DOCSLIB.ORG

University of Southampton Research Repository Eprints Soton

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
University of Southampton Research Repository Eprints Soton University of Southampton Research Repository ePrints Soton Copyright © and Moral Rights for this thesis are retained by the author and/or other copyright owners. A copy can be downloaded for personal non-commercial research or study, without prior permission or charge. This thesis cannot be reproduced or quoted extensively from without first obtaining permission in writing from the copyright holder/s. The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the copyright holders. When referring to this work, full bibliographic details including the author, title, awarding institution and date of the thesis must be given e.g. AUTHOR (year of submission) "Full thesis title", University of Southampton, name of the University School or Department, PhD Thesis, pagination http://eprints.soton.ac.uk UNIVERSITY OF SOUTHAMPTON FACULTY OF MEDICINE, HEALTH AND LIFE SCIENCES School of Biological Sciences DECONTAMINATION OF PRIONS, PRION-ASSOCIATED AMYLOID AND INFECTIVITY FROM SURGICAL STAINLESS STEEL – IMPLICATIONS FOR THE RISK OF IATROGENIC TRANSMISSION OF CJD By ROBERT HOWLIN Thesis submitted for the degree of Doctor of Philosophy September 2009 ABSTRACT FACULTY OF MEDICINE, HEALTH AND LIFE SCIENCES SCHOOL OF BIOLOGICAL SCIENCES Doctor of Philosophy DECONTAMINATION OF PRIONS, PRION-ASSOCIATED AMYLOID AND INFECTIVITY FROM SURGICAL STAINLESS STEEL – IMPLICATIONS FOR THE RISK OF IATROGENIC TRANSMISSION OF CJD By Robert Howlin The physicochemical nature of the infectious agent in prion diseases creates a significant challenge for decontamination services. It has been shown to be both resistant to standard methods of decontamination, used to inactivate viruses and bacteria, and to associate avidly with surgical stainless steel. Moreover, the pathophysiology of the variant, iatrogenic and sporadic forms of Creutzfeldt-Jakob Disease (CJD) suggests deposition of the infectious agent across a wide range of extraneural, lymphoid tissues, as well as in the skeletal muscle and blood. Coupled with the potential for asymptomatic carriers, there is a significant risk of iatrogenic transmission of CJD through both neurosurgical procedures and standard surgery. This PhD study was undertaken in order to improve methods of instrument decontamination and to evaluate prion detection techniques and their applicability for the assessment of prion inactivation and removal. The project has provided relevant, critical assessment of hospital decontamination procedures, in addition to guidance on how working protocols should be improved to provide a cleaner and safer end product for the patient. Moreover, laboratory studies have been performed to evaluate current methods of prion decontamination in the context of hospital procedures for instrument reprocessing. Challenges faced by sterile service departments, such as soil drying and surface degradation, have been addressed and their impact on the risk of iatrogenic transmission of prions has been investigated. Critically, the use of a fluorescent amyloid fluorophore for the detection of prion- associated amyloid as a marker for disease permitted the investigation of the role of amyloid in infectious disease under denaturing conditions. Correlation of this detection technique with the identification of PrP res by Western blot and infectious disease suggested that, whilst fluorescent detection of prion-associated amyloid was more sensitive than Western blot, PrP res detection was more specific relative to infectivity. Improved fluorophores, with greater sensitivity, have been evaluated which will enhance in situ detection of prions in the future. ii LIST OF CONTENTS SECTION TITLE PAGE TITLE PAGE……………………………………………………………………………..……i ABSTRACT……………………………………………………………………………………ii LIST OF CONTENTS…………………………………………………………………..…....iii LIST OF FIGURES AND TABLES…....…………………………………...……………. viii AUTHOR DECLARATION………………………………………………………………..xiii ACKNOWLEDGEMENTS………………………………………………………………...xiv PUBLICATIONS…………………………………………………………………………….xv LIST OF ABBREVIATIONS………………………...…………………………………….xvi CHAPTER 1 – INTRODUCTION TO PRIONS DISEASES……………………………....1 1.1. Introduction………………………………………………………………...2 1.2. The Prionopathies and their Epidemiology…………………………........2 1.3. PRNP and the Cellular Prion Protein…………………………………...10 1.3.1. The Normal Physiological Function(s) of PrP c…………………………….14 1.4. The Pathological Prion Protein…………………………………………..18 1.4.1. The Site of PrP res Conversion………………………………………………19 1.4.2. Important Molecular Structures in the Conversion of PrP c to PrP res ……….20 1.4.3. Evidence for an Auxiliary Factor in Prion Conversion…………………….23 1.4.4. Mechanism(s) of PrP res misfolding………………………………………...24 1.4.5. Aggregation, Fragmentation and Replication of PrP res …………………….26 1.5. The Infectious Agent…………...………………………………………....29 1.6. Prion Disease Pathogenesis………………………………………………32 1.6.1. Infection and Peripheral Replication……………………………………….33 1.6.2. Peripheral Migration and Neuroinvasion…………………………………..34 1.6.3. Neurodegeneration…………………………………………………………35 1.7. Factors Influencing Prion Disease Transmission……………………….37 1.7.1. Prion Strains………………………………………………………………..37 1.7.2. The Species Barrier………………………………………………………...39 1.7.3. Genetic Susceptibility……………………………………………………...40 iii 1.7.3.1. Asymptomatic carriers……………………………………………………………42 1.8. Iatrogenic Creutzfeldt-Jakob Disease…………………………………...43 1.9. Decontamination of Surgical Instruments………………………………45 1.10. Project Aims and Rationale……………………………………………....47 CHAPTER 2 – MATERIALS AND METHODS………………………………………..…49 2.1. Animals…………………………………………………………………….50 2.2. Strains and Preparation of brain tissue…………………………………50 2.2.1. ME7 Scrapie-infected Brain Homogenate…………………………………50 2.2.2. 263K Scrapie-infected Brain Homogenate………………………………...51 2.2.3. Preparation of Brain Sections………………………………………………51 2.3. Contamination of Test Surfaces………………………………………….52 2.3.1. Standard Stainless Steel Wires……………………………………………..52 2.3.2. Artificial Degraded Stainless Steel Wires………………………………….52 2.3.2.1. Conformation of wires surface tomography……………………………………52 2.3.3. Stainless Steel Tokens……………………………………………………...53 2.3.3.1. Contamination of stainless steel tokens by handling……………………….…53 2.4. Surface Decontamination Techniques…………………………………...53 2.4.1. Decontamination of Wires Using A High Temperature and Pressure Autoclave Treatment……………………………………………………….53 2.4.2. Decontamination Using Simulated Washer-Disinfector Cycles…………...54 2.4.3. Decontamination of Artificially Degraded Wires………………………….55 2.4.4. Decontamination of Wires: Methodology Correlation Study……………...56 2.5. Staining Techniques………………………………………………………56 2.5.1. General Protein Stain………………………………………………………57 2.5.2. Prion Amyloid Stain……………………………………………………….57 2.5.3. Thioflavin T/SYPRO Ruby Dual Staining Technique…………………….57 2.5.4. 2-(4’-Methylaminophenyl)Benzothiazol (BTA-1) Stain for Prion Amyloid……………………………………………………………...58 2.6. Analysis of Thiazole Analogues………………………………………….58 2.6.1. Assessment of Analogue Staining Efficiency……………………………...59 iv 2.6.2. Analysis of 2-(4’-Dimethylaminophenyl)-6-Methyloxybenzothiazole (28d) binding specificity………………………………..………………….59 2.6.3. Analysis of the Rate of Photobleaching of 2-(4’-Dimethylamino- phenyl)-6-Methyloxybenzothiazole (28d) relative to BTA-1…………...…60 2.6.4. Correlation of 2-(4’-Dimethylaminophenyl)-6-Methyloxybenzothiazole (28d) and BTA-1 Fluorescence with the Monoclonal Anti-PrP Antibody 6H4………………………………………………………………60 2.7. Episcopic Differential Interference Contrast Microscopy Coupled with Epi-Fluorescence (EDIC/EF)………………..….………..61 2.7.1. Epi-Fluorescence Filter Blocks…………………………………………….63 2.7.2. Statistical Analysis…………………………………………………………64 2.8. Western Blot………………………………..……………………………..64 2.8.1. Preparation of Samples – Suspension Studies……………………………..64 2.8.1.1. Exposure parameters intended for the preparation of homogenate samples for the antibody mapping of PrP res …….……………………………..64 2.8.2. Preparation of Samples – Surface Studies…………………………………65 2.8.3. Western Blot Protocol……………………………………………………...65 2.9. Animal Bioassay Studies………………………………………………….68 2.10. Hospital Sterile Service Department (SSD) Studies…………………….68 2.10.1. An Assessment of the Effectiveness of a Validated Washer- Disinfector Cleaning Cycle…………………………….…………………..68 2.10.2. An Assessment of the Acquisition of Proteinaceous Contamination Through Handling by SSD Staff in the Clean Room………………..……..69 CHAPTER 3 – ASPECTS OF THE DECONTAMINATION OF SURGICAL INSTRUMENTS IN HOSPITAL STERILE SERVICE DEPARTMENTS……………..72 3.1. Introduction……………………………………………………………….73 3.2. Materials and Methods…………………………………………………...74 3.3. Results…………………………………………………………………..…75 3.3.1. Evaluation of a Washer-Disinfector Cycle………………………………...75 3.3.2. Protein Contamination of Stainless Steel by Hand………………………...78 3.3.3. Protein Contamination of Surgical Instruments by Hand………………….79 v 3.3.4. The Effect of Autoclave Treatment on Protein Attachment to Stainless Steel……………………………………………………………....81 3.4. Discussion………………………………………………………………….82 CHAPTER 4 – DECONTAMINATION OF TISSUE PROTEIN AND PRION AMYLOID FROM SURGICAL STAINLESS STEEL DURING SIMULATED WASHER-DISINFECTOR CYCLES……………………………………………………...86 4.1. Introduction……………………………………………………………….87 4.2. Materials and Methods…………………………………………………...88 4.3. Results……………………………………………………………………..88 4.4. Discussion………………………………………………………………….94 CHAPTER 5 – THE EFFECT OF SURFACE DEGRADATION ON THE EFFICIENCY OF PRION DECONTAMINATION………………………………..……..98 5.1. Introduction………………………………………………………...……..99
Load more

Recommended publications
  • Assessment of Prion Uptake by Plants Using Protein Misfolding
    ASSESSMENT OF PRION UPTAKE BY PLANTS USING PROTEIN MISFOLDING CYCLIC AMPLIFICATION by Matthew W. Keating A dissertation submitted in partial fulfillment of the requirements for the degree of Master of Science (Civil and Environmental Engineering)\ at the UNIVERSITY OF WISCONSIN-MADISON 2014 Date of final oral examination: August 19th, 2014 The dissertation is approved by the following members of the Final Oral Committee: Christopher J. Johnson, Honorary Fellow, Pathobiological Sciences Sharon C. Long, Professor, Soil Science Katherine D. McMahon, Professor, Environmental Engineering Joel A. Pederson, Professor, Soil Science i DEDICATION To my family, whose guidance installed the belief that there was no limit to my success, and who taught me all you need is a thumbs up to express the utmost encouragement. And to my girlfriend, who has shown me what it feels like to be infinite. ii ACKNOWLEDGMENTS The completion of this report could not have been possible without the assistance of many people that I have worked with throughout the past couple of years at the University of Wisconsin-Madison. All of your contributions are sincerely appreciated. To start, my thesis advisors warrant special recognition: Joel Pedersen, for the opportunity to participate in this great project and for your encouragement in not only my research, but my growth as a scientist. Your willingness to challenge me academically and the always helpful feedback contributed enormously to the production of this thesis. I am indebted to you and the trust you displayed in me. Christopher Johnson, for always leaving your door open to me and my endless list of questions and having a great amount of patience with an engineer trying to thrive in the molecular biology field.
    [Show full text]
  • Neuroscience in Nazi Europe Part II: Resistance Against the Third Reich Lawrence A
    HISTORICAL REVIEW Neuroscience in Nazi Europe Part II: Resistance against the Third Reich Lawrence A. Zeidman ABSTRACT: Previously, I mentioned that not all neuroscientists collaborated with the Nazis, who from 1933 to 1945 tried to eliminate neurologic and psychiatric disease from the gene pool. Oskar and Cécile Vogt openly resisted and courageous ly protested against the Nazi regime and its policies, and have been discussed previously in the neurology literature. Here I discuss Alexander Mitscherlich, Haakon Saethre, Walther Spielmeyer, Jules Tinel, and Johannes Pompe. Other neuroscientists had ambivalent roles, including Hans Creutzfeldt, who has been discussed previously. Here, I discuss Max Nonne, Karl Bonhoeffer, and Oswald Bumke. The neuroscientists who resisted had different backgrounds and moti vations that likely influenced their behavior, but this group undoubtedly saved lives of colleagues, friends, and patients, or at least prevented forced sterilizations. By recognizing and understanding the actions of these heroes of neuroscience, we pay homage and realize how ethics and morals do not need to be compromised even in dark times. RÉSUMÉ: Neuroscience en Europe sous domination nazie, 2e partie : résistance contre le Troisième Reich. J’ai mentionné antéri eurement que tous les neuroscientifiques n’avaient pas collaboré avec les nazis qui, de 1933 à 1945, ont tenté d’éliminer la maladie neurologique et psychiatrique du patrimoine génétique. Oskar et Cécile Vogt se sont opposés ouvertement et ont protesté courageusement contre le régime nazi et ses politiques. Ce sujet a déjà été exposé dans la littérature neurologique. Je discute ici d’Alexander Mitscherlich, de Haakon Saethre, de Walther Spielmeyer, de Jules Tinel et de Johannes Pompe.
    [Show full text]
  • Saved Lives of Colleagues, Friends, and Patients, Or at Least Prevented Forced Sterilizations
    HISTORICAL REVIEW Neuroscience in Nazi Europe Part II: Resistance against the Third Reich Lawrence A. Zeidman ABSTRACT: Previously, I mentioned that not all neuroscientists collaborated with the Nazis, who from 1933 to 1945 tried to eliminate neurologic and psychiatric disease from the gene pool. Oskar and Cécile Vogt openly resisted and courageous ly protested against the Nazi regime and its policies, and have been discussed previously in the neurology literature. Here I discuss Alexander Mitscherlich, Haakon Saethre, Walther Spielmeyer, Jules Tinel, and Johannes Pompe. Other neuroscientists had ambivalent roles, including Hans Creutzfeldt, who has been discussed previously. Here, I discuss Max Nonne, Karl Bonhoeffer, and Oswald Bumke. The neuroscientists who resisted had different backgrounds and moti vations that likely influenced their behavior, but this group undoubtedly saved lives of colleagues, friends, and patients, or at least prevented forced sterilizations. By recognizing and understanding the actions of these heroes of neuroscience, we pay homage and realize how ethics and morals do not need to be compromised even in dark times. RÉSUMÉ: Neuroscience en Europe sous domination nazie, 2e partie : résistance contre le Troisième Reich. J’ai mentionné antéri eurement que tous les neuroscientifiques n’avaient pas collaboré avec les nazis qui, de 1933 à 1945, ont tenté d’éliminer la maladie neurologique et psychiatrique du patrimoine génétique. Oskar et Cécile Vogt se sont opposés ouvertement et ont protesté courageusement contre le régime nazi et ses politiques. Ce sujet a déjà été exposé dans la littérature neurologique. Je discute ici d’Alexander Mitscherlich, de Haakon Saethre, de Walther Spielmeyer, de Jules Tinel et de Johannes Pompe.
    [Show full text]
  • Creutzfeldt-Jakob Disease
    International Journal of Clinical Psychiatry 2016, 4(1): 1-7 DOI: 10.5923/j.ijcp.20160401.01 Neuropsychiatric Symptoms among the Major Categories of Creutzfeldt-Jakob Disease Richard P. Conti1,*, Jacqueline M. Arnone2 1Department of Psychology, Kean University, Union, USA 2Department of Nursing, Kean University, Union, USA Abstract Creutzfeldt-Jakob disease (CJD) is a progressive terminal neurodegenerative disease classified within the human prion disorders. There are four distinct categories of the disorder: variant, iatrogenic, sporadic and familial. Onset is typically precipitous with death occurring within a year of symptom commencement. Worldwide incidence is approximately one case per million per population each year. In the United States this translates to roughly 300 new cases a year. Presentation typically occurs between 50 and 70 years of age with median age onset of 60 and is without gender bias. Currently, no cure exists and treatment is only palliative for symptoms. Classic features of CJD include rapidly progressive dementia, myoclonus and ataxia, yet most case reports have demonstrated initial presentation in the form of nonspecific psychiatric and neurological symptoms. Since wide-ranging psychiatric symptoms are frequently the first indices of the disease, this paper reviews the symptoms across the four categories of CJD. Misdiagnosis early in the course of the disease is problematic and occurs most frequently from symptom heterogeneity. The preponderance of evidence suggests that since initial symptoms can occur with or without the hallmark signs of the disease, utilization of a global approach for early detection and diagnosis is warranted that is inclusive of repeated, supportive diagnostic tests performed at various points in time.
    [Show full text]
  • Mortuary Practices, Genetics and Other Factors Relevant to the Transmission of Kuru in Papua New Guinea
    Mortuary practices, genetics and other factors relevant to the transmission of kuru in Papua New Guinea Mr Jerome T Whitfield University College London PhD in Neurology 1 ‘I, Mr Jerome T Whitfield, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis.’ ................................................................... 2 Table of Contents Title page..............................................................................................1 Table of Contents .............................................................................. 3 List of Tables and Figures ............................................................... 36 Abstract ........................................................................................... 41 Introduction ..................................................................................... 44 Chapter 1: Prion diseases of humans and animals ........................ 49 Introduction .................................................................................... 49 Prion diseases of animals ............................................................... 53 Scrapie ......................................................................................... 54 Transmissible mink encephalopathy ......................................... 56 Chronic wasting disease in North American cervids ................ 58 Prion diseases of humans ..............................................................
    [Show full text]
  • Prion Characterization Using Cell Based Approaches
    University of Kentucky UKnowledge Theses and Dissertations--Microbiology, Microbiology, Immunology, and Molecular Immunology, and Molecular Genetics Genetics 2012 PRION CHARACTERIZATION USING CELL BASED APPROACHES Vadim Khaychuk University of Kentucky, [email protected] Right click to open a feedback form in a new tab to let us know how this document benefits ou.y Recommended Citation Khaychuk, Vadim, "PRION CHARACTERIZATION USING CELL BASED APPROACHES" (2012). Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics. 2. https://uknowledge.uky.edu/microbio_etds/2 This Doctoral Dissertation is brought to you for free and open access by the Microbiology, Immunology, and Molecular Genetics at UKnowledge. It has been accepted for inclusion in Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics by an authorized administrator of UKnowledge. For more information, please contact [email protected]. STUDENT AGREEMENT: I represent that my thesis or dissertation and abstract are my original work. Proper attribution has been given to all outside sources. I understand that I am solely responsible for obtaining any needed copyright permissions. I have obtained and attached hereto needed written permission statements(s) from the owner(s) of each third-party copyrighted matter to be included in my work, allowing electronic distribution (if such use is not permitted by the fair use doctrine). I hereby grant to The University of Kentucky and its agents the non-exclusive license to archive and make accessible my work in whole or in part in all forms of media, now or hereafter known. I agree that the document mentioned above may be made available immediately for worldwide access unless a preapproved embargo applies.
    [Show full text]
  • À Luz Do Biológico: Psiquiatria, Neurologia E Eugenia Nas Relações Brasil-Alemanha (1900-1942)
    Casa de Oswaldo Cruz – FIOCRUZ Programa de Pós-Graduação em História das Ciências e da Saúde PEDRO FELIPE NEVES DE MUÑOZ À LUZ DO BIOLÓGICO: PSIQUIATRIA, NEUROLOGIA E EUGENIA NAS RELAÇÕES BRASIL-ALEMANHA (1900-1942) Rio de Janeiro 2015 PEDRO FELIPE NEVES DE MUÑOZ À LUZ DO BIOLÓGICO: PSIQUIATRIA, NEUROLOGIA E EUGENIA NAS RELAÇÕES BRASIL-ALEMANHA (1900-1942) Tese de doutorado apresentada ao Curso de Pós-Graduação em História das Ciências e da Saúde da Casa de Oswaldo Cruz/FIOCRUZ, como requisito parcial para obtenção do Grau de Doutor. Área de Concentração: História das Ciências. Orientadora: Prof.ª Dr.ª Cristiana Facchinetti Coorientador: Prof. Dr. Stefan Rinke Rio de Janeiro 2015 PEDRO FELIPE NEVES DE MUÑOZ À LUZ DO BIOLÓGICO: PSIQUIATRIA, NEUROLOGIA E EUGENIA NAS RELAÇÕES BRASIL-ALEMANHA (1900-1942) Tese de doutorado apresentada ao Curso de Pós-Graduação em História das Ciências e da Saúde da Casa de Oswaldo Cruz-FIOCRUZ, como requisito parcial para obtenção do Grau de Doutor. Área de Concentração: História das Ciências. BANCA EXAMINADORA ___________________________________________________________________ Prof.ª Dr.ª Cristiana Facchinetti (COC/FIOCRUZ) - Orientadora ___________________________________________________________________ Prof. Dr. Stefan Rinke (LAI/FU Berlim) – Co-orientador ___________________________________________________________________ Prof. Dr. Francisco Carlos Teixeira da Silva (ECEME) ___________________________________________________________________ Prof.ª Dr.ª Yonissa Marmitt Wadi (UNIOESTE) ___________________________________________________________________
    [Show full text]
  • Christian-Albrechts-Universität Zu Kiel 350 Jahre Wirken in Stadt, Land Und Welt
    Oliver Auge (Hg.) Christian-Albrechts-Universität zu Kiel 350 Jahre Wirken in Stadt, Land und Welt Christian-Albrechts- Universität zu Kiel 350 Jahre Wirken in Stadt, Land und Welt Herausgegeben350 von Oliver Auge 1. Aulage 2015 © 2015 Wachholtz Verlag – Murmann Publishers, Kiel / Hamburg Das Werk, einschließlich aller seiner Teile, ist urheberrechtlich geschützt. Jede Verwertung ist ohne Zustimmung des Verlages unzulässig. Das gilt insbesondere für Vervielfältigungen, Übersetzungen, Mikroverilmungen und die Einspeicherung und Verarbeitung in elektronischen Systemen. Gesamtherstellung: Wachholtz Verlag Satz und Layout: Das Herstellungsbüro, Hamburg Printed in Germany ISBN 978-3-529-05905-6 Besuchen Sie uns im Internet: www.wachholtz-verlag.de Inhalt Torsten Albig 11 Grußwort des Ministerpräsidenten des Landes Schleswig-Holstein Lutz Kipp 13 Vorwort des Präsidenten der CAU Oliver Auge 19 Vorwort des Herausgebers Verhältnis zu Stadt und Staat Ulf Kämpfer 29 Lebendige Zweierbeziehung: Die CAU und die Landeshaupt- KIEL stadt Kiel Kristin Alheit 41 Die CAU und das Land Schleswig-Holstein KIEL Uta Kuhl 51 Wissenschaten und die Gelehr samkeit um ihrer selbst willen – Die Gottorfer Herzöge als Förderer der Wissenschat Olaf Mörke 67 Das Verhältnis von Universität und Staat im Spannungsfeld von Selbst- und Fremdbestimmung Swantje Piotrowski OLSAT H I · ·F T R E · I V D S I R L E 107 T R E E U U U S I Die Finanzierung der Christiana Albertina in der Frühen · C C T T T T ·HO T X R R R R R T U L G G E G U S ·S E E E E · A D · D D D D D D D D D D D D D D D L L S L · G T M M M O O L O · · · A A A I I I I I E I R R R R R R · S F · R X I D U E D · R G I · C D · U S Neuzeit 1665 bis 1800 Gerhard Fouquet 141 »Woher das Geld nehmen zur Verbesserung der Univer sität?« – Die Finanzen der Kieler Universität 1820 bis 1914 Klaus Gereon Beuckers 175 Gebaute Bildungspolitik.
    [Show full text]
  • Creutzfeldt-Jakob Disease
    Rev Bras Neurol 56(3):25-28, 2020. Historical note Creutzfeldt-Jakob disease: one hundred years of participation in the design of the transmissible spongiform encephalopathies Doença de Creutzfeldt-Jakob: cem anos de participação no desenho das encefalopatias espongiformes transmissíveis M. da Mota Gomes 1 ABSTRACT RESUMO Creutzfeldt and Jakob's disease (CJD) has its initial A doença de Creutzfeldt e Jakob (CJD) tem seu milestone in the publication issued 100 years ago marco inicial na publicação emitida há 100 anos que that precipitated its better clinical-pathological and precipitou seu melhor entendimento clínico- etiological understanding. Now, it is established that patológico e etiológico. Agora, está estabelecido que it belongs to the group of the prion diseases or pertence ao grupo da família das doenças de príons transmissible spongiform encephalopathies family. ou encefalopatias espongiformes transmissíveis. A CJD is itself divided into several types, the most própria CJD se divide em vários tipos, sendo o mais common being sporadic that is further subdivided comum o esporádico que também se subdivide de according to the anatomoclinical expression, but acordo com a expressão anatomoclínica, mas mainly due to its aetiology regarding prionic protein principalmente devido à sua etiologia em relação à or genotype. proteína priônica ou genótipo. Key words- Creutzfeldt-Jakob disease, spongiform Palavras-chave- Doença de Creutzfeldt-Jakob, encephalopathies, prion protein encefalopatias espongiformes, proteína prioníca _______________________________________________________________________________________________________ Associate Professor, Laboratory of History of Psychiatry, Neurology, and Mental Health. Institute of Psychiatry. Institute of Neurology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil Orcid: https://orcid.org/0000-0001-8889-2573 Corresponding author: [email protected] Revista Brasileira de Neurologia » Volume 56 » Nº 3 » JUL/AGO/SET 2020 25 M.
    [Show full text]
  • Chapter 1: a Death in Devizes Chapter 2: One in a Million
    Notes CHAPTER 1: A DEATH IN DEVIZES 1 David and Dorothy Churchill, interview by the author, Devizes, U.K., October 25, 2001. All subsequent quotes are from this interview unless other- wise noted. 2 D. Bateman et al., “Sporadic Creutzfeldt-Jakob Disease in a 18-Year-Old in the U.K.,” The Lancet 346 (1995): 1155–1156. 3 Robert G. Will et al., “Infectious and Sporadic Prion Diseases,” in Prion Biology and Diseases, ed. Stanley B. Prusiner (Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 1999), 465–507. CHAPTER 2: ONE IN A MILLION 1 http://www.whonamedit.com/doctor.cfm/91.html (last accessed March 6, 2003). 2 Hans Gerhard Creutzfeldt, “Über eine eigenartige herdförmige Erkrankung des Zentralnervensystems,” Zeitschrift für die gesamte Neurologie und Psychiatrie 57 (1920): 1–18. 3 Hans Gerhard Creutzfeldt, “On a Particular Focal Disease of the Central Nervous System (Preliminary Communication),” transl. E. P. Richardson, Jr., in Neurological Classics in Modern Translation, ed. David A. Rottenberg and Fred H. Hochberg (New York: Hafner Press, 1977), 98. 4 Ibid, 99. 5 Ibid. 6 http://www.whonamedit.com/doctor.cfm/738.html (last accessed March 6, 2003). 7 Hans Gerhard Creutzfeldt, Neurological Classics in Modern Translation, 96. 8 Alfons Jakob, “Concerning a Disorder of the Central Nervous System Clinically Resembling Multiple Sclerosis with Remarkable Anatomic Findings (Spastic Pseudosclerosis),” transl. E. P Richardson, Jr., in Neurological Classics in 239 240 NOTES Modern Translation, ed. David A. Rottenberg and Fred H. Hochberg (New York: Hafner Press, 1977), 116. 9 Ibid, 120. 10 Some researchers favored “Jakob-Creutzfeldt disease” to give due credit to Jakob, who was really the one to characterize and define the illness.
    [Show full text]
  • Neurologie Und Neurologen in Der NS-Zeit: Auswirkungen Und Folgen Von 1945 Bis Heute
    Leitthema Nervenarzt M. Martin2 ·H.Fangerau2 ·A.Karenberg1 DOI 10.1007/s00115-016-0144-7 1 Institut für Geschichte und Ethik der Medizin, Universität zu Köln, Köln, Deutschland © Springer-Verlag Berlin Heidelberg 2016 2 Institut für Geschichte, Theorie und Ethik der Medizin, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Deutschland Neurologie und Neurologen in der NS-Zeit: Auswirkungen und Folgen von 1945 bis heute Eine „Strategie“ im Umgang mit der NS- schahen unter Mitbeteiligung führender (1980 bis heute) wiederum lässt sich VergangenheitderMedizinbestandlange Repräsentanten der verfassten Ärzteschaft insbesondere durch den Abschied von Zeit darin, dass die Vertreter der orga- sowie medizinischer Fachgesellschaften der Zeitzeugenschaft14 [ ], symbolische nisierten Ärzteschaft in Deutschland die und ebenso unter maßgeblicher Beteili- Erinnerungsereignisse und einen Per- Meinung vertraten, es hätte eine durch gung von herausragenden Vertretern der spektivwechsel beschreiben, im Rahmen die Politik erzwungene „Gleichschal- universitären Medizin sowie von renom- dessen statt einer Struktur- und System- tung“ der Medizin, ihrer Organisationen mierten biomedizinischen Forschungsein- geschichtsschreibung eine Hinwendung und Institutionen gegeben. Medizinische richtungen [8]. zu den betroffenen Menschen (Tätern Verbrechen seien nur von einer kleinen wie Opfern) erfolgt. Zahl einzelne Ärzte begangen worden, DerUmgangmitdernationalsozialis- AuchderNeurologeundHirnforscher die zudem noch eher randständigen For- tischen Vergangenheit in den
    [Show full text]
  • Karl Georg Häusler Date of Birth 13Th of May 1975 in Halle / Saale, Germany
    Karl Georg Häusler Date of birth 13th of May 1975 in Halle / Saale, Germany Position MD; Dr. med.; Fully certified Neurologist Address Department of Neurology Charité – University Medicine Berlin Campus Benjamin Franklin Hindenburgdamm 30, 12203 Berlin, Germany Phone +49-30-8445-4244 Fax +49-30-8445-4264 e-mail [email protected] Professional Career, Awards 2010 Hans-Gerhard Creutzfeldt Scholarship of the Center for Stroke Research Berlin 2008 Fully certified Neurologist, Board Exam Neurology 2008 Ultrasound Certificate of qualification German Society for Clinical Neurophysiology 2006 Electroencephalography Certificate of qualification German Society for Clinical Neurophysiology 2004 - Member Critical Event Committee of the German Competence Net on Atrial Fibrillation 2002 - 2008 Neurological resident, Department of Neurology, Charité – University Medicine Berlin 2001 German Board Exam and Medical License (Rating: 1) 1997 - 1999 Doctoral thesis: Interferon-J differentially regulates the release of glial cytokines and chemokines. [summa cum laude] Prof. Dr. H. Kettenmann, Max Delbrück Center for Molecular Medicine, Berlin, Germany 1994 - 2001 Studies in medicine at the medical schools Berlin, Montreal, Zurich Publications x Häusler KG, Schmidt WU, Foehring F, Meisel C, Guenther C, Brunecker P, Kunze C, Helms T, Dirnagl U, Volk HD, Villringer A. Immune responses after acute ischemic stroke or myocardial infarction. Int J Cardiol. 2010 Nov 13. x Häusler KG, Koch L, Ueberreiter J, Coban N, Safak E, Kunze C, Villringer K, Endres M, Schultheiss HP, Fiebach JB, Schirdewan A. Safety and reliability of the insertable Reveal XT® recorder in patients undergoing 3T brain MRI. Heart Rhythm. 2010 Nov 8. x Häusler KG, Koch L, Ueberreiter J, Endres M, Schultheiss HP, Heuschmann PU, Schirdewan A, Fiebach JB.
    [Show full text]