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32 results on '"Copenhagen University Hospital-Copenhagen University Hospital"'

1. Genetic architecture of natural variation of cardiac performance from flies to humans

Author: Lionel Spinelli, Saswati Saha, Jaime A Castro Mondragon, Anaïs Kervadec, Michaela Lynott, Laurent Kremmer, Laurence Roder, Sallouha Krifa, Magali Torres, Christine Brun, Georg Vogler, Rolf Bodmer, Alexandre R Colas, Karen Ocorr, Laurent Perrin, Theories and Approaches of Genomic Complexity (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre for Molecular Medicine Norway (NCMM), Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, and Sanford Burnham Prebys Medical Discovery Institute
Subjects: General Immunology and Microbiology, General Neuroscience, Quantitative Trait Loci, Genetic Variation, Heart, General Medicine, General Biochemistry, Genetics and Molecular Biology, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, Drosophila melanogaster, Phenotype, Animals, Humans, Gene Regulatory Networks, Genome-Wide Association Study
Abstract: Deciphering the genetic architecture of human cardiac disorders is of fundamental importance but their underlying complexity is a major hurdle. We investigated the natural variation of cardiac performance in the sequenced inbred lines of the Drosophila Genetic Reference Panel (DGRP). Genome-wide associations studies (GWAS) identified genetic networks associated with natural variation of cardiac traits which were used to gain insights as to the molecular and cellular processes affected. Non-coding variants that we identified were used to map potential regulatory non-coding regions, which in turn were employed to predict transcription factors (TFs) binding sites. Cognate TFs, many of which themselves bear polymorphisms associated with variations of cardiac performance, were also validated by heart-specific knockdown. Additionally, we showed that the natural variations associated with variability in cardiac performance affect a set of genes overlapping those associated with average traits but through different variants in the same genes. Furthermore, we showed that phenotypic variability was also associated with natural variation of gene regulatory networks. More importantly, we documented correlations between genes associated with cardiac phenotypes in both flies and humans, which supports a conserved genetic architecture regulating adult cardiac function from arthropods to mammals. Specifically, roles for PAX9 and EGR2 in the regulation of the cardiac rhythm were established in both models, illustrating that the characteristics of natural variations in cardiac function identified in Drosophila can accelerate discovery in humans.
Published: 2022

2. Parameter estimates for trends and patterns of excess mortality among persons on antiretroviral therapy in high-income European settings

Author: Juan Berenguer, Christoph Wyen, M. John Gill, Sophie Abgrall, Ard van Sighem, Matthias Cavassini, Sophie Grabar, Jordi Casabona, Margaret T May, Julia del Amo, Antonella d'Arminio Monforte, Robert Zangerle, John Stover, Niels Obel, Jonathan A C Sterne, Fabrice Bonnet, Adam Trickey, Medical Research Council (Reino Unido), Department for International Development (Reino Unido), NIH - National Institute on Alcohol Abuse and Alcoholism (NIAAA) (Estados Unidos), National Institute for Health Research (Reino Unido), Unión Europea, Agence Nationale de Recherches sur le sida et les hépatites virales (Francia), Institut National de la Santé et de la Recherche Médicale (Francia), Ministero della Salute (Italia), Ministerio de Sanidad y Consumo (España), Ministerio de Ciencia e Innovación (España), Red de Investigación Cooperativa en Investigación en Sida (España), Swiss National Science Foundation, University of Bristol [Bristol], Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Paris Descartes - Paris 5 (UPD5), Hôpital Cochin [AP-HP], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospital General Universitario 'Gregorio Marañón' [Madrid], Instituto de Investigación Sanitaria Gregorio Marañón [Madrid, Spain] ( IiSGM), University Hospital of Cologne [Cologne], Centre d'Estudis Epidemiològics sobre les Infeccions de Transmissió Sexual i Sida de Catalunya (CEEISCAT), CIBER de Epidemiología y Salud Pública (CIBERESP), Università degli Studi di Milano = University of Milan (UNIMI), Ospedale San Paolo-Polo Universitario, ASST Santi Paolo e Carlo, Milan, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Université de Lausanne = University of Lausanne (UNIL), Instituto de Salud Carlos III [Madrid] (ISC), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), University of Calgary, Department of Infectious Diseases [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Gestionnaire, Hal Sorbonne Université, Medical Research Council (United Kingdom), Department for International Development (United Kingdom), National Institute on Alcohol Abuse and Alcoholism (United States), National Institute for Health Research (United Kingdom), European Union, Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (France), Institut National de la Santé et de la Recherche Médicale (France), and Red Española de Investigación en SIDA
Subjects: Adult, Male, 0301 basic medicine, Anti-HIV Agents, [SDV]Life Sciences [q-bio], Immunology, Population, HIV Infections, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Pharmacotherapy, Acquired immunodeficiency syndrome (AIDS), Risk Factors, death, cause-specific, medicine, Humans, Immunology and Allergy, 030212 general & internal medicine, Mortality, education, United Nations Programme on HIV/AIDS, education.field_of_study, Models, Statistical, business.industry, Developed Countries, Mortality rate, duration, HIV, cohort, Middle Aged, medicine.disease, Confidence interval, 3. Good health, AIDS, [SDV] Life Sciences [q-bio], Europe, Anti-HIV Agents/therapeutic use, Europe/epidemiology, Female, HIV Infections/drug therapy, HIV Infections/mortality, Mortality/trends, Editorial, 030104 developmental biology, Infectious Diseases, Cohort, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, business, Developed country, Demography, Cohort study
Abstract: Supplemental Digital Content is available in the text, Introduction: HIV cohort data from high-income European countries were compared with the UNAIDS Spectrum modelling parameters for these same countries to validate mortality rates and excess mortality estimates for people living with HIV (PLHIV) on antiretroviral therapy (ART). Methods: Data from 2000 to 2015 were analysed from the Antiretroviral Therapy Cohort Collaboration (ART-CC) for Austria, Denmark, France, Italy, the Netherlands, Spain, and Switzerland. Flexible parametric models were used to compare all-cause mortality rates in the ART-CC and Spectrum. The percentage of AIDS-related deaths and excess mortality (both are the same within Spectrum) were compared, with excess mortality defined as that in excess of the general population mortality. Results: Analyses included 94 026 PLHIV with 585 784 person-years of follow-up, from which there were 5515 deaths. All-cause annual mortality rates in Spectrum for 2000–2003 were 0.0121, reducing to 0.0078 in 2012–2015, whilst the ART-CC's corresponding annual mortality rates were 0.0151 [95% confidence interval (95% CI): 0.0130–0.0171] reducing to 0.0049 (95% CI: 0.0039–0.0060). The percentage of AIDS-related deaths in Spectrum was 74.7% in 2000–2003, dropping to 43.6% in 2012–2015. In the ART-CC, AIDS-related mortality constitutes 45.3% (95% CI: 38.4–52.9%) of mortality in 2000–2003 and 26.7% (95% CI: 19–46%) between 2012 and 2015. Excess mortality in the ART-CC was broadly similar to the Spectrum estimates, dropping from 75.3% (95% CI: 60.3–95.2%) in 2000–2003 to 30.7% (95% CI: 25.5–63.7%) in 2012–2015. Conclusion: All-cause mortality assumptions for PLHIV on ART in high-income European settings should be adjusted in Spectrum to be higher in 2000–2003 and decline more quickly to levels currently captured for recent years.
Published: 2019

3. Fructose malabsorption induces cholecystokinin expression in the ileum and cecum by changing microbiota composition and metabolism

Author: Philippe Gérard, Edek A. J. Williams, Jens F. Rehfeld, Ronaldo P. Ferraris, Sharon Barretto, Catherine Philippe, Chloé Melchior, Guillaume Gourcerol, Nicolas Lapaque, Pierre Larraufie, Christine Herberden, Hervé M. Blottière, Mahendra Mariadassou, Veronique Douard, J. Christopher Fritton, Daniel Vasiliauskas, Sandrine Ellero-Simatos, Fabienne Devime, Nathalie Dourmap, Lorraine Smith, Alexandra Grosfeld, Xufei Zhang, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Métabolisme et physiologie rénale (CRC - UMR_S 1138), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Rutgers New Jersey Medical School (NJMS), Rutgers University System (Rutgers), Institut des Neurosciences de Paris-Saclay (Neuro-PSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Mathématiques et Informatique Appliquées du Génome à l'Environnement ( MaIAGE), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Service d'Hépato-Gastroentérologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de physiologie digestive, urinaire, respiratoire et de l'exercice [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Department of Clinical Biochemistry [Rigshospitalet], Rigshospitalet [Copenhagen], Rutgers University [Newark], École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut des Neurosciences Paris-Saclay (NeuroPSI), Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Mathématiques et Informatique Appliquées du Génome à l'Environnement [Jouy-En-Josas] (MaIAGE), Institut National de la Recherche Agronomique (INRA), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Service de physiologie digestive, urinaire, respiratoire et de l'exercice [CHU Rouen], Copenhagen University Hospital-Copenhagen University Hospital, Institut Benjamin Delessert, INRA, China Scholarship Council (CSC), PERIGNON, Alain, Centre National de la Recherche Scientifique (CNRS)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, and Hôpital Charles Nicolle [Rouen]
Subjects: 0301 basic medicine, KHK, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Fructose malabsorption, Enteroendocrine cell, Biochemistry, Mice, chemistry.chemical_compound, Cecum, 0302 clinical medicine, Cholecystokinin, Mice, Knockout, 2. Zero hunger, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, digestive, oral, and skin physiology, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, medicine.anatomical_structure, hormones, hormone substitutes, and hormone antagonists, Biotechnology, medicine.medical_specialty, Ileum, Fructose, digestive system, Cell Line, Fructokinases, 03 medical and health sciences, Internal medicine, Genetics, medicine, Animals, Humans, propionate, Molecular Biology, Research, CCK, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Metabolism, medicine.disease, Gastrointestinal Microbiome, 030104 developmental biology, Endocrinology, Gene Expression Regulation, chemistry, Peptide YY, [SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, 030217 neurology & neurosurgery
Abstract: International audience; Current fructose consumption levels often overwhelm the intestinal capacity to absorb fructose. We investigated the impact of fructose malabsorption on intestinal endocrine function and addressed the role of the microbiota in this process. To answer this question, a mouse model of moderate fructose malabsorption [ketohexokinase mutant (KHK)-/-] and wild-type (WT) littermate mice were used and received a 20%-fructose (KHK-F and WT-F) or 20%-glucose diet. Cholecystokinin (Cck) mRNA and protein expression in the ileum and cecum, as well as preproglucagon (Gcg) and neurotensin (Nts) mRNA expression in the cecum, increased in KHK-F mice. In KHK-F mice, triple-label immunohistochemistry showed major up-regulation of CCK in enteroendocrine cells (EECs) that were glucagon-like peptide-1 (GLP-1)+/Peptide YY (PYY-) in the ileum and colon and GLP-1-/PYY- in the cecum. The cecal microbiota composition was drastically modified in the KHK-F in association with an increase in glucose, propionate, succinate, and lactate concentrations. Antibiotic treatment abolished fructose malabsorption-dependent induction of cecal Cck mRNA expression and, in mouse GLUTag and human NCI-H716 cells, Cck mRNA expression levels increased in response to propionate, both suggesting a microbiota-dependent process. Fructose reaching the lower intestine can modify the composition and metabolism of the microbiota, thereby stimulating the production of CCK from the EECs possibly in response to propionate.-Zhang, X., Grosfeld, A., Williams, E., Vasiliauskas, D., Barretto, S., Smith, L., Mariadassou, M., Philippe, C., Devime, F., Melchior, C., Gourcerol, G., Dourmap, N., Lapaque, N., Larraufie, P., Blottière, H. M., Herberden, C., Gerard, P., Rehfeld, J. F., Ferraris, R. P., Fritton, J. C., Ellero-Simatos, S., Douard, V. Fructose malabsorption induces cholecystokinin expression in the ileum and cecum by changing microbiota composition and metabolism.
Published: 2019

4. Identification of key tissue-specific, biological processes by integrating enhancer information in maize gene regulatory networks

Author: Anthony Venon, Julien Rozière, Johann Joets, Olivier Turc, Stéphanie Pateyron, Marieke L. Kuijjer, Maike Stam, Clémentine Vitte, Maud Fagny, Génétique Quantitative et Evolution - Le Moulon (Génétique Végétale) (GQE-Le Moulon), AgroParisTech-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre for Molecular Medicine Norway (NCMM), Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Leiden University Medical Center (LUMC), Swammerdam Institute for Life Sciences (SILS), University of Amsterdam [Amsterdam] (UvA), Écophysiologie des Plantes sous Stress environnementaux (LEPSE), Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut des Sciences des Plantes de Paris-Saclay (IPS2 (UMR_9213 / UMR_1403)), Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ANR-10-BTBR-0001,AMAIZING,Développer de nouvelles variétés de maïs pour une agriculture durable: une approche intégrée de la génomique à la sélection(2010), ANR-17-EURE-0007,SPS-GSR,Ecole Universitaire de Recherche de Sciences des Plantes de Paris-Saclay(2017), Investment for the Future ANR-10-BTBR-01-01 Amaizing program, Amaizing, Plant Development & (Epi)Genetics (SILS, FNWI), Universiteit Leiden, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), and Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0106 biological sciences, Systems biology, Gene regulatory network, Computational biology, Biology, Zea mays, 01 natural sciences, 03 medical and health sciences, mite, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Gene expression, Genetics, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, TIR transposon, Enhancer, gene regulatory networks, Transcription factor, Gene, Original Research, 030304 developmental biology, Epigenomics, 2. Zero hunger, 0303 health sciences, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], husk, Maize, DNA binding site, transcription factor binding sites, enhancers, transposable elements, 010606 plant biology & botany
Abstract: Enhancers are important regulators of gene expression during numerous crucial processes including tissue differentiation across development. In plants, their recent molecular characterization revealed their capacity to activate the expression of several target genes through the binding of transcription factors. Nevertheless, identifying these target genes at a genome-wide level remains a challenge, in particular in species with large genomes, where enhancers and target genes can be hundreds of kilobases away. Therefore, the contribution of enhancers to regulatory network is still poorly understood in plants. In this study, we investigate the enhancer-driven regulatory network of two maize tissues at different stages: leaves at seedling stage and husks (bracts) at flowering. Using a systems biology approach, we integrate genomic, epigenomic and transcriptomic data to model the regulatory relationship between transcription factors and their potential target genes. We identify regulatory modules specific to husk and V2-IST, and show that they are involved in distinct functions related to the biology of each tissue. We evidence enhancers exhibiting binding sites for two distinct transcription factor families (DOF and AP2/ERF) that drive the tissue-specificity of gene expression in seedling immature leaf and husk. Analysis of the corresponding enhancer sequences reveals that two different transposable element families (TIR transposon Mutator and MITE Pif/Harbinger) have shaped the regulatory network in each tissue, and that MITEs have provided new transcription factor binding sites that are involved in husk tissue-specificity.SignificanceEnhancers play a major role in regulating tissue-specific gene expression in higher eukaryotes, including angiosperms. While molecular characterization of enhancers has improved over the past years, identifying their target genes at the genome-wide scale remains challenging. Here, we integrate genomic, epigenomic and transcriptomic data to decipher the tissue-specific gene regulatory network controlled by enhancers at two different stages of maize leaf development. Using a systems biology approach, we identify transcription factor families regulating gene tissue-specific expression in husk and seedling leaves, and characterize the enhancers likely to be involved. We show that a large part of maize enhancers is derived from transposable elements, which can provide novel transcription factor binding sites crucial to the regulation of tissue-specific biological functions.
Published: 2020

5. Uptake of Tenofovir-Based Antiretroviral Therapy among HIV–HBV-Coinfected Patients in the EuroSIDA Study

Author: Jens D Lundgren, Anna Lisa Ridolfo, Jelena Smidt, Elena Kuzovatova, Stéphane De Wit, Roxana Radoi, Santiago Moreno, Djordje Jevtovic, Vesnadarjan Haziosmanovic, Helen Sambatakou, Lars Peters, Jose Zapirain, Amanda Mocroft, Chloe Orkin, Daniel Grint, Anna Grzeszczuk, Jürgen K. Rockstroh, Igor Karpov, Alexandra Calmy, Karine Lacombe, Magnus Gottfredsson, Department of Infectious Diseases [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, University College of London [London] (UCL), London School of Hygiene and Tropical Medicine (LSHTM), Instituto Ramon y Cajal de Investigacion Sanitaria [Madrid, Spain] (IRYCIS), Universidad de Alcalá - University of Alcalá (UAH), Hôpital Universitaire de Genève = University Hospitals of Geneva (HUG), Hippokration General Hospital, University of Athens Medical School [Athens], Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Pierre, Universitätsklinikum Bonn (UKB), Belarus State Medical University, University of Bialystok, Clinical Center University of Sarajevo, UNIVERSITY OF SARAJEVO - UNIVERZITET U SARAJEVU, Landspitali National University Hospital of Iceland, University of Iceland [Reykjavik], Victor Babeş University of Medicine and Pharmacy (UMFT), National Research Lobachevsky State University of Nizhny Novgorod (UNN), Royal London Hospital, Ospedale L. Sacco, IT University of Copenhagen (ITU), and Gestionnaire, Hal Sorbonne Université
Subjects: Male, 0301 basic medicine, HBsAg, [SDV]Life Sciences [q-bio], HIV Infections, Polyethylene Glycols, immune system diseases, Antiretroviral Therapy, Highly Active, Adefovir, Medicine, Pharmacology (medical), Prospective Studies, Coinfection, virus diseases, Entecavir, Middle Aged, Hepatitis B, Recombinant Proteins, Europe, [SDV] Life Sciences [q-bio], Infectious Diseases, Anti-Retroviral Agents, Lamivudine, Practice Guidelines as Topic, Female, medicine.drug, Adult, Cart, Hepatitis B virus, medicine.medical_specialty, Guanine, 030106 microbiology, Organophosphonates, Lower risk, 03 medical and health sciences, Hepatitis B, Chronic, Internal medicine, Drug Resistance, Viral, Humans, Tenofovir, Adverse effect, Pharmacology, Hepatitis B Surface Antigens, business.industry, Adenine, HIV, Interferon-alpha, medicine.disease, Drug Utilization, CD4 Lymphocyte Count, Discontinuation, DNA, Viral, business
Abstract: Background According to guidelines all HIV–HBV-coinfected patients should receive tenofovir-based combination antiretroviral therapy (cART). We aimed to investigate uptake and outcomes of tenofovir-based cART among HIV–HBV patients in the EuroSIDA study. Methods All hepatitis B surface antigen (HBsAg)+ patients followed up after 1 March 2002 were included. Changes in the proportion taking tenofovir-based cART over time were described. Poisson regression was used to investigate the relationship between tenofovir use and clinical events. Results 953 HIV–HBV patients were included. Median age was 41 years and patients were predominantly male (85%), White (82%) and ART-experienced (88%). 697 and 256 were from Western and Eastern Europe, respectively. 55 started cART during follow-up, the proportion starting with CD4+ T-cell count 3 decreased from 85% to 52% in the periods 2002–2006 to 2007–2015. Tenofovir use, among those taking cART, increased from 4% in 2002 to 73% in 2015. Compared to West, tenofovir use was lower in East in 2005 (7% versus 42%), and remained lower in 2015 (63% versus 76%). Among 602 patients taking tenofovir-based cART during follow-up, 155 (26%) discontinued tenofovir. 27 of all discontinuations were due to adverse effects. Only 14 started entecavir and/or adefovir after tenofovir discontinuation, whereas 10 started pegylated interferon. Tenofovir use was not significantly associated with lower risk of liver-related clinical events ( n=51), adjusted incidence rate ratio (IRR) 0.64 (95% CI 0.35, 1.18) for comparing patients on tenofovir with those off tenofovir. Conclusions Although use of tenofovir-based cART among HIV–HBV patients has increased across Europe, a substantial proportion are still starting cART late and are receiving suboptimal HBV therapy.
Published: 2017

6. Survey of diagnostic and treatment practices for multiple sclerosis in Europe

Author: G. Comi, Patrick Vermersch, Carlo Pozzilli, B. Tackenberg, P. S. Soerensen, Gilles Edan, H.-P. Hartung, M. Delvecchio, Ludwig Kappos, Oscar Fernández, G. Gionvannoni, Sten Fredrikson, Eva Havrdova, SDA Bocconi Scuola di Direzione Aziendale, Service de Neurologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Vision, Action et Gestion d'informations en Santé (VisAGeS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-SIGNAUX ET IMAGES NUMÉRIQUES, ROBOTIQUE (IRISA-D5), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes 1 (UR1), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Department of Clinical Neurosciences, Neurology Division, Karolinska Institutet, Queen Mary's School of Medicine and Dentistry, Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Department of Neurological Sciences, University of Roma 'La Sapienza', Danish Multiple Sclerosis Research Centre, Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Department of Neurology, Philipps Universität Marburg, Hospital Regional Universitario Carlos Haya, Service de Neurologie [Rennes] = Neurology [Rennes], CHU Pontchaillou [Rennes], Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), departmet of Neurology, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Department of neurology, Charles University [Prague] (CU), Department of Neurology [Suisse], University Hospital Basel [Basel], Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Philipps Universität Marburg = Philipps University of Marburg, CHU Lille, Inflammation: mécanismes et régulation et interactions avec la nutrition et les candidoses, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, European Charcot Foundation, Barillot, Christian, Fernã¡ndez, O., Delvecchio, M., Edan, G., Fredrikson, S., Gionvannoni, G., Hartung, H. . P., Havrdova, E., Kappos, L., Pozzilli, C., Soerensen, P. S., Tackenberg, B., Vermersch, P., Comi, Giancarlo, Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Université de Lille, Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale (INSERM), IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-CentraleSupélec-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Rennes (ENS Rennes)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)
Subjects: Male, MESH: Multiple Sclerosis, Relapsing-Remitting, Delphi Technique, Modified delphi, Disease, MESH: Health Care Surveys, Relapsing-Remitting, Spinal Puncture, MESH: Delphi Technique, MESH: Magnetic Resonance Imaging, 0302 clinical medicine, Surveys and Questionnaires, relapsingâ remitting, 030212 general & internal medicine, clinically isolated syndrome, radiologically isolated syndrome, relapsingâremitting, Adult, Disease Progression, Europe, Female, Humans, Magnetic Resonance Imaging, Multiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Neurologists, Health Care Surveys, Neurology, Neurology (clinical), Clinically isolated syndrome, 3. Good health, Clinical Practice, MESH: Disease Progression, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.medical_specialty, Steering committee, MESH: Spinal Puncture, relapsing−remitting, Disease activity, 03 medical and health sciences, medicine, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Mild form, MESH: Neurologists, MESH: Surveys and Questionnaires, MESH: Humans, business.industry, Multiple sclerosis, MESH: Adult, MESH: Multiple Sclerosis, medicine.disease, MESH: Male, Family medicine, Physical therapy, MESH: Europe, business, MESH: Female, 030217 neurology & neurosurgery
Abstract: International audience; Background and purpose - Up-to-date information is needed on the extent to which neurologists treating multiple sclerosis (MS) in Europe are integrating rapidly evolving diagnostic criteria, disease-modifying therapies and recommendations for monitoring disease activity into their clinical practice. Methods - A steering committee of MS neurologists used a modified Delphi process to develop case- and practice-based questions for two sequential surveys distributed to MS neurologists throughout Europe. Case-based questions were developed for radiologically isolated syndrome (RIS), clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS) and RRMS with breakthrough disease. Results - Multiple sclerosis neurologists from 11 European countries responded to survey 1 (n = 233) and survey 2 (n = 171). Respondents agreed that they would not treat the patients in the RIS or CIS cases but would treat a patient with a relatively mild form of RRMS. Choice of treatment was evenly distributed among first-line injectables and oral treatments for mild RRMS, and moved to second-line treatment as the RRMS case increased in severity. Additional results on RRMS with breakthrough disease are presented. Conclusions - Although there was general agreement on some aspects of treatment, responses to other management and clinical practice questions varied considerably. These results, which reflect current clinical practice patterns, highlight the need for additional MS treatment education and awareness and may help inform the development of MS practice guidelines in Europe.
Published: 2017

7. Surgical consensus guidelines on sentinel node biopsy (SNB) in patients with oral cancer

Author: Willem M.C. Klop, Remco de Bree, Bernhard Frerich, JF Tvedskov, Isabel Sassoon, Renaud Garrel, Jeremy McMahon, Naoyuki Kohno, Clare Schilling, M.G. Vigili, Richard Shaw, Georges Lawson, Sando J Stoeckli, Mark McGurk, David Cognetti, J. Alvarez, Stephen Y. Lai, Anders Christensen, Cyrus Kerawala, Christian von Buchwald, Anil K. D'Cruz, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/IREC/CARS - Computer Assisted Robotic Surgery, UCL - (MGD) Service d'oto-rhino-laryngologie, University of Freiburg [Freiburg], Kantonsspital St Gallen [Switzerland], University Medical Center [Utrecht], The University of Texas M.D. Anderson Cancer Center [Houston], Hospital Universitario Cruces = Cruces University Hospital, Copenhagen University Hospital, Department of Otorhinolaryngology, Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Jefferson (Philadelphia University + Thomas Jefferson University), Service d'ORL, Hôpital Gui de Chauliac (CHRU de Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Kyorin University School of Medicine [Tokyo, Japan], Kyorin University [Tokyo, Japan], The Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, NHS Foundation Trust [London], The Royal Marsden, Université Catholique de Louvain = Catholic University of Louvain (UCL), Southern General Hospital, Glasgow, King‘s College London, and University of Liverpool
Subjects: occult metastasis, medicine.medical_specialty, media_common.quotation_subject, education, MEDLINE, Oral squamous cell cancer, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, sentinel node biopsy, oral squamous cell cancer, 03 medical and health sciences, 0302 clinical medicine, Multidisciplinary approach, Voting, Journal Article, medicine, Medical physics, elective neck dissection, Operative technique, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, 030223 otorhinolaryngology, media_common, Sentinel node biopsy, Mouth neoplasm, business.industry, Occult metastasis, Head and neck cancer, Cancer, Sentinel node, medicine.disease, operative technique, 3. Good health, Otorhinolaryngology, Elective neck dissection, 030220 oncology & carcinogenesis, business
Abstract: International audience; Background : The eighth international symposium for sentinel node biopsy (SNB) in head and neck cancer was held in 2018. This consensus conference aimed to deliver current multidisciplinary guidelines. This document focuses on the surgical aspects of SNB for oral cancer.Method : Invited expert faculty selected topics requiring guidelines. Topics were reviewed and evidence evaluated where available. Data were presented at the consensus meeting, with live debate from panels comprising expert, nonexpert, and patient representatives followed by voting to assess the level of support for proposed recommendations. Evidence review, debate, and voting results were all considered in constructing these guidelines. Results/conclusion : A range of topics were considered, from patient selection to surgical technique and follow-up schedule. Consensus was not achieved in all areas, highlighting potential issues that would benefit from prospective studies. Nevertheless these guidelines represent an up-to-date pragmatic recommendation based on current evidence and expert opinion.
Published: 2019

8. Analgesic use — prevalence, biomonitoring and endocrine and reproductive effects

Author: Tania Serrano, Bernard Jégou, David Møbjerg Kristensen, Laurianne Lesné, Pierre Gaudriault, Sverine Mazaud-Guittot, Katharina M. Main, Department of Growth and Reproduction [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Danish Council for Independent Research (Medical Sciences), Fondation pour la Recherche Medicale, Inserm (Institut national de la sante et de la recherche medicale), Rennes 1 University, EHESP-School of Public Health, ANSM (Agence Nationale de la Securite du Medicament) [AAP-2012-037, HAP-2014-073], Université d'Angers (UA)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Meconium, 0301 basic medicine, Endocrinology, Diabetes and Metabolism, nonsteroidal antiinflammatory drugs, postmenopausal women, Ibuprofen, Endocrine Disruptors, Pharmacology, 0302 clinical medicine, Endocrinology, Pregnancy, persistent pulmonary-hypertension, education.field_of_study, Aspirin, 030219 obstetrics & reproductive medicine, Anti-Inflammatory Agents, Non-Steroidal, Commerce, Pregnancy Outcome, Environmental exposure, Analgesics, Non-Narcotic, 3. Good health, Prenatal Exposure Delayed Effects, acetylsalicylic-acid, Female, Over-the-counter, Drug Monitoring, Salicylic Acid, medicine.drug, low-dose aspirin, Analgesic, Population, Pain, intrauterine exposure, Congenital Abnormalities, 03 medical and health sciences, Environmental health, medicine, Humans, Pain Management, Endocrine system, Tooth, Deciduous, education, over-the-counter, Acetaminophen, prenatal paracetamol exposure, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Milk, Human, blood-plasma levels, business.industry, Environmental Exposure, medicine.disease, Molar, 030104 developmental biology, Urogenital Abnormalities, business, n-acetyl-4-aminophenol paracetamol
Abstract: International audience; Paracetamol and NSAIDs, in particular acetylsalicylic acid (aspirin) and ibuprofen, are among the most used and environmentally released pharmaceutical drugs. The differences in international trends in the sale and consumption of mild analgesics reflect differences in marketing, governmental policies, habits, accessibility, disease patterns and the age distribution of each population. Biomonitoring indicates ubiquitous and high human exposure to paracetamol and to salicylic acid, which is the main metabolite of acetylsalicylic acid. Furthermore, evidence suggests that analgesics can have endocrine disruptive properties capable of altering animal and human reproductive function from fetal life to adulthood in both sexes. Medical and public awareness about these health concerns should be increased, particularly among pregnant women.
Published: 2016

9. Unsupervised High-Dimensional Analysis Aligns Dendritic Cells across Tissues and Species

Author: Bjarne Bogen, Mahesh Choolani, Dedrick Kok Hong Chan, Tony Lim Kiat Hon, Charles-Antoine Dutertre, Jerry Kok Yen Chan, Florent Ginhoux, Anis Larbi, Sandrine Henri, Svetoslav Chakarov, Citra Nurfarah Zaini Mattar, Evan W. Newell, Naomi McGovern, Sofie Van Gassen, Jinmiao Chen, Simon Tavernier, Tam John Kit Chung, Michael Poidinger, Sergio Erdal Irac, Dorine Sichien, Hervé Luche, Ivy Low, Hermi Sumatoh, Sofie De Prijck, Gillian Low, Ker-Kan Tan, Bart N. Lambrecht, Even Fossum, Martin Guilliams, Yvan Saeys, Bernard Malissen, Charlotte L. Scott, Pulmonary Medicine, McGovern, Naomi [0000-0001-5200-2698], Apollo - University of Cambridge Repository, Department of Biomedical Molecular Biology [Ghent], Universiteit Gent = Ghent University (UGENT), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unit of Immunoregulation and Mucosal Immunology [Ghent, Belgium], VIB Inflammation Research Center [Ghent, Belgium], Program in Emerging Infectious Disease, Duke-NUS Medical School [Singapore], Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Department of Information Technology [Gent], Data Mining and Modeling for Biomedicine [Ghent, Belgium], Department of Internal Medicine [Ghent, Belgium], Experimental Fetal Medicine Group [Singapore], National University of Singapore (NUS)-Yong Loo Lin School of Medicine [Singapore], Department of Surgery [Singapore], Department of Pathology [Singapour], National University of Singapore (NUS), K.G. Jebsen Centre for Influenza Vaccine Research [Oslo, Norway], University of Oslo (UiO)-Oslo University Hospital [Oslo], Center for Immune Regulation [Oslo] (CIR), Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Department of Reproductive Medicine [Singapore], KK Women's and Children's Hospital [Singapore], Cancer and Stem Cell Biology Program [Singapore], Centre d'Immunophénomique (CIPHE), Department of Pulmonary Medicine [Rotterdam, The Netherlands], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Universiteit Gent = Ghent University [Belgium] (UGENT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Universiteit Gent, and HENRI, Sandrine
Subjects: EXPRESSION, 0301 basic medicine, Resource, STEADY-STATE, HOMEOSTASIS, BLOOD, [SDV.IMM] Life Sciences [q-bio]/Immunology, BONE-MARROW, Cellular differentiation, Immunology, Inflammation, Computational biology, Biology, Macaque, Flow cytometry, 03 medical and health sciences, Mice, 0302 clinical medicine, biology.animal, medicine, Immunology and Allergy, Macrophage, Animals, Humans, Mass cytometry, MACROPHAGES, SIGNALING CONTROLS, LYMPH-NODES, medicine.diagnostic_test, Biology and Life Sciences, hemic and immune systems, Cell Differentiation, Dendritic Cells, Flow Cytometry, CLONOGENIC PROGENITOR, Mice, Inbred C57BL, Protein Transport, 030104 developmental biology, Infectious Diseases, [SDV.IMM]Life Sciences [q-bio]/Immunology, Macaca, medicine.symptom, Conventional Dendritic Cell, Function (biology), RESPONSES, 030215 immunology
Abstract: Summary Dendritic cells (DCs) are professional antigen-presenting cells that hold great therapeutic potential. Multiple DC subsets have been described, and it remains challenging to align them across tissues and species to analyze their function in the absence of macrophage contamination. Here, we provide and validate a universal toolbox for the automated identification of DCs through unsupervised analysis of conventional flow cytometry and mass cytometry data obtained from multiple mouse, macaque, and human tissues. The use of a minimal set of lineage-imprinted markers was sufficient to subdivide DCs into conventional type 1 (cDC1s), conventional type 2 (cDC2s), and plasmacytoid DCs (pDCs) across tissues and species. This way, a large number of additional markers can still be used to further characterize the heterogeneity of DCs across tissues and during inflammation. This framework represents the way forward to a universal, high-throughput, and standardized analysis of DC populations from mutant mice and human patients., Graphical Abstract Image 1, Highlights • A conserved gating strategy aligns dendritic cells (DCs) in mouse and human tissues • Unsupervised computational analysis of flow cytometry data outperforms manual analysis • Mass cytometry reveals heterogeneity of DC subsets across mouse and human tissues • DC activation upon inflammation tracked by automated analysis of mass cytometry, Using unsupervised analysis of flow cytometry and mass cytometry data obtained from multiple mouse, macaque, and human tissues, Guilliams et al. provide a universal toolbox for the automated identification of dendritic cells. This framework represents the way forward to high-throughput and standardized analysis of dendritic cells from mutant mice and patients.
Published: 2016

10. Fate of manuscripts rejected by Intensive Care Medicine from 2013 to 2016: a follow-up analysis

Author: Ellen Deutsch, Elie Azoulay, Elisa Sala, Jean-François Timsit, Martin Lavillonnière, Anders Perner, Giuseppe Citerio, Samir Jaber, University of Milano-Bicocca [Italy], Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Department of Intensive Care [Rigshospitalet], Rigshospitalet [Copenhagen], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service de réanimation médicale, Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Citerio, G, Deutsch, E, Sala, E, Lavillonnière, M, Perner, A, Jaber, S, Timsit, J, Azoulay, E, Dipartimento di Medicina e Chirurgia = School of Medicine and Surgery [Monza], Università degli Studi di Milano-Bicocca [Milano] (UNIMIB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Copenhagen University Hospital-Copenhagen University Hospital, Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Publishing, medicine.medical_specialty, Manuscripts as Topic, Critical Care, business.industry, Journal, reviewing process, Pain medicine, [SDV]Life Sciences [q-bio], 030208 emergency & critical care medicine, Critical Care and Intensive Care Medicine, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Family medicine, Anesthesiology, Medicine, Humans, 030212 general & internal medicine, Periodicals as Topic, business, ComputingMilieux_MISCELLANEOUS, Forecasting
Abstract: International audience
Published: 2018

11. De novo mutations in MSL3 cause an X-linked syndrome marked by impaired histone H4 lysine 16 acetylation

Author: Olivier Vanakker, Maria Kirchhoff, Christian Gilissen, Jenny Morton, Ineke van der Burgt, Kelly Radtke, Tugce Aktas, Sarah Vergult, Diana Johnson, Tobias Rumpf, Tony Roscioli, André Reis, Alan Fryer, Salima El Chehadeh, Christel Thauvin-Robinet, Ange Line Bruel, Rolph Pfundt, Sander Pajusalu, David Francis, Asifa Akhtar, Iben Bache, Tiong Yang Tan, Vera M. Kalscheuer, Meredith Wilson, Björn Menten, Giuseppe Semplicio, Julien Thevenon, Richard Fisher, Yannis Duffourd, Gerhard Mittler, Witold G. Szymanski, M. Felicia Basilicata, Victoria McKay, Kristin Lindstrom, Han G. Brunner, Katrin Õunap, Jaya Ganesh, Claudia Isabelle Keller Valsecchi, Megan T. Cho, Laurence Faivre, MUMC+: DA Klinische Genetica (5), Klinische Genetica, RS: GROW - R4 - Reproductive and Perinatal Medicine, Max Planck Institute of Immunobiology and Epigenetics (MPI-IE), Max-Planck-Gesellschaft, Equipe GAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), FHU TRANSLAD (CHU de Dijon), Université Bourgogne Franche-Comté [COMUE] (UBFC), West Midlands Regional Genetics Laboratory and Clinical Genetics Unit, Birmingham Women's Hospital, Copenhagen University Hospitals, Radboud University Medical Center [Nijmegen], Center for Medical Genetics [Ghent], Ghent University Hospital, Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], GeneDx [Gaithersburg, MD, USA], Murdoch Children's Research Institute (MCRI), Department of Clinical Genetics [Copenhagen], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Institute of Human Genetics [Erlangen, Allemagne], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Department of Clinical Genetics (Sheffield Children’s NHS Foundation Trust), Sheffield Children's NHS Foundation Trust, Liverpool Women's NHS Foundation Trust, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), and Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
Subjects: Male, 0301 basic medicine, CHROMATIN, INTELLECTUAL DISABILITY, Chromosomal Proteins, Non-Histone, CHROMOSOME, Cohort Studies, Histones, Mice, Genes, X-Linked, MSL complex, Child, Cells, Cultured, Histone Acetyltransferases, Epigenomics, Acetylation, Genetic Diseases, X-Linked, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], Syndrome, Chromatin, Cell biology, DNA-Binding Proteins, DROSOPHILA, Histone, ACETYLTRANSFERASE, Child, Preschool, Female, Adolescent, Mice, Transgenic, Biology, Article, Histone H4, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Genetics, Animals, Humans, CELL-CYCLE, Epigenetics, DEACETYLASE, MOF, MSL3, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], DOSAGE COMPENSATION COMPLEX, Infant, Dosage compensation complex, PROTEIN INTERACTIONS, HEK293 Cells, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Neurodevelopmental Disorders, Case-Control Studies, Mutation, biology.protein, Histone deacetylase, Protein Processing, Post-Translational, Transcription Factors, Ultra-rare developmental disorders
Abstract: International audience; The etiological spectrum of ultra-rare developmental disorders remains to be fully defined. Chromatin regulatory mechanisms maintain cellular identity and function, where misregulation may lead to developmental defects. Here, we report pathogenic variations in MSL3, which encodes a member of the chromatin-associated male-specific lethal (MSL) complex responsible for bulk histone H4 lysine 16 acetylation (H4K16ac) in flies and mammals. These variants cause an X-linked syndrome affecting both sexes. Clinical features of the syndrome include global developmental delay, progressive gait disturbance, and recognizable facial dysmorphism. MSL3 mutations affect MSL complex assembly and activity, accompanied by a pronounced loss of H4K16ac levels in vivo. Patient-derived cells display global transcriptome alterations of pathways involved in morphogenesis and cell migration. Finally, we use histone deacetylase inhibitors to rebalance acetylation levels, alleviating some of the molecular and cellular phenotypes of patient cells. Taken together, we characterize a syndrome that allowed us to decipher the developmental importance of MSL3 in humans.
Published: 2018

12. Screening for heart transplantation and left ventricular assist system: results from the ScrEEning for advanced Heart Failure treatment (SEE-HF) study

Author: Lund, Lars H., Trochu, Jean-Noel, Meyns, Bart, Caliskan, Kadir, shaw, steven, Schmitto, Jan D., Schibilsky, David, Damme, Laura, Heatley, Jerry, Gustafsson, Finn, Cardiology, Karolinska Inst, Dept Med Biochem & Biophys, Solna, Sweden, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Cardiology, B2142, Rigshospitalet [Copenhagen], and Copenhagen University Hospital-Copenhagen University Hospital
Subjects: Left ventricular assist system, Mechanical circulatory support, [SDV]Life Sciences [q-bio], Screening, Heart failure, Heart transplantation
Abstract: International audience; BACKGROUND: Heart transplantation (HTx) and implantable left ventricular assist systems (LVAS) improve outcomes in advanced heart failure but may be underutilized. We hypothesized that screening can identify appropriate candidates. METHODS AND RESULTS: The ScrEEning for advanced Heart Failure treatment (SEE-HF) study was a multicentre prospective study screening patients with existing cardiac resynchronization therapy (CRT) and/or implantable cardioverter-defibrillator (ICD) for ejection fraction ≤40% and New York Heart Association (NYHA) class III-IV, and subsequently for guideline-based HTx and LVAS indication. Of 1722 (mean age 64 ± 14 years, 26% women) patients screened at eight centres in seven European countries, 121 (7.0%) were eligible and 99 (5.7%; mean age 61 ± 10 years, 19% women) patients were enrolled for detailed assessment. Twenty-six of the 99 enrolled patients (26%) were eligible for either HTx or LVAD (18 eligible for HTx; 7 eligible for LVAD; and 1 eligible for both). Eleven patients were listed for HTx and three received an LVAS. Eligible patients were 61 ± 8 years and 19% women, whereas those actually receiving intervention were 56 ± 8 years and 8% women. CONCLUSIONS: Among patients with CRT and/or ICD, a minority have NYHA class III-IV heart failure and ejection fraction ≤40%. Among these, however, more than one-quarter have an unrecognized need for HTx or LVAS. When patients are offered intervention based on screening, many decline. Discrepancies exist between clinical and patient equipoise. Clinical Trial Registration ClinicalTrials.gov Unique Identifier: NCT00894387.
Published: 2018

13. JASPAR 2018: update of the open-access database of transcription factor binding profiles and its web framework

Author: Oriol Fornes, Anthony Mathelier, Benoit Ballester, Jeanne Chèneby, Marius Gheorghe, Arnaud Stigliani, Ge Tan, François Parcy, Aziz Khan, David J. Arenillas, Robin van der Lee, Wyeth W. Wasserman, Klaas Vandepoele, Jaime A. Castro-Mondragon, Damir Baranasic, Albin Sandelin, Shubhada Rajabhau Kulkarni, Boris Lenhard, Adrien Bessy, Centre for Molecular Medicine Norway (NCMM), Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Rigshospitalet [Copenhagen], Department of Medical Genetics, Faculty of Medicine-Child and Family Research Institute-Centre for Molecular Medicine and Therapeutics-University of British Columbia (UBC), Physiologie cellulaire et végétale (LPCV), Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Theories and Approaches of Genomic Complexity (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Plant Systems Biology, VIB, and Department of Plant Biotechnology and Bioinformatics, Ghent University [Belgium] (UGENT), Computational Regulatory Genomics, Imperial College London, Institute of Clinical Sciences, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Bioinformatics Centre, Department of Biology [Copenhagen], Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Sars International Centre for Marine Molecular Biology, University of Bergen (UIB), Oslo University Hospital Radiumhospitalet, Genome Canada and Canadian Institutes of Health Research (On-Target Grants) [255ONT and BOP-149430], Natural Sciences and Engineering Research Council of Canada (Discovery Grant) [RGPIN-2017–06824], Independent Research Fund Denmark, Innovation Fund Denmark, Elixir Denmark, Wellcome Trust [106954], Biotechnology and Biological Sciences Research Council [BB/N023358/1], Medical Research Council UK [MC UP 1102/1], Weston Brain Institute: [20R74681], Research Foundation Flanders Grant [G001015N], Lundbeck Foundation, ANR-10- LABX-49-01,Labex GRAL,Labex GRAL, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute and Department of Medical Genetics, University of British Columbia (UBC), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Copenhagen University Hospital-Copenhagen University Hospital, Radboud University Medical Center [Nijmegen], Universiteit Gent = Ghent University [Belgium] (UGENT), Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute-University of British Columbia (UBC), Biotech Research and Innovation Centre (BRIC), University of Copenhagen = Københavns Universitet (KU), Center for Plant Systems Biology (PSB Center), Vlaams Instituut voor Biotechnologie [Ghent, Belgique] (VIB), Centre for Molecular Medicine and Therapeutics-University of British Columbia (UBC), Laboratoire de physiologie cellulaire végétale (LPCV), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), VIB Department of Plant Systems Biology, University of Bergen (UiB), ANR-10-LABX-0049,GRAL,Grenoble Alliance for Integrated Structural Cell Biology(2010), Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Universiteit Gent = Ghent University (UGENT), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), University of Copenhagen = Københavns Universitet (UCPH), Biotechnology and Biological Sciences Research Council (BBSRC), and Wellcome Trust
Subjects: 0301 basic medicine, REPRESENTATION, Nematodes, [SDV]Life Sciences [q-bio], 05 Environmental Sciences, SPECIFICITIES, DIVERSITY, Genome browser, computer.software_genre, Genome, Bioconductor, User-Computer Interface, 0302 clinical medicine, Databases, Genetic, Database Issue, Taxonomic rank, base de données, 0303 health sciences, Database, Web application framework, BIOINFORMATICS, Genomics, Plants, ARABIDOPSIS, Multiple species, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], GENOME, Insects, 030220 oncology & carcinogenesis, Vertebrates, Erratum, Life Sciences & Biomedicine, Protein Binding, EXPRESSION, Biochemistry & Molecular Biology, libre accès, Biology, 03 medical and health sciences, Open Access, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], JASPAR, Journal Article, Genetics, Animals, Humans, Position-Specific Scoring Matrices, 030304 developmental biology, Internet, Science & Technology, Binding Sites, LANDSCAPE, Fungi, Biology and Life Sciences, 06 Biological Sciences, Binding, SITE PREDICTIONS, 030104 developmental biology, DISCOVERY, profil, 08 Information and Computing Sciences, actualisation, Transcription factor, computer, facteur de transcription, Developmental Biology, Transcription Factors
Abstract: International audience; JASPAR (http://jaspar.genereg.net) is an open-access database of curated, non-redundant transcription factor (TF)-binding profiles stored as position frequency matrices (PFMs) and TF flexible models (TFFMs) for TFs across multiple species in six tax-onomic groups. In the 2018 release of JASPAR, the CORE collection has been expanded with 322 new PFMs (60 for vertebrates and 262 for plants) and 33 PFMs were updated (24 for vertebrates, 8 for plants and 1 for insects). These new profiles represent a 30% expansion compared to the 2016 release. In addition , we have introduced 316 TFFMs (95 for vertebrates , 218 for plants and 3 for insects). This release incorporates clusters of similar PFMs in each taxon and each TF class per taxon. The JASPAR 2018 CORE vertebrate collection of PFMs was used to predict TF-binding sites in the human genome. The predictions are made available to the scientific community through a UCSC Genome Browser track data hub. Finally , this update comes with a new web framework with an interactive and responsive user-interface, along with new features. All the underlying data can be retrieved programmatically using a RESTful API and through the JASPAR 2018 R/Bioconductor package .
Published: 2017

14. Year in review in Intensive Care Medicine 2014: I. Cardiac dysfunction and cardiac arrest, ultrasound, neurocritical care, ICU-acquired weakness, nutrition, acute kidney injury, and miscellaneous

Author: J. Randall Curtis, Pierre Singer, Antoni Torres, Matteo Bassetti, Jan Bakker, Samir Jaber, Anders Perner, Elie Azoulay, Antoine Vieillard-Baron, Laurent Papazian, Michael Joannidis, Martin Smith, Gordon S. Doig, Marcio Soares, Giuseppe Citerio, Jean-François Timsit, Margaret S. Herridge, Mark J. Peters, Maurizio Cecconi, Dominique Benoit, Neurointensive Care Unit, Ospedale S. Gerardo, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Infectious Diseases Division, Università degli studi di Genova = University of Genoa (UniGe), Ghent University Hospital, Ghent, Belgium, Department of Anaesthesia, St. Georges Healthcare NHS Trust, Harborview Medical Center and The University of Washington, Northern Clinical School Intensive Care Research Unit, Interdepartmental Division of Critical Care Medicine, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Department of Intensive Care, University Clinic Innsbruck, Unité de Recherche sur les Maladies Infectieuses Tropicales Emergentes (URMITE), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Department of Intensive Care [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, UCL Institute of Child Health and Great Ormond St Hospital, London, UK, General Intensive Care Department and Institute for Nutrition Research, Rabin Medical Center-Beilinson Hospital, The National Hospital for Neurology and Neurosurgery, Intensive Care Unit, Instituto Nacional de Câncer, Pulmonary Intensive Care Unit, Service de réanimation medico-chirurgicale [CHU Raymond-Poincaré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Intensive Care, Internal Medicine, University of Genoa (UNIGE), 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), Service de réanimation medico-chirurgicale, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Ambroise Paré [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Citerio, G, Bakker, J, Bassetti, M, Benoit, D, Cecconi, M, Curtis, J, Doig, G, Herridge, M, Jaber, S, Joannidis, M, Papazian, L, Perner, A, Peters, M, Singer, P, Smith, M, Soares, M, Torres, A, Vieillard Baron, A, Timsit, J, and Azoulay, E
Subjects: medicine.medical_specialty, business.industry, medicine.medical_treatment, Pain medicine, [SDV]Life Sciences [q-bio], Acute kidney injury, Neurointensive care, Disease, Year in Review 2014, Critical Care and Intensive Care Medicine, medicine.disease, 3. Good health, Intensive care, Anesthesiology, Review Intensive Care, Medicine, Renal replacement therapy, Cardiopulmonary resuscitation, business, Intensive care medicine, ComputingMilieux_MISCELLANEOUS
Abstract: Intensive Care Medicine is changing. New types of pa pers, such as “What’s New in Intensive Care?”, “Understanding the Disease” and “My Paper 20 Years Later”, form a stable proportion of the articles published in the 2014 issues. This diversification has been received with an extraordinary enthusiasm and appreciation by the worldwide readership, as evidenced by the massive number of hits and downloads. In this first of three 2014 “Year in Review” articles, we cover those papers published in Intensive Care Medicine during the past year which focus on cardiac arrest, ultrasonography in critically ill patients, neurocritical care, ICU-acquired weakness, nutrition, acute kidney injury, as well as a number of miscellaneous topics.
Published: 2015

15. An integrated expression atlas of miRNAs and their promoters in human and mouse

Author: de Rie, Yoko, Abugessaisa, Yoko, Alam, Tanvir, Arner, Yoko, Arner, Peter, Ha, Haitham, Aström, Gaby, Babina, Magda, Bertin, Yoko, Burroughs, Yoko, Carlisle, Ailsa, Daub, Yoko, Detmar, Michael, Deviatiiarov, Yoko, Fort, Yoko, Gebhard, Claudia, Goldowitz, Daniel, Guhl, Sven, Ha, Thomas, Harshbarger, Yoko, Hasegawa, Yoko, Hashimoto, Yoko, Herlyn, Meenhard, Heutink, Peter, Hitchens, Kelly, Hon, Yoko, Huang, Edward, Ishizu, Yoko, Kai, Chieko, Kasukawa, Yoko, Klinken, Peter, Lassmann, Yoko, Lecellier, Charles-Henri, Lee, Weonju, Lizio, Yoko, Makeev, Vsevolod, Mathelier, Anthony, Medvedeva, Yulia, Mejhert, Niklas, Mungall, Christopher, Noma, Yoko, Ohshima, Mitsuhiro, Okada-Hatakeyama, Yoko, Persson, Helena, Rizzu, Patrizia, Roudnicky, Filip, Sætrom, Pål, Sato, Hiroki, Severin, Yoko, Shin, Yoko, Swoboda, Rolf, Tarui, Yoko, Toyoda, Hiroo, Vitting-Seerup, Kristoffer, Winteringham, Louise, Yamaguchi, Yoko, Yasuzawa, Kayoko, Yoneda, Misako, Yumoto, Noriko, Zabierowski, Susan, Zhang, Peter, Wells, Christine, Summers, Kim, Kawaji, Hideya, Sandelin, Albin, Rehli, Michael, Hayashizaki, Yoshihide, Carninci, Piero, Forrest, Alistair, de Hoon, Michiel, de Rie, Derek, Abugessaisa, Imad, Arner, Erik, Ashoor, Haitham, Bertin, Nicolas, Burroughs, A Maxwell, Daub, Carsten, Deviatiiarov, Ruslan, Fort, Alexandre, Ha, Jayson, Ha, Akira, Ha, Kosuke, Hon, Chung Chau, Ishizu, Yuri, Kasukawa, Takeya, Lassmann, Timo, Lizio, Marina, Noma, Shohei, Ha, Mariko, Severin, Jessica, Shin, Jay, Tarui, Hiroshi, Ha, Yoshihide, Computat Biosci Res Ctr, Comp Elect & Math Sci & Engn Div, King Abdullah University of Science and Technology (KAUST), Department of medicine [Stockholm], Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Dept Dermatol & Allergy, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Clinical Genetics, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institute of Genetics and Selection of Industrial Microorganisms, GosNIIGenetika, Centre for Molecular Medicine Norway (NCMM), Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Department of Oncology, Lund University [Lund]-Clinical Sciences, RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), University of Copenhagen = Københavns Universitet (KU), Cold Spring Harbor Laboratory, RIKEN Center for Life Science Technologies (RIKEN CLST), Ctr Life Sci Technol, Div Gen Technol, Tsurumi Ku, Karolinska Institutet [Stockholm], Department of Genetic Medicine and Development [Geneva], Université de Genève (UNIGE), Riken Omics Science Center, and Riken Yokohama Institute
Subjects: 0301 basic medicine, FANTOM Consortium, Cells, Biomedical Engineering, Bioengineering, Biology, Applied Microbiology and Biotechnology, Genome, Article, Promoter Regions, 03 medical and health sciences, Mice, Genetic, Transcription (biology), metabolism [MicroRNAs], [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], microRNA, Gene expression, Transcriptional regulation, Gene silencing, Animals, Humans, genetics [MicroRNAs], Promoter Regions, Genetic, Cells, Cultured, Gene Library, Genetics, Cultured, Gene Expression Profiling, RNA, High-Throughput Nucleotide Sequencing, Molecular Sequence Annotation, Gene expression profiling, MicroRNAs, 030104 developmental biology, Good Health and Well Being, genetics [Promoter Regions, Genetic], ddc:660, Molecular Medicine, Generic health relevance, Biotechnology, methods [Gene Expression Profiling]
Abstract: International audience; MicroRNAs (miRNAs) are short non-coding RNAs with key roles in cellular regulation. As part of the fifth edition of the Functional Annotation of Mammalian Genome (FANTOM5) project, we created an integrated expression atlas of miRNAs and their promoters by deep-sequencing 492 short RNA (sRNA) libraries, with matching Cap Analysis Gene Expression (CAGE) data, from 396 human and 47 mouse RNA samples. Promoters were identified for 1,357 human and 804 mouse miRNAs and showed strong sequence conservation between species. We also found that primary and mature miRNA expression levels were correlated, allowing us to use the primary miRNA measurements as a proxy for mature miRNA levels in a total of 1,829 human and 1,029 mouse CAGE libraries. We thus provide a broad atlas of miRNA expression and promoters in primary mammalian cells, establishing a foundation for detailed analysis of miRNA expression patterns and transcriptional control regions.
Published: 2017

16. Delineation of the 3p14.1p13 microdeletion associated with syndromic distal limb contractures

Author: Michel Francoise, Patrick Callier, Steven A. Vokes, Susanne Kjaergaard, Laurence Duplomb, Thomas Lee Dahm, Julien Thevenon, Nicole Monnier, Marie Hélène Aubriot-Lorton, Frédéric Huet, Tara Montgomery, Haley O. Tucker, Clémence Ragon, Nathalie Marle, Katherine Neas, Francine Mugneret, Pierre-Simon Jouk, Joël Lunardi, Klaus Dieterich, Laurence Faivre, Christel Thauvin-Robinet, Anne Laure Mosca-Boidron, Joanne Dixon, Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Génétique des Anomalies du Développement ( GAD ), Université de Bourgogne ( UB ) -IFR100 - Structure fédérative de recherche Santé-STIC, Laboratoire de biochimie et génétique moléculaire, CHU Grenoble, Laboratoire de cytogénétique (CHU de Dijon), Centre de génétique et Centre de référence maladies rares et anomalies du développement et syndromes malformatifs du Centre Est, Département de Génétique et Procréation UF-Hôpital Couple Enfant de Grenoble-CHU Grenoble, Service de pédiatrie, Centre Hospitalier Wiliam Morey, Northern Genetics Service, Newcastle University [Newcastle], Department of Clinical Genetic, Rigshospitalet [Copenhagen], Central and Southern Regional Genetic Services, Wellington Hospital Private, Department of Pediatrics, Nordsjællands Hospital - Hillerød, Service de pédiatrie (CHU de Dijon), Service de Pathologie [CHU de Dijon], Section of Molecular Cell & Developmental Biology, Institute for Cellular and Molecular Biology-University of Texas at Austin [Austin], Graduate Program in Cell and Molecular Biology, University of Texas at Austin [Austin], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, Centre Hospitalier Chalon-sur-Saône William Morey, Department of Clinical Genetics [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, University of Texas at Austin [Austin]- Institute for Cellular and Molecular Biology, and Roux-Buisson, Nathalie
Subjects: Male, Pathology, medicine.medical_specialty, Contracture, [SDV]Life Sciences [q-bio], Locus (genetics), FOXP1, Biology, Mice, distal limb contractures, symbols.namesake, Exon, EIF4E3, Intellectual disability, Genetics, medicine, Animals, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 3p141p13 microdeletion, Genetics (clinical), Arthrogryposis, Chromosome Aberrations, Mice, Knockout, Sanger sequencing, Comparative Genomic Hybridization, [ SDV ] Life Sciences [q-bio], Extremities, Forkhead Transcription Factors, Syndrome, Microdeletion syndrome, medicine.disease, Blepharophimosis, Phenotype, Repressor Proteins, [SDV] Life Sciences [q-bio], array-CGH, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], symbols, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Chromosomes, Human, Pair 3, France, Carrier Proteins, intronic regulatory sequence
Abstract: International audience; Distal limb contractures (DLC) represent a heterogeneous clinical and genetic condition. Overall, 20–25% of the DLC are caused by mutations in genes encoding the muscle contractile apparatus. Large interstitial deletions of the 3p have already been diagnosed by standard chromosomal analysis, but not associated with a specific phenotype. We report on four patients with syndromic DLC presenting with a de novo 3p14.1p13 micro-deletion. The clinical features associated multiple contractures, feeding problems, developmental delay, and intellectual disability. Facial dysmorphism was constant with low-set posteriorly rotated ears and blepharophimosis. Review of previously reported cases with a precise mapping of the deletions, documented a 250 kb smallest region of overlap (SRO) necessary for DLC. This region contained one gene, EIF4E3, the first three exons of the FOXP1 gene, and an intronic enhancer of FOXP1 named hs1149. Sanger sequencing and locus quantification of hs1149, EIF4E3, and FOXP1 in a cohort of 11 French patients affected by DLC appeared normal. In conclusion, we delineate a new microdeletion syndrome involving the 3p14.1p13 locus and associated with DLC and severe developmental delay.
Published: 2014

17. A map of direct TF–DNA interactions in the human genome

Author: Benoit Ballester, Aziz Khan, Anthony Mathelier, Jeanne Chèneby, Marius Gheorghe, Geir Kjetil Sandve, Centre for Molecular Medicine Norway (NCMM), Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Department of Informatics [Oslo], Faculty of Mathematics and Natural Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Theories and Approaches of Genomic Complexity (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Institute for Cancer Research [Oslo], Oslo University Hospital [Oslo], and Spinelli, Lionel
Subjects: Chromatin Immunoprecipitation, ChIP-eat software, Interaction, Sequence analysis, [SDV]Life Sciences [q-bio], genetic processes, ReMap database, Single-nucleotide polymorphism, Plasma protein binding, Computational biology, Biology, Genome, chemistry.chemical_compound, 03 medical and health sciences, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, Humans, natural sciences, Transcription factor, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Binding Sites, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Human genome, Genome, Human, UniBind, Protein interaction, Chromosome Mapping, Computational Biology, High-Throughput Nucleotide Sequencing, DNA, Sequence Analysis, DNA, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [SDV] Life Sciences [q-bio], chemistry, 030220 oncology & carcinogenesis, Methods Online, Corrigendum, Chromatin immunoprecipitation, Algorithms, 030217 neurology & neurosurgery, Protein Binding, Transcription Factors
Abstract: Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is the most popular assay to identify genomic regions, called ChIP-seq peaks, that are bound in vivo by transcription factors (TFs). These regions are derived from direct TF–DNA interactions, indirect binding of the TF to the DNA (through a co-binding partner), nonspecific binding to the DNA, and noise/bias/artifacts. Delineating the bona fide direct TF–DNA interactions within the ChIP-seq peaks remains challenging. We developed a dedicated software, ChIP-eat, that combines computational TF binding models and ChIP-seq peaks to automatically predict direct TF–DNA interactions. Our work culminated with predicted interactions covering >2% of the human genome, obtained by uniformly processing 1983 ChIP-seq peak data sets from the ReMap database for 232 unique TFs. The predictions were a posteriori assessed using protein binding microarray and ChIP-exo data, and were predominantly found in high quality ChIP-seq peaks. The set of predicted direct TF–DNA interactions suggested that high-occupancy target regions are likely not derived from direct binding of the TFs to the DNA. Our predictions derived co-binding TFs supported by protein-protein interaction data and defined cis-regulatory modules enriched for disease- and trait-associated SNPs. We provide this collection of direct TF–DNA interactions and cis-regulatory modules through the UniBind web-interface (http://unibind.uio.no).
Published: 2019

18. SCRIB and PUF60 Are Primary Drivers of the Multisystemic Phenotypes of the 8q24.3 Copy-Number Variant

Author: Jacques S. Beckmann, Christelle Golzio, Nicholas Katsanis, Andrew Dauber, Małgorzata J.M. Nowaczyk, Susan Zeesman, Joel N. Hirschhorn, Francine M. Jodelka, Jill A. Rosenfeld, Danielle Martinet, Bruno Leheup, Cécile Guenot, Michelle L. Hastings, Susanne Kjaergaard, Sébastien Jacquemont, Janice Zunich, Maria Kibaek, UL, NGERE, Division of Endocrinology, Children's Hospital Boston, Harvard Medical School, Harvard Medical School [Boston] (HMS), Broad Institute [Cambridge], Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), Center for Human Disease Modeling, Duke University [Durham], Service de Génétique Médicale [CHUV Lausanne], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Service de Génétique Clinique [CHUV Lausanne], Department of Cell Biology and Anatomy [Chicago Medical School · Rosalind Franklin University], Chicago Medical School [Rosalind Franklin University], Rosalind Franklin University-Rosalind Franklin University, Department of Pediatrics [Odense University Hospital], Odense University Hospital, Department of Clinical Genetics [Copenhagen], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Service de Génétique Médicale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), McMaster University [Hamilton, Ontario], PerkinElmer, Inc., Indiana University School of Medicine, Indiana University System-Indiana University System, and Dept of Genetics, Harvard Medical School
Subjects: Male, Microcephaly, Developmental Disabilities, [SDV]Life Sciences [q-bio], medicine.disease_cause, 0302 clinical medicine, Genetics(clinical), Copy-number variation, Child, Zebrafish, Genetics (clinical), Genetics, 0303 health sciences, Mutation, Chromosome Mapping, RNA-Binding Proteins, Phenotype, [SDV] Life Sciences [q-bio], Child, Preschool, Gene Knockdown Techniques, RNA splicing, Female, RNA Splicing Factors, Erratum, Chromosomes, Human, Pair 8, SCRIB, Adolescent, DNA Copy Number Variations, Biology, Article, 03 medical and health sciences, Intellectual Disability, medicine, Animals, Humans, Allele, Alleles, 030304 developmental biology, Tumor Suppressor Proteins, Membrane Proteins, medicine.disease, Human genetics, Genetic architecture, Repressor Proteins, Gene Deletion, 030217 neurology & neurosurgery, HeLa Cells
Abstract: International audience; Copy-number variants (CNVs) represent a significant interpretative challenge, given that each CNV typically affects the dosage of multiple genes. Here we report on five individuals with coloboma, microcephaly, developmental delay, short stature, and craniofacial, cardiac, and renal defects who harbor overlapping microdeletions on 8q24.3. Fine mapping localized a commonly deleted 78 kb region that contains three genes: SCRIB, NRBP2, and PUF60. In vivo dissection of the CNV showed discrete contributions of the planar cell polarity effector SCRIB and the splicing factor PUF60 to the syndromic phenotype, and the combinatorial suppression of both genes exacerbated some, but not all, phenotypic components. Consistent with these findings, we identified an individual with microcephaly, short stature, intellectual disability, and heart defects with a de novo c.505C>T variant leading to a p.His169Tyr change in PUF60. Functional testing of this allele in vivo and in vitro showed that the mutation perturbs the relative dosage of two PUF60 isoforms and, subsequently, the splicing efficiency of downstream PUF60 targets. These data inform the functions of two genes not associated previously with human genetic disease and demonstrate how CNVs can exhibit complex genetic architecture, with the phenotype being the amalgam of both discrete dosage dysfunction of single transcripts and also of binary genetic interactions.
Published: 2013

19. Cutting Edge: Expression of XCR1 Defines Mouse Lymphoid-Tissue Resident and Migratory Dendritic Cells of the CD8α+ Type

Author: Bjarne Bogen, Laurence Ardouin, Thien-Phong Vu Manh, Samira Tamoutounour, Hiroaki Azukizawa, Hervé Luche, Even Fossum, Martin Guilliams, Marc Dalod, Bernard Malissen, Karine Crozat, Sandrine Henri, Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Center for Immune Regulation [Oslo] (CIR), Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Osaka University, Course of integrated medicine, Department of Dermatology, Lehrstuhl für Regelungstechnik [Erlangen], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Transcription, Genetic, MESH: Receptors, G-Protein-Coupled, MESH: Genetic Markers, Receptors, G-Protein-Coupled, Mice, 0302 clinical medicine, Cell Movement, MESH: DNA Fingerprinting, Immunology and Allergy, MESH: Animals, Receptor, MESH: Antigens, CD, MESH: Cell Movement, 0303 health sciences, MESH: Dendritic Cells, biology, hemic and immune systems, Cell biology, medicine.anatomical_structure, Lymphatic system, Integrin alpha M, [SDV.IMM]Life Sciences [q-bio]/Immunology, Receptors, Chemokine, Integrin alpha Chains, Genetic Markers, XCR1, Lymphoid Tissue, MESH: Mice, Transgenic, CD8 Antigens, Immunology, Mice, Transgenic, chemical and pharmacologic phenomena, Spleen, 03 medical and health sciences, Antigen, Antigens, CD, MESH: Mice, Inbred C57BL, medicine, Animals, Humans, MESH: Mice, Transcription factor, 030304 developmental biology, MESH: Humans, MESH: Transcription, Genetic, MESH: Integrin alpha Chains, Dendritic Cells, DNA Fingerprinting, Mice, Inbred C57BL, MESH: Lymphoid Tissue, biology.protein, MESH: Antigens, CD8, MESH: Receptors, Chemokine, 030215 immunology, XCL1
Abstract: Subsets of dendritic cells (DCs) have been described according to their functions and anatomical locations. Conventional DC subsets are defined by reciprocal expression of CD11b and CD8α in lymphoid tissues (LT), and of CD11b and CD103 in non-LT (NLT). Spleen CD8α+ and dermal CD103+ DCs share a high efficiency for Ag cross-presentation and a developmental dependency on specific transcription factors. However, it is not known whether all NLT-derived CD103+ DCs and LT-resident CD8α+ DCs are similar despite their different anatomical locations. XCR1 was previously described as exclusively expressed on mouse spleen CD8α+ DCs and human blood BDCA3+ DCs. In this article, we showed that LT-resident CD8α+ DCs and NLT-derived CD103+ DCs specifically express XCR1 and are characterized by a unique transcriptional fingerprint, irrespective of their tissue of origin. Therefore, CD8α+ DCs and CD103+ DCs belong to a common DC subset which is unequivocally identified by XCR1 expression throughout the body.
Published: 2011

20. Bi-directional routing of DNA mismatch repair protein human exonuclease 1 to replication foci and DNA double strand breaks

Author: Sascha Emilie Liberti, Vilhelm A. Bohr, Lene Juel Rasmussen, Guido Keijzers, Jean-Baptiste Charbonnier, Mylène Perderiset, Finn Cilius Nielsen, Jing Wang, Sofie Dabros Andersen, Alfred May, Simona Miron, Center for Healthy Aging [Copenhagen], Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Roskilde University, National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Imagerie intégrative de la molécule à l'organisme, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris], Department of Clinical Biochemistry [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Système membranaires, photobiologie, stress et détoxication (SMPSD), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), and 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)
Subjects: DNA Replication, Werner Syndrome Helicase, DNA repair, Recombinant Fusion Proteins, DNA mismatch repair, DNA polymerase II, Amino Acid Motifs, Replication foci, Biology, Biochemistry, DNA polymerase delta, Article, Double strand break, S Phase, Mice, 03 medical and health sciences, 0302 clinical medicine, Replication factor C, Proliferating Cell Nuclear Antigen, Animals, Humans, DNA Breaks, Double-Stranded, Molecular Biology, Replication protein A, Adaptor Proteins, Signal Transducing, 030304 developmental biology, 0303 health sciences, DNA clamp, RecQ Helicases, Lasers, hEXO1PCNA, DNA replication, Nuclear Proteins, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, DNA, Cell Biology, Molecular biology, DNA-Binding Proteins, Protein Transport, DNA Repair Enzymes, Exodeoxyribonucleases, Amino Acid Substitution, 030220 oncology & carcinogenesis, MutS Homolog 3 Protein, NIH 3T3 Cells, biology.protein, MutL Protein Homolog 1, HeLa Cells
Abstract: Human exonuclease 1 (hEXO1) is implicated in DNA metabolism, including replication, recombination and repair, substantiated by its interactions with PCNA, DNA helicases BLM and WRN, and several DNA mismatch repair (MMR) proteins. We investigated the sub-nuclear localization of hEXO1 during S-phase progression and in response to laser-induced DNA double strand breaks (DSBs). We show that hEXO1 and PCNA co-localize in replication foci. This apparent interaction is sustained throughout S-phase. We also demonstrate that hEXO1 is rapidly recruited to DNA DSBs. We have identified a PCNA interacting protein (PIP-box) region on hEXO1 located in its COOH-terminal ((788)QIKLNELW(795)). This motif is essential for PCNA binding and co-localization during S-phase. Recruitment of hEXO1 to DNA DSB sites is dependent on the MMR protein hMLH1. We show that two distinct hMLH1 interaction regions of hEXO1 (residues 390-490 and 787-846) are required to direct the protein to the DNA damage site. Our results reveal that protein domains in hEXO1 in conjunction with specific protein interactions control bi-directional routing of hEXO1 between on-going DNA replication and repair processes in living cells.
Published: 2011

21. Supraclavicular recurrence after early breast cancer: a curable condition?

Author: Merete Jensen, Erik Sandberg, Mette M. Kempel, Karina Dahl Steffensen, Vera Haahr, Ebbe Lindegaard Madsen, Anders N. Pedersen, Søren L. Jepsen, Karen Margrethe Windfeldt, Michael Andersson, Claudia Schöllkopf, Susanne Møller, P.G. Sørensen, Anne Roslind, Department of Oncology, Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Danish Breast Cancer Cooperative Group, Vejle Hospital, Viborg Hospital, Odense University Hospital, Aarhus University Hospital, Sønderborg Hospital, Herlev and Gentofte Hospital, Sydvestjyske Sygehus—Esbjerg, Hillerød Hospital, Roskilde Hospital, and Herning Hospital
Subjects: Adult, Oncology, Cancer Research, medicine.medical_specialty, Denmark, Salvage therapy, Breast Neoplasms, Disease-Free Survival, 030218 nuclear medicine & medical imaging, Cohort Studies, 03 medical and health sciences, Breast cancer, 0302 clinical medicine, Recurrence, Internal medicine, medicine, Humans, Aged, Proportional Hazards Models, Retrospective Studies, Supraclavicular, Univariate analysis, Proportional hazards model, business.industry, Remission Induction, Cancer, Retrospective cohort study, Middle Aged, Prognosis, medicine.disease, 3. Good health, Supraclavicular lymph nodes, Surgery, Treatment Outcome, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Multivariate Analysis, Disease Progression, Therapy, Breast disease, Neoplasm Recurrence, Local, business
Abstract: Udgivelsesdato: 2010-May-8 The prognosis of ipsilateral supraclavicular lymph node recurrence after early breast cancer appears to be worse than for other loco-regional recurrences, but better than for distant metastases. The purpose of the present study was to investigate the relationship between different types of salvage treatment and primary patient characteristics, treatment response, and survival after supraclavicular recurrence (SR) in a large patient population. From the Danish Breast Cancer Cooperative Group treatment database 1977-2003, 305 patients were identified with SR without distant disease as site of first recurrence. Salvage treatment types as well as other factors were related to response and survival. The median follow-up time for progression after SR was 25 months. Complete remission was 76% among patients receiving excision surgery, 67% with combined loco-regional and systemic therapy, and 48% with systemic therapy alone. Median progression-free survival (PFS) and overall survival was 18 and 29 months, respectively. The 5-year PFS probability was 15%. In univariate analysis, combination salvage therapy, negative nodal status and low malignancy grade were related to longer PFS. In multivariate analysis, salvage therapy and malignancy grade remained independent factors for survival. In conclusion, the prognosis of SR is generally poor. However, it appears to be a curable condition. An independent marker of improved outcome is local and systemic combination salvage treatment, which can be considered.
Published: 2010

22. Assessing prognosis and optimizing treatment in patients with postchemotherapy viable nonseminomatous germ-cell tumors (NSGCT): results of the sCR2 international study

Author: J. Bouzy, Hans-Joachim Schmoll, I. Chen, Gedske Daugaard, M. De Santis, Joerg T. Hartmann, U. De Giorgi, Aude Flechon, Karim Fizazi, G. Fromont, Jan Oldenburg, Ariane Dunant, Sergei Tjulandin, Roberto Salvioni, Sophie D. Fosså, Génomes et cancer (GC (FRE2939)), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Department of Pathobiology [Auburn], Auburn University (AU), College of Veterinary Medicine, Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Dept of Oncology, Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Laboratory of Clinical Genetics, Institute of Clinical Oncology, Departments of Clinical Cancer Research and genetics, and Rikshospitalet-Radiumhospitalet Trust
Subjects: Male, MESH: Orchiectomy, MESH: Combined Modality Therapy, Time Factors, International Cooperation, medicine.medical_treatment, 030232 urology & nephrology, MESH: Risk Assessment, Cohort Studies, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, MESH: Cohort Studies, MESH: Testicular Neoplasms, MESH: Treatment Outcome, MESH: Statistics, Nonparametric, MESH: Middle Aged, Biopsy, Needle, Hematology, Middle Aged, Neoplasms, Germ Cell and Embryonal, Prognosis, Combined Modality Therapy, Immunohistochemistry, Chemotherapy regimen, 3. Good health, MESH: Antineoplastic Combined Chemotherapy Protocols, Treatment Outcome, Oncology, Chemotherapy, Adjuvant, MESH: Chemotherapy, Adjuvant, MESH: Survival Analysis, 030220 oncology & carcinogenesis, MESH: Neoplasms, Germ Cell and Embryonal, Cohort study, Adult, MESH: Biopsy, Needle, medicine.medical_specialty, Adolescent, Urology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Risk Assessment, Disease-Free Survival, Statistics, Nonparametric, MESH: Multivariate Analysis, MESH: Prognosis, 03 medical and health sciences, Testicular Neoplasms, medicine, Humans, Progression-free survival, Survival analysis, Retrospective Studies, MESH: Adolescent, Chemotherapy, MESH: Humans, business.industry, MESH: Time Factors, MESH: Adult, MESH: Immunohistochemistry, MESH: Retrospective Studies, Retrospective cohort study, Seminoma, medicine.disease, Survival Analysis, MESH: Male, Surgery, MESH: International Cooperation, Multivariate Analysis, MESH: Disease-Free Survival, Germ cell tumors, business, Orchiectomy
Abstract: BACKGROUND: The purpose of this study was to validate a prognostic index [surgical complete response 1 (sCR1)] in patients with postchemotherapy viable nonseminomatous germ-cell tumors (NSGCT). PATIENTS AND METHODS: Data and specimens from 61 patients with normalized tumor markers and postchemotherapy viable nonteratomatous NSGCT treated in 13 institutions were collected. RESULTS: With a median follow-up of 5.4 years, the 5-year progression-free survival (PFS) rate was 65%; the 5-year overall survival (OS) rate was 72%. Favorable PFS was predicted by a complete resection
Published: 2008

23. European consensus conference on diagnosis and treatment of germ cell cancer: a report of the second meeting of the European Germ Cell Cancer Consensus group (EGCCCG): part I

Author: Robert Huddart, Johannes Classen, Roberto Salvioni, Rainer Souchon, Walter Albrecht, Xavier Garcia del Muro, Malcolm David Mason, Michael Bamberg, Johnathan Joffe, Jutta Scheiderbauer, Annette Dieing, Oscar Leiva Galvis, Niels E. Skakkebæk, Ronald de Wit, William G. Jones, Sophie D. Fosså, Kai Uwe Koehrmann, H. G. Derigs, Silke Gillessen, Martin Fenner, Sergei Tjulandin, C Clemm, Wolfgang Hoeltl, Padraig Warde, Aude Flechon, Luis Paz Ares, Pieter H.M. De Mulder, S. Kliesch, Nicola Nicolai, Thomas Powles, László Kisbenedek, Lothar Weissbach, Craig R. Nichols, Hans von der Maase, Michael Jewett, Jörg Pont, Markus A. Kuczyk, Volker Loy, Christian Wittekind, Peter Albers, Jose Ramon Germa-Lluch, Felix Sedlmayer, Giovanni Rosti, D. Ondruš, Pilar Laguna, Heinz Schmidberger, István Bodrogi, Gabriella Cohn-Cedermark, Eva Cavallin-Ståhl, Jörg Beyer, Tim Oliver, Arthur Gerl, Gedske Daugaard, Stefan Weinknecht, Tobias Pottek, Hans-Joachim Schmoll, Maike de Wit, Rolf Mueller, Maria De Santis, Michael Hartmann, Graham M. Mead, Oliver Rick, Jean Pierre Droz, Christian K. Kollmannsberger, Hans U. Schmelz, Karim Fizazi, Gosse O N Oosterhof, Lori Wood, Thomas Gauler, Aslam Sohaib, Susanne Krege, Ferran Algaba, Alan Horwich, Eva Winter, Stéphane Culine, Giorgio Pizzocaro, Olbjørn Klepp, Axel Heidenreich, Klaus Peter Dieckmann, Jörg T. Hartmann, Mark Schrader, Lajos Géczi, Carsten Bokemeyer, Department of Urology, Klinikum Kassel GmbH, Department of Molecular Genetics and Department of Chemotherapy, National Institute of Oncology, Endocrinologie moléculaire et cellulaire des cancers, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'oncologie Médicale, CRLCC Val d'Aurelle - Paul Lamarque, Dept of Oncology, Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Science et Ingénierie des Matériaux et Procédés (SIMaP), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Génomes et cancer (GC (FRE2939)), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Departments of Clinical Cancer Research and genetics, Rikshospitalet-Radiumhospitalet Trust, Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de biologie moléculaire des plantes (IBMP), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Dept of Urological Oncology, Phillips university, Academic Radiotherapy Unit, Institute of cancer research, Princess Margaret Hospital, University of Toronto, Department of Chemistry [Rochester], University of Rochester [USA], Department of Medical Oncology, Barts and The London Queen Mary's School of Medicine, Laboratoire Evolution, Génomes et Spéciation (LEGS), Centre National de la Recherche Scientifique (CNRS), Laboratory of Clinical Genetics, Institute of Clinical Oncology, Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and Medical Oncology
Subjects: Male, MESH: Combined Modality Therapy, Biopsy, Consensus Development Conferences as Topic, 030232 urology & nephrology, Membrane transport and intracellular motility [NCMLS 5], MESH: Biopsy, 0302 clinical medicine, Stage I Seminoma, MESH: Practice Guidelines as Topic, Medicine, Societies, Medical, MESH: Testicular Neoplasms, Consensus conference, MESH: Neoplasm Staging, Neoplasms, Germ Cell and Embryonal, Prognosis, Primary tumor, Combined Modality Therapy, 3. Good health, Europe, 030220 oncology & carcinogenesis, Practice Guidelines as Topic, MESH: Neoplasms, Germ Cell and Embryonal, medicine.medical_specialty, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Consensus, Urology, MESH: Societies, Medical, MEDLINE, MESH: Prognosis, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Testicular Neoplasms, Interventional oncology [UMCN 1.5], Humans, MESH: Consensus, Testicular cancer, Neoplasm Staging, Gynecology, MESH: Humans, business.industry, MESH: Consensus Development Conferences as Topic, medicine.disease, MESH: Male, Clinical trial, Germ cell cancer, Family medicine, Germ cell tumors, MESH: Europe, business
Abstract: Objectives: The first consensus report presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in the year 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the Amsterdam Medical Center, Amsterdam, The Netherlands. Methods: Medical oncologists, urological surgeons, radiation oncologists as well as pathologists from several European countries reviewed and discussed the data that had emerged since the 2002 conference, and incorporated the new data into updated and revised guidelines. As for the first meeting, the methodology of evidence-based medicine (EBM) was applied. The results of the discussion were compiled by the writing committee. All participants have agreed to this final update. Results: The first part of the consensus paper describes the clinical presentation of the primary tumor, its treatment, the importance and treatment of testicular intraepithelial neoplasia (TIN), histological classification, staging and prognostic factors, and treatment of stage I seminoma and non-seminoma. Conclusions: Whereas the vast majority of the recommendations made in 2004 remain valid 3 yr later, refinements in the treatment of early- and advanced-stage testicular cancer have emerged from clinical trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer. In addition, the particular needs of testicular cancer survivors have been acknowledged. (C) 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.
Published: 2008

24. The DESCARTES-Nantes survey of kidney transplant recipients displaying clinical operational tolerance identifies 35 new tolerant patients and 34 almost tolerant patients

Author: Michaela Prokopova, Friedrich Thaiss, Andries J. Hoitsma, Bruno Hurault de Ligny, Anja Mühlfeld, Séverine Martin, Oliver Gross, Władysław Sułowicz, Annick Massart, Judith Racapé, Miguel Angel Gentil Govantes, A. Yussim, Frieder Keller, Umberto Maggiore, Matthew Howse, Gian Benedetto Piredda, Ricardo Lauzurica, Magali Giral, Luis Antonio Jiménez del Cerro, Marie-Christine Moal, Tomas Reischig, François Glowacki, Jean-François Subra, Bénédicte Janbon, Consuelo De Biase, María José Pérez-Sáez, Marian Klinger, Goce Spasovski, Philippe Gatault, Gaetano La Manna, David Berglund, Cem Tugmen, Giovanni M. Frascà, Uyen Huynh-Do, Christophe Legendre, Annaïck Pallier, Christopher Dudley, Mélanie Chesneau, Laura Braun, Daniel Abramowicz, Karine Hadaya, Christian Noel, Evangeline Pillebout, Carmen Díaz-Corte, Julio Pascual, Ondrej Viklicky, Florence Villemain, Luigi Biancone, Ana Ramírez Puga, Marije C. Baas, Alain Le Moine, Marc Abramowicz, Frederike J. Bemelman, Rainer Oberbauer, Jean-Paul Soulillou, Nurhan Seyahi, Jadranka Buturović Ponikvar, Johan W. de Fijter, Maarten Naesens, Vania Cuna, Klemens Budde, Serhan Tuglular, Pierrick Guerif, Angel Alonso Hernandez, Piero Stratta, Arnaud Garnier, Hulya Colak, K. Clemente, Sophie Brouard, Marc Hazzan, Søren Schwartz Sørensen, Giuseppe Orlando, Daniel Serón, Luboslav Beňa, Quirino Lai, Francesco Pisani, Aisling E. Courtney, Alexandre Dufay, Mehmet Sukru Sever, Thomas Wekerle, Hervé Le Monies De Sagazan, Hakim Mazouz, Aljoša Kandus, Maria Carmen Cantarell, André Gaasbeek, Massart, A, Pallier, A, Pascual, J, Viklicky, O, Budde, K, Spasovski, G, Klinger ,M, Sever, MS, Sørensen, SS, Hadaya, K, Oberbauer, R, Dudley, C, De Fijter, JW, Yussim, A, Hazzan, M, Wekerle, T, Berglund, D, De Biase, C, Pérez-Sáez, MJ, Mühlfeld, A, Orlando, G, Clemente, K, Lai, Q, Pisani, F, Kandus, A, Baas, M, Bemelman, F, Ponikvar, JB, Mazouz ,H, Stratta, P, Subra, JF, Villemain, F, Hoitsma, A, Braun, L, Cantarell, MC, Colak, H, Courtney, A, Frasca, GM, Howse, M, Naesens, M, Reischig, T, Serón, D, Seyahi, N, Tugmen, C, Alonso Hernandez, A, Beňa, L, Biancone, L, Cuna, V, Díaz-Corte, C, Dufay, A, Gaasbeek, A, Garnier, A, Gatault, P, Gentil Govantes, MA, Glowacki, F, Gross, O, Hurault de Ligny, B, Huynh-Do, U, Janbon, B, Jiménez Del Cerro, LA, Keller, F, La Manna, Gaetano, Lauzurica, R, Le Monies De Sagazan, H, Thaiss, F, Legendre, C, Martin, S, Moal, MC, Noël, C, Pillebout, E, Piredda, GB, Puga, AR, Sulowicz, W, Tuglular, S, Prokopova, M, Chesneau, M, Le Moine, A, Guérif, P, Soulillou, JP, Abramowicz, M, Giral, M, Racapé, J, Maggiore, U, Brouard, S, Abramowicz, D, AII - Amsterdam institute for Infection and Immunity, Nephrology, Renal Unit [Brussels, Belgium] (ULB), Université libre de Bruxelles (ULB)-CUB Hôpital Erasme [Bruxelles, Belgium], Medical Genetics Department [Brussels, Belgium], Université libre de Bruxelles (ULB), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Nephrology [Barcelona, Spain] (Hospital del Mar), Hospital del Mar [Barcelona, Spain], Department of Nephrology [Prague, Czech Republic] (Transplant Center), Institute for Clinical and Experimental Medicine (IKEM), Department of Nephrology [Berlin, Germany], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Nephrology [Skopje, Macedonia], Ss. Cyril and Methodius University in Skopje, Nephrology and Transplantation Medicine [Wrocław, Poland], University of Wrocław [Poland] (UWr), Internal Medicine, Nephrology [Istanbul, Turkey], Istanbul School of Medicine [Istanbul, Turkey], Nephrology P [Copenhagen, Denmark], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Nephrology and Transplantation [Geneva, Switzerland], Geneva University Hospitals - HUG [Switzerland], Department of Medicine III–Nephrology, Hypertension and Renal Transplantation [Linz, Austria], Krankenhaus Elisabethinen Linz [Linz, Austria], Richard Bright Renal Centre [Bristol, UK], Southmead Hospital [Bristol, UK]-North Bristol NHS Trust [Bristol, UK], Department of Nephrology [Leiden, The Netherlands], Leiden University Medical Center (LUMC), Department of Transplantation [Tel Aviv, Israël] (Rabin Medical Center), Rabin Medical Center [Tel Aviv, Israël]-Tel Aviv University Sackler School of Medicine [Tel Aviv, Israël], Département de Néphrologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Department of Surgery [Vienna, Austria] (Section of Transplantation Immunology), Medizinische Universität Wien = Medical University of Vienna, Section of Clinical Immunology [Uppsala, Sweden] (Department of Immunology, Genetics and Pathology), Uppsala University, UOS Trapianti Rene Pancreas [Parma, Italy] (Centro Trapianti di Parma), Azienda Ospedaliero-Universitaria di Parma, Department of Nephrology [Aachen, Germany], University Hospital Aachen, Section of Transplantation [Winston-Salem, NC, USA] (Department of Surgery), Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center-Wake Forest Baptist Medical Center, U.O.C. Trapianti D’Organo [L’Aquila, Italy], Department of Nephrology [Ljubljana, Slovenia] (Renal Transplantation Centre Ljubljana), University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), Kidney Diseases [Nijmegen, The Netherlands], Radboudumc Nijmegen [The Netherlands], Renal Transplant Unit [Amsterdam, The Netherlands] (Department of Nephrology), Academic Medical Center [Amsterdam, Netherlands], Unité de Transplantation Rénale et Pancréatique [CHU Sud, Amiens] (Service de Néphrologie), CHU Amiens-Picardie, Department of Translational Medicine [Novara, Italy], Amedeo Avogadro University of Eastern Piedmont, Service de Néphrologie-Dialyse-Transplantation [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), service de Néphrologie et Transplantation Rénale [CHU Strasbourg] (Hôpital de jour de Néphrologie), Centre Hospitalier Universitaire de Strasbourg (CHU de Strasbourg )-Nouvel Hôpital Civil - NHC [Strasbourg], Pediatric Nephrology [Barcelona, Spain] (Vall d’Hebron Hospital), Universitat Autònoma de Barcelona (UAB)-Vall d'Hebron University Hospital [Barcelona], Department of Nephrology [Izmir, Turkey], Tepecik Training and Research Hospital [Izmir, Turkey], Regional Nephrology Unit [Belfast, UK], Belfast City Hospital [Belfast, UK], Nefrologia, Dialisi e Trapianto di rene [Ancona, Italy], AO Torrette Umberto I [Ancona, Italy], Nephrology/Transplantation [Liverpool, UK], Royal Liverpool University Hospital [Liverpool, UK], Department of Nephrology and Renal Transplantation [Leuven, Belgium], University Hospitals Leuven [Leuven]-Catholic University Leuven, Nephrology Ward [Pilsen, Czech Republic] (Department of Internal Medicine), University Hospital Pilsen [Pilsen, Czech Republic], Istanbul University, Servicio de Nefrología, Hospital Universitario, A Coruña, Transplant Centre, University Hospital Louis Pasteur Kosice, University of Turin, St. Orsola University Hospital, University of Bologna, Hospital Universitario Central de Asturias (HUCA), Service Néphrologie [Roubaix], Hôpital Victor Provo, Leids Universitair Medisch Centrum [Leiden, The Netherlands], Néphrologie - Médecine Interne - Hypertension Pédiatrique, Hôpital des Enfants, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service Néphrologie - Immunoclinique [CHRU Tours], Hôpital Bretonneau, Hospital Universitario Virgen del Rocío [Sevilla], Service de Néphrologie et Transplantation rénale [CHRU-lille], University Medicine Göttingen, Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), University of Bern [Bern, Switzerland] (University Hospital Bern ), Transplantation rénale [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Hospital General Universitario de Alicante, Universitätsklinikum Ulm - University Hospital of Ulm, Hospital Universitario Germans Trias I Pujol, University Hospital Hamburg-Eppendorf, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hémodialyse et de Néphrologie [Libourne], Hôpital Robert Boulin, CHRU - Service de néphrologie, dialyse et transplantation rénale, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Département de Néphrologie et transplantation [Hôpital Saint Louis - APHP], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Kidney Transplant Az. Osp. G. Brotzu, Hospital Universitario Insular de Gran Canaria, University Hospital in Krakow, Marmara School of Medicine Hastanesi, Institute of Transplantation Urology and Nephrology [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire, Research Center of Epidemiology, Biostatistics and Clinical Research, Nephrology-Renal Transplantation Department, Université libre de Bruxelles (ULB)-Universitair Ziekenhuis Antwerp, ERA-EDTA-DESCARTES working group, the Fonds Erasme (research grant), the Fonds Carine Vyghen, the Fonds Horlait-Dapsens, the RTRS Fondation de Coopération Scientiﬁque CENTAURE and the IHUCesti project., ANR-10-IBHU-0005,CESTI (TSI-IHU),Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU)(2010), Le Bihan, Sylvie, Instituts Hospitalo-Universitaires B - Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU) - - CESTI (TSI-IHU)2010 - ANR-10-IBHU-0005 - IBHU - VALID, Ss. Cyril and Methodius University in Skopje (UKIM), Tel Aviv University (TAU)-Rabin Medical Center [Tel Aviv, Israël], Università degli studi di Torino = University of Turin (UNITO), University of Bologna/Università di Bologna, Service Néphrologie, médecine interne et hypertension pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CUB Hôpital Erasme [Bruxelles, Belgium]-Université libre de Bruxelles (ULB), and Hadaya, Karine
Subjects: 0301 basic medicine, Nephrology, Graft Rejection, Male, medicine.medical_treatment, 030230 surgery, Kidney transplant, 0302 clinical medicine, Surveys and Questionnaires, Allograft survival, Kidney transplantation, ddc:616, Graft Survival/immunology, Survival Rate/trends, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Incidence, Graft Survival, Immunosuppression, operational tolerance, Transplantation, 3. Good health, Europe, Survival Rate, frequency, minimally immunosuppressed patients, Female, Hemodialysis, Graft Rejection/epidemiology/immunology/prevention & control, Homologous, Adult, medicine.medical_specialty, Ronyons -- Trasplantació -- Aspectes immunològics, Immunosuppression/methods, kidney transplantation, Europe/epidemiology, 03 medical and health sciences, Immune Tolerance/immunology, Internal medicine, medicine, Immune Tolerance, Humans, Transplantation, Homologous, Survival rate, Immunosuppression Therapy, graft survival, business.industry, medicine.disease, Kidney Transplantation, Transplant Recipients, Surgery, 030104 developmental biology, Operational tolerance, Human medicine, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Kidney recipients maintaining a prolonged allograft survival in the absence of immunosuppressive drugs and without evidence of rejection are supposed to be exceptional. The ERA-EDTA-DESCARTES working group together with Nantes University launched a European-wide survey to identify new patients, describe them and estimate their frequency for the first time. Methods Seventeen coordinators distributed a questionnaire in 256 transplant centres and 28 countries in order to report as many operationally tolerant patients (TOL; defined as having a serum creatinine
Published: 2015

25. Gonadotropin-releasing hormone neurones innervate kisspeptin neurones in the female mouse brain

Author: Jens D. Mikkelsen, Clive W. Coen, Zsolt Liposits, Barbara Vida, Fruzsina Rabi, Anett Szilvásy-Szabó, Alain Caraty, Imre Farkas, Imre Kalló, Zsuzsanna Bardóczi, Erik Hrabovszky, Tamas F. Molnar, Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine [Budapest] (KOKI), Hungarian Academy of Sciences (MTA)-Hungarian Academy of Sciences (MTA), Department of Neuroscience, Faculty of Information Technology, Pázmány Péter Catholic University, Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Department of Translational Neurobiology, Neurobiology Research Unit, Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Division of Women's Health, School of Medicine, King‘s College London, National Science Foundation of Hungary (OTKA K101326, OTKA K83710, OTKA K100722), European Community’s Seventh Framework Pro- gramme (FP7/2007–2013) under Grant Agreement 245009, Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Institut Français du Cheval et de l'Equitation [Saumur]-Institut National de la Recherche Agronomique (INRA)
Subjects: Endocrinology, Diabetes and Metabolism, Fluorescent Antibody Technique, Gonadotropin-releasing hormone, souris, reciprocal innervation, immunohistochimie, anteroventral periventricular nucleus, Gonadotropin-Releasing Hormone, Mice, 0302 clinical medicine, Endocrinology, Kisspeptin, rostral periventricular area of the third ventricle, Asymmetric synapse, neurone, Neural Pathways, arcuate nucleus, Neurons, 0303 health sciences, Kisspeptins, Microscopy, Confocal, Brain, asymmetric synapse, Immunohistochemistry, Hypothalamus, cerveau, Female, Anteroventral periventricular nucleus, hormones, hormone substitutes, and hormone antagonists, Autre (Sciences du Vivant), hormone grh, medicine.medical_specialty, endocrine system, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Ovariectomy, microscopie confocale, Neuropeptide, Mice, Inbred Strains, Neurotransmission, Biology, 03 medical and health sciences, Cellular and Molecular Neuroscience, Imaging, Three-Dimensional, femelle, Arcuate nucleus, Internal medicine, medicine, Animals, immunofluorescence, 030304 developmental biology, Third Ventricle, Endocrine and Autonomic Systems, kisspeptine, Arcuate Nucleus of Hypothalamus, Estrogens, Dendrites, Microscopy, Electron, nervous system, Synapses, oestrogen, Neuroscience, 030217 neurology & neurosurgery
Abstract: Kisspeptin (KP) neurones in the rostral periventricular area of the third ventricle (RP3V) and arcuate nucleus (Arc) are important elements in the neuronal circuitry regulating gonadotropin-releasing hormone (GnRH) secretion. KP and co-synthesised neuropeptides/neurotransmitters act directly on GnRH perikarya and processes. GnRH neurones not only form the final output pathway regulating the reproductive functions of the anterior pituitary gland, but also provide neuronal input to sites within the hypothalamus. The current double-label immunohistochemical studies investigated whether GnRH-immunoreactive (IR) projections to the RP3V and/or Arc establish morphological connections with KP-IR neurones at these sites. To optimise visualisation of KP immunoreactivity in, respectively, the RP3V and Arc, ovariectomised (OVX) oestrogen-treated and OVX oil-treated female mice were studied. Confocal laser microscopic analysis of immunofluorescent specimens revealed GnRH-IR axon varicosities in apposition to approximately 25% of the KP-IR neurones in the RP3V and 50% of the KP-IR neurones in the Arc. At the ultrastructural level, GnRH-IR neurones were seen to establish asymmetric synaptic contacts, which usually reflect excitatory neurotransmission, with KP-IR neurones in both the RP3V and Arc. Together with previous data, these findings indicate reciprocal connectivity between both of the KP cell populations and the GnRH neuronal system. The functional significance of the GnRH-IR input to the two separate KP cell populations requires electrophysiological investigation.
Published: 2013

26. Resveratrol inhibits steroidogenesis in human fetal adrenocortical cells at the end of first trimester

Author: Marie-Line Morvan, Olle Söder, Bruno Le Bizec, Jean-Philippe Antignac, Konstantin Svechnikov, Iuliia Savchuk, Tue Søeborg, Kristina Gemzell-Danielsson, Department of Women’s and Children’s Health, Pediatric Endocrinology Unit, Karolinska University Hospital [Stockholm], Karolinska Institute, UMR 1300 Biologie, Epidémiologie et Analyse du Risque, Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Biologie, Epidémiologie et Analyse du Risque (BioEpAR)-Santé animale (S.A.), PRES Université Nantes Angers Le Mans (UNAM), Laboratoire d'étude des Résidus et Contaminants dans les Aliments (LABERCA), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Department of Growth and Reproduction [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Department of Obstetrics and Gynecology, Helsinki University Central Hospital, European Union's Horizon 2020 research and innovation programme [634880], Swedish Research Council, Children's Cancer Fund, Frimurare Barnhuset Foundation, Kronprinsessan Lovisas Foundation, Sallskapet Barnavard, Stiftelsen Samariten, Stiftelsen Olle Engkvist Byggmastare, Stiftelsen Gunvor och Josef Aners, Stiftelsen Anna-Brita och Bo Castegrens Minne, and Stiftelsen Tornspiran
Subjects: 0301 basic medicine, medicine.medical_specialty, Steroidogenic enzymes, [SDV]Life Sciences [q-bio], Dehydroepiandrosterone, Resveratrol, Biology, 03 medical and health sciences, chemistry.chemical_compound, Cytochrome P450 Family 21, Pregnancy, Internal medicine, Stilbenes, medicine, Humans, Androstenedione, Cells, Cultured, Fetus, Adrenal cortex, Steroid 17-alpha-Hydroxylase, Lyase, In vitro, 3. Good health, Blot, Pregnancy Trimester, First, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Steroidogenesis, chemistry, Human fetal adrenocortical cells, Adrenal Cortex, Female, Steroids, Food Science, Biotechnology
Abstract: cope Resveratrol has a diverse array of healthful effects on metabolic parameters in different experimental paradigms but has also potential to inhibit steroidogenesis in rodent adrenals. The aim of the present study was to characterize the effects of resveratrol on human fetal adrenal steroidogenesis at gestational weeks (GW) 9–12. Methods and results Adrenals from aborted fetuses (GW10-12) were used to prepare primary cultures of human fetal adrenocortical cells (HFAC). HFAC were treated in the presence or absence of ACTH (10 ng/ml) with or without resveratrol (10 μM) for 24 hours. The production of steroids by HFAC was analyzed by gas and liquid chromatography coupled to tandem/mass spectrometry. The expression of steroidogenic enzymes at GW 9–12 was quantified by automated Western blotting. We observed that resveratrol significantly suppressed synthesis of dehydroepiandrosterone (DHEA), androstenedione and 11-deoxicortisol by ACTH-activated and unstimulated HFAC, which was associated with inhibition of the activities and expression of cytochromes 17α-hydroxylase/17,20 lyase (CYP17) and 21-hydroxylase (CYP21) in these fetal adrenocortical cells. Conclusion Our in vitro findings on the sensitivity of human fetal adrenal steroidogenesis to resveratrol at GW9-12 suggest that intake of this polyphenol at high doses by women who are at early stages of pregnancy is undesirable. This article is protected by copyright. All rights reserved
Published: 2016

27. A role for glutamate transporters in the regulation of insulin secretion

Author: Runhild Gammelsaeter, Romano Regazzi, David Attwell, Païkan Marcaggi, Thierry Coppola, Jon Storm-Mathisen, Farrukh A. Chaudhry, Vidar Gundersen, Division of Anatomy [Oslo], Department of Molecular Medicine [Oslo], Institute of Basic Medical Sciences [Oslo], Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Institute of Basic Medical Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Department of Physiology, University College of London [London] (UCL), Biotechnology center of Oslo, University of Oslo (UiO)-University of Oslo (UiO)-Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Département de Biologie Cellulaire et de Morphologie, Université de Lausanne (UNIL), Department of Neurology, and Rikshospitalet
Subjects: MESH: Hydrogen-Ion Concentration, Anatomy and Physiology, MESH: Secretory Vesicles, lcsh:Medicine, Gene Expression, MESH: Vesicular Glutamate Transport Proteins, MESH: Insulin-Secreting Cells, Membrane Potentials, Mice, 0302 clinical medicine, Insulin-Secreting Cells, Insulin Secretion, Vesicular Glutamate Transport Proteins, Molecular Cell Biology, Insulin, MESH: Animals, lcsh:Science, 0303 health sciences, Multidisciplinary, MESH: Amino Acid Transport Systems, Acidic, biology, Granule (cell biology), Glutamate receptor, Metabotropic glutamate receptor 6, MESH: Glutamic Acid, Animal Models, Hydrogen-Ion Concentration, Cell biology, Protein Transport, Glutamate dehydrogenase 1, Biochemistry, Excitatory Amino Acid Transporter 2, Medicine, Research Article, Signal Transduction, MESH: Protein Transport, MESH: Rats, Amino Acid Transport Systems, Acidic, Glutamic Acid, [SDV.CAN]Life Sciences [q-bio]/Cancer, Endocrine System, MESH: Insulin, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Signaling Pathways, Exocytosis, 03 medical and health sciences, Model Organisms, MESH: Membrane Potentials, Animals, Rats, Wistar, MESH: Mice, Biology, 030304 developmental biology, Endocrine Physiology, Secretory Vesicles, lcsh:R, Cell Membrane, Glutamic acid, MESH: Rats, Wistar, Neuroendocrinology, Rats, MESH: Excitatory Amino Acid Transporter 2, Metabotropic glutamate receptor, biology.protein, Rat, lcsh:Q, 030217 neurology & neurosurgery, MESH: Cell Membrane
Abstract: International audience; In the brain, glutamate is an extracellular transmitter that mediates cell-to-cell communication. Prior to synaptic release it is pumped into vesicles by vesicular glutamate transporters (VGLUTs). To inactivate glutamate receptor responses after release, glutamate is taken up into glial cells or neurons by excitatory amino acid transporters (EAATs). In the pancreatic islets of Langerhans, glutamate is proposed to act as an intracellular messenger, regulating insulin secretion from β-cells, but the mechanisms involved are unknown. By immunogold cytochemistry we show that insulin containing secretory granules express VGLUT3. Despite the fact that they have a VGLUT, the levels of glutamate in these granules are low, indicating the presence of a protein that can transport glutamate out of the granules. Surprisingly, in β-cells the glutamate transporter EAAT2 is located, not in the plasma membrane as it is in brain cells, but exclusively in insulin-containing secretory granules, together with VGLUT3. In EAAT2 knock out mice, the content of glutamate in secretory granules is higher than in wild type mice. These data imply a glutamate cycle in which glutamate is carried into the granules by VGLUT3 and carried out by EAAT2. Perturbing this cycle by knocking down EAAT2 expression with a small interfering RNA, or by over-expressing EAAT2 or a VGLUT in insulin granules, significantly reduced the rate of granule exocytosis. Simulations of granule energetics suggest that VGLUT3 and EAAT2 may regulate the pH and membrane potential of the granules and thereby regulate insulin secretion. These data suggest that insulin secretion from β-cells is modulated by the flux of glutamate through the secretory granules.
Published: 2011

28. On the origin and diffusion of BRCA1 c.5266dupC (5382insC) in European populations

Author: Bing Jian Feng, Thomas Hansen, Fergus J. Couch, Dominique Stoppa-Lyonnet, Finn Cilius Nielsen, Sona Ciernikova, David E. Goldgar, Celia M. T. Greenwood, Jacek Gronwald, Nancy Hamel, Bohdan Górski, Olga M. Sinilnikova, Mads Thomassen, Laima Tihomirova, Steven A. Narod, Irene Konstantopoulou, Evgeny N. Imyanitov, Jan Lubinski, Drakoulis Yannoukakos, William D. Foulkes, Lenka Foretova, Vladimir Zajac, Masaryk Memorial Cancer Institute, Service de Génétique Oncologique, INSTITUT CURIE, Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratory of Molecular Oncology, N.N. Petrov Institute of Oncology, Equipe 6, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Latvian Biomedical Research and Study Centre [Rīga], Department of Genetics and Pathology, Pomeranian Medical University-International Hereditary Cancer Centre, Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Department of Clinical Genetics, Rigshospitalet [Copenhagen]-University of Copenhagen ( KU ), Odense University Hospital, Molecular Diagnostics Laboratory, IRRP, National Centre for Scientific Research 'Demokritos', National Center for Scientific Research 'Demokritos' ( NCSR ), McGill University, Masaryk Memorial Cancer Institute (RECAMO), Institut Curie, Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Department of Clinical Genetics [Copenhagen], Rigshospitalet [Copenhagen], National Center for Scientific Research 'Demokritos' (NCSR), Institut Curie [Paris], Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Copenhagen University Hospital-Copenhagen University Hospital, and McGill University = Université McGill [Montréal, Canada]
Subjects: MESH : Genes, BRCA1, Genes, BRCA1, MESH : Genotype, MESH: Founder Effect, MESH : Breast Neoplasms, MESH : Microsatellite Repeats, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Genotype, 0302 clinical medicine, Gene Frequency, Ethnicity, MESH : Female, MESH : Gene Frequency, Genetics (clinical), Genetics, Ovarian Neoplasms, 0303 health sciences, education.field_of_study, MESH: Genetic Testing, MESH: Genetic Predisposition to Disease, MESH: European Continental Ancestry Group, Founder Effect, 3. Good health, Europe, MESH: Ovarian Neoplasms, MESH : Jews, 030220 oncology & carcinogenesis, Mutation (genetic algorithm), MESH: Jews, Microsatellite, MESH: Ethnic Groups, Female, Gene pool, MESH : Mutation, Brazil, MESH : Ethnic Groups, MESH: Mutation, Genotype, Population, MESH : Europe, MESH : Founder Effect, [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, Biology, White People, Article, MESH : European Continental Ancestry Group, 03 medical and health sciences, Molecular evolution, MESH : Genetic Testing, MESH: Gene Frequency, MESH : Brazil, Humans, Genetic Predisposition to Disease, Genetic Testing, education, Allele frequency, MESH : Haplotypes, 030304 developmental biology, MESH: Humans, MESH : Ovarian Neoplasms, Haplotype, MESH : Humans, MESH: Haplotypes, Haplotypes, Jews, Mutation, MESH : Genetic Predisposition to Disease, MESH: Microsatellite Repeats, MESH: Europe, MESH: Brazil, MESH: Female, MESH: Genes, BRCA1, MESH: Breast Neoplasms, Founder effect, Microsatellite Repeats
Abstract: The BRCA1 mutation c.5266dupC was originally described as a founder mutation in the Ashkenazi Jewish (AJ) population. However, this mutation is also present at appreciable frequency in several European countries, which raises intriguing questions about the origins of the mutation. We genotyped 245 carrier families from 14 different population groups (Russian, Latvian, Ukrainian, Czech, Slovak, Polish, Danish, Dutch, French, German, Italian, Greek, Brazilian and AJ) for seven microsatellite markers and confirmed that all mutation carriers share a common haplotype from a single founder individual. Using a maximum likelihood method that allows for both recombination and mutational events of marker loci, we estimated that the mutation arose some 1800 years ago in either Scandinavia or what is now northern Russia and subsequently spread to the various populations we genotyped during the following centuries, including the AJ population. Age estimates and the molecular evolution profile of the most common linked haplotype in the carrier populations studied further suggest that c.5266dupC likely entered the AJ gene pool in Poland approximately 400-500 years ago. Our results illustrate that (1) BRCA1 c.5266dupC originated from a single common ancestor and was a common European mutation long before becoming an AJ founder mutation and (2) the mutation is likely present in many additional European countries where genetic screening of BRCA1 may not yet be common practice.European Journal of Human Genetics advance online publication, 1 December 2010; doi:10.1038/ejhg.2010.203.
Published: 2010

29. A European consensus report on blood cell identification: terminology utilized and morphological diagnosis concordance among 28 experts from 17 countries within the European LeukemiaNet network WP10, on behalf of the ELN Morphology Faculty

Author: Gina Zini, Barbara J. Bain, Marc Maynadié, Giuseppe D'Onofrio, Bodil Laub Petersen, Krzysztof C. Lewandowski, John Meletis, Teresa Vallespi, Petra Kacirkova, Evangelos Terpos, André Tichelli, José Cortez, Estella Matutes, John M. Bennett, Peter Bettelheim, Torsten Haferlach, Marie C. Béné, Anna Porwit, Edgar Faber, Soledad Woessner, Hematology, Università cattolica del Sacro Cuore [Roma] (Unicatt), Pathology, St. Mary's Hospital, Otto Wagner Hospital, 3.Central Laboratory, Hematology Laboratory, Portuguese Oncology Institute, Hemato-Oncology, University Hospital Olomuc, Munich Leukemia Laboratory, MLL, Laboratory, The Institute of Hematology and Blood Transfusion, Medical University of Gdansk, Haematology, Royal Marsden Hospital, Service d'hématologie biologique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Internal Medicine, General Hospital Goudi, Department of Pathology [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Department of Pathology, Karolinska University Hospital [Stockholm], Theagenion Cancer Center, Hematology laboratory, University Hospital, Vall d'Hebron University Hospital [Barcelona], Cytohaematological school, Hospital del Mar, James P Wilmot Cancer Center, Service d'Immunologie [CHRU Nancy], and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
Subjects: Knowledge management, Glossary, Delphi Technique, Concordance, Delphi method, Harmonization, 030204 cardiovascular system & hematology, Terminology, 03 medical and health sciences, European LeukemiaNet, 0302 clinical medicine, Terminology as Topic, Medicine, Humans, Cell Lineage, computer.programming_language, Blood Cells, business.industry, Cell Differentiation, Hematology, Hematologic Diseases, 3. Good health, Identification (information), 030220 oncology & carcinogenesis, Immunology, business, computer, Delphi
Abstract: International audience; Lack of standardization of specimen processing procedures, staining, degree of skill in interpretation and terminology used still affects microscopic evaluation of peripheral blood and bone marrow cells. The new WHO classification, on the other hand, highlights the importance of morphological aspects for recognition of disease entities and better stratification of patients with myeloid neoplasms and, in particular, myelodysplastic syndromes (MDS). Within the activities of the WP10 of European LeukemiaNet Network, a Morphology Faculty of 28 expert morphologists from 17 European countries, initiated a project in February 2007 with the goal to increase the quality of diagnostics based on cytomorphology as the first technique worldwide and to support this by a web based consensus report, including a uniform nomenclature. Activities were mainly carried out via internet to find a final fully agreed cell name. In a final 2-day meting, cells without a full agreement were collectively reviewed and approved. At the end of the project 228 images with 604 labelled blood cells with the consensus name agreed by the EMF were available to be uploaded on the web for free consultancy.The appropriateness and the utility of the consensus method has been validated by an expert morphologist external to the EMF(JMB).
Published: 2010

30. Many putative endocrine disruptors inhibit prostaglandin synthesis

Author: Niels E. Skakkebæk, Jacob B. Hansen, Bernard Jégou, Søren Brunak, David Møbjerg Kristensen, Henrik Leffers, Hanne Frederiksen, Karine Audouze, Maria Lena Skalkam, Laurianne Lesné, Steffen Junker, Christèle Desdoits-Lethimonier, Brébion, Alice, Department of Growth and Reproduction [Rigshospitalet], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Center for Biological Sequence Analysis [Lyngby], Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Groupe d'Etude de la Reproduction Chez l'Homme et les Mammiferes (GERHM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Biomedical Sciences [Copenhagen], Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Department of Human Genetics, the European Commission (EU-F7 grants 212844 and 212502), the Villum Kann Rasmussen Foundation, the Novo Nordisk Foundation, INSERM, the Ministère de l'Enseignement Supérieur et de la Recherche, Technical University of Denmark [Lyngby] (DTU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)
Subjects: Male, antiandrogens, Health, Toxicology and Mutagenesis, Cell, Endocrine Disruptors, MESH: Dose-Response Relationship, Drug, parabens, benzophenones, prostaglandins, chemistry.chemical_compound, Mice, 0302 clinical medicine, Testis, MESH: Animals, Fatty Acid Synthesis Inhibitors, Mast Cells, Receptor, 0303 health sciences, phthalates, 030219 obstetrics & reproductive medicine, MESH: Testis, Chemistry, MESH: Mast Cells, Transfection, MESH: Endocrine Disruptors, 3. Good health, cyclooxygenase, medicine.anatomical_structure, Endocrine disruptor, Biochemistry, MESH: Cyclooxygenase 2, medicine.symptom, MESH: Rats, PPARs, Prostaglandin, 03 medical and health sciences, medicine, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, Animals, Humans, Mode of action, MESH: Mice, 030304 developmental biology, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, MESH: Humans, Dose-Response Relationship, Drug, Research, Public Health, Environmental and Occupational Health, MESH: Male, Rats, Mechanism of action, MESH: Prostaglandins, Cyclooxygenase 2, Prostaglandins, MESH: Fatty Acid Synthesis Inhibitors
Abstract: International audience; BACKGROUND: Prostaglandins (PGs) play key roles in development and maintenance of homeostasis of the adult body. Despite these important roles, it remains unclear whether the PG pathway is a target for endocrine disruption. However, several known endocrine-disrupting compounds (EDCs) share a high degree of structural similarity with mild analgesics. OBJECTIVES AND METHODS: Using cell-based transfection and transduction experiments, mass spectrometry, and organotypic assays together with molecular modeling, we investigated whether inhibition of the PG pathway by known EDCs could be a novel point of endocrine disruption. RESULTS: We found that many known EDCs inhibit the PG pathway in a mouse Sertoli cell line and in human primary mast cells. The EDCs also reduced PG synthesis in ex vivo rat testis, and this reduction was correlated with a reduced testosterone production. The inhibition of PG synthesis occurred without involvement of canonical PG receptors or the peroxisome proliferator-activated receptors (PPARs), which have previously been described as targets of EDCs. Instead, our results suggest that the compounds may bind directly into the active site of the cyclooxygenase (COX) enzymes, thereby obstructing the conversion of arachidonic acid to PG precursors without interfering with the expression of the COX enzymes. A common feature of the PG inhibitory EDCs is the presence of aromatic groups that may stabilize binding in the hydrophobic active site of the COX enzymes. CONCLUSION: Our findings suggest a hitherto unknown mode of action by EDCs through inhibition of the PG pathway and suggest new avenues to investigate effects of EDCs on reproductive and immunological disorders that have become increasingly common in recent decades.
Published: 2010

31. Reporting methods of blinding in randomized trials assessing nonpharmacological treatments

Author: David Moher, Candice Estellat, Philippe Ravaud, Isabelle Boutron, Asbjørn Hróbjartsson, Lydia Guittet, Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Département d'épidémiologie, biostatistique et recherche clinique, 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), Departement of Pediatrics, University of Ottawa [Ottawa]-Children's hospital of Eastern Ontario Research Institute, Department of Epidemiology and Community Medicine, University of Ottawa [Ottawa], Nordic Cochrane Centre, Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Gillet, Catherine, and Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Research design, medicine.medical_specialty, Blinding, Epidemiology, MEDLINE, Public Health and Epidemiology, lcsh:Medicine, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Double-Blind Method, Rheumatology, law, Research Methods, Medicine, Humans, 030212 general & internal medicine, Randomized Controlled Trials as Topic, Systematic reviews and meta-analyses, Evidence-Based Healthcare, business.industry, lcsh:R, General Medicine, 3. Good health, Clinical trial, Treatment evaluation, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Research Design, Meta-analysis, Physical therapy, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Surgery, Public Health, business, 030217 neurology & neurosurgery, Research Article
Abstract: Background Blinding is a cornerstone of treatment evaluation. Blinding is more difficult to obtain in trials assessing nonpharmacological treatment and frequently relies on “creative” (nonstandard) methods. The purpose of this study was to systematically describe the strategies used to obtain blinding in a sample of randomized controlled trials of nonpharmacological treatment. Methods and Findings We systematically searched in Medline and the Cochrane Methodology Register for randomized controlled trials (RCTs) assessing nonpharmacological treatment with blinding, published during 2004 in high-impact-factor journals. Data were extracted using a standardized extraction form. We identified 145 articles, with the method of blinding described in 123 of the reports. Methods of blinding of participants and/or health care providers and/or other caregivers concerned mainly use of sham procedures such as simulation of surgical procedures, similar attention-control interventions, or a placebo with a different mode of administration for rehabilitation or psychotherapy. Trials assessing devices reported various placebo interventions such as use of sham prosthesis, identical apparatus (e.g., identical but inactivated machine or use of activated machine with a barrier to block the treatment), or simulation of using a device. Blinding participants to the study hypothesis was also an important method of blinding. The methods reported for blinding outcome assessors relied mainly on centralized assessment of paraclinical examinations, clinical examinations (i.e., use of video, audiotape, photography), or adjudications of clinical events. Conclusions This study classifies blinding methods and provides a detailed description of methods that could overcome some barriers of blinding in clinical trials assessing nonpharmacological treatment, and provides information for readers assessing the quality of results of such trials., An assessment of blinding methods used in nonpharmacological trials published in one year in high-impact factor journals classifies methods used and describes methods that could overcome some barriers of blinding., Editors' Summary Background. Well-conducted “randomized controlled trials” are generally considered to be the most reliable source of information about the effects of medical treatments. In a randomized trial, the play of chance is used to decide whether each patient receives the treatment under investigation, or whether he/she is assigned to a “control” group receiving the standard treatment for their condition. This helps makes sure that the two groups of patients receiving the different treatments are equivalent at the start of the trial. Proper randomization also prevents doctors from deciding which treatment individual patients are given, which could distort the results. An additional technique used is “blinding,” which involves taking steps to prevent patients, doctors, or other people involved in the trial (e.g., those recording measurements) from finding out which patients have received which treatment. Properly done, blinding should make sure the results of a trial are more accurate. This is because in an unblinded study, participants may respond better if they know they have received a promising new treatment (or worse if they only got a placebo or an old drug). In addition, doctors and others in the research team may “want” a particular treatment to perform better in the trial, and unthinking bias could creep into their measurements or actions. However, blinding is not a simple, single step; the people carrying out the trial often have to set up a variety of different procedures. Why Was This Study Done? The authors of this study had already conducted research into the way in which blinding is done in trials involving drug (“pharmacological”) treatment. Their work was published in October 2006 in PLoS Medicine. However, concealing from patients the type of pill that they are being given is much easier than, for example, concealing whether or not they are having surgery or whether or not they are having psychotherapy. The authors therefore set out to look at the methods that are in use for blinding in nonpharmacological trials. They hoped that a better understanding of the different blinding methods would help people doing trials to design better trials in the future, and also help readers to interpret the quality of completed trials. What Did the Researchers Do and Find? The authors systematically searched the published medical literature to find all randomized, blinded drug trials published in just one year (2004) in a number of different “high-impact” journals (well-regarded journals whose articles are often mentioned in other articles). Then, they classified information from the published trial reports. They ended up with 145 trial reports, of which 123 described how blinding was done. The trials covered a wide range of medical conditions and types of treatment. The blinding methods used mainly involved the use of “sham” procedures. Thus, in 80% of the studies in which the treatment involved a medical device, a pretend device had been used to make patients in the control group think they were receiving treatment. In many of the treatments involving surgery, researchers had devised elaborate ways of making patients think they had had an operation. When the treatment involved manipulation (e.g. physiotherapy or chiropractic), fake “hands-on” techniques were given to the control patients. The authors of this systematic review classify all the other techniques that were used to blind both the patients and members of the research teams. They found that some highly innovative ideas have been successfully put into practice. What Do These Findings Mean? The authors have provided a detailed description of methods that could overcome some barriers of blinding in clinical trials assessing nonpharmacological treatment. The classification of the techniques used will be useful for other researchers considering what sort of blinding they will use in their own research. Additional Information. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040061. The James Lind Library has been created to help patients and researchers understand fair tests of treatments in health care by illustrating how fair tests have developed over the centuries ClinicalTrials.gov, a trial registry created by the US National Institutes of Health, has an introduction to understanding clinical trials The UK National Health Service National Electronic Library for Health has an introduction to controlled clinical trials The CONSORT statement is intended to strengthen evidence-based reporting of clinical trials
Published: 2006

32. Primary lymphoma of the lacrimal sac: an EORTC ophthalmic oncology task force study

Author: Elisabeth Ralfkiaer, Birgitte R Juhl, Franck Bacin, Peter Meyer, Tero Kivelä, B. Kantelip, Claudia Auw-Haedrich, Steffen Heegaard, Nicolas Ducrey, Marta Carrera, Sarah E. Coupland, Jan Ulrik Prause, Nicolai Christian Sjö, Lene Dissing Sjö, Jean Louis Kemeny, Bernard Delbosc, Eye Pathology Institute, University of Copenhagen ( KU ), Department of Pathology, Rigshospitalet [Copenhagen], Department of Ophthalmology, Helsinki University Central Hospital, University Hospital in Freiburg, Service d'ophtalmologie [Clermont-Ferrand], CHU Clermont-Ferrand, Department of Ophthalmic Pathology, Hospital of Bellvitge-University of Barcelona, Department of Cellular and Molecular Pathology, University of Liverpool, Service d'ophtalmologie [Besançon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Jules Gonin Hospital, Laboratoire d'anatomie pathologique [Besancon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz-Université de Franche-Comté ( UFC ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Laboratoire de pathologie, University of Basle, European Organization for Research and Treatment of Cancer, University of Copenhagen = Københavns Universitet (KU), Copenhagen University Hospital-Copenhagen University Hospital, Service d'ophtalmologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Service d'Anatomie pathologique [CHRU Besançon], Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), University of Copenhagen = Københavns Universitet (UCPH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), and Saas, Philippe
Subjects: Oncology, Pathology, MESH : Retrospective Studies, MESH : Aged, MESH: Antigens, Neoplasm, MESH : Lymphoma, Large B-Cell, Diffuse, MESH : Antigens, Neoplasm, MESH: Aged, 80 and over, MESH : Lymphoma, B-Cell, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, MESH: Lymphoma, B-Cell, Marginal Zone, MESH: Antigens, CD, MESH: Aged, MESH: Middle Aged, MALT lymphoma, Sensory Systems, Lacrimal sac, 3. Good health, MESH : Lymphoma, B-Cell, Marginal Zone, medicine.anatomical_structure, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Male, MESH: Lacrimal Apparatus Diseases, Lacrimal gland, Ophthalmic pathology, 03 medical and health sciences, Cellular and Molecular Neuroscience, Internal medicine, MESH : Antigens, CD, medicine, MESH : Middle Aged, MESH : Aged, 80 and over, MESH: Lymphoma, B-Cell, MESH : Lacrimal Apparatus Diseases, MESH: Humans, business.industry, Clinical Science - Extended Report, MESH : Humans, Cancer, MESH: Retrospective Studies, medicine.disease, MESH: Male, Dacryocystitis, Lymphoma, Ophthalmology, 030221 ophthalmology & optometry, MESH: Lymphoma, Large B-Cell, Diffuse, Tears, business, MESH: Female, Diffuse large B-cell lymphoma, Mucosa-associated lymphoid tissue
Abstract: International audience; AIM: To define the clinical and histopathological characteristics of primary lacrimal sac lymphoma in a predominantly white population. METHODS: Specimens of lacrimal sac lymphoma and follow up data were solicited from members of the Ophthalmic Oncology Task Force of the European Organization for Research and Treatment of Cancer (EORTC) and the European Ophthalmic Pathology Society (EOPS). Specimens were stained with haematoxylin and eosin and an immunohistochemical panel against leucocyte antigens was applied. Diagnosis was reached by consensus of five experienced pathologists according to the World Health Organization classification system. The histopathological findings were correlated with the clinical data. RESULTS: Of 15 primary lacrimal sac lymphomas, five (33%) were diffuse large B cell lymphoma (DLBCL), five (33%) were extranodal marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT lymphoma), three were classified as "transitional MALT lymphoma," being in transition from MALT lymphoma to DLBCL, and two were unclassified B cell lymphomas. Nine of the patients were female, and the median age at the time of diagnosis was 71 years (range 45-95 years). The most frequent presenting symptoms were epiphora (85%), swelling in the region of the lacrimal sac (79%), and dacryocystitis (21%). All but one patient presented in stage I. Systemic spread occurred in three of nine patients (33%). The 5 year overall survival was 65%. CONCLUSIONS: DLBCL and MALT lymphoma are equally common in the lacrimal sac in contrast with the remaining periorbital and/or orbital region where MALT lymphoma predominates.
Published: 2006

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32 results on '"Copenhagen University Hospital-Copenhagen University Hospital"'

1. Genetic architecture of natural variation of cardiac performance from flies to humans

2. Parameter estimates for trends and patterns of excess mortality among persons on antiretroviral therapy in high-income European settings

3. Fructose malabsorption induces cholecystokinin expression in the ileum and cecum by changing microbiota composition and metabolism

4. Identification of key tissue-specific, biological processes by integrating enhancer information in maize gene regulatory networks

5. Uptake of Tenofovir-Based Antiretroviral Therapy among HIV–HBV-Coinfected Patients in the EuroSIDA Study

6. Survey of diagnostic and treatment practices for multiple sclerosis in Europe

7. Surgical consensus guidelines on sentinel node biopsy (SNB) in patients with oral cancer

8. Analgesic use — prevalence, biomonitoring and endocrine and reproductive effects

9. Unsupervised High-Dimensional Analysis Aligns Dendritic Cells across Tissues and Species

10. Fate of manuscripts rejected by Intensive Care Medicine from 2013 to 2016: a follow-up analysis

11. De novo mutations in MSL3 cause an X-linked syndrome marked by impaired histone H4 lysine 16 acetylation

12. Screening for heart transplantation and left ventricular assist system: results from the ScrEEning for advanced Heart Failure treatment (SEE-HF) study

13. JASPAR 2018: update of the open-access database of transcription factor binding profiles and its web framework

14. Year in review in Intensive Care Medicine 2014: I. Cardiac dysfunction and cardiac arrest, ultrasound, neurocritical care, ICU-acquired weakness, nutrition, acute kidney injury, and miscellaneous

15. An integrated expression atlas of miRNAs and their promoters in human and mouse

16. Delineation of the 3p14.1p13 microdeletion associated with syndromic distal limb contractures

17. A map of direct TF–DNA interactions in the human genome

18. SCRIB and PUF60 Are Primary Drivers of the Multisystemic Phenotypes of the 8q24.3 Copy-Number Variant

19. Cutting Edge: Expression of XCR1 Defines Mouse Lymphoid-Tissue Resident and Migratory Dendritic Cells of the CD8α+ Type

20. Bi-directional routing of DNA mismatch repair protein human exonuclease 1 to replication foci and DNA double strand breaks

21. Supraclavicular recurrence after early breast cancer: a curable condition?

22. Assessing prognosis and optimizing treatment in patients with postchemotherapy viable nonseminomatous germ-cell tumors (NSGCT): results of the sCR2 international study

23. European consensus conference on diagnosis and treatment of germ cell cancer: a report of the second meeting of the European Germ Cell Cancer Consensus group (EGCCCG): part I

24. The DESCARTES-Nantes survey of kidney transplant recipients displaying clinical operational tolerance identifies 35 new tolerant patients and 34 almost tolerant patients

25. Gonadotropin-releasing hormone neurones innervate kisspeptin neurones in the female mouse brain

26. Resveratrol inhibits steroidogenesis in human fetal adrenocortical cells at the end of first trimester

27. A role for glutamate transporters in the regulation of insulin secretion

28. On the origin and diffusion of BRCA1 c.5266dupC (5382insC) in European populations

29. A European consensus report on blood cell identification: terminology utilized and morphological diagnosis concordance among 28 experts from 17 countries within the European LeukemiaNet network WP10, on behalf of the ELN Morphology Faculty

30. Many putative endocrine disruptors inhibit prostaglandin synthesis

31. Reporting methods of blinding in randomized trials assessing nonpharmacological treatments

32. Primary lymphoma of the lacrimal sac: an EORTC ophthalmic oncology task force study

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