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26 results on '"MESH : Lung"'

1. Infection-Mediated Priming of Phagocytes Protects against Lethal Secondary Aspergillus fumigatus Challenge

Author

Oumaïma Ibrahim-Granet, Amélie Savers, Bernhard Ryffel, Marianna Parlato, Gérard Eberl, Grégory Jouvion, Jean-Marc Cavaillon, Orhan Rasid, Matthias Brock, Cytokines et Inflammation, Institut Pasteur [Paris], School of Life Sciences, University of Nottingham, UK ( UON ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Histopathologie humaine et Modèles animaux, Immunologie et Neurogénétique Expérimentales et Moléculaires ( INEM ), Université d'Orléans ( UO ) -Centre National de la Recherche Scientifique ( CNRS ), Développement des Tissus Lymphoïdes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), This work was supported by funding from Institut Pasteur PTR 468 to OIG and AS, and the Transregio 124 'FungiNet' project A3 to AS and MB., University of Nottingham, UK (UON), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Institut Pasteur [Paris] (IP), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and BENEDIC, Bénédicte

Subjects
MESH : Bone Marrow, MESH : Spores, Fungal, medicine.medical_treatment, MESH : Cytokines, MESH: Flow Cytometry, Pathology and Laboratory Medicine, Aspergillosis, MESH: Phagocytes, Aspergillus fumigatus, Animal Cells, MESH : Aspergillosis, MESH: Animals, lcsh:Science, skin and connective tissue diseases, Lung, Disease Resistance, Fungal Pathogens, Phagocytes, Innate Immune System, MESH: Cytokines, Flow Cytometry, 3. Good health, [SDV] Life Sciences [q-bio], Aspergillus, Blood, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Aspergillus Fumigatus, Medical Microbiology, Spectrophotometry, Cytokines, MESH: Bone Marrow, Cytophotometry, Cellular Types, MESH : Receptors, Interleukin-8B, Immune Cells, Phagocytosis, Immunology, 030106 microbiology, Microbiology, 03 medical and health sciences, Microbial Pathogens, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Blood Cells, [ SDV ] Life Sciences [q-bio], Macrophages, lcsh:R, MESH: Host-Pathogen Interactions, Organisms, Biology and Life Sciences, Molecular Development, medicine.disease, Molds (Fungi), Mice, Inbred C57BL, 030104 developmental biology, lcsh:Q, Developmental Biology, 0301 basic medicine, Chemokine, Neutrophils, [SDV]Life Sciences [q-bio], lcsh:Medicine, MESH: Mice, Knockout, Receptors, Interleukin-8B, White Blood Cells, Spectrum Analysis Techniques, Bone Marrow, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, Immune Physiology, Medicine and Health Sciences, MESH : Lectins, C-Type, CXC chemokine receptors, MESH : Host-Pathogen Interactions, Mice, Knockout, Mice, Inbred BALB C, Multidisciplinary, Bone Marrow/immunology/metabolism, biology, MESH: Receptors, Interleukin-8B, Hematology, Spores, Fungal, MESH: Chemokines, Body Fluids, Cytokine, Cell Processes, Host-Pathogen Interactions, MESH : Phagocytes, Aspergillus fumigatus/immunology, Chemokines, Pathogens, Anatomy, MESH: Aspergillus fumigatus, Research Article, MESH : Flow Cytometry, MESH : Lung, MESH: Mice, Inbred BALB C, MESH: Disease Resistance, Mycology, MESH : Mice, Inbred C57BL, Research and Analysis Methods, Immune system, MESH: Mice, Inbred C57BL, MESH: Spores, Fungal, medicine, MESH : Disease Resistance, Animals, Lectins, C-Type, MESH: Lung, MESH : Chemokines, MESH: Aspergillosis, MESH : Mice, Inbred BALB C, Innate immune system, Fungi, Cell Biology, Aspergillosis/immunology/microbiology, biology.organism_classification, Immune System, MESH : Aspergillus fumigatus, physiology, biology.protein, MESH : Mice, Knockout, MESH : Animals, MESH: Lectins, C-Type
Abstract

International audience; Phagocytes restrict the germination of Aspergillus fumigatus conidia and prevent the establishment of invasive pulmonary aspergillosis in immunecompetent mice. Here we report that immunecompetent mice recovering from a primary A. fumigatus challenge are protected against a secondary lethal challenge. Using RAGγc knock-out mice we show that this protection is independent of T, B and NK cells. In protected mice, lung phagocytes are recruited more rapidly and are more efficient in conidial phagocytosis and killing. Protection was also associated with an enhanced expression of CXCR2 and Dectin-1 on bone marrow phagocytes. We also show that protective lung cytokine and chemokine responses are induced more rapidly and with enhanced dynamics in protected mice. Our findings support the hypothesis that following a first encounter with a non-lethal dose of A. fumigatus conidia, the innate immune system is primed and can mediate protection against a secondary lethal infection.

Published
2016

2. Ochratoxin A and T-2 Toxin Induce Clonogenicity and Cell Migration in Human Colon Carcinoma and Fetal Lung Fibroblast Cell Lines

Author

Abassi, Haila, Ayed-Boussema, Imen, Shirley, Sarah, Abid, Salwa, Bacha, Hassen, Laboratoire de Recherche sur les Substances Biologiquement Compatibles [Monastir] ( LRSBC ), Faculté de médecine dentaire de Monastir [Tunisie] ( FMDM ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Ministère Tunisien de l'Enseignement Supérieur et de la Recherche Scientifique et de la Technologie (Laboratoire de Recherche sur les Substances Biologiquement Compatibles (LRSBC), UMR 866 Lipides, Nutrition Cancer (Dijon), Laboratoire de Recherche sur les Substances Biologiquement Compatibles [Monastir] (LRSBC), Faculté de Médecine Dentaire de Monastir [Tunisie] (FMDM), Lipides - Nutrition - Cancer (U866) (LNC), and Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)

Subjects
MESH : Cell Line, MESH: Cell Line, Tumor, Aflatoxin B1, MESH : Lung, [ SDV.TOX ] Life Sciences [q-bio]/Toxicology, MESH : Wound Healing, MESH: T-2 Toxin, MESH : Mycotoxins, MESH: Mycotoxins, Cell Migration, Cell Line, MESH : Aflatoxin B1, Cell Movement, Cell Line, Tumor, T2-Toxin, MESH : T-2 Toxin, MESH : Ochratoxins, Humans, MESH : Cell Movement, MESH: Lung, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Clonogenicity, MESH: Cell Movement, Lung, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Colonic Neoplasms, Wound Healing, MESH: Humans, MESH : Cell Line, Tumor, MESH: Aflatoxin B1, MESH : Humans, MESH: Ochratoxins, Ochratoxin A, Mycotoxins, Ochratoxins, MESH: Cell Line, MESH: Wound Healing, T-2 Toxin, MESH : Colonic Neoplasms, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Colonic Neoplasms
Abstract

IF 3.02; International audience; T-2 toxin and Ochratoxin A (OTA) are toxic secondary metabolites produced by various fungi, and together they contaminate feedstuffs worldwide. T-2 toxin and OTA may exert carcinogenic action in rodent. Despite the various in vivo experiments, carcinogenicity of these two mycotoxins has not yet been proven for human. In this current study, we proposed to investigate, in Human colon carcinoma cells and fetal lung fibroblast-like cells transfected with MYC, the effect of T-2 toxin and OTA on cell clonogenicity and cell migration. Results of the present investigation showed that T2-toxin as well as OTA has an important clonogenic effect in all cell lines, suggesting that these mycotoxins could promote the transcription of c-myc gene. Furthermore, T-2 toxin and OTA enhanced the migration effect of HCT116 cells at very low concentrations, proposing that these mycotoxins may exhibit carcinogenesis-like properties in the studied cells.

Published
2016

3. Age-Associated Aggravation of Clinical Disease after Primary Metapneumovirus Infection of BALB/c Mice

Author

Serge Aho, Catherine Manoha, T. Petrella, Pierre Pothier, Cécile Pitoiset, Magali Darniot, Laboratoire Interactions Muqueuses Agents Transmissibles ( LIMA ), Université de Bourgogne ( UB ), Laboratoire de sérologie-virologie (CHU de Dijon), and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon )

Subjects
CD4-Positive T-Lymphocytes, MESH : Cytokines, CD8-Positive T-Lymphocytes, Antibodies, Viral, Severity of Illness Index, Mice, MESH : Female, Lung, MESH : Body Weight, Mice, Inbred BALB C, Paramyxoviridae Infections, MESH : Bronchoalveolar Lavage Fluid, biology, Respiratory tract infections, medicine.diagnostic_test, Age Factors, MESH : Plethysmography, MESH : CD8-Positive T-Lymphocytes, Respiratory Function Tests, Plethysmography, medicine.anatomical_structure, MESH : CD4-Positive T-Lymphocytes, Models, Animal, Cytokines, Female, MESH : Severity of Illness Index, Bronchoalveolar Lavage Fluid, MESH : Antibodies, Viral, Paramyxoviridae, MESH : Lung, Immunology, MESH : Neutralization Tests, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Microbiology, BALB/c, Human metapneumovirus, Neutralization Tests, Virology, MESH : Mice, MESH : Respiratory Function Tests, medicine, Animals, Humans, MESH : Mice, Inbred BALB C, Body Weight, MESH : Humans, Bronchiolitis obliterans organizing pneumonia, MESH : Paramyxoviridae Infections, biology.organism_classification, medicine.disease, MESH : Models, Animal, respiratory tract diseases, MESH : Metapneumovirus, Bronchoalveolar lavage, Insect Science, Pathogenesis and Immunity, Metapneumovirus, MESH : Age Factors, MESH : Animals, Respiratory tract
Abstract

Human metapneumovirus (hMPV) is associated with respiratory tract infections among children and adults. Because hMPV induces significant morbidity and mortality in the elderly, a model of hMPV infection in aged BALB/c mice was established. Young (8 weeks old) and aged (18 months old) mice were intranasally inoculated with hMPV. The infected mice showed respiratory dysfunction, as measured by plethysmography, a marked loss in weight (up to 24%), and severe histopathological abnormalities including bronchiolitis obliterans organizing pneumonia. However, clinical severity was far higher in the aged mice, and none of the young infected mice died. Although virus replication in the lung was greater in the older mice, clearance of virus was not delayed compared to young mice. Production of virus-specific antibody as well as neutralizing antibody was lower. Gamma interferon and monocyte chemotactic protein-1 levels in bronchoalveolar lavage fluid were significantly lower in older mice, whereas interleukin-6 and interleukin-4 levels were significantly higher. We observed by flow cytometry a significant increase in the CD4 + T lymphocytes ( P < 0.05) of the aged mice and no difference in CD8 + T-cell recruitment to the respiratory tract between the two groups. The present study investigated the effects of aging on the immunopathogenesis of hMPV infection and suggests that CD4 + T lymphocytes, the cytokine response, or a defect in humoral response may be associated with the increased disease severity observed in the aged mice.

Published
2009

4. Host-microbe interactions in distal airways: relevance to chronic airway diseases

Author

Martin , Clémence, Burgel , Pierre-Régis, Lepage , Patricia, Andréjak , Claire, De Blic , Jacques, Bourdin , Arnaud, Brouard , Jacques, Chanez , Pascal, Dalphin , Jean-Charles, Deslée , Gaetan, Deschildre , Antoine, Gosset , Philippe, Touqui , Lhousseine, Dusser , Daniel, Université de Bordeaux ( UB ), Hôpital Cochin, AP-HP, Université Paris Descartes, Service de pneumologie [CHU Cochin], CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), MICrobiologie de l'ALImentation au Service de la Santé humaine ( MICALIS ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, CHU Amiens-Picardie, Service de Pneumologie Allergologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] ( PhyMedExp ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Montpellier ( UM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Burgundy School of Business (BSB) - Ecole Supérieure de Commerce de Dijon Bourgogne (ESC) ( BSB ), Service des Maladies Respiratoires [Marseille], Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) - Hôpital Nord [CHU - APHM], Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Franche-Comté ( UFC ), Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims ( CHU Reims ), Service de pédiatrie, Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Hôpital Jeanne de Flandres, CHRU de Lille, Unité de défense innée et inflammation, Institut Pasteur [Paris], and Institut Pasteur de Lille

Subjects
MESH : Gastrointestinal Microbiome, [ SDV ] Life Sciences [q-bio], MESH : Bronchiectasis, MESH : Cystic Fibrosis, MESH : Lung, MESH : Humans, MESH : Microbiota, MESH : Pulmonary Disease, Chronic Obstructive, MESH : Asthma, MESH : Respiratory Tract Diseases, MESH : Host-Pathogen Interactions, MESH : Mycobacterium, [ SDV.EE.SANT ] Life Sciences [q-bio]/Ecology, environment/Health
Abstract

International audience; This article is the summary of a workshop, which took place in November 2013, on the roles of microorganisms in chronic respiratory diseases. Until recently, it was assumed that lower airways were sterile in healthy individuals. However, it has long been acknowledged that microorganisms could be identified in distal airway secretions from patients with various respiratory diseases, including cystic fibrosis (CF) and non-CF bronchiectasis, chronic obstructive pulmonary disease, asthma and other chronic airway diseases (e.g. post-transplantation bronchiolitis obliterans). These microorganisms were sometimes considered as infectious agents that triggered host immune responses and contributed to disease onset and/or progression; alternatively, microorganisms were often considered as colonisers, which were considered unlikely to play roles in disease pathophysiology. These concepts were developed at a time when the identification of microorganisms relied on culture-based methods. Importantly, the majority of microorganisms cannot be cultured using conventional methods, and the use of novel culture-independent methods that rely on the identification of microorganism genomes has revealed that healthy distal airways display a complex flora called the airway microbiota. The present article reviews some aspects of current literature on host-microbe (mostly bacteria and viruses) interactions in healthy and diseased airways, with a special focus on distal airways.

Published
2015

5. Fluticasone Propionate Inhibits Lipopolysaccharide-Induced Proinflammatory Response in Human Cystic Fibrosis Airway Grafts

Author

Jacky Jacquot, Claire Danel, Caroline Majer-Teboul, Edith Puchelle, Sandie Escotte, Jean-Michel Triglia, Daniel Dusser, Dominique Gaillard, Sylvie Benoit, Dynamique cellulaire et moléculaire de la muqueuse respiratoire, Université de Reims Champagne-Ardenne (URCA)-IFR53-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Anatomie et de Cytologie Pathologique (SACP), 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), Laboratoire d'histologie, cytologie, biologie cellulaire et moléculaire Pol Bouin, Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims), Biomolécules : interactions moléculaires, cellulaires et cellules-matrice extracellulaire (BIMCCME), Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de pneumologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), ORL et Chirurgie cervico-faciale pédiatrique - [Hôpitaux Timone et Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)- Hôpital Nord [CHU - APHM], Département de Pharmacologie Clinique (DPC), Laboratoire GlaxoSmithKline, Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU)- Hôpital Nord [CHU - APHM]-Assistance Publique - Hôpitaux de Marseille (APHM), Birembaut, Philippe, Université de Reims Champagne-Ardenne ( URCA ) -IFR53-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Anatomie et de Cytologie Pathologique ( SACP ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université de Reims Champagne-Ardenne ( URCA ) -Centre Hospitalier Universitaire de Reims ( CHU Reims ), Biomolécules : interactions moléculaires, cellulaires et cellules-matrice extracellulaire ( BIMCCME ), Université de Reims Champagne-Ardenne ( URCA ) -Centre Hospitalier Universitaire de Reims ( CHU Reims ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) - Hôpital Nord [CHU - APHM], and Département de Pharmacologie Clinique ( DPC )

Subjects
Lipopolysaccharides, Male, MESH: Inflammation, Cystic Fibrosis, Lipopolysaccharide, MESH : Cytokines, Anti-Inflammatory Agents, MESH : Body Fluids, MESH : Lipopolysaccharides, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Cystic fibrosis, Immunoenzyme Techniques, MESH: Body Fluids, Mice, chemistry.chemical_compound, 0302 clinical medicine, MESH : Child, MESH: Child, MESH : Female, MESH: Animals, Child, Lung, MESH: Cytokines, 0303 health sciences, MESH : Mice, Nude, Interleukin, MESH : Pseudomonas aeruginosa, respiratory system, Body Fluids, 3. Good health, Trachea, Pseudomonas aeruginosa, MESH: Pseudomonas aeruginosa, MESH : Tr, Cytokines, Molecular Medicine, Female, medicine.symptom, MESH : Interleukin-8, MESH: Cystic Fibrosis, MESH : Lung, MESH : Male, MESH : Trachea, Transplantation, Heterologous, Mice, Nude, MESH : Androstadienes, Inflammation, MESH : Anti-Inflammatory Agents, Proinflammatory cytokine, 03 medical and health sciences, MESH : Immunoenzyme Techniques, MESH : Cystic Fibrosis, MESH : Mice, MESH: Mice, Nude, MESH: Tr, medicine, Animals, Humans, MESH: Lung, Interleukin 8, MESH: Immunoenzyme Techniques, MESH: Mice, 030304 developmental biology, Pharmacology, MESH : Inflammation, MESH: Humans, business.industry, Interleukin-8, MESH : Humans, medicine.disease, MESH: Male, MESH: Interleukin-8, Androstadienes, 030228 respiratory system, chemistry, MESH: Androstadienes, MESH: Anti-Inflammatory Agents, Immunology, Fluticasone, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Respiratory epithelium, MESH : Animals, MESH: Lipopolysaccharides, business, Airway, MESH: Female, [ SDV.MHEP.PSR ] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, MESH: Trachea
Abstract

Airway inflammation, one of the major factors leading to lung damage in cystic fibrosis (CF) patients, is associated with an abnormal increase in proinflammatory cytokines. In this work, we demonstrate the increased release of the proinflammatory cytokines after lipopolysaccharide (LPS) stimulation: human interleukin (hIL)-8 in CF and non-CF airway xenografts, and hIL-6 and human growth-related oncogene-alpha (hGRO-alpha), which could be only analyzed in non-CF xenografts. Under basal conditions, we observed that hIL-8 was higher in CF xenografts compared with non-CF. We also report the anti-inflammatory effect of a glucocorticoid, fluticasone propionate (FP), on CF airway epithelium using a humanized model of airway inflammation developed in nude mice. In CF and non-CF tracheal xenografts, airway inflammation was induced by inoculating Pseudomonas aeruginosa LPS (4 h; 1 microg/ml) in the lumen of the xenografts. FP pretreatment (2 h; 10(-8) M) followed by P. aeruginosa LPS stimulation induced a significant reduction of LPS-induced hIL-8 release in airway liquid collected from CF and non-CF tracheal xenografts (85 and 80%, respectively). In non-CF tracheal xenografts, FP treatment before LPS stimulation induced a significant decrease in hIL-6 and hGRO-alpha. From these data, we suggest that FP exerts anti-inflammatory properties that may be appropriate to CF therapy, at an early stage of the disease. In addition, these results demonstrate that the humanized airway model of inflammation provides a relevant tool for analyzing the effects of anti-inflammatory drugs in different diseases in which airway inflammation is implicated.

Published
2002

6. Quantitative analysis of inflammatory cells infiltrating the cystic fibrosis airway mucosa

Author

C. Hubeau, J. P. Couetil, D. Hubert, Dominique Gaillard, E. Puchelle, D. Dusser, M. Lorenzato, Dynamique cellulaire et moléculaire de la muqueuse respiratoire, Université de Reims Champagne-Ardenne (URCA)-IFR53-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'histologie, cytologie, biologie cellulaire et moléculaire Pol Bouin, Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims), 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), Service de pneumologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Birembaut, Philippe, Université de Reims Champagne-Ardenne ( URCA ) -IFR53-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Reims Champagne-Ardenne ( URCA ) -Centre Hospitalier Universitaire de Reims ( CHU Reims ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]

Subjects
Male, MESH: Inflammation, MESH: Bronchiectasis, Pathology, MESH: Macrophages, Alveolar, Cystic Fibrosis, Lymphocyte, Cell Count, MESH : Cell Count, CD38, Lung Disease, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Epithelium, 0302 clinical medicine, T-Lymphocyte Subsets, Immunology and Allergy, MESH : Female, Mast Cells, Lung, Respiratory Tract Infections, MESH : E-Selectin, B-Lymphocytes, 0303 health sciences, MESH: Bronchi, MESH: Mast Cells, MESH : Adult, respiratory system, Intercellular Adhesion Molecule-1, MESH : Bronchi, Bronchiectasis, 3. Good health, medicine.anatomical_structure, Neutrophil Infiltration, MESH : Macrophages, Alveolar, MESH : Lung Transplantation, Female, MESH : Mast Cells, medicine.symptom, E-Selectin, Lung Transplantation, Adult, MESH: E-Selectin, medicine.medical_specialty, MESH: Cystic Fibrosis, MESH : Lung, MESH : Male, Plasma Cells, Immunology, Vascular Cell Adhesion Molecule-1, Bronchi, Inflammation, Biology, MESH : B-Lymphocytes, 03 medical and health sciences, Immune system, MESH : Bronchiectasis, MESH : Cystic Fibrosis, MESH: B-Lymphocytes, Macrophages, Alveolar, medicine, Humans, MESH: Lung, MESH : M, 030304 developmental biology, Bronchus, Mucous Membrane, MESH : Inflammation, MESH: Humans, MESH : Intercellular Adhesion Molecule-1, MESH: Cell Count, MESH: Intercellular Adhesion Molecule-1, MESH : Humans, MESH: Biological Markers, MESH: Adult, MESH : Epithelium, MESH: Male, MESH : Biological Markers, Transplantation, MESH: Epithelium, MESH: M, 030228 respiratory system, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, MESH: Lung Transplantation, MESH: Female, Biomarkers, [ SDV.MHEP.PSR ] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, CD8
Abstract

SUMMARYAirway inflammation represents a hallmark of the cystic fibrosis (CF) disease. However, the mucosal distribution of immune cells along the CF airways has not been clearly defined, particularly in intermediate bronchi and distal bronchioles. We analysed lung tissues collected at the time of transplantation from homozygous ΔF508+/+CF patients versus non-CF donors. Using immunohistochemistry, the distribution of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, polymorphonuclear neutrophils (PMN), mast cells, CD3+ T cells, including the CD4+ and CD8+ subsets, CD20+ B cells, CD38+ plasma cells and CD68+ macrophages, was analysed at lobar, segmental and distal levels of the bronchial tree. Using image cytometry, the number of cells per mm2 was assessed in the depth of the bronchial wall. In CF airways, alterations mainly consisted in lesions of the surface epithelium. Numerous immune cells were heterogeneously distributed all along the bronchial tree and mainly located in the mucosa, beneath the surface epithelium. Compared to non-CF donors, the lymphoid aggregates formed by B cells were significantly larger all along the CF airways (P = 0·001). The number of T lymphocytes was higher at the CF distal level (P = 0·035), where we observed an intense tissue damage. PMN preferentially accumulated (P = 0·033) in the CF surface epithelium, which overexpressed ICAM-1 but not VCAM-1 and E-selectin. These results highlight the nature of the inflammatory infiltrate in the CF airway mucosa and emphasize a prominent implication of PMN, B and T lymphocytes in the CF disease.

Published
2001

7. Relationship between the airway wall area and asthma control score in moderate persistent asthma

Author

Pierre-Yves Brillet, Yahya Ould-Hmeidi, Pascal Chanez, Catalin Fetita, Lukasz Adamek, Gaëlle Nachbaur, Margarete Ortner, Catherine Beigelman-Aubry, Philippe Grenier, Réponses Cellulaires et Fonctionnelles à l'Hypoxie (LRPH), Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-UFR SMBH, Université Pierre et Marie Curie - Paris 6 (UPMC), Département Advanced Research And Techniques For Multidimensional Imaging Systems (ARTEMIS), Institut Mines-Télécom [Paris] (IMT)-Télécom SudParis (TSP), Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), GlaxoSmithKline (GSK), GSK, Unité des Rickettsies et pathogènes émergents (URPE), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Département Advanced Research And Techniques For Multidimensional Imaging Systems (TSP - ARTEMIS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Réponses Cellulaires et Fonctionnelles à l'Hypoxie ( LRPH ), Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -UFR SMBH, Université Pierre et Marie Curie - Paris 6 ( UPMC ), Département Advanced Research And Techniques For Multidimensional Imaging Systems ( ARTEMIS ), Institut Mines-Télécom [Paris]-Télécom SudParis ( TSP ), Mathématiques Appliquées à Paris 5 ( MAP5 - UMR 8145 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National des Sciences Mathématiques et de leurs Interactions-Centre National de la Recherche Scientifique ( CNRS ), CHU Pitié-Salpêtrière [APHP], GlaxoSmithKline ( GSK ), Unité des Rickettsies et pathogènes émergents ( URPE ), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes ( URMITE ), Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR48, INSB-INSB-Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR48, and INSB-INSB-Centre National de la Recherche Scientifique ( CNRS )

Subjects
Male, MESH: Asthma, Body Surface Area, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [ SPI.SIGNAL ] Engineering Sciences [physics]/Signal and Image processing, 0302 clinical medicine, MESH : Cross-Sectional Studies, MESH: Body Surface Area, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, Asthma control, Forced Expiratory Volume, MESH : Tomography, X-Ray Computed, Medicine, MESH : Female, 030212 general & internal medicine, MESH: Bronchography, MESH : Bronchography, Lung, [ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging, Body surface area, MESH: Middle Aged, MESH: Bronchi, General Medicine, MESH : Adult, Bronchography, Middle Aged, respiratory system, MESH : Bronchi, medicine.anatomical_structure, Airway wall, MESH : Airway Remodeling, Airway Remodeling, MESH : Forced Expiratory Volume, Female, Radiology, MESH : Software, MESH: Tomography, X-Ray Computed, [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, MESH : Body Surface Area, Adult, medicine.medical_specialty, [ INFO.INFO-TS ] Computer Science [cs]/Signal and Image Processing, MESH : Lung, MESH : Male, Bronchi, MESH: Forced Expiratory Volume, MESH : Asthma, 03 medical and health sciences, MESH: Software, MESH: Cross-Sectional Studies, Humans, Radiology, Nuclear Medicine and imaging, MESH : Middle Aged, MESH: Lung, Asthma, MESH: Humans, business.industry, MESH : Humans, MESH: Adult, medicine.disease, MESH: Male, respiratory tract diseases, MESH: Airway Remodeling, Cross-Sectional Studies, 030228 respiratory system, business, Airway, Tomography, X-Ray Computed, MESH: Female, Asthma Control Test, Software
Abstract

International audience; OBJECTIVES: To assess the association between airway wall area and clinical asthma control, assessed by the Asthma Control Test (ACT). METHODS: This cross-sectional study evaluated 96 adults for asthma control ["at least well controlled" (ACT ≥ 20; n = 52) or "not well controlled" (ACT < 20; n = 44) and airway dimensions: luminal area (LA), wall area (WA) and WA%], obtained using automated dedicated software measurements from volumetric CT images. Results were analysed for segmental bronchi, subsegmental bronchi in the right upper lobe and basilar segments, both uncorrected and corrected for body surface area (BSA). RESULTS: For all bronchi corrected for BSA, there was no correlation between airway wall area and ACT score. There was a weak but statistically significant correlation between uncorrected WA and ACT score (r = -0.203; P = 0.047); WA values were numerically higher in the "not well-controlled" versus the "at least well-controlled asthma" subgroups. For sub-segmental bronchi, there was a correlation between the ACT score and both WA/BSA (r = -0.204; P = 0.047) and WA (r = -0.249; P = 0.014), and for upper lobe bronchi, between the ACT score and WA (r = -0.207; P = 0.044). CONCLUSION: We demonstrated a correlation between subsegmental bronchial airway measurements and clinical control of asthma; this is probably a reflection of airway remodelling and structural changes in chronic poorly controlled asthma. KEY POINTS : * Volumetric computed tomography offers new insights into bronchial morphology. * The relationship between current asthma control and airway wall abnormalities is assessed. * Some relationships between airway wall area and clinical control were demonstrated. * We observed less shape variation of bronchi in "not well-controlled" asthma patients.

Published
2013

8. 30-yr course and favorable outcome of alveolar echinococcosis despite multiple metastatic organ involvement in a non-immune suppressed patient

Author

Georges Mantion, Solange Bresson-Hadni, Jean-Philippe Miguet, Frédéric Grenouillet, Dominique A. Vuitton, Oleg Blagosklonov, Karine Bardonnet, Eric Delabrousse, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), WHO Collaborating Center on Prevention and Treatment of Human Echinococcosis, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Service de parasitologie et mycologie [CHRU de Besançon], Service de Médecine nucléaire, biophysique, isotopes [CHRU Besançon], AIREA 'association pour l'information et la recherche sur l'echinococcose alveolaire' Funding Text : This study was supported by a grant from AIREA 'association pour l'information et la recherche sur l'echinococcose alveolaire', Hôpital Jean Minjoz, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Université de Franche-Comté ( UFC ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Parasitologie-Mycologie CHU Besançon, and Dept. of Nucl. Med., Jean Minjoz Univ. Hosp., Besancon

Subjects
Lung Diseases, Male, medicine.medical_treatment, lcsh:QR1-502, Case Report, Disease, Liver transplantation, lcsh:Microbiology, DISEASE, Serology, MESH : Liver Diseases, MESH: Lung Diseases, Lung, MULTICENTER CLINICAL-TRIALS, LIVER-TRANSPLANTATION, MULTILOCULARIS INFECTION, FOLLOW-UP, DIFFERENTIATION, IMMUNODIAGNOSIS, IMPROVEMENT, RECURRENCE, DIAGNOSIS, [ SDV.MP.MYC ] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, MESH: Treatment Outcome, 0303 health sciences, MESH : Lung Diseases, Antinematodal Agents, Liver Diseases, MESH: Echinococcosis, Hepatic, MESH: Immunosuppression, Immunosuppression, General Medicine, MESH: Follow-Up Studies, MESH : Adult, Echinococcosis, MESH: Positron-Emission Tomography, 3. Good health, Mebendazole, MESH : Antinematodal Agents, Infectious Diseases, medicine.anatomical_structure, Treatment Outcome, medicine.drug, Microbiology (medical), Adult, MESH : Albendazole, medicine.medical_specialty, Echinococcosis, Hepatic, MESH: Liver Diseases, MESH : Male, MESH : Lung, MESH : Treatment Outcome, Albendazole, MESH: Mebendazole, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, medicine, MESH: Albendazole, Humans, lcsh:RC109-216, MESH: Lung, 030304 developmental biology, MESH : Mebendazole, Immunosuppression Therapy, Chemotherapy, MESH: Humans, 030306 microbiology, business.industry, lcsh:RM1-950, MESH : Humans, MESH : Positron-Emission Tomography, MESH : Follow-Up Studies, MESH: Adult, medicine.disease, MESH: Male, Surgery, lcsh:Therapeutics. Pharmacology, Positron-Emission Tomography, MESH : Immunosuppression, business, MESH : Echinococcosis, Hepatic, MESH: Antinematodal Agents, Follow-Up Studies
Abstract

We report the 30-yr history of a well-documented human case of alveolar echinococcosis, with a lung lesion at presentation followed by the discovery of a liver lesion, both removed by surgery. Subsequently, within the 13 years following diagnosis, metastases were disclosed in eye, brain and skull, as well as additional lung lesions. This patient had no immune suppression, and did not have the genetic background known to predispose to severe alveolar echinococcosis; it may thus be hypothesized that iterative multi-organ involvement was mostly due to the poor adherence to benzimidazole treatment for the first decade after diagnosis. Conversely, after a new alveolar echinococcosis recurrence was found in the right lung in 1994, the patient accepted to take albendazole continuously at the right dosage. After serology became negative and a fluoro-deoxy-glucose-Positron Emission Tomography performed in 2005 showed a total regression of the lesions in all organs, albendazole treatment could be definitively withdrawn. In 2011, the fluoro-deoxy-glucose-Positron Emission Tomography showed a total absence of parasitic metabolic activity and the patient had no clinical symptoms related to alveolar echinococcosis. The history of this patient suggests that multi-organ involvement and alveolar echinococcosis recurrence over time may occur in non-immune suppressed patients despite an apparently “radical” surgery. Metastatic dissemination might be favored by a poor adherence to chemotherapy. Combined surgery and continuous administration of albendazole at high dosage may allow alveolar echinococcosis patients to survive more than 30 years after diagnosis despite multi-organ involvement.

Published
2013

9. Functionalized single-walled carbon nanotubes containing traces of iron as new negative MRI contrast agents for in vivo imaging

Author

Doan , Bich-Thuy, Seguin , Johanne, Breton , Marie, Le Beherec , Ronan, Bessodes , Michel, Rodríguez-Manzo , Julio A, Banhart , Florian, Beloeil , Jean-Claude, Scherman , Daniel, Richard , Cyrille, Unité de pharmacologie chimique et génétique et d'imagerie (UPCGI - UMR 8151 / UMR_S 1022 ), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Institut de Physique et Chimie des Matériaux de Strasbourg (IPCMS), Université de Strasbourg (UNISTRA)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-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 d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de physique et de chimie des matériaux (IPCM), Unité de pharmacologie chimique et génétique et d'imagerie ( UPCGI - UMR 8151 / UMR_S 1022 ), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de biophysique moléculaire ( CBM ), Université d'Orléans ( UO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), and Institut de physique et de chimie des matériaux ( IPCM )

Subjects
MESH: Cell Death, Contrast Media, MESH : Iron, TOXICITY, MESH: Magnetic Resonance Imaging, X-Ray Diffraction, BIODISTRIBUTION, MAGNETIC-RESONANCE, MRI contrast agents, NANOPARTICLES, MESH: Animals, Lung, MESH: Iron, Cell Death, MESH : Hep G2 Cells, MESH: X-Ray Diffraction, Hep G2 Cells, Magnetic Resonance Imaging, CANCER, in vivo, Liver, MESH: Nanotubes, Carbon, MESH : Imaging, Three-Dimensional, functionalization, TOXICOLOGY, MESH : Lung, Iron, MESH: Hep G2 Cells, MESH: Imaging, Three-Dimensional, MESH : X-Ray Diffraction, Imaging, Three-Dimensional, MESH : Magnetic Resonance Imaging, MESH: Contrast Media, MESH : Mice, Animals, Humans, MESH: Lung, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, MESH : Contrast Media, MESH: Humans, carbon nanotubes, Nanotubes, Carbon, MESH : Humans, MESH : Liver, TRANSPORTERS, GADONANOTUBES, MICE, MESH : Cell Death, traces of iron, ENHANCED MRI, MESH : Nanotubes, Carbon, MESH : Animals, MESH: Liver
Abstract

International audience; Single-walled carbon nanotubes (SWCNTs) containing traces of iron oxide were functionalized by noncovalent lipid-PEG or covalent carboxylic acid function to supply new efficient MRI contrast agents for in vitro and in vivo applications. Longitudinal (r(1)) and transversal (r(2)) water proton relaxivities were measured at 300 MHz, showing a stronger T(2) feature as an MRI contrast agent (r(2)/r(1) = 190 for CO(2) H functionalisation). The r(2) relaxivity was demonstrated to be correlated to the presence of iron oxide in the SWNT-carboxylic function COOH, in comparison to iron-free ones. Biodistribution studies on mice after a systemic injection showed a negative MRI contrast in liver, suggesting the presence of the nanotubes in this organ until 48 h after i.v. injection. The presence of carbon nanotubes in liver was confirmed after ex vivo carbon extraction. Finally, cytotoxicity studies showed no apparent effect owing to the presence of the carbon nanotubes. The functionalized carbon nanotubes were well tolerated by the animals at the dose of 10 µg g(-1) body weight.

Published
2012

10. Acute lung, heart, liver, and pancreatic involvements with hyponatremia and retinochoroiditis in a 33-year-old French Guianan patient

Author

Matthieu Groh, Patrick Yeni, Daniel Ajzenberg, Magalie Demar, Véronique Joly, Dominique Aubert, Isabelle Villena, Sandrine Houze, Bernard Carme, Cécile Charlois-Ou, Alexandra Faussart, Stéphane Simon, Service des maladies infectieuses et tropicales, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Centre National de Référence (CNR) Toxoplasmose/Toxoplasma Biological Resource Center (BRC) (CNR Toxoplasmose-Toxoplasma BRC), CHU Limoges, Université de Limoges (UNILIM), Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Centre d'investigation clinique Antilles-Guyane (CIC - Antilles Guyane), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU de la Martinique [Fort de France]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Epidémiologie des parasitoses et mycoses tropicales, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), Unité des Maladies Infectieuses et Tropicales (UMIT), Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Service de maladies infectieuses et tropicales, AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Mère et enfant face aux infections tropicales (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Laboratoire de Recherche en Pathologie Infectieuse, Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Centre National de Référence (CNR) Toxoplasmose/Toxoplasma Biological Resource Center (BRC) ( CNR Toxoplasmose-Toxoplasma BRC ), Université de Limoges ( UNILIM ), Neuroépidémiologie Tropicale ( NET ), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST ), Université de Limoges ( UNILIM ) -Université de Limoges ( UNILIM ), Centre d'investigation clinique Antilles-Guyane ( CIC - Antilles Guyane ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU de la Martinique-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Université des Antilles et de la Guyane ( UAG ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Unité des Maladies Infectieuses et Tropicales ( UMIT ), AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Mère et enfant face aux infections tropicales ( MERIT - UMR_D 216 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut de Recherche pour le Développement ( IRD ), Université Paris Diderot - Paris 7 ( UPD7 ), 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), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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)-Université Paris Diderot - Paris 7 (UPD7), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), 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), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), and Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, Travel-Associated Diseases, Pathology, Choroiditis, RC955-962, Lung pathology, MESH: Choroiditis, 0302 clinical medicine, Arctic medicine. Tropical medicine, MESH : Myocardium, Neuroepidemiology, MESH : Pancreas, Lung, ComputingMilieux_MISCELLANEOUS, MESH: Guinea, 0303 health sciences, MESH : Guinea, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH : Adult, MESH : Hyponatremia, MESH: Pancreas, 3. Good health, Infectious Diseases, Liver, MESH: Toxoplasmosis, language, Medicine, Public aspects of medicine, RA1-1270, Liver pathology, Toxoplasmosis, Hyponatremia, Neglected Tropical Diseases, Adult, medicine.medical_specialty, MESH: Myocardium, Infectious Disease Control, MESH : Lung, MESH : Male, 030231 tropical medicine, Old French, MESH : Toxoplasmosis, 03 medical and health sciences, Parasitic Diseases, Lung heart, medicine, Humans, MESH: Lung, Pancreas, 030304 developmental biology, Symposium, MESH: Humans, business.industry, Myocardium, General surgery, MESH : Humans, Public Health, Environmental and Occupational Health, MESH : Liver, MESH: Adult, MESH: Male, language.human_language, MESH: Hyponatremia, Guinea, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH : Choroiditis, MESH: Liver
Abstract

1 Department of Infectious Diseases, Hopital Bichat, Paris Diderot University, Paris, France, 2 Department of Parasitology and Mycology, Hopital Bichat, Paris Diderot University, Paris, France, 3 National Reference Centre on Toxoplasmosis and Biological Resource Centre Toxoplasma, EA3800, Department of Parasitology and Mycology, CHU Maison Blanche, University of Reims Champagne-Ardenne, Reims, France, 4 INSERM UMR 1094, Tropical Neuroepidemiology, Department of Parasitology and Mycology, University of Limoges, Limoges, France, 5 EA 3593, Department of Parasitology and Mycology, Cayenne Hospital, University of the Antilles and Guyana, Cayenne, French Guiana

Published
2012

11. Serotonin 5-HT2B receptors are required for bone-marrow contribution to pulmonary arterial hypertension

Author

Corinne Collet, Ziad Mallat, Silvina L. Diaz, Arnauld Belmer, Luc Maroteaux, Stéphane Doly, Sarah Hatia, Francine Côté, Marc Humbert, Philippe Hervé, Jacques Callebert, Jean-Marie Launay, Laboratoire Logiciels Systèmes Réseaux (LSR - IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Logiciels Systèmes Réseaux ( LSR - IMAG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National Polytechnique de Grenoble ( INPG ) -Centre National de la Recherche Scientifique ( CNRS ), 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 biochimie et biologie moléculaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-IFR139, Service Pneumologie, Centre Chirurgical Marie Lannelongue (CCML), 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), Institut du Fer à Moulin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hématologie adulte, Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Hypertension arterielle pulmonaire physiopathologie et innovation thérapeutique, Centre Chirurgical Marie Lannelongue (CCML)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work has been supported by funds from the Centre National de la Recherche Scientifique, Inserm, the Université Pierre et Marie Curie, and by grants from the Fondation de France, the Fondation pour la Recherche Médicale, and the European Union (DEVANX). S.L.D. is supported by a Region Ile de France DIM STEM, A.B. by a SFPT, and S.D. by a Lefoulon-DeLalande fellowship., Maroteaux, Luc, Centre chirurgical Marie Lannelongue, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre chirurgical Marie Lannelongue, IFR139-Hôpital Lariboisière-Assistance publique - Hôpitaux de Paris (AP-HP), Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre de référence des mastocytoses-CHU Necker - Enfants Malades [AP-HP]-Centre National de la Recherche Scientifique ( CNRS ), and Centre chirurgical Marie Lannelongue-Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
Male, MESH : Bone Marrow, Pathology, MESH : Hypertension, Pulmonary, Myeloid, CD34, MESH : Models, Biological, 030204 cardiovascular system & hematology, Biochemistry, MESH: Mice, Knockout, MESH : Blood Chemical Analysis, Mice, MESH : Receptor, Serotonin, 5-HT2B, 0302 clinical medicine, Bone Marrow, Receptor, Serotonin, 5-HT2B, Familial Primary Pulmonary Hypertension, MESH : Female, Platelet, MESH: Animals, Receptor, Lung, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Mice, Knockout, 0303 health sciences, MESH: Bone Marrow Cells, MESH: Blood Chemical Analysis, Bone Marrow Stem Cell, Cell Differentiation, Hematology, 3. Good health, MESH: Proto-Oncogene Proteins c-kit, Proto-Oncogene Proteins c-kit, Blood, medicine.anatomical_structure, Female, MESH: Bone Marrow, MESH : Cell Differentiation, MESH: Cells, Cultured, MESH: Cell Differentiation, medicine.medical_specialty, Hypertension, Pulmonary, MESH : Lung, MESH : Male, Immunology, Bone Marrow Cells, Biology, Models, Biological, MESH : Proto-Oncogene Proteins c-kit, 03 medical and health sciences, MESH : Cells, Cultured, MESH : Mice, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, MESH: Blood, Animals, Humans, MESH: Lung, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Progenitor cell, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, 030304 developmental biology, MESH: Humans, MESH: Hypertension, Pulmonary, MESH : Humans, MESH: Models, Biological, MESH: Receptor, Serotonin, 5-HT2B, Cell Biology, MESH: Male, Cancer research, MESH : Mice, Knockout, MESH : Blood, MESH : Animals, Serotonin, Bone marrow, MESH: Female, Blood Chemical Analysis, MESH : Bone Marrow Cells
Abstract

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by lung endothelial dysfunction and vascular remodeling. Recently, bone marrow progenitor cells have been localized to PAH lungs, raising the question of their role in disease progression. Independently, serotonin (5-HT) and its receptors have been identified as contributors to the PAH pathogenesis. We hypothesized that 1 of these receptors, 5-HT2B, is involved in bone marrow stem cell mobilization that participates in the development of PAH and pulmonary vascular remodeling. A first study revealed expression of 5-HT2B receptors by circulating c-kit+ precursor cells, whereas mice lacking 5-HT2B receptors showed alterations in platelets and monocyte-macrophage numbers, and in myeloid lineages of bone marrow. Strikingly, mice with restricted expression of 5-HT2B receptors in bone marrow cells developed hypoxia or monocrotaline-induced increase in pulmonary pressure and vascular remodeling, whereas restricted elimination of 5-HT2B receptors on bone marrow cells confers a complete resistance. Moreover, ex vivo culture of human CD34+ or mice c-kit+ progenitor cells in the presence of a 5-HT2B receptor antagonist resulted in altered myeloid differentiation potential. Thus, we demonstrate that activation of 5-HT2B receptors on bone marrow lineage progenitors is critical for the development of PAH.

Published
2012

12. Toxicity of carbon dioxide: A review

Author

Thierry Jo Molina, Mireille Régnier, Jacques Bonte, Adeline Guais, Gérard Brand, Georges Grevillot, Sam Dukan, Mélanie Karrer, Laurence Jacquot, Laurent Schwartz, Algorithms and Models for Integrative Biology (AMIB ), Laboratoire d'informatique de l'École polytechnique [Palaiseau] (LIX), Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-Laboratoire de Recherche en Informatique (LRI), Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (EA 481) (NEURO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Laboratoire de chimie bactérienne (LCB), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Réactions et Génie des Procédés (LRGP), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biorébus, Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (EA 481) ( NEURO ), Université de Franche-Comté ( UFC ) -Université Bourgogne Franche-Comté [COMUE] ( UBFC ), Centre National de la Recherche Scientifique ( CNRS ), Laboratoire des Sciences du Génie Chimique ( LSGC ), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Laboratoire d'informatique de l'École polytechnique [Palaiseau] ( LIX ), Centre National de la Recherche Scientifique ( CNRS ) -École polytechnique ( X ), AP-HP Hôpital Raymond Poincaré [Garches], Biorebus, Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Franche-Comté (UFC), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [APHP], Centre National de la Recherche Scientifique (CNRS), Laboratoire des Sciences du Génie Chimique (LSGC), Institut National Polytechnique de Lorraine (INPL)-Centre National de la Recherche Scientifique (CNRS), Algorithms and Models for Integrative Biology ( AMIB ), École polytechnique ( X ) -Centre National de la Recherche Scientifique ( CNRS ) -École polytechnique ( X ) -Centre National de la Recherche Scientifique ( CNRS ) -Laboratoire de Recherche en Informatique ( LRI ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ) -Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique ( Inria ), Laboratoire de Neurosciences Intégratives et Cliniques - UFC ( NEURO ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Laboratoire de chimie bactérienne ( LCB ), Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Réactions et Génie des Procédés ( LRGP ), Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ), École polytechnique ( X ) -Centre National de la Recherche Scientifique ( CNRS ), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Hôpital Raymond Poincaré [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Central Nervous System, MESH : Carcinogens, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, [ SDV.TOX ] Life Sciences [q-bio]/Toxicology, Physiology, 010501 environmental sciences, Toxicology, Long term toxicity, MESH: Reproduction, MESH: Carbon Dioxide, Cardiovascular System, 01 natural sciences, Tobacco smoke, MESH: Carcinogens, Hypercapnia, chemistry.chemical_compound, MESH: Bicarbonates, MESH: Animals, [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Lung, Acidosis, 0303 health sciences, Inhalation, MESH : Central Nervous System, Reproduction, MESH : Reproduction, General Medicine, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, MESH : Carbon Dioxide, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Toxicity, Carbon dioxide, MESH: Acidosis, Respiratory, medicine.symptom, MESH : Lung, MESH : Bicarbonates, 03 medical and health sciences, MESH : Cardiovascular System, [ INFO.INFO-BI ] Computer Science [cs]/Bioinformatics [q-bio.QM], medicine, Animals, Humans, MESH: Central Nervous System, MESH: Lung, Carcinogen, 030304 developmental biology, 0105 earth and related environmental sciences, Fetus, MESH: Humans, MESH : Hypercapnia, business.industry, MESH: Cardiovascular System, MESH : Humans, Carbon Dioxide, MESH : Acidosis, Respiratory, Bicarbonates, chemistry, MESH: Hypercapnia, Carcinogens, MESH : Animals, Acidosis, Respiratory, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

Lien vers le texte intégral : http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21732636; International audience; The toxicity of carbon dioxide has been established for close to a century. A number of animal experiments have explored both acute and long-term toxicity with respect to the lungs, the cardiovascular system, and the bladder, showing inflammatory and possible carcinogenic effects. Carbon dioxide also induces multiple fetal malformations and probably reduces fertility in animals. The aim of the review is to recapitulate the physiological and metabolic mechanisms resulting from CO(2) inhalation. As smokers are exposed to a high level of carbon dioxide (13%) that is about 350 times the level in normal air, we propose the hypothesis that carbon dioxide plays a major role in the long term toxicity of tobacco smoke.

Published
2011

13. Identification of SPOCK2 as a susceptibility gene for bronchopulmonary dysplasia

Author

Pierre-Henri Jarreau, Emmanuelle Bouzigon, Johanna M. Huusko, Roberto Incitti, Ines Layouni, Jacques R. Bourbon, Richard Lenclen, Claude Danan, Florence Demenais, Mikko Hallman, Alice Hadchouel, Juliana Patkai, Christophe Delacourt, Xavier Durrmeyer, Marie-Laure Franco-Montoya, INSERM U955, équipe 4, Service de Pneumologie Allergologie [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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-PremUp Foundation, Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de réanimation néonatale de Créteil, CHI Créteil, Variabilité Génétique et Maladies Humaines, 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), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Department of pediatrics, Oulu University Hospital-Institute of Clinical Medicine, PremUp Foundation, Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de réanimation néonatale Port-Royal, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Réanimation Néonatale, CHI Poissy-Saint-Germain, Unité Fonctionnelle de Recherche Clinique, Programme Hospitalier de Recherche Clinique AOR 07 018, Assistance Publique - Hôpitaux de Paris. Hadchouel was funded by INSERM., CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-PremUp Foundation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Descartes - Paris 5 (UPD5)-CHI Créteil-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Descartes - Paris 5 (UPD5)-CHI Créteil-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Descartes - Paris 5 (UPD5)-CHI Créteil-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP]-PremUp Foundation, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Sorbonne Universités-Université Paris Descartes - Paris 5 ( UPD5 ) -CHI Créteil-Institut de Recherche pour le Développement ( IRD ) -Université Paris-Sud - Paris 11 ( UP11 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Sorbonne Universités-Université Paris Descartes - Paris 5 ( UPD5 ) -CHI Créteil-Institut de Recherche pour le Développement ( IRD ) -Université Paris-Sud - Paris 11 ( UP11 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Sorbonne Universités-Université Paris Descartes - Paris 5 ( UPD5 ) -CHI Créteil-Institut de Recherche pour le Développement ( IRD ) -Université Paris-Sud - Paris 11 ( UP11 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ), and CHU Cochin [AP-HP]

Subjects
Male, Pathology, Gene Expression, MESH : Genotype, Disease, Critical Care and Intensive Care Medicine, MESH: Animals, Newborn, MESH: Genotype, 0302 clinical medicine, Polymorphism (computer science), MESH : Female, MESH: Animals, MESH: Bronchopulmonary Dysplasia, Finland, Bronchopulmonary Dysplasia, 0303 health sciences, education.field_of_study, MESH : Rats, MESH : Animals, Newborn, MESH: Polymorphism, Single Nucleotide, MESH: Finland, MESH : Polymorphism, Single Nucleotide, Respiratory disease, MESH: Infant, Newborn, MESH: Genetic Predisposition to Disease, Gestational age, MESH: European Continental Ancestry Group, MESH : Proteoglycans, 3. Good health, MESH : Infant, Premature, medicine.anatomical_structure, MESH: Proteoglycans, Female, Proteoglycans, MESH : Genome-Wide Association Study, Infant, Premature, MESH : Finland, MESH : Bronchopulmonary Dysplasia, Pulmonary and Respiratory Medicine, MESH: Infant, Premature, medicine.medical_specialty, MESH: Gene Expression, Genotype, MESH: Rats, MESH : Lung, MESH : Male, Population, Black People, MESH : Infant, Newborn, Polymorphism, Single Nucleotide, White People, Article, MESH : African Continental Ancestry Group, premature, lung, MESH : European Continental Ancestry Group, 03 medical and health sciences, 030225 pediatrics, Intensive care, medicine, Animals, Humans, Genetic Predisposition to Disease, MESH: Lung, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, education, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, development, 030304 developmental biology, Lung, MESH: Humans, business.industry, MESH : Humans, Infant, Newborn, medicine.disease, infant, MESH: Male, Rats, MESH : Gene Expression, Animals, Newborn, Bronchopulmonary dysplasia, Immunology, MESH: Genome-Wide Association Study, MESH : Genetic Predisposition to Disease, MESH : Animals, MESH: African Continental Ancestry Group, DNA microarrays, business, MESH: Female, Genome-Wide Association Study
Abstract

International audience; RATIONALE: Bronchopulmonary dysplasia is the most common chronic respiratory disease in premature infants. Genetic factors might contribute to bronchopulmonary dysplasia susceptibility. OBJECTIVES: To identify genetic variants involved in bronchopulmonary dysplasia through a genome-wide association study. METHODS: We prospectively evaluated 418 premature neonates (gestational age

Published
2011

14. IL-1 and IL-23 mediate early IL-17A production in pulmonary inflammation leading to late fibrosis

Author

Lizette Fick, Rachel Vacher, Alain Fautrel, Maria Leite-de-Moraes, Isabelle Couillin, Bernhard Ryffel, Sabine Charron, Paméla Gasse, Marc Le Bert, Marie-Laure Michel, François Huaux, Gérard Eberl, Nicolas Riteau, Vincent Lagente, Valérie F. J. Quesniaux, Franco Di Padova, Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), 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), Hépatotoxicité et xénobiotiques, Plate-forme d'histopathologie, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Foie, métabolismes et cancer, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Novartis Pharma AG, Institute of Immunology and Infectious Disease and Molecular Medicine, Foie, métabolismes et cancer, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Développement des Tissus Lymphoïdes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Catholique de Louvain = Catholic University of Louvain (UCL), UCL - SSS/IREC/LTAP - Louvain Centre for Toxicology and Applied Pharmacology, Brébion, Alice, Université de Rennes (UR)-Université de Rennes (UR)-Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Couillin, Isabelle, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, Immunologie et embryologie moléculaires (IEM), Immunologie et embryologie moléculaires ( IEM ), Université d'Orléans ( UO ) -Centre National de la Recherche Scientifique ( CNRS ), 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 ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140-Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140-Foie, métabolismes et cancer, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Microenvironnement et remodelage, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Université Catholique de Louvain ( UCL ), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), and Université d'Orléans (UO) - Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Pulmonology, MESH: Flow Cytometry, MESH : Interleukin-23 Subunit p19, Idiopathic pulmonary fibrosis, Mice, MESH : Bleomycin, 0302 clinical medicine, Fibrosis, T-Lymphocyte Subsets, MESH: Interleukin-1beta, Pulmonary fibrosis, Interleukin 23, MESH: Animals, Immune Response, Lung, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, MESH : Reverse Transcriptase Polymerase Chain Reaction, Lung Injury, Flow Cytometry, MESH : Enzyme-Linked Immunosorbent Assay, MESH : Mice, Transgenic, MESH: Bleomycin, 3. Good health, Medicine, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Immune Cells, Science, Immunology, Bleomycin, MESH : Interleukin-1beta, 03 medical and health sciences, Biology, MESH : Pneumonia, Immunity, Pneumonia, medicine.disease, MESH : T-Lymphocyte Subsets, Mice, Inbred C57BL, chemistry, Interleukin-23 Subunit p19, MESH : Transforming Growth Factor beta1, MESH: Female, Neutrophils, Pulmonary Fibrosis, MESH: Interleukin-17, Interleukin-1beta, MESH: T-Lymphocyte Subsets, Inflammatory diseases, Interleukin-23, MESH: Mice, Knockout, chemistry.chemical_compound, MESH: Transforming Growth Factor beta1, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH : Lung Injury, MESH : Female, Enzyme-linked immunoassays, Mice, Knockout, MESH: Interleukin-23, Multidisciplinary, Reverse Transcriptase Polymerase Chain Reaction, Interleukin-17, MESH: Enzyme-Linked Immunosorbent Assay, medicine.anatomical_structure, MESH: Lung Injury, Female, medicine.symptom, Research Article, MESH: Pneumonia, MESH : Flow Cytometry, MESH: Mice, Transgenic, MESH : Male, MESH : Lung, T cells, Inflammation, Mice, Transgenic, Enzyme-Linked Immunosorbent Assay, MESH: Interleukin-23 Subunit p19, MESH : Mice, Inbred C57BL, MESH : Interleukin-17, Immunopathology, Lung injury, Interstitial Lung Diseases, MESH : Pulmonary Fibrosis, Transforming Growth Factor beta1, MESH: Mice, Inbred C57BL, MESH : Mice, medicine, Animals, MESH: Lung, MESH: Mice, 030304 developmental biology, MESH: Pulmonary Fibrosis, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Male, MESH : Interleukin-23, MESH : Mice, Knockout, MESH : Animals, Collagens, 030215 immunology
Abstract

BackgroundIdiopathic pulmonary fibrosis is a devastating as yet untreatable disease. We demonstrated recently the predominant role of the NLRP3 inflammasome activation and IL-1β expression in the establishment of pulmonary inflammation and fibrosis in mice.MethodsThe contribution of IL-23 or IL-17 in pulmonary inflammation and fibrosis was assessed using the bleomycin model in deficient mice.ResultsWe show that bleomycin or IL-1β-induced lung injury leads to increased expression of early IL-23p19, and IL-17A or IL-17F expression. Early IL-23p19 and IL-17A, but not IL-17F, and IL-17RA signaling are required for inflammatory response to BLM as shown with gene deficient mice or mice treated with neutralizing antibodies. Using FACS analysis, we show a very early IL-17A and IL-17F expression by RORγt(+) γδ T cells and to a lesser extent by CD4αβ(+) T cells, but not by iNKT cells, 24 hrs after BLM administration. Moreover, IL-23p19 and IL-17A expressions or IL-17RA signaling are necessary to pulmonary TGF-β1 production, collagen deposition and evolution to fibrosis.ConclusionsOur findings demonstrate the existence of an early IL-1β-IL-23-IL-17A axis leading to pulmonary inflammation and fibrosis and identify innate IL-23 and IL-17A as interesting drug targets for IL-1β driven lung pathology.

Published
2011

15. Spatiotemporal motion estimation for respiratory-correlated imaging of the lungs

Author

Jef Vandemeulebroucke, Simon Rit, Jan Kybic, Patrick Clarysse, David Sarrut, Calvat, Pascal, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé ( CREATIS ), 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 ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'InfoRmatique en Image et Systèmes d'information ( LIRIS ), Université Lumière - Lyon 2 ( UL2 ) -École Centrale de Lyon ( ECL ), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ) -Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ), Center for Machine Perception, Czech Technical University in Prague ( CTU ), 4 - Imagerie Tomographique et Radiothérapie, Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), CCIN2P3, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Tomographique et Radiothérapie, Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Czech Technical University in Prague (CTU), and Electronics and Informatics

Subjects
Time Factors, respiratory motion, MESH : Movement, MESH : Four-Dimensional Computed Tomography, Movement, MESH : Lung, Diaphragm, Physics::Medical Physics, MESH: Movement, MESH : Models, Biological, Thoracic Radiotherapy, Models, Biological, MESH : Artifacts, 4D Ct, Deformable Registration, Image Processing, Computer-Assisted, Organ Motion, MESH: Lung, [ SDV.IB ] Life Sciences [q-bio]/Bioengineering, Four-Dimensional Computed Tomography, 4-Dimensional Computed-Tomography, Lung, Ct, Deformations, MESH: Respiration, [SDV.IB] Life Sciences [q-bio]/Bioengineering, MESH: Four-Dimensional Computed Tomography, Respiration, MESH: Time Factors, MESH: Models, Biological, MESH: Image Processing, Computer-Assisted, MESH : Respiration, Mr-Images, MESH: Artifacts, MESH: Diaphragm, Nonrigid Registration, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Reconstruction, MESH : Diaphragm, Artifacts, MESH : Image Processing, Computer-Assisted, Model, MESH : Time Factors
Abstract

International audience; PURPOSE: Four-dimensional computed tomography (4D CT) can provide patient-specific motion information for radiotherapy planning and delivery. Motion estimation in 4D CT is challenging due to the reduced image quality and the presence of artifacts. We aim to improve the robustness of deformable registration applied to respiratory-correlated imaging of the lungs, by using a global problem formulation and pursuing a restrictive parametrization for the spatiotemporal deformation model. METHODS: A spatial transformation based on free-form deformations was extended to the temporal domain, by explicitly modeling the trajectory using a cyclic temporal model based on B-splines. A global registration criterion allowed to consider the entire image sequence simultaneously and enforce the temporal coherence of the deformation throughout the respiratory cycle. To ensure a parametrization capable of capturing the dynamics of respiratory motion, a prestudy was performed on the temporal dimension separately. The temporal parameters were tuned by fitting them to diaphragm motion data acquired for a large patient group. Suitable properties were retained and applied to spatiotemporal registration of 4D CT data. Registration results were validated using large sets of landmarks and compared to consecutive spatial registrations. To illustrate the benefit of the spatiotemporal approach, we also assessed the performance in the presence of motion-induced artifacts. RESULTS: Cubic B-splines gave better or similar fitting results as lower orders and were selected because of their inherently stronger regularization. The fitting and registration errors increased gradually with the temporal control point spacing, representing a trade-off between achievable accuracy and sensitivity to noise and artifacts. A piecewise smooth trajectory model, allowing for a discontinuous change of speed at end-inhale, was found most suitable to account for the sudden changes of motion at this breathing phase. The spatiotemporal modeling allowed a reduction of the number of parameters of 45%, while maintaining registration accuracy within 0.1 mm. The approach reduced the sensitivity to artifacts. CONCLUSIONS: Spatiotemporal registration can provide accurate motion estimation for 4D CT and improves the robustness to artifacts.

Published
2011

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

Author

Jacques R. Bourbon, Virginie Masse, Jelena Martinovic, Bernard Thébaud, Caroline Elie, Olivier Boucherat, Alexandra Benachi, Christophe Delacourt, Marie-Laure Franco-Montoya, Centre de Recherche en Cancérologie, Université Laval, Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), PremUp Foundation, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Sorbonne Universités-Université Paris Descartes - Paris 5 ( UPD5 ) -CHI Créteil-Institut de Recherche pour le Développement ( IRD ) -Université Paris-Sud - Paris 11 ( UP11 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ), Service de foetopathologie, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Department of Pediatrics-Division of Neonatology, University of Alberta [Edmonton], Service d'Obstétrique et Gynécologie, Université Laval [Québec] (ULaval), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], University of Alberta, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Descartes - Paris 5 (UPD5)-CHI Créteil-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Guellaen, Georges

Subjects
Vascular Endothelial Growth Factor A, MESH : Hypertension, Pulmonary, Physiology, Angiogenesis, Neovascularization, 0302 clinical medicine, MESH: Pregnancy, Pregnancy, MESH : Angiopoietin-2, MESH : Angiopoietin-1, MESH : Female, Lung, 0303 health sciences, biology, Neovascularization, Pathologic, Nitric Oxide Synthase Type III, Receptor, TIE-2, MESH: Receptor, TIE-2, 3. Good health, Nitric oxide synthase, Vascular endothelial growth factor A, medicine.anatomical_structure, 030220 oncology & carcinogenesis, MESH : Vascular Endothelial Growth Factor A, Female, medicine.symptom, MESH: Nitric Oxide Synthase Type III, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Hypertension, Pulmonary, MESH : Lung, MESH : Nitric Oxide Synthase Type III, Article, Angiopoietin-2, 03 medical and health sciences, MESH: Angiopoietin-1, MESH: Angiopoietin-2, Physiology (medical), Internal medicine, medicine, Angiopoietin-1, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Receptor, TIE-2, Humans, MESH: Lung, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, MESH: Humans, MESH: Hypertension, Pulmonary, business.industry, MESH: Vascular Endothelial Growth Factor A, MESH : Humans, Congenital diaphragmatic hernia, MESH : Neovascularization, Pathologic, Cell Biology, medicine.disease, Pulmonary hypertension, MESH : Pregnancy, Endocrinology, biology.protein, business, MESH: Neovascularization, Pathologic, MESH: Female
Abstract

International audience; Lung hypoplasia (LH) is a life-threatening congenital abnormality with various causes. It involves vascular bed underdevelopment with abnormal arterial muscularization leading to pulmonary hypertension. Because underlying molecular changes are imperfectly known and sometimes controversial, we determined key factors of angiogenesis along intrauterine development, focusing at the angiopoietin (ANG)/Tie-2 system. Lung specimens from medical terminations of pregnancy (9-37 wk) were used, including LH due to congenital diaphragmatic hernia (CDH) or other causes, and nonpulmonary disease samples were used as controls. ELISA determination indicated little ANG-1 change during pregnancy and no effect of LH, whereas Tie-2 declined similarly between 9 and 37 wk in LH and controls. By contrast, ANG-2 markedly increased in LH from 24 wk, whereas it remained stable in controls. Because VEGF increased also, this was interpreted as an attempt to overcome vascular underdevelopment. Hypothesizing that its inefficiency might be due to impaired downstream mechanism, endothelial nitric oxide synthase (eNOS) was determined by semiquantitative Western blot and found to be reduced by approximately 75%, mostly in the instance of CDH. In conclusion, angiogenesis remains defective in hypoplastic lungs despite reactive enhancement of VEGF and ANG-2 production, which could be due, at least in part, to insufficient eNOS expression.

Published
2010

17. A capsid-encoded PPxY-motif facilitates adenovirus entry

Author

Baptist Jammart, Zsolt Ruzsics, Eric J. Kremer, Daniel Henaff, Sigrid Seelmeir, Harald Wodrich, Carolina Segura-Morales, Christopher M. Wiethoff, Olivier Coux, Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Max Von Pettenkofer Institute (MVP), Ludwig-Maximilians-Universität München (LMU), Centre de recherche en Biologie Cellulaire (CRBM), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Loyola University Medical Center (LUMC), Microbiologie cellulaire et moléculaire et pathogénicité ( MCMP ), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique ( CNRS ), Institut de Recherche en Infectiologie de Montpellier ( IRIM ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Montpellier ( UM ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Max Von Pettenkofer Institute ( MVP ), Ludwig-Maximilians-Universität München, Centre de recherches de biochimie macromoléculaire ( CRBM ), Université Montpellier 1 ( UM1 ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -IFR122-Centre National de la Recherche Scientifique ( CNRS ), Loyola University Medical Center ( LUMC ), Automatic mesh generation and advanced methods ( Gamma3 ), Institut Charles Delaunay ( ICD ), Université de Technologie de Troyes ( UTT ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Technologie de Troyes ( UTT ) -Centre National de la Recherche Scientifique ( CNRS ) -Inria Saclay - Ile de France, and Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria )

Subjects
MESH: Osteosarcoma, Nedd4 Ubiquitin Protein Ligases, MESH : Capsid Proteins, MESH: Microtubule-Organizing Center, NEDD4, Retinal Pigment Epithelium, Microtubules, MESH : Ubiquitination, Conserved sequence, MESH: Endosomal Sorting Complexes Required for Transport, Adenovirus Infections, Human, MESH: Protein Structure, Tertiary, Ubiquitin, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, Biology (General), Internalization, Virology/Virion Structure, Assembly, and Egress, Lung, Conserved Sequence, MESH : Microtubules, MESH: Capsid Proteins, media_common, MESH : Adenoviruses, Human, 0303 health sciences, Osteosarcoma, MESH : Osteosarcoma, MESH: Conserved Sequence, MESH: Microtubules, 030302 biochemistry & molecular biology, MESH : Adenovirus Infections, Human, MESH: Retinal Pigment Epithelium, 3. Good health, Cell biology, MESH : Epithelial Cells, MESH : Microtubule-Organizing Center, MESH: Adenovirus Infections, Human, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Capsid, MESH : Retinal Pigment Epithelium, MESH: Epithelial Cells, MESH : Protein Structure, Tertiary, Research Article, MESH: Adenoviruses, Human, MESH: Cell Line, Tumor, Endosome, QH301-705.5, media_common.quotation_subject, Ubiquitin-Protein Ligases, MESH : Lung, Immunology, Endosomes, Biology, Microbiology, 03 medical and health sciences, Viral entry, MESH : Conserved Sequence, Virology, Cell Line, Tumor, Genetics, Humans, MESH: Lung, Molecular Biology, 030304 developmental biology, MESH: Humans, Endosomal Sorting Complexes Required for Transport, MESH : Cell Line, Tumor, Adenoviruses, Human, MESH : Humans, Ubiquitination, Epithelial Cells, RC581-607, Virology/Host Invasion and Cell Entry, MESH: Ubiquitin-Protein Ligases, Protein Structure, Tertiary, MESH: Endosomes, biology.protein, MESH : Endosomal Sorting Complexes Required for Transport, MESH : Endosomes, MESH: Ubiquitination, Parasitology, Capsid Proteins, MESH : Ubiquitin-Protein Ligases, Immunologic diseases. Allergy, Microtubule-Organizing Center
Abstract

Viruses use cellular machinery to enter and infect cells. In this study we address the cell entry mechanisms of nonenveloped adenoviruses (Ads). We show that protein VI, an internal capsid protein, is rapidly exposed after cell surface attachment and internalization and remains partially associated with the capsid during intracellular transport. We found that a PPxY motif within protein VI recruits Nedd4 E3 ubiquitin ligases to bind and ubiquitylate protein VI. We further show that this PPxY motif is involved in rapid, microtubule-dependent intracellular movement of protein VI. Ads with a mutated PPxY motif can efficiently escape endosomes but are defective in microtubule-dependent trafficking toward the nucleus. Likewise, depletion of Nedd4 ligases attenuates nuclear accumulation of incoming Ad particles and infection. Our data provide the first evidence that virus-encoded PPxY motifs are required during virus entry, which may be of significance for several other pathogens., Author Summary Viruses exploit cellular functions during entry and exit of cells. To redirect cellular functions for their own purpose, viruses encode high-affinity binding sites for key-cellular factors. One such domain is the PPxY motif, which is present in structural proteins of several, mainly enveloped viruses. This motif binds to ubiquitin ligases of the Nedd4 family and recruits their function to sites of virus budding from cells. Here we show that adenoviruses also encode a PPxY motif in the internal structural protein VI and that the PPxY motif has an unprecedented function in virus entry. Adenoviruses with mutations in the protein VI PPxY motif undergo normal endosomal uptake and membrane penetration but have reduced infectivity, altered intracellular targeting and lack efficient gene-delivery. We also find that protein VI is ubiquitylated by Nedd4 ligases in a PPxY dependent manner following partial capsid disassembly and displays rapid intracellular movement. Depletion of Nedd4 ligases also alters virus movement within cells during entry and reduces viral infectivity. Given that PPxY motifs are important for virus exit our findings might have uncovered an additional function for PPxY motifs in virus entry, potentially expanding the significance of PPxY motifs and functionally related domains for viral replication.

Published
2010

18. Pulmonary effects of keratinocyte growth factor in newborn rats exposed to hyperoxia.: KGF effects in hyperoxia-exposed rat pups

Author

Franco-Montoya, Marie-Laure, Bourbon, Jacques, Durrmeyer, Xavier, Lorotte, Stephanie, Jarreau, Pierre-Henri, Delacourt, Christophe, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), PremUp Foundation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Descartes - Paris 5 (UPD5)-CHI Créteil-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7), Service de réanimation néonatale de Créteil, CHI Créteil, Service de réanimation néonatale Port-Royal, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Mondor de Recherche Biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Institut de Recherche pour le Développement ( IRD ) -Université Paris-Sud - Paris 11 ( UP11 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ) -CHI Créteil-Université Paris Descartes - Paris 5 ( UPD5 ) -Sorbonne Universités-Institut National de la Santé et de la Recherche Médicale ( INSERM ), and CHU Cochin [AP-HP]

Subjects
MESH: Pulmonary Surfactant-Associated Protein B, MESH: Pulmonary Alveoli, lung protection, MESH : DNA, MESH: Rats, Sprague-Dawley, MESH: Animals, Newborn, MESH: Pregnancy, developing lung, MESH : Receptor, Epidermal Growth Factor, MESH : Cell Proliferation, MESH: CCAAT-Enhancer-Binding Protein-alpha, MESH : CCAAT-Enhancer-Binding Protein-alpha, MESH : Female, MESH: Animals, MESH : Fibroblast Growth Factor 7, MESH : Bronchoalveolar Lavage Fluid, MESH : Gene Expression Regulation, MESH : Rats, MESH : Animals, Newborn, MESH: DNA, respiratory system, MESH: Gene Expression Regulation, MESH: Survival Analysis, MESH : Hyperoxia, MESH: Cell Adhesion Molecules, MESH: Rats, MESH : Lung, MESH : Transforming Growth Factor alpha, MESH: Transforming Growth Factor alpha, MESH: Receptor, Epidermal Growth Factor, MESH : Phospholipids, MESH : Cell Adhesion Molecules, MESH: Hyperoxia, MESH: Cell Proliferation, bronchopulmonary dysplasia, MESH: Lung, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, alveolar epithelial cell, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Phospholipids, MESH: Humans, MESH: Bronchoalveolar Lavage Fluid, MESH: Apoptosis, MESH : Humans, lung inflammation, MESH: Fibroblast Growth Factor 7, MESH : Rats, Sprague-Dawley, respiratory tract diseases, MESH : Pregnancy, MESH : Animals, MESH : Survival Analysis, MESH : Pulmonary Alveoli, MESH : Pulmonary Surfactant-Associated Protein B, MESH: Female, MESH : Apoptosis
Abstract

International audience; Acute lung injury and compromised alveolar development characterize bronchopulmonary dysplasia (BPD) of the premature neonate. High levels of keratinocyte growth factor (KGF), a cell-cell mediator with pleiotrophic lung effects, are associated with low BPD risk. KGF decreases mortality in hyperoxia-exposed newborn rodents, a classic model of injury-induced impaired alveolarization, although the pulmonary mechanisms of this protection are poorly defined. These were explored through in vitro and in vivo approaches in the rat. Hyperoxia decreased by 30% the rate of wound closure of a monolayer of fetal alveolar epithelial cells, due to cell death, which was overcome by recombinant human KGF (100 ng/ml). In rat pups exposed to >95% O2 from birth, increased viability induced by intraperitoneal injection of KGF (2 microg/g body wt) every other day was associated with prevention of neutrophil influx in bronchoalveolar lavage (BAL), prevention of decreases in whole lung DNA content and cell proliferation rate, partial prevention of apoptosis increase, and a markedly increased proportion of surfactant protein B-immunoreactive cells in lung parenchyma. Increased lung antioxidant capacity is likely to be due in part to enhanced CAAT/enhancer binding protein alpha expression. By contrast, KGF neither corrected changes induced by hyperoxia in parameters of lung morphometry that clearly indicated impaired alveolarization nor had any significant effect on tissue or BAL surfactant phospholipids. These findings evidence KGF alveolar epithelial cell protection, enhancing effects on alveolar repair capacity, and anti-inflammatory effects in the injured neonatal lung that may account, at least in part, for its ability to reduce mortality. They argue in favor of a therapeutic potential of KGF in the injured neonatal lung.

Published
2009

19. [The contribution of CT-guided transthoracic lung biopsy to the diagnosis of organizing pneumonia]

Author

Metzger, F., Pernet, D., Manzoni, P., Ranfaing, E., Dalphin, J.-C., Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre National de la Recherche Scientifique ( CNRS ), and Dalphin, Jean-Charles

Subjects
MESH: Pneumonia, MESH : Lung, MESH : Male, MESH : Child, Preschool, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, MESH: Biopsy, MESH : Child, MESH: Child, MESH : Tomography, X-Ray Computed, MESH : Female, MESH : Middle Aged, MESH: Lung, MESH: Humans, MESH: Middle Aged, MESH : Pneumonia, MESH : Humans, MESH: Child, Preschool, MESH: Adult, MESH : Adult, MESH: Male, respiratory tract diseases, MESH : Biopsy, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, MESH: Tomography, X-Ray Computed, MESH: Female, [ SDV.MHEP.PSR ] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
Abstract

International audience; BACKGROUND: Organizing pneumonia is a pulmonary disease with variable clinical and radiological features and with many differential diagnoses. Diagnosis is based on histology obtained by either transbronchial or surgical lung biopsy but these techniques have several disadvantages. The aim of this study was to evaluate the diagnostic yield of CT-guided transthoracic lung biopsy in organizing pneumonia and to compare it to the usual diagnostic tools. METHODS: Six cases of organizing pneumonia diagnosed with CT-guided lung biopsy are reported and discussed. A review of literature concerning the role of CT-guided lung biopsy in the diagnosis of organizing pneumonia was performed. RESULTS: CT-guided transthoracic lung biopsies provided a higher rate of adequate samples than transbronchial biopsies (92-100% versus 77-86%). The samples were larger, which reduced the risks of misdiagnosis and increased the diagnostic yield (88-97% versus 26-55% in pulmonary nodules and 42-100% versus 66-75% in diffuse pulmonary disease). Complications were rare and generally not serious. CONCLUSION: CT-guided transthoracic lung biopsy may be considered in place of transbronchial biopsy in the diagnosis of organizing pneumonia. Surgical lung biopsy remains the reference method for diagnosis.

Published
2008

20. Matrix metalloproteinase gene polymorphisms and bronchopulmonary dysplasia: identification of MMP16 as a new player in lung development

Author

Isabelle Halphen, Marie-Laure Franco-Montoya, Pierre-Henri Jarreau, Claude Danan, Fabrice Decobert, Jacques R. Bourbon, Emmanuel Martin, Alice Hadchouel, Olivier Boucherat, Serge Amselem, Alexandra Benachi, Christophe Delacourt, Institut Mondor de recherche biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), PremUp Foundation, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Sorbonne Universités-Université Paris Descartes - Paris 5 ( UPD5 ) -CHI Créteil-Institut de Recherche pour le Développement ( IRD ) -Université Paris-Sud - Paris 11 ( UP11 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ), Service de réanimation néonatale Port-Royal, CHU Cochin [AP-HP], Service de médecine néonatale de Port-Royal, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 ( UPD5 ), IntegraGen, Service d'Obstétrique et Gynécologie, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Bases moléculaires et cellulaires des maladies génétiques, Unité Fonctionnelle de Recherche Clinique, CHI Créteil, Faculté de Médecine, IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Institut Mondor de recherche biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Descartes - Paris 5 (UPD5)-CHI Créteil-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Guellaen, Georges

Subjects
Male, MMP2, MESH : Polymorphism, Genetic, MESH : Prospective Studies, lcsh:Medicine, MESH: Rats, Sprague-Dawley, Matrix metalloproteinase, Rats, Sprague-Dawley, 0302 clinical medicine, MESH: Matrix Metalloproteinase 16, MESH: Animals, MESH : Female, Prospective Studies, lcsh:Science, Lung, MESH: Bronchopulmonary Dysplasia, Bronchopulmonary Dysplasia, 0303 health sciences, Multidisciplinary, MESH : Gene Expression Regulation, MESH : Rats, MESH: Infant, Newborn, MESH: Surface-Active Agents, Gestational age, respiratory system, Respiratory Medicine/Respiratory Pediatrics, MESH: Gene Expression Regulation, Trachea, medicine.anatomical_structure, MESH : Infant, Premature, MMP14, Female, MMP16, Infant, Premature, Research Article, MESH: Infant, Premature, MESH : Bronchopulmonary Dysplasia, MESH: Rats, MESH : Trachea, MESH : Lung, MESH : Male, Single-nucleotide polymorphism, Biology, MESH : Infant, Newborn, Andrology, Surface-Active Agents, 03 medical and health sciences, 030225 pediatrics, MESH: Polymorphism, Genetic, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Animals, Humans, MESH: Lung, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Polymorphism, Genetic, MESH: Humans, lcsh:R, MESH : Humans, Infant, Newborn, MESH : Matrix Metalloproteinase 16, Matrix Metalloproteinase 16, medicine.disease, MESH: Prospective Studies, MESH: Male, MESH : Rats, Sprague-Dawley, Rats, Gene Expression Regulation, Bronchopulmonary dysplasia, Immunology, lcsh:Q, MESH : Surface-Active Agents, Pediatrics and Child Health/Neonatology, MESH : Animals, MESH: Female, MESH: Trachea, Developmental Biology
Abstract

International audience; BACKGOUND: Alveolarization requires coordinated extracellular matrix remodeling, a process in which matrix metalloproteinases (MMPs) play an important role. We postulated that polymorphisms in MMP genes might affect MMP function in preterm lungs and thus influence the risk of bronchopulmonary dysplasia (BPD). METHODS AND FINDINGS: Two hundred and eighty-four consecutive neonates with a gestational age of

Published
2008

21. [Occupational interstitial lung diseases]

Author

De Vuyst, Paul, Dalphin, Jean-Charles, Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)

Subjects
MESH: Occupational Diseases, MESH : Lung Diseases, Interstitial, MESH: Humans, MESH : Lung, MESH : Humans, MESH : Occupational Diseases, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Occupational Diseases, MESH : Tomography, X-Ray Computed, Humans, MESH: Lung, Lung Diseases, Interstitial, Tomography, X-Ray Computed, MESH: Tomography, X-Ray Computed, Lung, MESH: Lung Diseases, Interstitial, [ SDV.MHEP.PSR ] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
Abstract

International audience; Pneumoconioses are induced by the inhalation of mineral or metallic dust. The incidence has decreased in the industrialized countries, but these diseases still exist. Diseases diagnosed nowadays may result from exposures that date back several decades. Besides, industry continuously creates new types of exposure and produces novel materials and alloys. Unusual exposures, sometimes in small workshops or in independent workers, may still cause severe diseases. In case of exposure to some metals, like beryllium, diseases may occur in susceptible subjects even at low levels of exposure. Medical and social consequences of misdiagnosis may be important. The diagnostic contribution of high resolution computed tomography (HRCT) scan is very important, as this technique is sensitive and specific. Pathological, mineralogical, and immunological techniques are useful in the differential diagnosis. Hypersensitivity pneumonitis is a granulomatous interstitial disease of the lungs due to immune reactions following chronic inhalation of antigens, to which the subject has been previously sensitised. Diagnosis is based on associated clinical and paraclinical signs which are not specific. Clinical approach is essential. It allows to suspect the diagnosis in view of respiratory symptoms, inspiratory crackles and the identification of a hazardous environment. Serological tests, bronchoalveolar lavage and HRCT scan are required to confirm diagnosis. Early removal of exposure prevents the occurrence of chronic respiratory failure. Corticosteroids can be used in severe forms during few weeks.

Published
2007

22. Hybrid gadolinium oxide nanoparticles: multimodal contrast agents for in vivo imaging

Author

Stéphane Roux, Jean-Luc Bridot, Jean-Luc Coll, Bassem Hiba, Marc Janier, Claire Billotey, Sophie Laurent, Luce Vander Elst, Olivier Tillement, Pascal Perriat, Robert N. Muller, Véronique Josserand, Anne-Charlotte Faure, Charlotte Rivière, Laboratoire de Physico-Chimie des Matériaux Luminescents (LPCML), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Laboratoire de RMN, Université de Mons-Hainaut, NanoH-sas, Centre de Recherche et d'Application en Traitement de l'Image et du Signal (CREATIS), 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)-École Supérieure Chimie Physique Électronique de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM U823, équipe 5 (cibles diagnostiques ou thérapeutiques et vectorisation de drogues dans le cancer du poumon), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Matériaux, ingénierie et science [Villeurbanne] (MATEIS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physico-Chimie des Matériaux Luminescents ( LPCML ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche et d'Application en Traitement de l'Image et du Signal ( CREATIS ), 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 ) -École Supérieure Chimie Physique Électronique de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut d'oncologie/développement Albert Bonniot de Grenoble ( INSERM U823 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Matériaux, ingénierie et science [Villeurbanne] ( MATEIS ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ) -Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ), Hurbin, Amandine, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Fluorescence-lifetime imaging microscopy, MESH : Siloxanes, Nanoparticle, Contrast Media, Gadolinium, 02 engineering and technology, [SPI.MAT] Engineering Sciences [physics]/Materials, MESH : Gadolinium, 01 natural sciences, Biochemistry, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Polyethylene Glycols, MESH: Magnetic Resonance Imaging, [SPI.MAT]Engineering Sciences [physics]/Materials, Paramagnetism, Mice, Colloid and Surface Chemistry, Nuclear magnetic resonance, Heterocyclic Compounds, MESH: Animals, Lung, medicine.diagnostic_test, Chemistry, MESH : Rats, MESH : Polyethylene Glycols, MESH : Mice, Nude, 021001 nanoscience & nanotechnology, Magnetic Resonance Imaging, Liver, Covalent bond, MESH : Organometallic Compounds, 0210 nano-technology, Preclinical imaging, MESH : Fluorescence, Siloxanes, MESH: Rats, MESH: Heterocyclic Compounds, MESH : Lung, Mice, Nude, [SDV.CAN]Life Sciences [q-bio]/Cancer, 010402 general chemistry, Catalysis, Fluorescence, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH : Magnetic Resonance Imaging, MESH: Contrast Media, PEG ratio, MESH : Mice, medicine, Organometallic Compounds, MESH: Mice, Nude, Animals, MESH: Lung, MESH: Siloxanes, MESH: Mice, MESH : Contrast Media, MESH: Fluorescence, MESH : Liver, Magnetic resonance imaging, MESH: Organometallic Compounds, General Chemistry, 0104 chemical sciences, Rats, MESH : Heterocyclic Compounds, MESH: Polyethylene Glycols, MESH : Nanoparticles, Nanoparticles, MESH : Animals, Luminescence, MESH: Gadolinium, MESH: Nanoparticles, MESH: Liver
Abstract

International audience; Luminescent hybrid nanoparticles with a paramagnetic Gd2O 3 core were applied as contrast agents for both in vivo fluorescence and magnetic resonance imaging. These hybrid particles were obtained by encapsulating Gd2O3 cores within a polysiloxane shell which carries organic fluorophores and carboxylated PEG covalently tethered to the inorganic network. Longitudinal proton relaxivities of these particles are higher than the positive contrast agents like Gd-DOTA which are commonly used for clinical magnetic resonance imaging. Moreover these particles can be followed up by fluorescence imaging. This study revealed that these particles suited for dual modality imaging freely circulate in the blood vessels without undesirable accumulation in lungs and liver.

Published
2007

23. Influence of occupational factors on lung function in French dairy farmers. A 5-year longitudinal study

Author

Jean-Jacques Laplante, Elisabeth Monnet, Jean-Charles Dalphin, H. Chaudemanche, R. Fury, Isabelle Thaon, A. G. Venier, Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Agents pathogènes et inflammation - UFC (EA 4266) (API), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), and Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)

Subjects
Male, Veterinary medicine, Longitudinal study, MESH : Oxygen, MESH: Dairying, MESH: Respiratory Function Tests, 0302 clinical medicine, Surveys and Questionnaires, Epidemiology, MESH : Female, Longitudinal Studies, Social Change, MESH: Longitudinal Studies, Lung, Lung function, MESH : Allergens, Oxygen saturation (medicine), 2. Zero hunger, MESH : Longitudinal Studies, MESH: Middle Aged, MESH: Immunoglobulin E, Age Factors, MESH : Questionnaires, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, Middle Aged, MESH : Adult, 030210 environmental & occupational health, Respiratory Function Tests, Dairying, Female, Smoking status, France, MESH: Oxygen, Adult, medicine.medical_specialty, MESH: Allergens, MESH : Lung, MESH : Male, MESH : Sex Factors, MESH : Social Change, MESH : Immunoglobulin E, Antibodies, MESH : Antibodies, Occupational medicine, 03 medical and health sciences, Sex Factors, MESH: Sex Factors, Environmental health, medicine, MESH : Respiratory Function Tests, Humans, MESH: Lung, MESH : Middle Aged, MESH: Social Change, MESH : France, Dairy farming, MESH: Age Factors, MESH: Humans, business.industry, MESH: Antibodies, MESH: Questionnaires, MESH : Humans, Public Health, Environmental and Occupational Health, MESH: Adult, Allergens, Immunoglobulin E, MESH: Male, MESH: France, Oxygen, 030228 respiratory system, Agriculture, MESH : Dairying, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH : Age Factors, business, MESH: Female
Abstract

Background Dairy farming is associated with a high prevalence of respiratory disorders but the respective influence of occupational exposures, environmental, and individual factors on lung function remain unclear. Methods In 1994 and 1999, dairy farmers were examined in the Doubs province, France. Spirometric measures and allergological tests were performed. Medical and professional data were obtained by questionnaires. A multiple linear regression analysis was performed. Results An accelerated decline in lung function parameters was associated with age, male sex, traditional farm (as opposed to modern farms), and a high rate of total IgE (P

Published
2006

24. Evidence for a control of plasma serotonin levels by 5-hydroxytryptamine(2B) receptors in mice

Author

Jean-Marie Launay, Katell Peoc'h, Juan Miguel Esteve, Philippe Hervé, Claire Tournois, Luc Maroteaux, Jacques Callebert, Ludovic Drouet, Service de Biochimie et de Biologie moléculaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Faculté de Pharmacie, Institut du Fer à Moulin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Faculté de Pharmacie-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Faculté de Pharmacie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Faculté de Pharmacie-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Male, MESH : Hypertension, Pulmonary, MESH: Mice, Mutant Strains, MESH : Serotonin, [ SDV.MHEP.PSM ] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Anoxia, Stimulation, 030204 cardiovascular system & hematology, Pharmacology, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Mice, 0302 clinical medicine, MESH : Receptor, Serotonin, 5-HT2B, Receptor, Serotonin, 5-HT2B, MESH : Female, MESH: Animals, Hypoxia, Receptor, Lung, Serotonin transporter, 0303 health sciences, biology, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH : Pulmonary Artery, 3. Good health, MESH: Serotonin 5-HT2 Receptor Antagonists, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Serotonin 5-HT2 Receptor Antagonists, Molecular Medicine, Female, medicine.symptom, Agonist, Serotonin, medicine.medical_specialty, Serotonin uptake, MESH : Anoxia, medicine.drug_class, Hypertension, Pulmonary, MESH : Lung, MESH : Male, MESH: Pulmonary Artery, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Pulmonary Artery, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, MESH : Mice, medicine, Animals, MESH: Lung, MESH: Mice, 030304 developmental biology, MESH: Hypertension, Pulmonary, MESH: Receptor, Serotonin, 5-HT2B, [ SDV.SP.PHARMA ] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [ SDV.GEN.GA ] Life Sciences [q-bio]/Genetics/Animal genetics, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Hypoxia (medical), medicine.disease, Pulmonary hypertension, Mice, Mutant Strains, MESH: Male, MESH : Mice, Mutant Strains, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, Endocrinology, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, biology.protein, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, MESH: Serotonin, MESH : Animals, MESH : Serotonin 5-HT2 Receptor Antagonists, MESH: Female, [ SDV.MHEP.PSR ] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
Abstract

International audience; A correlation between high plasma serotonin levels and total pulmonary resistance was reported in more than 80% of pulmonary hypertensive patients. When submitted to chronic hypoxia (10% O(2) for more than 3 weeks), wild-type mice develop lung vascular remodeling and pulmonary hypertension. We previously reported that, in contrast, the development of these hypoxia-dependent alterations is totally abolished in mice with permanent (genetic) or transient (pharmacologic) inactivation of the serotonin 5-hydroxytryptamine (5-HT)(2B) receptor. In the present study, we asked whether 5-HT(2B) receptors could be involved in the control of plasma serotonin levels. Further investigating the chronic hypoxic mouse model of pulmonary hypertension, we first show that in wild-type mice, plasma serotonin levels and 5-HT(2B) receptors expression were significantly increased after chronic exposure to hypoxia. This increase appeared before significant changes in remodeling factors could be detected and persisted when the pathology was established. Conversely, in mice with either genetically or pharmacologically inactive 5-HT(2B) receptors, plasma serotonin levels were not modified by chronic hypoxia. We then confirmed that 5-HT(2B) receptors can control plasma serotonin levels by providing in vivo evidence that an acute agonist stimulation of 5-HT(2B) receptor triggers a transient increase in plasma serotonin that is serotonin transporter dependent and blocked by 5-HT(2B) receptor-selective antagonist or genetic ablation. Our data support the notion that a 5-HT(2B) receptor-dependent regulation of serotonin uptake is implicated in the control of plasma serotonin levels.

Published
2006

25. Serotonin transporter inhibition prevents and reverses monocrotaline-induced pulmonary hypertension in rats

Author

Serge Adnot, Bernadette Raffestin, Saadia Eddahibi, William Raoul, Patricia Zadigue, Dominique Rideau, Rima Benferhat, Christophe Guignabert, Michel Hamon, Physiopathologie et Thérapeutiques Respiratoires, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10, Service de chirurgie thoracique et d'anatomopathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Hôtel Dieu, Département de physiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP]-Université Paris Descartes - Paris 5 (UPD5), Neuropsychopharmacologie moléculaire, cellulaire et fonctionnelle, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), This research was supported by grants from INSERM, the Ministère de la Recherche, the Délégation à la Recherche Clinique de l'AP-HP, and the Fondation de France. We are grateful to the pharmaceutical companies Janssen, Lilly, Lundbeck, Roche, and SmithKline Beecham for generously donating the drugs used in this study., Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR10, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Hôtel Dieu, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré-Université Paris Descartes - Paris 5 ( UPD5 ), and Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
MESH : Hypertension, Pulmonary, MESH : Monocrotaline, muscle, MESH: Receptor, Serotonin, 5-HT1B, MESH: Receptor, Serotonin, 5-HT1D, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 030204 cardiovascular system & hematology, [ SDV.BA ] Life Sciences [q-bio]/Animal biology, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, MESH : Serotonin Plasma Membrane Transport Proteins, Muscle, Smooth, Vascular, MESH: Monocrotaline, chemistry.chemical_compound, 0302 clinical medicine, MESH : Receptor, Serotonin, 5-HT2A, MESH : Cell Proliferation, MESH: Up-Regulation, Medicine, MESH: Animals, MESH: Serotonin Plasma Membrane Transport Proteins, Neurotransmitter, Receptor, MESH : Up-Regulation, Lung, Serotonin transporter, remodeling, Serotonin Plasma Membrane Transport Proteins, Monocrotaline, biology, MESH : Rats, [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [SDV.BA]Life Sciences [q-bio]/Animal biology, [ CHIM.THER ] Chemical Sciences/Medicinal Chemistry, MESH: Muscle, Smooth, Vascular, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Up-Regulation, MESH: Serotonin Uptake Inhibitors, medicine.anatomical_structure, Serotonin 5-HT2 Receptor Antagonists, Cardiology and Cardiovascular Medicine, Selective Serotonin Reuptake Inhibitors, smooth, medicine.medical_specialty, MESH: Rats, MESH : Lung, Hypertension, Pulmonary, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Serotonin 5-HT1 Receptor Antagonists, 03 medical and health sciences, Downregulation and upregulation, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Physiology (medical), Internal medicine, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, MESH: Cell Proliferation, Fluoxetine, pulmonary heart disease, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], MESH: Fluoxetine, Animals, MESH: Lung, Cell Proliferation, MESH: Hypertension, Pulmonary, business.industry, MESH : Serotonin Uptake Inhibitors, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, Monocyte, MESH: Receptor, Serotonin, 5-HT2A, MESH : Fluoxetine, MESH : Muscle, Smooth, Vascular, medicine.disease, Pulmonary hypertension, Rats, MESH : Receptor, Serotonin, 5-HT1B, Endocrinology, 030228 respiratory system, chemistry, biology.protein, MESH : Receptor, Serotonin, 5-HT1D, Serotonin, MESH : Animals, business, [ SDV.MHEP.PSR ] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background—Progression of pulmonary hypertension (PH) is associated with increased lung expression of the serotonin transporter (5-HTT), which leads to hyperplasia of the pulmonary artery smooth muscle cells (PA-SMCs). Given the postulated causal relation between 5-HTT overexpression and PH, we herein investigated whether the highly selective 5-HTT inhibitor fluoxetine prevented and/or reversed PH induced by monocrotaline (MCT) in rats. Selective 5-HT1B/1D, 5-HT2A, and 5-HT2Breceptor antagonists were used for comparative testing.Methods and Results—MCT injection (60 mg/kg SC) was followed by an early peak in lung 5-HTT expression on day 1, which preceded the onset of PH. Established PH on day 15 was associated with a sustained 5-HTT increase. Continued fluoxetine treatment completely prevented PA-SMC proliferation and PH development and also suppressed the late 5-HTT increase, without affecting the early peak. The 5-HT receptor antagonists did not affect PH. Fluoxetine (10 mg · kg−1· d−1PO) started 3 weeks after MCT injection completely reversed established PH, normalizing PA pressure and structure. MCT-induced PH was also associated with increased expression of various cytokines, but only interleukin-1β and monocyte chemotactic protein-1 increased at the early phase and stimulated 5-HTT expression by cultured PA-SMCs.Conclusion—Upregulation of lung 5-HTT induced by MCT appears necessary to initiate the development of pulmonary vascular remodeling, whereas a sustained increase in 5-HTT expression may underlie both the progression and the maintenance of MCT-induced PH. Complete reversal of established PH by fluoxetine provides a rationale for new therapeutic strategies in human PH.

Published
2005

26. Cytosolic phospholipase A2α mediates Pseudomonas aeruginosa LPS-induced airway constriction of CFTR −/− mice

Author

Y. Wu, Takao Shimizu, Mario Ollero, Fariel Dif, M. Lagranderie, Lhousseine Touqui, Mohammad Abolhassani, Michel Chignard, N. Uozumi, Défense innée et inflammation, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Immunothérapie, Institut Pasteur [Paris], Centre de recherche Croissance et signalisation ( UMR_S 845 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Biochemistry and Molecular Biology, The University of Tokyo, this work was supported by the French association 'Vaincre la Mucoviscidose' and the Foundation Legs Poix, Paris., Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche Croissance et signalisation (UMR_S 845), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Department of Biochemistry and Molecular Biology [Tokyo], Graduate School of Science [Tokyo], The University of Tokyo (UTokyo)-The University of Tokyo (UTokyo), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and BMC, Ed.

Subjects
Chemokine CXCL2, Pharmacology, Cystic fibrosis, Mice, 0302 clinical medicine, MESH : Arachidonic Acids, MESH: Animals, Enzyme Inhibitors, Lung, 0303 health sciences, Arachidonic Acid, MESH: Dinoprostone, MESH : Pseudomonas aeruginosa, MESH: Bronchoconstriction, Neutrophil Infiltration, MESH: Mice, Inbred CFTR, Arachidonic acid, Bronchoalveolar Lavage Fluid, Pulmonary and Respiratory Medicine, MESH : Leukotrienes, MESH: Group IV Phospholipases A2, Dinoprostone, 03 medical and health sciences, MESH: Cyclooxygenase Inhibitors, MESH : Cystic Fibrosis, MESH: Arachidonic Acids, Cyclooxygenase Inhibitors, Aspirin, Group IV Phospholipases A2, MESH : Pneumonia, MESH : Administration, Intranasal, lcsh:Diseases of the respiratory system, Pneumonia, medicine.disease, MESH : Disease Models, Animal, respiratory tract diseases, 030228 respiratory system, chemistry, Immunology, MESH : Bronchoconstriction, MESH : Aspirin, MESH: Disease Models, Animal, MESH: Lipopolysaccharides, [ SDV.MHEP.PSR ] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Lipopolysaccharides, Time Factors, Cystic Fibrosis, MESH : Lipopolysaccharides, Phospholipase, medicine.disease_cause, MESH: Mice, Knockout, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, MESH : Mice, Inbred CFTR, MESH : Group IV Phospholipases A2, chemistry.chemical_compound, MESH: Administration, Intranasal, Prostaglandin E2, Mice, Knockout, MESH : Bronchoalveolar Lavage Fluid, MESH : Cyclooxygenase Inhibitors, respiratory system, MESH : Chemokine CXCL2, MESH : Neutrophil Infiltration, MESH: Enzyme Inhibitors, Pseudomonas aeruginosa, MESH: Pseudomonas aeruginosa, Bronchoconstriction, medicine.symptom, MESH : Time Factors, medicine.drug, Leukotrienes, MESH: Pneumonia, MESH : Dinoprostone, MESH: Cystic Fibrosis, MESH : Lung, Arachidonic Acids, Biology, MESH : Arachidonic Acid, MESH : Mice, medicine, Animals, Mice, Inbred CFTR, MESH: Chemokine CXCL2, Plethysmograph, MESH: Lung, Pediatrics, Perinatology, and Child Health, MESH: Aspirin, MESH: Mice, Administration, Intranasal, 030304 developmental biology, lcsh:RC705-779, MESH : Enzyme Inhibitors, MESH: Leukotrienes, MESH: Bronchoalveolar Lavage Fluid, business.industry, Research, MESH: Time Factors, MESH: Arachidonic Acid, Disease Models, Animal, MESH: Neutrophil Infiltration, Pediatrics, Perinatology and Child Health, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, MESH : Mice, Knockout, MESH : Animals, Airway, business
Abstract

Background Lungs of cystic fibrosis (CF) patients are chronically infected with Pseudomonas aeruginosa. Increased airway constriction has been reported in CF patients but underplaying mechanisms have not been elucidated. Aim: to examine the effect of P. aeruginosa LPS on airway constriction in CF mice and the implication in this process of cytosolic phospholipase A2α (cPLA2α), an enzyme involved in arachidonic acid (AA) release. Methods Mice were instilled intra-nasally with LPS. Airway constriction was assessed using barometric plethysmograph. MIP-2, prostaglandin E2 (PGE2), leukotrienes and AA concentrations were measured in BALF using standard kits and gas chromatography. Results LPS induced enhanced airway constriction and AA release in BALF of CF compared to littermate mice. This was accompanied by increased levels of PGE2, but not those of leukotrienes. However, airway neutrophil influx and MIP-2 production remained similar in both mouse strains. The cPLA2α inhibitor arachidonyl trifluoro-methyl-ketone (ATK), but not aspirin which inhibit PGE2 synthesis, reduced LPS-induced airway constriction. LPS induced lower airway constriction and PGE2 production in cPLA2α -/- mice compared to corresponding littermates. Neither aspirin nor ATK interfered with LPS-induced airway neutrophil influx or MIP-2 production. Conclusions CF mice develop enhanced airway constriction through a cPLA2α-dependent mechanism. Airway inflammation is dissociated from airway constriction in this model. cPLA2α may represent a suitable target for therapeutic intervention in CF. Attenuation of airway constriction by cPLA2α inhibitors may help to ameliorate the clinical status of CF patients.

Published
2010

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