Thursday, August 29, 2013

In vitro prion protein conversion suggests risk of bighorn sheep (Ovis canadensis) to transmissible spongiform encephalopathies

In vitro prion protein conversion suggests risk of bighorn sheep (Ovis canadensis) to transmissible spongiform encephalopathies
 
In vitro prion protein conversion suggests risk of bighorn sheep (Ovis canadensis) to transmissible spongiform encephalopathies
 
Aaron R Morawski124, Christina M Carlson23, Haeyoon Chang2 and Christopher J Johnson2*
 
* Corresponding author: Christopher J Johnson cjjohnson@usgs.gov
 
Author Affiliations
 
1 Department of Bacteriology, University of Wisconsin, Madison, WI, USA
 
2 USGS National Wildlife Health Center, Madison, WI, USA
 
3 Program in Cellular and Molecular Biology, University of Wisconsin, Madison, WI, USA
 
4 Present address: National Institutes of Health, 9000 Rockville Pike, Bethesda 20892, Maryland, USA
 
For all author emails, please log on.
 
BMC Veterinary Research 2013, 9:157 doi:10.1186/1746-6148-9-157
 
Published: 9 August 2013 Abstract Background Transmissible spongiform encephalopathies (TSEs) affect both domestic sheep (scrapie) and captive and free-ranging cervids (chronic wasting disease; CWD). The geographical range of bighorn sheep (Ovis canadensis; BHS) overlaps with states or provinces that have contained scrapie-positive sheep or goats and areas with present epizootics of CWD in cervids. No TSEs have been documented in BHS, but the susceptibility of this species to TSEs remains unknown.
 
Results We acquired a library of BHS tissues and found no evidence of preexisting TSEs in these animals. The prion protein gene (Prnp) in all BHS in our library was identical to scrapie-susceptible domestic sheep (A136R154Q171 genotype). Using an in vitro prion protein conversion assay, which has been previously used to assess TSE species barriers and, in our study appears to recollect known species barriers in mice, we assessed the potential transmissibility of TSEs to BHS. As expected based upon Prnp genotype, we observed BHS prion protein conversion by classical scrapie agent and evidence for a species barrier between transmissible mink encephalopathy (TME) and BHS. Interestingly, our data suggest that the species barrier of BHS to white-tailed deer or wapiti CWD agents is likely low. We also used protein misfolding cyclic amplification to confirm that CWD, but not TME, can template prion protein misfolding in A136R154Q171 genotype sheep.
 
Conclusions Our results indicate the in vitro conversion assay used in our study does mimic the species barrier of mice to the TSE agents that we tested. Based on Prnp genotype and results from conversion assays, BHS are likely to be susceptible to infection by classical scrapie. Despite mismatches in amino acids thought to modulate prion protein conversion, our data indicate that A136R154Q171 genotype sheep prion protein is misfolded by CWD agent, suggesting that these animals could be susceptible to CWD. Further investigation of TSE transmissibility to BHS, including animal studies, is warranted. The lack of reported TSEs in BHS may be attributable to other host factors or a lack of TSE surveillance in this species.
 
Keywords: Bighorn sheep; Scrapie; Chronic wasting disease; Transmissible mink encephalopathy; Species barrier
 
 
Discussion Using the CER assay, we found evidence that this method recapitulates known species barriers of laboratory mice to TSEs and data to suggest that BHS could be susceptible to classical scrapie and CWD, and less susceptible to TME. Our present investigation and previous studies by others [23,24] suggest that the CER assay can be a valuable addition to other in vitro and in vivo measures of TSE species barriers such as cell-free conversions, PMCA and animal bioassays. Advantages of the CER assay include its low cost, short experimental timeframe and replacement of living animals with tissue samples (which need not be from transgenic mice or perfused). Additionally, the assay does not use radiation, reaction conditions are identical regardless of species or strain of TSE agent and, in our hands, the CER assay is robust and forgiving. Disadvantages of the assay include poor sensitivity compared to PMCA precluding the use of CER as a means to detect PrPTSE, the PrPres product of conversion reactions is not known to be infectious and, importantly, the CER assay is less well-established than other methods of assessing species barriers which makes interpreting reductions in conversion ratios in the absence of other corroborating data difficult. For example, the correlation between a 50% CER and TSE transmission parameters (e.g. disease penetrance, length of incubation period) following experimental challenge remains undefined and further work is needed to characterize this assay for use in species where bioassay data are not available. Nonetheless, in our current study we did find a similar pattern of PrPres formation when either CER or PMCA was used for conversion. Further studies comparing the two techniques is an interesting future direction.
 
We are not aware of any studies examining natural transmission of scrapie from domestic sheep to BHS, but in light of the sequence identity of BHS and domestic A136R154Q171 sheep prion proteins, we must consider scrapie a potential risk to BHS. Efforts to keep domestic sheep and BHS separated, as are prudent to prevent transmission of other pathogens from domestic sheep to BHS [30], are likely warranted around scrapie-infected farms. Further supporting the concept that BHS are at risk for acquiring scrapie is a report of the disease in mouflon (Ovis orientalis), another species of wild sheep [31].
 
In Figure 1, we show the overlap of BHS range with states and provinces known to have had scrapie cases since 2008. Reduced numbers of scrapie outbreaks in recent years, due to disease eradication efforts, may underrepresent the exposure of BHS to scrapie in years prior to 2008. Long-term environmental scrapie contamination may also still be contributing to BHS exposure to disease agent many years after scrapie outbreaks. If incubation periods of scrapie in BHS are greater than five years, exposure of BHS to pre-2008 scrapie flocks may only now have the potential to manifest as disease in BHS. The lack of current evidence for scrapie transmission to BHS could simply be due to insufficient surveillance, but other explanations, such as different susceptibilities by varying routes of exposure between domestic sheep and BHS or BHS being a “dead-end” host for scrapie, should also be explored. Sheep with Prnp genotype V136R154Q171 have been considered to be most -susceptible to classical scrapie and selective breeding efforts have focused on reducing the numbers of these animals in domestic sheep flocks across the U.S. as a scrapie risk reduction measure. Recent research, however, by Gonzalez et al. strongly suggests that Prnp genotype of the recipient sheep is not the sole factor determining its scrapie susceptibility in vivo[32]. In carrying out a series of codon 136 homologous, semi-homologous, and heterologous transmissions of two different natural scrapie isolates into domestic sheep, the study authors conclude that Prnp genotype alone cannot account for the diversity of disease phenotypes observed and that the “scrapie phenotype in sheep results from a complex interaction between source, donor and recipient factors” [32]. The susceptibility of BHS to scrapie is almost certainly dictated by this same interplay. More work is needed to explore the role of scrapie genetics on potential BHS disease transmission, as are analyses of BHS Prnp genetics using more geographically disparate samples.
 
The finding that white-tailed deer CWD agent could convert sheep PrPC to PrPres in either CER assays (Figure 6) or PMCA (Additional file 2) was notable given the sequence variations found between BHS or domestic sheep and white-tailed deer prion proteins (Figure 2), including serine to asparagine and asparagine to threonine changes in the “rigid loop” portion of the protein thought to control species susceptibility to CWD [33,34]. By CER assay, we similarly found conversion of BHS PrPC by wapiti CWD heterozygous methionine/leucine at position 132. In wapiti, animals heterozygous or homozygous for leucine at prion protein amino acid 132 (L132) have a lengthened CWD incubation period [35] and L132 appears to limit CWD, but not classical scrapie, susceptibility in a transgenic mouse model [36]. Despite these amino acid mismatches, including those in the “rigid loop”, the CWD agents were still effective at misfolding PrPC from BHS. In previous studies, we have also found that voles, which have mismatches in the “rigid loop” portion of the protein, are susceptible PrP misfolding and infection by cervid CWD [37,38].
 
Previous work on the species barrier of sheep to CWD has been equivocal. Using cell-free conversion assays, Raymond et al. found that A136Q171 domestic sheep PrPC was not especially-well converted by CWD agent, but was the non-cervid substrate, among six tested species, that yielded the most PrPres[21]. In an animal study, Hamir et al. intracerebrally challenged eight domestic sheep of various Prnp genotypes with mule deer CWD [39]. One clinically-positive (heterozygous A/V136R154Q171) and one preclinical sheep (homozygous A136R154Q171) were identified at the conclusion of the study, indicating that sheep can be infected by CWD, although transmission is not especially facile.
 
The results of our conversion assays appear to be supported by in vivo work by Béringue et al. which indicate that V136R154Q171 ovinized transgenic mice challenged with wapiti CWD harbor high levels of splenic PrPres, indicating that sheep PrPC is susceptible to misfolding by CWD agent [40]. At least one group has failed to observe clinical TSE signs in BHS when they were housed with a facility with CWD-infected animals [7]. Our results in combination with those of Béringue et al., suggest that the lack of CWD transmission to BHS was not due to inability of BHS PrPC to be misfolded by CWD agent, but must derive from other factors.
 
In our investigation, we used white-tailed deer and wapiti CWD, but have not yet investigated BHS prion protein conversion by mule deer CWD. Given the sequence similarity among cervid Prnp genes and our evidence that white-tailed deer and wapiti CWD can convert BHS PrPC to PrPres, we expect CWD from the various species to behave similarly. In a previous report, Li et al. found less PrPres generation in domestic sheep substrates when templated by wapiti CWD [23] than we found for BHS in our study. The genotype of the domestic sheep substrate in the previous study is unclear and differences between the sheep prion protein sequences or other species-specific differences could explain the limited conversion that they observed. Alternatively, differences in the genotypes of the wapiti CWD isolates used in the two studies could also explain variations in PrPres levels in sheep substrates.
 
Conclusion The results from our study suggest that the CER assay has the potential to be a useful tool to screen TSE species barriers. Further comparisons with PMCA and bioassays will clarify the best uses of the assay and help to define CER that are < 100%. We found that BHS are unlikely to have resistance to domestic sheep classical scrapie due to their Prnp genotype. Our conversion reactions suggest that the species barrier protecting BHS from CWD may not be large and further studies, including in vivo experiments, are warranted. These animal challenge studies need not necessarily be performed in BHS, but could rather use Prnp genotype A136R154Q171 domestic sheep or existing transgenic mouse models [41]. Additionally, investigation into the susceptibility of BHS to atypical forms of scrapie is also an interesting future direction.
 
 
 
 
 
Deadly Diseases Could Strike Bighorn Sheep
 
Released: 8/28/2013 1:18:09 PM
 
Contact Information: U.S. Department of the Interior, U.S. Geological Survey Office of Communications and Publishing 12201 Sunrise Valley Dr, MS 119 Reston, VA 20192 Gail Moede Rogall 1-click interview Phone: 608-270-2438
 
Marisa Lubeck 1-click interview Phone: 303-202-4765
 
 Declining bighorn sheep populations may be vulnerable to some of the fatal diseases, including chronic wasting disease (CWD), that are found in their western U.S. habitats, according to a new U.S. Geological Survey study.
 
USGS National Wildlife Health Center (NWHC) research showed that bighorn sheep are likely susceptible to the deadly neurological diseases scrapie and CWD, which are occurring in or near natural bighorn sheep environments. These fatal diseases are caused by mysterious proteins called prions, and are known to infect domestic sheep (scrapie) and non-domestic deer, elk, and moose (CWD). The USGS study is published in the journal BMC Veterinary Research, and is available online.
 
"Bighorn sheep are economically and culturally important to the western U.S.," said Dr. Christopher Johnson, USGS scientist and senior author of the report. "Understanding future risks to the health of bighorn sheep is key to proper management of the species."
 
USGS laboratory tests found evidence that bighorn sheep could be vulnerable to CWD from either white-tailed deer or elk, and to a domestic sheep prion disease known as scrapie. However, none of a small number of bighorn sheep sampled in the study showed evidence of infection.
 
"Our results do not mean that bighorns get, or will eventually get, prion diseases," Johnson said. "However, wildlife species like bighorn sheep are increasingly exposed to areas where CWD occurs as the disease expands to new geographical areas and increases in prevalence."
 
The laboratory test results could be useful to wildlife managers because bighorn sheep habitats overlap with farms and ranches with scrapie-infected sheep and regions where CWD is common in deer, elk, and moose.
 
Bighorn sheep populations in western North America have declined from habitat loss and, more recently, epidemics of fatal pneumonia thought to be transmitted to them from domestic sheep. Prion diseases are another possible threat to this valuable species.
 
For more information on prion diseases such as CWD, please visit the USGS NWHC website.
 
 
 
 
 
Friday, July 26, 2013
 
Voluntary Scrapie Program USA UPDATE July 26, 2013 increase in FY 2013 is not statistically meaningful due to the sample size
 
 
 
 
Thursday, March 29, 2012
 
atypical Nor-98 Scrapie has spread from coast to coast in the USA 2012
 
NIAA Annual Conference April 11-14, 2011San Antonio, Texas
 
 
 
 
Wednesday, February 16, 2011
 
IN CONFIDENCE
 
SCRAPIE TRANSMISSION TO CHIMPANZEES
 
IN CONFIDENCE
 
 
 
 
Sunday, December 12, 2010
 
EFSA reviews BSE/TSE infectivity in small ruminant tissues News Story 2 December 2010
 
 
 
 
Sunday, April 18, 2010
 
SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010
 
 
 
 
Saturday, July 6, 2013
 
Small Ruminant Nor98 Prions Share Biochemical Features with Human Gerstmann-Sträussler-Scheinker Disease and Variably Protease-Sensitive Prionopathy
 
Research Article
 
 
 
 
Thursday, August 15, 2013
 
The emergence of novel BSE prions by serial passages of H-type BSE in bovinized mice
 
 
 
 
snip...
 
 
Stability comparison of BSE to other cattle-passaged TSEs
 
In addition to comparing the different BSE strains, we also used the stability assay to characterize the biochemical properties of other TSEs passaged into cattle. Scrapie and CWD are both transmissible into cattle by IC inoculation, leading to PrPSc accumulation--but not significant spongiform changes--in the brain [29,30]. Transmissible mink encephalopathy has been hypothesized to have originated from the feeding of downer cattle, possibly carrying atypical, L-type BSE, to farm-raised mink [37]. We wanted to determine if the profiles of PrPSc from these TSEs passaged in cattle brain were distinguishable from each other or from other BSE strains, with potential implications for understanding strain origins and/or improving (non-BSE) TSE diagnosis in cattle.
 
snip...
 
Keywords
 
Bovine spongiform encephalopathy, BSE, ELISA, Prion, PrP, Scrapie, Stability, Transmissible spongiform encephalopathy, TSE
 
ISSN 1746-6148 Article type Research article Submission date 12 April 2013 Acceptance date 12 August 2013 Publication date 15 August 2013 Article URL http://www.biomedcentral.com/1746-6148/9/167 Like all articles in BMC journals, this peer-reviewed article can be downloaded, printed and distributed freely for any purposes (see copyright notice below). Articles in BMC journals are listed in PubMed and archived at PubMed Central. For information about publishing your research in BMC journals or any BioMed Central journal, go to http://www.biomedcentral.com/info/
 
 
 
 
snip...see full text and more here ;
 
 
 
Thursday, August 15, 2013
 
Stability properties of PrPSc from cattle with experimental transmissible spongiform encephalopathies: use of a rapid whole homogenate, protease-free assay
 
 
 
 
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
 
 
 
 
 
 
TSS
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Monday, August 26, 2013

The Presence of Disease-Associated Prion Protein in Skeletal Muscle of Cattle Infected with Classical Bovine Spongiform Encephalopathy

Journal of Veterinary Medical Science Article ID: 13-0363 Language: English Japanese Previous Article |Next Article http://dx.doi.org/10.1292/jvms.13-0363 DN/JST.JSTAGE/jvms/13-0363

 

Advance Publication

 

 

The Presence of Disease-Associated Prion Protein in Skeletal Muscle of Cattle Infected with Classical Bovine Spongiform Encephalopathy

 

 

Hiroyuki OKADA1), Kohtaro MIYAZAWA1), Shigeo FUKUDA2), Yoshifumi IWAMARU1), Morikazu IMAMURA1), Kentaro MASUJIN1), Yuichi MATSUURA1), Takashi FUJII2), Kei FUJII2), Soichi KAGEYAMA2), Miyako YOSHIOKA1), Yuichi MURAYAMA1), Takashi YOKOYAMA1)

 

1) National Institute of Animal Health, National Agriculture and Food Research Organization 2) Hokkaido Animal Research Center, Hokkaido Research Organization

 

 [Advance Publication] Released 2013/08/27 received 2013/07/16 accepted 2013/08/13 Keywords: BSE, muscle spindle, prion, skeletal muscle

 

Full Text PDF [832K]

 

Abstracts

 

The aim of this study was to investigate the presence of disease-associated prion protein (PrPSc) in the skeletal muscle of cattle infected with classical bovine spongiform encephalopathy (C-BSE). The study was carried out systematically in 12 different muscle samples from 43 (3 field and 40 experimental) cases of C-BSE; however, muscle spindles were not available in many of these cases. Therefore, analysis became restricted to a total of 31 muscles in 23 cattle. Even after this restriction, low levels of PrPSc were detected in the muscle spindles of the masseter, intercostal, triceps brachii, psoas major, quadriceps femoris and semitendinosus muscles from 3 field and 6 experimental clinical-stage cases. The present data indicate that small amounts of PrPSc are detectable by immunohistochemistry in the skeletal muscles of animals terminally affected with C-BSE.

 

 

 


 

 

full text pdf here ;

 

 


 

 

 

Monday, March 19, 2012

 

Infectivity in Skeletal Muscle of Cattle with Atypical Bovine Spongiform Encephalopathy PLoS One. 2012; 7(2): e31449.

 


 

 

 

***Infectivity in skeletal muscle of BASE-infected cattle

 


 

 

 

Wednesday, May 2, 2012

 

ARS FLIP FLOPS ON SRM REMOVAL FOR ATYPICAL L-TYPE BASE BSE RISK HUMAN AND ANIMAL HEALTH

 


 

 

 

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
 
 
 
 
Sunday, July 21, 2013
 
Biochemical Characteristics and PrPSc Distribution Pattern in the Brains of Cattle Experimentally Challenged with H-type and L-type Atypical BSE
 
 
 
 

Thursday, August 15, 2013

 

Stability properties of PrPSc from cattle with experimental transmissible spongiform encephalopathies: use of a rapid whole homogenate, protease-free assay

 


 

 

 

Thursday, August 15, 2013

 

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

 


 

 

Envt.07:

Pathological Prion Protein (PrPTSE) in Skeletal Muscles of Farmed and Free Ranging White-Tailed Deer Infected with Chronic Wasting Disease

Martin L. Daus,1,† Johanna Breyer,2 Katjs Wagenfuehr,1 Wiebke Wemheuer,2 Achim Thomzig,1 Walter Schulz-Schaeffer2 and Michael Beekes1 1Robert Koch Institut; P24 TSE; Berlin, Germany; 2Department of Neuropathology, Prion and Dementia Research Unit, University Medical Center Göttingen; Göttingen, Germany †Presenting author; Email: dausm@rki.de

Chronic wasting disease (CWD) is a contagious, rapidly spreading transmissible spongiform encephalopathy (TSE) occurring in cervids in North America. Despite efficient horizontal transmission of CWD among cervids natural transmission of the disease to other species has not yet been observed. Here, we report a direct biochemical demonstration of pathological prion protein PrPTSE and of PrPTSE-associated seeding activity in skeletal muscles of CWD-infected cervids. The presence of PrPTSE was detected by Western- and postfixed frozen tissue blotting, while the seeding activity of PrPTSE was revealed by protein misfolding cyclic amplification (PMCA). The concentration of PrPTSE in skeletal muscles of CWD-infected WTD was estimated to be approximately 2000- to 10000-fold lower than in brain tissue. Tissue-blot-analyses revealed that PrPTSE was located in muscle- associated nerve fascicles but not, in detectable amounts, in myocytes. The presence and seeding activity of PrPTSE in skeletal muscle from CWD-infected cervids suggests prevention of such tissue in the human diet as a precautionary measure for food safety, pending on further clarification of whether CWD may be transmissible to humans.

http://www.landesbioscience.com/journals/prion/Prion5-Supp-PrionEnvironment.pdf?nocache=1333529975



Wednesday, April 06, 2011

 

Presence and Seeding Activity of Pathological Prion Protein (PrPTSE) in Skeletal Muscles of White-Tailed Deer Infected with Chronic Wasting Disease

 


 

 

 

Sunday, November 21, 2010

 

Preclinical Deposition of Pathological Prion Protein in Muscle of Experimentally Infected Primates and potential Iatrogenic TSE there from Preclinical Deposition of Pathological Prion Protein in Muscle of Experimentally Infected Primates

 


 

 

 


EMBO reports AOP Published online: 11 April 2003



Widespread PrPSc accumulation in muscles of hamsters orally infected with scrapie



Achim Thomzig, Christine Kratzel, Gudrun Lenz, Dominique KrÒ¼ger & Michael Beekes Robert Koch-Institut, P26, Nordufer 20, D-13353 Berlin, Germany

Received 13 February 2003; Accepted 13 March 2003; Published online 11 April 2003.

Abstract :

Scrapie, bovine spongiform encephalopathy and chronic wasting disease are orally communicable, transmissible spongiform encephalopathies (TSEs). As zoonotic transmissions of TSE agents may pose a risk to human health, the identification of reservoirs for infectivity in animal tissues and their exclusion from human consumption has become a matter of great importance for consumer protection. In this study, a variety of muscles from hamsters that were orally challenged with scrapie was screened for the presence of a molecular marker for TSE infection, PrPSc (the pathological isoform of the prion protein PrP). Sensitive western blotting revealed consistent PrPSc accumulation in skeletal muscles from forelimb and hindlimb, head, back and shoulder, and in tongue. Previously, our animal model has provided substantial baseline information about the peripheral routing of infection in naturally occurring and orally acquired ruminant TSEs. Therefore, the findings described here highlight further the necessity to investigate thoroughly whether muscles of TSE-infected sheep, cattle, elk and deer contain infectious agents.


http://www.emboreports.org/

 

snip...see;

 

 

Monday, June 22, 2009

 

PrPTSE in muscle-associated lymphatic tissue during the preclinical stage of mice orally-infected with BSE

 


 

 

 

 

Friday, December 05, 2008

 

Detection of Prion Infectivity in Fat Tissues of Scrapie-Infected Mice

 


 

 

 

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

 


 

 

 

 

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

 


 

 

 

 

TSS
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Thursday, August 15, 2013

Stability properties of PrPSc from cattle with experimental transmissible spongiform encephalopathies: use of a rapid whole homogenate, protease-free assay

Stability properties of PrPSc from cattle with experimental transmissible spongiform encephalopathies: use of a rapid whole homogenate, protease-free assay
 
Catherine E Vrentas1 Email: catherine.vrentas@ars.usda.gov Justin J Greenlee1 Email: justin.greenlee@ars.usda.gov Thierry Baron2 Email: Thierry.BARON@anses.fr Maria Caramelli3 Email: Maria.Caramelli@izsto.it Stefanie Czub4 Email: stefanie.czub@inspection.gc.ca Eric M Nicholson1* * Corresponding author Email: eric.nicholson@ars.usda.gov
 
1 Virus and Prion Disease Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, 1920 Dayton Road, Ames, IA 50010, USA
 
2 Agence Nationale de Sécurité Sanitaire (Anses)-Lyon, 31 Avenue Tony Garnier, 69364, Lyon Cedes 07, France
 
3 Istituto Zooprofilattico Sperimentale Piemonte Liguria e Valle d'Aost, Via Bologna 148, 10154 Torino, Italy
 
4 National & OIE Reference Laboratories for BSE NCAD/CFIA, Township Road 9-1 (Box 640), Lethbridge/Alberta, Canada
 
Abstract
 
Background
 
Transmissible Spongiform Encephalopathies (TSEs), including scrapie in sheep, chronic wasting disease (CWD) in cervids, transmissible mink encephalopathy (TME), and bovine spongiform encephalopathy (BSE), are fatal diseases of the nervous system associated with accumulation of misfolded prion protein (PrPSc). Different strains of TSEs exist, associated with different PrPSc conformations that can be probed by the stability assay, in which PrPSc is treated with increasing concentrations of the denaturant guanidine hydrochloride (GdnHCl).
 
Results
 
Here, we provide the first comprehensive application of a rapid, protease-free version of the GdnHCl stability assay to brain tissue from cattle experimentally infected with various TSE isolates. Consistent with previous findings from a single Japanese isolate, the L-type isolates of BSE are not distinguishable from classical BSE in this assay. In contrast, H-type isolates of BSE, including our unique isolate of E211K BSE, exhibit higher stability than classical BSE, suggesting that its increased protection against protease digestion at the BSE Nterminus is associated with a higher stability in GdnHCl. While the difference in stability in our version of the assay is likely not large enough for effective use in a diagnostic laboratory setting, the use of alternative experimental conditions may enhance this effect. TSEs from other natural host species that have been passaged in cattle, including CWD and TME, were not distinguishable from classical BSE, while isolates of cattle passaged scrapie exhibited a slight increase in stability as compared to classical BSE.
 
Conclusions
 
These results suggest that the core of PrPSc, as probed in this assay, has similar stability properties among cattle-passaged TSE isolates and that the conformational differences that lead to changes in the proteinase K cleavage site do not cause large changes in the stability of PrPSc from TSE-affected cattle. However, the stability differences observed here will provide a basis of comparison for new isolates of atypical BSE observed in the future and in other geographic locations, especially in the case of H-type BSE.
 
snip...
 
Stability comparison of BSE to other cattle-passaged TSEs
 
In addition to comparing the different BSE strains, we also used the stability assay to characterize the biochemical properties of other TSEs passaged into cattle. Scrapie and CWD are both transmissible into cattle by IC inoculation, leading to PrPSc accumulation--but not significant spongiform changes--in the brain [29,30]. Transmissible mink encephalopathy has been hypothesized to have originated from the feeding of downer cattle, possibly carrying atypical, L-type BSE, to farm-raised mink [37]. We wanted to determine if the profiles of PrPSc from these TSEs passaged in cattle brain were distinguishable from each other or from other BSE strains, with potential implications for understanding strain origins and/or improving (non-BSE) TSE diagnosis in cattle.
 
 
snip...
 
 
Keywords
 
Bovine spongiform encephalopathy, BSE, ELISA, Prion, PrP, Scrapie, Stability, Transmissible spongiform encephalopathy, TSE
 
ISSN 1746-6148 Article type Research article Submission date 12 April 2013 Acceptance date 12 August 2013 Publication date 15 August 2013 Article URL http://www.biomedcentral.com/1746-6148/9/167 Like all articles in BMC journals, this peer-reviewed article can be downloaded, printed and distributed freely for any purposes (see copyright notice below). Articles in BMC journals are listed in PubMed and archived at PubMed Central. For information about publishing your research in BMC journals or any BioMed Central journal, go to http://www.biomedcentral.com/info/
 
 
 
 
 
 
Sunday, July 21, 2013
 
Biochemical Characteristics and PrPSc Distribution Pattern in the Brains of Cattle Experimentally Challenged with H-type and L-type Atypical BSE
 
 
 
 
 
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
 
 
 
 
 
 
Saturday, July 6, 2013

 

Small Ruminant Nor98 Prions Share Biochemical Features with Human Gerstmann-Sträussler-Scheinker Disease and Variably Protease-Sensitive Prionopathy

 

Research Article

 


 

 

 

Tuesday, July 2, 2013

 

APHIS USDA Administrator Message to Stakeholders: Agency Vision and Goals Eliminating ALL remaining BSE barriers to export market

 


 

 

 

Thursday, June 13, 2013

 

Experimental interspecies transmission studies of the transmissible spongiform encephalopathies to cattle: comparison to bovine spongiform encephalopathy in cattle

 


 

 

 

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

 


 

 

 
Monday, June 3, 2013

 

Unsuccessful oral transmission of scrapie from British sheep to cattle

 


 

 

 snip...

 

 
A kind greetings from Bacliff, Texas !

 

 

I have often pondered if the whole damn mad cow follies started over here in the USA, and somehow, the USA shipped it over to the UK ?

 

 

It happened with S. Korea and CWD, via Canada. see ;

 

 

The disease was confirmed only in elk in the Republic of Korea in 2001, 2004 and 2005. Epidemiological investigations showed that CWD was introduced via importation of infected elk from Canada between 1994 and 1997.

 

 


 

 

 

but I still am not so sure that the mad cow follies did not start long ago right here in the USA i.e. Richard Marsh and deadstock downer cattle to those mink, and then the USA shipped it to hell and back. just pondering out loud here. ...tss

 

 

 

The exact same recipe for B.S.E. existed in the U.S. for years

 

and years. In reading over the Qualitative Analysis of BSE

 

Risk Factors-1, this is a 25 page report by the

 

USDA:APHIS:VS. It could have been done in one page. The

 

first page, fourth paragraph says it all;

 

"Similarities exist in the two countries usage of continuous

 

rendering technology and the lack of usage of solvents,

 

however, large differences still remain with other risk factors

 

which greatly reduce the potential risk at the national level."

 

Then, the next 24 pages tries to down-play the high risks of

 

B.S.E. in the U.S., with nothing more than the cattle to sheep

 

ratio count, and the geographical locations of herds and flocks.

 

That's all the evidence they can come up with, in the next 24

 

pages.

 

 

 

Something else I find odd, page 16;

 

 

 

"In the United Kingdom there is much concern for a specific

 

continuous rendering technology which uses lower

 

temperatures and accounts for 25 percent of total output. This

 

technology was _originally_ designed and imported from the

 

United States. However, the specific application in the

 

production process is _believed_ to be different in the two

 

countries."

 

 

 

A few more factors to consider, page 15;

 

 

 

"Figure 26 compares animal protein production for the two

 

countries. The calculations are based on slaughter numbers,

 

fallen stock estimates, and product yield coefficients. This

 

approach is used due to variation of up to 80 percent from

 

different reported sources. At 3.6 million tons, the United

 

States produces 8 times more animal rendered product than

 

the United Kingdom."

 

 

 

"The risk of introducing the BSE agent through sheep meat and

 

bone meal is more acute in both relative and absolute terms in

 

the United Kingdom (Figures 27 and 28). Note that sheep

 

meat and bone meal accounts for 14 percent, or 61 thousand

 

tons, in the United Kingdom versus 0.6 percent or 22 thousand

 

tons in the United States. For sheep greater than 1 year, this is

 

less than one-tenth of one percent of the United States supply."

 

"The potential risk of amplification of the BSE agent through

 

cattle meat and bone meal is much greater in the United States

 

where it accounts for 59 percent of total product or almost 5

 

times more than the total amount of rendered product in the

 

United Kingdom."

 

 

 

Considering, it would only take _one_ scrapie infected sheep

 

to contaminate the feed. Considering Scrapie has run rampant

 

in the U.S. for years, as of Aug. 1999, 950 scrapie infected

 

flocks. Also, Considering only one quarter spoonful of scrapie

 

infected material is lethal to a cow. Considering all this, the

 

sheep to cow ration is meaningless. As I said, it's 24 pages of

 

B.S.e.

 

To be continued...

 

Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA

 

 

_____________________________________________________________________

 

 

 

 

 


 

 

 

 

Qualitative Assessment Considering the comparative factors presented, with the exception of some similarities in rendering practices, epidemiologic factors believed conducive to the introduction of BSE in the United Kingdom are significantly different in the United States. This is supported by the following points: Similar changes in the rendering practices have occurred in both countries. Continuous rendering accounts for the vast majority of all product produced. From 1977 to 1982, the portion of United Kingdom product rendered using hydrocarbon solvents dropped from 70 per-cent to 10 percent. Within the United States the decline was at least 5 years earlier with very little if any solvent in current use.

 

see full text ;

 

 

 


 

 

 

 

TME in mink was documented in the early 1960s. it was first thought that the TME out break was from scrapie infected sheep, until a investigation was done on feed practices at these mink facilities, and it was later found that the mink had been fed 95%+ dead stock downer cows. and later, the Late Richard Marsh tried to warn the feds of the pending mad cow debacle. they refused to listen. ... some interesting reading on pages 26 to 33

 

 


 

 

 

 

1979

 

TME originates from feeding mink, scrapie infected materials...

 


 

 

 

 

Evidence That Transmissible Mink Encephalopathy Results from Feeding Infected Cattle

 

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...

 

 


 

 


 

 


 

 

 

 

Tuesday, July 21, 2009

 

Transmissible mink encephalopathy - review of the etiology

 

Folia Neuropathologica 2/2009

 

full text of the article:

 

Transmissible mink encephalopathy – review of the etiology

 

Folia Neuropathol 2009; 47 (2): 195-204

 

snip...

 

A possible clue was provided during the Stetsonville TME outbreak in which the rancher fed his mink commercial feed (e.g., poultry, fish, cereal) and fresh meat primarily from sick or downer dairy cattle within a 50-mile radius of his ranch [37]. He did not recall including sheep products in his homemade feed ration. Upon reviewing prior TME outbreaks in the U.S. and Canada, in all four cases in which records were available and were not linked to a commercial feed plant, downer cattle were also included in the mink diet. The Stetsonville TME isolate, and subsequently additional TME isolates, were transmitted to cattle by intracerebral inoculation and the Stetsonville TME isolate was the first confirmed case of experimental transmission of a TSE/prion disease to cattle. What was striking was that upon experimental transmission of cattle TME back into mink by the oral and intracerebral routes, the incubation periods were similar to that found for mink passaged TME. Hence, the pathogenicity of the Stetsonville TME agent in mink was not altered upon passage into cattle, suggesting that a previously unrecognized TSE/prion disease in cattle may be the source of TME infection. Additional studies strongly suggest that TME has similarities to L-type BSE in transgenic mice compared to H-type or classical BSE [2]. Since the L-type BSE does not appear to be an infectious form of TSE/prion disease, the proposal by Marsh [35,37] that a rare TSE in cattle may be the source of TME infection seems plausible. This is particularly the case in Wisconsin, which has had the majority of TME in the USA and is a prominent dairy state with aged cattle being a primary source of fresh meat for mink ration. Since mink are a sentinel host it is not surprising that they may have been a key host in amplifying a rare cattle TSE disease. Another possible explanation for the high incidence of TME in Wisconsin is based on the recent identification of a mutation in the prion protein gene in cattle with atypical BSE. There may be cattle breeding stock in Wisconsin that carry a mutation in the prion protein gene that is linked to late onset disease and are also the source of TSE infection for mink TME outbreaks described in the 1960s and 1985.

 

snip...

 

To this end, mink were shown to be sensitive to scrapie [23,24]. Of interest, following i.c. inoculation with the UK source of scrapie from a Suffolk sheep only a single animal developed the disease. In contrast, American sources B-834 and B-957 from Suffolk sheep readily transmitted to mink. Also, in another outbreak of TME in Stetsonville, Wisconsin, USA, the affected mink were apparently fed with downer cattle but not scrapie-affected sheep [32], and thus TME may result from BSE transmission from cattle to mink [37]. TME is readily transmitted to cattle [26]. The suggestion that TME may result from transmission from infected cattle but not sheep was supported by recent data on phenotypic similarities of TME in cattle and L-type bovine spongiform encephalopathy (BSE) transmitted to ovine transgenic mice (TgOvPrP4) [2]. To this end, L-type of BSE and TME in TgOvPrP4 presented similar molecular mass of all 3 bands of PrPd. Unglycosylated PrPd in L-type BSE, bovine TME and typical BSE has the same molecular mass of approximately 18 kDa in contrast to that of diglycosylated PrPd species which was lower by 0.5-0.8 kDa in L-type BSE and bovine TME as compared to typical BSE. Furthermore, L-type BSE and bovine TME transmitted to TgOvPrP4 mice presented spongiform change of low intensity but PrPd was strongly expressed including amyloid plaques. Mink were also susceptible to BSE [44]. ...

 

 

snip...

 

 

please see full text and more here;

 

 


 

 

 

 

Saturday, December 01, 2007

 

 

Phenotypic Similarity of Transmissible Mink Encephalopathy in Cattle and L-type Bovine Spongiform Encephalopathy in a Mouse Model

 

 

Volume 13, Number 12–December 2007 Research

 

Phenotypic Similarity of Transmissible Mink Encephalopathy in Cattle and L-type Bovine Spongiform Encephalopathy in a Mouse Model

 

Thierry Baron,* Anna Bencsik,* Anne-Gaëlle Biacabe,* Eric Morignat,* andRichard A. Bessen†*Agence Française de Sécurité Sanitaire des Aliments–Lyon, Lyon, France; and†Montana State University, Bozeman, Montana, USA

 

Abstract

 

Transmissible mink encepholapathy (TME) is a foodborne transmissible spongiform encephalopathy (TSE) of ranch-raised mink; infection with a ruminant TSE has been proposed as the cause, but the precise origin of TME is unknown. To compare the phenotypes of each TSE, bovine-passaged TME isolate and 3 distinct natural bovine spongiform encephalopathy (BSE) agents (typical BSE, H-type BSE, and L-type BSE) were inoculated into an ovine transgenic mouse line (TgOvPrP4). Transgenic mice were susceptible to infection with bovine-passaged TME, typical BSE, and L-type BSE but not to H-type BSE. Based on survival periods, brain lesions profiles, disease-associated prion protein brain distribution, and biochemical properties of protease-resistant prion protein, typical BSE had a distint phenotype in ovine transgenic mice compared to L-type BSE and bovine TME.The similar phenotypic properties of L-type BSE and bovine TME in TgOvPrP4 mice suggest that L-type BSE is a much more likely candidate for the origin of TME than is typical BSE.

 

snip...

 

Conclusion

 

These studies provide experimental evidence that the Stetsonville TME agent is distinct from typical BSE but has phenotypic similarities to L-type BSE in TgOvPrP4 mice. Our conclusion is that L-type BSE is a more likely candidate for a bovine source of TME infection than typical BSE. In the scenario that a ruminant TSE is the source for TME infection in mink, this would be a second example of transmission of a TSE from ruminants to non-ruminants under natural conditions or farming practices in addition to transmission of typical BSE to humans, domestic cats, and exotic zoo animals(37). The potential importance of this finding is relevant to L-type BSE, which based on experimental transmission into humanized PrP transgenic mice and macaques, suggests that L-type BSE is more pathogenic for humans than typical BSE (24,38).

 

 


 

 


 

 

 

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"

 

 

Emmanuel Comoy,1,† Valérie Durand,1 Evelyne Correia,1 Sophie Freire,1 Jürgen Richt,2 Justin Greenlee,3 Juan-Maria Torres,4 Paul Brown,1 Bob Hills5 and Jean-Philippe Deslys1

 

1Atomic Energy Commission; Fontenay-aux-Roses, France; 2Kansas State University; Manhattan, KS USA; 3USDA; Ames, IA USA; 4INIA; Madrid, Spain; 5Health Canada; Ottawa, ON Canada†Presenting author; Email: emmanuel.comoy@cea.fr

 

 

The epidemiology of Transmissible mink encephalopathy (TME) indicates an alimentary origin. Several inter-species transmission experiments have not succeeded in establishing with certainty any natural reservoir of this prion strain, although both ovine and bovine sources have been suspected. Cattle exposed to TME develop a spongiform encephalopathy that is distinct from classical Bovine Spongiform Encephalopathy (c-BSE).

 

Inoculation of c-BSE to cynomolgus macaque provided early evidence of a possible risk to humans, and remains an important model to define the risk of both primary (oral transmission from cattle to primate) and secondary (intravenous intra-species transmission) exposures. We have also evaluated the transmissibility of other cattle prion strains to macaques, including L- and H- atypical forms of BSE, namely BSE-L and BSE-H, and cattle-adapted TME.

 

BSE-L induced a neurological disease distinct from c-BSE. Peripheral exposures demonstrate the transmissibility of BSE-L by oral, intravenous, and intra-cerebral routes, with incubation periods similar to c-BSE. Cattle-adapted TME also induced a rapid disease in cynomolgus macaque. The clinical features, lesion profile, and biochemical signature of the induced disease was similar to the features observed in animals exposed to BSE-L, suggesting a link between the two prion strains. Secondary transmissions to a common host (transgenic mouse overexpressing bovine PrP) of cattle-TME and BSE-L before or after passage in primates induced diseases with similar incubation periods: like the c-BSE strain, these cattle strains maintained their distinctive features regardless of the donor species and passages.

 

If the link between TME and BSE-L is confirmed, our results would suggest that BSE-L in North America may have existed for decades, and highlight a possible preferential transmission of animal prion strains to primates after passage in cattle.

 

 

 

=====================end...tss====================

 

 

link url not available, please see PRION 2011 ;

 

 


 

 


 

 


 

 

 

 

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.

 

 

 


 

 


 

 


 

 

 

 

1992

 

NEW BRAIN DISORDER

 

3. WHAT ABOUT REPORTS OF NEW FORM OF BSE ?

 

THE VETERINARY RECORD HAS PUBLISHED AN ARTICLE ON A NEW BRAIN DISORDER OF CATTLE DISCOVERED THROUGH OUR CONTROL MEASURES FOR BSE. ALTHOUGH IT PRESENTS SIMILAR CLINICAL SIGNS TO BSE THERE ARE MAJOR DIFFERENCES IN HISTOPATHOLOGY AND INCUBATION PERIODS BETWEEN THE TWO. MUST EMPHASISE THAT THIS IS _NOT_ BSE.

 

4. IS THIS NEW BRAIN DISORDER A THREAT ?

 

WE DO NOT EVEN KNOW WHETHER THE AGENT OF THIS DISEASE IS TRANSMISSIBLE. IN ANY CASE, CASES SO FAR IDENTIFIED HAD SHOWN SIMILAR SYMPTOMS TO THOSE OF BSE, AND THEREFORE HAVE BEEN SLAUGHTERED AND INCINERATED, SO THAT IF A TRANSMISSIBLE AGENT WERE INVOLVED IT WOULD HAVE BEEN ELIMINATED. ...

 


 

 

 

 

Tuesday, November 17, 2009

 

SEAC NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS (IBNC) FROM THE VETERINARY LABORATORIES AGENCY (VLA) SEAC 103/1

 


 

 

 

 

NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS

 

 

"All of the 15 cattle tested showed that the brains had abnormally accumulated PrP"

 

 

2009

 

 


 

 

 

 

''THE LINE TO TAKE'' ON IBNC $$$ 1995 $$$

 

 

1995

 

page 9 of 14 ;

 

30. The Committee noted that the results were unusual. the questioned whether there could be coincidental BSE infection or contamination with scrapie. Dr. Tyrell noted that the feeling of the committee was that this did not represent a new agent but it was important to be prepared to say something publicly about these findings. A suggested line to take was that these were scientifically unpublishable results but in line with the policy of openness they would be made publicly available and further work done to test their validity. Since the BSE precautions were applied to IBNC cases, human health was protected. Further investigations should be carried out on isolations from brains of IBNC cases with removal of the brain and subsequent handling under strict conditions to avoid the risk of any contamination.

 

31. Mr. Bradley informed the Committee that the CVO had informed the CMO about the IBNC results and the transmission from retina and he, like the Committee was satisfied that the controls already in place or proposed were adequate. ...

 

 

snip... see full text

 

 


 

 


 

 

 

 

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

 

 


 

 

 

 

 

 

 

 

image

 

 

 

 

 

 

see ;

 

 

 

 

 

EVIDENCE OF SCRAPIE IN SHEEP AS A RESULT OF FOOD BORNE EXPOSURE



This is provided by the statistically significant increase in the incidence of sheep scrape from 1985, as determined from analyses of the submissions made to VI Centres, and from individual case and flock incident studies.

 


 

 

 

 

 

 

THE RISK OF TRANSMISSION OF BSE TO SHEEP VIA FEED

 

 




 

 

 

 

 

 

 

 

image

 

 

 

 

 

 


 

 

 

 

 

 

 

Prusiner vs Maff on BSE brains, and delaying science for profits $

 

 

 

 

 

 

 

 

image

 

 

 

 

 

 

 


 

 

 

 


 

 

 

 


 

 

 

 

 

image

 

 

 

 

 

 

 

 

image

 

 

 

 

 

 

 


 

 

 

 

 

 

 

 

 

image

 

 

 

 

 

 

 

 


 

 

 

 

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"

 


 

 

 

 

snip...see full text ;

 

 

Monday, June 3, 2013

 

Unsuccessful oral transmission of scrapie from British sheep to cattle

 


 

 

 
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
http://creutzfeldt-jakob-disease.blogspot.com/2013/08/creutzfeldt-jakob-disease-cjd-cases.html

 

 

 

 

Sent: Tuesday, August 13, 2013 3:58 PM
Subject: Idiopathic Brainstem Neuronal Chromatolysis (IBNC): a novel prion protein related disorder of cattle?
 

Greetings Honorable Science Advisory Council et al @ DEFRA,
 
 
I wish to ask a question about something I have seen no updates on, that concerns me.
 
 
IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS IBNC or what I some times call, IBNC BSE.
 
 
I have seen nothing in the scientific literature updated on this in years, since around 2008, then it was like it fell off the face of the earth ?
 
can you please give me some sort of update on the IBNC BSE science to date ?
 
how many cases of IBNC BSE have been detected ?
 
is there an ongoing surveillance for this the IBNC BSE, and are the BSE test even capable of detecting it ?
 
could the USA and or North America even detect, if they were even looking for it ?
 
latest studies, if any more since "All of the 15 cattle tested showed that the brains had abnormally accumulated PrP" ?
 
 
 
 
thank you,
 
kind regards,
terry
 
 
 
references as follows ;
 
 
snip...end...tss
 

 

 

 
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