Author: "Frank Martiniuk" / Topic: medicine.disease - Searchworks@Jio Institute Digital Library Search Results

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39 results on '"Frank Martiniuk"'

1. Association of Adenosine Deaminase (ADA) +22 G->A (rs73598374) Genotype in Latino Adult Obese

Author: Melissa Watt, Kyle Yocum, Fritz Francois, Alexander H. Wong, Gilbert Smolenski, Frank Martiniuk, Kahmun Lo, Kam-Meng Tchou-Wong, Angela Chen, Arthur Nadas, Ian Fagan, Chelsea O’Koren, Anna Barangan, and Esme Cribb
Subjects: medicine.medical_specialty, Type 1 diabetes, biology, business.industry, medicine.disease, Adenosine, Obesity, Endocrinology, Adenosine deaminase, Internal medicine, Genotype, medicine, biology.protein, SNP, Allele, business, Body mass index, medicine.drug
Abstract: Obesity is a health burden that currently affects over 13% of the global adult population, consisting of over 650 million adults. Obesity is evaluated based on a body mass index (BMI) scale, which is calculated as weight in kilograms divided by the square of height in meters. Adults with a BMI greater than 30kg/m2 are considered to be obese while adults with a BMI greater than 40kg/m2 are considered morbidly obese. Adenosine deaminase (ADA) is a polymorphic enzyme that plays an important role in both immune functions and the regulation of intracellular and extracellular concentrations of adenosine. Three alleles of the ADA gene (ADA1, ADA2, ADA6) are associated with type 1 diabetes mellitus (DM1). ADA2/6 may increase susceptibility to DM1 in females. Given the evidence linking obesity with DM1, we wanted to determine whether a correlation exists between ADA2 allele and obesity. The ADA2 (+22 G->A, rs73598374) SNP changes the amino acid at position 8 from aspartic acid (Asp8)(D) to asparagine (Asn)(N). In this study, we present significant evidence of association between the ADA2 allele and obesity or BMIs greater than 25 in the Latino adult but not in the Caucasian population and therefore, may be a risk for obesity and its complications such as DM1.
Published: 2021
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2. Preclinical studies for plant-based oral enzyme replacement therapy (Oral-ERT) in Pompe disease knockout mice with transgenic tobacco seeds expressing human GAA (tobrhGAA)

Author: Peter Meinke, Justin Martiniuk, David Reimer, Nancy Rossi, Ruby Gupta, Benedikt Schoser, Angelo Kambitsis, Adra Mack, Mariel Nigro, Sussan Saleh, John Arvanitopoulos, Leslie Sheppard Bird, Shoreh Miller, Elena Arvanitopoulos, Feng Wu, Gregory Voronin, Kam-Meng Tchou-Wong, and Frank Martiniuk
Subjects: Glycogen, business.industry, Transgene, Genetic enhancement, Enzyme replacement therapy, Pharmacology, medicine.disease, chemistry.chemical_compound, chemistry, Oral administration, Glycogen storage disease type II, Knockout mouse, medicine, business, Alglucosidase alfa, medicine.drug
Abstract: Genetic deficiency of acid α-glucosidase (GAA) results in glycogen storage disease type II (GSDII) or Pompe disease (PD) encompassing at least four clinical subtypes of varying severity (infantile; childhood, juvenile and late onset). Our objective is to develop an innovative and affordable approach for enzyme replacement therapy (ERT) via oral administration (Oral-ERT) to maintain a sustained, therapeutic level of enzyme on a daily basis to improve efficacy of treatment and quality of life for people living with Pompe disease. A consensus at a 2019 US Acid Maltase Deficiency (AMDA) conference suggested that a multi-pronged approach including gene therapy, diet, exercise, etc. must be evaluated for a successful treatment of Pompe disease. Tobacco seeds contain the metabolic machinery that is more compatible with mammalian glycosylation-phosphorylation and processing. Previously, we have shown that a lysate from transgenic tobacco seeds expressing human GAA (tobrhGAA) was enzymatically active and can correct enzyme deficiency in cultured PD cells and in adult lymphocytes of Pompe patients and in vivo in disease-relevant tissues in GAA knockout (KO) mice when administered IP.We have extended these pre-clinical studies in PD knockout (KO) mice with ground tobrhGAA seeds that supports proof-of-concept for Oral-ERT for future clinical trials. Briefly in GAA KO mice, Oral-ERT with ground tobrhGAA seeds showed significant reversal of fore-limb and hind-limb muscle weakness, increased motor coordination/balance/strength and mobility, improved spontaneous learning, increased GAA baseline activity in tissues, reduced glycogen in tissues and negible serum titers to GAA. Pharmacokinetics showed maximum serum GAA concentration (Cs) at 8-10 hr and peak urine excretion at 10-12 hr. The tobrhGAA was taken up in PD fibroblast, lymphoid and myoblast cells. Enzyme kinetics compared favorably or superior to placental hGAA, plus alglucosidase alfa or other rhGAAs for Km, Vmax, pH optima, thermal heat stability and IC50 for inhibitors. The tobrhGAA in seeds was extremely stable stored for 15 years at room temperature. NGS-genome sequencing of the tobrhGAA and wild-type plants and RNA expression profiles was performed and will be posted on our website. Thus, Oral-ERT with ground tobrhGAA seeds is an innovative approach that overcomes some of the challenges of alglucosidase alfa-ERT and provides a more effective, safe and significantly less expensive treatment.
Published: 2021
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3. Leprosy as a model to understand cancer immunosurveillance and T cell anergy

Author: Tina Rendini, Frank Martiniuk, Andrew J. Park, and William R. Levis
Subjects: 0301 basic medicine, T-Lymphocytes, T cell, medicine.medical_treatment, Immunology, Tuberculoid leprosy, Lymphocyte Activation, Models, Biological, 03 medical and health sciences, 0302 clinical medicine, Cancer immunotherapy, Leprosy, Neoplasms, medicine, Animals, Humans, Immunology and Allergy, Mycobacterium leprae, Immunity, Cellular, Lepromatous leprosy, biology, Cell Biology, medicine.disease, biology.organism_classification, Immunosurveillance, 030104 developmental biology, medicine.anatomical_structure, Immunoediting, 030220 oncology & carcinogenesis, Nivolumab
Abstract: Leprosy is a disease caused by Mycobacterium leprae that presents on a spectrum of both clinical manifestations and T cell response. On one end of this spectrum, tuberculoid leprosy is a well-controlled disease, characterized by a cell-mediated immunity and immunosurveillance. On the opposite end of the spectrum, lepromatous leprosy is characterized by M. leprae proliferation and T cell anergy. Similar to progressive tumor cells, M. leprae escapes immunosurveillance in more severe forms of leprosy. The mechanisms by which M. leprae is able to evade the host immune response involve many, including the alterations of lipid droplets, microRNA, and Schwann cells, and involve the regulation of immune regulators, such as the negative checkpoint regulators CTLA-4, programmed death 1, and V-domain Ig suppressor of T cell activation—important targets in today’s cancer immunotherapies. The means by which tumor cells become able to escape immunosurveillance through negative checkpoint regulators are evidenced by the successes of treatments, such as nivolumab and ipilimumab. Many parallels can be drawn between the immune responses seen in leprosy and cancer. Therefore, the understanding of how M. leprae encourages immune escape during proliferative disease states has potential to add to our understanding of cancer immunotherapy.
Published: 2016
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4. Increasing Virulence in Leprosy Indicated by Global Mycobacterium spp

Author: Tina Rendini, Frank Martiniuk, and William R Levis
Subjects: Letter, Epidemiology, Yersinia pestis, Antitubercular Agents, lcsh:Medicine, Drug resistance, medicine.disease_cause, Global Health, Communicable Diseases, Emerging, Disease Outbreaks, 0302 clinical medicine, fleas, leptospirosis, Public Health Surveillance, Mycobacterium lepromatosis, 030212 general & internal medicine, bacteria, Mycobacterium leprae, Lucio's phenomenon, Singapore, biology, Virulence, Zoonosis, transmission, lice, Infectious Diseases, Geography, Democratic Republic of the Congo, Leprosy, pneumonic plague, multidrug therapy, Lucio’s phenomenon, Microbiology (medical), China, autochthonous, 030231 tropical medicine, India, leprae, lcsh:Infectious and parasitic diseases, Microbiology, 03 medical and health sciences, Drug Resistance, Bacterial, medicine, Madagascar, Humans, lcsh:RC109-216, armadillo, Letters to the Editor, leprosy bonita, M. leprae, Plague, Increasing Virulence in Leprosy Indicated by Global Mycobacterium spp, lcsh:R, zoonosis, ectoparasite, medicine.disease, biology.organism_classification, United States, Africa, Investigation of Pneumonic Plague, Madagascar, Mycobacterium
Published: 2017

5. Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

Author: John Hardy, Nick C. Fox, Lena Lilius, Christine Van Broeckhoven, Mindy J. Katz, Carlos Cruchaga, Joshua W. Miller, Carol Brayne, Letizia Concari, Christopher Shaw, Minerva M. Carrasquillo, Richard Mayeux, Anne Boland, Charles DeCarli, Helena C. Chui, Laura B. Cantwell, Yoland Aladro Benito, Chuang Kuo Wu, Elaine R. Peskind, Andrew McDavid, M. Ilyas Kamboh, Amanda Smith, Pascual Sánchez-Juan, Jean-François Deleuze, Jayanadra J. Himali, Thomas H. Mosley, Thomas J. Montine, Chuanhai Cao, Andreas J. Forstner, Thomas G. Beach, Robert Barber, Miquel Aguilar, Liming Qu, Jerome I. Rotter, Matthew J. Huentelman, Christiane Reitz, Christopher J. O'Donnell, Steven G. Younkin, Bradley T. Hyman, Bruce L. Miller, Rachelle S. Doody, Eric B. Larson, Ronald L. Hamilton, Todd E. Golde, Steven E. Arnold, Melissa E. Garcia, Rachel Raybould, Lena Kilander, Mark A. Sager, Kevin Morgan, Kathryn L. Lunetta, William Perry, Joseph D. Buxbaum, Craig S. Atwood, Thomas D. Bird, Michael Conlon O'Donovan, Robert Olaso, Juan Fortea, Susanne Moebus, Lisa L. Barnes, Rachel Marshall, Huntington Potter, Mercè Boada, Shahzad Ahmad, Paolo Caffarra, Daniel C. Marson, Jonathan L. Haines, Perrie M. Adams, John M Olichney, Lars Lannfelt, Stefanie Heilmann-Heimbach, Markus M. Nöthen, Shubhabrata Mukherjee, John Malamon, Xue Wang, Christopher S. Carlson, Karen Ritchie, Roger N. Rosenberg, Paul K. Crane, Alexa S. Beiser, Céline Bellenguez, Robert C. Green, Maria Urbano, Petra Proitsi, John Powell, Elisa Majounie, Ammar Al-Chalabi, Hakon Hakonarson, Yogen Patel, Martin Scherer, Julie Williams, Richard B. Lipton, Vincent Dermecourt, Adam L. Boxer, Gerard D. Schellenberg, David G. Clark, Anita L. DeStefano, Joel H. Kramer, Victoria Alvarez, Nandini Badarinarayan, Oscar L. Lopez, Chris Corcoran, Ubaldo Bonuccelli, Donald R. Royall, James Bowen, Monica Diez Fairen, Tricia A. Thornton-Wells, Nilufer Ertekin-Taner, Florence Pasquier, Martin Ingelsson, Yi Zhao, John R. Gilbert, Valentina Escott-Price, Amanda B. Kuzma, Fabienne Garzia, Reinhard Heun, Otto Valladares, Andrew J. Saykin, Sara Ortega-Cubero, Liana G. Apostolova, Henry L. Paulson, John K Kauwe, Imelda Barber, Carolina Ceballos Diaz, Douglas Galasko, M. Arfan Ikram, Lluís Tárraga, Carlo Caltagirone, Joan S. Reisch, Wolfgang Maier, Bruno Vellas, Rebecca Sims, Angela Hodges, Matthew P. Frosch, Isabel Henández, Annakaisa Haapasalo, Thor Aspelund, Håkan Thonberg, Aimee Pierce, Roger L. Albin, Wayne W. Poon, Rebecca Sussams, Amy Braddel, Ranjan Duara, Albert V. Smith, Kirk C. Wilhelmsen, Gianfranco Spalletta, Simon Lovestone, Peter Passmore, Ana Frank-García, Cynthia M. Carlsson, Jade Chapman, Nathan D. Price, Philip L. De Jager, John M. Ringman, Seung Hoan Choi, Nicola Denning, Michael John Owen, Clinton T. Baldwin, Amalia C. Bruni, Denis A. Evans, Rudolph E. Tanzi, Dominique Campion, Laura Fratiglioni, Alberto Lleó, Per Hoffmann, Carole Dufouil, Charlotte Forsell, Alun Meggy, Charlene Thomas, Robert S. Stern, James B. Leverenz, Tatiana Foroud, William W. Seeley, James J. Lah, Brian A. Lawlor, Kenneth B. Fallon, Matthias Riemenschneider, Ryan M. Huebinger, Regina M. Carney, Clinton B. Wright, Didier Hannequin, Deborah Blacker, Anne Kinhult-Ståhlbom, Ekaterina Rogaeva, Andrew P. Lieberman, Bernardino Ghetti, Linda J. Van Eldik, Bernadette McGuinness, Thomas Fairchild, Margaret A. Pericak-Vance, Ashok Raj, Reinhold Schmidt, Ronald C. Petersen, Harald Hampel, María J. Bullido, Steven L. Carroll, Maria Candida Deniz Naranjo, Kathleen A. Welsh-Bohmer, Myriam Fornage, Joseph F. Quinn, Caroline Graff, Claudia L. Satizabal, Patrice L. Whitehead, David Wallon, Christopher Medway, Lindsay A. Farrer, Vilmundur Gudnason, Peter St George-Hyslop, Pau Pastor, Frank Jessen, Erin L. Abner, Johanna Jakobsdottir, Hieab H.H. Adams, Roberta Cecchetti, Walter A. Kukull, Thomas S. Wingo, Michelle K. Lupton, Valur Emilsson, Susan M. McCurry, Simon Mead, Hilkka Soininen, Sandra Weintraub, Amy Gerrish, Lindy E. Harrell, Lina Keller, Jean-Charles Lambert, Denise Harold, Stephen Todd, Wei Gu, Maura Gallo, Najaf Amin, Lenore J. Launer, Eleonora Sacchinelli, Mikko Hiltunen, Cécile Dulary, Eliecer Coto, Xueqiu Jian, Nathalie Fievet, Patrizia Mecocci, Sarah Taylor, Eric Boerwinkle, Maria Serpente, Ronald G. Munger, Ina Giegling, Carlo Masullo, Aoibhinn Lynch, Eliezer Masliah, Anne M. Koivisto, Chang En Yu, Qiong Yang, Benedetta Nacmias, Wayne C. McCormick, Kristelle Brown, Alessio Squassina, Deborah C. Mash, Brian W. Kunkle, Makrina Daniilidou, Alison Goate, David Carrell, Kara L. Hamilton-Nelson, Sandra Barral, Vincent Chouraki, Kristel Sleegers, Frank J. Wolters, Joseph E. Parisi, Iwona Kłoszewska, Ronald C. Kim, Sonia Moreno-Grau, Marina Arcaro, Carmen Muñoz Fernadez, Vernon S. Pankratz, Duane Beekly, Sabrina Pichler, Gislain Septier, Delphine Bacq, Amanda J. Myers, Adam C. Naj, Frank Martiniuk, Sudha Seshadri, Badri N. Vardarajan, Joshua A. Sonnen, M.-Marsel Mesulam, Howard J. Rosen, James T. Becker, Chiara Fenoglio, Ge Li, Alberto Pilotto, Mary Sano, Olivier Hanon, Honghuang Lin, Jean Paul G. Vonsattel, W. T. Longstreth, Daniela Galimberti, David C. Rubinsztein, RoseMarie Brundin, Vilmantas Giedraitis, Christine M. Hulette, Peter Holmans, Martin Dichgans, Maria Vronskaya, Céline Derbois, Michelangelo Mancuso, Constantine G. Lyketsos, Christophe Tzourio, Jacques Epelbaum, Raffaele Maletta, Mariet Allen, Hong-Dong Li, James R. Burke, Rik Vandenberghe, David G. Mann, Bruce M. Psaty, Lawrence S. Honig, Beth A. Dombroski, Erik D. Roberson, Cornelia M. van Duijn, Benjamin Grenier-Boley, Seppo Helisalmi, Jean-François Dartigues, Russell H. Swerdlow, Paola Bossù, Ashley R. Winslow, Elio Scarpini, Lesley Jones, Sebastien Engelborghs, John Q. Trojanowski, Jeffrey Kaye, Jenny Lord, Chiara Cupidi, Janet A. Johnston, Dan Rujescu, Feroze Golamaully, Anne Braae, Rafael Blesa, L. Adrienne Cupples, Dennis W. Dickson, Gail P. Jarvik, David W. Fardo, David H. Cribbs, Michael Gill, Jose Bras, Allan I. Levey, Jennifer Williamson, Rhodri Thomas, John C. Morris, Lei Yu, Debby W. Tsuang, Annette M. Hartmann, John H. Growdon, John Collinge, Claudine Berr, Fernando Rivadeneira, Oliver Peters, Albert Hofman, Frank M. LaFerla, Vivianna M. Van Deerlin, James Uphill, David A. Bennett, Onofre Combarros, Gudny Eiriksdottir, Jeremy D. Burgess, Melanie L. Dunstan, Elizabeth Crocco, Keeley J. Brookes, Robert R. Graham, Lon S. Schneider, Eden R. Martin, Matt Hill, Neill R. Graff-Radford, Joseph T. Hughes, Vincenzo Solfrizzi, Taniesha Morgan, Antonio Ciaramella, Bruno Dubois, Juan C. Troncoso, Paolo Bosco, Jordi Clarimón, Daniel H. Geschwind, Virginia Boccardi, Barry Reisberg, Timothy W. Behrens, Annette L. Fitzpatrick, Salvatore Spina, Alexis Brice, Eileen H. Bigio, Marla Gearing, Jeffrey M. Burns, Carol A. Miller, Marilyn S. Albert, Sven J. van der Lee, Sandro Sorbi, C. Dirk Keene, Daniel Levy, Antonio Daniele, Eric M. Reiman, Paramita Chakrabarty, Oscar Sotolongo-Grau, Helena Schmidt, Francesco Panza, Murray A. Raskind, Rita Guerreiro, Gyungah Jun, Anna Karydas, Markus Leber, Harry V. Vinters, Cory C. Funk, Charles C. White, Jill R. Murrell, Sid E. O'Bryant, Nigel J. Cairns, Josée Dupuis, Ann C. McKee, Julie A. Schneider, Megan L. Grove, Malcolm B. Dick, Bradley F. Boeve, Jennifer A. Brody, Sanjay Asthana, Agustín Ruiz, Stefan Herms, Yuning Chen, David Craig, Neil W. Kowall, Maria Donata Orfei, JoAnn T. Tschanz, Florentino Sanchez Garcia, Manuel Mayhaus, Alfredo Ramirez, James Turton, André G. Uitterlinden, Davide Seripa, Lee-Way Jin, Kelley Faber, Maria C. Norton, Shuo Li, Steven H. Ferris, Steffi G. Riedel-Heller, Joshua C. Bis, Li-San Wang, Johannes Kornhuber, Peter Paul De Deyn, Martin R. Farlow, Randall L. Woltjer, Gary W. Beecham, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Hospital of the University of Pennsylvania (HUP), Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Icelandic Heart Association [Kopavogur, Iceland] (IHA), John P. Hussman Institute for Human Genomics [Miami, FL, USA], University of Miami [Coral Gables], Institut de Biologie François JACOB (JACOB), 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), Department of Medicine, University of Washington [Seattle], Dr. John T. Macdonald Foundation [Miami, FL, USA] (Department of Human Genetics), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Department of Genomics [Bonn, Germany] (Institute of Human Genetics), University of Bonn-Institute of Human Genetics [Bonn, Germany], Department of Molecular Genetics, Institut Català de Neurociències Aplicades [Barcelona, Spain], Well Advanced Solutions, Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], The University of Texas Health Science Center at Houston (UTHealth), Columbia University [New York], University of Eastern Finland, Life & Brain Center - Department of Genomics, Rheinische Friedrich-Wilhelms-Universität Bonn, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), John P. Hussman Institute for Human Genomics, Neurobiologie de la Croissance et de la Senescence, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Emmy Noether Project (SFB 833), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Boston University [Boston] (BU), Department of Genomics, Institute for Systems Biology [Seattle, WA, USA], Universitätsklinikum Bonn (UKB), Centre of Excellence for Robotic Vision [Canberra], Australian Research Council [Canberra] (ARC), Neuroscience and Mental Health Research Institute [Cardiff, UK] (School of Medicine), Boston University School of Medicine (BUSM), Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, University of Pennsylvania [Philadelphia], Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Department of Epidemiology and Biostatistics, ERASMUS, Hospital Universitario Doctor Negrín [Las Palmas de Gran Canaria, Spain], Department of Neurodegenerative Diseases, University of Mississippi Medical Center (UMMC), Pathology and Laboratory Medicine [Philadelphia, PA, USA] (Penn Neurodegeneration Genomics Center), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bioinformatics, GlaxoSmithKline, Aging Research Center [Karolinska Institutet] (ARC ), Stockholm University-Karolinska Institutet [Stockholm], University of Nottingham, UK (UON), University of Texas Health Science Center, Department of Neurobiology, Caring Sciences and Society (NVS), University of Bari Aldo Moro (UNIBA), Ageing Group, Centre for Public Health, Queen's University [Belfast] (QUB), Mayo Clinic [Jacksonville], Maurice Wohl Clinical Neuroscience Institut, King‘s College London, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo] (IRCCS), Università degli Studi di Perugia (UNIPG), Framingham Heart Study, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), CHU Rouen, Normandie Université (NU), Universidad Autonoma de Madrid (UAM), Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), University of Florida [Gainesville] (UF), University of Parma = Università degli studi di Parma [Parme, Italie], Center for Cognitive Disorders AUSL [Parma, Italy], School of Public Health [Boston], Uppsala University, Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Xi'an Jiaotong University (Xjtu), Department of Public health and Caring Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden, Institute of Gerontology and Geriatrics, Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Geriatric Medicine and Metabolic Diseases, Departments of Nuclear Medicine, University Medical Centre Hamburg-Eppendorf [Hamburg, Germany], University of Texas Southwestern Medical Center [Dallas], University of Cologne, Laboratoire d'Etudes et de Recherche en Informatique d'Angers (LERIA), Université d'Angers (UA), Johns Hopkins University (JHU), Universität Leipzig [Leipzig], University of Iceland [Reykjavik], Metacohorts Consortium, Harvard School of Public Health, Catholic University of Rome, Medical University Graz, Baylor College of Medicine (BCM), Baylor University, University of North Texas Health Science Center [Fort Worth], Santa Lucia Foundation (IRCCS), Nextel S.A. [Bilbao], Massachusetts General Hospital [Boston], Department of Pathology and Laboratory Medicine and Indiana Alzheimer disease Center, Indiana University School of Medicine, Indiana University System-Indiana University System, Joint Institute for the Study of the Atmosphere and Ocean (JISAO), Beijing University of Technology, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Saul B. Korey Department of Neurology, Albert Einstein College of Medicine [New York]-Yeshiva University, Utah State University (USU), Fundació per la Recerca Biomèdica i Social Mútua Terrassa [Barcelona, Spain], Hospital Universitario Mutua de Terrassa, Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Department of neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland, Department of neurology, University of Eastern Finland-University Hospital of Kuopio-University of Eastern Finland-University Hospital of Kuopio, Medical University of Łódź (MUL), University of Leicester, MRC Prion Unit, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Milan, Fondazione Istituto di Ricerca e Cura Carattere Scientifico [Rome], Università degli Studi di Roma Tor Vergata [Roma], Saarland University Hospital, Universitat Autònoma de Barcelona (UAB), Regional Neurogenetic Centre [Lamezia Terme, Italy] (CRN - ASP Catanzaro), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Universidade do Porto, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Experimental and Clinical Pharmacology, St. James Hospital and Trinity College [Dublin, Ireland], School of Medicine [Dublin], Trinity College Dublin, University of Sheffield [Sheffield], Lancaster University, University of Michigan [Ann Arbor], University of Michigan System, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, University of Wisconsin-Madison, Rush Alzheimer Disease Center [Chicago, IL, États-Unis], Rush University Medical Center [Chicago], Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), 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]), School of Engineering [Cardiff], Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Northwestern University Feinberg School of Medicine, Mayo Clinic [Rochester], Swedish Medical Center [Seattle, WA, USA], University of California [San Francisco] (UCSF), University of California, Duke University [Durham], University of Kansas Medical Center [Lawrence], Laboratory of Molecular Neuropsychiatry, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Washington University in Saint Louis (WUSTL), University of South Florida [Tampa] (USF), Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Medical University of South Carolina [Charleston] (MUSC), University of Southern California (USC), Los Alamos National Laboratory (LANL), Centre de biologie du développement (CBD), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Neurology Department, University of California, Davis (UCDavis-Neuro), University of California [Davis] (UC Davis), University of California [Irvine] (UCI), Mount Sinai Medical Center, Indiana State University, University of Alabama at Birmingham [ Birmingham] (UAB), University of Kentucky, New York University [New York] (NYU), NYU System (NYU), Department of Medical and Molecular Genetics, Department of Epidemiology and biostatistics, VU University Medical Center [Amsterdam], Emory University [Atlanta, GA], Department of Neurology, University of California-University of California-David Geffen School of Medicine [Los Angeles], Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Department of Medical Genetics, HMNC Brain Health, Alzheimer Disease Research Laboratory, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Oregon Health and Science University [Portland] (OHSU), Cleveland Clinic, Laboratoire d'Informatique, Systèmes, Traitement de l'Information et de la Connaissance (LISTIC), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Department of Psychiatry, School of Medicine-Johns Hopkins University and Johns Hopkins Bayview Medical Center, Douglas Mental Health University Institute [Montréal], McGill University = Université McGill [Montréal, Canada], Department of neurosciences, University of California [San Diego] (UC San Diego), Department of Physics and Astronomy [Fort Worth], Texas Christian University (TCU), Department of Computer Science [University of California, Davis], Indiana University System, Institute for Aging and Alzheimer’s Disease Research [Fort Worth] (IAADR), Department of Laboratory Medicine and Pathology, Mayo Clinic, Institute for Memory Impairments and Neurological Disorders [Irvine], University of Colorado Anschutz [Aurora], Tanz Center Research in Neurodegenerative Diseases [Toronto], University of Toronto, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Keck School of Medicine [Los Angeles], Indiana University [South Bend], Massachusetts General Hospital, Novartis Institutes for Biomedical Research [Cambridge, MA, USA], Departments of Pathology and Laboratory Medicine (Neuropathology) and Neurology, UCLA Medical Center-David Geffen School of Medicine [Los Angeles], University of California-University of California-University of California [Los Angeles] (UCLA), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Institut de Génomique d'Evry (IG), 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)-Université Paris-Saclay, University of Antwerp (UA), Institute Born-Bunge, Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], University of Kuopio, Centre Mémoire de Ressources et de Recherche [Lille-Bailleul] (CMRR), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Roger Salengro [Lille], Laboratoire d'Analyse Génomique, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Inserm-U1167, Dpt Gériatrie [CHU Broca], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neuroépidémiologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Epidemiology, University of Washington, School of Medicine [Los Angeles], Albert Einstein College of Medicine [New York], IdiPAZ - Instituto de Investigación La Paz [Madrid, Spain], Instituto de Física Teórica UAM/CSIC (IFT), Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Department of Internal Medicine, University of Central Asturias [Oviedo, Spain], Human Genome Sequencing Center, Baylor College of Medicine, Baylor University-Baylor University, Department of Epidemiology, Erasmus Medical Centre, Translational Genomics Research Institute [Phoenix, AZ, USA], University of Arizona, Banner Alzheimer's Institute [Phoenix, AZ, États-Unis], University of Texas Health Science Center at San Antonio [San Antonio], Mount Sinai School of Medicine, Department of Psychiatry-Icahn School of Medicine at Mount Sinai [New York] (MSSM), Department. of Neurological Sciences, University of Milan, IRCCS Ospedale Maggiore Policlinico, Centre for Research in Neurodegenerative Diseases, VA Puget Sound Health Care System/GRECC [Seattle, WA, USA], University of Pisa - Università di Pisa, Pfizer Worldwide Research and Development [Cambridge, MA, USA], Università cattolica del Sacro Cuore [Piacenza e Cremona] (Unicatt), Texas Tech University Health Sciences Center, Texas Tech University [Lubbock] (TTU), Saarland University [Saarbrücken], University of Bonn, Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Cambridge Institute for Medical Research (CIMR), Department of Molecular Neurosciences, Institute of Neurology, UCL, Institute of Psychiatry, Institute of psychiatry, University of British Columbia (UBC), the Clinical Neuroscience Research Group, University of Manchester [Manchester]-Greater Manchester Neurosciences Centre, Aristotle University of Thessaloniki, Memory and Dementia Centre, 3rd Department of Neurology, G. Pa, University of Barcelona, University of Southampton, Department of Psychiatry [Oxford] (POWIC), University of Oxford [Oxford]-The Warneford Hospital, School of Psychology [Cardiff University], Department of Medical Sciences, UCL, Institute of Neurology [London], Washington University School of Medicine, Netherlands Genomics Initiative, Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), School of Medecine, Center for Translational and Computational Neuroimmunology [New York, NY, États-Unis] (CTCN), Department of Neurology [New York, NY, États-Unis], Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York]-Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York], School of Life Sciences, Department of Neuroscience, Mayo Clinic Jacksonville, Icelandic Heart Association, Heart Preventive Clinic and Research Institute, Klinik für Psychiatrie, Martin-Luther-University Halle-Wittenberg, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Clínica Universidad de Navarra [Pamplona], Neurodegenerative Brain Diseases Group, VIB, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University-Medical Research Council, Brigham Young University (BYU), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, The Gertrude H Sergivesky Center, Columbia University College of Physicians and Surgeons, Genetic Epidemiology Unit, Section of Clinical and Molecular Neurogenetics, Universität zu Lübeck [Lübeck], University of Pennsylvania - Department of Pathology & Laboratory Medecine, Framingham Heart Study [Framingham, MA, USA], ANR-10-IAHU-0006,IHU-A-ICM,Institut de Neurosciences Translationnelles de Paris(2010), European Project: 29845,LSH-ACC-MENTOR, University of Pennsylvania-University of Pennsylvania, Universität Bonn = University of Bonn-Institute of Human Genetics [Bonn, Germany], Universität Leipzig-Universität Leipzig, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), University of Pennsylvania, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Università degli Studi di Perugia = University of Perugia (UNIPG), Universidad Autónoma de Madrid (UAM), Università degli studi di Parma = University of Parma (UNIPR), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Universität Leipzig, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Yeshiva University- Albert Einstein College of Medicine [New York], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Università degli Studi di Milano = University of Milan (UNIMI), Saarland University Hospital (UKS), Università degli Studi di Firenze = University of Florence (UniFI), Universidade do Porto = University of Porto, University of California (UC)-University of California (UC), University of California [San Francisco] (UC San Francisco), University of California (UC), University of Kansas Medical Center [Kansas City, KS, USA], Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), University of California [Irvine] (UC Irvine), University of Kentucky (UK), University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles], Department of Computer Science [Univ California Davis] (CS - UC Davis), University of California (UC)-University of California (UC)-University of California [Los Angeles] (UCLA), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Groupe de recherche clinique Alzheimer Precision Medicine (GRC 21 - APM), Sorbonne Université (SU), Universidad Autónoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), University of Texas Health Science Center at San Antonio [San Antonio, Tx, USA], Universität Bonn = University of Bonn, University of Oxford-The Warneford Hospital, Medical Research Council-Cardiff University, Universität zu Lübeck = University of Lübeck [Lübeck], Epidemiology, Neurology, Gastroenterology & Hepatology, Internal Medicine, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Eberhard Karls Universität Tübingen, IRCCS 'Casa Sollievo della Sofferenza', Centro de Investigación Biomédica en Red para Enfermedades Neurodegenerativas (Ciberned), University of Florida [Gainesville], University of Parma, Troubles cognitifs dégénératifs et vasculaires (U1171), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-INSERM, Yeshiva University- Albert Einstein College of Medicine, Institut d’Électronique, de Microélectronique et de Nanotechnologie (IEMN) - UMR 8520 (IEMN), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Université Polytechnique Hauts-de-France (UPHF)-Ecole Centrale de Lille-Université Polytechnique Hauts-de-France (UPHF)-Institut supérieur de l'électronique et du numérique (ISEN), Autonomous University of Barcelona (UAB), Università degli Studi di Firenze [Firenze], Universidade do Porto [Porto], 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 (UGA), Washington University in St Louis, University of South Florida (USF), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, McGill University, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique (CNRS), Neuropsychiatrie : recherche épidémiologique et clinique, Alzheimer Precision Medicine GRC n°21 (APM), CHU Pitié-Salpêtrière [APHP], Albert Einstein College of Medicine, Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Spain] (CSIC), Università Cattolica del S. Cuore - Catholic University of the Sacred Hearth, University of Florence (UNIFI), CIBER de Enfermedades Neurodegenerativas (CIBERNED), Universität zu Lübeck [Lübeck] - University of Lübeck [Lübeck], [ANR-10-IAIHU-06],« Investissements d'avenir » ,Agence nationale de la recherche (ANR), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Icahn School of Medicine at Mount Sinai [New York] (MSSM)-Department of Psychiatry, van der Lee, Sven J [0000-0003-1606-8643], Naj, Adam C [0000-0002-9621-2942], Badarinarayan, Nandini [0000-0002-6944-748X], Chouraki, Vincent [0000-0002-4698-1794], Graham, Robert R [0000-0001-7151-4277], Hoffmann, Per [0000-0002-6573-983X], Smith, Albert V [0000-0003-1942-5845], Satizabal, Claudia L [0000-0002-1115-4430], Brody, Jennifer A [0000-0001-8509-148X], Wolters, Frank J [0000-0003-2226-4050], Lupton, Michelle K [0000-0002-7274-7299], Lin, Honghuang [0000-0003-3043-3942], Adams, Hieab H [0000-0003-3687-2508], Giedraitis, Vilmantas [0000-0003-3423-2021], Pasquier, Florence [0000-0001-9880-9788], Chen, Yuning [0000-0002-7358-7055], Bossù, Paola [0000-0002-1432-0078], Ghetti, Bernardino [0000-0002-1842-8019], Yang, Qiong [0000-0002-3658-1375], Aspelund, Thor [0000-0002-7998-5433], Bullido, María J [0000-0002-6477-1117], Rivadeneira, Fernando [0000-0001-9435-9441], Rubinsztein, David C [0000-0001-5002-5263], Al-Chalabi, Ammar [0000-0002-4924-7712], Tsolaki, Magda [0000-0002-2072-8010], De Jager, Philip L [0000-0002-8057-2505], Dickson, Dennis W [0000-0001-7189-7917], Van Broeckhoven, Christine [0000-0003-0183-7665], Ikram, M Arfan [0000-0003-0372-8585], Amouyel, Philippe [0000-0001-9088-234X], Lambert, Jean-Charles [0000-0003-0829-7817], Apollo - University of Cambridge Repository, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 APM), Berr, Claudine, Institut de Neurosciences Translationnelles de Paris - - IHU-A-ICM2010 - ANR-10-IAHU-0006 - IAHU - VALID, and Mentoring of LifeSciHealth-Multipliers in the Accession Candidate Countries - LSH-ACC-MENTOR - 29845 - OLD
Subjects: 0301 basic medicine, Linkage disequilibrium, [SDV]Life Sciences [q-bio], Medizin, Sequence Homology, Genome-wide association study, genetics [Alzheimer Disease], metabolism [Microglia], Linkage Disequilibrium, 0302 clinical medicine, genetics [Protein Interaction Maps], genetics [Membrane Glycoproteins], Gene Frequency, Immunologic, genetics [Adaptor Proteins, Signal Transducing], Receptors, genetics [Exome], Odds Ratio, Innate, genetics [Receptors, Immunologic], Exome, Protein Interaction Maps, genetics [Genetic Predisposition to Disease], Receptors, Immunologic, ABI3 protein, human, Genetics, Adaptor Proteins, Signal Transducing, Alzheimer Disease, Amino Acid Sequence, Case-Control Studies, Gene Expression Profiling, Genetic Predisposition to Disease, Genotype, Humans, Immunity, Innate, Membrane Glycoproteins, Microglia, Phospholipase C gamma, Sequence Homology, Amino Acid, Polymorphism, Single Nucleotide, Adaptor Proteins, Single Nucleotide, 3. Good health, [SDV] Life Sciences [q-bio], Amino Acid, Settore MED/26 - NEUROLOGIA, genetics [Phospholipase C gamma], [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Alzheimer's disease, Common disease-common variant, Biology, Article, 03 medical and health sciences, ddc:570, medicine, Journal Article, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Polymorphism, Allele frequency, TREM2 protein, human, TREM2, Case-control study, Signal Transducing, Immunity, medicine.disease, R1, Minor allele frequency, genetics [Immunity, Innate], 030104 developmental biology, Human medicine, 030217 neurology & neurosurgery
Abstract: International audience; We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10-8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10-10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10-10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10-14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.
Published: 2017
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6. Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis

Author: Marla Gearing, David G. Clark, Steven L. Carroll, Marianne Johnstone, Darwin L. Conwell, Gregory A. Cote, Sandra Weintraub, Matthew P. Frosch, Stuart Sherman, Badri N. Vardarajan, Joshua A. Sonnen, Lindy E. Harrell, Peter B. Cotton, Lisa L. Barnes, Lawrence S. Honig, Carol A. Miller, Adam Slivka, Michelle A. Anderson, Nadine M. Melhem, David A. Bennett, Joel H. Kramer, Jill P. Smith, Michele D. Lewis, Mary Ganguli, Jean Paul Vonsatte, Thomas J. Montine, Lee-Way Jin, Kenneth B. Fallon, Marilyn S. Albert, Eliezer Masliah, John H. Growdon, Barry Reisberg, Chuanhai Cao, Patricia L. Kramer, Douglas J. Hartman, Allan I. Levey, Jennifer Williamson, Vivianna M. Van Deerlin, Wayne W. Poon, Alison Goate, Vijay P. Singh, Bernie Devlin, Christiane Reitz, Ann C. McKee, Amanda Smith, Neill R. Graff-Radford, Walter A. Kukul, John Baillie, Andres Gelrud, Ranjan Duara, Thomas D. Bird, Clinton B. Wright, Deborah Blacker, Chiao-Feng Lin, Ge Li, Ronald C. Kim, Deborah C. Mash, Debby W. Tsuang, John P. Neoptolemos, Timothy B. Gardner, Kathryn L. Lunetta, Steven G. Younkin, Kara L. Hamilton-Nelson, Ronald L. Hamilton, F. Yesim Demirci, Eric M. Reiman, Charles DeCarli, John M Olichney, Richard Mayeux, Gregory A. Jicha, Michael R. O'Connell, Matt Tector, Eileen H. Bigio, Jonathan D. Glass, M. Ilyas Kamboh, Randall E. Brand, Christopher Lawrence, Steven E. Arnold, Jessica LaRusch, Elaine R. Peskind, David H. Cribbs, M.-Marsel Mesulam, Constantine G. Lyketsos, Michelle L. Kienholz, Frank M. LaFerla, Duane Beekly, Kelley Faber, Salvatore Spina, Gyungah Jun, Thiruvengadam Muniraj, Erik D. Roberson, Anna Karydas, Steven H. Ferris, Bruce L. Miller, Randall L. Woltjer, Li-San Wang, Lon S. Schneider, John C. Morris, John Q. Trojanowski, Jeffrey Kaye, Joseph E. Parisi, Nilufer Ertekin-Taner, Harry V. Vinters, Lidiya Orlichenko, Robert Barber, Chris E. Forsmark, Mary Sano, Bimaljit S. Sandhu, Peter A. Banks, Martin R. Farlow, Bradley T. Hyman, Joseph F. Quinn, Gary W. Beecham, James A. DiSario, Hakon Hakonarson, Daniel C. Marson, Adam C. Naj, Frank Martiniuk, Oscar L. Lopez, Mary E. Money, Julia Mayerle, William Greenhalf, Kathryn Roeder, Adam L. Boxer, Christine M. Hulette, Gerard D. Schellenberg, Georgios I. Papachristou, Douglas Galasko, James R. Burke, Donna B. Stolz, Murray A. Raskind, Peter Simon, Linda J. Van Eldik, Robert A. Hawes, Chang En Yu, Tatiana Foroud, Jonathan L. Haines, Stephen R. Wisniewski, William W. Seeley, Dhiraj Yadav, James J. Lah, C. Mel Wilcox, Sid Gilman, Liana G. Apostolova, Howard J. Rosen, Clinton T. Baldwin, Robert S. Stern, Narcis O. Zarnescu, Dennis W. Dickson, Margaret A. Pericak-Vance, Ashok Raj, Stephen T. Amann, Joseph D. Buxbaum, Ronald C. Petersen, Robert C. Green, David C. Whitcomb, Rudolph E. Tanzi, Lindsay A. Farrer, Helena C. Chui, Laura B. Cantwell, Wendy J. Mack, Samer Alkaade, Nigel J. Cairns, Thomas G. Beach, Frank Ulrich Weiss, Alyssa M. Krasinskas, Elizabeth Head, Nalini M. Guda, Julie A. Schneider, Malcolm B. Dick, Roger N. Rosenberg, Jill R. Murrel, Otto Valladares, Andrew J. Saykin, Huntington Potter, John R. Gilbert, Neil W. Kowall, Joseph Romagnuolo, Markus M. Lerch, Aimee Pierce, Roger L. Albin, John M. Ringman, James B. Leverenz, Carlos Cruchaga, Joshua W. Miller, Lei Yu, M. Michael Barmada, Lambertus Klei, Andrew P. Lieberman, Bernardino Ghetti, Robert Sutton, Kathleen A. Welsh-Bohmer, Juan C. Troncoso, Edward H. Koo, Elizabeth Crocco, Eden R. Martin, Daniel H. Geschwind, and Regina M. Carney
Subjects: Male, Pancreatic disease, Pancreatitis, Alcoholic, Genome-wide association study, Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Sex Factors, Gene Frequency, Genotype, Genetics, medicine, PRSS2, Humans, Genetic Predisposition to Disease, Trypsin, Allele, Allele frequency, Homozygote, Genetic Variation, medicine.disease, 3. Good health, Hemizygote, 030220 oncology & carcinogenesis, Immunology, Claudins, Mutation, Trypsinogen, Pancreatitis, 030211 gastroenterology & hepatology, Female, Genome-Wide Association Study
Abstract: Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR and SPINK1 variants were associated with pancreatitis risk. We now report two associations at genome-wide significance identified and replicated at PRSS1-PRSS2 (P < 1 × 10(-12)) and X-linked CLDN2 (P < 1 × 10(-21)) through a two-stage genome-wide study (stage 1: 676 cases and 4,507 controls; stage 2: 910 cases and 4,170 controls). The PRSS1 variant likely affects disease susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous in males) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men (male hemizygote frequency is 0.26, whereas female homozygote frequency is 0.07).
Published: 2012

7. Expression of Sox10 and c-kit in Sinonasal Mucosal Melanomas Arising in the Chinese Population

Author: Robert Shibata, Shu Yi Wang, Frank Martiniuk, Herman Yee, Qian Yao, Beverly Y. Wang, Max Xiangtian Kong, and Hong Gang Liu
Subjects: Adult, Male, Pathology, medicine.medical_specialty, Gene mutation, Stain, S100 protein, Pathology and Forensic Medicine, Asian People, Biomarkers, Tumor, medicine, Humans, Melanoma, Aged, Original Paper, Mucous Membrane, biology, SOXE Transcription Factors, CD117, Middle Aged, medicine.disease, Immunohistochemistry, Staining, Proto-Oncogene Proteins c-kit, Oncology, Otorhinolaryngology, Monoclonal, biology.protein, Female, Paranasal Sinus Neoplasms
Abstract: Sinonasal mucosal melanomas (SNMM) of the head and neck regions are rare and aggressive malignancies. Although they can affect patients of any ethnicity, they are more numerous in Chinese patients. The diagnosis and treatment of these tumors can be challenging. Recent studies have reported that Sox10 is a sensitive melanocytic marker for cutaneous melanoma (Nonaka et al. in Am J Surg Pathol 32:1291–1298, 2008). In addition, a CD117 (c-kit) gene mutation has been identified in cutaneous melanomas, indicating that there may be potential therapeutic benefits of tyrosine kinase inhibitors, such as Imatinib. The purpose of this study was to detect and test the immunohistochemical expression of Sox10 and c-kit in mucosal melanomas (MM) arising in the nasal cavities of Chinese patients. Twenty eight patients with mucosal melanomas of the nasal cavity were treated in two major hospitals in China. All cases had been locally diagnosed as primary SNMM. We confirmed all diagnoses with positive immunohistochemical stains for S100 and HMB-45. Additionally, automated immunohistochemistry was performed using a goat polyclonal Sox10 antibody and a monoclonal c-kit antibody counterstained using a standard avidin–biotin complex method. Immunohistochemical positive expression of Sox10 was defined by nuclear stain; and positivity for c-kit resulted in a distinct membranous staining. The extent of nuclear positivity for Sox10 and membranous stain for c-kit was graded by 4 board certified pathologists as follows: 1+, 1–25 % of positive tumor cells; 2+, 25–50 %; 3+, 50–75 %; and 4+, ≥75 %. Sox10 nuclear expression was found in all cases (100 %), with 4+ staining in 26 out of 28 cases (92.8 %) and 3+ staining in two cases with (7.1 %). The overall positivity for S100 staining was 23 out of 28 (82.1 %), with 1+ staining in 10 cases, 2+ staining in 6 cases, 3+ staining in 7 cases, and no staining in 5 cases. The sensitivity and intensity of Sox10 immunohistochemistry were both higher than with S100 immunohistochemistry. Immunopositivity of membranous stain for c-kit (CD117) was seen in 24 out of 28 cases (85.7 %), including 6 tumors that were 4+, eight that were 3+, six that were 2+, and four that showed 1+ staining. Our results demonstrate that Sox10 is a sensitive marker for SNMM and it may possess diagnostic value in addition to that of S100 protein. The expression of c-kit in the majority of MMs suggests that it may be useful in the assessment of these tumors for potential treatment with tyrosine kinase inhibitors.
Published: 2012
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8. Collision Tumor of Primary Laryngeal Mucosal Melanoma and Invasive Squamous Cell Carcinoma with IL-17A and CD70 Gene Over-Expression

Author: Sasis Sirikanjanapong, Frank Martiniuk, Milan R. Amin, Hideko Kamino, Biana G. Lanson, and Beverly Y. Wang
Subjects: Male, Larynx, Pathology, medicine.medical_specialty, Case Report, Vocal Cords, Biology, Pathology and Forensic Medicine, RAR-related orphan receptor gamma, Biomarkers, Tumor, Carcinoma, medicine, Humans, Neoplasm Invasiveness, Laryngeal Neoplasms, Melanoma, CD70, Regulation of gene expression, Mucous Membrane, Reverse Transcriptase Polymerase Chain Reaction, Interleukin-17, Mucosal melanoma, FOXP3, Neoplasms, Second Primary, Middle Aged, medicine.disease, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, Oncology, Otorhinolaryngology, Carcinoma, Squamous Cell, CD27 Ligand
Abstract: The most common primary malignancy of the larynx is the squamous cell carcinoma (SCC). The primary malignant melanoma is quite rare in this location. Less than 60 cases of laryngeal melanomas have been reported to date. To our knowledge, collision primary malignant melanoma and invasive squamous cell carcinoma in the vocal cords has not been reported. We report a 53-year-old male patient who was diagnosed with a collision tumor of laryngeal melanoma and invasive SCC. Multiple Th17 pathway related genes including CTLA-4, IL-17A-F, PLZF, FoxP3, RorγT, CD27, and CD70 were analyzed by reverse transcriptase-polymerase chain reaction (Rt–PCR) in this case. Both IL-17A and CD70 genes were detected in this case of collision tumor. The results may define useful biomarkers for early diagnosis of mucosal melanoma and open an immunotherapeutic field for clinical management with the potential benefit from the immunomodulators that enhance both genes.
Published: 2010
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9. The effects of normal aging and ApoE genotype on the levels of CSF biomarkers for Alzheimer's disease

Author: Lidia Glodzik-Sobanska, Raymond Zinkowski, Elizabeth Pirraglia, Miroslaw Brys, Lisa Mosconi, Susan De Santi, Pankaj D. Mehta, Mony J. de Leon, Kaj Blennow, Martin J. Sadowski, Domenico Praticò, Kenneth Rich, Frank Martiniuk, Remigiusz Switalski, and Leslie A. Saint Louis
Subjects: Adult, Male, Apolipoprotein E, Senescence, Aging, medicine.medical_specialty, Isoprostane, Genotype, Amyloid beta, Apolipoprotein E4, DNA Mutational Analysis, tau Proteins, Biology, Dinoprost, Article, chemistry.chemical_compound, Apolipoproteins E, Cerebrospinal fluid, Gene Frequency, Alzheimer Disease, Internal medicine, mental disorders, medicine, Humans, Genetic Predisposition to Disease, Phosphorylation, Aged, Aged, 80 and over, Amyloid beta-Peptides, Polymorphism, Genetic, General Neuroscience, Middle Aged, medicine.disease, Peptide Fragments, Oxidative Stress, Endocrinology, chemistry, biology.protein, Female, Neurology (clinical), Tauopathy, Geriatrics and Gerontology, Alzheimer's disease, Biomarkers, Developmental Biology
Abstract: While cerebrospinal fluid (CSF) biomarkers are of use in the prediction and diagnosis of Alzheimer’s disease our understanding of the background effects of age and the ApoE genotype is limited. Seventy-eight community-based normal volunteers (mean age 60 ± 10 years, range 36–86) were examined to determine the relationships between CSF measures of total tau (T-tau), hyperphosphorylated tau (P-tau 231), amyloid beta (Aβ42/Aβ40 ratio), and isoprostane (IP) with age and ApoE genotype. The results showed that age by ε4 genotype interactions were found for P-tau231 (β = 1.82; p < 0.05) and IP (β = 1.6; p < 0.05). T-tau CSF concentration increased with age. The increasing CSF concentrations of P-tau and IP in ε4 carriers suggest that early tauopathy and oxidative stress may be related to the increased risk for AD. The data also suggest that T-tau changes are more age dependent than Aβ changes. The evidence that P-tau231 and IP are the earliest markers for the neuronal damage related to AD awaits longitudinal study. © 2007 Elsevier Inc. All rights reserved.
Published: 2009
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10. The role of the armadillo and sooty mangabey monkey in human leprosy

Author: William R. Levis, Heather K. Hamilton, Aloys Cabrera, Frank Martiniuk, and John Wolf
Subjects: Animal Experimentation, Armadillos, Simian Acquired Immunodeficiency Syndrome, HIV Infections, Dermatology, medicine.disease_cause, Cercocebus atys, Acquired immunodeficiency syndrome (AIDS), Leprosy, Zoonoses, biology.animal, medicine, Animals, Humans, Animal testing, biology, Transmission (medicine), Monkey Diseases, Zoonosis, HIV, Simian immunodeficiency virus, medicine.disease, biology.organism_classification, Macaca mulatta, Virology, Mycobacterium leprae, Armadillo, Immunology, Sooty mangabey, Simian Immunodeficiency Virus
Abstract: Background The armadillo was the first animal model of leprosy. Its role in the transmission of leprosy remains controversial. The sooty mangabey model of leprosy led to the discovery that rhesus monkeys were more susceptible to leprosy when coinfected with simian immunodeficiency virus (SIV), but that leprosy may play a protective role against acquired immunodeficiency syndrome (AIDS) mortality. Recently, molecular methods have been developed for leprosy and may help resolve the role of zoonoses in leprosy. Observations The recent identification of a case of leprosy in a native-born American on the east coast of the USA and the identification of leprosy as an immunologic reconstitution inflammatory syndrome (IRIS) in human immunodeficiency virus (HIV)-positive cases raise the question of what role zoonoses may play in leprosy. Conclusions Leprosy in armadillos and sooty mangabeys has been manipulated by human experimentation. In the case of the armadillo, further study, including molecular techniques, is required to elucidate the role of the armadillo as a zoonosis in human leprosy. Experimentation with the sooty mangabey led to the discovery of an interaction between SIV and leprosy in rhesus monkeys, and prompted the continued investigation of the relationship between HIV and leprosy.
Published: 2008
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11. Correction of Glycogen Storage Disease Type II by Enzyme Replacement with a Recombinant Human Acid Maltase Produced by Over-Expression in a CHO-DHFRneg Cell Line

Author: William N. Rom, Nina Raben, Paul H. Plotz, Eleni Arvanitopoulos, Alfred E. Slonim, Frank Martiniuk, Agnes Chen, and Vincent Donnabella
Subjects: congenital, hereditary, and neonatal diseases and abnormalities, Gene Dosage, Biophysics, CHO Cells, Motor Activity, Biochemistry, Monocytes, law.invention, Mice, law, Cricetinae, Dihydrofolate reductase, Glycogen storage disease type II, medicine, Animals, Humans, Lymphocytes, RNA, Messenger, Immunoelectrophoresis, Molecular Biology, Mice, Knockout, Mannosephosphates, biology, Glycogen Storage Disease Type II, Chinese hamster ovary cell, nutritional and metabolic diseases, alpha-Glucosidases, Cell Biology, Enzyme replacement therapy, Fibroblasts, medicine.disease, Molecular biology, Recombinant Proteins, Enzyme assay, Blotting, Southern, Tetrahydrofolate Dehydrogenase, Methotrexate, Phenotype, biology.protein, Recombinant DNA, Acid alpha-glucosidase, Glucan 1,4-alpha-Glucosidase, Maltase, Gene Deletion
Abstract: Inherited genetic deficiency of lysosomal acid alpha glucosidase or acid maltase (GAA) results in the autosomal recessive glycogen storage disease type II (GSD II). To investigate whether we could generate a functional recombinant human GAA (rhGAA) for enzyme replacement therapy, we subcloned the cDNAs for human GAA and mouse dihydrofolate reductase (DHFR) into DHFRneg Chinese hamster ovary cells and established a stable cotransformant that expressed rhGAA. We cultured the recombinant cells in media with progressively increasing concentrations of methotrexate and found that human GAA enzyme activity increased to over 2,000 IU per gram protein. Importantly, the human GAA enzyme activity correlated to equivalent amounts of human GAA protein by rocketimmunoelectrophoresis. We confirmed that the human GAA enzyme activity corresponded to an amplification in human GAA mRNA by Northern analysis and human GAA cDNA copy number by Southern analysis. Exposing the rhGAA to human GSDII fibroblast cells or patient's lymphocytes or monocytes resulted in uptake of the rhGAA and reversal of the enzymatic defect. Mannose-6-phosphate in the media blocked uptake. GAA −/− mice were treated with the rhGAA at 1 mg/kg, which resulted in heterozygous levels of GAA in tissues, most notably skeletal muscle, heart and diaphragm after two infusions. More importantly, after multiple infusions, hind, and fore-limb muscle weakness was reversed. This rhGAA would be ideal for enzyme replacement therapy in GSD II.
Published: 2000
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12. Leprosy as Immune Reconstitution Inflammatory Syndrome in HIV-positive Persons

Author: Thomas H. Rea, Michael S. Glickman, William R. Levis, Aloys Cabrera, Shaline D. Rao, Frank Martiniuk, Jerome Giovinazzo, and William N. Rom
Subjects: Microbiology (medical), medicine.medical_specialty, HAART, Epidemiology, 030231 tropical medicine, hsp65, letter, lcsh:Medicine, Leprostatic agent, Tuberculoid leprosy, Dapsone, heat shock 65, lcsh:Infectious and parasitic diseases, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Immune reconstitution inflammatory syndrome, medicine, lcsh:RC109-216, Letters to the Editor, Mycobacterium leprae, Lepromatous leprosy, biology, medicine.diagnostic_test, business.industry, lcsh:R, HIV, medicine.disease, biology.organism_classification, Dermatology, 3. Good health, Infectious Diseases, Skin biopsy, Immunology, RFLP, Leprosy, business, subclinical, leprosy, medicine.drug
Abstract: To the Editor: More than 2 decades ago, when HIV was first detected, many investigators predicted the rise of leprosy secondary to opportunistic infection (1). Recently, the phenomenon of immune reconstitution inflammatory syndrome (IRIS), or leprosy reversal response, has received attention. IRIS often occurs secondary to initiating highly active antiretroviral therapy (HAART). The first indications of an interaction between HIV and Mycobacterium leprae occurred only recently, with the identification of IRIS after initiation of HAART in patients with HIV and previously undetected leprosy. A review by Pustianowski et al. discusses the paradox of HIV and leprosy with IRIS (2). In addition, Lawn et al. described the first case of IRIS after the onset of HAART in a patient who had tuberculoid leprosy that was never confirmed by molecular analysis (3). Multiple reports (4–7) unmasked subclinical Hansen disease (M. leprae infection) occurring with HAART or spontaneously (8). In case reports by Lu et al. (6) and Sharma et al. (7), leprosy was associated with erythema nodosum leprosum. Pereira et al. discovered that patients known to have HIV and leprosy, when treated with HAART manifested a type 1 reversal reaction, acute leprosy inflammatory episode (4), or IRIS. We describe the first, to our knowledge, 2 cases in the United States of HIV and leprosy infections in which IRIS has occurred after HAART initiation and which has been confirmed by molecular analysis. Three skin-biopsy samples, 2 from patient 1 and 1 from patient 2, were analyzed to confirm the presence of M. leprae. Patient 1 met the diagnostic criteria for leprosy according to biopsy result; patient 2’s case was compatible with such criteria. Each patient was treated for leprosy, and each responded favorably. The purpose of our case study was to confirm M. leprae DNA in skin samples. The skin specimens were paraffin-embedded slides. DNA was extracted by standard molecular biologic methods that used xylene. PCR amplified the M. leprae heat shock protein 65 gene (hsp65). After amplification, restriction fragment-length polymorphism (RFLP)–polyacrylamide gel electrophoresis (PAGE) was performed with HaeIII (6). Patient 1 was a 60-year-old Hispanic man who was first evaluated in Los Angeles, California, with skin lesions covering >50% of his body. He reported having erythematous scaly plaques that had been waxing and waning for several months. Several skin biopsy samples were taken, and an HIV test was conducted; results showed that he had lepromatous leprosy and was HIV positive. Biopsy specimens were both Fite stain positive for numerous acid-fast bacilli. Three months after HAART was initiated, repeat skin biopsy samples were taken from nodules that had recently developed on his right arm and torso. Histologic assessment showed Fite stain–positive granulomatous dermatitis with many foamy cells. He was treated for leprosy and is continuing HAART. Patient 2 was a 37-year-old West African black man from Burkina Faso who was evaluated in New York for gram-negative bacteremia. He was admitted and treated for disseminated salmonellosis and was found to be HIV positive. His T-lymphocyte count was 7/μL. He was promptly prescribed HAART and responded well to treatment: his T-cell count rose to 112/μL during 5 months and is currently >700/μL. Within 2 years of HAART initiation, multiple anesthetic, hypopigmented skin macules that failed to resolve over 6 months developed. These macules developed further into nodules. Punch biopsy results were consistent with granulomatous dermatitis. Fite stain was negative for acid-fast bacilli, but leprosy was diagnosed on the basis of anesthesia localized to his skin lesions. When the biopsy samples were taken, the patient was receiving dapsone in addition to HAART. Rifampin treatment was started subsequent to biopsies. PCR amplification for M. leprae hsp65 was positive for all 3 samples. Thus, mycobacterial DNA was present in both patients. The RFLP analysis results are shown in the Figure. The hsp65 RFLP pattern for patient 1 was identical to those described by Martiniuk et al. (9) and for the wild-type pattern for patient 2, as shown by Lu et al. (6), thus demonstrating the presence of M. leprae DNA in these samples. Figure Polyacrylamide gel electrophoresis–restriction fragment length polymorphism of PCR amplicons digested with HaeIII with standards. STDs, sexually transmitted diseases; Pat., patient; WT, wild type. Previous studies have highlighted the low rate of HIV and leprosy co-infection. For example in Ethiopia, Frommel et al. noted that, before HAART was available in resource-poor settings, increased HIV seropositivity did not alter the natural course of leprosy nor increase the number of patients with M. leprae (10). Nevertheless, positive reports of IRIS and leprosy after initiation of HAART have been reported from other nations (3–5). If this syndrome can be detected even in the mildly leprosy–endemic United States (8), an increase in similar cases in areas where HIV and leprosy occur in higher frequency can be anticipated.
Published: 2007

13. Production of a functional human acid maltase in tobacco seeds: biochemical analysis, uptake by human GSDII cells, and in vivo studies in GAA knockout mice

Author: Matteo Busconi, Serena Reggi, William N. Rom, Kam-Meng Tchou-Wong, Frank Martiniuk, and Corrado Fogher
Subjects: Bioengineering, Biology, Applied Microbiology and Biotechnology, Biochemistry, Article, law.invention, Mice, law, Complementary DNA, Glycogen storage disease type II, Tobacco, medicine, Animals, Humans, Recombinant human acid maltase, Enzyme replacement, Molecular Biology, chemistry.chemical_classification, Mice, Knockout, Transgenic tobacco plants, Mice, Inbred BALB C, Glycogen Storage Disease Type II, food and beverages, Biological activity, alpha-Glucosidases, General Medicine, Enzyme replacement therapy, Pompe’s disease, medicine.disease, Plants, Genetically Modified, Settore AGR/07 - GENETICA AGRARIA, Enzyme, chemistry, Seeds, Recombinant DNA, Acid alpha-glucosidase, Female, Glucan 1,4-alpha-Glucosidase, Maltase, Biotechnology
Abstract: Genetic deficiency of acid alpha glucosidase (GAA) results in glycogen storage disease type II (GSDII) or Pompe's disease. To investigate whether we could generate a functional recombinant human GAA enzyme (tobrhGAA) in tobacco seeds for future enzyme replacement therapy, we subcloned the human GAA cDNA into the plant expression plasmid-pBI101 under the control of the soybean β-conglycinin seed-specific promoter and biochemically analyzed the tobrhGAA. Tobacco seeds contain the metabolic machinery that is more compatible with mammalian glycosylation-phosphorylation and processing. We found the tobrhGAA to be enzymatically active was readily taken up by GSDII fibroblasts and in white blood cells from whole blood to reverse the defect. The tobrhGAA corrected the enzyme defect in tissues at 7 days after a single dose following intraperitoneal (IP) administration in GAA knockout (GAA(-/-)) mice. Additionally, we could purify the tobrhGAA since it bound tightly to the matrix of Sephadex G100 and can be eluted by competition with maltose. These data demonstrate indirectly that the tobrhGAA is fully functional, predominantly proteolytically cleaved and contains the minimal phosphorylation and mannose-6-phosphate residues essential for biological activity.
Published: 2013

14. Primary mucosal melanoma arising from the eustachian tube with CTLA-4, IL-17A, IL-17C, and IL-17E upregulation

Author: Beverly Y. Wang, Sasis Sirikanjanapong, William R. Levis, Mark D. DeLacure, Seth M. Lieberman, Calvin Wei, and Frank Martiniuk
Subjects: Male, Pathology, medicine.medical_specialty, Eustachian tube, medicine.medical_treatment, Ear neoplasm, Article, Downregulation and upregulation, medicine, Humans, CTLA-4 Antigen, Melanoma, Ear Neoplasms, business.industry, Eustachian Tube, Interleukin-17, Mucosal melanoma, FOXP3, Immunotherapy, Middle Aged, medicine.disease, Up-Regulation, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, Otorhinolaryngology, CTLA-4, business
Abstract: Primary malignant melanoma arising from the eustachian tube is extremely rare. We report the case of a 63-year-old white man who presented with a 1-month history of left-sided hearing loss and aural fullness. Flexible fiberoptic laryngoscopy detected a blue-purple mass that appeared to arise from the left lateral nasopharynx. Computed tomography demonstrated an enhancing mass arising from an orifice of the left eustachian tube. The tumor was debulked endoscopically and was confirmed to have originated in the left eustachian tube. Histologically, the tumor was made up of heavily pigmented pleomorphic spindle cells with frequent mitoses. The tumor cells were immunohistochemically positive for S-100 protein, HMB-45, Melan-A, and PNL-2. The final diagnosis was a mucosal malignant melanoma. We also performed a nested polymerase chain reaction assay for several genes of interest, including CTLA-4, IL-17A, IL-17B, IL-17C, IL-17D, IL-17E, IL-17F, PLZF, Foxp3, RORγt, CD27, and CD70. These genes have been studied mainly in cutaneous melanomas, especially for the development of immunotherapy, but only very limited studies have been done on mucosal melanomas. Our investigation found upregulation of CTLA-4, IL-17A, IL-17C, and IL-17E. Based on our finding of CTLA-4 upregulation, it may be suggested that our patient might have had low antitumor immunity and that he might have benefited from CTLA-4 blockade. On the other hand, upregulation of IL-17A and IL-17E might reflect increased antitumor immunity, which could suggest that patients with a mucosal melanoma might benefit from immunomodulators associated with the effect of T17. These genes also have great potential to help melanoma patients obtain tailored treatment, and they can be used as biomarkers for predicting prognosis.
Published: 2013

15. Assessment of the genetic variance of late-onset Alzheimer's disease

Author: Perry G. Ridge, Kaitlyn B. Hoyt, Kevin Boehme, Shubhabrata Mukherjee, Paul K. Crane, Jonathan L. Haines, Richard Mayeux, Lindsay A. Farrer, Margaret A. Pericak-Vance, Gerard D. Schellenberg, John S.K. Kauwe, Perrie M. Adams, Marilyn S. Albert, Roger L. Albin, Liana G. Apostolova, Steven E. Arnold, Sanjay Asthana, Craig S. Atwood, Clinton T. Baldwin, Robert C. Barber, Michael M. Barmada, Lisa L. Barnes, Sandra Barral, Thomas G. Beach, James T. Becker, Gary W. Beecham, Duane Beekly, David A. Bennett, Eileen H. Bigio, Thomas D. Bird, Deborah Blacker, Bradley F. Boeve, James D. Bowen, Adam Boxer, James R. Burke, Jeffrey M. Burns, Joseph D. Buxbaum, Nigel J. Cairns, Laura B. Cantwell, Chuanhai Cao, Chris S. Carlson, Cynthia M. Carlsson, Regina M. Carney, Minerva M. Carrasquillo, Steven L. Carroll, Helena C. Chui, David G. Clark, Jason Corneveaux, David H. Cribbs, Elizabeth A. Crocco, Carlos Cruchaga, Philip L. De Jager, Charles DeCarli, F. Yesim Demirci, Malcolm Dick, Dennis W. Dickson, Rachelle S. Doody, Ranjan Duara, Nilufer Ertekin-Taner, Denis A. Evans, Kelley M. Faber, Thomas J. Fairchild, Kenneth B. Fallon, David W. Fardo, Martin R. Farlow, Steven Ferris, Tatiana M. Foroud, Matthew P. Frosch, Douglas R. Galasko, Marla Gearing, Daniel H. Geschwind, Bernardino Ghetti, John R. Gilbert, Alison M. Goate, Neill R. Graff-Radford, Robert C. Green, John H. Growdon, Hakon Hakonarson, Ronald L. Hamilton, Kara L. Hamilton-Nelson, John Hardy, Lindy E. Harrell, Lawrence S. Honig, Ryan M. Huebinger, Matthew J. Huentelman, Christine M. Hulette, Bradley T. Hyman, Gail P. Jarvik, Gregory A. Jicha, Lee-Way Jin, Gyungah Jun, M. Ilyas Kamboh, Anna Karydas, Mindy J. Katz, Jeffrey A. Kaye, Ronald Kim, Neil W. Kowall, Joel H. Kramer, Walter A. Kukull, Brian W. Kunkle, Frank M. LaFerla, James J. Lah, Eric B. Larson, James B. Leverenz, Allan I. Levey, Ge Li, Andrew P. Lieberman, Chiao-Feng Lin, Richard B. Lipton, Oscar L. Lopez, Kathryn L. Lunetta, Constantine G. Lyketsos, Wendy J. Mack, Daniel C. Marson, Eden R. Martin, Frank Martiniuk, Deborah C. Mash, Eliezer Masliah, Wayne C. McCormick, Susan M. McCurry, Andrew N. McDavid, Ann C. McKee, Marsel Mesulam, Bruce L. Miller, Carol A. Miller, Joshua W. Miller, Thomas J. Montine, John C. Morris, Jill R. Murrell, Amanda J. Myers, Adam C. Naj, Sid O'Bryant, John M. Olichney, Vernon S. Pankratz, Joseph E. Parisi, Amanda Partch, Henry L. Paulson, William Perry, Elaine Peskind, Ronald C. Petersen, Aimee Pierce, Wayne W. Poon, Huntington Potter, Joseph F. Quinn, Ashok Raj, Murray Raskind, Eric M. Reiman, Barry Reisberg, Joan S. Reisch, Christiane Reitz, John M. Ringman, Erik D. Roberson, Ekaterina Rogaeva, Howard J. Rosen, Roger N. Rosenberg, Donald R. Royall, Mark A. Sager, Mary Sano, Andrew J. Saykin, Julie A. Schneider, Lon S. Schneider, William W. Seeley, Amanda G. Smith, Joshua A. Sonnen, Salvatore Spina, Peter St George-Hyslop, Robert A. Stern, Russell H. Swerdlow, Rudolph E. Tanzi, Tricia A. Thornton-Wells, John Q. Trojanowski, Juan C. Troncoso, Debby W. Tsuang, Otto Valladares, Vivianna M. Van Deerlin, Linda J. Van Eldik, Badri N. Vardarajan, Harry V. Vinters, Jean Paul Vonsattel, Li-San Wang, Sandra Weintraub, Kathleen A. Welsh-Bohmer, Jens R. Wendland, Kirk C. Wilhelmsen, Jennifer Williamson, Thomas S. Wingo, Ashley R. Winslow, Sarah Wishnek, Randall L. Woltjer, Clinton B. Wright, Chuang-Kuo Wu, Steven G. Younkin, Chang-En Yu, and Lei Yu
Subjects: 0301 basic medicine, Male, Risk, Aging, Neuroscience(all), Clinical Neurology, Datasets as Topic, Genome-wide association study, Single-nucleotide polymorphism, Receptors, Cell Surface, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Amyloid beta-Protein Precursor, 0302 clinical medicine, Alzheimer Disease, Genetic variation, medicine, Genetics, Humans, Allele, Receptors, Immunologic, Genetic variance, Aged, Aged, 80 and over, Membrane Glycoproteins, TREM2, General Neuroscience, Genetic disorder, Genetic Variation, Alzheimer's disease, Explained variation, medicine.disease, Genetic architecture, 3. Good health, Ageing, 030104 developmental biology, Female, Neurology (clinical), Geriatrics and Gerontology, Netrin Receptors, 030217 neurology & neurosurgery, Genome-Wide Association Study, Developmental Biology
Abstract: Alzheimer's disease (AD) is a complex genetic disorder with no effective treatments. More than 20 common markers have been identified, which are associated with AD. Recently, several rare variants have been identified in Amyloid Precursor Protein (APP), Triggering Receptor Expressed On Myeloid Cells 2 (TREM2) and Unc-5 Netrin Receptor C (UNC5C) that affect risk for AD. Despite the many successes, the genetic architecture of AD remains unsolved. We used Genome-wide Complex Trait Analysis to (1) estimate phenotypic variance explained by genetics; (2) calculate genetic variance explained by known AD single nucleotide polymorphisms (SNPs); and (3) identify the genomic locations of variation that explain the remaining unexplained genetic variance. In total, 53.24% of phenotypic variance is explained by genetics, but known AD SNPs only explain 30.62% of the genetic variance. Of the unexplained genetic variance, approximately 41% is explained by unknown SNPs in regions adjacent to known AD SNPs, and the remaining unexplained genetic variance outside these regions.
Published: 2016
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16. Topical TLR7 agonist imiquimod can induce immune-mediated rejection of skin metastases in patients with breast cancer

Author: Tsivia Hochman, Sylvia Adams, Amy Tiersten, Nina Bhardwaj, James L. Speyer, Sandra Demaria, Leonard Liebes, Judith D. Goldberg, Nicholas Shuman, Silvia C. Formenti, Deborah Axelrod, Yelena Novik, Derya Unutmaz, Luis Chiriboga, Tze-Chiang Meng, Lina Kozhaya, and Frank Martiniuk
Subjects: Oncology, Agonist, Cancer Research, Tumor microenvironment, medicine.medical_specialty, business.industry, medicine.drug_class, Imiquimod, TLR7, medicine.disease, Article, Clinical trial, Breast cancer, Immune system, Immunity, Internal medicine, Immunology, Medicine, business, medicine.drug
Abstract: Purpose: Skin metastases of breast cancer remain a therapeutic challenge. Toll-like receptor 7 agonist imiquimod is an immune response modifier and can induce immune-mediated rejection of primary skin malignancies when topically applied. Here we tested the hypothesis that topical imiquimod stimulates local antitumor immunity and induces the regression of breast cancer skin metastases. Experimental Design: A prospective clinical trial was designed to evaluate the local tumor response rate of breast cancer skin metastases treated with topical imiquimod, applied 5 d/wk for 8 weeks. Safety and immunologic correlates were secondary objectives. Results: Ten patients were enrolled and completed the study. Imiquimod treatment was well tolerated, with only grade 1 to 2 transient local and systemic side effects consistent with imiquimod's immunomodulatory effects. Two patients achieved a partial response [20%; 95% confidence interval (CI), 3%–56%]. Responders showed histologic tumor regression with evidence of an immune-mediated response, showed by changes in the tumor lymphocytic infiltrate and locally produced cytokines. Conclusion: Topical imiquimod is a beneficial treatment modality for breast cancer metastatic to skin/chest wall and is well tolerated. Importantly, imiquimod can promote a proimmunogenic tumor microenvironment in breast cancer. Preclinical data generated by our group suggest superior results with a combination of imiquimod and ionizing radiation and we are currently testing in patients whether the combination can further improve antitumor immune and clinical responses. Clin Cancer Res; 18(24); 6748–57. ©2012 AACR.
Published: 2012

17. Evidence for a role of the rare p.A152T variant in MAPT in increasing the risk for FTD-spectrum and Alzheimer's diseases

Author: Jason Lee, Ranjan Duara, Michael A. Slifer, Kenneth B. Fallon, Thomas J. Montine, Beth A. Dombroski, Peter St George-Hyslop, Debby W. Tsuang, Patricia L. Kramer, Duane Beekly, Ronald C. Petersen, Carl W. Cotman, Helena C. Chui, Alison Goate, Michelle K. Lupton, Sid Gilman, Thomas G. Beach, A. Karydas, Andrew McDavid, Susan M. McCurry, William G. Ellis, Bradley T. Hyman, Badri N. Vardarajan, Joshua A. Sonnen, Neill R. Graff-Radford, Robert Barber, Elisavet Preza, Paul Gallins, Lawrence S. Honig, Adam C. Naj, Frank Martiniuk, Jacek Biernat, Christopher S. Carlson, Richard J. Caselli, Huntington Potter, Chris Zarow, Christine M. Hulette, Hakon Hakonarson, Oscar L. Lopez, Alexandra I. Soto-Ortolaza, Eric Klein, Margaret A. Pericak-Vance, Ashok Raj, Marla Gearing, Kathryn L. Lunetta, Adam L. Boxer, Gerard D. Schellenberg, John H. Growdon, Ramon Diaz-Arrastia, Wayne W. Poon, James R. Burke, Michael D. Geschwind, Douglas Galasko, Ruchita Rajbhandary, Eric M. Reiman, Gregory A. Jicha, Steven L. Carroll, Robert S. Stern, Vivianna M. Van Deerlin, Murray A. Raskind, Carol A. Miller, Ekaterina Rogaeva, Carlos Cruchaga, Joshua W. Miller, Matthew J. Huentelman, Joseph E. Parisi, Charles C. DeCarli, Eliezer Masliah, Didier Hannequin, Deborah Blacker, Michael L. Shelanski, Roger L. Albin, Mary Sano, Paul K. Crane, David G. Clark, Jean Paul G. Vonsattel, Mary Ganguli, John Hardy, John Powell, Charles DeCarli, Ronald C. Kim, Charles D. Smith, Jonathan D. Glass, M. Ilyas Kamboh, Steven E. Arnold, Gyungah Jun, Gail P. Jarvik, Anna Karydas, Suzee E. Lee, Carol F. Lippa, Allan I. Levey, Eckhard Mandelkow, Petra Nowotny, Dennis W. Dickson, Jennifer Williamson, John Q. Trojanowski, Isabelle Le Ber, Zbigniew K. Wszolek, Jeffrey Kaye, Eric B. Larson, Matthew P. Frosch, Harry V. Vinters, David A. Bennett, Joseph D. Buxbaum, Sandra Weintraub, Charles L. White, Lindy E. Harrell, Jonathan L. Haines, Minerva M. Carrasquillo, Robert O. Kenet, Lindsay A. Farrer, Robert C. Green, Wayne C. McCormick, Richard Mayeux, Denis A. Evans, Erik D. Roberson, Bruno Giordani, Liana G. Apostolova, Virginia M.-Y. Lee, Elizabeth Finger, Subashchandrabose Chinnathambi, Clinton T. Baldwin, Satish Kumar, Christiane Reitz, Steven H. Ferris, Randall L. Woltjer, Li-San Wang, Elaine R. Peskind, Thomas D. Bird, Eden R. Martin, Ryan J. Uitti, Martin R. Farlow, Amanda J. Myers, Jason J. Corneveaux, Gary W. Beecham, James D. Bowen, Juan C. Troncoso, Daniel H. Geschwind, Ann C. McKee, Roger N. Rosenberg, Bruce L. Miller, Daniel C. Marson, Jeffrey L. Cummings, Salvatore Spina, Regina M. Carney, Lee-Way Jin, Yvette Bordelon, Jean Paul Vonsattel, John R. Gilbert, Simon Lovestone, Kelley Faber, Mario F. Mendez, Laura B. Cantwell, Philip L. De Jager, John M. Ringman, Elizabeth Head, Wendy J. Mack, Giovanni Coppola, Nigel J. Cairns, Nilufer Ertekin-Taner, Nancy Johnson, Jacqueline L. Buros, Wallace W. Tourtellotte, Julie A. Schneider, Rosa Rademakers, Malcolm B. Dick, Ian R. A. Mackenzie, Andrew J. Saykin, Bradley F. Boeve, John S. K. Kauwe, Neil W. Kowall, Eva Maria Mandelkow, Andrew Kertesz, Lon S. Schneider, Joseph F. Quinn, F. Yesim Demirci, John C. Morris, Barry Reisberg, Andrew P. Lieberman, Bernardino Ghetti, Kathleen A. Welsh-Bohmer, Edward H. Koo, Alden Y. Huang, Walter A. Kukull, Alexis Brice, Eileen H. Bigio, M.-Marsel Mesulam, Steven T. DeKosky, Jorge L. Juncos, Neil Graff-Radford, M. Michael Barmada, Rudolph E. Tanzi, Owen A. Ross, Jason Karlawish, Tatiana Foroud, William W. Seeley, James J. Lah, Deborah C. Mash, Chuanhai Cao, Daniel P. Perl, A. Boxer, Matt Baker, Steven G. Younkin, Ronald L. Hamilton, Renee L. Sears, Jessica Lane, and Alzheimer's Dis Genetics Consortiu
Subjects: Risk, Genotype, epidemiology [Alzheimer Disease], Tau protein, epidemiology [Frontotemporal Dementia], Locus (genetics), genetics [Alzheimer Disease], MAPT protein, human, tau Proteins, Disease, Progressive supranuclear palsy, Alzheimer Disease, ddc:570, Genetic variation, Rare mutations, mental disorders, Genetics, medicine, Humans, Genetic Predisposition to Disease, Molecular Biology, Gene, Biology, genetics [Frontotemporal Dementia], Genetics (clinical), Aged, biology, Association Studies Articles, Genetic Variation, General Medicine, Middle Aged, medicine.disease, eye diseases, nervous system diseases, Chemistry, genetics [tau Proteins], Haplotypes, Clinical diagnosis, Frontotemporal Dementia, biology.protein, Human medicine
Abstract: Rare mutations in the gene encoding for tau (MAPT, microtubule-associated protein tau) cause frontotemporal dementia-spectrum (FTD-s) disorders, including FTD, progressive supranuclear palsy (PSP) and corticobasal syndrome, and a common extended haplotype spanning across the MAPT locus is associated with increased risk of PSP and Parkinson's disease. We identified a rare tau variant (p.A152T) in a patient with a clinical diagnosis of PSP and assessed its frequency in multiple independent series of patients with neurodegenerative conditions and controls, in a total of 15 369 subjects. Tau p.A152T significantly increases the risk for both FTD-s (n = 2139, OR = 3.0, CI: 1.6-5.6, P = 0.0005) and Alzheimer's disease (AD) (n = 3345, OR = 2.3, CI: 1.3-4.2, P = 0.004) compared with 9047 controls. Functionally, p.A152T (i) decreases the binding of tau to microtubules and therefore promotes microtubule assembly less efficiently; and (ii) reduces the tendency to form abnormal fibers. However, there is a pronounced increase in the formation of tau oligomers. Importantly, these findings suggest that other regions of the tau protein may be crucial in regulating normal function, as the p.A152 residue is distal to the domains considered responsible for microtubule interactions or aggregation. These data provide both the first genetic evidence and functional studies supporting the role of MAPT p.A152T as a rare risk factor for both FTD-s and AD and the concept that rare variants can increase the risk for relatively common, complex neurodegenerative diseases, but since no clear significance threshold for rare genetic variation has been established, some caution is warranted until the findings are further replicated.
Published: 2012
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18. Correlation between Serum and Plasma Antibody Titers to Mycobacterial Antigens ▿

Author: Rafael Prados-Rosales, Frank Martiniuk, Jacqueline M. Achkar, Xian Yu, Michael Siev, and Arturo Casadevall
Subjects: Microbiology (medical), Adult, Male, Serum, Tuberculosis, Clinical Biochemistry, Immunology, HIV Infections, Biology, Serology, Mannans, Plasma, Bacterial Proteins, medicine, Immunology and Allergy, Clinical Laboratory Immunology, Humans, Antigens, Bacterial, Plasma samples, Antibody titer, Malate Synthase, Mycobacterium tuberculosis, Middle Aged, medicine.disease, Virology, Antibodies, Bacterial, Mycobacterium bovis, Mycobacterial antigen, Female, Antibody detection
Abstract: The ability to utilize serum or plasma samples interchangeably is useful for tuberculosis (TB) serology. We demonstrate a strong correlation between antibody titers to several mycobacterial antigens in serum versus plasma from HIV-infected and non-HIV-infected TB and non-TB patients ( r = 0.99 to 0.89; P < 0.0001). Plasma and serum can be used interchangeably in the same antibody detection assays.
Published: 2010

19. Hyperimmunoglobulin E syndrome with a novel STAT3 mutation

Author: Sarina B. Elmariah, Robert Anolik, Frank Martiniuk, Stephanie Lehrhoff, William R. Levis, and Henry J Votava
Subjects: Past medical history, medicine.medical_specialty, business.industry, Dermatology, General Medicine, Gene mutation, Acute Pharyngitis, Staphylococcal infections, medicine.disease, Otitis, medicine, Eczematous dermatitis, medicine.symptom, Hyperimmunoglobulin E syndrome, business, Staphylococcal Skin Infections
Abstract: A 35-year-old man with severe eczematous dermatitis and recurrent staphylococcal skin infections, some of which required hospitalization, is presented. Other medical concerns include recurrent oral staphylococcal infections, otitis media, ocular herpes simplex virus keratitis, asthma, steroid-induced gastritis, steroid-induced cataracts, recurrent upper respiratory infections, and acute pharyngitis. Past medical history includes retained dentition of six primary teeth, two episodes of childhood pneumonia that required hospitalization, and three wrist and ankle fractures. Laboratory data showed an eosinophil count of 2,400 cells/ml; the highest IgE level was 17,028 IU/mL. Considering the clinical and laboratory findings, the diagnosis of hyperimmunoglobulin E syndrome was made. DNA sequencing showed a novel signal transducer and activator of transcription 3 (STAT3) gene mutation within intron 12, specifically adenine to cytosine, two base pairs upstream of exon 13.
Published: 2009

20. Identification of a Missense Mutation in an Adult-Onset Patient with Glycogenosis Type II Expressing Only One Allele

Author: Mark F. Mehler, M Bodkin, Nan Zhong, Kurt Hirschhorn, S. Tzall, Frank Martiniuk, and R. Hirschhorn
Subjects: medicine.medical_specialty, Transcription, Genetic, Molecular Sequence Data, Biology, Polymerase Chain Reaction, Cell Line, chemistry.chemical_compound, Internal medicine, Glycogen storage disease type II, Genetics, medicine, Humans, Missense mutation, Allele, Codon, Molecular Biology, Gene, Alleles, Gene Library, chemistry.chemical_classification, Base Sequence, Glycogen, Glycogen Storage Disease Type II, alpha-Glucosidases, Cell Biology, General Medicine, Blotting, Northern, medicine.disease, Blotting, Southern, Enzyme, Endocrinology, chemistry, Mutagenesis, Mutation, Acid alpha-glucosidase, Glucan 1,4-alpha-Glucosidase, Maltase, Polymorphism, Restriction Fragment Length
Abstract: The lysosomal enzyme acid alpha glucosidase (GAA) or acid maltase is deficient in glycogen storage disease type II. We sought to determine the molecular basis for the disease in an adult-onset patient, unusual for very low enzyme activity similar to that seen with the infantile-onset form and with a previously reported defect in phosphorylation. We constructed cDNA and genomic DNA libraries from the patient's cell line (GM 1935) and determined the nucleotide sequence of the coding region. There were three base-pair substitutions in one allele (C1935 to A; G2446 to A and C2780 to T), all predicting amino acid changes (Asp-645 to Glu; Val-816 to Ile and Thr-927 to Ile). To determine which of the three base-pair substitutions resulted in loss of enzyme activity, we next utilized primer-directed mutagenesis and transient gene expression in an SV40-immortalized GAA-deficient fibroblast cell line. Only the construct containing the G2446 to A mutation (Val-816 to Ile) lost GAA enzyme activity, while the other two substitutions (including the Thr-927 to Ile change that predicts a loss of a potential site for N-linked glycosylation and mannose phosphorylation) each resulted in enzyme activity equal to the control. Analysis of RFLPs in genomic DNA, as well as sequence analysis for the three base-pair alterations, indicated that the patient was a genetic compound. We next digested PCR-amplified cDNA (reverse-transcribed from RNA) with Aat II to detect the base-pair 1935 substitution and found that virtually all of the mRNA was derived from the allele with the three base-pair substitutions.(ABSTRACT TRUNCATED AT 250 WORDS)
Published: 1991
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21. Molecular origin of endemic leprosy in New York City

Author: Aloys Cabrera, Jo-Ann Latkowski, Thormika Keo, William N. Rom, Frank Martiniuk, and William R. Levis
Subjects: Microbiology (medical), Gerontology, DNA, Bacterial, Male, Endemic Diseases, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Indigenous, Foreign born, Leprosy, Genotype, Medicine, Humans, Mycobacterium leprae, Skin, biology, business.industry, biology.organism_classification, medicine.disease, Infectious Diseases, New York City, Immunocompetence, business, Demography
Abstract: We report an indigenous case of leprosy in New York City in an immunocompetent patient who was infected with a Mycobacterium leprae genotype that is consistent with an exogenous origin. Physicians in the eastern United States should be alerted that, although most patients who develop leprosy in the United States are foreign born, native-born Americans are also susceptible to the infection.
Published: 2008

22. Rarity of the Alzheimer Disease–ProtectiveAPPA673T Variant in the United States

Author: Nigel J. Cairns, Maria C. Norton, Eric B. Larson, Eliezer Masliah, Julie A. Schneider, Malcolm B. Dick, John S. K. Kauwe, Marilyn S. Albert, Neil W. Kowall, Amanda Partch, JoAnn T. Tschanz, Lindsay A. Farrer, Wayne W. Poon, Nilufer Ertekin-Taner, Barry Reisberg, Timothy W. Behrens, Huntington Potter, Kenneth B. Fallon, Brian W. Kunkle, Duane Beekly, Adam C. Naj, Frank Martiniuk, Marla Gearing, Andrew P. Lieberman, Jonathan L. Haines, Ronald L. Hamilton, David G. Clark, Peter St George-Hyslop, Martin R. Farlow, Lisa L. Barnes, Murray A. Raskind, Deborah Blacker, Aimee Pierce, Bernardino Ghetti, Kathleen A. Welsh-Bohmer, Patricia L. Kramer, Joseph F. Quinn, Eric M. Reiman, Matthew P. Frosch, Kathryn L. Lunetta, Gail P. Jarvik, Roger N. Rosenberg, John Q. Trojanowski, Alison Goate, John H. Growdon, Linda J. Van Eldik, Roger L. Albin, Liana G. Apostolova, Christine M. Hulette, Eileen H. Bigio, William Perry, Josue D. Gonzalez Murcia, Clinton B. Wright, Allan I. Levey, Margaret A. Pericak-Vance, Ashok Raj, Jennifer Williamson, Clinton T. Baldwin, Oscar L. Lopez, James R. Burke, Joel H. Kramer, Edward H. Koo, Bradley T. Hyman, Tatiana Foroud, Vivianna M. Van Deerlin, James B. Leverenz, William W. Seeley, Paul K. Crane, Sarah Wishnek, Debby W. Tsuang, Christopher S. Carlson, F. Yesim Demirci, Steven H. Ferris, Charles DeCarli, Laura B. Cantwell, John M. Ringman, Carol A. Miller, Li-San Wang, Mary Sano, M. Ilyas Kamboh, Lisa A. Cannon-Albright, Elizabeth Crocco, R. C. Kim, Gyungah Jun, Anna Karydas, John M Olichney, James T. Becker, Randall L. Woltjer, Carlos Cruchaga, Joshua W. Miller, Elaine R. Peskind, Robert R. Graham, Steven E. Arnold, Joseph D. Buxbaum, Tricia A. Thornton-Wells, Kaj Blennow, Robert C. Green, Gerard D. Schellenberg, Erik D. Roberson, Gary W. Beecham, Douglas Galasko, Beth A. Dombroski, Thomas G. Beach, Wendy J. Mack, Eden R. Martin, John C. Morris, Badri N. Vardarajan, Daniel H. Geschwind, Daniel C. Marson, Jill R. Murrell, Chuanhai Cao, David A. Bennett, Ann C. McKee, Neill R. Graff-Radford, Robert S. Stern, Lee-Way Jin, Constantine G. Lyketsos, Salvatore Spina, Ekaterina Rogaeva, Wayne C. McCormick, Jean Paul Vonsattel, Mary Ganguli, Elizabeth Head, Chris Corcoran, Lei Yu, Ranjan Duara, Kelley Faber, Andrew McDavid, Helena C. Chui, John R. Gilbert, Amanda G. Smith, Chang-En Yu, Robert Barber, Richard Mayeux, James D. Bowen, Hakon Hakonarson, Juan C. Troncoso, Dennis W. Dickson, Ronald C. Petersen, Deborah C. Mash, Bruce L. Miller, Henrik Zetterberg, Joshua A. Sonnen, Jeffrey Kaye, M. Michael Barmada, L. Schneider, Rudolph E. Tanzi, Otto Valladares, Andrew J. Saykin, Ronald G. Munger, Thomas J. Montine, A. Boxer, Steven G. Younkin, Harry V. Vinters, Frank M. LaFerla, Nicole Schupf, Christiane Reitz, Walter A. Kukull, Chiao-Feng Lin, Kara L. Hamilton-Nelson, M.-Marsel Mesulam, Steven T. DeKosky, Howard J. Rosen, Lawrence S. Honig, Steven L. Carroll, Susan M. McCurry, Joseph E. Parisi, Thomas D. Bird, James J. Lah, Bradley F. Boeve, Gregory A. Jicha, Jonathan D. Glass, Regina M. Carney, Sandra Weintraub, David H. Cribbs, Lindy E. Harrell, and Ge Li
Subjects: Male, medicine.medical_specialty, Genotype, Population, Locus (genetics), Article, Amyloid beta-Protein Precursor, Alzheimer Disease, Internal medicine, Medicine and Health Sciences, medicine, Humans, Allele, education, Prospective cohort study, Aged, Genetic association, Aged, 80 and over, Sweden, Genetics, education.field_of_study, business.industry, Case-control study, Protective Factors, medicine.disease, United States, Pedigree, Case-Control Studies, Female, Neurology (clinical), Alzheimer's disease, Age of onset, business
Abstract: Importance Recently, a rare variant in the amyloid precursor protein gene ( APP ) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States. Objective To determine the frequency of the APP A673T variant in a large group of elderly cognitively normal controls and AD cases from the United States and in 2 case-control cohorts from Sweden. Design, Setting, and Participants Case-control association analysis of variant APP A673T in US and Swedish white individuals comparing AD cases with cognitively intact elderly controls. Participants were ascertained at multiple university-associated medical centers and clinics across the United States and Sweden by study-specific sampling methods. They were from case-control studies, community-based prospective cohort studies, and studies that ascertained multiplex families from multiple sources. Main Outcomes and Measures Genotypes for the APP A673T variant were determined using the Infinium HumanExome V1 Beadchip (Illumina, Inc) and by TaqMan genotyping (Life Technologies). Results The A673T variant genotypes were evaluated in 8943 US AD cases, 10 480 US cognitively normal controls, 862 Swedish AD cases, and 707 Swedish cognitively normal controls. We identified 3 US individuals heterozygous for A673T, including 1 AD case (age at onset, 89 years) and 2 controls (age at last examination, 82 and 77 years). The remaining US samples were homozygous for the alanine (A673) allele. In the Swedish samples, 3 controls were heterozygous for A673T and all AD cases were homozygous for the A673 allele. We also genotyped a US family previously reported to harbor the A673T variant and found a mother-daughter pair, both cognitively normal at ages 72 and 84 years, respectively, who were both heterozygous for A673T; however, all individuals with AD in the family were homozygous for A673. Conclusions and Relevance The A673T variant is extremely rare in US cohorts and does not play a substantial role in risk for AD in this population. This variant may be primarily restricted to Icelandic and Scandinavian populations.
Published: 2015
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23. Modification of the natural history of adult-onset acid maltase deficiency by nutrition and exercise therapy

Author: Jennifer Minikes, Frank Martiniuk, Linda Bulone, Joseph A. Galanko, Efrat Slonim, Teresia Goldberg, and Alfred E. Slonim
Subjects: Adult, Male, medicine.medical_specialty, Physiology, Vital Capacity, Disease, Gastroenterology, Cellular and Molecular Neuroscience, Muscular Diseases, Physiology (medical), Internal medicine, medicine, Dietary Carbohydrates, Humans, Prospective Studies, Prospective cohort study, Myopathy, Muscle, Skeletal, Aged, Food, Formulated, business.industry, Glycogen Storage Disease Type II, Respiratory disease, Exercise therapy, Middle Aged, medicine.disease, Exercise Therapy, Respiratory Function Tests, Compliance (physiology), Natural history, Endocrinology, Treatment Outcome, Respiratory failure, Physical Fitness, Disease Progression, Patient Compliance, Female, Neurology (clinical), Dietary Proteins, Nutrition Therapy, medicine.symptom, business, Respiratory Insufficiency
Abstract: Adult-onset acid maltase deficiency is an inherited lysosomal skeletal-muscle disease characterized by progressive myopathy and respiratory failure, for which there is no known therapy. In an uncontrolled, prospective study, we evaluated whether adherence to high-protein and low-carbohydrate nutrition and exercise therapy (NET) can slow the progressive deterioration of muscle function in this disease. Thirty-four patients have been treated with NET for periods of 2-10 years (mean 4.5 +/- 2.5). Pre-NET rate of muscle function deterioration, as measured by the Walton scale, was compared to post-NET rate. Twenty-six patients were deemed to be consistently compliant with NET. Difference between pre-NET slope of muscle function deterioration to that of post-NET slope in compliant patients was -0.29 (95% CI -0.19, 0.39) (P < 0.0001). We conclude that compliance with NET can slow deterioration of muscle function and improve the natural history of adult-onset acid maltase deficiency. Muscle Nerve, 2006.
Published: 2006

24. New GAA mutations in Japanese patients with GSDII (Pompe disease)

Author: Toshiyuki Yamamoto, Norio Sakuragawa, Frank Martiniuk, Akira Oka, Eiji Nanba, Haruaki Ninomiya, Jian-Hua Feng, Yuki Ohsaki, Judy R. Pipo, Seiichi Tsujino, and Kousaku Ohno
Subjects: Adult, Male, Adolescent, Mutant, Biology, medicine.disease_cause, chemistry.chemical_compound, Developmental Neuroscience, Asian People, Polymorphism (computer science), Glycogen storage disease type II, medicine, Humans, Gene, Loss function, Genetics, Mutation, COS cells, Polymorphism, Genetic, Glycogen, Glycogen Storage Disease Type II, alpha-Glucosidases, Exons, medicine.disease, Neurology, chemistry, Child, Preschool, Pediatrics, Perinatology and Child Health, Female, Neurology (clinical)
Abstract: Glycogen storage disease type II (Pompe disease) is inherited by autosomal recessive transmission and caused by a deficiency of acid alpha-glucosidase (GAA), resulting in impaired degradation and lysosomal accumulation of glycogen. The GAA gene, responsible for this disease, has been mapped to chromosome 17q25.2-25.3. To date, more than 70 disease-causing mutations have been identified. In this study, we present four mutations found in three Japanese patients with the juvenile form of glycogen storage disease type II; three of these mutations were new (R224W, S619R, and R660H). The pathogenicity of these new mutations was verified by the loss of function of the mutant enzymes expressed in COS cells.
Published: 2003

25. Mutation at the catalytic site (M519V) in glycogen storage disease type II (Pompe disease)

Author: Nan Zhong, Maryann L. Huie, Rochelle Hirschhorn, Frank Martiniuk, and Agnes Chen
Subjects: Male, Genetics, Base Sequence, Glycogen Storage Disease Type II, DNA Mutational Analysis, Molecular Sequence Data, Infant, Disease, Biology, medicine.disease, Polymerase Chain Reaction, Mutation, Glycogen storage disease type II, Mutation (genetic algorithm), medicine, Humans, Amino Acid Sequence, Genetics (clinical)
Published: 1994
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26. Helios gene gun particle delivery for therapy of acid maltase deficiency

Author: Eleni Arvanitopoulos, Paul Plotz, Linda Bulone, William N. Rom, Alfred E. Slonim, Frank Martiniuk, Agnes Chen, Nina Raben, Adra Mack, and Vincent Donnabella
Subjects: Adult, medicine.medical_specialty, DNA, Complementary, Cell, Genetic Vectors, Cytomegalovirus, Biology, In Vitro Techniques, Gene gun, Cell Line, chemistry.chemical_compound, Mice, Internal medicine, Glycogen storage disease type II, Genetics, medicine, Animals, Humans, Myopathy, Receptor, Promoter Regions, Genetic, Molecular Biology, Mice, Knockout, Glycogen, Glycogen Storage Disease Type II, Infant, Newborn, alpha-Glucosidases, Cell Biology, General Medicine, Biolistics, medicine.disease, Hypotonia, Recombinant Proteins, Disease Models, Animal, Endocrinology, medicine.anatomical_structure, Biochemistry, chemistry, Antibody Formation, medicine.symptom, Glucan 1,4-alpha-Glucosidase, Maltase
Abstract: Autosomal recessive deficiency of lysosomal acid maltase (GAA) or glycogen storage disease type II (GSDII) results in a spectrum of phenotypes including a rapidly fatal infantile disorder (Pompe's), juvenile, and a late-onset adult myopathy. The infantile onset form presents as hypotonia with massive accumulation of glycogen in skeletal and heart muscle, with death due to cardiorespiratory failure. Adult patients with the slowly progressive form develop severe skeletal muscle weakness and respiratory failure. Particle bombardment is a safe, efficient physical method in which high-density, subcellular-sized particles are accelerated to high velocity to carry DNA into cells. Because it does not depend on a specific ligand, receptor, or biochemical features on cell surfaces, particle-mediated gene transfer can be readily applied to a variety of systems. We evaluated particle bombardment as a delivery system for therapy of GSDII. We utilized a vector carrying the CMV promoter linked to the human GAA cDNA. Human GSDII cell lines (fibroblasts and lymphoid) as well as ex vivo with adult-onset peripheral blood cells (lymphocytes and monocytes) were transiently transfected by bombardment with a Helios gene gun delivering gold particles coated with the GAA expression plasmid. All cell types showed an increase in human GAA activity greater than 50% of normal activity. Subsequently, GAA -/- mice were treated every 2 weeks for 4 months by particle bombardment to the epidermis of the lower back and hind limbs. Muscle weakness in the hind and forelimbs was reversed. These data suggest that particle delivery of the GAA cDNA by the Helios gene gun may be a safe, effective treatment for GSDII.
Published: 2002

27. Erythema nodosum leprosum, Sweet's syndrome, and human immunodeficiency virus may be related through an overlap in immunopathogenesis

Author: William R. Levis, Nada Elbuluk, and Frank Martiniuk
Subjects: Sweet's syndrome, Erythema nodosum leprosum, business.industry, Immunology, Human immunodeficiency virus (HIV), medicine, Dermatology, medicine.disease_cause, medicine.disease, business, Virology
Published: 2010
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28. Identification of two subtypes of infantile acid maltase deficiency

Author: Teresia Goldberg, Linda Bulone, Steven Ritz, Frank Martiniuk, Alfred E. Slonim, and Agnes Chen
Subjects: Male, medicine.medical_specialty, medicine.medical_treatment, Generalized muscle weakness, Cardiomyopathy, Assisted ventilation, Gastroenterology, Internal medicine, medicine, Intubation, Maltase deficiency, Humans, Age of Onset, Alglucosidase alfa, Left ventricular outflow obstruction, business.industry, Glycogen Storage Disease Type II, Hypertrophic cardiomyopathy, Infant, medicine.disease, Prognosis, Endocrinology, Pediatrics, Perinatology and Child Health, cardiovascular system, Female, New York City, business, medicine.drug
Abstract: Infantile patients with acid maltase deficiency have severe hypertrophic cardiomyopathy, left ventricular outflow obstruction, and generalized muscle weakness and die before 1 year of age. We identified 12 infants with acid maltase deficiency who had a similar clinical presentation but less severe cardiomyopathy and absence of left ventricular outflow obstruction, and 9 of 12 had longer survival with assisted ventilation and supplemental intubation.
Published: 2000

29. Leprosy in a native-born American from the eastern United States

Author: William R. Levis, Frank Martiniuk, and Aloys Cabrera
Subjects: business.industry, medicine, Ethnology, Dermatology, Leprosy, medicine.disease, business, Native-Born
Published: 2007
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30. Carrier frequency for glycogen storage disease type II in New York and estimates of affected individuals born with the disease

Author: Eleni Arvanitopoulos, William N. Rom, Ying Chen, Frank Martiniuk, Nina Raben, Agnes Chen, Paul H. Plotz, Bruce A. Hanna, Adra Mack, William J. Codd, and Phil Alcabes
Subjects: Adult, Male, medicine.medical_specialty, Heterozygote, Adolescent, New York, Disease, Internal medicine, Glycogen storage disease type II, medicine, Humans, Child, Alglucosidase alfa, Genetics (clinical), Aged, Aged, 80 and over, Carrier signal, business.industry, Glycogen Storage Disease Type II, Infant, Newborn, Infant, Middle Aged, medicine.disease, Endocrinology, Child, Preschool, Acid alpha-glucosidase, Female, business, medicine.drug
Published: 1998

31. The gene for lysosomal protein CD63 is normal in patients with Hermansky-Pudlak syndrome

Author: Frank Martiniuk, Linda W. Armstrong, and William N. Rom
Subjects: Pulmonary and Respiratory Medicine, Adult, Pathology, medicine.medical_specialty, Pulmonary Fibrosis, Blotting, Western, DNA Mutational Analysis, Platelet Membrane Glycoproteins, Biology, medicine.disease_cause, Polymerase Chain Reaction, Cell Line, Antigens, CD, Pulmonary fibrosis, medicine, Humans, RNA, Messenger, Gene, Messenger RNA, Mutation, CD63, Tetraspanin 30, Structural gene, Nucleotide Mapping, Middle Aged, medicine.disease, Oculocutaneous albinism, eye diseases, Albinism, Oculocutaneous, Female, Hermansky–Pudlak syndrome, Cell Adhesion Molecules
Abstract: Hermansky-Pudlak syndrome (HPS) is one of the few genetic disorders associated with severe pulmonary fibrosis. Fifty percent of affected patients die as a result of respiratory insufficiency. Fibrosis is thought to be caused by the accumulation of ceroid, an insoluble fluorescent lipoprotein, both extracellularly and in the lysosomes of alveolar macrophages. In addition to pulmonary fibrosis, HPS is characterized by oculocutaneous albinism and a reduction in the number of platelet dense bodies. CD63 is a protein that was described originally in platelet lysosomes. It localizes to the membranes of melanosomes and platelet dense bodies. CD63 is decreased dramatically in the lysosomes and dense bodies of patients with HPS. We theorized that CD63, a membrane protein common to lysosomes, melanosomes, and platelet dense bodies, may play a role in HPS. We sought to characterize the gene coding for this protein in HPS lymphoid cell lines. The coding region for CD63 was sequenced in control and HPS cell lines. Messenger RNA from HPS and normal cell lines was examined by Northern analysis. Genomic DNA from the same cell lines was examined by Southern analysis and polymerase chain reaction (PCR). CD63 protein in lymphoid cell lines and peripheral blood monocytes was compared by Western analysis. We found no mutations in the coding region of CD63 in an HPS cell line. We also found no diminution in the quantity of CD63 RNA by Northern analysis and no gross defects in the structural gene by PCR and Southern analysis, suggesting that the CD63 structural gene, promoter, and untranslated regions were normal. Western analysis showed that the 43-kDa protein was present in control and HPS lymphoid cell lines and peripheral blood monocytes in equivalent amounts. Although CD63 is an attractive candidate for the primary defect of HPS, the disease is probably not caused by a mutation in the CD63 gene.
Published: 1998

32. Leprosy masquerading as lupus

Author: William R. Levis, Miguel Sanchez, Frank Martiniuk, James R. Alberti, and Aloys Cabrera
Subjects: medicine.medical_specialty, Systemic lupus erythematosus, business.industry, medicine, Dermatology, Leprosy, Differential diagnosis, medicine.disease, business
Published: 2005
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33. Acid alpha-glucosidase deficiency: identification and expression of a missense mutation (S529V) in a Japanese adult phenotype

Author: Jun Tohyama, Norio Sakuragawa, Frank Martiniuk, Hiroyuki Tsunoda, Toshio Ohshima, and Masayuki Sasaki
Subjects: Adult, congenital, hereditary, and neonatal diseases and abnormalities, Nonsense mutation, Molecular Sequence Data, Biology, Polymerase Chain Reaction, Exon, Japan, Glycogen storage disease type II, Genetics, medicine, Missense mutation, Humans, Gene, Genetics (clinical), Transition (genetics), Base Sequence, Glycogen Storage Disease Type II, nutritional and metabolic diseases, alpha-Glucosidases, medicine.disease, Phenotype, Mutation (genetic algorithm), Mutation, Glucan 1,4-alpha-Glucosidase
Abstract: We report a missense mutation in an adult Japanese patient with acid alpha-glucosidase (GAA) deficiency. A TC to GT transition at nucleotides 1585-1586, was identified. This transition resulted in an amino acid substitution of Ser-529 to Val (S529V) in exon 11. We also have demonstrated that the S529V mutation abolishes the catalytic activity of the enzyme. Our data suggest that this mutation is the cause of the clinical manifestation known as adult-onset GAA deficiency. The missense mutation described here is a new mutation, and the first identified in Japanese patients with GAA deficiency.
Published: 1996

34. 489 IL-1β-511c Allele Is Associated with Increased Risk of Colonic Adenomas in Obesity

Author: Guillermo I. Perez-Perez, Michael Dorfman, Fritz Francois, Maryann L. Huie, and Frank Martiniuk
Subjects: medicine.medical_specialty, Increased risk, Endocrinology, Hepatology, business.industry, Internal medicine, Gastroenterology, medicine, Allele, medicine.disease, business, Obesity
Published: 2008
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35. A genetic linkage map of chromosome 17

Author: Heather McFarlane, Laurie J. Ozelius, Rochelle Hirschhorn, Anil Menon, James F. Gusella, Frank Martiniuk, S. Tzall, and Jonathan L. Haines
Subjects: Genetics, Genetic Markers, Male, Recombination, Genetic, Chi-Square Distribution, Gene map, Genetic Linkage, Data interpretation, Chromosome, Chromosome Mapping, Genetic linkage map, Biology, medicine.disease, Chromosome 17 (human), Genetic linkage, Data Interpretation, Statistical, medicine, Humans, Physical mapping, Female, Neurofibromatosis, Software, Chromosomes, Human, Pair 17
Abstract: We have developed a genetic linkage map of 19 markers (including nine genes) on human chromosome 17, providing 13 reference points along virtually the entire length of this chromosome. The map covers an estimated 149 cM in length (sex-averaged), with a total length of 214 cM in females and 95 cM in males. This sex difference appears to be significant along virtually the entire length of the map. This map will be useful both for providing reference points for fine structure genetic and physical mapping and for genetic linkage studies of diseases, including von Recklinghausen neurofibromatosis and Charcot-Marie-Tooth disease.
Published: 1990

36. Differential expression of adenosine deaminase isozymes in acute leukemia

Author: William Z. Borer, Henry Rappaport, Howard Ratech, and Frank Martiniuk
Subjects: Adult, Myeloid, Adenosine Deaminase, Immunology, Purine nucleoside phosphorylase, Nucleoside Deaminases, Biology, Biochemistry, Isozyme, Myelogenous, Adenosine deaminase, hemic and lymphatic diseases, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, medicine, Tumor Cells, Cultured, Humans, Child, Aged, Acute leukemia, Myeloid leukemia, hemic and immune systems, Cell Biology, Hematology, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, medicine.disease, Molecular biology, Isoenzymes, Leukemia, Leukemia, Myeloid, Acute, medicine.anatomical_structure, Purine-Nucleoside Phosphorylase, biology.protein, Blast Crisis
Abstract: Total adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) activities were measured in cell samples from 13 cases of de novo acute leukemia and from three cases of chronic myeloid leukemia in blast crisis (CMLBC). These cases could be separated into lymphoid and nonlymphoid types on the basis of enzyme activity, with two misclassifications. However, PNP activity added little or no discriminatory information. Analysis for expression of the various molecular weight (mol wt) ADA isozymes, ADA1 (40 Kd) and ADA2 (110 Kd), revealed that ADA2 was expressed exclusively in nonlymphoid cells whereas ADA1 was found in both lymphoid and nonlymphoid cell types. Identification of ADA2 divided these leukemia cases into lymphoid and nonlymphoid types with no misclassifications (P = .0002; Fisher's exact test). Acute nonlymphoblastic leukemia (ANLL) with a monocytic component tended to have a greater percentage of ADA2 than ANLL without a monocytic component. These studies suggest that ADA2 may be a novel biochemical marker for an immature nonlymphoid cell.
Published: 1988

37. Adenosine deaminase activity in normal tissues and tissues from a child with severe combined immunodeficiency and adenosine deaminase deficiency

Author: Fred S. Rosen, Frank Martiniuk, and Rochelle Hirschhorn
Subjects: medicine.medical_specialty, Adenosine Deaminase, Lymphoid Tissue, Immunology, Electrophoresis, Starch Gel, Spleen, Nucleoside Deaminases, Thymus Gland, Pathology and Forensic Medicine, Adenosine deaminase, Internal medicine, medicine, Immunology and Allergy, Humans, chemistry.chemical_classification, Severe combined immunodeficiency, Kidney, Lung, biology, Immunologic Deficiency Syndromes, medicine.disease, Adenosine deaminase deficiency, Molecular Weight, medicine.anatomical_structure, Lymphatic system, Endocrinology, Enzyme, chemistry, biology.protein
Abstract: We determined and partially characterized adenosine deaminase activity (ADA) in normal tissues and in tissues from a patient with ADA deficiency and severe combined immunodeficiency. Normal lymphoid tissues (and particularly thymus) contained the highest ADA activity which was present primarily as the less heat-stable, low molecular weight form of the enzyme. These same lymphoid tissues in the patient contained the lowest relative amounts of residual ADA activity when compared with the relative residual activity in liver, lung, and kidney. The residual ADA activity in liver was not found to differ from the normal in distribution between different molecular weight forms (an abnormality previously reported in spleen of another patient). However, an abnormality in distribution between electrophoretic forms of the enzyme was found. The fact that the major clinically deleterious effects of ADA deficiency are observed in the lymphoid system may correlate with the high levels of activity as well as with the predominance of the less heat-stable, free RBC form of the enzyme found in these tissues.
Published: 1978

38. A NOTCH2 single nucleotide polymorphism is associated with colorectal adenoma location in a multi-ethnic screening group

Author: Nelson F. Sanchez, Frank Martiniuk, Fritz Francois, Maryann L. Huie, Bryan Stierman, Angela Chen, and Said Saab
Subjects: medicine.medical_specialty, Hepatology, Group (periodic table), business.industry, Internal medicine, Gastroenterology, medicine, Ethnic group, Single-nucleotide polymorphism, Colorectal adenoma, medicine.disease, business

39. Endemic Leprosy in New York City

Author: Lilly-Rose Paraskevas, Trudy I Spencer, John S. Spencer, Mark Jacobson, William R. Levis, and Frank Martiniuk
Subjects: Gerontology, business.industry, Medicine, Dermatology, General Medicine, Leprosy, business, medicine.disease, Article

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