Transmission properties of atypical Creutzfeldt-Jakob disease: a clue to disease etiology?
Atsushi Kobayashia,
Piero Parchib,c,
Masahito Yamadad,
Paul Browne,
Daniela Saverionic,
Yuichi Matsuuraf,
Atsuko Takeuchia,
Shirou Mohria and
Tetsuyuki Kitamotoa#
+ Author Affiliations
aDepartment of Neurological Science, Tohoku University Graduate School of Medicine, Sendai, Japan
bIRCCS, Istituto delle Scienze Neurologiche, Bologna, Italy
cDepartment of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
dDepartment of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
eLaboratoire Français des Biotechnologies (LFB), Les Ulis, France
fInfluenza and Prion Disease Research Center, National Institute of Animal Health, Tsukuba, Japan.
ABSTRACT
The genotype at polymorphic codon 129 of the PRNP gene has a profound influence on both phenotypic expression and prion strain susceptibility in humans. For example, while the most common sporadic Creutzfeldt-Jakob disease (CJD) subtype, sporadic CJD-MM1 (M1 strain), induces a single phenotype after experimental transmission regardless of the codon 129 genotype of the recipient animal, the phenotype elicited by sporadic CJD-VV2 (V2 strain), the second most common subtype, varies according to the host codon 129 genotype. In particular, the propagation of the V2 strain in codon 129 methionine homozygotes has only been linked to acquired forms of CJD such as plaque-type dura mater graft-associated CJD (dCJD), a subgroup of iatrogenic CJD with distinctive phenotypic features, but never observed in sporadic CJD. In the present study, we describe atypical CJD cases carrying the codon 129 methionine homozygosity, in a neurosurgeon and in a patient with a medical history of neurosurgery without dural grafting, showing the distinctive phenotypic features and transmission properties of plaque-type dCJD. These findings raise the possibility that the two cases, previously considered as sporadic CJD, might actually be acquired CJD caused by infection with the V2 strain. Thus, careful analyses of phenotypic features and transmission properties in atypical cases may be useful to distinguish acquired from sporadic cases of CJD.
IMPORTANCE Susceptibility and phenotypic expression of Creutzfeldt-Jakob disease (CJD) depend on both the prion strain and genotype at polymorphic codon 129 of the PRNP gene. For example, propagation of the second most common sporadic CJD strain (V2 strain) into the codon 129 methionine homozygotes has been linked to plaque-type dura mater graft-associated CJD (dCJD), a subgroup of iatrogenic CJD with distinctive phenotypic features, but never observed in sporadic CJD. In the present study, we describe atypical CJD cases in a neurosurgeon and in a patient with a medical history of neurosurgery without dural grafting, showing the distinctive phenotypic features and transmission properties of plaque-type dCJD. These findings raise the possibility that the two cases, previously considered as sporadic CJD, might actually be acquired CJD caused by infection with the V2 strain.
FOOTNOTES
↵#Coresponding author:
Tetsuyuki Kitamoto; Department of Neurological Science, Tohoku University Graduate School of Medicine, Sendai, Japan; E-mail, kitamoto@med.tohoku.ac.jp
Copyright © 2015, American Society for Microbiology. All Rights Reserved.
http://jvi.asm.org/content/early/2015/01/19/JVI.03183-14.abstract?papetoc
Sunday, October 27, 2013
A Kiss of a Prion: New Implications for Oral Transmissibility
http://transmissiblespongiformencephalopathy.blogspot.com/2013/10/a-kiss-of-prion-new-implications-for.html
UPDATE* NOVEMBER 16, 2014
vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ???
Friday, January 10, 2014
Greetings again Friends, Neighbors, and Colleagues,
I would kindly like to follow up on ‘vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ???’ ran across an old paper from 1984, that some might find interest in, and I will update the link with this old science paper from 1984, a 2010 paper from Japan, and some information on scrapie transmission. The paper from Japan first, then the 1984 paper, and then the scrapie transmission studies.
***The occurrence of contact cases raises the possibility that transmission in families may be effected by an unusually virulent strain of the agent.
http://transmissiblespongiformencephalopathy.blogspot.com/2014/01/vpspr-sgss-sffi-tse-iatrogenic-by.html
From: Terry S. Singeltary Sr.
Sent: Saturday, November 15, 2014 9:29 PM
To: Terry S. Singeltary Sr.
Subject: THE EPIDEMIOLOGY OF CREUTZFELDT-JAKOB DISEASE R. G. WILL 1984
THE EPIDEMIOLOGY OF CREUTZFELDT-JAKOB DISEASE
R. G. WILL
1984
snip...
http://transmissiblespongiformencephalopathy.blogspot.com/2014/01/vpspr-sgss-sffi-tse-iatrogenic-by.html
Friday, January 10, 2014
vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ???
http://transmissiblespongiformencephalopathy.blogspot.com/2014/01/vpspr-sgss-sffi-tse-iatrogenic-by.html
Tuesday, December 30, 2014
TSEAC USA Reason For Recalls Blood products, collected from a donors considered to be at increased risk for Creutzfeldt-Jakob Disease (CJD), were distributed END OF YEAR REPORT 2014
http://tseac.blogspot.com/2014/12/tseac-usa-reason-for-recalls-blood.html
Sunday, December 14, 2014
ALERT new variant Creutzfeldt Jakob Disease nvCJD or vCJD, sporadic CJD strains, TSE prion aka Mad Cow Disease United States of America Update December 14, 2014 Report
http://transmissiblespongiformencephalopathy.blogspot.com/2014/12/alert-new-variant-creutzfeldt-jakob.html
Thursday, January 15, 2015
41-year-old Navy Commander with sporadic Creutzfeldt–Jakob disease CJD TSE Prion: Case Report
http://creutzfeldt-jakob-disease.blogspot.com/2015/01/41-year-old-navy-commander-with.html
Saturday, January 17, 2015
*** Becky Lockhart 46, Utah’s first female House speaker, dies diagnosed with the extremely rare Creutzfeldt-Jakob disease
http://creutzfeldt-jakob-disease.blogspot.com/2015/01/becky-lockhart-46-utahs-first-female.html
http://www.regulations.gov/#!documentDetail;D=APHIS-2014-0107-0003
who’s kidding whom $$$ i.e. USDA INC AND THE OIE
2014
***Moreover, L-BSE has been transmitted more easily to transgenic mice overexpressing a human PrP [13,14] or to primates [15,16] than C-BSE.
***It has been suggested that some sporadic CJD subtypes in humans may result from an exposure to the L-BSE agent.
*** Lending support to this hypothesis, pathological and biochemical similarities have been observed between L-BSE and an sCJD subtype (MV genotype at codon 129 of PRNP) [17], and between L-BSE infected non-human primate and another sCJD subtype (MM genotype) [15].
snip...
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4213560/pdf/viruses-06-03766.pdf
Monday, October 10, 2011
EFSA Journal 2011 The European Response to BSE: A Success Story
snip...
EFSA and the European Centre for Disease Prevention and Control (ECDC) recently delivered a scientific opinion on any possible epidemiological or molecular association between TSEs in animals and humans (EFSA Panel on Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical BSE prions as the only TSE agents demonstrated to be zoonotic so far
*** but the possibility that a small proportion of human cases so far classified as "sporadic" CJD are of zoonotic origin could not be excluded.
*** Moreover, transmission experiments to non-human primates suggest that some TSE agents in addition to Classical BSE prions in cattle (namely L-type Atypical BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic wasting disease (CWD) agents) might have zoonotic potential.
snip...
http://www.efsa.europa.eu/en/efsajournal/pub/e991.htm?emt=1
http://www.efsa.europa.eu/en/efsajournal/doc/e991.pdf
Thursday, August 12, 2010
Seven main threats for the future linked to prions
First threat
The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed.
*** Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans.
*** These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.
Second threat
snip...
http://www.neuroprion.org/en/np-neuroprion.html
*** HUMAN MAD COW DISEASE nvCJD TEXAS CASE NOT LINKED TO EUROPEAN TRAVEL CDC ***
Sunday, November 23, 2014
*** Confirmed Variant Creutzfeldt-Jakob Disease (variant CJD) Case in Texas in June 2014 confirmed as USA case NOT European ***
the patient had resided in Kuwait, Russia and Lebanon. The completed investigation did not support the patient's having had extended travel to European countries, including the United Kingdom, or travel to Saudi Arabia. The specific overseas country where this patient’s infection occurred is less clear largely because the investigation did not definitely link him to a country where other known vCJD cases likely had been infected.
http://vcjd.blogspot.com/2014/11/confirmed-variant-creutzfeldt-jakob.html
*** U.S.A. 50 STATE BSE MAD COW CONFERENCE CALL Jan. 9, 2001
http://tseac.blogspot.com/2011/02/usa-50-state-bse-mad-cow-conference.html
Wednesday, October 09, 2013
WHY THE UKBSEnvCJD ONLY THEORY IS SO POPULAR IN IT'S FALLACY, £41,078,281 in compensation REVISED
http://creutzfeldt-jakob-disease.blogspot.com/2013/10/why-ukbsenvcjd-only-theory-is-so.html
Tuesday, March 11, 2014
Science and Technology Committee Oral evidence: Blood, tissue and organ screening, HC 990 Wednesday 5 March 2014 SPORADIC CJD
Actually, it is nearer 2 per million per year of the population will develop sporadic CJD, but your lifetime risk of developing sporadic CJD is about 1 in 30,000. So that has not really changed. When people talk about 1 per million, often they interpret that as thinking it is incredibly rare. They think they have a 1-in-a-million chance of developing this disease. You haven’t. You’ve got about a 1-in-30,000 chance of developing it.
http://creutzfeldt-jakob-disease.blogspot.com/2014/03/science-and-technology-committee-oral.html
Sunday, March 09, 2014
A Creutzfeldt-Jakob Disease (CJD) Lookback Study: Assessing the Risk of Blood Borne Transmission of Classic Forms of Creutzfeldt-Jakob Disease
*** FDA TSEAC CIRCUS AND TRAVELING ROAD SHOW FOR THE TSE PRION DISEASES ***
http://creutzfeldt-jakob-disease.blogspot.com/2014/03/a-creutzfeldt-jakob-disease-cjd.html
Friday, February 14, 2014
Creutzfeldt-Jakob disease (CJD) biannual update (February 2014), with briefing on novel human prion disease National CJD Research and Surveillance Unit NCJDRSU
http://creutzfeldt-jakob-disease.blogspot.com/2014/02/creutzfeldt-jakob-disease-cjd-biannual.html
Tuesday, February 11, 2014
Novant Health Forsyth Medical Center Information on potential CJD exposure
http://creutzfeldt-jakob-disease.blogspot.com/2014/02/novant-health-forsyth-medical-center.html
Thursday, April 17, 2014
Novant: Three more may have been exposed to disease CJD
http://creutzfeldt-jakob-disease.blogspot.com/2014/04/novant-three-more-may-have-been-exposed.html
Wednesday, January 15, 2014
*** INFECTION PREVENTION AND CONTROL OF CJD, VCJD AND OTHER HUMAN PRION DISEASES IN HEALTHCARE AND COMMUNITY SETTINGS Variably Protease-Sensitive Prionopathy (VPSPr) January 15, 2014
http://transmissiblespongiformencephalopathy.blogspot.com/2014/01/infection-prevention-and-control-of-cjd.html
Saturday, November 16, 2013
Management of neurosurgical instruments and patients exposed to creutzfeldt-jakob disease 2013 December
Infect Control Hosp Epidemiol.
http://creutzfeldt-jakob-disease.blogspot.com/2013/11/management-of-neurosurgical-instruments.html
Tuesday, May 28, 2013
Late-in-life surgery associated with Creutzfeldt-Jakob disease: a methodological outline for evidence-based guidance
http://creutzfeldt-jakob-disease.blogspot.com/2013/05/late-in-life-surgery-associated-with.html
Wednesday, November 27, 2013
NHS failed to sterilise surgical instruments contaminated with 'mad cow' disease
http://transmissiblespongiformencephalopathy.blogspot.com/2013/11/nhs-failed-to-sterilise-surgical.html
Thursday, January 23, 2014
Medical Devices Containing Materials Derived from Animal Sources (Except for In Vitro Diagnostic Devices) [Docket No. FDA–2013–D–1574]
http://transmissiblespongiformencephalopathy.blogspot.com/2014/01/medical-devices-containing-materials.html
Thursday, April 12, 2012
Health professions and risk of sporadic Creutzfeldt–Jakob disease, 1965 to 2010
Eurosurveillance, Volume 17, Issue 15, 12 April 2012
Research articles
http://creutzfeldt-jakob-disease.blogspot.com/2012/04/health-professions-and-risk-of-sporadic.html
Tuesday, May 28, 2013
Late-in-life surgery associated with Creutzfeldt-Jakob disease: a methodological outline for evidence-based guidance
http://creutzfeldt-jakob-disease.blogspot.com/2013/05/late-in-life-surgery-associated-with.html
Tuesday, May 21, 2013
CJD, TSE, PRION, BLOOD Abstracts of the 23rd Regional Congress of the International Society of Blood Transfusion, Amsterdam, The Netherlands, June 2-5, 2013
http://transmissiblespongiformencephalopathy.blogspot.com/2013/05/cjd-tse-prion-blood-abstracts-of-23rd.html
Tuesday, March 5, 2013
Use of Materials Derived From Cattle in Human Food and Cosmetics; Reopening of the Comment Period FDA-2004-N-0188-0051 (TSS SUBMISSION)
FDA believes current regulation protects the public from BSE but reopens comment period due to new studies
http://transmissiblespongiformencephalopathy.blogspot.com/2013/03/use-of-materials-derived-from-cattle-in_6452.html
Thursday, October 25, 2012
Current limitations about the cleaning of luminal endoscopes and TSE prion risk factors there from
Article in Press
http://creutzfeldt-jakob-disease.blogspot.com/2012/10/current-limitations-about-cleaning-of.html
Saturday, January 16, 2010
Evidence For CJD TSE Transmission Via Endoscopes 1-24-3 re-Singeltary to Bramble et al
Evidence For CJD/TSE Transmission Via Endoscopes
From Terry S. Singletary, Sr flounder@wt.net 1-24-3
Terry S. Singeltary Sr., P.O. BOX 42, Bacliff, Texas 77518 USA
http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html
Professor Michael Farthing wrote:
Louise Send this to Bramble (author) for a comment before we post. Michael
http://creutzfeldt-jakob-disease.blogspot.com/2010/01/evidence-for-cjd-tse-transmission-via.html
Tuesday, July 31, 2012
11 patients may have been exposed to fatal disease Creutzfeldt-Jakob Disease CJD Greenville Memorial Hospital
http://creutzfeldt-jakob-disease.blogspot.com/2012/07/11-patients-may-have-been-exposed-to.html
Thursday, August 02, 2012
CJD case in Saint John prompts letter to patients Canada CJD case in Saint John prompts letter to patients
http://creutzfeldt-jakob-disease.blogspot.com/2012/08/cjd-case-in-saint-john-prompts-letter.html
Saturday, February 12, 2011
Another Pathologists dies from CJD, another potential occupational death ?
another happenstance of bad luck, a spontaneous event from nothing, or friendly fire ???
http://creutzfeldt-jakob-disease.blogspot.com/2011/02/another-pathologists-dies-from-cjd.html
Thursday, July 08, 2010
GLOBAL CLUSTERS OF CREUTZFELDT JAKOB DISEASE - A REVIEW 2010
http://creutzfeldt-jakob-disease.blogspot.com/2010/07/global-clusters-of-creutzfeldt-jakob.html
Sunday, May 10, 2009
Meeting of the Transmissible Spongiform Encephalopathies Committee On June 12, 2009 (Singeltary submission)
http://tseac.blogspot.com/2009/05/meeting-of-transmissible-spongiform.html
Thursday, January 29, 2009
Medical Procedures and Risk for Sporadic Creutzfeldt-Jakob Disease, Japan, 1999-2008
(WARNING TO Neurosurgeons and Ophthalmologists)
Volume 15, Number 2-February 2009 Research
http://creutzfeldt-jakob-disease.blogspot.com/2009/01/medical-procedures-and-risk-for.html
Wednesday, August 20, 2008
Tonometer disinfection practice in the United Kingdom: A national survey
http://creutzfeldt-jakob-disease.blogspot.com/2008/08/tonometer-disinfection-practice-in.html
Tuesday, August 12, 2008
Biosafety in Microbiological and Biomedical Laboratories Fifth Edition 2007 (occupational exposure to prion diseases)
http://creutzfeldt-jakob-disease.blogspot.com/2008/08/biosafety-in-microbiological-and.html
Monday, December 31, 2007
Risk Assessment of Transmission of Sporadic Creutzfeldt-Jakob Disease in Endodontic Practice in Absence of Adequate Prion Inactivation
http://creutzfeldt-jakob-disease.blogspot.com/2007_12_01_archive.html
Subject: CJD: update for dental staff
Date: November 12, 2006 at 3:25 pm PST
1: Dent Update. 2006 Oct;33(8):454-6, 458-60.
CJD: update for dental staff.
http://seac992007.blogspot.com/2008/06/seac-2008-one-hundredth-meeting-of.html
Friday, July 19, 2013
Beaumont Hospital in Dublin assessing patients for CJD
http://creutzfeldt-jakob-disease.blogspot.com/2013/07/beaumont-hospital-in-dublin-assessing.html
Saturday, September 21, 2013
CJD CONFIRMED in patient at New Hampshire Department of Health and Human Services (DHHS), Catholic Medical Center (CMC), and the Manchester Health Department (MHD)
http://creutzfeldt-jakob-disease.blogspot.com/2013/09/cjd-confirmed-in-patient-at-new.html
Thursday, September 26, 2013
Minimise transmission risk of CJD and vCJD in healthcare settings Guidance
http://creutzfeldt-jakob-disease.blogspot.com/2013/09/minimise-transmission-risk-of-cjd-and.html
Tuesday, April 01, 2014
Questions linger in U.S. CJD cases 2005, and still do in 2014
http://creutzfeldt-jakob-disease.blogspot.com/2014/04/questions-linger-in-us-cjd-cases-2005.html
CJD QUESTIONNAIRE USA
http://cjdquestionnaire.blogspot.com/2007/11/cjd-questionnaire.html
http://cjdquestionnaire.blogspot.com/
CJD VOICE
http://creativegumbo.net/cjdvoice/
*** 1: J Neurol Neurosurg Psychiatry 1994 Jun;57(6):757-8
Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery.
Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC.
Laboratory of Central Nervous System Studies, National Institute of
Neurological Disorders and Stroke, National Institutes of Health,
Bethesda, MD 20892.
Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.
PMID: 8006664 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8006664&dopt=Abstract
New studies on the heat resistance of hamster-adapted scrapie agent: Threshold survival after ashing at 600°C suggests an inorganic template of replication
http://www.pnas.org/content/97/7/3418.full
Prion Infected Meat-and-Bone Meal Is Still Infectious after Biodiesel Production
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2493038/
Detection of protease-resistant cervid prion protein in water from a CWD-endemic area
http://www.landesbioscience.com/journals/prion/NicholsPRION3-3.pdf
A Quantitative Assessment of the Amount of Prion Diverted to Category 1 Materials and Wastewater During Processing
http://onlinelibrary.wiley.com/doi/10.1111/j.1539-6924.2012.01922.x/abstract
Rapid assessment of bovine spongiform encephalopathy prion inactivation by heat treatment in yellow grease produced in the industrial manufacturing process of meat and bone meals
http://transmissiblespongiformencephalopathy.blogspot.com/2013/07/rapid-assessment-of-bovine-spongiform.html
PPo4-4:
Survival and Limited Spread of TSE Infectivity after Burial
http://www.prion2010.org/bilder/prion_2010_program_latest_w_posters_4_.pdf?139&PHPSESSID=a30a38202cfec579000b77af81be3099
*** The potential impact of prion diseases on human health was greatly magnified by the recognition that interspecies transfer of BSE to humans by beef ingestion resulted in vCJD. While changes in animal feed constituents and slaughter practices appear to have curtailed vCJD, there is concern that CWD of free-ranging deer and elk in the U.S. might also cross the species barrier. Thus, consuming venison could be a source of human prion disease. Whether BSE and CWD represent interspecies scrapie transfer or are newly arisen prion diseases is unknown. Therefore, the possibility of transmission of prion disease through other food animals cannot be ruled out. There is evidence that vCJD can be transmitted through blood transfusion. There is likely a pool of unknown size of asymptomatic individuals infected with vCJD, and there may be asymptomatic individuals infected with the CWD equivalent. These circumstances represent a potential threat to blood, blood products, and plasma supplies.
http://cdmrp.army.mil/prevfunded/nprp/NPRP_Summit_Final_Report.pdf
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
To the Editor: In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.
Terry S. Singeltary, Sr Bacliff, Tex
1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323.
http://jama.jamanetwork.com/article.aspx?articleid=1031186
26 March 2003
Terry S. Singeltary, retired (medically) CJD WATCH
I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs in the USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, there should be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc?
http://www.neurology.org/content/60/2/176/reply#neurology_el_535
2 January 2000
British Medical Journal
U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well
http://www.bmj.com/rapid-response/2011/10/28/us-scientist-should-be-concerned-cjd-epidemic-us-well
15 November 1999
British Medical Journal
vCJD in the USA * BSE in U.S.
http://www.bmj.com/rapid-response/2011/10/28/re-vcjd-usa-bse-us
The Lancet Infectious Diseases, Volume 3, Issue 8, Page 463, August 2003 doi:10.1016/S1473-3099(03)00715-1Cite or Link Using DOI
Tracking spongiform encephalopathies in North America
Original
Xavier Bosch
“My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever since. What I have found is that we have not been told the truth. CWD in deer and elk is a small portion of a much bigger problem.” 49-year—old Singeltary is one of a number of people who have remained largely unsatisfied after being told that a close relative died from a rapidly progressive dementia compatible with spontaneous Creutzfeldt—Jakob ...
http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(03)00715-1/abstract
Suspect symptoms
What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?
28 Mar 01
Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.
Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in mice as sCJD.
"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb...
http://www.newscientist.com/article/mg16922840.300-like-lambs-to-the-slaughter.html
Evidence for zoonotic potential of ovine scrapie prions
Hervé Cassard,1, n1 Juan-Maria Torres,2, n1 Caroline Lacroux,1, Jean-Yves Douet,1, Sylvie L. Benestad,3, Frédéric Lantier,4, Séverine Lugan,1, Isabelle Lantier,4, Pierrette Costes,1, Naima Aron,1, Fabienne Reine,5, Laetitia Herzog,5, Juan-Carlos Espinosa,2, Vincent Beringue5, & Olivier Andréoletti1, Affiliations Contributions Corresponding author Journal name: Nature Communications Volume: 5, Article number: 5821 DOI: doi:10.1038/ncomms6821 Received 07 August 2014 Accepted 10 November 2014 Published 16 December 2014 Article tools Citation Reprints Rights & permissions Article metrics
Abstract
Although Bovine Spongiform Encephalopathy (BSE) is the cause of variant Creutzfeldt Jakob disease (vCJD) in humans, the zoonotic potential of scrapie prions remains unknown. Mice genetically engineered to overexpress the human prion protein (tgHu) have emerged as highly relevant models for gauging the capacity of prions to transmit to humans. These models can propagate human prions without any apparent transmission barrier and have been used used to confirm the zoonotic ability of BSE. Here we show that a panel of sheep scrapie prions transmit to several tgHu mice models with an efficiency comparable to that of cattle BSE. The serial transmission of different scrapie isolates in these mice led to the propagation of prions that are phenotypically identical to those causing sporadic CJD (sCJD) in humans. These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
Subject terms: Biological sciences• Medical research At a glance
http://www.nature.com/ncomms/2014/141216/ncomms6821/full/ncomms6821.html
The Pathological Protein:
Mad Cow, Chronic Wasting, and Other Deadly Prion Diseases
Philip Yam
''Answering critics like Terry Singeltary, who feels that the US undercounts CJD, Schonberger _conceded_ that the current surveillance system has errors but stated that most of the errors will be confined to the older population''....end
snip...
His combative, blunt, opinion- ated style sometimes borders on obsessive ranting that earns praise from some officials and researchers but infuriates others especially when he repeats his conviction that "the government has lied to us, the feed industry has lied to us all over a buck." As evidence, Singeltary cites the USDA's testing approach, which targets downer cows and examined 19,900 of them in 2002. To him, the USDA should test 1 mil- lion cattle, because the incidence of BSE may be as low as one in a mil- lion, as it was in some European countries. That the U.S. does not, he thinks, is a sign that the government is really not interested in finding mad cows because of fears of an economic disaster.
Singeltary got into the field of transmissible spongiform encepha- lopathy in 1997, just after his mother died of sporadic CJD. She had an especially aggressive version the Heidenhain variant that first causes the patient to go blind and then to deteriorate rapidly She died just ten weeks after her symptoms began. Singeltary, who said he had watched his grandparents die of cancer, considered her death by CJD to be much, much worse: "It's something you never forget." Her uncon- trollable muscle twitching became so bad "that it took three of us to hold her one time," Singeltary recalled. "She did everything but levitate in bed and spin her head."
http://www.amazon.com/The-Pathological-Protein-Chronic-Diseases/dp/0387955089
14th ICID International Scientific Exchange Brochure -
Final Abstract Number: ISE.114
Session: International Scientific Exchange
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America update October 2009
T. Singeltary
Bacliff, TX, USA
Background:
An update on atypical BSE and other TSE in North America. Please remember, the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been documented in North America, along with the typical scrapie's, and atypical Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these TSE in different species have been rendered and fed to food producing animals for humans and animals in North America (TSE in cats and dogs ?), and that the trading of these TSEs via animals and products via the USA and Canada has been immense over the years, decades.
Methods:
12 years independent research of available data
Results:
I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc.
Conclusion:
I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena's. Restricting the reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route.
http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf
re-Self-Propagative Replication of Ab Oligomers Suggests Potential Transmissibility in Alzheimer Disease
Received July 24, 2014; Accepted September 16, 2014; Published November 3, 2014
Singeltary comment ;
http://www.plosone.org/annotation/listThread.action?root=82860
RE: re-Human Prion Diseases in the United States
part 2 flounder replied to flounder on 02 Jan 2010 at 21:26 GMT
No competing interests declared.
see full text ;
http://www.plosone.org/annotation/listThread.action?root=363
*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary reply ;
http://www.plosone.org/annotation/listThread.action;jsessionid=635CE9094E0EA15D5362B7D7B809448C?root=7143
"Löcher wie in einem Schweizer Käse" hat auch Terry Singeltary im Regelwerk der FDA ausgemacht. Der Texaner kam auf einem tragischen Umweg zu dem Thema: Nachdem seine Mutter 1997 binnen weniger Wochen an der Creutzfeldt-Jakob-Krankheit gestorben war, versuchte er, die Ursachen der Infektion aufzuspüren. Er klagte auf die Herausgabe von Regierungsdokumenten und arbeitete sich durch Fachliteratur; heute ist er überzeugt, dass seine Mutter durch die stetige Einnahme von angeblich kräftigenden Mitteln erkrankte, in denen - völlig legal - Anteile aus Rinderprodukten enthalten sind.
Von der Fachwelt wurde Singeltary lange als versponnener Außenseiter belächelt. Doch mittlerweile sorgen sich auch Experten, dass ausgerechnet diese verschreibungsfreien Wundercocktails zur Stärkung von Intelligenz, Immunsystem oder Libido von den Importbeschränkungen ausgenommen sind. Dabei enthalten die Pillen und Ampullen, die in Supermärkten verkauft werden, exotische Mixturen aus Rinderaugen; dazu Extrakte von Hypophyse oder Kälberföten, Prostata, Lymphknoten und gefriergetrocknetem Schweinemagen. In die USA hereingelassen werden auch Blut, Fett, Gelatine und Samen. Diese Stoffe tauchen noch immer in US-Produkten auf, inklusive Medizin und Kosmetika. Selbst in Impfstoffen waren möglicherweise gefährliche Rinderprodukte enthalten. Zwar fordert die FDA schon seit acht Jahren die US-Pharmaindustrie auf, keine Stoffe aus Ländern zu benutzen, in denen die Gefahr einer BSE-Infizierung besteht. Aber erst kürzlich verpflichteten sich fünf Unternehmen, darunter Branchenführer wie GlaxoSmithKline, Aventis und American Home Products, ihre Seren nur noch aus unverdächtigem Material herzustellen.
"Its as full of holes as Swiss Cheese" says Terry Singeltary of the FDA regulations. ...
http://www.spiegel.de/spiegel/print/d-18578755.html
New York Times Magazine The Case of the Cherry Hill Cluster By D.T. MAX
Published: March 28, 2004
snip...
Skarbek did not know how to surmount this objection. But she was a go-getter. She wasn't about to give up on her cluster so easily. Fortunately, she was in contact with Terry Singeltary. She had seen his name quoted often on the Web in articles on C.J.D. and mad cow. Singeltary lost his mother to an extremely rare strain of sporadic C.J.D. in 1997. Soon after, he learned that a year earlier to the day, the mother of his next-door neighbor died of the disease. Since that time, he has become convinced that these sporadic cases are not sporadic at all, that mad cow is now a disease of humans in America. He said he believes that his mother was accidentally infected during surgery and the mother of his neighbor from taking nutritional supplements made from high-risk bovine tissue, which he calls ''mad cow in a pill.''
Singeltary has a sloping face and slicked-back hair. He is nearsighted, with small blue eyes. He looks like Lewis Carroll's White Rabbit. From his living room in Bacliff, Tex., he dominates the listservs and message boards of an online debate over sporadic C.J.D. -- the scientists who say it exists; the heartbroken family members who doubt it. Early, deep in his grief, he would sign his e-mail messages to scientists, ''I am the madson of a deadmom who died of madcow.'' Singeltary turned out to be helpful for Skarbek. He pointed her to a paper that was published in 2002 in the journal of the European Molecular Biology Organization by John Collinge, the premier prion researcher in England. Collinge argued that experiments conducted in mice suggest that infections with mad cow can sometimes look like sporadic C.J.D. Collinge accepted the implications: he recommended that ''serious consideration should be given'' to the idea that some of the more recent sporadic C.J.D. cases in Europe were in fact related to mad cow disease.
http://www.artsci.wustl.edu/~anthro/articles/The%20Case%20of%20the%20Cherry%20Hill%20Cluster.htm
Sunday, January 11, 2015
Docket No. APHIS-2014-0107 Bovine Spongiform Encephalopathy; Importation of Animals and Animal Products Singeltary Submission
http://www.regulations.gov/#!documentDetail;D=APHIS-2014-0107-0003
http://bovineprp.blogspot.com/2015/01/docket-no-aphis-2014-0107-bovine.html
Evidence for zoonotic potential of ovine scrapie prions
Hervé Cassard,1, n1 Juan-Maria Torres,2, n1 Caroline Lacroux,1, Jean-Yves Douet,1, Sylvie L. Benestad,3, Frédéric Lantier,4, Séverine Lugan,1, Isabelle Lantier,4, Pierrette Costes,1, Naima Aron,1, Fabienne Reine,5, Laetitia Herzog,5, Juan-Carlos Espinosa,2, Vincent Beringue5, & Olivier Andréoletti1, Affiliations Contributions Corresponding author Journal name: Nature Communications Volume: 5, Article number: 5821 DOI: doi:10.1038/ncomms6821 Received 07 August 2014 Accepted 10 November 2014 Published 16 December 2014 Article tools Citation Reprints Rights & permissions Article metrics
Abstract
Although Bovine Spongiform Encephalopathy (BSE) is the cause of variant Creutzfeldt Jakob disease (vCJD) in humans, the zoonotic potential of scrapie prions remains unknown. Mice genetically engineered to overexpress the human prion protein (tgHu) have emerged as highly relevant models for gauging the capacity of prions to transmit to humans. These models can propagate human prions without any apparent transmission barrier and have been used used to confirm the zoonotic ability of BSE. Here we show that a panel of sheep scrapie prions transmit to several tgHu mice models with an efficiency comparable to that of cattle BSE. The serial transmission of different scrapie isolates in these mice led to the propagation of prions that are phenotypically identical to those causing sporadic CJD (sCJD) in humans. These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.
Subject terms: Biological sciences• Medical research At a glance
http://www.nature.com/ncomms/2014/141216/ncomms6821/full/ncomms6821.html
Suspect symptoms
What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?
28 Mar 01 Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.
Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in mice as sCJD.
"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb...
2001
Suspect symptoms
What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?
28 Mar 01
Like lambs to the slaughter
31 March 2001
by Debora MacKenzie Magazine issue 2284.
FOUR years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.
Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.
Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in mice as sCJD.
"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb.
Scrapie has been around for centuries and until now there has been no evidence that it poses a risk to human health. But if the French finding means that scrapie can cause sCJD in people, countries around the world may have overlooked a CJD crisis to rival that caused by BSE.
Deslys and colleagues were originally studying vCJD, not sCJD. They injected the brains of macaque monkeys with brain from BSE cattle, and from French and British vCJD patients. The brain damage and clinical symptoms in the monkeys were the same for all three. Mice injected with the original sets of brain tissue or with infected monkey brain also developed the same symptoms.
As a control experiment, the team also injected mice with brain tissue from people and animals with other prion diseases: a French case of sCJD; a French patient who caught sCJD from human-derived growth hormone; sheep with a French strain of scrapie; and mice carrying a prion derived from an American scrapie strain. As expected, they all affected the brain in a different way from BSE and vCJD. But while the American strain of scrapie caused different damage from sCJD, the French strain produced exactly the same pathology.
"The main evidence that scrapie does not affect humans has been epidemiology," says Moira Bruce of the neuropathogenesis unit of the Institute for Animal Health in Edinburgh, who was a member of the same team as Deslys. "You see about the same incidence of the disease everywhere, whether or not there are many sheep, and in countries such as New Zealand with no scrapie." In the only previous comparisons of sCJD and scrapie in mice, Bruce found they were dissimilar.
But there are more than 20 strains of scrapie, and six of sCJD. "You would not necessarily see a relationship between the two with epidemiology if only some strains affect only some people," says Deslys. Bruce is cautious about the mouse results, but agrees they require further investigation. Other trials of scrapie and sCJD in mice, she says, are in progress.
People can have three different genetic variations of the human prion protein, and each type of protein can fold up two different ways. Kretschmar has found that these six combinations correspond to six clinical types of sCJD: each type of normal prion produces a particular pathology when it spontaneously deforms to produce sCJD.
But if these proteins deform because of infection with a disease-causing prion, the relationship between pathology and prion type should be different, as it is in vCJD. "If we look at brain samples from sporadic CJD cases and find some that do not fit the pattern," says Kretschmar, "that could mean they were caused by infection."
There are 250 deaths per year from sCJD in the US, and a similar incidence elsewhere. Singeltary and other US activists think that some of these people died after eating contaminated meat or "nutritional" pills containing dried animal brain. Governments will have a hard time facing activists like Singeltary if it turns out that some sCJD isn't as spontaneous as doctors have insisted.
Deslys's work on macaques also provides further proof that the human disease vCJD is caused by BSE. And the experiments showed that vCJD is much more virulent to primates than BSE, even when injected into the bloodstream rather than the brain. This, says Deslys, means that there is an even bigger risk than we thought that vCJD can be passed from one patient to another through contaminated blood transfusions and surgical instruments.
http://www.newscientist.com/article/mg16922840.300-like-lambs-to-the-slaughter.html
why do we not want to do TSE transmission studies on chimpanzees $
5. A positive result from a chimpanzee challenged severly would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.
snip...
R. BRADLEY
http://collections.europarchive.org/tna/20080102222950/http://www.bseinquiry.gov.uk/files/yb/1990/09/23001001.pdf
1: J Infect Dis 1980 Aug;142(2):205-8
Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.
Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.
Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.
snip...
The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.
PMID: 6997404
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract
Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias"
Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.
snip...
76/10.12/4.6
http://web.archive.org/web/20010305223125/www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf
Nature. 1972 Mar 10;236(5341):73-4.
Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).
Gibbs CJ Jr, Gajdusek DC.
Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0
Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)
C. J. GIBBS jun. & D. C. GAJDUSEK
National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland
SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey (Macaca fascicularis) with an incubation period of more than 5 yr from the time of intracerebral inoculation of scrapie-infected mouse brain. The animal developed a chronic central nervous system degeneration, with ataxia, tremor and myoclonus with associated severe scrapie-like pathology of intensive astroglial hypertrophy and proliferation, neuronal vacuolation and status spongiosus of grey matter. The strain of scrapie virus used was the eighth passage in Swiss mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton, Berkshire).
http://www.nature.com/nature/journal/v236/n5341/abs/236073a0.html
http://scrapie-usa.blogspot.com/2010/04/scrapie-and-atypical-scrapie.html
Saturday, December 13, 2014
*** Terry S. Singeltary Sr. Publications TSE prion disease Peer Review ***
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA
snip...
http://transmissiblespongiformencephalopathy.blogspot.com/2014/12/terry-s-singeltary-sr-publications-tse.html
layperson
Thank you,
Sincerely,
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518 flounder9@verizon.net