Thursday, November 14, 2013

A Novel Prion Disease Associated with Diarrhea and Autonomic Neuropathy

Original Article

 

A Novel Prion Disease Associated with Diarrhea and Autonomic Neuropathy

 

Simon Mead, M.D., Sonia Gandhi, M.D., Jon Beck, B.Sc., Diana Caine, Ph.D., Dillip Gallujipali, M.D., Christopher Carswell, M.D., Harpreet Hyare, M.D., Susan Joiner, M.Sc., Hilary Ayling, B.Sc., Tammaryn Lashley, Ph.D., Jacqueline M. Linehan, B.Sc., Huda Al-Doujaily, M.Sc., Bernadette Sharps, B.Sc., Tamas Revesz, M.D., Malin K. Sandberg, Ph.D., Mary M. Reilly, M.D., Martin Koltzenburg, M.D., Alastair Forbes, M.D., Peter Rudge, M.D., Sebastian Brandner, M.D., Jason D. Warren, M.D., Jonathan D.F. Wadsworth, Ph.D., Nicholas W. Wood, M.D., Janice L. Holton, M.D., and John Collinge, M.D.

 

N Engl J Med 2013; 369:1904-1914November 14, 2013DOI: 10.1056/NEJMoa1214747

 

Background

 

Human prion diseases, although variable in clinicopathological phenotype, generally present as neurologic or neuropsychiatric conditions associated with rapid multifocal central nervous system degeneration that is usually dominated by dementia and cerebellar ataxia. Approximately 15% of cases of recognized prion disease are inherited and associated with coding mutations in the gene encoding prion protein (PRNP). The availability of genetic diagnosis has led to a progressive broadening of the recognized spectrum of disease.

 

Methods

 

We used longitudinal clinical assessments over a period of 20 years at one hospital combined with genealogical, neuropsychological, neurophysiological, neuroimaging, pathological, molecular genetic, and biochemical studies, as well as studies of animal transmission, to characterize a novel prion disease in a large British kindred. We studied 6 of 11 affected family members in detail, along with autopsy or biopsy samples obtained from 5 family members.

 

Results

 

We identified a PRNP Y163X truncation mutation and describe a distinct and consistent phenotype of chronic diarrhea with autonomic failure and a length-dependent axonal, predominantly sensory, peripheral polyneuropathy with an onset in early adulthood. Cognitive decline and seizures occurred when the patients were in their 40s or 50s. The deposition of prion protein amyloid was seen throughout peripheral organs, including the bowel and peripheral nerves. Neuropathological examination during end-stage disease showed the deposition of prion protein in the form of frequent cortical amyloid plaques, cerebral amyloid angiopathy, and tauopathy. A unique pattern of abnormal prion protein fragments was seen in brain tissue. Transmission studies in laboratory mice were negative.

 

Conclusions

 

Abnormal forms of prion protein that were found in multiple peripheral tissues were associated with diarrhea, autonomic failure, and neuropathy. (Funded by the U.K. Medical Research Council and others.)

 

Supported by grants from the U.K. Medical Research Council (MRC) (in part to Dr. Reilly), the Reta Lila Weston Institute of Neurological Studies (to Dr. Holton and Ms. Ayling), Alzheimer's Research UK (to Drs. Holton, Revesz, and Lashley), the Multiple System Atrophy Trust (to Drs. Holton and Revesz), the National Institute for Health Research (NIHR) Biomedical Research Centre at the University College London Hospitals NHS Foundation Trust and University College London, the NIHR Dementia Biomedical Research Unit, the National Institutes of Neurological Diseases and Stroke and Office of Rare Diseases Research (U54NS065712, to Dr. Reilly), a Wellcome Trust Senior Clinical Fellowship (to Dr. Warren), and a Wellcome Trust/MRC Neurodegeneration award (WT089698).

 

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

 

Drs. Mead and Gandhi and Drs. Holton and Collinge contributed equally to this article.

 

We thank the patients and their families, caregivers, and physicians for providing medical histories and assessments for use in the patient reports; Ray Young for assistance with the original figures; Kerrie Venner for assistance with electron microscopy; and Prof. Bernardino Ghetti for helpful discussions.

 

 Source Information

 

From the Medical Research Council (MRC) Prion Unit (S.M., J.B., C.C., S.J., J.M.L., H.A.-D., B.S., M.K.S., S.B., J.D.F.W., J.C.), Department of Molecular Neuroscience (S.G., N.W.W.), and Dementia Research Centre, Department of Neurodegenerative Disease (J.D.W.), and MRC Centre for Neuromuscular Diseases (M.M.R.), University College London (UCL) Institute of Neurology; the National Prion Clinic (S.M., D.C., D.G., H.H., P.R., J.C.), National Hospital for Neurology and Neurosurgery (M.K.), UCL Hospitals National Health Service Trust (A.F.); and the Queen Square Brain Bank (H.A., T.L., T.R., J.L.H.) — all in London.

 

Address reprint requests to Dr. Collinge at the MRC Prion Unit, UCL Institute of Neurology, Queen Sq., London WC1N 3BG, United Kingdom, or at j.collinge@prion.ucl.ac.uk.

 


 

 Wednesday, November 13, 2013

 

Spontaneous Generation of Infectious Prion Disease in Transgenic Mice

 


 

Wednesday, November 13, 2013

 

Atypical Scrapie Prions from Sheep and Lack of Disease in Transgenic Mice Overexpressing Human Prion Protein

 


 

CJD Mark Tami: To ask the Secretary of State for Health (1) what steps his Department has put in place to monitor the number of people who carry the abnormal prion protein which causes variant Creutzfeldt-Jakob disease; [174628]

 

(2) when he plans that screening of the abnormal prion protein which causes variant Creutzfeldt-Jakob disease will be introduced; [174631]

 

(3) what assessment he has made of the number of people who carry the abnormal prion protein which causes variant Creutzfeldt-Jakob disease. [174633]

 

12 Nov 2013 : Column 615W

 

Jane Ellison: The presence of abnormal prion protein is currently taken as a marker for asymptomatic carriage of variant Creutzfeldt-Jakob disease or for symptomatic infection. A recent study to assess carriage by looking at stored appendix tissue samples, first published in the Health Protection Report in August 2012, found abnormal prion protein in 16 appendices out of 32,441 samples. This suggests a prevalence of about 1 in 2,000.

 

There is no monitoring of people who may carry the abnormal prion protein; all appendix prevalence studies are anonymised.

 

No routine screening can yet take place as there are no suitable validated screening tests for abnormal prion protein available. The Department, together with the United Kingdom Blood Services, continues to monitor, scientific research and development in this area.

 


 

Monday, October 14, 2013

 

Researchers estimate one in 2,000 people in the UK carry variant CJD proteins

 


 

Tuesday, October 29, 2013

 

VARIANT CJD PRESENTS DIFFERENTLY IN OLDER PATIENTS

 


 

Wednesday, October 09, 2013

 

*** WHY THE UKBSEnvCJD ONLY THEORY IS SO POPULAR IN IT'S FALLACY, £41,078,281 in compensation REVISED

 


 

Thursday, October 10, 2013

 

CJD REPORT 1994 increased risk for consumption of veal and venison and lamb

 


 

Friday, August 16, 2013

 

*** Creutzfeldt-Jakob disease (CJD) biannual update August 2013 U.K. and Contaminated blood products induce a highly atypical prion disease devoid of PrPres in primates

 


 

WHAT about the sporadic CJD TSE proteins ?

 

WE now know that some cases of sporadic CJD are linked to atypical BSE and atypical Scrapie, so why are not MORE concerned about the sporadic CJD, and all it’s sub-types $$$

 

Creutzfeldt-Jakob Disease CJD cases rising North America updated report August 2013

 

*** Creutzfeldt-Jakob Disease CJD cases rising North America with Canada seeing an extreme increase of 48% between 2008 and 2010 ***

 


 

Sunday, October 13, 2013

 

CJD TSE Prion Disease Cases in Texas by Year, 2003-2012

 


 

Saturday, November 2, 2013

 

Recommendation of the Swiss Expert Committee for Biosafety on the classification of activities using prion genes and prion protein January 2013

 


 

Saturday, November 2, 2013

 

APHIS Finalizes Bovine Import Regulations in Line with International Animal Health Standards while enhancing the spread of BSE TSE prion mad cow type disease around the Globe

 


 

I AGREE WITH MR. BULLARD, it’s all about trade and money, BSE TSE PRION aka mad cow type disease and sound science there from, was thrown out the window by the USDA et al that fateful day in December 23, 2003, when the USDA lost it’s ‘gold card’ of supposedly being BSE FREE, (that was and still is a sad joke though), that’s when mad cow junk science was adopted by the USDA...

 

see why below...kind regards, terry

 

Monday, November 4, 2013

 

*** R-CALF Bullard new BSE rule represents the abrogation of USDA’s responsibility to protect U.S. consumers and the U.S. cattle herd from the introduction of foreign animal disease

 


 

*** Saturday, November 2, 2013 ***

 

Exploring the risks of a putative transmission of BSE to new species

 


 

Wednesday, September 25, 2013

 

Presence of subclinical infection in gene-targeted human prion protein transgenic mice exposed to atypical BSE

 


 

I ask Professor Kong ; Thursday, December 04, 2008 3:37 PM

 

Subject: RE: re--Chronic Wating Disease (CWD) and Bovine Spongiform Encephalopathies (BSE): Public Health Risk Assessment ''IS the h-BSE more virulent than typical BSE as well, or the same as cBSE, or less virulent than cBSE? just curious.....'' Professor Kong reply ;

 

.....snip

 

''As to the H-BSE, we do not have sufficient data to say one way or another, but we have found that H-BSE can infect humans. I hope we could publish these data once the study is complete. Thanks for your interest.''

 

Best regards, Qingzhong Kong, PhD Associate Professor Department of Pathology Case Western Reserve University Cleveland, OH 44106 USA END...TSS

 

Thursday, December 04, 2008 2:37 PM

 

"we have found that H-BSE can infect humans."

 

personal communication with Professor Kong. ...TSS

 

BSE-H is also transmissible in our humanized Tg mice. The possibility of more than two atypical BSE strains will be discussed.

 

Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.

 


 


 

please see below from PRION2013 ;

 

*** This study imply the possibility that the novel BSE prions with high virulence in cattle will be emerged during intraspecies transmission.

 

AD.56: The emergence of novel BSE prions by serial passages of H-type BSE in bovinized mice

 

Kentaro Masujin, Naoko Tabeta, Ritsuko Miwa, Kohtaro Miyazawa, Hiroyuki Okada, Shirou Mohri and Takashi Yokoyama National Institute of Animal Health; Tsukuba, Japan

 

H-type bovine spongiform encephalopathy (BSE) is an atypical form of BSE, and has been detected in several European countries, and North America. Transmission studies of H-type BSE led to the emergence of the classical BSE (C-BSE) phenotypes during passages in inbred wild type and bovinized PrP-overexpressing transgenic mice. In this study, we conducted serial passages of Canadian H-type BSE isolate in bovinized PrP-overexpressing transgenic mice (TgBoPrP). H-type BSE isolate was transmitted to TgBoPrP with incubation periods of 320 ± 12.2 d at primary passage. The incubation period of 2nd and 3rd passage were constant (~= 220 d), no clear differences were observed in their biological and biochemical properties. However, at the forth passage, 2 different BSE phenotypes were confirmed; one is shorter survival times (109 ± 4 d) and the other is longer survival times. TgBoPrP mice with longer incubation period showed the H-type phenotype of PrPsc profile and pathology. However, those of shorter incubation period were different phenotypes from previously existed BSE prions (C-BSE, L-type BSE, and H-type BSE).

 

*** This study imply the possibility that the novel BSE prions with high virulence in cattle will be emerged during intraspecies transmission.

 


 

www.landesbioscience.com

 

please see ;

 

Thursday, August 15, 2013

 

The emergence of novel BSE prions by serial passages of H-type BSE in bovinized mice

 


 

Sunday, September 1, 2013

 

*** Evaluation of the Zoonotic Potential of Transmissible Mink Encephalopathy

 

We previously described the biochemical similarities between PrPres derived from L-BSE infected macaque and cortical MM2 sporadic CJD: those observations suggest a link between these two uncommon prion phenotypes in a primate model (it is to note that such a link has not been observed in other models less relevant from the human situation as hamsters or transgenic mice overexpressing ovine PrP [28]). We speculate that a group of related animal prion strains (L-BSE, c-BSE and TME) would have a zoonotic potential and lead to prion diseases in humans with a type 2 PrPres molecular signature (and more specifically type 2B for vCJD)

 

snip...

 

Together with previous experiments performed in ovinized and bovinized transgenic mice and hamsters [8,9] indicating similarities between TME and L-BSE, the data support the hypothesis that L-BSE could be the origin of the TME outbreaks in North America and Europe during the mid-1900s.

 


 

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...

 


 


 

see follow-up here about North America BSE Mad Cow TSE prion risk factors, and the ever emerging strains of Transmissible Spongiform Encephalopathy in many species here in the USA, including humans ;

 


 

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...

 


 


 


 

 Wednesday, November 13, 2013

 

CJD House of Commons Tuesday 12 November 2013

 


 

 Sunday, December 12, 2010

 

EFSA reviews BSE/TSE infectivity in small ruminant tissues News Story 2 December 2010

 


 

Wednesday, January 18, 2012

 

Selection of Distinct Strain Phenotypes in Mice Infected by Ovine Natural Scrapie Isolates Similar to CH1641 Experimental Scrapie

 

Journal of Neuropathology & Experimental Neurology: February 2012 - Volume 71 - Issue 2 - p 140–147

 


 

Thursday, July 14, 2011

 

Histopathological Studies of "CH1641-Like" Scrapie Sources Versus Classical Scrapie and BSE Transmitted to Ovine Transgenic Mice (TgOvPrP4)

 


 

Wednesday, January 18, 2012

 

BSE IN GOATS CAN BE MISTAKEN FOR SCRAPIE

 

February 1, 2012

 


 

Thursday, December 23, 2010

 

Molecular Typing of Protease-Resistant Prion Protein in Transmissible Spongiform Encephalopathies of Small Ruminants, France, 2002-2009

 

Volume 17, Number 1 January 2011

 


 

Thursday, November 18, 2010

 

Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy following passage in sheep

 


 

Monday, December 14, 2009

 

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types

 

(hmmm, this is getting interesting now...TSS)

 

Sporadic CJD type 1 and atypical/ Nor98 scrapie are characterized by fine (reticular) deposits,

 

see also ;

 

All of the Heidenhain variants were of the methionine/ methionine type 1 molecular subtype.

 


 

see full text ;

 

Monday, December 14, 2009

 

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types

 


 

Thursday, July 21, 2011

 

A Second Case of Gerstmann-Sträussler-Scheinker Disease Linked to the G131V Mutation in the Prion Protein Gene in a Dutch Patient Journal of Neuropathology & Experimental Neurology:

 

August 2011 - Volume 70 - Issue 8 - pp 698-702

 


 

Friday, March 09, 2012

 

Experimental H-type and L-type bovine spongiform encephalopathy in cattle: observation of two clinical syndromes and diagnostic challenges

 

Research article

 


 

Thursday, June 23, 2011

 

Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits

 


 

Thursday, February 14, 2013

 

*** The Many Faces of Mad Cow Disease Bovine Spongiform Encephalopathy BSE and TSE prion disease

 


 

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

 


 

Tuesday, March 05, 2013

 

A closer look at prion strains Characterization and important implications

 

Prion 7:2, 99–108; March/April 2013; © 2013 Landes Bioscience

 


 

Thursday, January 26, 2012

 

Facilitated Cross-Species Transmission of Prions in Extraneural Tissue

 

Science 27 January 2012: Vol. 335 no. 6067 pp. 472-475 DOI: 10.1126/science.1215659

 


 

Saturday, February 11, 2012

 

Prion cross-species transmission efficacy is tissue dependent

 


 

Thursday, January 26, 2012

 

The Risk of Prion Zoonoses

 

Science 27 January 2012: Vol. 335 no. 6067 pp. 411-413 DOI: 10.1126/science.1218167

 


 

Monday, April 25, 2011

 

Experimental Oral Transmission of Atypical Scrapie to Sheep

 

Volume 17, Number 5-May 2011

 


 

Sunday, April 18, 2010

 

SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010

 


 

Thursday, November 18, 2010

 

Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy following passage in sheep

 


 

Wednesday, January 19, 2011

 

EFSA and ECDC review scientific evidence on possible links between TSEs in animals and humans Webnachricht 19 Januar 2011

 


 

Monday, June 27, 2011

 

Comparison of Sheep Nor98 with Human Variably Protease-Sensitive Prionopathy and Gerstmann-Sträussler-Scheinker Disease

 


 

Thursday, November 18, 2010

 

Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy following passage in sheep

 


 

Tuesday, September 24, 2013

 

NORDION (US), INC., AND BIOAXONE BIOSCIENCES, INC., Settles $90M Mad Cow TSE prion Contamination Suit Cethrin(R)

 

Case 0:12-cv-60739-RNS Document 1 Entered on FLSD Docket 04/26/2012 Page 1 of 15

 


 

with great sadness and disgust, I must inform you that our federal government has failed us again, and chose the industry over sound science, with regards to TSE prion disease, aka mad cow type disease...tss

 

Saturday, November 2, 2013

 

APHIS Finalizes Bovine Import Regulations in Line with International Animal Health Standards while enhancing the spread of BSE TSE prion mad cow type disease around the Globe

 


 

Monday, November 4, 2013

 

R-CALF Bullard new BSE rule represents the abrogation of USDA’s responsibility to protect U.S. consumers and the U.S. cattle herd from the introduction of foreign animal disease

 


 

 TSS

Wednesday, November 13, 2013

Spontaneous Generation of Infectious Prion Disease in Transgenic Mice

***Spontaneous appearance of infectivity reported in transgenic mice expressing a mutated BoPrP and in mice expressing mutated mouse PrP reported by Stöhr et al. (40) supports the hypothesis that infectious TSE prions, could originate by a random genetic mutation that can induce de novo generation of infectious prions, and that this mechanism could constitute a source of prion diversity. ***These considerations enable us to hypothesize that the BSE epidemic could have begun by a random genetic mutation that was able to generate de novo infectious prions, which were included in meat and bone meal fed to cattle and then broadly expanded in the cattle population. According to this hypothesis, a key strategy for controlling BSE would involve preventing cows from consuming products from cows with spontaneous cases of BSE.***

 

 

 

 

Volume 19, Number 12—December 2013 Research

 

Spontaneous Generation of Infectious Prion Disease in Transgenic Mice

 

Juan-María TorresComments to Author , Joaquín Castilla, Belén Pintado, Alfonso Gutiérrez-Adan, Olivier Andréoletti, Patricia Aguilar-Calvo, Ana-Isabel Arroba, Beatriz Parra-Arrondo, Isidro Ferrer, Jorge Manzanares, and Juan-Carlos Espinosa Author affiliations: Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Madrid, Spain (J.-M. Torres, J. Castilla, B. Pintado, A. Gutiérrez-Adán P. Aguilar-Calvo, A.-I. Arroba, B. Parra-Arrondo, J.-C. Espinosa); Basque Foundation for Science, Bilbao, Spain (J. Castilla); Ecole Nationale Vétérinaire de Toulouse, Toulouse, France (O. Andréoletti); Hospitalet de Llobregat, Barcelona, Spain (I. Ferrer); Universidad Miguel Hernandez, Sant Joan d´Alacant, Spain (J. Manzanares)

 

Abstract

 

We generated transgenic mice expressing bovine cellular prion protein (PrPC) with a leucine substitution at codon 113 (113L). This protein is homologous to human protein with mutation 102L, and its genetic link with Gerstmann–Sträussler–Scheinker syndrome has been established. This mutation in bovine PrPC causes a fully penetrant, lethal, spongiform encephalopathy. This genetic disease was transmitted by intracerebral inoculation of brain homogenate from ill mice expressing mutant bovine PrP to mice expressing wild-type bovine PrP, which indicated de novo generation of infectious prions. Our findings demonstrate that a single amino acid change in the PrPC sequence can induce spontaneous generation of an infectious prion disease that differs from all others identified in hosts expressing the same PrPC sequence. These observations support the view that a variety of infectious prion strains might spontaneously emerge in hosts displaying random genetic PrPC mutations.

 

snip...

 

 The new 113L BSE prion generated shares some phenotypic features with the classical BSE-C prion when inoculated in the same Tg110 mouse line according to various criteria: 1) apparent molecular mass of PrPres, 2) PrPres glycosylation pattern, 3) lack of immunoreactivity with mAb 12B2, 4) pattern of labeling with mAbs Saf84 and R145, 5) detectable PrPres in spleens of infected animals, and 6) spatial distribution of PrPres in brain. However, the vacuolation profile in brain was distinct from those of all known bovine prion strains (classical BSE-C, atypical BSE-H, and atypical BSE-L prions). These differences were maintained after subsequent passages, indicating that the novel prion, spontaneously produced by transgenic mice expressing mutant 113LBoPrP, is distinct from all known bovine prion strains, although it shares many phenotypic features with the classical BSE-C prion.

 

These observations demonstrate that mutations in bovine PrP can result in spontaneous generation of infectious prion diseases and support the hypothesis of a genetic origin for the epidemic BSE prion. Different features exhibited by the new 113L-BSE prion, compared with those of the classical BSE prion, suggest that if the origin of BSE was genetic, it is unlikely that the causal mutation would be related to the 113L mutation. However, slight phenotypic differences observed could be the results of evolution of the epidemic BSE prion in field conditions in cattle, which must be different from those of our transgenic mouse model. Although BoPrP with the 113L mutation has not been found in nature, a potential pathogenic mutation (E211K) within PrP has been recently reported in a cow with an H-type BSE phenotype (39). This mutation is equivalent to a common mutation (E200K) in humans, which is associated with genetic TSEs.

 

Spontaneous appearance of infectivity reported in transgenic mice expressing a mutated BoPrP and in mice expressing mutated mouse PrP reported by Stöhr et al. (40) supports the hypothesis that infectious TSE prions, could originate by a random genetic mutation that can induce de novo generation of infectious prions, and that this mechanism could constitute a source of prion diversity. These considerations enable us to hypothesize that the BSE epidemic could have begun by a random genetic mutation that was able to generate de novo infectious prions, which were included in meat and bone meal fed to cattle and then broadly expanded in the cattle population. According to this hypothesis, a key strategy for controlling BSE would involve preventing cows from consuming products from cows with spontaneous cases of BSE.

 

 Dr Torres is lead researcher scientist in the Prions Group at the Centro de Investigación en Sanidad Animal–Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Madrid, Spain. His research interests include prion strain characterization and evolution and the pathogenesis of prion diseases and their effects on human and animal health.

 

Acknowledgment

 

This study was supported by grants from the Spanish Ministerio de Ciencia e Innovación (EET2002-5168 and AGL2009-11553-C02-02) and the European Union (FP7-2009-CT-222887 and FP7-2009-CT-228394).

 


 

let's take a closer look at this new prionpathy or prionopathy, and then let's look at the g-h-BSEalabama mad cow.

 

This new prionopathy in humans? the genetic makeup is IDENTICAL to the g-h-BSEalabama mad cow, the only _documented_ mad cow in the world to date like this, ......wait, it get's better. this new prionpathy is killing young and old humans, with LONG DURATION from onset of symptoms to death, and the symptoms are very similar to nvCJD victims, OH, and the plaques are very similar in some cases too, bbbut, it's not related to the g-h-BSEalabama cow, WAIT NOW, it gets even better, the new human prionpathy that they claim is a genetic TSE, has no relation to any gene mutation in that family. daaa, ya think it could be related to that mad cow with the same genetic make-up ??? there were literally tons and tons of banned mad cow protein in Alabama in commerce, and none of it transmitted to cows, and the cows to humans there from ??? r i g h t $$$

 

ALABAMA MAD COW g-h-BSEalabama

 

In this study, we identified a novel mutation in the bovine prion protein gene (Prnp), called E211K, of a confirmed BSE positive cow from Alabama, United States of America. This mutation is identical to the E200K pathogenic mutation found in humans with a genetic form of CJD. This finding represents the first report of a confirmed case of BSE with a potential pathogenic mutation within the bovine Prnp gene. We hypothesize that the bovine Prnp E211K mutation most likely has caused BSE in "the approximately 10-year-old cow" carrying the E221K mutation.

 


 


 

 

 

***Spontaneous appearance of infectivity reported in transgenic mice expressing a mutated BoPrP and in mice expressing mutated mouse PrP reported by Stöhr et al. (40) supports the hypothesis that infectious TSE prions, could originate by a random genetic mutation that can induce de novo generation of infectious prions, and that this mechanism could constitute a source of prion diversity. ***These considerations enable us to hypothesize that the BSE epidemic could have begun by a random genetic mutation that was able to generate de novo infectious prions, which were included in meat and bone meal fed to cattle and then broadly expanded in the cattle population. According to this hypothesis, a key strategy for controlling BSE would involve preventing cows from consuming products from cows with spontaneous cases of BSE.***

 

 

 

her healthy calf also carried the mutation (J. A. Richt and S. M. Hall PLoS Pathog. 4, e1000156; 2008).

 

This raises the possibility that the disease could occasionally be genetic in origin. Indeed, the report of the UK BSE Inquiry in 2000 suggested that the UK epidemic had most likely originated from such a mutation and argued against the scrapierelated assumption. Such rare potential pathogenic PRNP mutations could occur in countries at present considered to be free of BSE, such as Australia and New Zealand. So it is important to maintain strict surveillance for BSE in cattle, with rigorous enforcement of the ruminant feed ban (many countries still feed ruminant proteins to pigs). Removal of specified risk material, such as brain and spinal cord, from cattle at slaughter prevents infected material from entering the human food chain. Routine genetic screening of cattle for PRNP mutations, which is now available, could provide additional data on the risk to the public. Because the point mutation identified in the Alabama animals is identical to that responsible for the commonest type of familial (genetic) CJD in humans, it is possible that the resulting infective prion protein might cross the bovine–human species barrier more easily. Patients with vCJD continue to be identified. The fact that this is happening less often should not lead to relaxation of the controls necessary to prevent future outbreaks.

 

Malcolm A. Ferguson-Smith Cambridge University Department of Veterinary Medicine, Madingley Road, Cambridge CB3 0ES, UK e-mail: maf12@cam.ac.uk Jürgen A. Richt College of Veterinary Medicine, Kansas State University, K224B Mosier Hall, Manhattan, Kansas 66506-5601, USA

 

NATURE|Vol 457|26 February 2009

 


 

 

Saturday, August 14, 2010

 

***BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and VPSPr PRIONPATHY

 

*** (see mad cow feed in COMMERCE IN ALABAMA...TSS)

 


 

 

However, a BSE expert said that consumption of infected material is the only known way that cattle get the disease under natural conditons.

 

***“In view of what we know about BSE after almost 20 years experience, contaminated feed has been the source of the epidemic,” said Paul Brown, a scientist retired from the National Institute of Neurological Diseases and Stroke.

 

BSE is not caused by a microbe. It is caused by the misfolding of the so-called “prion protein” that is a normal constituent of brain and other tissues. If a diseased version of the protein enters the brain somehow, it can slowly cause all the normal versions to become misfolded. It is possible the disease could arise spontaneously, though such an event has never been recorded, Brown said.

 


 

 

*** What irks many scientists is the USDA’s April 25 statement that the rare disease is “not generally associated with an animal consuming infected feed.”

 

The USDA’s conclusion is a “gross oversimplification,” said Dr. Paul Brown, one of the world’s experts on this type of disease who retired recently from the National Institutes of Health. "(The agency) has no foundation on which to base that statement.”

 


 

 However, a BSE expert said that consumption of infected material is the only known way that cattle get the disease under natural conditons.

 

“In view of what we know about BSE after almost 20 years experience, contaminated feed has been the source of the epidemic,” said Paul Brown, a scientist retired from the National Institute of Neurological Diseases and Stroke.

 

BSE is not caused by a microbe. It is caused by the misfolding of the so-called “prion protein” that is a normal constituent of brain and other tissues. If a diseased version of the protein enters the brain somehow, it can slowly cause all the normal versions to become misfolded. It is possible the disease could arise spontaneously, though such an event has never been recorded, Brown said.

 


 

 

*** Saturday, November 2, 2013 ***

 

Exploring the risks of a putative transmission of BSE to new species

 


 

 

Wednesday, September 25, 2013

 

Presence of subclinical infection in gene-targeted human prion protein transgenic mice exposed to atypical BSE

 


 

 

I ask Professor Kong ; Thursday, December 04, 2008 3:37 PM

 

Subject: RE: re--Chronic Wating Disease (CWD) and Bovine Spongiform Encephalopathies (BSE): Public Health Risk Assessment ''IS the h-BSE more virulent than typical BSE as well, or the same as cBSE, or less virulent than cBSE? just curious.....'' Professor Kong reply ;

 

.....snip

 

''As to the H-BSE, we do not have sufficient data to say one way or another, but we have found that H-BSE can infect humans. I hope we could publish these data once the study is complete. Thanks for your interest.''

 

Best regards, Qingzhong Kong, PhD Associate Professor Department of Pathology Case Western Reserve University Cleveland, OH 44106 USA END...TSS

 

Thursday, December 04, 2008 2:37 PM

 

"we have found that H-BSE can infect humans."

 

personal communication with Professor Kong. ...TSS

 

BSE-H is also transmissible in our humanized Tg mice. The possibility of more than two atypical BSE strains will be discussed.

 

Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.

 


 


 

 

please see below from PRION2013 ;

 

 

*** This study imply the possibility that the novel BSE prions with high virulence in cattle will be emerged during intraspecies transmission.

 

AD.56: The emergence of novel BSE prions by serial passages of H-type BSE in bovinized mice

 

Kentaro Masujin, Naoko Tabeta, Ritsuko Miwa, Kohtaro Miyazawa, Hiroyuki Okada, Shirou Mohri and Takashi Yokoyama National Institute of Animal Health; Tsukuba, Japan

 

H-type bovine spongiform encephalopathy (BSE) is an atypical form of BSE, and has been detected in several European countries, and North America. Transmission studies of H-type BSE led to the emergence of the classical BSE (C-BSE) phenotypes during passages in inbred wild type and bovinized PrP-overexpressing transgenic mice. In this study, we conducted serial passages of Canadian H-type BSE isolate in bovinized PrP-overexpressing transgenic mice (TgBoPrP). H-type BSE isolate was transmitted to TgBoPrP with incubation periods of 320 ± 12.2 d at primary passage. The incubation period of 2nd and 3rd passage were constant (~= 220 d), no clear differences were observed in their biological and biochemical properties. However, at the forth passage, 2 different BSE phenotypes were confirmed; one is shorter survival times (109 ± 4 d) and the other is longer survival times. TgBoPrP mice with longer incubation period showed the H-type phenotype of PrPsc profile and pathology. However, those of shorter incubation period were different phenotypes from previously existed BSE prions (C-BSE, L-type BSE, and H-type BSE).

 

*** This study imply the possibility that the novel BSE prions with high virulence in cattle will be emerged during intraspecies transmission.

 


 

www.landesbioscience.com

 

please see ;

 

Thursday, August 15, 2013

 

The emergence of novel BSE prions by serial passages of H-type BSE in bovinized mice

 


 

Sunday, September 1, 2013

 

*** Evaluation of the Zoonotic Potential of Transmissible Mink Encephalopathy

 

We previously described the biochemical similarities between PrPres derived from L-BSE infected macaque and cortical MM2 sporadic CJD: those observations suggest a link between these two uncommon prion phenotypes in a primate model (it is to note that such a link has not been observed in other models less relevant from the human situation as hamsters or transgenic mice overexpressing ovine PrP [28]). We speculate that a group of related animal prion strains (L-BSE, c-BSE and TME) would have a zoonotic potential and lead to prion diseases in humans with a type 2 PrPres molecular signature (and more specifically type 2B for vCJD)

 

snip...

 

Together with previous experiments performed in ovinized and bovinized transgenic mice and hamsters [8,9] indicating similarities between TME and L-BSE, the data support the hypothesis that L-BSE could be the origin of the TME outbreaks in North America and Europe during the mid-1900s.

 


 

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...

 


 


 

see follow-up here about North America BSE Mad Cow TSE prion risk factors, and the ever emerging strains of Transmissible Spongiform Encephalopathy in many species here in the USA, including humans ;

 


 

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...

 


 

PRIONOPATHY OR PRIONOBALONEY $$$

 


 


 

 Conclusion/Significance: Our results point to a possibly higher degree of pathogenicity of BASE than classical BSE in primates and also raise a question about a possible link to one uncommon subset of cases of apparently sporadic CJD. Thus, despite the waning epidemic of classical BSE, the occurrence of atypical strains should temper the urge to relax measures currently in place to protect public health from accidental contamination by BSE-contaminated products.

 


 


 


 


 

 SPONTANEOUS TSE

 

Perspectives BIOMEDICINE: A Fresh Look at BSE Bruce Chesebro*

 

Mad cow disease, or bovine spongiform encephalopathy (BSE), is the cattle form of a family of progressive brain diseases. These diseases include scrapie in sheep, Creutzfeldt-Jakob disease (CJD) in humans, and chronic wasting disease (CWD) in deer and elk. They are also known as either "prion diseases" because of the association of a misfolded cellular prion protein in pathogenesis or "transmissible spongiform encephalopathies" (TSEs) because of the spongelike nature of the damaged brain tissue (1).

 

The recent discovery of two BSE-infected cows, one in Canada and one in the United States, has dramatically increased concern in North America among meat producers and consumers alike over the extent to which BSE poses a threat to humans as well as to domestic and wild animals. The European BSE epidemic of the late-1980s seems to have been initiated a decade earlier in the United Kingdom by changes in the production of meat and bone meal (MBM) from rendered livestock, which led to contamination of MBM with the BSE infectious agent. Furthermore, the fact that UK farmers fed this rendered MBM to younger animals and that this MBM was distributed to many countries may have contributed to the ensuing BSE epidemic in the United Kingdom and internationally (2).

 

Despite extensive knowledge about the spread of BSE through contaminated MBM, the source of BSE in Europe remains an unsolved mystery (2). It has been proposed that BSE could be derived from a cross-species infection, perhaps through contamination of MBM by scrapie-infected sheep tissues (see the figure). Alternatively, BSE may have been an endemic disease in cattle that went unnoticed because of its low level of horizontal transmission. Lastly, BSE might have originated by "spontaneous" misfolding of the normal cellular prion protein into the disease-associated abnormal isoform (3), which is postulated to be the infectious agent or "prion."

 

Five possible sources of BSE in North American cattle. Sheep, deer, and elk could spread prion diseases (TSEs) to cattle through direct animal contact or contamination of pastures. Endemic BSE has not been proven to exist anywhere in the world, but it is difficult to exclude this possibility because of the inefficient spread of BSE infectivity between individual animals (2). BSE caused by spontaneous misfolding of the prion protein has not been proven. CREDIT: KATHARINE SUTLIFF/SCIENCE

 

snip...

 

Nevertheless, the idea that BSE might originate due to the spontaneous misfolding of prion proteins has received renewed interest in the wake of reports suggesting the occurrence of atypical BSE (9-11). These results imply that new strains of cattle BSE might have originated separately from the main UK outbreak. Where and how might such strains have originated? Although such rare events cannot be studied directly, any number of sources of the original BSE strain could also explain the discovery of additional BSE strains in cattle (see the figure). However, it would be worrisome if spontaneous BSE were really a valid etiology because such a mechanism would be impossible to prevent--unlike other possible scenarios that could be controlled by large-scale eradication of TSE-positive animals.

 

Another way to look at this problem is to examine evidence for possible spontaneous TSE disease in other animals besides cattle. Spontaneous BSE would be extremely difficult to detect in cattle, where horizontal spread is minimal. However, in the case of the sheep TSE disease, scrapie, which spreads from ewes to lambs at birth as well as between adults, spontaneous disease should be detectable as new foci of clinical infection. In the early 1950s scrapie was eradicated in both Australia and New Zealand, and the mainland of both these countries has remained scrapie-free ever since. This scrapie-free status is not the result of selection of sheep resistant to scrapie because sheep from New Zealand are as susceptible as their UK counterparts to experimental scrapie infection (12). These experiments of man and nature appear to indicate that spontaneous clinical scrapie does not occur in sheep. Similarly, because CWD is known to spread horizontally, the lack of CWD in the deer or elk of eastern North America but its presence in western regions would also argue against a spontaneous disease mechanism. This is particularly noteworthy in New Zealand, where there are large numbers of deer and elk farms and yet no evidence of spontaneous CWD. If spontaneous scrapie does not occur in sheep or deer, this would suggest that spontaneous forms of BSE and sporadic Creutzfeldt-Jakob disease (sCJD) are unlikely to be found in cattle or humans. The main caveat to this notion is that spontaneous disease may arise in some animal species but not others. In humans, sCJD--which is considered by some researchers to begin by spontaneous misfolding of the prion protein--usually takes more than 50 years to appear. Thus, in animals with a shorter life-span, such as sheep, deer, and cattle, an analogous disease mechanism might not have time to develop.

 

What can we conclude so far about BSE in North America? Is the BSE detected in two North American cows sporadic or spontaneous or both? "Sporadic" pertains to the rarity of disease occurrence. "Spontaneous" pertains to a possible mechanism of origin of the disease. These are not equivalent terms. The rarity of BSE in North America qualifies it as a sporadic disease, but this low incidence does not provide information about cause. For the two reported North American BSE cases, exposure to contaminated MBM remains the most likely culprit. However, other mechanisms are still possible, including cross-infection by sheep with scrapie or cervids with CWD, horizontal transmission from cattle with endemic BSE, and spontaneous disease in individual cattle. Based on our understanding of other TSEs, the spontaneous mechanism is probably the least likely. Thus, "idiopathic" BSE--that is, BSE of unknown etiology--might be a better term to describe the origin of this malady. ...

 

snip...full text ;

 


 

 DR. DEHAVEN: “All right. I think we've got three different questions in there, and I'll try to touch on each one of them.

 

“First of all, let me correct just a technical issue, and that is you mentioned 1 in 10,000. And actually our surveillance system currently is designed, the one that we have in place now is designed to detect 1 positive in 1 million cattle, and I gave some numbers between 200,000 and 268,000 that would allow us to detect 1 in 10 million as opposed to 1 in 10,000.

 

“So we would, if we were able to collect in the ballpark of those numbers of samples then we with increasing numbers of samples have an increasingly statistically valid sample from which to determine, one, whether or not the disease exists and, if so, at what prevalence level.

 

“So our real emphasis is to test as many of those animals as we can, ensure that we get an appropriate geographical distribution, but not setting a specific number as far as a target. Again, consistent with the recommendation from the International Review Team, their recommendation was to test all of them.

 

“So that's consistent with where we're going is to test as many as we possibly can.

 

*** “As far as spontaneous cases, that is a very difficult issue. There is no evidence to prove that spontaneous BSE occurs in cattle; but here again it's an issue of proving a negative. We do know that CJD, the human version of the disease, does occur spontaneously in humans at the rate of about 1 in 1 million. We don't have enough data to definitively say that spontaneous cases of BSE in cattle occur or do not occur.

 

“Again, it's a very difficult situation to prove a negative.

 

“So a lot of research is ongoing. Certainly if we do come up with any positive samples in the course of this surveillance we will be looking at that question in evaluating those samples but no scientifically hard evidence to confirm or refute whether or not spontaneous cases of BSE occur.

 

snip...

 


 


 

 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...

 


 

 Thursday, August 12, 2010

 

 Seven main threats for the future linked to prions

 


 


 

Tuesday, November 02, 2010

 

 BSE – ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only) diagnostic criteria CVL 1992

 


 

 Atypical BSE in Cattle

 

 BSE has been linked to the human disease variant Creutzfeldt Jakob Disease (vCJD). The known exposure pathways for humans contracting vCJD are through the consumption of beef and beef products contaminated by the BSE agent and through blood transfusions. However, recent scientific evidence suggests that the BSE agent may play a role in the development of other forms of human prion diseases as well. These studies suggest that classical type of BSE may cause type 2 sporadic CJD and that H-type atypical BSE is connected with a familial form of CJD.

 

 To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

 

snip...see full text ;

 


 

Friday, April 19, 2013

 

Bovine Spongiform Encephalopathy (BSE) Feed Safety Support Program Grants Fiscal Year 2011: October 1, 2010 - September 30, 2011 FDA

 


 


 

 

 

 J. clin. Path., 25, Suppi. (Roy. Coll. Path.), 6, 110-114

 

Scrapie-a personal view

 

l. H. PATTISON

 

From the ARC Institute for Research on Animal Diseases, Compton, Newbury, Berkshire

 

The first published reference to the transmissible agent as something other than a virus was by Parry (1962), who called it a provirus, defined as something that was formed inside an affected animal but had no independent outside existence. The next published suggestion that the scrapie agent might be odd was my own (Pattison, 1965) when I said that ' . . . if the transmissible agent of scrapie is a living virus, it is a virus of a kind as yet unrecognized.' This conclusion was based on a long series of unsuccessful attempts to inactivate the scrapie agent by heroic methods, including treatment with 12% formalin for 28 months. But what is a 'virus'? If by 'virus' is meant something that will negotiate an antibacterial filter and can be passed indefinitely through animals, apparently increasing in quantity as it goes, then the scrapie agent is a virus. If, however, a virus has to contain nucleic acid, then I believe that D. A. Haig and M. C. Clarke at Compton and their collaborator Tikvah Alper at the Hammersmith Hospital have shown beyond reasonable doubt by their studies with ultraviolet irradiation that the scrapie agent does not contain nucleic acid and is not a virus (Alper, Haig, and Clarke, 1966; Alper, Cramp, Haig, and Clarke,

 

114

 

1967; Haig, Clarke, Blum, and Alper, 1969; Latarjet, Muel, Haig, Clarke, and Alper, 1970).

 

References

 

Alper, T., Cramp, W. A., 1faig, D. A., and Clarke, M. C. (1967). Does the agent of scrapie replicate without nucleic acid? Nature (Lond.), 214, 764-766.

 

Alper. T., Haig, D. A., and Clarke, M. C. (1966). The exceptionally small size of the scrapie agent. Biochem. biophys. Res. Comnmun., 22, 278-284.

 

Bertrand, I., Carre, ff., and Lucam, F. (1937). La 'tremblante' du mouton. Ann. Anat. path. med.-chir., 14, 565-586.

 

Besnoit, C., and Morel, C. (1898). Note sur les lesions nerveuses de Ia tremblante du mouton. Rev. vet. Toulouse, 23, 397-400.

 

Brownlee, A. (1940). Histopathological studies of scrapie, an obscure disease of sheep. Vet. J., 96, 254-264.

 

Chandler, R. L. (1961). Encephalopathy in mice produced by inoculation with scrapie brain material. Lancet, 1, 1378-1379. Chandler, R. L. (1962). Encephalopathy in mice. (Letter). Lancet, 1, 107-108.

 

Cuille, J., and Chelle, P. L. (1936). La maladie dite tremblante du mouton est-elle inoculable? C.R. Acad. Sci. (Paris), 203, 1552-1554.

 

Cuille, J. and Chelle, P. L. (1938). La tremblante du mouton est-elle determinee par un virus filterable? C.R. Acad. Sci. (Paris), 206, 1687-1688.

 

Cuille, J., and Chelle, P. L. (1939). Transmission experimentale de la tremblante a la chevre. C.R. Acad. Sci. (Paris), 208, 1058-1060.

 

Field, E. J. (1969). Slow virus infections of the nervous system. Int. Rev. exp. Path., 8, 129-239.

 

I. H. Pattison Field, E. J., and Windsor, G. D. (1965). Cultural characters of scrapie mouse brain. Res. vet. Sci., 6, 130-132.

 

Gajdusek, D. C., Gibbs, C. J., Jr., and Alpers, M. (1966). Experimental transmission of a kuru-like syndrome to chimpanzees. Nature (Lond.), 209, 794-796.

 

Gordon, W. S. (1957). Discussion to Palmer, A. C. Studies in scrapie. Vet. Rec., 69, 1324-1327.

 

Gordon, W. S. (1966). Review of work on scrapie at Compton, England, 1952-1964. In Report of Scrapie Seminar, Washington D.C., ARS 91-53, pp. 19-36.

 

Gustafson, D. P., and Kanitz, C. L. (1965). Evidence of the presence of scrapie in cell cultures of brain. In Slow, Latent and Temperate Virus Infections (NINDB Monograph No. 2), pp. 221-236, edited by D. C. Gajdusek, C. J. Gibbs, Jr., and M. Alpers, National Institute of Health, Washington D.C.

 

Hadlow, W. J. (1959). Scrapie and kuru. Lancet, 2, 289-290.

 

Haig, D. A., and Clarke, M. C. (1971). Multiplication of the scrapie agent. Nature (Lond.), 234, 106-107.

 

Haig, D. A., Clarke, M. C., Blum, E., and Alper, T. (1969). Further studies on the inactivation of the scrapie agent by ultraviolet light. J. gen. Virol., 5, 455-457.

 

Haig, D. A., and Pattison, I. H. (1967) In-vitro growth of pieces of brain from scrapie-affected mice. J. Path. Bact., 93, 724-727.

 

Latarjet, R., Muel, B., 1-faig, D. A., Clarke, M. C., and Alper, T. (1970). Inactivation of the scrapie agent by near monochromatic ultraviolet light. Nature (Lond.), 227, 1341-1343.

 

Morris, J. A., and Gajdusek, D. C. (1963). Encephalopathy in mice following inoculation of scrapie sheep brain. Nature (Lond.), 197, 1084-1086.

 

Parry, H. B. (1962). Scrapie: a transmissible and hereditary disease of sheep. Heredity, 17, 75-105.

 

Pattison, I. H. (1965). Resistance of the scrapie agent to formalin. J. comp. Path., 75, 159-164.

 

Pattison, I. H., Gordon, W. S., and Millson, G. C. (1959). Experimental production of scrapie in goats. J. comp. Path., 69, 300-312.

 

Pattison, 1. H., and Millson, G. C. (1961). Scrapie produced experimentally in goats with special reference to the clinical syndrome. J. comp. Path., 71, 101-108.

 

Roche-Lubin (1848). Memoire pratique sur la maladie des b8tes a laine connue sous les noms de prurigo lombaire, maladie convulsive, trembleuse, tremblante, etc. Rec. Med. vet. Ser 3, 5, 698-7 14.

 

Stamp, J. T. (1960). Scrapie and scrapie research at Animal Diseases Research Association, Moredun Institute, Edinburgh. In U.S. Department of Agriculture Special Meetings on Scrapie, ARS 91-22, pp. 13-22.

 

Stamp, J. T., Brotherston, J. G., Ziotnik, I., Mackay, J. M. K., and Smith, W. (1959). Further studies on scrapie. J. comp. Path., 69, 268-280.

 

Stockman, S. (1926). Contribution to the study of the disease known as scrapie. J. comp. Path., 39, 42-71.

 

Thormar, H. (1971). Slow infections of the central nervous system. Z. Neurol., 199, 1-23 and 151-166.

 

Wilson, D. R. (1952). Scrapie. Vet. Rec., 64, 468.

 

Wilson, D. R., Anderson, R. D., and Smith, W. (1950). Studies in scrapie. J. comp. Path., 60, 267-282.

 


 

 4.2.9 A further hypothesis to explain the occurrence of BSE is the emergence or selection of a strain or strains of the scrapie agent pathogenic for cattle. Mutations of the scrapie agent. which can occur after a single passage in mice. have been well documented (9). This phenomenon cannot be dismissed for BSE. but given the form of the epidemic and the geographically widespread occurrence of BSE, such a hypothesis" would require the emergence of a mutant scrapie strain simultaneously in a large . number of sheep flocks, or cattle. throughout the country. Also. if it resulted "from a localised chance transmission of the scrapie strain from sheep to cattle giving rise , . to a mutant. a different pattern of disease would have been expected: its range would '. have increased with time. Thus the evidence from Britain is against the disease being due to a new strain of the agent, but we note that in the United States from 1984 to 1988 outbreaks of scrapie in sheep flocks are reported to have Increased markedly. now being nearly 3 times as high as during any previous period (18).

 


 

If the scrapie agent is generated from ovine DNA and thence causes disease in other species, then perhaps, bearing in mind the possible role of scrapie in CJD of humans (Davinpour et al, 1985), scrapie and not BSE should be the notifiable disease. ...

 


 

 ALSO, SEE Scrapie Mission, Texas, did not produce _typical_ BSE... see page 17 here ;

 

3.57 The experiment which might have determined whether BSE and scrapie were caused by the same agent (ie, the feeding of natural scrapie to cattle) was never undertaken in the UK. It was, however, performed in the USA in 1979, when it was shown that cattle inoculated with the scrapie agent endemic in the flock of Suffolk sheep at the United States Department of Agriculture in Mission, Texas, developed a TSE quite unlike BSE.339 The findings of the initial transmission, though not of the clinical or neurohistological examination, were communicated in October 1988 to Dr Watson, Director of the CVL, following a visit by Dr Wrathall, one of the project leaders in the Pathology Department of the CVL, to the United States Department of Agriculture.340 The results were not published at this point, since the attempted transmission to mice from the experimental cow brain had been inconclusive. The results of the clinical and histological differences between scrapie-affected sheep and cattle were published in 1995. Similar studies in which cattle were inoculated intracerebrally with scrapie inocula derived from a number of scrapie-affected sheep of different breeds and from different States, were carried out at the US National Animal Disease Centre.341 The results, published in 1994, showed that this source of scrapie agent, though pathogenic for cattle,

 

*** did not produce the same clinical signs of brain lesions characteristic of BSE. ***

 

3.58 There are several possible reasons why the experiment was not performed in the UK. It had been recommended by Sir Richard Southwood (Chairman of the Working Party on Bovine Spongiform Encephalopathy) in his letter to the Permanent Secretary of MAFF, Mr (now Sir) Derek Andrews, on 21 June 1988,342 though it was not specifically recommended in the Working Party Report or indeed in the Tyrrell Committee Report (details of the Southwood Working Party and the Tyrell Committee can be found in vol. 4: The Southwood Working Party, 1988–89 and vol. 11: Scientists after Southwood respectively). The direct inoculation of scrapie into calves was given low priority, because of its high cost and because it was known that it had already taken place in the USA.343 It was also felt that the results of such an experiment would be hard to interpret. While a negative result 337 Fraser, H., Bruce, M., Chree, A., McConnell, I. and Wells, G. (1992) Transmission of Bovine Spongiform Encephalopathy and Scrapie to Mice, Journal of General Virology, 73, 1891–7; Bruce, M., Chree, A., McConnell, I., Foster, J., Pearson, G. and Fraser, H. (1994) Transmission of Bovine Spongiform Encephalopathy and Scrapie to Mice: Strain Variation and the Species Barrier, Philosophical Transactions of the Royal Society of London, Series B, Biological Sciences, 343, 405–11 338 Bruce, M., Will, R., Ironside, J., McConell, I., Drummond, D., Suttie, A., McCordie, L., Chree, A., Hope, J., Birkett, C., Cousens, S., Fraser, H. and Bostock, C. (1997) Transmissions to Mice Indicate that ‘New Variant’ CJD is Caused by the BSE Agent, Nature, 389, 498–501 339 Clark, W., Hourrigan, J. and Hadlow, W. (1995) Encephalopathy in Cattle Experimentally Infected with the Scrapie Agent, American Journal of Veterinary Research, 56, 606–12 340 YB88/10.00/1.1 341 Cutlip, R., Miller, J., Race, R., Jenny, A., Katz, J., Lehmkuhl, H., Debey, B. and Robinson, M. (1994) Intracerebral Transmission of Scrapie to Cattle, Journal of Infectious Diseases, 169, 814–20 342 YB88/6.21/1.2 343 YB88/11.17/2.4 SCIENCE 84 would be informative, a positive result would need to demonstrate that when scrapie was transmitted to cattle, the disease which developed in cattle was the same as BSE.344 Given the large number of strains of scrapie and the possibility that BSE was one of them, it would be necessary to transmit every scrapie strain to cattle separately, to test the hypothesis properly. Such an experiment would be expensive. Secondly, as measures to control the epidemic took hold, the need for the experiment from the policy viewpoint was not considered so urgent. It was felt that the results would be mainly of academic interest.345 3.59 Nevertheless, from the first demonstration of transmissibility of BSE in 1988, the possibility of differences in the transmission properties of BSE and scrapie was clear. Scrapie was transmissible to hamsters, but by 1988 attempts to transmit BSE to hamsters had failed. Subsequent findings increased that possibility.

 


 


 


 

In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - APRIL-MAY 1989 - G A H Wells

 

snip...

 

PAGE 31

 

Appendix I

 

VISIT TO USA - DR A E WRATHALL - INFO ON BSE AND SCRAPIE

 

1. Dr Clark lately of the Scrapie Research Unit, Mission Texas has successfully transmitted ovine and caprine scrapie to cattle. The experimental results have not been published but there are plans to do this. This work was initiated in 1978. A summary of it is:-

 

Expt A 6 Her x Jer calves born in 1978 were inoculated as follows with a 2nd Suffolk scrapie passage:-

 

i/c 1ml i/m, 5ml; s/c 5ml; oral 30ml.

 

1/6 went down after 48 months with a scrapie/BSE-like disease.

 

Expt B 6 Her or Jer or HxJ calves were inoculated with angora Goat virus 2/6 went down similarly after 36 months.

 

Expt C Mice inoculated from brains of calves/cattle in expts A & B were resistant, only 1/20 going down with scrapie and this was the reason given for not publishing.

 

Diagnosis in A, B, C was by histopath. No reports on SAF were given.

 

Dr Warren Foote indicated success so far in eliminating scrapie in offspring from experimentally- (and naturally) infected sheep by ET. He had found difficulty in obtaining emhryos from naturally infected sheep (cf SPA).

 

3. Prof. A Robertson gave a brief account of BSE. The US approach was to

 

PAGE 32

 

accord it a very low profile indeed. Dr A Thiermann showed the picture in the "Independent" with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs. BSE was not reported in USA.

 

4. Scrapie incidents (ie affected flocks) have shown a dramatic increase since 1978. In 1953 when the National Control Scheme was started there were 10-14 incidents, in 1978 - 1 and in 1988 so far 60.

 

5. Scrapie agent was reported to have been isolated from a solitary fetus.

 

6. A western blotting diagnostic technique (? on PrP} shows some promise.

 

7. Results of a questionnaire sent to 33 states on the subject of the national sheep scrapie programme survey indicated;

 

17/33 wished to drop it 6/33 wished to develop it 8/33 had few sheep and were neutral

 

Information obtained from Dr Wrathall's notes of a meeting of the U.S. Animal Health Association at Little Rock, Arkansas Nov. 1988.

 

please see ;

 

In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - APRIL-MAY 1989 - G A H Wells

 


 

PAGE 31

 

Appendix I

 

VISIT TO USA - DR A E WRATHALL - INFO ON BSE AND SCRAPIE

 

1. Dr Clark lately of the Scrapie Research Unit, Mission Texas has successfully transmitted ovine and caprine scrapie to cattle. The experimental results have not been published but there are plans to do this. This work was initiated in 1978. A summary of it is:-

 

Expt A 6 Her x Jer calves born in 1978 were inoculated as follows with a 2nd Suffolk scrapie passage:-

 

i/c 1ml i/m, 5ml; s/c 5ml; oral 30ml.

 

1/6 went down after 48 months with a scrapie/BSE-like disease.

 

Expt B 6 Her or Jer or HxJ calves were inoculated with angora Goat virus 2/6 went down similarly after 36 months.

 

Expt C Mice inoculated from brains of calves/cattle in expts A & B were resistant, only 1/20 going down with scrapie and this was the reason given for not publishing.

 

Diagnosis in A, B, C was by histopath. No reports on SAF were given.

 

Dr Warren Foote indicated success so far in eliminating scrapie in offspring from experimentally- (and naturally) infected sheep by ET. He had found difficulty in obtaining emhryos from naturally infected sheep (cf SPA).

 

3. Prof. A Robertson gave a brief account of BSE. The US approach was to

 

PAGE 32

 

accord it a very low profile indeed. Dr A Thiermann showed the picture in the "Independent" with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs. BSE was not reported in USA.

 

4. Scrapie incidents (ie affected flocks) have shown a dramatic increase since 1978. In 1953 when the National Control Scheme was started there were 10-14 incidents, in 1978 - 1 and in 1988 so far 60.

 

5. Scrapie agent was reported to have been isolated from a solitary fetus.

 

6. A western blotting diagnostic technique (? on PrP} shows some promise.

 

7. Results of a questionnaire sent to 33 states on the subject of the national sheep scrapie programme survey indicated;

 

17/33 wished to drop it 6/33 wished to develop it 8/33 had few sheep and were neutral

 

Information obtained from Dr Wrathall's notes of a meeting of the U.S. Animal Health Association at Little Rock, Arkansas Nov. 1988.

 

kind regards,

 

 Terry S. Singeltary Sr., Bacliff, Texas USA -July 29, 2000-

 

please see ;

 


 


 

Their concern deepened as they experimented with ways to sanitize the holding pens in Fort Collins and Sybille. All the deer and elk in the contaminated pens at Sybille were killed, and the pens were left empty for six months to a year. When deer and elk were reintroduced to the pens, they were animals that weren't known to have had direct contact with infected deer and elk. In spite of these efforts, elk in the pens came down with chronic wasting disease within five years after the attempt at sterilizing the facility.

 

In Fort Collins, the effort was even more intense. All the deer and elk in the facility were killed and buried. Then personnel plowed up the soil in the pens in an effort to bury possible disease organisms and sprayed structures and pastures repeatedly with a strong disinfectant. A year later, they took twelve elk calves from the wild and released them in the sanitized holding areas. In the next five years, two of these elk died from chronic wasting disease.

 


 

Saturday, June 25, 2011

 

Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque

 

"BSE-L in North America may have existed for decades"

 


 

 Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.

 

snip...

 

The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...

 


 

 *** Saturday, November 2, 2013 ***

 

Exploring the risks of a putative transmission of BSE to new species

 


 

Wednesday, October 30, 2013

 

SPECIFIED RISK MATERIAL (SRM) CONTROL VERIFICATION TASK FSIS NOTICE 70-13 10/30/13

 


 

 ***Together with previous experiments performed in ovinized and bovinized transgenic mice and hamsters [8,9] indicating similarities between TME and L-BSE, the data support the hypothesis that L-BSE could be the origin of the TME outbreaks in North America and Europe during the mid-1900s.

 


 

 Tuesday, September 24, 2013

 

NORDION (US), INC., AND BIOAXONE BIOSCIENCES, INC., Settles $90M Mad Cow TSE prion Contamination Suit Cethrin(R)

 

*** Case 0:12-cv-60739-RNS Document 1 Entered on FLSD Docket 04/26/2012 Page 1 of 15 ***

 


 

with great sadness and disgust, I must inform you that our federal government has failed us again, and chose the industry over sound science, with regards to TSE prion disease, aka mad cow type disease...tss

 

Saturday, November 2, 2013

 

APHIS Finalizes Bovine Import Regulations in Line with International Animal Health Standards while enhancing the spread of BSE TSE prion mad cow type disease around the Globe

 


 

Monday, November 4, 2013

 

R-CALF Bullard new BSE rule represents the abrogation of USDA’s responsibility to protect U.S. consumers and the U.S. cattle herd from the introduction of foreign animal disease

 


 

 

 

TSS