DOCSLIB.ORG

A Profile of Differential DNA Methylation in Sporadic Human Prion Disease Blood: Precedent, Implications and Clinical Promise

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
A Profile of Differential DNA Methylation in Sporadic Human Prion Disease Blood: Precedent, Implications and Clinical Promise A profile of differential DNA methylation in sporadic human prion disease blood: precedent, implications and clinical promise A thesis submitted in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Neuroscience from University College London Luke Child Dabin MRC Prion Unit at UCL Institute of Prion Diseases University College London 2019 Page 1 Declaration I, Luke Child Dabin, attest that the work presented in this thesis is my own. Where information has been derived from others it has been indicated in this thesis. Page 2 Dedication This thesis is dedicated to my family, through whose principles, encouragement and faith in me I have managed to achieve what I have achieved thus far. But it is also dedicated to Badass Cat, who after over a decade of friendship, multiple surgeries, two years living feral and subsisting on local farmers’ livestock, having being hit by two cars consecutively in the space of seconds and returning a day later unharmed yet coated in something else’s blood, recovering from an abscess the vet deemed inoperable on the day of a scheduled euthanasia, and repeatedly arriving home totally unflustered despite having been caught on barbed wire, finally passed from this mortal coil in 2018. Rest in peace, you magnificent bastard. Page 3 Acknowledgements I have been tremendously fortunate to receive supervision, advice and support from my two supervisors, Dr. Emmanuelle Viré and Professor Simon Mead. Having arrived at UCL after two years in Tokyo during which I spent most of my time out of the lab and away from the literature (and with a degree in Biochemistry which focused mostly on protein biology rather than genetics, let alone epigenetics), without their tuition and patience I would not have been able to achieve what I have over the last five years. They enabled me to begin, continue and complete this work, and I cannot overstate the importance of their tutorage. It has been a true privilege. There are many, many scientists whose advice and collaboration have been incredibly helpful over the course of this work. Dr Ankur Chakravarty, Dr Holger Hummerich and Dr. Tyler Gorrie-Stone provided me with advice and support as I learned how to use R, a statistical tool which has and will continue to prove essential to my work. Professor Stephan Beck gave me his time to discuss the technical aspects of epigenetic data and how to thoroughly analyse it, which given his authority within the field was priceless. Professors Jonathan Mill and Katie Lunnon kindly welcomed me to their laboratory for two weeks to learn pyrosequencing, and Dr. Adam Smith and Dr. Rebecca Smith lent me their valuable time to train and advise me on proper experimental design. This technique proved essential for much of this work and I am glad to count them as friends. Dr. Peter Sarkies, Dr. Tony Bélicard and Sheeba Singh welcomed me to their laboratory for pyrosequencing and were tremendously helpful. It is no exaggeration to say that at least half of this PhD rests on their generosity, and I cannot overstate my thanks. Dr. Mina Ryten and Professor Sebastian Brandner examined me for my MPhil-PhD upgrade. They were interested in my work, asked difficult questions and raised points for further consideration, and I am grateful for their time and advice. Professor Brandner and Dr. Zane Jaunmuktane also helped plan further work which will lead to an investigation of brain-derived DNA. Dr. Jaunmuktane spent many hours with myself and Dr. Viré in the containment level 3 laboratory dissecting prion- infected brain tissue, which considering her incredibly busy schedule was and is tremendously appreciated. Page 4 The National Prion Clinic staff have been enormously supportive, answering my questions about the clinical aspects of prion disease and providing clinical data for a range of interesting analyses. For the latter I am very grateful to Joanna Field, Irina Neves Simoes and Rachel Knight who helped me identify patient samples and connect them with clinical metrics. Dr. Akin Nihat, Dr. Hans Odd, Professor Peter Rudge and Dr. Tze-How Mok collected patient and control blood samples for me which are, obviously, beyond value. I am also very grateful to Rachel Raybould at Cardiff and Vale Hospital who provided control DNA samples, which were essential for this work. As well as the National Prion Clinic, I worked closely with the Genetics, Epigenetics and Bioinformatics (née Human Genetics) group of the MRC Institute of Prion Disease at UCL and as a result am indebted to several group members. Fernando Guntoro is one of the newest members of the group and will be continuing the group’s DNA methylation project. As well as being a genial and enthusiastic scientist, his advice regarding machine learning was incredibly helpful during the final months of my PhD. James Uphill has recently left the group, but his knowledge of patient sample locations, his diligence and his humour were much appreciated during the first half of my PhD. I have very fond memories of James’ antics, and his presence at Wednesday group meetings is missed. Gary Adamson left the group relatively early on in the course of my studies, but was cheerful, helpful and unfailingly “got” my jokes. He, James and Ron had just finished cataloguing the group’s inventory of over 50,000 DNA samples as I began my PhD. Without this resource my work would have been next to impossible, and Gary’s sense of order and attention to detail doubtlessly contributed immensely to this titanic effort. Penny Norsworth’s work and my own have not overlapped extensively, but in the face of low morale and fatigue her cheerfulness, supply of Dilbert comics and daily coffee shop runs have fuelled no small part of this manuscript. Ron Druyeh, master of the Ultra-Low Temperature freezers, has also moved on from the group. My work with frozen blood, serum and DNA samples stored in off- site containment level 3 laboratories would have been impossible without Ron, and his diligence and work ethic were inspirational. Page 5 Tracy Campbell has been tirelessly supportive when it comes to identifying samples and connected data. Above and beyond this, however, were her advice and patience during the early stages of my PhD as I began to extract DNA from prion patient blood. Her years of experience working in the group have benefited me when I had questions about rare aspects of the disease, and it’s been a pleasure to spot her when extracting patient DNA or setting up sequencing reactions. Andrew Thompson shares our office space and is a warm and thoughtful colleague. His clinical insight into facets of prion disease pathology and treatment has emerged in his questions and comments when I presented my work to the department and frequently led to invaluable discussions and new ideas. I have shared space with many people and cannot thank them all, but Amir Mayahi, Dr. Azadeh Khalili-Shirazi, David Ruegg, Professor Elizabeth Fisher, Dr. Frances Wiseman, Jackie Linehan, Dr. Jonathan Wadsworth, Kevin Williams, Dr. Laszlo Hosszu, Dr. Malin Sandberg, Mark Batchelor, Nunu Anora, Professor Parmjit Jat, Samantha McCleod, Dr. Sylvia Purro, Tamsin Nazari and Ryan Peter have all helped me on many occasions during my PhD, been friendly and approachable, and exemplify the scientific ideal of very nice but clever people working together to solve hard problems. I’ll miss them all. I must also thank other PhD students for moral support but also mentorship and advice. The foremost of these is Carolin Cyran who is a fellow Wolfson PhD student. Carolin has been a pleasure to share space, time, food and conversation with, and has been a patient soundboard for all my questions (of which there have been many) no matter how stupid (as previous). I am indebted to her and am delighted to have been able to celebrate her many successes over the previous years, which have been inspiring. I must thank several PhD students who have passed through or remained in our group, namely Emma Jones, François Kroll, Ines Whitworth, Julia Ravey and Thanos Dimitriadis. It has been exciting to meet you, share ideas and experiences and also pints in the King and Queen, and I wish you all the very best in your futures. There is a plethora of other students and friends without whom quite a difficult journey would have been more painful. I owe particular thanks to Alan Mejia-Maza, Dr. Alexandra Philiastides, Bernie Simone, Caroline Casey, Claudia Cannovò, Dr. David Thomas, Francesca De Giorgio, Grace O’Reagan, Heather Whittaker, Dr. Page 6 Justin Tosh, Madeleine Reilly, Nora Thoeng, Dr. Prasanth Sivakumar, Dr. Ruchi Kumari Kaushik and Dr. Xun Choong. I wish to highlight Dr. Laura Pulford for her enthusiastic support and statistical advice, who was a shining star in the Institute of Neurology student office, and who died towards the end of her PhD. I deeply miss her. I have friends who have supported me through tough times during my PhD who deserve gratitude. Caitlin Greenwood is a PhD student at Bristol with whom I have shared the woes and anxieties of the PhD experience, and who has unfailingly given me sound advice on handling problems and encouraged me to consider my health as a priority. Dr. Jonny Scaramanga has been a touchstone for PhD-related concerns and provided thoughtful comments on balancing the weights of qualitative and quantitative data. Melissa Liau has been a tremendously supportive and patient partner and has helped keep me sane when obstacles seem insurmountable. Dr. James Bonner and Dr. Karen Frudd have inspired me throughout the course of their PhD and provided much needed friendship and sympathy throughout my own studies.
Load more

Recommended publications
  • Epidemiology Bulletin
    VIRGINIA EPIDEMIOLOGY BULLETIN Robert B. Stroube, M.D., M.P.H., Health Commissioner Christopher Novak, M.D., M.P.H., Editor Suzanne R. Jenkins, V.M.D., M.P.H., Acting State Epidemiologist Vickie L. O’Dell, Layout Editor January 2005 Volume 105, No. 1 Transmissible Spongiform Encephalopathies (TSEs) A little over one year ago, on Decem- of diseases known as transmissible ber 25, 2003, the US Department of Agri- spongiform encephalopathies (TSEs). This a b culture (USDA) confirmed the diagnosis article is part of the Virginia Department of bovine spongiform encephalopathy of Health’s efforts to improve surveillance (BSE, or “mad cow disease”) in a single for TSEs in Virginia to better understand 1 dairy cow in Washington state. As a re- the disease as well as to detect any conversion sult, the USDA expanded and intensified changes in disease patterns. its national testing program for BSE. From June 1, 2004, to January 2, 2005, 167,476 Overview of TSEs alpha-helices beta-sheets cattle were tested. Not a single positive TSEs are a group of relatively rare pro- 2 animal was found. gressive neurodegenerative disorders that In May 2004, the New Jersey Depart- affect both humans and animals. They are Figure 1. (a) A healthy cellular ment of Health and Senior Services distinguished by long incubation periods, prion protein contains only alpha- (NJDHSS) and the Centers for Disease characteristic spongiform changes of the helices. (b) The pathogenic isoform Control and Prevention (CDC) reported brain associated with neuronal loss, and with alpha-helical structures on a suspected cluster of Creutzfeldt- the lack of a detectable immune or inflam- converted to beta-sheets.6 Jakob disease (CJD) cases (including one matory response.
    [Show full text]
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
    Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
    [Show full text]
  • Course Material and Quiz Answer Form (PDF)
    California Association for Medical Laboratory Technology Distance Learning Program PRION DISEASES Course # DL-983 by Rebecca Rosser, MA Education & Development Consultant - Laboratory Kaiser Permanente SCPMG Regional Reference Laboratory North Hollywood, CA Approved for 1.0 CE CAMLT is approved by the California Department of Public Health as a CA CLS Accrediting Agency (#21) Level of Difficulty: Intermediate 39656 Mission Blvd. Phone: 510.792.4441 Fremont, CA 94539 FAX: 510.792.3045 Notification of Distance Learning Deadline DON’T PUT YOUR LICENSE IN JEOPARDY! This is a reminder that all the continuing education units required to renew your license/certificate must be earned no later than the expiration date printed on your license/certificate. If some of your units are made up of Distance Learning courses, please allow yourself enough time to retake the test in the event you do not pass on the first attempt. CAMLT urges you to earn your CE units early! DISTANCE LEARNING ANSWER SHEET Please Circle the one best answer COURSE NAME: PRION DISEASES COURSE # DL-983 NAME ____________________________________ LIC. # ____________________ DATE ____________ SIGNATURE (REQUIRED) ___________________________________________________________________ EMAIL_______________________________________________________________________________________ ADDRESS _____________________________________________________________________________ STREET CITY STATE/ZIP 1.0 CE – FEE: $12.00 (MEMBER) | $22.00 (NON-MEMBER) PAYMENT METHOD: [ ] CHECK OR [ ] CREDIT CARD # _____________________________________ TYPE – VISA OR MC EXP. DATE ________ | SECURITY CODE: ___ - ___ - ___ 1. a b c d 2. a b c d 3. a b c d 4. a b c d 5. a b c d 6. a b c d 7. a b c d 8. a b c d 9. a b c d 10.
    [Show full text]
  • Cell Science & Stem Cell Research
    Yervand E. Karapetyan, J Cell Sci Ther 2012, 3:8 http://dx.doi.org/10.4172/2157-7013.S1.022 2nd World Congress on Cell Science & Stem Cell Research November 12-14, 2012 Hilton San Antonio Airport, USA Long double stranded RNA is present in scrapie infected cells and tissues Yervand E. Karapetyan Oncological Dispensary, Artsakh Republic he nature of the infectious agent causing scrapie and other Transmissible Spongiform Encephalopathies remains an enigma Tdespite decades of research efforts. The protein-only prion hypothesis posits that abnormal conformer of a host protein is the infectious agent. Virus and virino theories include host-independent nucleic acid as the genome of the infectious agent in addition to protein component (in case of virino a host protein and in case of virus a viral protein). Viral or sub-viral nucleic acids have long been sought in scrapie to explain the existence of multiple agent strains. Many different approaches were undertaken to find such nucleic acid. Despite that no scrapie specific nucleic acid sequences have been found in infected cells or tissues. Most viruses induce synthesis of long double stranded RNA (dsRNA) during their replication in cells. Therefore the presence of long dsRNA would be an indication of viral infection in cells. J2 monoclonal antibody against long dsRNA is a great tool for easy screening of cells and tissues for the presence of suspected unknown viral infection. This antibody has not been used for testing of scrapie infected tissues. Evidence is presented here for long dsRNA in scrapie infected cells and tissues. Such dsRNA is also found in scrapie free tissue culture cells.
    [Show full text]
  • Stroke Genetics and Genomics
    Faculdade de Medicina da Universidade de Lisboa Unidade Neurológica de Investigação Clínica PhD Thesis Stroke Genetics and Genomics Tiago Krug Coelho Host Institution: Instituto Gulbenkian de Ciência Supervisor at Instituto Gulbenkian de Ciência: Doctor Sofia Oliveira Supervisor at Faculdade de Medicina da Universidade de Lisboa: Professor José Ferro PhD in Biomedical Sciences Specialization in Neurosciences 2010 Stroke Genetics and Genomics A ciência tem, de facto, um único objectivo: a verdade. Não esgota perfeitamente a sua tarefa se não descobre a causa do todo. Chiara Lubich i Stroke Genetics and Genomics ii Stroke Genetics and Genomics A impressão desta dissertação foi aprovada pela Comissão Coordenadora do Conselho Científico da Faculdade de Medicina de Lisboa em reunião de 28 de Setembro de 2010. iii Stroke Genetics and Genomics iv Stroke Genetics and Genomics As opiniões expressas são da exclusiva responsabilidade do seu autor. v Stroke Genetics and Genomics vi Stroke Genetics and Genomics Abstract ABSTRACT This project presents a comprehensive approach to the identification of new genes that influence the risk for developing stroke. Stroke is the leading cause of death in Portugal and the third leading cause of death in the developed world. It is even more disabling than lethal, and the persistent neurological impairment and physical disability caused by stroke have a very high socioeconomic cost. Moreover, the number of affected individuals is expected to increase with the current aging of the population. Stroke is a “brain attack” cutting off vital blood and oxygen to the brain cells and it is a complex disease resulting from environmental and genetic factors.
    [Show full text]
  • Isolation of a Cdna Clone Encoding the Leader Peptide of Prion Protein and Expression of the Homologous Gene in Various Tissues
    Proc. Nail. Acad. Sci. USA Vol. 83, pp. 6377-6381, September 1986 Biochemistry Isolation of a cDNA clone encoding the leader peptide of prion protein and expression of the homologous gene in various tissues (scrapie/scraple-associated fibril protein/membrane protein/prion hypothesis) NIKOLAos K. ROBAKIS*, PRITHvi R. SAWH*, GLORIA C. WOLFE*, RICHARD RUBENSTEIN*, RICHARD I. CARP*', AND MICHAEL A. INNISt *New York State Office of Mental Retardation and Developmental Disabilities, Institute for Basic Research, 1050 Forest Hill Road, Staten Island, NY 10314; and tCetus Corporation, Emeryville, CA 94608 Communicated by Fotis C. Kafatos, May 19, 1986 ABSTRACT We have isolated a hamster cDNA clone been proposed as the major structural component of the representing the coding sequences for the entire precursor of scrapie agent (14). Recently, it has been shown that NrP 27-30 prion protein (PrP) 27-30. This clone encodes a protein of 254 is encoded by a host gene, which is expressed at similar levels residues and contains an in-frame ATG codon 42 bases in normal and scrapie-infected brains. The partial nucleotide upstream from the one previously reported. Analysis of the sequence of the mRNA encoding the NrP 27-30 precursor predicted amino acid sequence suggests that the NrP precursor protein was also described (15). Immunological evidence protein contains an amino-terminal signal sequence, and a suggests that NrP 27-30 derives from the proteolytic cleavage membrane-spanigdomain in the carboxyl terminus. Cleav- of a larger precursor, NrP 33-35 (15, 16). age of the signal peptide would produce a mature protein of 232 Here we report the isolation and characterization of a amino acids.
    [Show full text]
  • Identification of Biomarkers of Metastatic Disease in Uveal
    Identification of biomarkers of metastatic disease in uveal melanoma using proteomic analyses Thesis submitted in accordance with the requirements of the University of Liverpool for the degree of Doctor in Philosophy Martina Angi June 2015 To Mario, the wind beneath my wings 2 Acknowledgments First and foremost, I would like to acknowledge my primary supervisor, Prof. Sarah Coupland, for encouraging me to undergo a PhD and for supporting me in this long journey. I am truly grateful to Dr Helen Kalirai for being the person I could always turn to, for a word of advice on cell culture as much as on parenting skills. I would also like to acknowledge Prof. Bertil Damato for being an inspiration and a mentor; and Dr Sarah Lake and Dr Joseph Slupsky for their precious advice. I would like to thank Dawn, Haleh, Fidan and Fatima for becoming my family away from home, and the other members of the LOORG for the fruitful discussions and lovely cakes. I would like to acknowledge Prof. Heinrich Heimann and the clinical team at LOOC, especially Sisters Hebbar, Johnston, Hachuela and Kaye, for their admirable dedication to UM patients and for their invaluable support to clinical research. I would also like to thank the members of staff in St Paul’s theatre and Simon Biddolph and Anna Ikin in Pathology for their precious help in sample collection. I am grateful to Dr Rosalind Jenkins who guided my first steps in the mysterious word of proteomics, and to Dr Deb Simpsons and Prof. Rob Beynon for showing me its beauty.
    [Show full text]
  • Vaccines and How They Work Vaccines and How They Work Vaccines and How They Work Npi Reference Guide on Vaccines and Vaccine Safety 5
    VACCINES AND HOW THEY WORK VACCINES AND HOW THEY WORK VACCINES AND HOW THEY WORK NPI REFERENCE GUIDE ON VACCINES AND VACCINE SAFETY 5 GLOSSARY TERMS VACCINES AND HOW THEY WORK Acquired immunity Immunization Acute Influenza Infectious Diseases Antibody Innate immunity Antigen Lymphocytes Infectious diseases have been the bane of human existence throughout history. Association Macrophage Evidence of infection has been found in mummified remains from ancient Egypt1 Asthma Measles 2 Attenuated vaccines Mumps and elsewhere, and in the oral and written histories of all cultures. The Black Death Autoimmune disease Neisseria meningitidis of the Middles Ages,3 the decimation of the native peoples of the Americas by B cell Neonate imported disease4 and the worldwide influenza epidemic of 19184 are vivid reminders Bacteria Pathogens Booster Pentavalent vaccine that infectious diseases have profoundly shaped our world and have the potential to Bordetella pertussis Pertussis do so again. Cases Pneumococcal disease Causal association Pneumococcal polysaccharide Infectious diseases are caused by organisms that are able to exploit the human body Cell-mediated response Pneumonia so that they may grow and reproduce. In general, these organisms are tiny and can Chemokines Polysaccharide Chickenpox Polysaccharide vaccine exist in our lungs, blood or other body tissues and organs. They gain access to us Chronic Protein through the air we breathe, the food and water we ingest, or damage to our skin. Clostridium tetani Rabies Disease-causing agents (pathogens) include bacteria and viruses.5 Combination vaccine Recombinant DNA technology Conjugate vaccine Risk Bacteria are tiny and can be seen only with the aid of a microscope.
    [Show full text]
  • PRODUCT SPECIFICATION Prest Antigen C9orf64 Product
    PrEST Antigen C9orf64 Product Datasheet PrEST Antigen PRODUCT SPECIFICATION Product Name PrEST Antigen C9orf64 Product Number APrEST90167 Gene Description chromosome 9 open reading frame 64 Alternative Gene MGC10999 Names Corresponding Anti-C9orf64 (HPA066190) Antibodies Description Recombinant protein fragment of Human C9orf64 Amino Acid Sequence Recombinant Protein Epitope Signature Tag (PrEST) antigen sequence: SDDLLKKLLKGEMLSYGDRQEVEIRGCSLWCVELIRDCLLELIEQKGEKP NGEINSILLDYYLWDYAHDHREDMKGIPFHRIRCIY Fusion Tag N-terminal His6ABP (ABP = Albumin Binding Protein derived from Streptococcal Protein G) Expression Host E. coli Purification IMAC purification Predicted MW 28 kDa including tags Usage Suitable as control in WB and preadsorption assays using indicated corresponding antibodies. Purity >80% by SDS-PAGE and Coomassie blue staining Buffer PBS and 1M Urea, pH 7.4. Unit Size 100 µl Concentration Lot dependent Storage Upon delivery store at -20°C. Avoid repeated freeze/thaw cycles. Notes Gently mix before use. Optimal concentrations and conditions for each application should be determined by the user. Product of Sweden. For research use only. Not intended for pharmaceutical development, diagnostic, therapeutic or any in vivo use. No products from Atlas Antibodies may be resold, modified for resale or used to manufacture commercial products without prior written approval from Atlas Antibodies AB. Warranty: The products supplied by Atlas Antibodies are warranted to meet stated product specifications and to conform to label descriptions when used and stored properly. Unless otherwise stated, this warranty is limited to one year from date of sales for products used, handled and stored according to Atlas Antibodies AB's instructions. Atlas Antibodies AB's sole liability is limited to replacement of the product or refund of the purchase price.
    [Show full text]
  • The Clinicians' Guide to Creutzfeldt-Jakob Disease
    Henry Ford Hospital Medical Journal Volume 35 Number 1 Article 17 3-1987 The Clinicians' Guide to Creutzfeldt-Jakob Disease Thomas H. Swanson Follow this and additional works at: https://scholarlycommons.henryford.com/hfhmedjournal Part of the Life Sciences Commons, Medical Specialties Commons, and the Public Health Commons Recommended Citation Swanson, Thomas H. (1987) "The Clinicians' Guide to Creutzfeldt-Jakob Disease," Henry Ford Hospital Medical Journal : Vol. 35 : No. 1 , 76-83. Available at: https://scholarlycommons.henryford.com/hfhmedjournal/vol35/iss1/17 This Article is brought to you for free and open access by Henry Ford Health System Scholarly Commons. It has been accepted for inclusion in Henry Ford Hospital Medical Journal by an authorized editor of Henry Ford Health System Scholarly Commons. Special Feature The Clinicians' Guide to Creutzfeldt-Jakob Disease Thomas H. Swanson, MD* Creutzfeldt-Jakob disease, a transmissible, rapidly progressive dementia of unknown etiology, mimics Alzheimer's disease, presents in middle life, and affects many central nervous system structures. The disease progresses in three distinct stages, culminating in death. Its occurrence is sporadic and its distribution worldwide. Pathological changes are varied, but spongy degeneration ofthe neuropil is classic. Research on scrapie, the anirrml model of Creutzfeldt-Jakob disease, has demonstrated that this unconventional, slow disease is transmitted via a small (less than 50,000 mW) particle, which is composed principally of protein. How this infectious particle, variably rmmed prion, virino, or slow virus, invokes disease or is transmitted is unclear The agent does not evoke a host immune response, nor does it appear to contain nucleic acid.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2013/0022974 A1 Chinnaiyan Et Al
    US 2013 0022974A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2013/0022974 A1 Chinnaiyan et al. (43) Pub. Date: Jan. 24, 2013 (54) DNA METHYLATION PROFILES IN CANCER Publication Classification (75) Inventors: Arul M. Chinnaiyan, Plymouth, MI (51) Int. Cl. (US); Mohan Saravana Dhanasekaran, Ann Arbor, MI (US); Jung Kim, CI2O I/68 (2006.01) Northville, MI (US) (52) U.S. Cl. ...................................................... 435/6.11 (73) Assignee: THE REGENTS OF THE UNIVERSITY OF MICHIGAN, Ann (57) ABSTRACT Arbor, MI (US) (21) Appl. No.: 13/523,545 The present invention relates to compositions and methods (22) Filed: Jun. 14, 2012 for cancer diagnosis, research and therapy, including but not limited to, cancer markers. In particular, the present invention Related U.S. Application Data relates to methylation levels of genes (e.g., in CGI islands of (60) Provisional application No. 61/498,296, filed on Jun. the promoter regions) as diagnostic markers and clinical tar 17, 2011. gets for prostate cancer. Patent Application Publication Jan. 24, 2013 Sheet 1 of 30 US 2013/0022974 A1 Figure 1 A SS 838 s & S&s&&xis&3:38 a. a. a. a. a. a. a. a. a. 888& R is Patent Application Publication Jan. 24, 2013 Sheet 2 of 30 US 2013/0022974 A1 &- 3838; iiirage::c Benign Adja Patent Application Publication Jan. 24, 2013 Sheet 3 of 30 US 2013/0022974 A1 Figure 3 N = 6619 tique TSS Else.” (6077 Unique Reiseg Genes) t S S SS &S .S. SMyy Na3S S Nd: - alie Nic23 Ci (pg islands Cin 5'Shore of CpG islands On 3 Shore of CpG islands On Non-CpG islancis Patent Application Publica US 2013/0022974 A1 ty?un81 Patent Application Publication Jan.
    [Show full text]
  • Larina Carroll Thesis February 9 2018 FINAL for SUBMISSION
    Functional Genomics Studies of Atlantic Salmon (Salmo salar) Development, and Sac Fry Responses to Chronic Incremental Hyperthermia By: Larina A. Carroll A thesis submitted to the Department of Biology and the School of Graduate Studies in partial fulfilment of the requirements for the degree of Master of Science Ocean Sciences Centre and Department of Biology, Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada ABSTRACT Functional genomics techniques, including the 32K cGRASP microarray and real-time quantitative polymerase chain reaction (QPCR), were used to study gene expression in a single Atlantic salmon cohort: 1) during embryonic and early sac fry development; and 2) after sac fry were exposed to chronic incremental hyperthermia (water temperature increased by 1 °C every 24 hours, from 7.4 to 21.4 °C). The first study focused on the transcript expression of four microarray-identified paralogous γM-crystallin genes as well as four paralogous α-sHSP genes. The four α-sHSPs, as well as cryGM4-like and cryGM3-like, were shown by QPCR as higher expressed at hatch or post-hatch stage relative to eye-up stage (although the degree of induction varied between paralogues). This research provides possible evidence of divergent transcript expression (i.e., regulation) of duplicated genes, suggesting that some of the paralogues studied may have diverged functionally. These results provide insight into the evolutionary relationships between these genes, and may provide evidence of neofunctionalization following GD events. The second study focused on four microarray-identified genes of interest (trypsin-1 precursor, chymotrypsin b, ferritin middle subunit, and ubiquitin) as well as the four paralogous α-sHSP genes.
    [Show full text]