Search

Your search keyword '"TAN, Yossan-Var"' showing total 50 results
Start Over Author "TAN, Yossan-Var"
50 results on '"TAN, Yossan-Var"'

2. Reductions in synaptic proteins and selective alteration of prepulse inhibition in male C57BL/6 mice after postnatal administration of a VIP receptor (VIPR2) agonist

Author

Ago, Yukio, Condro, Michael C, Tan, Yossan-Var, Ghiani, Cristina A, Colwell, Christopher S, Cushman, Jesse D, Fanselow, Michael S, Hashimoto, Hitoshi, and Waschek, James A

Subjects
Pediatric, Schizophrenia, Brain Disorders, Behavioral and Social Science, Mental Health, Neurosciences, Underpinning research, 1.1 Normal biological development and functioning, Mental health, Neurological, Good Health and Well Being, Animals, Animals, Newborn, Disks Large Homolog 4 Protein, Fear, Female, Guanylate Kinases, Interpersonal Relations, Male, Membrane Proteins, Mice, Mice, Inbred C57BL, Motor Activity, Nerve Tissue Proteins, Peptides, Cyclic, Pregnancy, Prepulse Inhibition, Receptors, Vasoactive Intestinal Peptide, Type II, Reflex, Startle, Signal Transduction, Synapses, Synaptophysin, Vasoactive Intestinal Peptide, VPAC2 receptor, Prepulse inhibition, PSD-95, Mouse, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

RationaleAn abundance of genetic and epidemiologic evidence as well as longitudinal neuroimaging data point to developmental origins for schizophrenia and other mental health disorders. Recent clinical studies indicate that microduplications of VIPR2, encoding the vasoactive intestinal peptide (VIP) receptor VPAC2, confer significant risk for schizophrenia and autism spectrum disorder. Lymphocytes from patients with these mutations exhibited higher VIPR2 gene expression and VIP responsiveness (cAMP induction), but mechanisms by which overactive VPAC2 signaling may lead to these psychiatric disorders are unknown.ObjectivesWe subcutaneously administered the highly selective VPAC2 receptor agonist Ro 25-1553 to C57BL/6 mice from postnatal day 1 (P1) to P14 to determine if overactivation of VPAC2 receptor signaling during postnatal brain maturation affects synaptogenesis and selected behaviors.ResultsWestern blot analyses on P21 revealed significant reductions of synaptophysin and postsynaptic density protein 95 (PSD-95) in the prefrontal cortex, but not in the hippocampus in Ro 25-1553-treated mice. The same postnatally restricted treatment resulted in a disruption in prepulse inhibition of the acoustic startle measured in adult mice. No effects were observed in open-field locomotor activity, sociability in the three-chamber social interaction test, or fear conditioning or extinction.ConclusionOveractivation of the VPAC2 receptor in the postnatal mouse results in a reduction in synaptic proteins in the prefrontal cortex and selective alterations in prepulse inhibition. These findings suggest that the VIPR2-linkage to mental health disorders may be due in part to overactive VPAC2 receptor signaling during a critical time of synaptic maturation.

Published
2015

3. Calcium Signaling via Orai1 Is Essential for Induction of the Nuclear Orphan Receptor Pathway To Drive Th17 Differentiation

Author

Kim, Kyun-Do, Srikanth, Sonal, Tan, Yossan-Var, Yee, Ma-Khin, Jew, Marcus, Damoiseaux, Robert, Jung, Michael E, Shimizu, Saki, An, Dong Sung, Ribalet, Bernard, Waschek, James A, and Gwack, Yousang

Subjects
Medical Physiology, Biomedical and Clinical Sciences, Autoimmune Disease, Brain Disorders, Neurodegenerative, Neurosciences, 5.1 Pharmaceuticals, 1.1 Normal biological development and functioning, Underpinning research, Development of treatments and therapeutic interventions, Inflammatory and immune system, Animals, Calcium Channel Blockers, Calcium Channels, Calcium Signaling, Cell Differentiation, Cell Line, Encephalomyelitis, Autoimmune, Experimental, Humans, Ions, Mice, NFATC Transcription Factors, Nuclear Receptor Subfamily 1, Group F, Member 1, Nuclear Receptor Subfamily 1, Group F, Member 3, ORAI1 Protein, Orphan Nuclear Receptors, Promoter Regions, Genetic, Protein Binding, Response Elements, Small Molecule Libraries, Th1 Cells, Th17 Cells, Th2 Cells, Immunology, Biochemistry and cell biology
Abstract

Orai1 is the pore subunit of Ca(2+) release-activated Ca(2+) (CRAC) channels that stimulate downstream signaling pathways crucial for T cell activation. CRAC channels are an attractive therapeutic target for alleviation of autoimmune diseases. Using high-throughput chemical library screening targeting Orai1, we identified a novel class of small molecules that inhibit CRAC channel activity. One of these molecules, compound 5D, inhibited CRAC channel activity by blocking ion permeation. When included during differentiation, Th17 cells showed higher sensitivity to compound 5D than Th1 and Th2 cells. The selectivity was attributable to high dependence of promoters of retinoic-acid-receptor-related orphan receptors on the Ca(2+)-NFAT pathway. Blocking of CRAC channels drastically decreased recruitment of NFAT and histone modifications within key gene loci involved in Th17 differentiation. The impairment in Th17 differentiation by treatment with CRAC channel blocker was recapitulated in Orai1-deficient T cells, which could be rescued by exogenous expression of retinoic-acid-receptor-related orphan receptors or a constitutive active mutant of NFAT. In vivo administration of CRAC channel blockers effectively reduced the severity of experimental autoimmune encephalomyelitis by suppression of differentiation of inflammatory T cells. These results suggest that CRAC channel blockers can be considered as chemical templates for the development of therapeutic agents to suppress inflammatory responses.

Published
2014

7. Effective targeting of microglial P2X7 following intracerebroventricular delivery of nanobodies and nanobody-encoding AAVs

Author

Pinto-Espinoza, Carolina, primary, Guillou, Charlotte, additional, Rissiek, Björn, additional, Wilmes, Maximilian, additional, Javidi, Ehsan, additional, Schwarz, Nicole, additional, Junge, Marten, additional, Haag, Friedrich, additional, Liaukouskaya, Nastassia, additional, Wanner, Nicola, additional, Nicke, Annette, additional, Stortelers, Catelijne, additional, Tan, Yossan-Var, additional, Adriouch, Sahil, additional, Magnus, Tim, additional, and Koch-Nolte, Friedrich, additional

Published
2022
Full Text
View/download PDF

12. Editorial: GPCR in Inflammatory and Cancer Diseases

Author

Couvineau, Alain, Gomariz, Rosa P., and Tan, Yossan-Var

Subjects
Inflammation, SARS-CoV-2, neuropeptides, COVID-19, Neurodegenerative Diseases, Inflammatory Bowel Diseases, Autoimmune Diseases, Receptors, G-Protein-Coupled, COVID-19 Drug Treatment, Arthritis, Rheumatoid, Drug Combinations, Endocrinology, Editorial, GPCR, cancer, Humans, Angiotensin-Converting Enzyme 2, Phentolamine, Gastrointestinal Neoplasms, Vasoactive Intestinal Peptide
Published
2020

20. Spatial proximity between the VPAC1 receptor and the amino terminus of agonist and antagonist peptides reveals distinct sites of interaction

Author

Ceraudo, Emilie, Hierso, Régine, Tan, Yossan-Var, Murail, Samuel, Rouyer-Fessard, Christiane, Nicole, Pascal, Robert, Jean-Claude, Jamin, Nadège, Neumann, Jean-Michel, Robberecht, Patrick, Laburthe, Marc, Couvineau, Alain, Ceraudo, Emilie, Hierso, Régine, Tan, Yossan-Var, Murail, Samuel, Rouyer-Fessard, Christiane, Nicole, Pascal, Robert, Jean-Claude, Jamin, Nadège, Neumann, Jean-Michel, Robberecht, Patrick, Laburthe, Marc, and Couvineau, Alain

Abstract

Vasoactive intestinal peptide (VIP) plays a major role in pathophysiology. Our previous studies demonstrated that the VIP sequence 6-28 interacts with the N-terminal ectodomain (N-ted) of its receptor, VPAC1. Probes for VIP and receptor antagonist PG97- 269 were synthesized with a photolabile residue/Bpa at various positions and used to explore spatial proximity with VPAC1. PG97-269 probes with Bpa at position 0, 6, and 24 behaved as high-affinity receptor antagonists (Ki=12, 9, and 7 nM, respectively). Photolabeling experiments revealed that the [Bpa0]-VIP probe was in physical contact with VPAC1 Q135, while [Bpa0]-PG97- 269 was covalently bound to G62 residue of N-ted, indicating different binding sites. In contrast, photolabeling with [Bpa6]- and [Bpa 24]-PG97-269 showed that the distal domains of PG97-269 interacted with N-ted, as we previously showed for VIP. Substitution with alanine of the K143, T144, and T147 residues located in the first transmembrane domain of VPAC1 induced a loss of receptor affinity (IC 50=1035, 874, and 2070 nM, respectively), and pharmacological studies using VIP2-28 indicated that these three residues play an important role in VPAC1 interaction with the first histidine residue of VIP. These data demonstrate that VIP and PG97-269 bind to distinct domains of VPAC1. © FASEB., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2012

22. Small molecule blockers reveal an important role for Orai1-NFAT-orphan receptor pathway in Th17 differentiation (P5169)

Author

Kim, Kyun-Do, primary, Srikanth, Sonal, additional, Tan, Yossan-Var, additional, Yee, Ma-Khin, additional, Jew, Marcus, additional, Damoiseaux, Robert, additional, Jung, Michael E, additional, Shimizu, Saki, additional, An, Dong Sung, additional, Waschek, James A, additional, Ribalet, Bernard, additional, and Gwack, Yousang, additional

Published
2013
Full Text
View/download PDF

25. Spatial proximity between the VPAC1 receptor and the amino terminus of agonist and antagonist peptides reveals distinct sites of interaction

Author

Ceraudo, Emilie, primary, Hierso, Régine, additional, Tan, Yossan‐Var, additional, Murail, Samuel, additional, Rouyer‐Fessard, Christiane, additional, Nicole, Pascal, additional, Robert, Jean‐Claude, additional, Jamin, Nadège, additional, Neumann, Jean‐Michel, additional, Robberecht, Patrick, additional, Laburthe, Marc, additional, and Couvineau, Alain, additional

Published
2012
Full Text
View/download PDF

31. Characterization of the New Photoaffinity Probe (Bz2-K24)-VIP.

Author

TAN, YOSSAN‐VAR, COUVINEAU, ALAIN, LACAPERE, JEAN JACQUES, and LABURTHE, MARC

Subjects
*PHOTOAFFINITY labeling, *AFFINITY labeling, *MUTAGENESIS, *GENETIC mutation, *PEPTIDES
Abstract

Site-directed mutagenesis and molecular modeling demonstrated that the N-terminal ectodomain of the VPAC1 receptor is a major site of vasoactive intestinal peptide (VIP) binding. Previous studies with the [Bpa6]-VIP and [Bpa22]-VIP probes (substitution with the photoactivable Bpa for the residues 6 and 22 in VIP) showed spatial approximation between the amino acids 6 and 22 of VIP and the 104-108 and 109-119 sequences within the N-terminal ectodomain of the receptor, respectively. Here, we characterize the new probe (Bz2-K24)-VIP (substitution with the photoreactive Bz2-K for the residue 24 in VIP). After photolabeling and sequential digestions of the receptor, the 121-133 sequence of the N-terminal ectodomain was identified as the site of interaction. The N-terminal ectodomain of the VPAC1 receptor is therefore an affinity trap for the central part of VIP, at least between residues 6 and 24. [ABSTRACT FROM AUTHOR]

Published
2006
Full Text
View/download PDF

32. Diffuse Pharmacophoric Domains of Vasoactive Intestinal Peptide (VIP) and Further Insights into the Interaction of VIP with the N-terminal Ectodomain of Human YPAC1 Receptor by Photoaffinity...

Author

Tan, Yossan-Var, Couvineau, Alain, and Laburthe, Marc

Subjects
*VASOACTIVE intestinal peptide, *GASTROINTESTINAL hormones, *AMINO acids, *MEMBRANE proteins, *G proteins, *DIGESTIVE enzymes, *PANCREATIC secretions
Abstract

The widespread 28-amino acid neuropeptide vasoactive intestinal peptide (VIP) exerts its many biological effects through interaction with serpentine class II G protein-coupled receptors named VPAC receptors. We previously provided evidence for a physical contact between the side chain at position 22 of VIP and the Nterminal ectodomain of the hVPAC1 receptor (Tan, Y. V., Couvineau, A., Van Rampelbergh, J., and Laburthe, M. (2003) J. Biol. Chem. 278, 36531-36536). We explored here the contact site between hVPAC1 receptor and the side chain at position 6 of VIP by photoafflnity labeling. The photoreactive para-benzoyl-L-Phe (Bpa) was substituted for Phe6 in VIP resulting in [Bpa6]-VIP, which was shown to be a hVPAC1 receptor agonist in Chinese hamster ovary cells stably expressing the recombinant receptor. After obtaining the covalent 125I-[Bpa6VIP]·hVPAC1 receptor complex, it was sequentially cleaved by cyanogen bromide, peptide N-glycosidase F, endopeptidase Glu-C, and trypsin, and the cleavage products were analyzed by electrophoresis. The data demonstrated that 125I-[Bpa6-VIP] were covalently attached to the short 104-108 fragment within the Nterminal ectodomain of the receptor. The data were confirmed by creation of a receptor mutant with new CNBr cleavage site. In a three-dimensional model of the receptor N-terminal ectodomain, this fragment was located on one edge of the putative VIP-binding groove and was adjacent to the fragment covalently attached to the side chain at position 22 of VIP. Altogether these data showed that the central part of VIP, at least between Phe6 and Tyr22, interacts with the N-terminal ectodomain of the hVPAC1 receptor. [ABSTRACT FROM AUTHOR]

Published
2004
Full Text
View/download PDF

33. Calcium Signaling via Orai1 Is Essential for Induction of the Nuclear Orphan Receptor Pathway To Drive Th17 Differentiation.

Author

Kyun-Do Kim, Srikanth, Sonal, Tan, Yossan-Var, Ma-Khin Yee, Jew, Marcus, Damoiseaux, Robert, Jung, Michael E., Shimizu, Saki, Dong Sung An, Ribalet, Bernard, Waschek, James A., and Yousang Gwack

Subjects
*T cells, *AUTOIMMUNE diseases, *SMALL molecules, *RETINOIC acid receptors, *T helper cells
Abstract

Orai1 is the pore subunit of Ca2+ release-activated Ca2+ (CRAC) channels that stimulate downstream signaling pathways crucial for T cell activation. CRAC channels are an attractive therapeutic target for alleviation of autoimmune diseases. Using highthroughput chemical library screening targeting Orai1, we identified a novel class of small molecules that inhibit CRAC channel activity. One of these molecules, compound 5D, inhibited CRAC channel activity by blocking ion permeation. When included during differentiation, Th17 cells showed higher sensitivity to compound 5D than Th1 and Th2 cells. The selectivity was attributable to high dependence of promoters of retinoic-acid-receptor-related orphan receptors on the Ca2+-NFAT pathway. Blocking of CRAC channels drastically decreased recruitment of NFAT and histone modifications within key gene loci involved in Th17 differentiation. The impairment in Th17 differentiation by treatment with CRAC channel blocker was recapitulated in Orai1- deficient T cells, which could be rescued by exogenous expression of retinoic-acid-receptor-related orphan receptors or a constitutive active mutant of NFAT. In vivo administration of CRAC channel blockers effectively reduced the severity of experimental autoimmune encephalomyelitis by suppression of differentiation of inflammatory T cells. These results suggest that CRAC channel blockers can be considered as chemical templates for the development of therapeutic agents to suppress inflammatory responses. [ABSTRACT FROM AUTHOR]

Published
2014
Full Text
View/download PDF

34. Understanding Pathogenesis and Care Challenges of Immune Reconstitution Inflammatory Syndrome in Fungal Infections

Author

Olivier Lortholary, Claire Aguilar, Sarah Dellière, Blandine Rammaert, Romain Guery, Lucienne Chatenoud, Fanny Lanternier, Sophie Candon, Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris], and TAN, Yossan-Var

Subjects
0301 basic medicine, Microbiology (medical), 030106 microbiology, Cryptococcus, fungal immunity, Plant Science, Review, urologic and male genital diseases, Pathogenesis, 03 medical and health sciences, Immune system, Immune reconstitution inflammatory syndrome, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Histoplasma, medicine, Iris (anatomy), mycoses, lcsh:QH301-705.5, Ecology, Evolution, Behavior and Systematics, Aspergillus, invasive fungal infections, biology, business.industry, urogenital system, fungi, medicine.disease, biology.organism_classification, immune reconstitution inflammatory syndrome, 3. Good health, medicine.anatomical_structure, lcsh:Biology (General), Immunology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Etiology, business
Abstract

Immune deficiency of diverse etiology, including human immunodeficiency virus (HIV), antineoplastic agents, immunosuppressive agents used in solid organ recipients, immunomodulatory therapy, and other biologics, all promote invasive fungal infections. Subsequent voluntary or unintended immune recovery may induce an exaggerated inflammatory response defining immune reconstitution inflammatory syndrome (IRIS), which causes significant mortality and morbidity. Fungal-associated IRIS raises several diagnostic and management issues. Mostly studied with Cryptococcus, it has also been described with other major fungi implicated in human invasive fungal infections, such as Pneumocystis, Aspergillus, Candida, and Histoplasma. Furthermore, the understanding of IRIS pathogenesis remains in its infancy. This review summarizes current knowledge regarding the clinical characteristics of IRIS depending on fungal species and existing strategies to predict, prevent, and treat IRIS in this patient population, and tries to propose a common immunological background to fungal IRIS.

Published
2018
Full Text
View/download PDF

35. Possible role of CYP2B6 genetic polymorphisms in ifosfamide-induced encephalopathy: report of three cases

Author

Jeremy Bellien, Céline Verstuyft, Bruno Filhon, Thomas Duflot, Fabien Lamoureux, Robinson Joannides, Tony Pereira, Nathalie Massy-Guillemant, Aude Marie-Cardine, UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Hôpital Charles Nicolle [Rouen], CHU Rouen, Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Barrière et passage des médicaments, Université Paris-Sud - Paris 11 (UP11)-IFR141, Endothélium, valvulopathies et insuffisance cardiaque (EnVI), and TAN, Yossan-Var

Subjects
CYP2B6, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], Encephalopathy, Pharmacology, 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, parasitic diseases, Genotype, medicine, Pharmacology (medical), Allele, Genotyping, ComputingMilieux_MISCELLANEOUS, Ifosfamide, CYP3A4, business.industry, bacterial infections and mycoses, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, Pharmacogenetics, medicine.drug
Abstract

Ifosfamide (IFA) is a potent alkylating antitumoral agent, but its use is limited by neurological side effects. IFA is a racemic mixture of two enantiomeric forms, R-IFA and S-IFA with a stereoselective metabolism by CYP3A4 and CYP2B6, leading either to bioactive or to toxic pathways. In three consecutive cases of pediatric patients who exhibited IFA-induced encephalopathy (IIE), genotyping of clinically relevant single-nucleotide polymorphisms associated with decreased CYP3A4 and CYP2B6 activities was performed. Genetic investigations revealed the presence of CYP2B6 rs4803419 (C>T) in one patient while the two others carried the CYP2B6*6 allelic variant. All patients carried CYP3A4 wild-type genotype (CYP3A4*1/*1). Because CYP2B6-deficient alleles may be responsible for an increased conversion of S-IFA into neurotoxic metabolites, screening for CYP2B6 polymorphisms may help to avoid IIE and improve clinical outcomes.

Published
2018
Full Text
View/download PDF

36. Efficacy of Immunotherapy in Patients with Metastatic Mucosal or Uveal Melanoma

Author

Mona Amini-Adle, Pierre Marcant, Yannick Le Corre, Caroline Dutriaux, Nora Kramkimel, Anne Bénédicte Duval Modeste, N. Litrowski, C. Lesage, Nicolas Meyer, Amir Khammari, Caroline Gaudy-Marqueste, C. Mignard, Aurélie Deschamps Huvier, Eve Maubec, Thierry Lesimple, Laurent Mortier, Florence Brunet-Possenti, L. Visseaux, Géraldine Jeudy, A. Stefan, Marie-Françoise Avril, Sabiha Trabelsi, Henri Montaudié, François Aubin, Pascal Joly, Laurent Machet, André Gillibert, Marie-Thérèse Leccia, Jean-Philippe Arnault, Nathalie Beneton, E. Wierzbicka-Hainaut, Dan Lipsker, Service de dermatologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), CHU Bordeaux [Bordeaux], Clinical and Translational Research in Skin Cancer (CRCINA-ÉQUIPE 2), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), 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), Service de Dermatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Cochin [AP-HP], Hôpital Claude Huriez [Lille], CHU Lille, Département d'oncologie médicale [Rennes], CRLCC Eugène Marquis (CRLCC), Département de dermatologie, CHU Marseille, CHU Marseille, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de dermatologie (CHRU de Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Département de dermatologie, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Hôpital Saint-Jacques-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Département de la santé publique [CHU Strasbourg], CHU Strasbourg, Centre Hospitalier Le Mans (CH Le Mans), Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de dermatologie [CHU d'Amiens-Picardie], CHU Amiens-Picardie, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service de dermatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de Dermatologie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Dermatology Department, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Département Pluridisciplinaire de Médecine, Dermatologie, CHU Grenoble-Hôpital Michallon, Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Saint-André, 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), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université Paris Descartes - Paris 5 (UPD5), Hôpital de la Timone [CHU - APHM] (TIMONE), Université Francois Rabelais [Tours], Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Universitaire [Grenoble] (CHU), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Hôpital Avicenne [AP-HP], Université Paris 13 (UP13), PRES Université Nantes Angers Le Mans (UNAM), Université de Strasbourg (UNISTRA), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Groupe Hospitalier du Havre Hôpital Jacques Monod (MONTIVILLIERS) (GHH), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), and TAN, Yossan-Var

Subjects
0301 basic medicine, medicine.medical_specialty, Article Subject, medicine.medical_treatment, Gastroenterology, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, medicine, Stage (cooking), Chemotherapy, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Melanoma, Mucosal melanoma, Retrospective cohort study, Immunotherapy, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cohort, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, Research Article
Abstract

Background: The objective was to assess the response rate and survival of patients with metastatic mucosal melanoma (MM) and uveal melanoma (UM) treated with anti-CTLA-4 or anti-PD-1 monoclonal antibodies (mAbs).Methods: A multicenter retrospective study was performed in 25 dermatology departments in France. All patients with stage III-C to IV MM or UM who were treated with anti-CTLA-4 or anti-PD-1 mAbs between 2008 and 2016 were included and compared after adjustment for main prognostic factors with a second cohort of patients treated with chemotherapy. Tumor response was evaluated according to RECIST v. 1.1 criteria at Week 12.Results: Four-hundred-and-thirty-nine patients were included, 229 MM (151 immunotherapy, 78 chemotherapy) and 210 UM (100 immunotherapy, 110 chemotherapy). Response rates of MM patients treated with immunotherapy were 18/151 (11.9%; 95% CI:7.2%-18.2%), versus 11/78 (14.1%, 95% CI:7.3%-23.8%) in patients treated with chemotherapy (p=0.87). No tumor response was observed in UM patients treated with immunotherapy, versus 4/110 responses (3.6%, 95% CI:1.0-9.0%) in patients treated with chemotherapy (p=0.15). The adjusted overall survival (OS) of MM patients treated with immunotherapy was longer than that of patients treated with chemotherapy HR=0.62 (95% CI: 0.43-0.91), p=0.014, with an unadjusted median OS of 15.97 months [interquartile range (IQR)=6.89-27.11] and 8.82 months [IQR=5.02-14.92], respectively. The adjusted OS of UM patients treated with immunotherapy was not significantly different from that of patients treated with chemotherapy (HR=0.98, 95% CI: 0.66-1.44) p=0.92, with an unadjusted median OS of 13.38 months [IQR=6.03-29.57] and 11.02 months [IQR=6.13-23.93], respectively.Conclusion: Immunotherapy significantly improves OS for MM. The prognosis of metastatic UM remains poor., Immunotherapy significantly improves OS for MM. The prognosis of metastatic UM remains poor.

Published
2018
Full Text
View/download PDF

37. Late effects after hematopoietic stem cell transplantation for β-thalassemia major: the French national experience

Author

Nathalie Aladjidi, Marilyne Poirée, Catherine Paillard, Ilhem Rahal, Claire Galambrun, Imane Agouti, Mauricette Michallet, Pauline Simon, Yves Bertrand, Dominique Steschenko, Ibrahim Yakoub-Agha, Pascal Auquier, Régis Peffault de Latour, Marie Pierre Castex, Isabelle Thuret, Nathalie Garnier, Catherine Badens, Caroline Thomas, Corinne Pondarré, Gérard Michel, Patrick Lutz, Anderson Loundou, Pierre-Simon Rohrlich, Jean Hugues Dalle, Christophe Piguet, Jean Louis Stephan, Despina Moshous, Pierre Frange, Claire Berger, Gérard Socié, Françoise Bernaudin, Anne Lambilliotte, Cécile Dumesnil, TAN, Yossan-Var, Aix-Marseille Université - Faculté de médecine (AMU MED), Aix Marseille Université (AMU), Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL), Centre d'Investigation Clinique [CHU Clermont-Ferrand] (CIC 1405), Institut National de la Santé et de la Recherche Médicale (INSERM)-Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, 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), CHI Créteil, Unité d'Hémato-Immunologie pédiatrique [Hôpital Robert Debré, Paris], Service d'Immuno-hématologie pédiatrique [Hôpital Robert Debré, Paris], Hôpital Robert Debré-Hôpital Robert Debré, Hopital Saint-Louis [AP-HP] (AP-HP), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Service de pédiatrie, CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Unités d'Activité Médicale [Lille] (UAM), Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Pédiatrie médicale - Spécialités médicales [CHU Limoges], CHU Limoges, Service d'Hémato-oncologie Pédiatrique, CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Centre de référence maladie rare Thalassémie, Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), CHU Rouen, Normandie Université (NU), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Allergologie et d'Immunologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hopital L'Archet-II, Service d'hématologie pédiatrique-oncologie, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU de Nantes, CHU Pointe-à-Pitre/Abymes [Guadeloupe], Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Hôpital de la Timone [CHU - APHM] (TIMONE), AORC APHM 2011 (Appel d’Offre de Recherche Clinique), Service d'Allergologie et d'Immunologie [CHRU Toulouse], CHRU Toulouse, Univers, Transport, Interfaces, Nanostructures, Atmosphère et environnement, Molécules (UMR 6213) (UTINAM), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)

Subjects
Delayed puberty, Pediatrics, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Thalassemia, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Hematopoietic stem cell transplantation, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, medicine, Young adult, business.industry, Retrospective cohort study, Hematology, medicine.disease, 3. Good health, Transplantation, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.symptom, business, Busulfan, 030215 immunology, medicine.drug
Abstract

International audience; In this retrospective study, we evaluate long-term complications in nearly all β-thalassemia-major patients who successfully received allogeneic hematopoietic stem cell transplantation in France. Ninety-nine patients were analyzed with a median age of 5.9 years at transplantation. The median duration of clinical follow up was 12 years. All conditioning regimens were myeloablative, most were based on busulfan combined with cyclophosphamide, and more than 90% of patients underwent a transplant from a matched sibling donor. After transplantation, 11% of patients developed thyroid dysfunction, 5% diabetes, and 2% heart failure. Hypogonadism was present in 56% of females and 14% of males. Female patients who went on to normal puberty after transplant were significantly younger at transplantation than those who experienced delayed puberty (median age 2.5 vs. 8.7 years). Fertility was preserved in 9 of 27 females aged 20 years or older and 2 other patients became pregnant following oocyte donation. In addition to patient’s age and higher serum ferritin levels at transplantation, time elapsed since transplant was significantly associated with decreased height growth in multivariate analysis. Weight growth increased after transplantation particularly in females, 36% of adults being overweight at last evaluation. A comprehensive long-term monitoring, especially of endocrine late effects, is required after hematopoietic stem cell transplantation for thalassemia.

Published
2018
Full Text
View/download PDF

38. Bullous pemphigoid, a dermatosis of the elderly

Author

Hebert, Vivien, Joly, Pascal, CHU Rouen, Normandie Université (NU), Service de dermatologie [Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), and TAN, Yossan-Var

Subjects
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Skin Diseases, Vesiculobullous, integumentary system, Bullous pemphigoid, [SDV]Life Sciences [q-bio], Dermatologie du sujet âgé, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, eye diseases, Autoimmune Diseases, [SDV] Life Sciences [q-bio], La pemphigoïde bulleuse, dermatose bulleuse auto-immune, Pemphigoid, Bullous, autoimmune bullous disease, Humans, une dermatose du sujet âgé, skin and connective tissue diseases, Pemphigoïde bulleuse, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, Aged, Autoantibodies, Skin
Abstract

Bullous pemphigoid, a dermatosis of the elderly. Bullous pemphigoid is the most common autoimmune bullous disease and affects almost exclusively the elderly. Its occurrence is related to the presence of pathogenic autoantibodies directed against structural proteins (BP180 and BP230) of the protein adhesion complex of the dermo-epidermal junction: the hemi-desmosome. Bullous pemphigoid is classically characterized by pruritus and the appearance of blisters on an inflammatory background with a symmetrical topography: thighs, arms and trunk. Blisters eventually break, leading to erosions. Mucosal involvement is rare. Histology of a cutaneous biopsy finds a subepidermal blister containing eosinophils. Direct immunofluorescence confirms the diagnosis by the presence of linear deposits of IgG and C3 along the epidermal basement membrane. The reference treatment is the superpotent topical corticosteroid therapy (clobetasol propionate).La pemphigoïde bulleuse, une dermatose du sujet âgé. La pemphigoïde bulleuse est la dermatose bulleuse auto-immune la plus fréquente et elle touche quasi exclusivement la personne âgée. Sa survenue est liée à la présence d’autoanticorps pathogènes dirigés contre des protéines de structure (BP180 et BP230) du complexe protéique d’adhésion de la jonction dermo-épidermique : l’hémidesmosome. La pemphigoïde bulleuse se manifeste classiquement par un prurit et l’apparition de bulles sur fond inflammatoire avec une topographie symétrique : cuisses, bras, tronc. Les bulles finissent par se rompre, laissant la place à des érosions. L’atteinte muqueuse est rare. L’histologie d’une biopsie cutanée montre une bulle sous-épidermique contenant des polynucléaires éosinophiles. L’immuno- fluorescence directe affirme le diagnostic par la présence de dépôts linéaires d’immunoglobuline de type G et de C3 le long de la membrane basale épidermique. Le traitement de référence est la corticothérapie locale très forte (propionate de clobétasol).

Published
2017

39. Deep intronic hotspot variant explaining rhabdoid tumor predisposition syndrome in two patients with atypical teratoid and rhabdoid tumor

Author

Pascale Varlet, Laurence Brugières, Thierry Frebourg, Annie Laquerrière, Gaëlle Pierron, Stéphanie Puget, Olivier Delattre, Julien Masliah-Planchon, Franck Bourdeaut, Damien Bodet, Christelle Dufour, Arnault Tauziède-Espariat, Emmanuèle Lechapt-Zalcman, Pascale Schneider, CH Belfort-Montbéliard, Pathologie cellulaire : aspects moléculaires et viraux / Pathologie et Virologie Moléculaire, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), Service de neurochirurgie 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), Centre de Psychiatrie et Neurosciences (U894), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hémato-immuno-oncologie pédiatrique [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), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Anatomie et Cytologie Pathologique [CHU Rouen], Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Hypoxie, physiopathologies cérébrovasculaire et tumorale (CERVOxy), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Unit of Somatic Genomics, Department of Genetics, Institut Curie [Paris], Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Génétique Somatique, Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and TAN, Yossan-Var

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], Short Report, Biology, Bioinformatics, Germline, Rhabdoid Tumor Predisposition Syndrome, 03 medical and health sciences, 0302 clinical medicine, Germline mutation, Molecular genetics, Genetics, medicine, Humans, SMARCB1, Cells, Cultured, Germ-Line Mutation, Rhabdoid Tumor, Genetics (clinical), Teratoma, Cytogenetics, Infant, SMARCB1 Protein, Introns, Human genetics, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, 030220 oncology & carcinogenesis, Medical genetics, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract

About one third of patients with rhabdoid tumors (RT) harbor a heterozygous germline variant in SMARCB1. Molecular diagnosis therefore keeps a crucial place in the diagnosis of RT, and genetic counseling should be systematically recommended. However, immunohistochemistry has progressively replaced molecular tools to assess the status of SMARCB1 in tumors; the necessity of analyzing SMARCB1 status in the tumor may thus be less considered by neuropathologists and pediatric neuro-oncologists. In the present manuscript as aforementioned, we report on two patients with bifocal RT in the first month of life and in whom no germline variant was initially found in the SMARCB1 coding sequence. Careful analysis of SMARCB1 status in the tumors revealed that only one of the two inactivating hits was found in the coding sequence. By sequencing the tumor cells RNA, we were able to detect an insertion with an abnormal sequence, due to the same intronic variant of SMARCB1, which led to the exonisation of the first intron. This cryptic variant was absent in the germline DNA of both patients. Of note, we previously reported one patient with the same deep intronic variant in the germline in a soft tissue RT. To our mind, this additional report on two patients clearly demonstrates that this intronic variant is a new hotspot that should now be systematically added to the germline screening of SMARCB1. We therefore recommend searching for and cautiously interpreting germline analysis if SMARCB1 has not been extensively studied in the tumor.

Published
2017
Full Text
View/download PDF

40. Cardiac iron overload in chronically transfused patients with thalassemia, sickle cell anemia, or myelodysplastic syndrome

Author

Amandine Baptiste, Thibaud Lefebvre, Olivier Ernst, Emmanuelle Chauzit, Jean-Pierre Vannier, Agnès Guerci-Bresler, Christian Rose, Zoubida Karim, Hervé Puy, Aspasia Stamatoullas, Mariane De Montalembert, Valentine Brousse, Krimo Bouabdallah, Mohamed Touati, C. Dumesnil, Agnès Lahary, Marina Cavazzana, Caroline Elie, Jean-Antoine Ribeil, Service de pédiatrie générale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Centre de Référence de la Drépanocytose-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de pédiatrie générale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service d'Hématologie Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Hématologie, Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Micro-Environnement et Régulation Cellulaire Intégrée (MERCI), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), Hôpital Charles Nicolle [Rouen], Service d'Hématologie biologique [CHU Limoges], CHU Limoges, Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Département de Biothérapie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], CHU Bordeaux [Bordeaux], Hôpital Cochin [AP-HP], Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'informatique médicale et biostatistiques [CHU Necker], Radiologie interventionnelle, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie, Hôpital Saint-Vincent-de-Paul, TAN, Yossan-Var, Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre de Référence de la Drépanocytose, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Male, Blood transfusion, Physiology, Thalassemia, medicine.medical_treatment, [SDV]Life Sciences [q-bio], lcsh:Medicine, 030204 cardiovascular system & hematology, Gastroenterology, Physical Chemistry, Biochemistry, Diagnostic Radiology, 0302 clinical medicine, hemic and lymphatic diseases, Medicine and Health Sciences, Erythropoiesis, 10. No inequality, Child, lcsh:Science, Multidisciplinary, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, Chelation, Radiology and Imaging, Heart, Hematology, Middle Aged, Magnetic Resonance Imaging, Sickle cell anemia, Clinical Laboratory Sciences, 3. Good health, [SDV] Life Sciences [q-bio], Chemistry, Genetic Diseases, 030220 oncology & carcinogenesis, Physical Sciences, Female, Anatomy, Research Article, Adult, medicine.medical_specialty, Iron Overload, Adolescent, Anemia, Imaging Techniques, Iron, Anemia, Sickle Cell, Research and Analysis Methods, Iron Chelating Agents, 03 medical and health sciences, Autosomal Recessive Diseases, Hepcidin, Diagnostic Medicine, Internal medicine, medicine, Humans, Blood Transfusion, Clinical Genetics, Ferritin, Sickle Cell Disease, Chemical Bonding, business.industry, Transfusion Medicine, Myelodysplastic syndromes, Myocardium, lcsh:R, Biology and Life Sciences, Proteins, Protein Complexes, medicine.disease, Hematopoiesis, Hemoglobinopathies, Myelodysplastic Syndromes, biology.protein, Cardiovascular Anatomy, lcsh:Q, business, Physiological Processes, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

The risk and clinical significance of cardiac iron overload due to chronic transfusion varies with the underlying disease. Cardiac iron overload shortens the life expectancy of patients with thalassemia, whereas its effect is unclear in those with myelodysplastic syndromes (MDS). In patients with sickle cell anemia (SCA), iron does not seem to deposit quickly in the heart. Our primary objective was to assess through a multicentric study the prevalence of cardiac iron overload, defined as a cardiovascular magnetic resonance T2*8 ECs in the past year, and age older than 6 years. We included from 9 centers 20 patients with thalassemia, 41 with SCA, and 25 with MDS in 2012-2014. Erythrocytapharesis did not consistently prevent iron overload in patients with SCA. Cardiac iron overload was found in 3 (15%) patients with thalassemia, none with SCA, and 4 (16%) with MDS. The liver iron content (LIC) ranged from 10.4 to 15.2 mg/g dry weight, with no significant differences across groups (P = 0.29). Abnormal T2* was not significantly associated with any of the measures of transfusion or chelation. Ferritin levels showed a strong association with LIC. Non-transferrin-bound iron was high in the thalassemia and MDS groups but low in the SCA group (P

Published
2017
Full Text
View/download PDF

41. VPAC1 receptor (Vipr1)-deficient mice exhibit ameliorated experimental autoimmune encephalomyelitis, with specific deficits in the effector stage

Author

Yuqi Wang, Bhavaani Jayaram, Laurine Becquet, Catalina Abad, Yossan-Var Tan, James A. Waschek, M. Sue O'Dorisio, University of California [Los Angeles] (UCLA), University of California, Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Iowa [Iowa City], BMC, BMC, Department of Psychiatry [Los Angeles, USA], University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles], University of California (UC)-University of California (UC), Department of Pediatrics and Holden Comprehensive Cancer Center [Iowa City, USA], University of Iowa [Iowa City]-Carver College of Medicine, University of Iowa, This work was supported by the National Multiple Sclerosis Society RG4859,TA3048_A_1, RG-1501-02646, the National Institutes of Health (NIH)HD04612, and the ARSEP (Fondation pour l’aide à la recherche sur la scléroseen plaques)., University of California-University of California-David Geffen School of Medicine [Los Angeles], University of California-University of California, University of California (UC), and TAN, Yossan-Var

Subjects
0301 basic medicine, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Neuroimmunomodulation, [SDV]Life Sciences [q-bio], Immunology, Vasoactive intestinal peptide, Neuropeptide, Biology, Multiple sclerosis, 03 medical and health sciences, Cellular and Molecular Neuroscience, Internal medicine, medicine, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Receptor, Experimental autoimmune encephalomyelitis, VPAC1, Effector, General Neuroscience, medicine.disease, In vitro, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, Endocrinology, Neurology, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], VIPR1, hormones, hormone substitutes, and hormone antagonists, Ex vivo
Abstract

International audience; Background: Vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase-activating polypeptide (PACAP) are two highly homologous neuropeptides. In vitro and ex vivo experiments repeatedly demonstrate that these peptides exert pronounced immunomodulatory (primarily anti-inflammatory) actions which are mediated by common VPAC1 and VPAC2 G protein-coupled receptors. In agreement, we have shown that mice deficient in PACAP ligand or VPAC2 receptors exhibit exacerbated experimental autoimmune encephalomyelitis (EAE). However, we observed that VIP-deficient mice are unexpectedly resistant to EAE, suggesting a requirement for this peptide at some stage of disease development. Here, we investigated the involvement of VPAC1 in the development of EAE using a VPAC1-deficient mouse model.Methods: EAE was induced in wild-type (WT) and VPAC1 knockout (KO) mice using myelin oligodendrocyte glycoprotein 35–55 (MOG35–55), and clinical scores were assessed continuously over 30 days. Immune responses in the spinal cords were determined by histology, real-time PCR and immunofluorescence, and in the draining lymph nodes by antigen-recall assays. The contribution of VPAC1 expression in the immune system to the development of EAE was evaluated by means of adoptive transfer and bone marrow chimera experiments. In other experiments, VPAC1 receptor analogs were given to WT mice.Results: MOG35–55-induced EAE was ameliorated in VPAC1 KO mice compared to WT mice. The EAE-resistant phenotype of VPAC1 KO mice correlated with reduced central nervous system (CNS) histopathology and cytokine expression in the spinal cord. The immunization phase of EAE appeared to be unimpaired because lymph node cells from EAE-induced VPAC1 KO mice stimulated in vitro with MOG exhibited robust proliferative and Th1/Th17 responses. Moreover, lymph node and spleen cells from KO mice were fully capable of inducing EAE upon transfer to WT recipients. In contrast, WT cells from MOG-immunized mice did not transfer the disease when administered to VPAC1 KO recipients, implicating a defect in the effector phase of the disease. Bone marrow chimera studies suggested that the resistance of VPAC1-deficient mice was only minimally dependent on the expression of this receptor in the immunogenic/hematopoietic compartment. Consistent with this, impaired spinal cord inductions of several chemokine mRNAs were observed in VPAC1 KO mice. Finally, treatment of WT mice with the VPAC1 receptor antagonist PG97-269 before, but not after, EAE induction mimicked the clinical phenotype of VPAC1 KO mice.Conclusions: VPAC1 gene loss impairs the development of EAE in part by preventing an upregulation of CNS chemokines and invasion of inflammatory cells into the CNS. Use of VPAC1 antagonists in WT mice prior to EAE induction also support a critical role for VPAC1 signaling for the development of EAE.

Published
2016
Full Text
View/download PDF

42. The apoptotic members CD95, BclxL, and Bcl-2 cooperate to promote cell migration by inducing Ca(2+) flux from the endoplasmic reticulum to mitochondria

Author

Pierre Vacher, Marine Malleter, Yves Gouriou, Chi Li, L. Debure, Patrick Legembre, E. Lepvrier, Vanessa Delcroix, Amélie Fouqué, Mehdi Hammadi, Michel Ovize, Thomas Ducret, Chemistry, Oncogenesis, Stress and Signaling (COSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Bergonié - CRLCC Bordeaux, Hospices Civils de Lyon, Departement de Neurologie (HCL), CIC CHU Lyon (inserm), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), ARC, Fondation ARC pour la Recherche sur le Cancer, Ligue Contre le Cancer, CA106599, NIH, National Institutes of Health, CA175003, NIH, National Institutes of Health, GM106386, NIH, National Institutes of Health, Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Institut Bergonié [Bordeaux], UNICANCER, Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and TAN, Yossan-Var

Subjects
0301 basic medicine, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], bcl-X Protein, Down-Regulation, Apoptosis, Triple Negative Breast Neoplasms, Mitochondrion, Biology, Endoplasmic Reticulum, Models, Biological, 03 medical and health sciences, 0302 clinical medicine, Cell Movement, Animals, Humans, Calcium Signaling, fas Receptor, Molecular Biology, PI3K/AKT/mTOR pathway, Calcium signaling, Mice, Knockout, Original Paper, Cell growth, Endoplasmic reticulum, Voltage-Dependent Anion Channel 1, Cell migration, Cell Biology, 3. Good health, Cell biology, Mitochondria, [SDV] Life Sciences [q-bio], 030104 developmental biology, 030220 oncology & carcinogenesis, Mitochondrial Membranes, [SDV.IMM]Life Sciences [q-bio]/Immunology, Calcium, Female, bcl-Associated Death Protein, Calcium Channels, Signal transduction, BH3 Interacting Domain Death Agonist Protein, Protein Binding
Abstract

International audience; Metalloprotease-processed CD95L (cl-CD95L) is a soluble cytokine that implements a PI3K/Ca 2+ signaling pathway in triple-negative breast cancer (TNBC) cells. Accordingly, high levels of cl-CD95L in TNBC women correlate with poor prognosis, and administration of this ligand in an orthotopic xenograft mouse model accelerates the metastatic dissemination of TNBC cells. The molecular mechanism underlying CD95-mediated cell migration remains unknown. Here, we present genetic and pharmacologic evidence that the anti-apoptotic molecules BclxL and Bcl-2 and the pro-apoptotic factors BAD and BID cooperate to promote migration of TNBC cells stimulated with cl-CD95L. BclxL was distributed in both endoplasmic reticulum (ER) and mitochondrion membranes. The mitochondrion-localized isoform promoted cell migration by interacting with voltage-dependent anion channel 1 to orchestrate Ca 2+ transfer from the ER to mitochondria in a BH3-dependent manner. Mitochondrial Ca 2+ uniporter contributed to this flux, which favored ATP production and cell migration. In conclusion, this study reveals a novel molecular mechanism controlled by BclxL to promote cancer cell migration and supports the use of BH3 mimetics as therapeutic options not only to kill tumor cells but also to prevent metastatic dissemination in TNBCs.

Published
2016
Full Text
View/download PDF

43. Efficacy of Biological-Targeted Treatments in Takayasu Arteritis

Author

Mékinian, Arsène, Comarmond, Cloé, Resche-Rigon, Mathieu, Mirault, Tristan, Kahn, Jean Emmanuel, Lambert, Marc, Sibilia, Jean, Néel, Antoine, Cohen, Pascal, Hie, Miguel, Berthier, Sabine, Marie, Isabelle, Lavigne, Christian, Anne Vandenhende, Marie, Muller, Géraldine, Amoura, Zahir, Devilliers, Herve, Abad, Sébastien, Hamidou, Mohamed, Guillevin, Loic, Dhote, Robin, Godeau, Bertrand, Messas, Emmanuel, Cacoub, Patrice, Fain, Olivier, Saadoun, David, Service de Médecine Interne [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Foch [Suresnes], Laboratoire des signaux et systèmes (L2S), Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine interne [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence du Lupus Systémique, Syndrome des Anticorps Anti-phospholipides et Maladies Auto-immunes Systémiques Rares [CHU Pitié Salpêtrière], Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], Institut E3M [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut E3M [CHU Pitié-Salpêtrière], Service de Médecine Interne (SOC 1 et SOC 2) [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Médecine Interne [CHU 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), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine interne [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine interne [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Immunologie - Immunopathologie - Immunothérapie (I3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de médecine interne, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut E3M [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Service de médecine interne [CHU Saint-Antoine], TAN, Yossan-Var, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre National de Référence du Lupus Systémique, Syndrome des Anticorps Anti-phospholipides et Maladies Auto-immunes Systémiques Rares[CHU Pitié Salpêtrière], Service de Médecine Interne [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Hôpital Avicenne, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Jean Verdier [Bondy], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)

Subjects
[SDV] Life Sciences [q-bio], [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], [SDV.IMM]Life Sciences [q-bio]/Immunology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2015
Full Text
View/download PDF

44. Evans Syndrome in Children: Long-Term Outcome in a Prospective French National Observational Cohort

Author

Nathalie eAladjidi, Helder eFernandes, Thierry eLeblanc, Amelie eVareliette, Frédéric eRieux-Laucat, Yves eBertrand, Hervé eChambost, Marlène ePasquet, Françoise eMazingue, Corinne eGuitton, Isabelle ePellier, Françoise eRoqueplan-Bellmann, Corinne eArmari-Alla, Caroline eThomas, Aude eMarie-Cardine, Odile eLejars, Fanny eFouyssac, Sophie eBayart, Patrick eLutz, Christophe ePiguet, Eric eJeziorski, Pierre eRohrlich, Philippe eLemoine, Damien eBodet, Catherine ePaillard, Gerard eCouillault, Frédéric eMillot, Alain eFischer, Yves ePerel, Guy eLeverger, Service d'Hémato-oncologie Pédiatrique, CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, CHU Bordeaux [Bordeaux], Unité d'Hémato-Immunologie pédiatrique [Hôpital Robert Debré, Paris], Service d'Immuno-hématologie pédiatrique [Hôpital Robert Debré, Paris], Hôpital Robert Debré-Hôpital Robert Debré, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'hématologie, immunologie biologiques et cytogénétique, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, 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), Hôpital de la Tronche, Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service d'Hématologie et d'Oncologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hématogoie pédiatrique, hôpital Sud, Service de pédiatrie, CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Service de Pédiatrie médicale - Spécialités médicales [CHU Limoges], CHU Limoges, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'hématologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre d'Investigation Clinique [CHU Clermont-Ferrand] (CIC 1405), Institut National de la Santé et de la Recherche Médicale (INSERM)-Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de pédiatrie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Developpement Normal et Pathologique du Système 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), Collège de France - Chaire Médecine expérimentale (A. Fischer), Collège de France (CdF (institution)), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Univers, Transport, Interfaces, Nanostructures, Atmosphère et environnement, Molécules (UMR 6213) (UTINAM), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Chaire Médecine expérimentale (A. Fischer), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and TAN, Yossan-Var

Subjects
Pediatrics, medicine.medical_specialty, Evans syndrome, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, cohort study, medicine, Children, autoimmune hemolytic anemia, ComputingMilieux_MISCELLANEOUS, Original Research, child, Cytopenia, business.industry, Autoimmune Cytopenia, lcsh:RJ1-570, lcsh:Pediatrics, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Pediatrics, Perinatology and Child Health, Cohort, immune thrombocytopenic purpura, [SDV.IMM]Life Sciences [q-bio]/Immunology, Observational study, Autoimmune hemolytic anemia, business, 030215 immunology, Cohort study
Abstract

Evans syndrome (ES) is a rare autoimmune disorder whose long-term outcome is not well known. In France, a collaborative pediatric network set up via the National Rare Disease Plan now provides comprehensive clinical data in children with this disease. Patients aged less than 18 years at the initial presentation of autoimmune cytopenia have been prospectively included into a national observational cohort since 2004. The definition of ES was restricted to the simultaneous or sequential association of autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP). Cases were deemed secondary if associated with a primitive immunodeficiency or systemic lupus erythematosus. In December 2014, we analyzed the data pertaining to 156 children from 26 centers with ES whose diagnosis was made between 1981 and 2014. Median age (range) at the onset of cytopenia was 5.4 years (0.2–17.2). In 85 sequential cases, the time lapse between the first episodes of AIHA and ITP was 2.4 years (0.1–16.3). The follow-up period as from ES diagnosis was 6.5 years (0.1–28.8). ES was secondary, revealing another underlying disease, in 10% of cases; various associated immune manifestations (mainly lymphoproliferation, other autoimmune diseases, and hypogammaglobulinemia) were observed in 60% of cases; and ES remained primary in 30% of cases. Five-year ITP and AIHA relapse-free survival were 25 and 61%, respectively. Overall, 69% of children required one or more second-line immune treatments, and 15 patients (10%) died at the age of 14.3 years (1.7–28.1). To our knowledge, this is the first consistent long-term clinical description of this rare syndrome. It underscores the high rate of associated immune manifestations and the burden of long-term complications and treatment toxicity. Future challenges include (1) the identification of the underlying genetic defects inducing immune dysregulation and (2) the need to better characterize patient subgroups and second-line treatment strategies.

Published
2015
Full Text
View/download PDF

45. TP53 transcription factor for the NEDD9/HEF1/Cas-L gene: potential targets in Non-Small Cell Lung

Author

Rousseau, Benedicte, Jacquot, Catherine, Le Palabe, Julie, Malleter, Marine, Tomasoni, Christophe, Boutard, Tifenn, Sakanyan, Vehary, Roussakis, Christos, Institut de Recherche Interdisciplinaire sur les enjeux Sociaux - sciences sociales, politique, santé (IRIS), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-École des hautes études en sciences sociales (EHESS)-Université Paris 13 (UP13), Laboratoire d'Ethologie Expérimentale et Comparée (LEEC), Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), ProtNeteomix, TAN, Yossan-Var, Université Paris 13 (UP13)-École des hautes études en sciences sociales (EHESS)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris sciences et lettres (PSL), Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC), and Cibles et Médicaments des Infections et de l'Immunité (IICiMed)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

International audience; Lung cancer is a serious public health problem. Although there has been significant progress in chemotherapy, non-small cell lung cancer is still resistant to current treatments, primarily because of the slow rate of cell development. It is thus important to find new molecules directed against targets other than proliferation agents. Considering the high proportion of mutant proteins in tumor cells, and the high rate of mutation of the TP53 gene in all cancers, and in NSCLC in particular, this gene is a perfect target. Certain new molecules have been shown to restore the activity of mutated p53 protein, for example PRIMA-1, which reactivates the His273 mutant p53. In a previous study, we presented triazine A190, a molecule with a cytostatic activity that blocks cells in the G1 phase and induces apoptosis. Here, we show that A190 not only restores mutant p53 activity, but also induces an overexpression of the NEDD9 gene, leading to apoptotic death. These findings might offer hope for the development of new targeted therapies, specific to tumor cells, which spare healthy cells.

Published
2015
Full Text
View/download PDF

46. Rhabdomyosarcomas in children with neurofibromatosis type I: A national historical cohort

Author

Crucis, Anne, Richer, Wilfrid, Brugières, Laurence, Bergeron, Christophe, Marie-Cardine, Aude, Stéphan, Jean-Louis, Girard, Pauline, Corradini, Nadège, Munzer, Martine, Lacour, Brigitte, Minard-Colin, Veronique, Sarnacki, Sabine, Ranchere-Vince, Dominique, Orbach, Daniel, Bourdeaut, Franck, TAN, Yossan-Var, Département des urgences pédiatriques [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), Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), Service d'Oncologie, Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie pédiatrique, CHU Saint-Etienne, Centre de Recherches en Psychologie Cognition et Communication (CRPCC EA 1285), Université de Bretagne Sud (UBS)-Université de Brest (UBO)-MEN : EA1285-Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Département d'Oncologie Pédiatrique [CHU Nantes], Hôpital Mère-Enfant, CHU de Nantes, Service d'hématologie-oncologie pédiatrique, Centre Hospitalier Universitaire de Reims (CHU Reims), Registre National des Tumeurs Solides de l'Enfant (RNTSE), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Cancéropôle du Grand Est, Université Paris-Saclay, Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon, Institut Curie [Paris], Unité de Génétique Somatique, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN)

Subjects
[SDV] Life Sciences [q-bio], [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], [SDV.IMM]Life Sciences [q-bio]/Immunology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2015
Full Text
View/download PDF

47. VPAC2 (vasoactive intestinal peptide receptor type 2) receptor deficient mice develop exacerbated experimental autoimmune encephalomyelitis with increased Th1/Th17 and reduced Th2/Treg responses

Author

James A. Waschek, Catalina Abad, Robert Lopez, Yossan-Var Tan, Yuqi Wang, Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Veolia Environnement Recherche et Innovation (VERI), Veolia France, Veolia Recherche & Innovation (VeRI), Veolia Environnement (FRANCE), and TAN, Yossan-Var

Subjects
medicine.medical_specialty, Encephalomyelitis, Autoimmune, Experimental, [SDV.IMM] Life Sciences [q-bio]/Immunology, Regulatory T cell, [SDV]Life Sciences [q-bio], Immunology, Vasoactive intestinal peptide, Gene Expression, Biology, T-Lymphocytes, Regulatory, Article, Proinflammatory cytokine, 03 medical and health sciences, Behavioral Neuroscience, Interferon-gamma, Mice, 0302 clinical medicine, Internal medicine, medicine, Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], RNA, Messenger, Receptor, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Cell Proliferation, Mice, Knockout, 0303 health sciences, Endocrine and Autonomic Systems, Vasoactive intestinal peptide receptor, Experimental autoimmune encephalomyelitis, Interleukin-17, FOXP3, medicine.disease, [SDV] Life Sciences [q-bio], Mice, Inbred C57BL, Endocrinology, medicine.anatomical_structure, Spinal Cord, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, Receptors, Vasoactive Intestinal Peptide, Type II, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Interleukin-4, 030217 neurology & neurosurgery, VIPR2
Abstract

Vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase-activating polypeptide (PACAP) are two structurally-related neuropeptides with widespread expression in the central and peripheral nervous systems. Although these peptides have been repeatedly shown to exert potent anti-inflammatory actions when administered in animal models of inflammatory disease, mice deficient in VIP and PACAP were recently shown to exhibit different phenotypes (ameliorated and exacerbated, respectively) in response to experimental autoimmune encephalomyelitis (EAE). Therefore, elucidating what are the specific immunoregulatory roles played by each of their receptor subtypes (VPAC1, VPAC2, and PAC1) is critical. In this study, we found that mice with a genetic deletion of VIPR2, encoding the VPAC2 receptor, exhibited exacerbated (MOG35-55)-induced EAE compared to wild type mice, characterized by enhanced clinical and histopathological features, increased proinflammatory cytokines (TNF-α, IL-6, IFN-γ (Th1), and IL-17 (Th17)) and reduced anti-inflammatory cytokines (IL-10, TGFβ, and IL-4 (Th2)) in the CNS and lymph nodes. Moreover, the abundance and proliferative index of lymph node, thymus and CNS CD4(+)CD25(+)FoxP3(+) Tregs were strikingly reduced in VPAC2-deficient mice with EAE. Finally, the in vitro suppressive activity of lymph node and splenic Tregs from VPAC2-deficient mice was impaired. Overall, our results demonstrate critical protective roles for PACAP and the VPAC2 receptor against autoimmunity, promoting the expansion and maintenance of the Treg pool.

Published
2014

48. Arterial thoracic outlet syndrome

Author

Isabelle Marie, Mathilde Leclercq, Service de Médecine Interne [CHU 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), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and TAN, Yossan-Var

Subjects
Adult, Male, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], Treatment outcome, MEDLINE, Subclavian Artery, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, X ray computed, medicine, Humans, Pharmacology (medical), ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 030203 arthritis & rheumatology, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Cervical Rib, Arterial thoracic outlet syndrome, [SDV] Life Sciences [q-bio], Thoracic Outlet Syndrome, Treatment Outcome, [SDV.IMM]Life Sciences [q-bio]/Immunology, Radiology, business, Tomography, X-Ray Computed, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience

Published
2014
Full Text
View/download PDF

49. Antineutrophil Cytoplasmic Antibodies Associated With Infective Endocarditis

Author

Isabelle Marie, Jean-François Ménard, A. Lesourd, Nicolas Girszyn, Hervé Levesque, V. Langlois, François Caron, Laboratoire de Sciences de la Terre (LST), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Service des maladies infectieuses et tropicales [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Institut Fédératif de Recherches Multidisciplinaires sur les Peptides (IFRMP 23), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Equipe Quantification en Imagerie Fonctionnelle (QuantIF-LITIS), Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Service de Médecine Interne [CHU Rouen], Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Henri Becquerel-Université de Rouen Normandie (UNIROUEN), Université Le Havre Normandie (ULH), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA), Service de Médecine Interne [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Advanced Learning Evolutionary Algorithms (ALEA), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel)-Centre National de la Recherche Scientifique (CNRS), and TAN, Yossan-Var

Subjects
Male, Aortic valve, [SDV]Life Sciences [q-bio], Heart Valve Diseases, urologic and male genital diseases, Gastroenterology, 0302 clinical medicine, Bicuspid Aortic Valve Disease, immune system diseases, Mitral valve, Young adult, Aged, 80 and over, Endocarditis, biology, Mortality rate, General Medicine, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], C-Reactive Protein, medicine.anatomical_structure, Aortic Valve, Infective endocarditis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Mitral Valve, Female, Research Article, Adult, Heart Defects, Congenital, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Observational Study, Antibodies, Antineutrophil Cytoplasmic, Young Adult, 03 medical and health sciences, Internal medicine, medicine, Humans, cardiovascular diseases, Serum Albumin, Aged, Anti-neutrophil cytoplasmic antibody, 030203 arthritis & rheumatology, business.industry, C-reactive protein, medicine.disease, Surgery, biology.protein, business, 030217 neurology & neurosurgery
Abstract

International audience; To determine the prevalence of antineutrophil cytoplasmic antibodies (ANCA) in patients with infective endocarditis (IE) in internal medicine; and to compare clinical and biochemical features and outcome between patients exhibiting IE with and without ANCA.Fifty consecutive patients with IE underwent ANCA testing. The medical records of these patients were reviewed.Of the 50 patients with IE, 12 exhibited ANCA (24%). ANCA-positive patients with IE exhibited: longer duration between the onset of first symptoms and IE diagnosis (P = 0.02); and more frequently: weight loss (P = 0.017) and renal impairment (P = 0.08), lower levels of C-reactive protein (P = 0.0009) and serum albumin (P = 0.0032), involvement of both aortic and mitral valves (P = 0.009), and longer hospital stay (P = 0.016). Under multivariate analysis, significant factors for ANCA-associated IE were: longer hospital stay (P = 0.004), lower level of serum albumin (P = 0.02), and multiple valve involvement (P = 0.04). Mortality rate was 25% in ANCA patients; death was because of IE complications in all these patients.Our study identifies a high prevalence of ANCA in unselected patients with IE in internal medicine (24%). Our findings further underscore that ANCA may be associated with a subacute form of IE leading to multiple valve involvement and more frequent renal impairment. Because death was due to IE complications in all patients, our data suggest that aggressive therapy may be required to improve such patients’ outcome.

Published
2016
Full Text
View/download PDF

50. The vasoactive intestinal peptide (VIP) alpha-Helix up to C terminus interacts with the N-terminal ectodomain of the human VIP/Pituitary adenylate cyclase-activating peptide 1 receptor: photoaffinity, molecular modeling, and dynamics.

Author

Ceraudo E, Murail S, Tan YV, Lacapère JJ, Neumann JM, Couvineau A, and Laburthe M

Subjects
Animals, Binding Sites, CHO Cells, Computer Simulation, Cricetinae, Cricetulus, Humans, Kinetics, Magnetic Resonance Spectroscopy, Models, Molecular, Protein Binding, Protein Structure, Secondary, Protein Structure, Tertiary, Receptors, Vasoactive Intestinal Polypeptide, Type I genetics, Vasoactive Intestinal Peptide genetics, Receptors, Vasoactive Intestinal Polypeptide, Type I chemistry, Receptors, Vasoactive Intestinal Polypeptide, Type I metabolism, Vasoactive Intestinal Peptide chemistry, Vasoactive Intestinal Peptide metabolism
Abstract

The neuropeptide vasoactive intestinal peptide (VIP) strongly impacts on human pathophysiology and does so through interaction with class II G protein-coupled receptors. We characterized the C terminus-binding site of VIP in the N-terminal ectodomain (N-ted) of the human VPAC1 receptor: 1) The probe [(125)I-Bpa(28)]VIP in which the C-terminal residue (Asn(28)) is substituted by a photoreactive p-benzoyl-l-Phe (Bpa) was used to photolabel the receptor. After receptor cleavage and Edman sequencing, it was shown that Asn(28) of VIP is in contact with Lys(127) in the receptor N-ted. Taking into account previous data, it follows that the C-terminal and central parts of VIP from Asn(28) to Phe(6) lie in the N-ted. 2) A three-dimensional model of the N-ted was constructed, the fold being identified as a Sushi domain with two antiparallel beta-sheets and three disulfide bonds. The nuclear magnetic resonance structure of VIP was then docked into this model by taking into account the constraint provided by photoaffinity experiments with [(125)I-Bpa(28)]VIP. It appeared that VIP runs parallel to the beta3-beta4 antiparallel sheets. 3) We performed molecular dynamic simulations over 14 nsec of the complex between VIP and receptor N-ted and the free N-ted. The structural model of the free N-ted is stable, and VIP tends to further stabilize the N-ted structure more especially in the loops connecting the beta-sheets. These structural studies provide a detailed molecular understanding of the VIP-receptor interaction.

Published
2008
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results