the physiopathology of neurodegenerative or neuroinflammatory disorders has now emerged, the glial expression pattern of estrogen receptors (ER) in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE) remains undefined. We found that nuclear ERalpha is expressed by reactive astrocytes in the white matter cord during chronic EAE in mice, and that estradiol treatment after EAE onset alleviated ongoing EAE symptoms and was associated in the spinal cord white matter with a reduction of astroglial reactivity, leukocytic infiltration and axonal loss. In order to investigate the astrocytic expression of ERalpha in MS, archival paraffin sections from frontal cortex of secondary progressive MS patients and control subjects were used for double immunocytochemistry. ERalpha was hardly detected in the white matter tracts of control subjects, or around blood vessels where increased GFAP staining was observed in control subject 1 (Wegener case). In the grey matter, moderate ERalpha immunoreactivy in astrocytic fibers could be observed in layer I, particularly for astrocytes contacting dilated blood vessels in control subject 1. Otherwise, cortical astrocytes with several processes and in close proximity to blood vessels were not stained for ERalpha in control and MS subjects. In the normal appearing white matter of MS patients, astrocytes expressed relatively low levels of extranuclear ERalpha compared to those in the white matter at the rim of chronic plaques (identified by the lack of Sudan black staining). In contrast, reactive astrocytes in the demyelinating white matter (as assessed by lower Sudan black staining and CD68 immunoreactivity on adjacent sections) exhibited nuclear ERalpha staining whereas ERalpha was not evidenced in chronic plaques though dense GFAP immunoreactive fibers were detected. Herein, we show for the first time that ERalpha is expressed by reactive astrocytes in MS white matter, with a nuclear staining that could be only observed in demyelinating lesions. These data support white matter astroglia cells as an important direct target for estrogen anti-inflammatory actions in MS.
Published: 2010
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39. Multistatic sonar imaging: comparisons between the matched filtering method and a reconstruction method based on the Kirchhoff approximation

Author: Franck Daout, Caroline Herve, Françoise Schmitt, Jean-Pierre Sessarego, Régine Guillermin, Laboratoire de Mécanique et d'Acoustique [Marseille] (LMA ), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Institut de transplantation et de recherche en transplantation (ITERT), Groupe d'Electromagnétisme Appliqué (GEA), Université Paris Nanterre (UPN), collaboration Univeristé de Paris X (F. Schmitt, F. Daout), and Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)
Subjects: Synthetic aperture radar, Image formation, [SPI.ACOU]Engineering Sciences [physics]/Acoustics [physics.class-ph], Acoustics and Ultrasonics, Gaussian, antenne synthétique, Reconstruction algorithm, sonar, 01 natural sciences, [PHYS.MECA.ACOU]Physics [physics]/Mechanics [physics]/Acoustics [physics.class-ph], symbols.namesake, Fourier transform, Robustness (computer science), 0103 physical sciences, Electronic engineering, symbols, Synthetic aperture sonar, Deconvolution, 010301 acoustics, Algorithm, multistatique, Music, Mathematics
Abstract: In this study, comparisons are made between two imaging techniques in the context of the Multistatic Synthetic Aperture Sonar (SAS): the Matched Filtering method and a reconstruction method based on the Kirchhoff Approximation (KA). The Matched Filtering Algorithm (MFA) is the classical method used for image formation purposes in synthetic aperture systems. In this method the field diffracted by the target is approached by the "point scatterers" model. One of the first objective of this work is to develop a more complex and more realistic model than the well known "point scatterers" model. In addition, the aim is to get not only the shape and the size of target but also some quantitative information about its physical properties. Thus, a forward model based on the KA is proposed to get a more realistic description of the scattered field and a reconstruction method has been obtained through the use of a 2-D Fourier transform of this forward model. The algorithm hence obtained is named: "Imaging Reconstruction Algorithm in the Kirchhoff Approximation" (IRAKA). In this paper the IRAKA is compared to the MFA in order to check its capability to reconstruct target shape. Images of 2-D targets of circular and elliptic cross-sections are reconstructed with the MFA and with the IRAKA from both numerical data and tank experimental data. These imaging methods are compared in terms of quality of the shape reconstruction and in terms of their robustness to noise in a given multistatic configuration. Both algorithms are also used to reconstruct images of a 2-D target of circular cross-section in a multistatic forward looking SAS context. With a good Signal to Noise Ratio (SNR) we get better results with the IRAKA than with the MFA in terms of the quality of target shape reconstruction. In presence of additive white Gaussian circular noise, the MFA off course, gives better results than the IRAKA. Nevertheless, using a technique of stabilization of the deconvolution, it has been possible to improve the performances of the IRAKA even in presence of additive noise.
Published: 2010

40. Anticorps monoclonaux en transplantation

Author: Vanhove, Bernard, Immunointervention dans les allo et xénotransplantations, and Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN
Subjects: Transplantation, anticorps monoclonaux, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract: National audience; Dans les années 1970, les anticorps polyclonaux antilymphocytes ont démontré leur efficacité en transplantation. Puis, après leur découverte par Kohler et Milstein en 1975, les anticorps monoclonaux (Acm) ont été utilisés pour affiner la spécificité de l'immunosuppression. Certains ont connu un développement clinique et font désormais partie de l'arsenal thérapeutique. Beaucoup d'autres sont encore en développement et ont pour ambition de se substituer à l'immunosuppression pharmacologique en induisant des mécanismes de régulation immunologique.
Published: 2009

41. Potential role of soluble ST2 protein in idiopathic nephrotic syndrome recurrence following kidney transplantation

Author: Jeanne Naulet, Laurent Tesson, Maud Kamal, Asta Valanciuté, Ludmilla Le Berre, Yohann Foucher, Sarah Bruneau, Djillali Sahali, Jacques Dantal, Jean-Paul Soulillou, Caroline Hervé, Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Institut de transplantation et de recherche en transplantation (ITERT), 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), and Guellaen, Georges
Subjects: Nephrology, Male, Nephrotic Syndrome, 030232 urology & nephrology, MESH: Rats, Sprague-Dawley, Gastroenterology, MESH: Kidney Transplantation, Rats, Sprague-Dawley, Mice, 0302 clinical medicine, Focal segmental glomerulosclerosis, MESH: Child, Chlorocebus aethiops, Secondary Prevention, MESH: Animals, Child, Kidney transplantation, Cell Line, Transformed, MESH: Receptors, Cell Surface, 0303 health sciences, Proteinuria, MESH: Middle Aged, Glomerulonephritis, Middle Aged, 3. Good health, MESH: COS Cells, MESH: Young Adult, COS Cells, Female, MESH: Rats, Inbred Lew, medicine.symptom, Adult, medicine.medical_specialty, Adolescent, MESH: Rats, Receptors, Cell Surface, MESH: Rats, Inbred BUF, 03 medical and health sciences, Young Adult, Internal medicine, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Cell Line, Transformed, Rats, Inbred BUF, MESH: Mice, 030304 developmental biology, Retrospective Studies, MESH: Adolescent, MESH: Humans, business.industry, MESH: Biological Markers, MESH: Adult, MESH: Retrospective Studies, medicine.disease, Interleukin-1 Receptor-Like 1 Protein, Kidney Transplantation, MESH: Cercopithecus aethiops, MESH: Male, Rats, MESH: Recurrence, Transplantation, Endocrinology, Rats, Inbred Lew, MESH: Nephrotic Syndrome, business, Nephrotic syndrome, MESH: Female, Biomarkers, Kidney disease
Abstract: International audience; BACKGROUND: Corticosteroid-resistant idiopathic nephrotic syndrome (INS) recurs rapidly after transplantation in 30% to 50% of transplant recipients, suggesting the presence of 1 or more circulating factors that alter the glomerular filtration barrier. We investigated the possible role in INS recurrence of soluble ST2 (sST2) protein, a marker of T helper type 2 (T(H)2) cells and a factor predicted to be regulated by the transcription factor c-Maf; involvement of sST2 protein would be consistent with the observation that both T(H)2 cells and c-Maf appear to be activated during INS relapse. STUDY DESIGN: Retrospective observational study. SETTING & PARTICIPANTS: Patients with biopsy-proven corticosteroid-resistant INS who had undergone kidney transplantation between September 1983 and April 2007 (n = 71). A control group consisting of proteinuric transplant recipients with kidney failure unrelated to INS (n = 34). PREDICTOR: Patients who developed INS recurrence after transplantation (n = 31) were compared with those in whom INS did not recur (n = 40) and the control group. Recurrence of INS was defined as urine protein excretion greater than 2 g/d immediately after transplantation that persisted at greater than 1 g/d despite treatment or a kidney graft biopsy showing minimal change glomerulonephritis or focal segmental glomerulosclerosis. OUTCOMES & MEASUREMENTS: Urine protein excretion in the 3 groups was 5.0 g/d (range, 1.3 to 10.5), 0.14 g/d (range, 0 to 0.46), and 4.3 g/d (range, 3 to 6.2). The sST2 protein was analyzed both quantitatively and qualitatively in patient sera, and its activity was tested in vitro on a mouse podocyte cell line and in vivo in rats. RESULTS: sST2 protein levels were significantly increased after transplantation in patients with INS recurrence compared with the 2 other groups (617.5 versus 23 pg/mL; P < 0.001 and 158.5 pg/mL; P < 0.01 respectively). However, patients with recurrence expressed a normal sST2 isoform, and the sST2 protein was unable to induce podocyte injury in vitro or trigger proteinuria in rats. LIMITATIONS: Pretransplantation and posttransplantation sera do not always represent paired samples. CONCLUSIONS: These data suggest that sST2 protein is a marker of INS recurrence that does not seem to be involved in the development of INS.
Published: 2009
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42. Transgenic porcine embryonic xenografts as a treatment for Parkinson's disease in non-human primates

Author: Aron, B.R., Padoan, A., Vadori, M., Boldrin, M., Cavicchioli, Lionel, de Benedictis, G.M., Fante, F., Seveso, M., Sgarabotto, D., Jan, Charlie, Daguin, V., Naveilhan, P., Neveu, I., Soulillou, J.P., Vanhove, B., Plat, Martine, Botté, Françoise, Venturi, Eric, Denaro, L., Manara, R., Zampieri, P., d'Avella, D., Rubello, D., Ancona, E., Hantraye, P., Cozzi, Elena, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), ura2210, Centre National de la Recherche Scientifique (CNRS), Universita di Padova, Consortium for Research in Organ Transplantation (CORIT), Azienda Ospedaliera di Padova, Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Centre hospitalier universitaire de Nantes (CHU Nantes), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Unité Expérimentale de Physiologie Animale de l‘Orfrasiére (UE PAO), Institut National de la Recherche Agronomique (INRA), Università degli Studi di Perugia (UNIPG), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Padova = University of Padua (Unipd), Consorzio per la Ricerca sul Trapianto d'Organ = Consortium for Research in Organ Transplantation (CORIT), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Perugia = University of Perugia (UNIPG), and ProdInra, Migration
Subjects: [SDV] Life Sciences [q-bio], XENOGREFFE, EMBRYON PORCIN TRANSGENIQUE, [SDV]Life Sciences [q-bio], [INFO]Computer Science [cs], [INFO] Computer Science [cs], ComputingMilieux_MISCELLANEOUS
Abstract: Communication orale LB IXA O-1; International audience
Published: 2009

43. Pathological lesions in colonic biopsies during Parkinson's disease

Author: Yann Touchefeu, J. P. Galmiche, Emmanuel Coron, S Vrignaud, Michel Neunlist, Thibaud Lebouvier, Pascal Derkinderen, Philippe Naveilhan, S. Bruley des Varannes, Philippe Damier, Tanguy Chaumette, Neuropathies du système nerveux entérique et pathologies digestives, implication des cellules gliales entériques, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), Clinique neurologique, Hôpital Laennec, CIC - Nantes, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'anesthésie et réanimation chirurgiale, Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, and Neunlist, Michel
Subjects: Male, Pathology, medicine.medical_specialty, Parkinson's disease, Colon, Biopsy, Population, Context (language use), Substantia nigra, Pilot Projects, Enteric Nervous System, Dopamine, medicine, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], education, Pathological, Aged, education.field_of_study, business.industry, Dopaminergic, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Parkinson Disease, Submucous Plexus, medicine.disease, Immunohistochemistry, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Case-Control Studies, Nerve Degeneration, alpha-Synuclein, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Enteric nervous system, business, Constipation, medicine.drug
Abstract: Parkinson’s disease (PD) is a neurodegenerative condition that affects 1% of the population over 65 years of age. The two pathological hallmarks of PD are a loss of dopaminergic neurons in the substantia nigra (SN) and the presence of cytoplasmic eosinophilic inclusions termed Lewy bodies (LBs), whose main component is phosphorylated α-synuclein.1 This degeneration of SN neurons leads to a dopamine deficiency responsible for the major motor symptoms. Nevertheless, it has become increasingly evident that PD is a multicentric neurodegenerative process that also affects neuronal structures outside the SN.2 In this context, various reports performed on surgical or autopsy specimens have shown that the enteric nervous system (ENS) is affected during PD.3 4 However, it is still a matter of debate whether these alterations occur early in the course of the disease. This is mainly due to a lack of accessibility to the ENS in the living patients. Therefore, demonstrating (1) the ability to study the ENS using routine colonic biopsies and (2) the presence of lesions characteristics …
Published: 2008
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44. Superiority of bone marrow-derived dendritic cells over monocyte-derived ones for the expansion of regulatory T cells in the macaque

Author: Philippe Moullier, Régis Josien, Fabienne Rolling, Maria-Cristina Cuturi, Jack-Yves Deschamps, Elise Chiffoleau, Gaelle Beriou, Michèle Heslan, Brigitte Alliot-Licht, Joanna Ashton-Chess, Aurélie Moreau, Vecteurs viraux et transfert de gènes in vivo, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Harvard Medical School [Boston] (HMS), Développement et Pathologie du Tissu Musculaire (DPTM), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Nantes, Ecole Nationale Vétérinaire de Nantes, Faculté de Médecine, and Université Francois Rabelais [Tours]
Subjects: [SDV]Life Sciences [q-bio], CD14, Lipopolysaccharide Receptors, chemical and pharmacologic phenomena, Antigens, CD34, Bone Marrow Cells, Biology, Lymphocyte Activation, T-Lymphocytes, Regulatory, Monocytes, Immunophenotyping, medicine, Animals, IL-2 receptor, Antigen-presenting cell, Transplantation, Monocyte, Interleukin-2 Receptor alpha Subunit, FOXP3, hemic and immune systems, Dendritic cell, Dendritic Cells, NONHUMAN PRIMATE, T REGULATORY CELLS, Macaca fascicularis, medicine.anatomical_structure, Immunology, Models, Animal, Bone marrow
Abstract: Regulatory T cells (Treg) have been identified as playing a pivotal role in the control of tolerance and in the suppression of pathologic immune responses in autoimmune diseases, transplantation, and graft-versus-host disease. Treg expanded ex vivo by dendritic cells could be potential reagents to promote antigen-specific tolerance in vivo. However, in vivo studies have been carried out mostly in rodents and will need validation in primates before clinical application. We characterized macaque dendritic cell derived either from bone marrow with and without prior CD34+ cell selection (BMDC), or from CD14+ peripheral blood mononuclear cells (Mo-DC). We demonstrate that with a semi-mature phenotype, BMDC are superior to Mo-DC in their capacity to expand freshly isolated allogeneic macaque CD4+ CD25+ CD127- Foxp3+ Treg in vitro in the presence of interleukin-2. Moreover, the expanded Treg maintain their phenotype and suppressive activity. These data provide a step toward the use of macaque dendritic cell to expand Treg for future preclinical testing.
Published: 2008
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45. The clinical spectrum of IgM-related amyloidosis: a French nationwide retrospective study of 72 patients

Author: Richard Delarue, Mathilde Hunault-Berger, Olivier Tournilhac, Arnaud Jaccard, Philippe Rodon, Pierre Morel, Marc Bernard, Arnaud Hot, Mohamed Hamidou, Benjamin Terrier, Fadi Fakhouri, Olivier Gisserot, Jean-Paul Fermand, Bernard Grosbois, Caroline Elie, Jacques Dantal, Véronique Leblond, Valérie Coiteux, Jean-Luc Harousseau, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Service d'immuno-hématologie 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), Fédération des maladies infectieuses, CHU Clermont-Ferrand, Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Institut de transplantation et de recherche en transplantation (ITERT), Laboratoire Hubert Curien [Saint Etienne] (LHC), Institut d'Optique Graduate School (IOGS)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Service de Médecine interne et immunologie clinique [Rennes] = internal medicine and clinical immunology [Rennes], CHU Pontchaillou [Rennes], Laboratoire de physique des milieux ionisés et applications (LPMIA), Université Henri Poincaré - Nancy 1 (UHP)-Centre National de la Recherche Scientifique (CNRS), Service d'immunologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service de néphrologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Service de médecine interne, Physique des milieux ionisés et applications (LPMIA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations ( PMRIL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université de Nantes ( UN ) -IFR26-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -ITUN, Institut de transplantation et de recherche en transplantation ( ITERT ), Laboratoire Hubert Curien [Saint Etienne] ( LHC ), Institut d'Optique Graduate School ( IOGS ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Centre National de la Recherche Scientifique ( CNRS ), Physique des milieux ionisés et applications ( LPMIA ), Université Henri Poincaré - Nancy 1 ( UHP ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP)
Subjects: Male, Pathology, MESH: Remission Induction, MESH : Retrospective Studies, medicine.medical_treatment, MESH : Aged, MESH : Alkylating Agents, MESH: Antigens, CD20, Hematopoietic stem cell transplantation, Gastroenterology, MESH: Antibodies, Monoclonal, 0302 clinical medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Treatment Outcome, Aged, 80 and over, MESH: Middle Aged, MESH: Heart Diseases, Amyloidosis, MESH: Immunologic Factors, Remission Induction, Hematopoietic Stem Cell Transplantation, Antibodies, Monoclonal, General Medicine, MESH: Immunoglobulin M, 3. Good health, Survival Rate, 030220 oncology & carcinogenesis, MESH : Paraproteinemias, Rituximab, medicine.medical_specialty, Alkylating Agents, MESH: Serum Albumin, 03 medical and health sciences, MESH: Lymphatic Diseases, MESH : Antigens, CD20, MESH : Hematopoietic Stem Cell Transplantation, AL amyloidosis, Humans, Immunologic Factors, MESH : Middle Aged, MESH : Aged, 80 and over, Lymphatic Diseases, Aged, Retrospective Studies, MESH: Humans, MESH : Humans, MESH: Adult, MESH: Retrospective Studies, medicine.disease, MESH : Amyloidosis, Complication, MESH: Female, Lung Diseases, Paraproteinemias, Antibodies, Monoclonal, Murine-Derived, MESH: Lung Diseases, MESH: Paraproteinemias, MESH: Aged, 80 and over, MESH : Purines, MESH : Female, Prospective cohort study, MESH: Aged, MESH : Lung Diseases, MESH : Lymphatic Diseases, MESH: Purines, Middle Aged, MESH : Adult, MESH : Survival Rate, Hematologic Response, MESH: Alkylating Agents, Treatment Outcome, MESH : Antibodies, Monoclonal, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, France, medicine.drug, Adult, Heart Diseases, MESH: Survival Rate, MESH : Immunoglobulin M, MESH : Male, MESH : Treatment Outcome, MESH : Immunologic Factors, MESH : Serum Albumin, Internal medicine, medicine, MESH: Amyloidosis, MESH : France, Serum Albumin, MESH: Hematopoietic Stem Cell Transplantation, MESH : Remission Induction, business.industry, Retrospective cohort study, MESH : Heart Diseases, Antigens, CD20, MESH: Male, MESH: France, Immunoglobulin M, Purines, business, 030215 immunology
Abstract: International audience; Immunoglobulin M (IgM)-related amyloidosis remains a rare and little-known complication of monoclonal IgM-associated disorders. We sought to determine the clinical and laboratory presentation, response to treatment, and outcome of patients with IgM-related amyloidosis in the era of new therapeutic approaches. We conducted a retrospective study in 29 French centers to identify patients with monoclonal IgM and biopsy-proven amyloidosis; we reviewed patients' records and collected relevant clinical and laboratory data. We identified 72 patients with IgM-related amyloidosis. Systemic primary amyloidosis (AL) was present in 64, peritumoral AL in 5, and systemic secondary amyloidosis (AA) in 3 patients. A peculiar pattern of relatively frequent lymph node (31%) and lung (17%) involvement was noted in patients with systemic AL amyloidosis. Response to alkylating agents was poor, with a hematologic response in 37%, a complete remission in 0%, and an organ response in 21%. Response to hematopoietic stem cell transplantation showed a hematologic response in 100% with complete remission in 75% and an organ response in 75%. Purine analogs and rituximab induced a hematologic response in 73% and 60%, respectively, with complete remission in 9% and 0% and an organ response in 55% and 0%, respectively. In multivariate analysis, prognostic factors for survival were serum albumin level < or =3.5 g/dL (p = 0.018) and heart involvement (p = 0.0034). Further prospective studies are needed in patients with IgM-related amyloidosis, with special emphasis on treatment options: hematopoietic stem cell transplantation and purine analogs could represent the most effective therapies. The identification of adverse prognostic factors of survival could be useful for those managing and making treatment decisions for these patients.
Published: 2008
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46. Activity-dependent regulation of tyrosine hydroxylase expression in the enteric nervous system

Author: Chevalier, Julien, Derkinderen, Pascal, Gomes, Priya, Thinard, Reynald, Naveilhan, Philippe, Vanden Berghe, Pieter, Neunlist, Michel, Neunlist, Michel, Neuropathies du système nerveux entérique et pathologies digestives, implication des cellules gliales entériques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes (UN), Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), Clinique neurologique, Hôpital Laennec, Center for Gastroenterological Research, Université Catholique de Louvain = Catholic University of Louvain (UCL), Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Agence Nationale de la Recherche (ANR) Nutrisens Action Spécifique of the University of Nantes Fonds voor Wetenschappelijk Onderzoek (FWO) France Parkinson ADPLA (association des parkinsoniens de Loire Atlantique) Féderation des groupements de Parkinsoniens (Vendée), and Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Neurons, Veratridine, Calcium Channels, L-Type, Tyrosine 3-Monooxygenase, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Cyclic AMP-Dependent Protein Kinases, Electric Stimulation, Enteric Nervous System, Gene Expression Regulation, Enzymologic, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Potassium Chloride, Rats, Intestines, Rats, Sprague-Dawley, Pregnancy, Alimentary, Cyclic AMP, Animals, Calcium, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Extracellular Signal-Regulated MAP Kinases, Cells, Cultured, Protein Kinase C
Abstract: International audience; The regulation of neuromediator expression by neuronal activity in the enteric nervous system (ENS) is currently unknown. Using primary cultures of ENS derived from rat embryonic intestine, we have characterized the regulation of tyrosine hydroxylase (TH), a key enzyme involved in the synthesis of dopamine. Depolarization induced either by 40 mm KCl, veratridine or by electrical field stimulation produced a robust and significant increase in the proportion of TH immunoreactive (TH-IR) neurons (total neuronal population was identified with PGP9.5 or Hu) compared to control. This increase in the proportion of TH-IR neurons was significantly reduced by the sodium channel blocker tetrodotoxin (0.5 mum), demonstrating that neuronal activity was critically involved in the effects of these depolarizing stimuli. KCl also increased the proportion of VIP-IR but not nNOS-IR enteric neurons. The KCl-induced increase in TH expression was partly reduced in the presence of the nicotinic receptor antagonist hexamethonium (100 mum), of noradrenaline (1 mum) and of the alpha(2)-adrenoreceptor agonist clonidine (1 mum). Combining pharmacological and calcium imaging studies, we have further shown that L-type calcium channels were involved in the increase of TH expression induced by KCl. Finally, using specific inhibitors, we have shown that both protein kinases A and C as well as the extracellular signal-regulated kinases were required for the increase in the proportion of TH-IR neurons induced by KCl. These results are the first demonstration that TH phenotype of enteric neurons can be regulated by neuronal activity. They could also set the basis for the study of the pathways and mechanisms involved in the neurochemical plasticity observed both during ENS development and in inflammatory enteric neuropathies.
Published: 2008
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47. Related fibroblast growth factor receptor genes exist in the human genome

Author: Elisabeth Houssaint, Marie-Claude Gesnel, P R Blanquet, Breathnach R, Champion-Arnaud P, Alicia Torriglia, Yves Courtois, Recherche sur les effecteurs lymphocytaires T, Institut National de la Santé et de la Recherche Médicale (INSERM), Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Gérontologie, Neurobiologie des processus adaptatifs (NPA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie des Maladies Oculaires : Innovations Therapeutiques, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR58-Institut National de la Santé et de la Recherche Médicale (INSERM), Departmento de Bioquimica, Facultad de Medicina, Universidad de la Republica, Développement, vieillissement et pathologie de la rétine, and Torriglia, Alicia
Subjects: MESH: Oligonucleotide Probes, Basic fibroblast growth factor, MESH: Amino Acid Sequence, Filaggrin Proteins, MESH: Receptors, Fibroblast Growth Factor, MESH: Base Sequence, chemistry.chemical_compound, MESH: Animals, Cloning, Molecular, MESH: Receptors, Cell Surface, Multidisciplinary, MESH: Kinetics, MESH: DNA, Fibroblast growth factor receptor, MESH: Fibroblast Growth Factors, Research Article, Molecular Sequence Data, Receptors, Cell Surface, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Transfection, MESH: Sequence Homology, Nucleic Acid, Cell Line, FGF9, Sequence Homology, Nucleic Acid, MESH: Gene Library, Animals, Humans, MESH: Cloning, Molecular, Amino Acid Sequence, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Genome, Human, Gene Library, MESH: Molecular Sequence Data, MESH: Humans, FGF10, Base Sequence, Genome, Human, Fibroblast growth factor receptor 2, MESH: Transfection, DNA, Fibroblast growth factor receptor 4, Fibroblast growth factor receptor 3, FGF1, Receptors, Fibroblast Growth Factor, Molecular biology, MESH: Cell Line, Fibroblast Growth Factors, Kinetics, chemistry, Oligonucleotide Probes
Abstract: International audience; We have isolated, from a human tumor cDNA library, a gene encoding a putative receptor-like protein-tyrosine kinase that we call TK14. The amino acid sequence of the TK14 protein is closely related to the available partial sequence of the mouse protein bek, and more distantly related to the sequences of a chicken basic fibroblast growth factor receptor (73% sequence homology) and the apparent human equivalent of this receptor, the FLG protein (encoded by the fms-like tyrosine kinase gene). Overexpression of the TK14 protein by transfection of COS-1 cells with the corresponding cDNA in a simian virus 40-based expression vector leads to the appearance of new cell-surface binding sites for both acidic and basic fibroblast growth factors. This has been demonstrated by specific binding assays and chemical cross-linking experiments using 125I-labeled growth factors. It appears, therefore, that the human genome contains at least two distinct genes, for TK14 and FLG, that code for related fibroblast growth factor receptors.
Published: 1990
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48. Semi-Markov model: evolution analysis of chronic diseases

Author: Foucher, Yohann, Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Université Montpellier I, Jean-Pierre Daurès(jean-pierre.daures@inserm.fr), and Foucher, Yohann
Subjects: kidney, temps-dépendant, [SDV]Life Sciences [q-bio], rein, HIV, VIH, parametric, frailty, survival, time-dependent, multi-état, paramétrique, [SDV] Life Sciences [q-bio], multistate, survie, processus, fragilité, process, ROC, semi-Markov, transplantation
Abstract: The study of the evolution of a patient constitutes an important field in clinical research. Recently, the development of the multi-state models allows to study this dynamics by taking into account several health states. In this manuscript, we use the semi-markovian models. This type of process distinguishes the durations in the states and the trajectories of the transitions, contrary to the traditional markovian approach. We proposed several adaptations to apply this type of model: the interval-censoring, the choice of the distributions of the durations and the introduction of the covariates. A goodness-of-fit statistic is also proposed to check the stationnarity assumption. Lastly, an original method, including the theory of the ROC curves, is presented to define relevant health states. These developments are mainly applied to kidney transplant recipient follow-up (DIVAT database)., L'étude de l'évolution du pronostic de santé d'un patient constitue un domaine important en recherche clinique. Récemment, le développement des modèles multi-états a permis d'étudier cette dynamique en prenant en compte plusieurs états de santé. Dans ce manuscrit, nous utilisons plus particulièrement les modèles semi-markoviens. Ce type de processus distingue les temps de séjour dans les états et les trajectoires des transitions, contrairement à l'approche markovienne classique. Nous avons proposé plusieurs adaptations pour pouvoir appliquer ce type de modèle : la censure par intervalle, le choix des distributions des temps d'attente et l'introduction des covariables. Un test d'adéquation est aussi proposé pour vérifier l'hypothèse de stationnarité. Enfin, une méthode originale, incluant la théorie des courbes ROC, est présentée pour définir des états de santé pertinents au regard du pronostic. Ces développements sont principalement appliqués à une cohorte de patients greffés rénaux (base de données DIVAT).
Published: 2007

49. Modèles semi-Markoviens : Application à l'analyse de l'évolution de pathologies chroniques

Author: Foucher, Yohann, Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Université Montpellier I, and Jean-Pierre Daurès(jean-pierre.daures@inserm.fr)
Subjects: kidney, temps-dépendant, [SDV]Life Sciences [q-bio], rein, HIV, VIH, parametric, frailty, survival, time-dependent, multi-état, paramétrique, multistate, survie, processus, fragilité, process, ROC, semi-Markov, transplantation
Abstract: The study of the evolution of a patient constitutes an important field in clinical research. Recently, the development of the multi-state models allows to study this dynamics by taking into account several health states. In this manuscript, we use the semi-markovian models. This type of process distinguishes the durations in the states and the trajectories of the transitions, contrary to the traditional markovian approach. We proposed several adaptations to apply this type of model: the interval-censoring, the choice of the distributions of the durations and the introduction of the covariates. A goodness-of-fit statistic is also proposed to check the stationnarity assumption. Lastly, an original method, including the theory of the ROC curves, is presented to define relevant health states. These developments are mainly applied to kidney transplant recipient follow-up (DIVAT database).; L'étude de l'évolution du pronostic de santé d'un patient constitue un domaine important en recherche clinique. Récemment, le développement des modèles multi-états a permis d'étudier cette dynamique en prenant en compte plusieurs états de santé. Dans ce manuscrit, nous utilisons plus particulièrement les modèles semi-markoviens. Ce type de processus distingue les temps de séjour dans les états et les trajectoires des transitions, contrairement à l'approche markovienne classique. Nous avons proposé plusieurs adaptations pour pouvoir appliquer ce type de modèle : la censure par intervalle, le choix des distributions des temps d'attente et l'introduction des covariables. Un test d'adéquation est aussi proposé pour vérifier l'hypothèse de stationnarité. Enfin, une méthode originale, incluant la théorie des courbes ROC, est présentée pour définir des états de santé pertinents au regard du pronostic. Ces développements sont principalement appliqués à une cohorte de patients greffés rénaux (base de données DIVAT).
Published: 2007

50. [Renal and urinary tract disease national research program]

Author: Stengel, Bénédicte, Antignac, Corinne, Baverel, Gabriel, Choukroun, Gabriel, Cussenot, Olivier, Dussaule, Jean-Claude, Friedlander, Gérard, Lang, Philippe, Lelièvre-Pégorier, Martine, Massy, Ziad, Monteiro, Renato, Parini, Angelo, Soulillou, Jean Paul, Baud, Laurent, Ronco, Pierre, Recherche en épidémiologie et biostatistique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropathies héréditaires et rein en développement, 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), 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), Faculté de médecine, RTH Laennec, Université de Picardie Jules Verne (UPJV), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (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), 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 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), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Paris Descartes - Paris 5 (UPD5)-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), Affectations Mineralisantes du Systeme Cardiovasculaire : Calcifications Arterielles et Valvulaires Aortiques, Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de transplantation et de recherche en transplantation (ITERT), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN), Immunointervention dans les allo et xénotransplantations, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM)-ITUN, Remodelage et Reparation du Tissu Renal, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Simon, Marie Francoise, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Picardie, CHU Amiens-Picardie, CHU Tenon [APHP], 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 ), 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 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), 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 ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Picardie Jules Verne ( UPJV ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de médecine moléculaire de Rangueil ( I2MR ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de transplantation et de recherche en transplantation ( ITERT ), Université de Nantes ( UN ), and Université de Nantes ( UN ) -IFR26-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -ITUN
Subjects: Urologic Diseases, MESH: Kidney Diseases, MESH: Humans, MESH : Urologic Diseases, Incidence, Research, MESH : Foundations, MESH : Humans, MESH : Research, Kidney Transplantation, MESH : Incidence, MESH: Urologic Diseases, MESH: Kidney Transplantation, MESH: France, MESH: Research, MESH: Foundations, MESH : Kidney Diseases, Humans, MESH : Kidney Transplantation, Kidney Diseases, France, MESH: Incidence, MESH : France, Foundations
Abstract: International audience; The National Institute of Health and Medical Research (Inserm), the Society of Nephrology, and the French Kidney Foundation recognized the need to create a National Research Program for kidney and urinary tract diseases. They organized a conference gathering 80 researchers to discuss the state-of-the art and evaluate the strengths and weaknesses of kidney and urinary tract disease research in France, and to identify research priorities. From these priorities emerged 11 of common interest: 1) conducting epidemiologic studies; 2) conducting large multicenter cohorts of well-phenotyped patients with blood, urine and biopsy biobanks; 3) developing large scale approach: transcriptomics, proteomics, metabolomics; 4) developing human and animal functional imaging techniques; 5) strengthening the expertise in renal pathology and electrophysiology; 6) developing animal models of kidney injury; 7) identifying nontraumatic diagnostic and prognostic biomarkers; 8) increasing research on the fetal programming of adult kidney diseases; 9) encouraging translational research from bench to bedside and to population; 10) creating centers grouping basic and clinical research workforces with critical mass and adequate logistic support; 11) integrating and developing european research programs.
Published: 2007
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