Monday, September 02, 2013

Atypical BSE: role of the E211K prion polymorphism

Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
 
Location: Virus and Prion Research Unit
 
Title: Atypical BSE: role of the E211K prion polymorphism
 
 
Greenlee, Justin
 
Submitted to: American Veterinary Medical Association Abstract
 
Publication Type: Abstract Only
 
Publication Acceptance Date: May 1, 2013
 
Publication Date: July 19, 2013
 
Citation: Greenlee, J.J. 2013.
 
Atypical BSE: role of the E211K prion polymorphism.
 
2013 American Veterinary Medical Association (AVMA) Annual Convention, July 19-23, 2013, Chicago, Illinois. Paper No. 13920. p. 45.
 
Technical Abstract:
 
Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases that naturally affect several species including human beings. These chronic diseases are associated with the accumulation of a protease-resistant, disease-associated isoform of the prion protein (PrPSc) in the central nervous system and other tissues, depending on the species affected. In humans, TSEs can be acquired through exposure to infectious material, inherited as germline polymorphisms in the prion gene (prnp), or occur spontaneously. Bovine spongiform encephalopathy (BSE) or mad cow disease cases can be subclassified into at least 3 distinct disease forms with the predominant form known as classical BSE and the others collectively referred to as atypical BSE. Atypical BSE is further subdivided into H-type and L-type cases that are distinct from classical BSE and from each other on the basis of their unique molecular profiles. Both atypical BSE subtypes are believed to have arisen spontaneously and today researchers are investigating atypical BSE as a possible origin of classical BSE that was a feed-borne epidemic primarily affecting cattle in Europe where BSE-contaminated animal protein sources derived from central nervous system tissues were previously fed to ruminants. Several hypotheses have been proposed to explain atypical BSE cases. At the forefront of this discussion is the possibility that both H-type and L-type BSE may be spontaneous diseases in cattle. Support for atypical BSE occurring spontaneously is drawn from parallels to sporadic prion disease in humans, specifically, occurrence in older hosts and a comparable low incidence rate. Furthermore, atypical BSE occurs as isolated, sporadic cases in contrast to the clustering of cases observed for feedborne classical BSE. Recognition of a spontaneous prion disease in cattle, coupled with evidence indicating atypical BSE can convert to classical BSE upon serial passage in mice, has broad implications for our understanding of the origins of the classical form of the disease. In 2006 a critical discovery was made when one case of H-type BSE was associated with a heritable mutation in the prion protein gene referred to as E211K. This case was diagnosed in the U.S. and led to the identification of a new prion protein (prnp) allele, K211, that is associated with H-type BSE and is heritable. This presentation will present data demonstrating a rapid onset of disease in an animal with the E211K mutation following experimental inoculation with H-type BSE from the original E211K H-type BSE case. Interestingly, disease associated prion protein was widespread in neural tissues this animal, and antemortem retinal thinning and functional deficits of the visual system were observed prior to the onset of clinical disease. The existence of genetic forms of BSE offers new explanations for the potential origins of BSE.
 
 Last Modified: 09/01/2013
 
 
 
 
 
 
hvCJD...visual symptoms...just more coincidences, and another happenstance of bad luck $$$
 
 
> sCJDMM1-2 should be considered as a separate entity at this time.
 
> All of the Heidenhain variants were of the methionine/ methionine type 1 molecular subtype.
 
 
 
 
 
 
 
WHAT ABOUT those old studies at Mission, Texas, where USA scrapie was transmitted to USA cattle, but the results was not c-BSE. IT was a different TSE.
 
WHAT ABOUT atypical Nor-98 Scrapie in the USA, and TSE there from to other species ???
 
The key word here is diverse. What does diverse mean?
 
If USA scrapie transmitted to USA bovine does not produce pathology as the UK c-BSE, then why would CJD from there look like UK vCJD?"
 
 
see ;
 
Sunday, September 25, 2011 Clinical Heidenhain Variant Of Sporadic Creutzfeldt-Jakob Disease (CJD) With Co-occurrence Of Prion Protein Types 1 and 2
 
 
 
 
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.
 
 
 
 
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)
 
 
 
 
 
***It also suggests a similar cause or source for atypical BSE in these countries.
 
 
 
P.9.21
 
Molecular characterization of BSE in Canada
 
Jianmin Yang1, Sandor Dudas2, Catherine Graham2, Markus Czub3, Tim McAllister1, Stefanie Czub1 1Agriculture and Agri-Food Canada Research Centre, Canada; 2National and OIE BSE Reference Laboratory, Canada; 3University of Calgary, Canada
 
Background: Three BSE types (classical and two atypical) have been identified on the basis of molecular characteristics of the misfolded protein associated with the disease. To date, each of these three types have been detected in Canadian cattle.
 
Objectives: This study was conducted to further characterize the 16 Canadian BSE cases based on the biochemical properties of there associated PrPres. Methods: Immuno-reactivity, molecular weight, glycoform profiles and relative proteinase K sensitivity of the PrPres from each of the 16 confirmed Canadian BSE cases was determined using modified Western blot analysis.
 
Results: Fourteen of the 16 Canadian BSE cases were C type, 1 was H type and 1 was L type. The Canadian H and L-type BSE cases exhibited size shifts and changes in glycosylation similar to other atypical BSE cases. PK digestion under mild and stringent conditions revealed a reduced protease resistance of the atypical cases compared to the C-type cases. N terminal- specific antibodies bound to PrPres from H type but not from C or L type. The C-terminal-specific antibodies resulted in a shift in the glycoform profile and detected a fourth band in the Canadian H-type BSE.
 
Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan. This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada. ***It also suggests a similar cause or source for atypical BSE in these countries.
 
 
 
 
 
Saturday, August 4, 2012
 
*** Final Feed Investigation Summary - California BSE Case - July 2012
 
 
 
 
 
 
 
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.”
 
“We can’t say it’s not feed related,” agreed Dr. Linda Detwiler, an official with the USDA during the Clinton Administration now at Mississippi State.
 
In the May 1 email to me, USDA’s Cole backed off a bit. “No one knows the origins of atypical cases of BSE,” she said
 
 
Saturday, May 26, 2012
 
Are USDA assurances on mad cow case 'gross oversimplification'?
 
 
 
 
 
 
 
Monday, March 25, 2013
 
Minnesota Firm Recalls Bone-In Ribeye That May Contain Specified Risk Materials Recall Release CLASS II RECALL FSIS-RC-024-2013
 
 
 
Ohio Department of Agriculture and Ohio Department of Health
 
Governor
 
John R. Kasich
 
Lieutenant Governor
 
Mary Taylor
 
ODA Director
 
James Zehringer
 
ODH Director
 
Theodore E. Wymyslo, M.D.
 
DT: July 14, 2011
 
TO: Health Commissioners, Directors of Environmental Health and Interested Parties
 
RE: Recall Announcement (ODA/ODH) 2011-076
 
Valley Farm Meats (DBA Strasburg Provision, Inc) Issues Precautionary Recall for Beef Products Due to Possible Contamination with Prohibited Materials
 
snip...end...TSS
 
 
=========================================
 
 
Ohio Department of Agriculture and Ohio Department of Health
 
Governor
 
John R. Kasich Lieutenant Governor Mary Taylor ODA Director James Zehringer ODH Director Theodore E. Wymyslo, M.D.
 
DT: July 14, 2011
 
TO: Health Commissioners, Directors of Environmental Health and Interested Parties
 
RE: Recall Announcement (ODA/ODH) 2011-076
 
Valley Farm Meats (DBA Strasburg Provision, Inc) Issues Precautionary Recall for Beef Products Due to Possible Contamination with Prohibited Materials
 
[STRASBURG, Ohio] – Valley Farm Meats (DBA Strasburg Provision, Inc) of Strasburg, OH announces a voluntary recall of an unknown amount of beef products that may contain the spinal cord and vertebral column, which are considered specified risk materials (SRMs). SRMs must be removed from cattle over 30 months of age in accordance with federal and state regulations. SRMs are tissues that are known to contain the infective agent in cattle infected with Bovine Spongiform Encephalopathy (BSE), as well as materials that are closely associated with these potentially infective tissues. Therefore, federal and state regulations prohibit SRMs from use as human food to minimize potential human exposure to the BSE agent.
 
The products subject to recall include all beef products slaughtered and processed by or purchased from Valley Farm Meats retail store, 1317 N. Wooster Ave NW, Strasburg, OH 44680 or purchased from Ed Lind Livestock and Poultry, 3333 Church Rd B, Medina, Ohio 44256. These products were produced between 01/28/2011 and 07/05/2011 and offered for sale from 01/28/2011 through 07/11/2011. The package labels or beef carcasses may bear the Ohio mark of inspection and “Est. 80”, however products processed through Ed Lind Livestock and Poultry may not contain such markings. The problem was discovered through routine inspection activities by the Ohio Department of Agriculture’s Division of Meat Inspection. The Department has received no reports of illnesses associated with consumption of this product. The United States Department of Agriculture’s Food Safety and Inspection Service classifies this type of potential contamination as a low health risk, however individuals concerned about an illness should contact a health care provider. Because of potential product contamination, Valley Farm Meats urges its customers who have purchased the suspect product(s) not to eat them and to return them to the company. Customers may bring those designated packages to Valley Farm Meats, 1317 N Wooster Avenue NW, Strasburg, OH 44680 during regular business hours or call the company’s owner, Paul Berry at 330-878-5557.
 
 
 
 
see old FSIS example of SRM recalls from the past ;
 
 
 
 
Saturday, December 15, 2012
 
*** Bovine spongiform encephalopathy: the effect of oral exposure dose on attack rate and incubation period in cattle -- an update 5 December 2012
 
 
 
 
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
 
 
 
 
SEE FULL TEXT OF ALL THIS HERE ;
 
 
2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006
 
 
 
 
 Atypical BSE in Cattle
 
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.
 
This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.
 
 
 
 
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.
 
This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.
 
 
 
 
P.4.23
 
Transmission of atypical BSE in humanized mouse models
 
Liuting Qing1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5, Qingzhong Kong1 1Case Western Reserve University, USA; 2Instituto Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research Institute, Poland; 5Kansas State University (Previously at USDA National Animal Disease Center), USA
 
Background: Classical BSE is a world-wide prion disease in cattle, and the classical BSE strain (BSE-C) has led to over 200 cases of clinical human infection (variant CJD). Atypical BSE cases have been discovered in three continents since 2004; they include the L-type (also named BASE), the H-type, and the first reported case of naturally occurring BSE with mutated bovine PRNP (termed BSE-M). The public health risks posed by atypical BSE were largely undefined.
 
Objectives: To investigate these atypical BSE types in terms of their transmissibility and phenotypes in humanized mice. Methods: Transgenic mice expressing human PrP were inoculated with several classical (C-type) and atypical (L-, H-, or Mtype) BSE isolates, and the transmission rate, incubation time, characteristics and distribution of PrPSc, symptoms, and histopathology were or will be examined and compared.
 
Results: Sixty percent of BASE-inoculated humanized mice became infected with minimal spongiosis and an average incubation time of 20-22 months, whereas only one of the C-type BSE-inoculated mice developed prion disease after more than 2 years. Protease-resistant PrPSc in BASE-infected humanized Tg mouse brains was biochemically different from bovine BASE or sCJD. PrPSc was also detected in the spleen of 22% of BASE-infected humanized mice, but not in those infected with sCJD. Secondary transmission of BASE in the humanized mice led to a small reduction in incubation time.*** The atypical BSE-H strain is also transmissible with distinct phenotypes in the humanized mice, but no BSE-M transmission has been observed so far.
 
Discussion: Our results demonstrate that BASE is more virulent than classical BSE, has a lymphotropic phenotype, and displays a modest transmission barrier in our humanized mice. 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.
 
 
 
 
P26 TRANSMISSION OF ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY (BSE) IN HUMANIZED MOUSE MODELS
 
Liuting Qing1, Fusong Chen1, Michael Payne1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5*, and Qingzhong Kong1 1Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA; 2CEA, Istituto Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research Institute, Poland; 5Kansas State University, Diagnostic Medicine/Pathobiology Department, Manhattan, KS 66506, USA. *Previous address: USDA National Animal Disease Center, Ames, IA 50010, USA
 
Classical BSE is a world-wide prion disease in cattle, and the classical BSE strain (BSE-C) has led to over 200 cases of clinical human infection (variant CJD). Two atypical BSE strains, BSE-L (also named BASE) and BSE-H, have been discovered in three continents since 2004. The first case of naturally occurring BSE with mutated bovine PrP gene (termed BSE-M) was also found in 2006 in the USA. The transmissibility and phenotypes of these atypical BSE strains/isolates in humans were unknown. We have inoculated humanized transgenic mice with classical and atypical BSE strains (BSE-C, BSE-L, BSE-H) and the BSE-M isolate. We have found that the atypical BSE-L strain is much more virulent than the classical BSE-C.*** The atypical BSE-H strain is also transmissible in the humanized transgenic mice with distinct phenotype, but no transmission has been observed for the BSE-M isolate so far.
 
III International Symposium on THE NEW PRION BIOLOGY: BASIC SCIENCE, DIAGNOSIS AND THERAPY 2 - 4 APRIL 2009, VENEZIA (ITALY)
 
 
 
 
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.
 
 
 
 
 
 
 
please see ;
 
 
 
Thursday, August 15, 2013
 
The emergence of novel BSE prions by serial passages of H-type BSE in bovinized mice
 
 
 
 
Thursday, August 15, 2013
 
Stability properties of PrPSc from cattle with experimental transmissible spongiform encephalopathies: use of a rapid whole homogenate, protease-free assay
 
 
 
Monday, March 19, 2012
 
Infectivity in Skeletal Muscle of Cattle with Atypical Bovine Spongiform Encephalopathy
 
PLoS One. 2012; 7(2): e31449.
 
 
 
Monday, August 26, 2013
 
The Presence of Disease-Associated Prion Protein in Skeletal Muscle of Cattle Infected with Classical Bovine Spongiform Encephalopathy
 
 
 
Tuesday, June 11, 2013
 
Weld County Bi-Products dba Fort Morgan Pet Foods 6/1/12 significant deviations from requirements in FDA regulations that are intended to reduce the risk of bovine spongiform encephalopathy (BSE) within the United States
 
 
 
Thursday, June 6, 2013
 
BSE TSE PRION USDA FDA MAD COW FEED COMPLIANCE REPORT and NAI, OAI, and VAI ratings as at June 5, 2013
 
 
 
Tuesday, July 2, 2013
 
APHIS USDA Administrator Message to Stakeholders: Agency Vision and Goals Eliminating ALL remaining BSE barriers to export market
 
 
 
Wednesday, July 28, 2010
 
Atypical prion proteins and IBNC in cattle DEFRA project code SE1796 FOIA Final report
 
 
 
IN CONFIDENCE
 
BSE ATYPICAL LESION DISTRIBUTION
 
 
 
Tuesday, November 02, 2010
 
BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only) diagnostic criteria CVL 1992
 
 
 
Thursday, May 02, 2013
 
Chronic Wasting Disease (CWD) Texas Important Update on OBEX ONLY TEXTING
 
 
 
OBEX ONLY
 
USDA 2003
 
We have to be careful that we don't get so set in the way we do things that we forget to look for different emerging variations of disease. We've gotten away from collecting the whole brain in our systems. We're using the brain stem and we're looking in only one area. In Norway, they were doing a project and looking at cases of Scrapie, and they found this where they did not find lesions or PRP in the area of the obex. They found it in the cerebellum and the cerebrum. It's a good lesson for us. Ames had to go back and change the procedure for looking at Scrapie samples. In the USDA, we had routinely looked at all the sections of the brain, and then we got away from it. They've recently gone back. Dr. Keller: Tissues are routinely tested, based on which tissue provides an 'official' test result as recognized by APHIS.
 
Dr. Detwiler: That's on the slaughter. But on the clinical cases, aren't they still asking for the brain? But even on the slaughter, they're looking only at the brainstem. We may be missing certain things if we confine ourselves to one area.
 
snip.............
 
Dr. Detwiler: It seems a good idea, but I'm not aware of it. Another important thing to get across to the public is that the negatives do not guarantee absence of infectivity. The animal could be early in the disease and the incubation period. Even sample collection is so important. If you're not collecting the right area of the brain in sheep, or if collecting lymphoreticular tissue, and you don't get a good biopsy, you could miss the area with the PRP in it and come up with a negative test. There's a new, unusual form of Scrapie that's been detected in Norway. We have to be careful that we don't get so set in the way we do things that we forget to look for different emerging variations of disease. We've gotten away from collecting the whole brain in our systems. We're using the brain stem and we're looking in only one area. In Norway, they were doing a project and looking at cases of Scrapie, and they found this where they did not find lesions or PRP in the area of the obex. They found it in the cerebellum and the cerebrum. It's a good lesson for us. Ames had to go back and change the procedure for looking at Scrapie samples. In the USDA, we had routinely looked at all the sections of the brain, and then we got away from it. They've recently gone back.
 
Dr. Keller: Tissues are routinely tested, based on which tissue provides an 'official' test result as recognized by APHIS .
 
Dr. Detwiler: That's on the slaughter. But on the clinical cases, aren't they still asking for the brain? But even on the slaughter, they're looking only at the brainstem. We may be missing certain things if we confine ourselves to one area.
 
snip...
 
FULL TEXT;
 
Completely Edited Version PRION ROUNDTABLE
 
Accomplished this day, Wednesday, December 11, 2003, Denver, Colorado
 
END...TSS
 
 
snip...see ;
 
 
Tuesday, November 02, 2010
 
IN CONFIDENCE
 
The information contained herein should not be disseminated further except on the basis of "NEED TO KNOW".
 
BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only) diagnostic criteria CVL 1992
 
 
 
 
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
 
 
 
 
Tuesday, July 14, 2009 U.S.
 
Emergency Bovine Spongiform Encephalopathy Response Plan Summary and BSE Red Book
 
Date: February 14, 2000 at 8:56 am PST
 
WHERE did we go wrong $$$
 
 
 
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"
 
 
 
Thursday, June 20, 2013
 
atypical, BSE, CWD, Scrapie, Captive Farmed shooting pens (livestock), Wild Cervids, Rectal Mucosa Biopsy 2012 USAHA Proceedings, and CJD TSE prion Update
 
 
 
*** PRION2013 ***
 
Sunday, August 25, 2013
 
Prion2013 Chronic Wasting Disease CWD risk factors, humans, domestic cats, blood, and mother to offspring transmission
 
 
 
Thursday, August 08, 2013
 
Characterization of the first case of naturally occurring chronic wasting disease in a captive red deer (Cervus elaphus) in North America
 
 
 
Friday, August 09, 2013
 
CWD TSE prion, plants, vegetables, and the potential for environmental contamination
 
 
 
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.
 
 
 
Sunday, July 21, 2013
 
Welsh Government and Food Standards Agency Wales Joint Public Consultation on the Proposed Transmissible Spongiform Encephalopathies (Wales) Regulations 2013 Singeltary Submission WG18417
 
 
 
Thursday, May 30, 2013
 
World Organization for Animal Health (OIE) has upgraded the United States' risk classification for mad cow disease to "negligible" from "controlled", and risk further exposing the globe to the TSE prion mad cow type disease
 
U.S. gets top mad-cow rating from international group and risk further exposing the globe to the TSE prion mad cow type disease
 
 
 
 
 
Sunday, August 11, 2013
 
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
 
 
 
 
 
 
Prion2013
 
 
Oral.05: Contaminated blood products induce a highly atypical prion disease devoid of PrPres in primates
 
 
Emmanuel Corney,1 Nina Jaffre,1 Jacqueline Mikol,1 Valerie Durand,1 Christelle Jas-Duval,1,2 Sophie Luccantoni-Freire,1 Evelyne Correia,1 Nathalie Lescoutra-Etcheqaray,3 Nathalie Streichenberqer,4 Stephane Haik,5 Chryslain Sumian,3 Paul Brown1 and Jean-Philippe Deslys1
 
 
1Commissariat a l'Energie Atomique; Institute of Emerging Diseases and Innovative Therapies (iMETI); Division of Prions and Related Diseases (SEPIA); Fontenay-aux- Roses, France; 2EFS·Nord de France; Lille, France; 3MacoPharm; Tourcoing, France; 4Hospices Civils de Lyon; Prion Unit; Neurobiology Department; Bron, France; 5Inserm; U 975·CNRS; UMR 7225 - Universite Pierre et Marie Curie; Paris, France
 
 
Background, Concerns about the blood-borne risk of prion infection have been confirmed by the occurrence in the UK of four transfusion-related infections of vCJD and an apparently silent infection in an hemophiliac patient. Asymptomatic incubation periods in prion diseases can extend over decades in humans. We present here unexpected results of experiments evaluating blood transmission risk in a non-human primate model.
 
 
Material and Methods, Cynomolgus macaques were inoculated with brain or blood specimens from vCJD infected humans or monkeys. Neuropathological and biochemical findings were obtained using current methods used for human patients.
 
 
Results, Thirteen out of 23 primates exposed to various human or macaque blood products exhibited a previously undescribed myelopathic syndrome, devoid of the classical features of prion disease, notably abnormal prion protein (PrPres) deposition, whereas the 14 corresponding brain-inoculated donor animals and 1 transfused animal exhibited the classical vCJD pattern. In passage experiments, plasma transfusion induced the same atypical phenotype after two years (again, with no detectable PrPres), whereas the intracerebral inoculation of spinal cord led to a typical prion disease with cerebral spongiosis and PrPres accumulation in the brain of the primate recipient. Interestingly, passage experiments in transgenic mice were largely unsuccessful.
 
 
In another experiment designed to test the efficacy of antiprion filters, three recipients of filtered red blood cells suspended in plasma are still healthy 4.5 y after transfusion whereas the recipients of unfiltered inocula died after 2.5 y with the atypical neurological profile.
 
 
Conclusion. We describe a new fatal neurological myelopathic syndrome in monkeys exposed to various vCJD/BSE-infected blood components.
 
 
Secondary transmission in primates confirms
 
 
(I) the transmissibility of this myelopathy, and
 
 
(2) its prion origin which could not be diagnosed as such in the first recipients.
 
 
This myelopathy might be compared in some respects to certain forms of human lower motor neuron disease, including neuromyelitis optica, the flail arm syndrome of amyotrophic lateral sclerosis (ALS), and the recently described FOSMN (facial onset sensory and motor neuronopathy) syndrome.
 
 
 
 
 
 
 
 
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
 
 
 
 
Saturday, July 6, 2013
 
*** Small Ruminant Nor98 Prions Share Biochemical Features with Human Gerstmann-Sträussler-Scheinker Disease and Variably Protease-Sensitive Prionopathy
 
Research Article
 
 
 
Sunday, March 31, 2013
 
Creutzfeldt Jakob Disease CJD worlds youngest documented victim, 11 years old, shall we pray
 
 
 
Monday, January 14, 2013
 
Gambetti et al USA Prion Unit change another highly suspect USA mad cow victim to another fake name i.e. sporadic FFI at age 16 CJD Foundation goes along with this BSe
 
 
 
Monday, December 31, 2012
 
Creutzfeldt Jakob Disease and Human TSE Prion Disease in Washington State, 2006–2011-2012
 
 
 
Saturday, December 29, 2012
 
MAD COW USA HUMAN TSE PRION DISEASE DECEMBER 29 2012 CJD CASE LAB REPORT
 
 
 
MAD COW USDA ATYPICAL L-TYPE BASE BSE, the rest of the story...
 
 
 
Tuesday, November 6, 2012
 
Transmission of New Bovine Prion to Mice, Atypical Scrapie, BSE, and Sporadic CJD, November-December 2012 update
 
 
 
Tuesday, June 26, 2012
 
Creutzfeldt Jakob Disease Human TSE report update North America, Canada, Mexico, and USDA PRION UNIT as of May 18, 2012
 
type determination pending Creutzfeldt Jakob Disease (tdpCJD), is on the rise in Canada and the USA
 
 
 
Saturday, March 5, 2011
 
MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA
 
 
 
Sunday, February 12, 2012
 
National Prion Disease Pathology Surveillance Center Cases Examined1 (August 19, 2011) including Texas
 
 
 
Monday, August 9, 2010
 
Variably protease-sensitive prionopathy: A new sporadic disease of the prion protein or just more Prionbaloney ?
 
 
 
Wednesday, March 28, 2012
 
VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE ...price of prion poker goes up again $
 
OR-10 15:25 - 15:40 VARIABLY PROTEASE-SENSITIVE PRIONOPATHY IS TRANSMISSIBLE IN BANK VOLES Nonno
 
 
 
Sunday, August 09, 2009
 
CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009
 
 
 
Tuesday, August 18, 2009
 
BSE-The Untold Story - joe gibbs and singeltary 1999 – 2009
 
 
 
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...
 
 
 
 
 TSS

posted by Terry S. Singeltary Sr. at 4:34 PM

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