59 results match your criteria: "United Kingdom J.-C.B.; and UMR 894 INSERM-Universite Paris 5[Affiliation]"
Genes from a translational analysis support a multifactorial nature of white matter hyperintensities.
Stroke
February 2015
From the Centre for Cognitive Ageing and Cognitive Epidemiology (L.M.L., M.V.H., S.M.M., M.E.B., J.S., I.J.D., J.M.W.), Division of Neuroimaging Sciences, Brain Research Imaging Centre, (M.V.H., S.M.M., M.E.B., J.M.W.) and Academic Neuropathology (C.S.), Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, Medical Genetics Section, University of Edinburgh Centre for Genomics and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom (W.D.H., S.E.H., D.J.P.); Department of Bioengineering, Imperial College London, London, United Kingdom (E.B.); BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom (M.M., J.M., D.G., A.D.); Department of Biostatistics, Boston University School of Public Health, MA (Q.Y.); The Framingham Heart Study, Boston, MA (Q.Y., S.S.); The Human Genetics Center and Institute of Molecular Medicine, The University of Texas Health Science Center, Houston (M.F.); Departments of Epidemiology, Radiology and Neurology, Erasmus Medical Center, Rotterdam, The Netherlands (M.A.I.); Netherlands Consortium for Healthy Aging, Leiden, The Netherlands (M.A.I.); 12 INSERM U740 (Paris 7 University) and U708 (Bordeaux University), Bordeaux, France (S.D.); Department of Neurology, Lariboisière Hospital, 7 University, DHU Neurovasc Paris Sorbonne, Paris, France (S.D.); University of Versailles Saint-Quentin-en-Yvelines, Versailles, France (S.D.); Department of Neurology, Boston University School of Medicine, MA (S.D., S.S.); Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, MD (L.L.); Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle (J.C.B.); and Clinical Division of Neurogeri
Background And Purpose: White matter hyperintensities (WMH) of presumed vascular origin increase the risk of stroke and dementia. Despite strong WMH heritability, few gene associations have been identified. Relevant experimental models may be informative.
View Article and Find Full Text PDFWhite matter perivascular spaces are related to cortical superficial siderosis in cerebral amyloid angiopathy.
Stroke
October 2014
From the Stroke Research Group, Department of Brain Repair and Rehabilitation, National Hospital for Neurology and Neurosurgery (A.C., D.J.W.), Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery (R.H.J.), and Department of Brain Repair and Rehabilitation (R.H.J.), UCL Institute of Neurology, London, United Kingdom; Department of Neurology, Cliniques Universitaires UCL Saint Luc, Brussels, Belgium (A.P.); Department of Neurology, CHU Dinant Godinne (Y.V., P.L.) and Institute of Neuroscience (Y.V., P.L.), Université Catholique de Louvain, Brussels, Belgium; Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom (J.-C.B.); and UMR 894 INSERM-Université Paris 5, Sorbonne Paris Cité, Paris, France (J.-C.B.).
Background And Purpose: We set out to investigate whether MRI-visible centrum semiovale perivascular spaces (CSO-PVS), a potential biomarker of impaired interstitial fluid drainage in sporadic cerebral amyloid angiopathy, is associated with cortical superficial siderosis (cSS), reflecting recurrent hemorrhage from severe leptomeningeal and superficial cortical vascular amyloid.
Methods: Retrospective multicenter cohort study of possible/probable cerebral amyloid angiopathy according to the Boston criteria. PVS were rated in basal ganglia and CSO (CSO-PVS) on axial T2-weighted sequences, using a validated 4-point visual rating scale and were classified as high (score>2) or low degree (score≤2) for prespecified analyses.
Influence of stroke infarct location on functional outcome measured by the modified rankin scale.
Stroke
June 2014
From the Department of Neurology (B.C., A.G., C.G., G.T.), Department of Computational Neuroscience (N.D.F., M.Z., C.H.), and Department of Neuroradiology (S.S., J.F.), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Radiology (IDI), Girona Biomedical Research Institute (IDIBGI), Hospital Universitari de Girona Dr Josep Trueta, Girona, Spain (S.P., J.P.); Department of Neurology, Hospices Civils de Lyon, Lyon, France (T.-H.C.); Centre de Psychiatrie & Neurosciences, Inserm U894, Centre Hospitalier Sainte Anne, Sorbonne Paris Cité, Paris, France (J.-C.B.); Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom (J.A., J.-C.B.); and Department of Neuroradiology, Aarhus University Hospital and Center of Functionally Integrative Neuroscience/MINDLab, Aarhus University, Aarhus, Denmark (L.O.).
Background And Purpose: In the early days after ischemic stroke, information on structural brain damage from MRI supports prognosis of functional outcome. It is rated widely by the modified Rankin Scale that correlates only moderately with lesion volume. We therefore aimed to elucidate the influence of lesion location from early MRI (days 2-3) on functional outcome after 1 month using voxel-based lesion symptom mapping.
View Article and Find Full Text PDFGenome-wide association study for circulating tissue plasminogen activator levels and functional follow-up implicates endothelial STXBP5 and STX2.
Arterioscler Thromb Vasc Biol
May 2014
From National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA (J.H., A.D.J., C.J.O.); Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD (J.H., A.D.J., C.J.O.); MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland, United Kingdom (J.E.H., V.V., A.F.W., C.H.); The Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY (M.Y., C.J.L.); Departments of Cardiology (S.T., J.W.J.), Gerontology and Geriatrics (S.T., A.J.M.d.C., R.G.J.W.), and Molecular Epidemiology (P.E.S.), Leiden University Medical Center, the Netherlands; Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, the Netherlands (F.W.A.); Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, the Netherlands (F.W.A.); Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, United Kingdom (F.W.A.); Cardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine (M.S.-L., L.F., P.E., A.H.), Karolinska Institutet, Karolinska University Hospital, Solna, Stockholm, Sweden; INSERM UMRS 937, Pierre et Marie Curie University, Paris, France (D.-A.T., V.T., T.O.M., F.C.); ICAN Institute for Cardiometabolism and Nutrion, Paris, France (D.-A.T., V.T., F.C.); Departments of Public Health Sciences (W.M.C., B.B.W., F.C.) and Biochemistry and Molecular Genetics (M.M.S.), Center for Public Health Genomics, University of Virginia, Charlottesville, VA; Departments of Epidemiology (N.L.S., B.M.P., B.M.), Medicine (B.M.P., J.C.B.), and Health Services (B.M.P.), University of Washington, Seattle, WA; Group Health Research Institute, Group Health Cooperative, Seattle, WA (N.L.S., B.M.P.); Seattle Epidemiologic Research and Information Center, VA Office of Research and
Article Synopsis
- Researchers analyzed data from 14 studies involving nearly 27,000 participants to find genetic factors influencing the levels of tissue plasminogen activator (tPA), a key enzyme in blood clot breakdown.
- They identified three significant genetic loci associated with tPA levels: one linked to the STXBP5 gene on chromosome 6, another near the PLAT gene on chromosome 8, and a third related to the STX2 gene on chromosome 12.
- Functional tests showed that silencing STXBP5 reduces tPA release from cells, while silencing STX2 increases it, suggesting these genes play important roles in regulating tPA levels.
Idelalisib and rituximab in relapsed chronic lymphocytic leukemia.
N Engl J Med
March 2014
Weill Cornell Medical College (R.R.F.), Memorial Sloan-Kettering Cancer Center (A.D.Z.), the Department of Medicine, and Columbia University Medical Center (N.L.) - all in New York; U.S. Oncology Research, Springfield, OR (J.P.S.); Stanford University School of Medicine, Stanford (S.E.C.), and Gilead Sciences, Foster City (M.A., D.M.J., L.L.M., D.L., T.M.J., R.D.D.) - both in California; Lombardi Comprehensive Cancer Center, Georgetown University Hospital, Washington, DC (B.D.C.); Fred Hutchinson Cancer Research Center, University of Washington, Seattle (J.M.P.); St. James's University Hospital, Leeds (P.H.), and Royal Liverpool University Hospital, Liverpool (A.R.P.) - both in the United Kingdom; Hofstra North Shore-LIJ School of Medicine, New Hyde Park, New York (J.C.B.); University of California San Diego, Moores Cancer Center, La Jolla (T.J.K.); Sarah Cannon Research Institute, Nashville (I.F.); Universita Vita-Salute San Raffaele, Instituto Scientifico San Raffaele, Milan (P.G.); David Geffen School of Medicine, University of California Los Angeles, Los Angeles (H.E.); Florida Cancer Specialists, Englewood (T.E.); Centre Hospitalier Lyon-Sud, Pierre-Bénite, France (B.C.); Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago (S.M.); University of Ulm, Ulm (S.S.), and University of Cologne, Cologne (P.C., M.H.) - both in Germany; and University of Texas M.D. Anderson Cancer Center, Houston (S.M.O.).
Background: Patients with relapsed chronic lymphocytic leukemia (CLL) who have clinically significant coexisting medical conditions are less able to undergo standard chemotherapy. Effective therapies with acceptable side-effect profiles are needed for this patient population.
Methods: In this multicenter, randomized, double-blind, placebo-controlled, phase 3 study, we assessed the efficacy and safety of idelalisib, an oral inhibitor of the delta isoform of phosphatidylinositol 3-kinase, in combination with rituximab versus rituximab plus placebo.
Multilocus genetic risk score associates with ischemic stroke in case-control and prospective cohort studies.
Stroke
February 2014
From the Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany (R.M., M.D.); Stroke and Dementia Research Centre, St George's University of London, London, United Kingdom (S.B., H.S.M.); Laboratory of Neurogenetics (M.A.N.) and Laboratory of Epidemiology and Population Sciences (L.J.L.), National Institute on Aging, National Institutes of Health, Bethesda, MD; Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health (E.G.H.) and Center for Translational Neuroscience and Mental Health Research (C.L.), University of Newcastle, Callaghan, NSW, Australia; Center for Bioinformatics, Biomarker Discovery and Information-Based Medicine, Hunter Medical Research Institute, New Lambton, NSW, Australia (E.G.H.); Department of Neurology, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA (W.J.D., J.R.); Department of Medicine, University of Maryland School of Medicine, Baltimore, MD (Y.-C.C., B.D.M.); Department of Veterans Affairs and Veterans Affairs Medical Center, Baltimore Geriatric Research, Education, and Clinical Center (GRECC), Baltimore, MD (Y.-C.C., B.D.M.); Department of Epidemiology (C.A.I.-V., B.F.J.V., M.A.I., C.M.v.D.), Department of Neurology (C.A.I.-V., M.A.I.), and Department of Radiology (B.F.J.V., M.A.I.), Erasmus MC University Medical Center, Rotterdam, The Netherlands; Cardiovascular Health Research Unit (J.C.B., B.M.P.), Department of Medicine (J.C.B., B.M.P.), Department of Epidemiology (B.M.P.), and Department of Health Services (B.M.P.), University of Washington, Seattle, WA; Institute for Molecular Medicine (A.Y.J., M.F.) and Human Genetics Center (M.F.), University of Texas Health Science Center at Houston; Department of Neurology, Boston University School of Medicine, Boston, MA (A.L.d.S., S.S.); Department of Biostatistics, Boston University School of Public Health, Boston, MA (A.L.d.S.); The National Heart, Lung and
Background And Purpose: Genome-wide association studies have revealed multiple common variants associated with known risk factors for ischemic stroke (IS). However, their aggregate effect on risk is uncertain. We aimed to generate a multilocus genetic risk score (GRS) for IS based on genome-wide association studies data from clinical-based samples and to establish its external validity in prospective population-based cohorts.
View Article and Find Full Text PDFA molecular marker of artemisinin-resistant Plasmodium falciparum malaria.
Nature
January 2014
1] Institut Pasteur du Cambodge, Malaria Molecular Epidemiology Unit, Phnom Penh, Cambodia [2].
Plasmodium falciparum resistance to artemisinin derivatives in southeast Asia threatens malaria control and elimination activities worldwide. To monitor the spread of artemisinin resistance, a molecular marker is urgently needed. Here, using whole-genome sequencing of an artemisinin-resistant parasite line from Africa and clinical parasite isolates from Cambodia, we associate mutations in the PF3D7_1343700 kelch propeller domain ('K13-propeller') with artemisinin resistance in vitro and in vivo.
View Article and Find Full Text PDFShared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants.
Stroke
January 2014
From the Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany (M.D., R. Malik); Munich Cluster for Systems Neurology (SyNergy), Munich, Germany (M.D.); Institut für Medizinische Biometrie und Statistik (I.R.K.), and Institut für integrative und experimentelle Genomik (J.E.), Universität zu Lübeck, Lübeck, Germany; Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Germany (I.R.K.); Department of Neurology and Center for Human Genetic Research (J.R.), and Cardiology Division (C.J.O.D.), Massachusetts General Hospital, Boston; Harvard Medical School, Boston, MA (J.R.); Program in Medical and Population Genetics (J.R.), and Program in Medical and Population Genetics (S.K.), Broad Institute of Harvard and MIT, Cambridge, MA; Clinical Trial Service Unit and Epidemiological Studies Unit (R.C., J.C.H.), Wellcome Trust Centre for Human Genetics (H.W., M. Farrall), Department of Cardiovascular Medicine (M. Farrall), and Stroke Prevention Research Unit, Nuffield Department of Clinical Neuroscience (P.M.R.), John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom; deCODE Genetics, Reykjavik, Iceland (S.G., G.T., U.T., K.S.); Department of Medicine, University of Maryland School of Medicine, Baltimore (B.D.M.); Department of Medicine, Stanford University School of Medicine, Stanford, CA (T.L.A.); Center for Translational Neuroscience and Mental Health Research, University of Newcastle, New South Wales, Australia (C.L.); Hunter Medical Research Institute, New South Wales, Australia (C.L.); National Heart, Lung and Blood Institute and NHLBI's Framingham Heart Study, MA (C.J.O.D., S.S.); University of Texas Health Science Center at Houston (M. Fornage); Cardiovascular Health Research Unit, Department of Epidemiology (B.M.P.), Department of Medicine (B.M.P.), Department of Health Services (B.M.P.), and Cardiovascular Health Research Unit, Department of Medicine (J.C.B.), University
Background And Purpose: Ischemic stroke (IS) and coronary artery disease (CAD) share several risk factors and each has a substantial heritability. We conducted a genome-wide analysis to evaluate the extent of shared genetic determination of the two diseases.
Methods: Genome-wide association data were obtained from the METASTROKE, Coronary Artery Disease Genome-wide Replication and Meta-analysis (CARDIoGRAM), and Coronary Artery Disease (C4D) Genetics consortia.
Impact of physiologically based pharmacokinetic modeling and simulation in drug development.
Drug Metab Dispos
December 2013
Department of Drug Metabolism and Pharmacokinetics, GlaxoSmithKline, Ware, Hertfordshire, United Kingdom (C.E.S., A.H.P., J.C.B.), King of Prussia, Pennsylvania (T.T., G.T.), and Research Triangle Park, North Carolina (G.T.G.).
Physiologically based pharmacokinetic modeling and simulation can be used to predict the pharmacokinetics of drugs in human populations and to explore the effects of varying physiologic parameters that result from aging, ethnicity, or disease. In addition, the effects of concomitant medications on drug exposure can be investigated; prediction of the magnitude of drug interactions can impact regulatory communications or internal decision-making regarding the requirement for a clinical drug interaction study. Modeling and simulation can also help to inform the design and timings of clinical drug interaction studies, resulting in more efficient use of limited resources and improved planning in addition to promoting mechanistic understanding of observed drug interactions.
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