Real-time quaking-induced conversion A highly sensitive assay for prion detection
Ryuichiro Atarashi,1,* Kazunori Sano,1,2 Katsuya Satoh1 and Noriyuki Nishida1,2 1Department of Molecular Microbiology and Immunology; Graduate School of Biomedical Sciences; 2Global COE Program; Nagasaki University; Nagasaki, Japan
We recently developed a new in vitro amplification technology, designated “real-time quaking-induced conversion (RT-QUIC),” for detection of the abnormal form of prion protein (PrPSc) in easily accessible specimens such as cerebrospinal fluid (CSF). After assessment of more than 200 CSF specimens from Japanese and Australian patients, we found no instance of a false positive, and more than 80% accuracy for the correct diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD). Furthermore, the RT-QUIC can be applied to other prion diseases, including scrapie, chronic wasting disease (CWD) and bovine spongiform encephalopathy (BSE), and is able to quantify prion seeding activity when combined with an end-point dilution of samples. These results indicate that the RT-QUIC, with its high sensitivity and specificity, will be of great use as an early, rapid and specific assay for prion diseases.
snip...
Further Progress in RT-QUIC Technology Recently, Caughey’s group demonstrated that our RT-QUIC could be successfully applied to the detection of hamster and sheep scrapie, deer chronic wasting disease (CWD) and vCJD.28,29 Additionally, our team has been able to detect BSE at a sensitivity equivalent to that of sCJD (manuscript in preparation). In addition, the RT-QUIC can rapidly determine the relative prion concentration when used in combination with end-point dilution analysis.29 In another very recent study, Caughey’s team showed that enrichment of PrPSc in plasma by immunoprecipitation employing the PrP aggregate-specific monoclonal IgM antibody 15B3 greatly enhances the sensitivity of RT-QUIC, especially when coupled with a substrate replacement step.28 Together, these studies demonstrated the wide-ranging application of RT-QUIC to clinical and basic research on human and animal prion diseases.
snip...
Key words: RT-QUIC, real-time quaking-induced conversion, prion, CJD, Creutzfeldt-Jakob disease, CSF, cerebrospinal fluid
Submitted: 06/10/11
Accepted: 06/28/11 DOI:
*Correspondence to: Ryuichiro Atarashi; Email: atarashi@nagasaki-u.ac.jp
see full text ;
http://www.landesbioscience.com/journals/prion/AtarashiPRI5-3.pdf
Oral.42: Prion Seeding Activity in Cerebrospinal Fluid from Sporadic Creutzfeldt-Jakob Disease Patients Using Real-Time QuIC Analysis: A Potential New Diagnostic Test?
Lynne I. McGuire,1,† Alexander H. Peden,1 Nigel Appleford,2 Gary Mallinson,2 Christina Orru,3 Jason Wilham,3 Greg Raymond,3 Mary Andrews,1 Mark W. Head,1 Byron Caughey,3 Robert Will,1 Richard Knight1 and Alison Green,1
1 NCJDSU, University of Edinburgh; Edinburgh, UK; 2 Bristol Institute for Transfusion Sciences, NHS Blood and Transplant; Bristol, UK; 3 Laboratory of Persistent Viral Disease, NIAID Rocky Mountain Laboratories, National Institutes of Health; Hamilton, MT USA†Presenting author; Email: lmcguir1@staffmail.ed.ac.uk
Since its introduction into the diagnostic criteria for sporadic CJD in 1998, the analysis of cerebrospinal fluid (CSF) for 14-3-3 has become a widely accepted investigation in patients with suspected sporadic CJD. However, a number of reports have raised concerns about its lack of specificity. This has prompted the search for a more specific and disease-related pre-mortem diagnostic test for sporadic CJD. The ability of PrPSc to convert PrPC into protease-resistance isoforms has been exploited using a variety of techniques such as protein misfolding cyclic amplification (PMCA) and quaking induced conversion (QuIC). A recent adaptation of QuIC (real-time QuIC) has been described which incorporates thioflavin T (ThT) in the reaction mixture. The ThT binds to the aggregated PrP causing a change in the ThT emission spectrum that can be monitored in real-time. Recent studies have shown that CSF samples from hamsters inoculated with experimental scrapie, sheep with scrapie and patients with sporadic CJD can be correctly identified using real-time QuIC.1,2 We now describe the findings of an investigation into the value of real-time QuIC in the diagnosis of sCJD. A blinded panel of CSF samples from 56 neuropathologically confirmed cases of sCJD and from 53 patients who were initially suspected of having sCJD but who were found to have an alternative diagnosis were analyzed. Of the 56 patients with sCJD 51 were found to give a positive response with real-time QuIC. In contrast only one patient from the control group was found to be positive. The sensitivity and specificity was 91% and 98%, respectively. The corresponding sensitivity and specificity of CSF 14-3-3 was 91% and 55%, respectively. These results suggest that real-time QuIC has the potential to be a more specific pre-mortem CSF test for sCJD than CSF 14-3-3.
References
1. Atarashi R, Satoh K, Sano K, Fuse T, Yamanaka H, Yamaguchi N, et al. Ultrasensitive human prion detection in cerebrospinal fluids by real-time quaking induced conversion. Prion 2010; 4:214
2. Wilham JM, Orru CD, Benssen RA, Atarashi R, Sano K, Race B, et al. Rapid end-point quantitation of prion seeding activity with sensitivity comparable to bioassays. PLoS 2010; 6:1-15
http://www.prion2011.ca/files/PRION_2011_-_Posters_(May_5-11).pdf
i guess the next question would be, is the USDA et al going to use _any_ test in numbers large enough to detect TSE in the bovine ???
Thursday, July 28, 2011
An Update on the Animal Disease Traceability Framework July 27, 2011
http://naiscoolyes.blogspot.com/2011/07/update-on-animal-disease-traceability.html
Saturday, July 23, 2011
CATTLE HEADS WITH TONSILS, BEEF TONGUES, SPINAL CORD, SPECIFIED RISK MATERIALS (SRM's) AND PRIONS, AKA MAD COW DISEASE
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/cattle-heads-with-tonsils-beef-tongues.html
JULY 2011 PRION TSE UPDATE NORTH AMERICA
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"
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/transmissibility-of-bse-l-and-cattle.html
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...
http://web.archive.org/web/20030516051623/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf
Sunday, June 26, 2011
Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/risk-analysis-of-low-dose-prion.html
Thursday, June 23, 2011
Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/experimental-h-type-bovine-spongiform.html
Wednesday, June 15, 2011
Galveston, Texas - Isle port moves through thousands of heifers headed to Russia, none from Texas, Alabama, or Washington, due to BSE risk factor
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/galveston-texas-isle-port-moves-through.html
Thursday, February 10, 2011
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY REPORT UPDATE CANADA FEBRUARY 2011 and how to hide mad cow disease in Canada Current as of: 2011-01-31
http://madcowtesting.blogspot.com/2011/02/transmissible-spongiform-encephalopathy.html
Friday, March 4, 2011
Alberta dairy cow found with mad cow disease
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/alberta-dairy-cow-found-with-mad-cow.html
Monday, June 20, 2011 2011
Annual Conference of the National Institute for Animal Agriculture ATYPICAL NOR-98 LIKE SCRAPIE UPDATE USA
http://nor-98.blogspot.com/2011/06/2011-annual-conference-of-national.html
Thursday, July 14, 2011
Histopathological Studies of “CH1641-Like” Scrapie Sources Versus Classical Scrapie and BSE Transmitted to Ovine Transgenic Mice (TgOvPrP4)
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/histopathological-studies-of-ch1641.html
Monday, June 27, 2011
Comparison of Sheep Nor98 with Human Variably Protease-Sensitive Prionopathy and Gerstmann-Sträussler-Scheinker Disease
http://prionopathy.blogspot.com/2011/06/comparison-of-sheep-nor98-with-human.html
Thursday, June 2, 2011
USDA scrapie report for April 2011 NEW ATYPICAL NOR-98 SCRAPIE CASES Pennsylvania AND California
http://nor-98.blogspot.com/2011/06/usda-scrapie-report-for-april-2011-new.html
Wednesday, July 06, 2011
Swine Are Susceptible to Chronic Wasting Disease by Intracerebral Inoculation
(see tonnage of mad cow feed in commerce USA...tss)
http://chronic-wasting-disease.blogspot.com/2011/07/swine-are-susceptible-to-chronic.html
Monday, June 27, 2011
Zoonotic Potential of CWD: Experimental Transmissions to Non-Human Primates
http://chronic-wasting-disease.blogspot.com/2011/06/zoonotic-potential-of-cwd-experimental.html
Thursday, May 26, 2011
Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey
Journal of the American Dietetic Association Volume 111, Issue 6 , Pages 858-863, June 2011.
http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/travel-history-hunting-and-venison.html
Tuesday, June 14, 2011
Clinical research in CJD at a U.S. clinical prion research center: CJD Quinacrine Study results and improved diagnosis of prion disease
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/clinical-research-in-cjd-at-us-clinical.html
Saturday, March 5, 2011
MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html
Tuesday, April 26, 2011
sporadic CJD RISING Text and figures of the latest annual report of the NCJDRSU covering the period 1990-2009 (published 11th March 2011)
http://creutzfeldt-jakob-disease.blogspot.com/2011/04/sporadic-cjd-rising-text-and-figures-of.html
Wednesday, June 29, 2011
TSEAC Meeting August 1, 2011 donor deferral Saudi Arabia vCJD risk blood and blood products
http://tseac.blogspot.com/2011/06/tseac-meeting-august-1-2011-donor.html
Friday, June 17, 2011
Treatable neurological disorders misdiagnosed as Creutzfeldt-Jakob disease
http://creutzfeldt-jakob-disease.blogspot.com/2011/06/treatable-neurological-disorders.html
Saturday, January 22, 2011
Alzheimer's, Prion, and Neurological disease, and the misdiagnosis there of, a review 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/alzheimers-prion-and-neurological.html
Wednesday, July 20, 2011
Canadian Researchers Receive $2.9 Million to Protect Against Prion Disease Outbreaks, Develop Novel Therapies to Treat Alzheimer's, Parkinson's and ALS
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/canadian-researchers-receive-29-million.html
http://bse-atypical.blogspot.com/
http://chronic-wasting-disease.blogspot.com/
http://nor-98.blogspot.com/
http://scrapie-usa.blogspot.com/
http://transmissible-mink-encephalopathy.blogspot.com/
http://creutzfeldt-jakob-disease.blogspot.com/
http://sporadicffi.blogspot.com/
http://kuru-tse.blogspot.com/
http://prionopathy.blogspot.com/
http://transmissiblespongiformencephalopathy.blogspot.com/
TSS
Showing posts with label CJD. Show all posts
Showing posts with label CJD. Show all posts
Friday, July 29, 2011
Wednesday, July 20, 2011
Canadian Researchers Receive $2.9 Million to Protect Against Prion Disease Outbreaks, Develop Novel Therapies to Treat Alzheimer’s, Parkinson’s and ALS
Canadian Researchers Receive $2.9 Million to Protect Against Prion Disease Outbreaks, Develop Novel Therapies to Treat Alzheimer’s, Parkinson’s and ALS
Scientists find increasing connection between development of prion disease and common human neurodegenerative disorders
July 13, 2011 (Vancouver, BC) – Collaborative research groups at nine different universities, involving 55 different investigators across Canada, are poised to make significant advances in the understanding of prion and prion-like diseases in humans and animals. These include the development of an oral vaccine to help stop the spread of chronic wasting disease (CWD) in wild deer and elk populations and novel approaches to treat human neurodegenerative disorders like ALS (Lou Gehrig's disease), Alzheimer’s and Parkinson’s diseases, thanks to $2.9 million in funding announced by PrioNet Canada.
The goal of the funding which supports 11 projects is two-fold, explains Dr. Neil Cashman, Scientific Director of PrioNet Canada, one of Canada’s Network of Centres of Excellence. “By working with our partners, we aim to continue to protect Canada against classical prion diseases like chronic wasting disease and mad cow disease (bovine spongiform encephalopathy or BSE), and we’re also providing benefit to Canadians through the development of innovative therapeutics to treat neurodegenerative diseases like Alzheimer’s, Parkinson’s and ALS.”
The researchers will use the funds to better understand the biology of prion disease, to develop strategies to manage prion disease outbreaks and minimize the impacts, and to apply learnings of prion diseases to the treatment of human neurodegenerative disorders.
Prion diseases are fatal, infectious and transmissible diseases of humans and animals associated with a ‘sponge-like’ degeneration of brain tissue. In animals, the most common prion diseases include BSE, scrapie in sheep and goats, and CWD in deer and elk. In 2003, Canada’s beef and related industries were faced with worldwide closing of trade after a domestic case of BSE was found in Alberta. Canada’s economic loss stemming from this event is estimated at more than $6 billion. Some examples of prion diseases in humans include fatal and sporadic familial insomnia, Creutzfeldt-Jakob disease (CJD) and its many varieties, and Kuru. Some examples of the ground-breaking work supported by PrioNet’s recent funding include:
• Immunotherapies to treat ALS: Five PrioNet researchers at the University of British Columbia, University of Alberta and University of Toronto are focusing on a newly-recognized molecular mechanism of ALS, a misfolded protein called SOD-1. By identifying the parts of the protein that are exposed when it is misfolded in disease, researchers are able to design immunotherapies that can target those areas, interrupting the slow progression of paralysis and eventual death characterized by the disorder. Two animal models have already demonstrated responsiveness to the new immunotherapies and work is now underway to develop a therapy for humans. “We are hoping these discoveries could prove to be a magic bullet for ALS,” said Dr. Cashman, who serves as principal investigator for the multi-disciplinary research team.
• Oral vaccine to control chronic wasting disease in the wild: Prion diseases like chronic wasting disease are continuing to spread throughout the Canadian prairie’s wild deer and elk populations and ten PrioNet researchers in Saskatoon and British Columbia are working on an oral vaccine to stop the spread. “The danger is that prion diseases are evolving and new strains are emerging,” noted Dr. Scott Napper, a Research Scientist with the Vaccine and Infectious Disease Organization in Saskatoon and principal investigator on the project. Dr. Napper’s group is focusing on an oral vaccine that can withstand extreme temperatures and will effectively attract elk and deer in the wild. Similar oral vaccines are already used to control rabies in Eastern Canada, where food packets containing the vaccine are widely distributed for consumption by fox and raccoon populations.
• Framework to minimize the impact of chronic wasting disease: Principal investigator Dr. Ellen Goddard from the University of Alberta along with nine co-investigators are working to identify the risk factors associated with chronic wasting disease in wild deer and elk populations, how they can be managed and what public policy recommendations should be put in place to try and mitigate the effects. The primary goal is to monitor the many unknowns that remain about the impact of CWD in the wild, such as the potential risk to hunters who consume infected animals and the potential interface between wild and domestic animals. “The risk management framework around BSE showed that even though countries were aware of the disease in their cattle, they completely underestimated the economic impact and the public response,” notes Dr. Goddard. “We’re doing the work ahead of the game while CWD is still manageable and while effective policies can be put into place to control it, to help anticipate and prevent the impacts.”
• Understanding ‘good versus bad’ prions in order to develop drugs: The first step to designing drugs to treat prion and prion-like diseases is to understand how prion proteins change shape when they become “misfolded” in disease. Dr. Christoph Borchers, a Professor in the Department of Biochemistry and Microbiology and Director of the University of Victoria-Genome BC Proteomics Centre is collaborating with researchers from the University of Alberta and University of Western Ontario to characterize the changes that occur to the three-dimensional structure of prion fibrils (small, nerve-like fibres) as well as the molecular mechanisms that lead to those changes. Using a combination of protein chemistry and mass spectrometry, they are working to explain what occurs when a ‘good’ prion protein changes to a ‘bad’ one during disease development. The information is crucial to designing drugs that can interfere with those changes, effectively curbing the spread of prion and prion-like diseases.
About PrioNet Canada (www.prionetcanada.ca) One of Canada’s Networks of Centres of Excellence, PrioNet Canada is a pan-Canadian research network that is developing strategies to help solve the food, health safety, and socioeconomic problems associated with prion diseases. The network brings together academia, industry, and public sector partners through its multidisciplinary research projects, training programs, events, and commercialization activities to help derive maximum socioeconomic benefits for Canadians. PrioNet is hosted by the University of British Columbia and the Vancouver Coastal Health Research Institute in Vancouver.
- 30 -
Media information or to set up interviews: Gail Bergman or Christina Vetro Gail Bergman PR Tel: (905) 886-1340 or (905) 886-3345 E-mail: info@gailbergmanpr.com
Last Updated: 7/13/2011 11:27:59 AM
http://www.prionetcanada.ca/detail.aspx?menu=12&dt=293779&app=70&cat1=211&tp=12&lk=no
All Other Emerging and Zoonotic Infectious Diseases CDC's FY 2012 request of $52,658,000 for all other emerging and zoonotic infectious disease activities is a decrease of $13,607,000 below the FY 2010 level,
which includes the elimination of Prion activities ($5,473,000),
a reduction for other cross-cutting infectious disease activities, and administrative savings. These funds support a range of critical emerging and zoonotic infectious disease programs such Lyme Disease, Chronic Fatigue Syndrome, and Special Pathogens, as well as other activities described below.
http://www.cdc.gov/fmo/topic/Budget%20Information/appropriations_budget_form_pdf/FY2012_CDC_CJ_Final.pdf
" the FY 2010 level, which includes the elimination of Prion activities ($5,473,000), "
USDA MAD COW PROBLEMS SOLVED $$$
NOT !
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"
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/transmissibility-of-bse-l-and-cattle.html
Sunday, June 26, 2011
Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/risk-analysis-of-low-dose-prion.html
Thursday, June 23, 2011
Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/experimental-h-type-bovine-spongiform.html
Wednesday, June 15, 2011
Galveston, Texas - Isle port moves through thousands of heifers headed to Russia, none from Texas, Alabama, or Washington, due to BSE risk factor
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/galveston-texas-isle-port-moves-through.html
Saturday, July 23, 2011
CATTLE HEADS WITH TONSILS, BEEF TONGUES, SPINAL CORD, SPECIFIED RISK MATERIALS (SRM's) AND PRIONS, AKA MAD COW DISEASE
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/cattle-heads-with-tonsils-beef-tongues.html
Thursday, June 2, 2011
USDA scrapie report for April 2011 NEW ATYPICAL NOR-98 SCRAPIE CASES Pennsylvania AND California
http://nor-98.blogspot.com/2011/06/usda-scrapie-report-for-april-2011-new.html
Monday, June 20, 2011 2011
Annual Conference of the National Institute for Animal Agriculture ATYPICAL NOR-98 LIKE SCRAPIE UPDATE USA
http://nor-98.blogspot.com/2011/06/2011-annual-conference-of-national.html
Monday, June 27, 2011
Comparison of Sheep Nor98 with Human Variably Protease-Sensitive Prionopathy and Gerstmann-Sträussler-Scheinker Disease
http://prionopathy.blogspot.com/2011/06/comparison-of-sheep-nor98-with-human.html
Monday, November 30, 2009
USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH CODE
http://nor-98.blogspot.com/2009/11/usda-and-oie-collaborate-to-exclude.html
I strenuously urge the USDA and the OIE et al to revoke the exemption of the legal global trading of atypical Nor-98 scrapie TSE. ...TSS
Friday, February 11, 2011
Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues
http://nor-98.blogspot.com/2011/02/atypicalnor98-scrapie-infectivity-in.html
Thursday, November 18, 2010
Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy following passage in sheep
http://bse-atypical.blogspot.com/2010/11/increased-susceptibility-of-human-prp.html
Sunday, October 3, 2010
Scrapie, Nor-98 atypical Scrapie, and BSE in sheep and goats North America, who's looking ?
http://nor-98.blogspot.com/2010/10/scrapie-nor-98-atypical-scrapie-and-bse.html
Wednesday, July 06, 2011
Swine Are Susceptible to Chronic Wasting Disease by Intracerebral Inoculation
(see tonnage of mad cow feed in commerce USA...tss)
http://chronic-wasting-disease.blogspot.com/2011/07/swine-are-susceptible-to-chronic.html
Monday, June 27, 2011
Zoonotic Potential of CWD: Experimental Transmissions to Non-Human Primates
http://chronic-wasting-disease.blogspot.com/2011/06/zoonotic-potential-of-cwd-experimental.html
Please see the following warning from CDC about prion TSE consumption in North America ;
Thursday, May 26, 2011
Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey
Journal of the American Dietetic Association Volume 111, Issue 6 , Pages 858-863, June 2011.
http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/travel-history-hunting-and-venison.html
Tuesday, July 19, 2011
Neuroanatomical Distribution of Disease-Associated Prion Protein in Cases of Bovine Spongiform Encephalopathy Detected by Fallen Stock Surveillance in Japan
http://bse-atypical.blogspot.com/2011/07/neuroanatomical-distribution-of-disease.html
Saturday, March 5, 2011
MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html
Oral.01: Changing Spectrum of Prions
Stanley Prusiner
University of California San Francisco, Institute for Neurodegenerative Diseases; San Francisco, CA USA
Prions are self-propagating forms of proteins found in eukaryotes. Prions are created from benign, cellular precursor proteins by a posttranslational modification that is self-perpetuating. Often the prion form of the protein is aggregated and assembles into amyloid polymers. Prions can be inherited both genetically and epigenetically. In neurodegenerative diseases, the formation of prions is heritable through mutations in the gene encoding the cellular form of the prion protein. In fungi, the prion state is epigenetically transferred from mother to daughter cells.
Historically, prions were confined to a small group of infectious CNS illnesses including Creutzfeldt-Jakob disease (CJD) and kuru of humans, scrapie of sheep, bovine spongiform encephalopathy, and chronic wasting disease of deer and elk. CJD can present as an infectious, inherited or sporadic illness. In all three manifestations of the disease, the cellular prion protein (PrPC) refolds into the disease-causing isoform (PrPSc). A truncated form of PrPSc readily polymerizes into amyloid fibrils and forms PrP amyloid plaques. Prion strains composed of different conformers of PrPScSc have been identified. Subsequently, prions were recognized in fungi and studied extensively using yeast. Recently, self-propagation of altered proteins that cause several neurodegenerative diseases, including Alzheimer disease and the tauopathies, has been demonstrated using cultured cell and transgenic mouse models. Increasing evidence argues that the Ab peptide acts as a prion in that it stimulates the de-novo formation of more Ab peptide. Similarly, the aggregates of Tau provoke the assembly of more aggregated Tau. In addition, fetal grafts of substantia nigra in patients with advanced Parkinson’s disease exhibit Lewy bodies, arguing that a-synuclein may act as a prion. Misfolded a-synuclein is thought to transit from the patient’s neurons to those in the graft, where it stimulates the de-novo formation of aberrantly folded a-synuclein into Lewy bodies.
The spread of misprocessed proteins in the human CNS is also consistent with the Ab peptide, hyperphosphorylated Tau and misfolded a-synuclein being prions. In Alzheimer disease, Ab plaques and neurofibrillary tangles (NFTs) begin in the entorhinal cortex and spread throughout the brain. In a delayed form of traumatic brain injury, NFTs appear to spread outward from points of impact. Misfolded a-synuclein has been found along the vagus nerve where it appears to migrate retrograde into the CNS.
Increasing evidence that posttranslationally altered proteins are responsible for the major neurodegenerative diseases widens the spectrum of prion disorders. Moreover, prions with glutamine/asparagine-rich regions like those in yeast and aplysia have given unique insights into the normal function of alternatively processed, self-propagating proteins.
Oral.33: Transmission of Alzheimer Disease and Type 2 Diabetes by a Prion Mechanism
Claudio Soto,1,† Natalia Salvadores-Bersezio,1 Ines Moreno-Gonzalez,1 Claudia Duran-Aniotz,1, 2 Akihiko Urayama,1 Lisbell Estrada,3 Diego Morales-Scheihing1, 2 and Rodrigo Morales1
1Protein Misfolding Disorders Lab, Mitchell Center for Alzheimer Disease and Related Brain Disorders, Department of Neurology; University of Texas Medical School at Houston; Houston, TX USA; 2Facultad de Medicina, Universidad de Los Andes; Santiago, Chile; 3 Universidad Catolica de Chile; Santiago, Chile†Presenting author; Email: Claudio.Soto@uth.tmc.edu
Alzheimer disease (AD) and type 2 diabetes (T2D) are the most prevalent diseases of the group of protein misfolding disorders (PMDs). A hallmark event in the pathology of AD and T2D involves the misfolding, aggregation and accumulation of Ab and IAPP, respectively. Considering that the molecular mechanisms responsible for protein misfolding and aggregation in PMDs are strikingly similar to the process of prion replication we hypothesize that all these diseases have the inherent capability of being transmissible. Recent exciting studies from various groups have provided strong proof-of-concept for the transmission of the pathological hallmarks of various PMDs in an experimental setting. In this presentation we will provide further evidence for the induction of AD and T2D features in animal models of these diseases upon intra-cerebral and intra-peritoneal inoculation of tissue homogenates containing Ab and IAPP aggregates, respectively. One of the key questions regarding prion-like transmissibility of other PMDs is whether this phenomenon can occur by practically relevant routes of exposure. To study this issue, we assessed whether these diseases can be induced by transfusion of blood from animals exhibiting large quantities of cerebral or pancreatic aggregates. Blood transfusion was chosen because is a medically relevant route of exposure to potentially infectious material and because the data in animals and even in humans is solid to support blood transfusion as a route of prion infection in TSEs. Our results show that infusion of blood from old AD or T2D transgenic mice into young animals significantly accelerates the onset of pathological and clinical abnormalities associated to these diseases. Our results indicate that the two most prevalent PMDs can be initiated by exposure to misfolded protein aggregates, which replicate in the body in a similar manner as infectious prions. These findings may open a new avenue to understand the origin of AD and T2D and may provide new strategies for disease intervention and prevention.
PPPM.18: Induction of Ab Amyloidogenesis In Vivo by Blood Transfusion
Rodrigo Morales,1,† Claudia Duran-Aniotz,1, 2 Akihiko Urayama,1 Lisbell Estrada,3 Diego Morales-Scheihing1, 2 and Claudio Soto1
1University of Texas Health Science Center at Houston; Houston, TX USA; 2Universidad de Los Andes; Santiago, Chile; 3Universidad Catolica de Chile; Santiago, Chile†Presenting author; Email: Rodrigo.MoralesLoyola@uth.tmc.edu
Alzheimer disease (AD) is the most common type of senile dementia. Disease manifestation is characterized by progressive impairment of memory and cognition which is triggered by synaptic dysfunction and neuronal loss. Compelling evidence suggests that misfolding and aggregation of Ab is a hallmark event in the disease pathogenesis. An important unanswered question related to AD involves its etiology since over 90% of the AD cases arise sporadically. Interestingly, misfolding and aggregation of proteins is the main feature of other diseases -termed Protein Misfolding Disorders (PMDs)] which include Transmissible Spongiform Encephalopathies (TSEs), among others. Convincing experimental evidences have shown that the only component of the infectious agent in TSEs is the misfolded form of the prion protein. Strikingly, the molecular mechanisms responsible for prion replication are very similar to the process of amyloid formation in all PMDs, suggesting that all these diseases have the inherent capability of being transmissible. Recent reports have shown that intra-cerebral and intra-peritoneal administration of brain homogenates containing Ab aggregates can accelerate the generation of senile plaques in mice models of AD. However, it remains to be demonstrated if this phenomenon can occur by more relevant routes of administration. The aim of this study was to assess whether AD pathogenesis can be induced intravenously, mimicking the know transmission of prion diseases through blood transfusion. For this purpose we used young tg2576 mice which were injected with blood obtained from 12 months old tg2576 mice (AD-blood) that contains a substantial quantity of cerebral Ab deposits. Mice were sacrificed at 250 days old, a time in which these animals scarcely develop Ab deposits. Interestingly, we observed that infusion of AD-blood induces substantial Ab accumulation in animals that without treatment or injected with wild type blood would barely have any detectable Ab lesion. Plaque deposition was mainly present in cortex and hippocampus, being more abundant in the former. In addition, we observed a decrease in memory in mice challenged with AD-blood. Other features such as brain inflammation and synaptic integrity were also measured. Importantly, similar results were obtained in a second and independent experiment performed in a double transgenic mouse model that develops AD plaques as early as 4 months old. Our results indicate that an AD-like pathogenesis can be induced by intravenous administration of AD-blood, presumably through induction of protein misfolding in a similar way as prion diseases. These findings may open a new avenue to understand the origin of sporadic AD and may provide new strategies for disease intervention and prevention.
PPPM.20: Prion-Like Propagation and Neurotoxicity of Recombinant a-Synuclein Aggregates Initiated by Dimerization
Alireza Roostaee† and Xavier Roucou
University of Sherbrooke; Sherbrooke, QC Canada†Presenting author; Email: alireza.roostaee@usherbrooke.ca
Misfolding of the a-Synuclein (a-Syn) protein and subsequent formation of amyloid fibrils or toxic aggregates are neuropathological hallmarks of Parkinson’s Disease (PD). However, a detailed characterization of the mechanism of a-synuclein aggregation/fibrillogenesis and transmission of toxic aggregates has not yet been achieved. In this study, the rates of a-Syn aggregation were compared for wild-type (wt) as well as a chimeric form of a-Syn containing an inducible Fv dimerizing domain (a-SynFv) with the capacity to form homodimers in the presence of a divalent ligand (AP20187). Here we report the increased oligomerization and fibril formation rate of recombinant a-SynFv in the presence of AP20187, in comparison to wt a-Syn or a-SynFv in the absence of divalent ligand. In addition, dimerization of a-SynFv accelerated structural transition from random coil into b-sheet conformation, which is characteristic of a-Syn aggregates. a-SynFv oligomers, but not corresponding monomers or amyloid fibrils, induced neurotoxicity when injected into the hippocampus of wt mice. These recombinant aggregates were amplified by the protein misfolding cyclic amplification (PMCA) method, providing first evidence for the in vitro propagation of synthetic a-Syn aggregates. Our results provide direct evidence for similarities between a-Syn and prion propagation and neutoxicity at the molecular level.
http://www.prion2011.ca/files/PRION_2011_-_Posters_(May_5-11).pdf
Wednesday, April 27, 2011
GENERATION ALZHEIMER'S: THE DEFINING DISEASE OF THE BABY BOOMERS
http://betaamyloidcjd.blogspot.com/2011/04/generation-alzheimers-defining-disease.html
Saturday, January 22, 2011
Alzheimer's, Prion, and Neurological disease, and the misdiagnosis there of, a review 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/alzheimers-prion-and-neurological.html
Friday, September 3, 2010
Alzheimer's, Autism, Amyotrophic Lateral Sclerosis, Parkinson's, Prionoids, Prionpathy, Prionopathy, TSE
http://betaamyloidcjd.blogspot.com/2010/09/alzheimers-autism-amyotrophic-lateral.html
Thursday, December 23, 2010
Alimentary prion infections: Touch-down in the intestine, Alzheimer, Parkinson disease and TSE mad cow diseases $ The Center for Consumer Freedom
http://betaamyloidcjd.blogspot.com/2010/12/alimentary-prion-infections-touch-down.html
TSS
Scientists find increasing connection between development of prion disease and common human neurodegenerative disorders
July 13, 2011 (Vancouver, BC) – Collaborative research groups at nine different universities, involving 55 different investigators across Canada, are poised to make significant advances in the understanding of prion and prion-like diseases in humans and animals. These include the development of an oral vaccine to help stop the spread of chronic wasting disease (CWD) in wild deer and elk populations and novel approaches to treat human neurodegenerative disorders like ALS (Lou Gehrig's disease), Alzheimer’s and Parkinson’s diseases, thanks to $2.9 million in funding announced by PrioNet Canada.
The goal of the funding which supports 11 projects is two-fold, explains Dr. Neil Cashman, Scientific Director of PrioNet Canada, one of Canada’s Network of Centres of Excellence. “By working with our partners, we aim to continue to protect Canada against classical prion diseases like chronic wasting disease and mad cow disease (bovine spongiform encephalopathy or BSE), and we’re also providing benefit to Canadians through the development of innovative therapeutics to treat neurodegenerative diseases like Alzheimer’s, Parkinson’s and ALS.”
The researchers will use the funds to better understand the biology of prion disease, to develop strategies to manage prion disease outbreaks and minimize the impacts, and to apply learnings of prion diseases to the treatment of human neurodegenerative disorders.
Prion diseases are fatal, infectious and transmissible diseases of humans and animals associated with a ‘sponge-like’ degeneration of brain tissue. In animals, the most common prion diseases include BSE, scrapie in sheep and goats, and CWD in deer and elk. In 2003, Canada’s beef and related industries were faced with worldwide closing of trade after a domestic case of BSE was found in Alberta. Canada’s economic loss stemming from this event is estimated at more than $6 billion. Some examples of prion diseases in humans include fatal and sporadic familial insomnia, Creutzfeldt-Jakob disease (CJD) and its many varieties, and Kuru. Some examples of the ground-breaking work supported by PrioNet’s recent funding include:
• Immunotherapies to treat ALS: Five PrioNet researchers at the University of British Columbia, University of Alberta and University of Toronto are focusing on a newly-recognized molecular mechanism of ALS, a misfolded protein called SOD-1. By identifying the parts of the protein that are exposed when it is misfolded in disease, researchers are able to design immunotherapies that can target those areas, interrupting the slow progression of paralysis and eventual death characterized by the disorder. Two animal models have already demonstrated responsiveness to the new immunotherapies and work is now underway to develop a therapy for humans. “We are hoping these discoveries could prove to be a magic bullet for ALS,” said Dr. Cashman, who serves as principal investigator for the multi-disciplinary research team.
• Oral vaccine to control chronic wasting disease in the wild: Prion diseases like chronic wasting disease are continuing to spread throughout the Canadian prairie’s wild deer and elk populations and ten PrioNet researchers in Saskatoon and British Columbia are working on an oral vaccine to stop the spread. “The danger is that prion diseases are evolving and new strains are emerging,” noted Dr. Scott Napper, a Research Scientist with the Vaccine and Infectious Disease Organization in Saskatoon and principal investigator on the project. Dr. Napper’s group is focusing on an oral vaccine that can withstand extreme temperatures and will effectively attract elk and deer in the wild. Similar oral vaccines are already used to control rabies in Eastern Canada, where food packets containing the vaccine are widely distributed for consumption by fox and raccoon populations.
• Framework to minimize the impact of chronic wasting disease: Principal investigator Dr. Ellen Goddard from the University of Alberta along with nine co-investigators are working to identify the risk factors associated with chronic wasting disease in wild deer and elk populations, how they can be managed and what public policy recommendations should be put in place to try and mitigate the effects. The primary goal is to monitor the many unknowns that remain about the impact of CWD in the wild, such as the potential risk to hunters who consume infected animals and the potential interface between wild and domestic animals. “The risk management framework around BSE showed that even though countries were aware of the disease in their cattle, they completely underestimated the economic impact and the public response,” notes Dr. Goddard. “We’re doing the work ahead of the game while CWD is still manageable and while effective policies can be put into place to control it, to help anticipate and prevent the impacts.”
• Understanding ‘good versus bad’ prions in order to develop drugs: The first step to designing drugs to treat prion and prion-like diseases is to understand how prion proteins change shape when they become “misfolded” in disease. Dr. Christoph Borchers, a Professor in the Department of Biochemistry and Microbiology and Director of the University of Victoria-Genome BC Proteomics Centre is collaborating with researchers from the University of Alberta and University of Western Ontario to characterize the changes that occur to the three-dimensional structure of prion fibrils (small, nerve-like fibres) as well as the molecular mechanisms that lead to those changes. Using a combination of protein chemistry and mass spectrometry, they are working to explain what occurs when a ‘good’ prion protein changes to a ‘bad’ one during disease development. The information is crucial to designing drugs that can interfere with those changes, effectively curbing the spread of prion and prion-like diseases.
About PrioNet Canada (www.prionetcanada.ca) One of Canada’s Networks of Centres of Excellence, PrioNet Canada is a pan-Canadian research network that is developing strategies to help solve the food, health safety, and socioeconomic problems associated with prion diseases. The network brings together academia, industry, and public sector partners through its multidisciplinary research projects, training programs, events, and commercialization activities to help derive maximum socioeconomic benefits for Canadians. PrioNet is hosted by the University of British Columbia and the Vancouver Coastal Health Research Institute in Vancouver.
- 30 -
Media information or to set up interviews: Gail Bergman or Christina Vetro Gail Bergman PR Tel: (905) 886-1340 or (905) 886-3345 E-mail: info@gailbergmanpr.com
Last Updated: 7/13/2011 11:27:59 AM
http://www.prionetcanada.ca/detail.aspx?menu=12&dt=293779&app=70&cat1=211&tp=12&lk=no
All Other Emerging and Zoonotic Infectious Diseases CDC's FY 2012 request of $52,658,000 for all other emerging and zoonotic infectious disease activities is a decrease of $13,607,000 below the FY 2010 level,
which includes the elimination of Prion activities ($5,473,000),
a reduction for other cross-cutting infectious disease activities, and administrative savings. These funds support a range of critical emerging and zoonotic infectious disease programs such Lyme Disease, Chronic Fatigue Syndrome, and Special Pathogens, as well as other activities described below.
http://www.cdc.gov/fmo/topic/Budget%20Information/appropriations_budget_form_pdf/FY2012_CDC_CJ_Final.pdf
" the FY 2010 level, which includes the elimination of Prion activities ($5,473,000), "
USDA MAD COW PROBLEMS SOLVED $$$
NOT !
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"
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/transmissibility-of-bse-l-and-cattle.html
Sunday, June 26, 2011
Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/risk-analysis-of-low-dose-prion.html
Thursday, June 23, 2011
Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/experimental-h-type-bovine-spongiform.html
Wednesday, June 15, 2011
Galveston, Texas - Isle port moves through thousands of heifers headed to Russia, none from Texas, Alabama, or Washington, due to BSE risk factor
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/galveston-texas-isle-port-moves-through.html
Saturday, July 23, 2011
CATTLE HEADS WITH TONSILS, BEEF TONGUES, SPINAL CORD, SPECIFIED RISK MATERIALS (SRM's) AND PRIONS, AKA MAD COW DISEASE
http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/cattle-heads-with-tonsils-beef-tongues.html
Thursday, June 2, 2011
USDA scrapie report for April 2011 NEW ATYPICAL NOR-98 SCRAPIE CASES Pennsylvania AND California
http://nor-98.blogspot.com/2011/06/usda-scrapie-report-for-april-2011-new.html
Monday, June 20, 2011 2011
Annual Conference of the National Institute for Animal Agriculture ATYPICAL NOR-98 LIKE SCRAPIE UPDATE USA
http://nor-98.blogspot.com/2011/06/2011-annual-conference-of-national.html
Monday, June 27, 2011
Comparison of Sheep Nor98 with Human Variably Protease-Sensitive Prionopathy and Gerstmann-Sträussler-Scheinker Disease
http://prionopathy.blogspot.com/2011/06/comparison-of-sheep-nor98-with-human.html
Monday, November 30, 2009
USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH CODE
http://nor-98.blogspot.com/2009/11/usda-and-oie-collaborate-to-exclude.html
I strenuously urge the USDA and the OIE et al to revoke the exemption of the legal global trading of atypical Nor-98 scrapie TSE. ...TSS
Friday, February 11, 2011
Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues
http://nor-98.blogspot.com/2011/02/atypicalnor98-scrapie-infectivity-in.html
Thursday, November 18, 2010
Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy following passage in sheep
http://bse-atypical.blogspot.com/2010/11/increased-susceptibility-of-human-prp.html
Sunday, October 3, 2010
Scrapie, Nor-98 atypical Scrapie, and BSE in sheep and goats North America, who's looking ?
http://nor-98.blogspot.com/2010/10/scrapie-nor-98-atypical-scrapie-and-bse.html
Wednesday, July 06, 2011
Swine Are Susceptible to Chronic Wasting Disease by Intracerebral Inoculation
(see tonnage of mad cow feed in commerce USA...tss)
http://chronic-wasting-disease.blogspot.com/2011/07/swine-are-susceptible-to-chronic.html
Monday, June 27, 2011
Zoonotic Potential of CWD: Experimental Transmissions to Non-Human Primates
http://chronic-wasting-disease.blogspot.com/2011/06/zoonotic-potential-of-cwd-experimental.html
Please see the following warning from CDC about prion TSE consumption in North America ;
Thursday, May 26, 2011
Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey
Journal of the American Dietetic Association Volume 111, Issue 6 , Pages 858-863, June 2011.
http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/travel-history-hunting-and-venison.html
Tuesday, July 19, 2011
Neuroanatomical Distribution of Disease-Associated Prion Protein in Cases of Bovine Spongiform Encephalopathy Detected by Fallen Stock Surveillance in Japan
http://bse-atypical.blogspot.com/2011/07/neuroanatomical-distribution-of-disease.html
Saturday, March 5, 2011
MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html
Oral.01: Changing Spectrum of Prions
Stanley Prusiner
University of California San Francisco, Institute for Neurodegenerative Diseases; San Francisco, CA USA
Prions are self-propagating forms of proteins found in eukaryotes. Prions are created from benign, cellular precursor proteins by a posttranslational modification that is self-perpetuating. Often the prion form of the protein is aggregated and assembles into amyloid polymers. Prions can be inherited both genetically and epigenetically. In neurodegenerative diseases, the formation of prions is heritable through mutations in the gene encoding the cellular form of the prion protein. In fungi, the prion state is epigenetically transferred from mother to daughter cells.
Historically, prions were confined to a small group of infectious CNS illnesses including Creutzfeldt-Jakob disease (CJD) and kuru of humans, scrapie of sheep, bovine spongiform encephalopathy, and chronic wasting disease of deer and elk. CJD can present as an infectious, inherited or sporadic illness. In all three manifestations of the disease, the cellular prion protein (PrPC) refolds into the disease-causing isoform (PrPSc). A truncated form of PrPSc readily polymerizes into amyloid fibrils and forms PrP amyloid plaques. Prion strains composed of different conformers of PrPScSc have been identified. Subsequently, prions were recognized in fungi and studied extensively using yeast. Recently, self-propagation of altered proteins that cause several neurodegenerative diseases, including Alzheimer disease and the tauopathies, has been demonstrated using cultured cell and transgenic mouse models. Increasing evidence argues that the Ab peptide acts as a prion in that it stimulates the de-novo formation of more Ab peptide. Similarly, the aggregates of Tau provoke the assembly of more aggregated Tau. In addition, fetal grafts of substantia nigra in patients with advanced Parkinson’s disease exhibit Lewy bodies, arguing that a-synuclein may act as a prion. Misfolded a-synuclein is thought to transit from the patient’s neurons to those in the graft, where it stimulates the de-novo formation of aberrantly folded a-synuclein into Lewy bodies.
The spread of misprocessed proteins in the human CNS is also consistent with the Ab peptide, hyperphosphorylated Tau and misfolded a-synuclein being prions. In Alzheimer disease, Ab plaques and neurofibrillary tangles (NFTs) begin in the entorhinal cortex and spread throughout the brain. In a delayed form of traumatic brain injury, NFTs appear to spread outward from points of impact. Misfolded a-synuclein has been found along the vagus nerve where it appears to migrate retrograde into the CNS.
Increasing evidence that posttranslationally altered proteins are responsible for the major neurodegenerative diseases widens the spectrum of prion disorders. Moreover, prions with glutamine/asparagine-rich regions like those in yeast and aplysia have given unique insights into the normal function of alternatively processed, self-propagating proteins.
Oral.33: Transmission of Alzheimer Disease and Type 2 Diabetes by a Prion Mechanism
Claudio Soto,1,† Natalia Salvadores-Bersezio,1 Ines Moreno-Gonzalez,1 Claudia Duran-Aniotz,1, 2 Akihiko Urayama,1 Lisbell Estrada,3 Diego Morales-Scheihing1, 2 and Rodrigo Morales1
1Protein Misfolding Disorders Lab, Mitchell Center for Alzheimer Disease and Related Brain Disorders, Department of Neurology; University of Texas Medical School at Houston; Houston, TX USA; 2Facultad de Medicina, Universidad de Los Andes; Santiago, Chile; 3 Universidad Catolica de Chile; Santiago, Chile†Presenting author; Email: Claudio.Soto@uth.tmc.edu
Alzheimer disease (AD) and type 2 diabetes (T2D) are the most prevalent diseases of the group of protein misfolding disorders (PMDs). A hallmark event in the pathology of AD and T2D involves the misfolding, aggregation and accumulation of Ab and IAPP, respectively. Considering that the molecular mechanisms responsible for protein misfolding and aggregation in PMDs are strikingly similar to the process of prion replication we hypothesize that all these diseases have the inherent capability of being transmissible. Recent exciting studies from various groups have provided strong proof-of-concept for the transmission of the pathological hallmarks of various PMDs in an experimental setting. In this presentation we will provide further evidence for the induction of AD and T2D features in animal models of these diseases upon intra-cerebral and intra-peritoneal inoculation of tissue homogenates containing Ab and IAPP aggregates, respectively. One of the key questions regarding prion-like transmissibility of other PMDs is whether this phenomenon can occur by practically relevant routes of exposure. To study this issue, we assessed whether these diseases can be induced by transfusion of blood from animals exhibiting large quantities of cerebral or pancreatic aggregates. Blood transfusion was chosen because is a medically relevant route of exposure to potentially infectious material and because the data in animals and even in humans is solid to support blood transfusion as a route of prion infection in TSEs. Our results show that infusion of blood from old AD or T2D transgenic mice into young animals significantly accelerates the onset of pathological and clinical abnormalities associated to these diseases. Our results indicate that the two most prevalent PMDs can be initiated by exposure to misfolded protein aggregates, which replicate in the body in a similar manner as infectious prions. These findings may open a new avenue to understand the origin of AD and T2D and may provide new strategies for disease intervention and prevention.
PPPM.18: Induction of Ab Amyloidogenesis In Vivo by Blood Transfusion
Rodrigo Morales,1,† Claudia Duran-Aniotz,1, 2 Akihiko Urayama,1 Lisbell Estrada,3 Diego Morales-Scheihing1, 2 and Claudio Soto1
1University of Texas Health Science Center at Houston; Houston, TX USA; 2Universidad de Los Andes; Santiago, Chile; 3Universidad Catolica de Chile; Santiago, Chile†Presenting author; Email: Rodrigo.MoralesLoyola@uth.tmc.edu
Alzheimer disease (AD) is the most common type of senile dementia. Disease manifestation is characterized by progressive impairment of memory and cognition which is triggered by synaptic dysfunction and neuronal loss. Compelling evidence suggests that misfolding and aggregation of Ab is a hallmark event in the disease pathogenesis. An important unanswered question related to AD involves its etiology since over 90% of the AD cases arise sporadically. Interestingly, misfolding and aggregation of proteins is the main feature of other diseases -termed Protein Misfolding Disorders (PMDs)] which include Transmissible Spongiform Encephalopathies (TSEs), among others. Convincing experimental evidences have shown that the only component of the infectious agent in TSEs is the misfolded form of the prion protein. Strikingly, the molecular mechanisms responsible for prion replication are very similar to the process of amyloid formation in all PMDs, suggesting that all these diseases have the inherent capability of being transmissible. Recent reports have shown that intra-cerebral and intra-peritoneal administration of brain homogenates containing Ab aggregates can accelerate the generation of senile plaques in mice models of AD. However, it remains to be demonstrated if this phenomenon can occur by more relevant routes of administration. The aim of this study was to assess whether AD pathogenesis can be induced intravenously, mimicking the know transmission of prion diseases through blood transfusion. For this purpose we used young tg2576 mice which were injected with blood obtained from 12 months old tg2576 mice (AD-blood) that contains a substantial quantity of cerebral Ab deposits. Mice were sacrificed at 250 days old, a time in which these animals scarcely develop Ab deposits. Interestingly, we observed that infusion of AD-blood induces substantial Ab accumulation in animals that without treatment or injected with wild type blood would barely have any detectable Ab lesion. Plaque deposition was mainly present in cortex and hippocampus, being more abundant in the former. In addition, we observed a decrease in memory in mice challenged with AD-blood. Other features such as brain inflammation and synaptic integrity were also measured. Importantly, similar results were obtained in a second and independent experiment performed in a double transgenic mouse model that develops AD plaques as early as 4 months old. Our results indicate that an AD-like pathogenesis can be induced by intravenous administration of AD-blood, presumably through induction of protein misfolding in a similar way as prion diseases. These findings may open a new avenue to understand the origin of sporadic AD and may provide new strategies for disease intervention and prevention.
PPPM.20: Prion-Like Propagation and Neurotoxicity of Recombinant a-Synuclein Aggregates Initiated by Dimerization
Alireza Roostaee† and Xavier Roucou
University of Sherbrooke; Sherbrooke, QC Canada†Presenting author; Email: alireza.roostaee@usherbrooke.ca
Misfolding of the a-Synuclein (a-Syn) protein and subsequent formation of amyloid fibrils or toxic aggregates are neuropathological hallmarks of Parkinson’s Disease (PD). However, a detailed characterization of the mechanism of a-synuclein aggregation/fibrillogenesis and transmission of toxic aggregates has not yet been achieved. In this study, the rates of a-Syn aggregation were compared for wild-type (wt) as well as a chimeric form of a-Syn containing an inducible Fv dimerizing domain (a-SynFv) with the capacity to form homodimers in the presence of a divalent ligand (AP20187). Here we report the increased oligomerization and fibril formation rate of recombinant a-SynFv in the presence of AP20187, in comparison to wt a-Syn or a-SynFv in the absence of divalent ligand. In addition, dimerization of a-SynFv accelerated structural transition from random coil into b-sheet conformation, which is characteristic of a-Syn aggregates. a-SynFv oligomers, but not corresponding monomers or amyloid fibrils, induced neurotoxicity when injected into the hippocampus of wt mice. These recombinant aggregates were amplified by the protein misfolding cyclic amplification (PMCA) method, providing first evidence for the in vitro propagation of synthetic a-Syn aggregates. Our results provide direct evidence for similarities between a-Syn and prion propagation and neutoxicity at the molecular level.
http://www.prion2011.ca/files/PRION_2011_-_Posters_(May_5-11).pdf
Wednesday, April 27, 2011
GENERATION ALZHEIMER'S: THE DEFINING DISEASE OF THE BABY BOOMERS
http://betaamyloidcjd.blogspot.com/2011/04/generation-alzheimers-defining-disease.html
Saturday, January 22, 2011
Alzheimer's, Prion, and Neurological disease, and the misdiagnosis there of, a review 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/alzheimers-prion-and-neurological.html
Friday, September 3, 2010
Alzheimer's, Autism, Amyotrophic Lateral Sclerosis, Parkinson's, Prionoids, Prionpathy, Prionopathy, TSE
http://betaamyloidcjd.blogspot.com/2010/09/alzheimers-autism-amyotrophic-lateral.html
Thursday, December 23, 2010
Alimentary prion infections: Touch-down in the intestine, Alzheimer, Parkinson disease and TSE mad cow diseases $ The Center for Consumer Freedom
http://betaamyloidcjd.blogspot.com/2010/12/alimentary-prion-infections-touch-down.html
TSS
Sunday, June 26, 2011
Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque
Bio.039: Risk Analysis of Low-Dose Prion Exposures in Cynomolgus Macaque
Emmanuel Comoy,1,† Nina Jaffre,1 Jacqueline Mikol,1 Valérie Durand,1 Sophie Freire,1 Evelyne Correia,1 Maurizio Pocchiari,2 Bob Hills,3 Paul Brown1 and Jean-Philippe Deslys1
1 Atomic Energy Commission; Fontenay-aux-Roses, France; 2 Istituto Superiore di Sanita; Roma, Italy; 3 Health Canada; Ottawa, ON Canada†Presenting author; Email: emmanuel.comoy@cea.fr
On the basis of 200,000 clinical BSE cases recorded in UK, it has been estimated that nearly 2,000,000 infected but undiagnosed cattle would have entered the human food chain. To date, only 171 clinical cases of vCJD have been reported, suggesting a high species barrier between cattle and humans. However, transmission experiments in primates would instead suggest a low cattle-to-primate species barrier.
This apparent paradox could be partly explained by a very heterogeneous exposure of consumers; either a low number of people exposed to a high amount of infectivity, or a high number of people (10,000- to 100,000-fold more) exposed to a very low amount of infectivity. The existence of subclinical or preclinical cases with extended periods of incubation in individuals exposed to low doses of infectivity remains to be answered, and bears heavily on the issue of potential secondary exposures through surgical procedures and blood (and tissue) donations
We inoculated cynomolgus macaques with serial dilutions of BSE-infected material. High dose-inoculated animals developed typical clinical disease with all the pathognomonic hallmarks, and incubation periods ranging from 3–8 years. Among low-dosed animals, some developed clinical signs with atypical patterns after extensive incubation periods, exhibiting lesion and biochemical profiles that differed sharply from the typical disease picture. Despite the presence of neurological signs and neuronal lesions, classical lesions of spongiosis and presence of cerebral PrPres were inconstant, or even absent. These observations suggest that low-dose exposure, which would have been the most frequent occurrence during the period of risk, could induce a non-typical pathology that may not be recognized as "prion disease."
link url not available, please see PRION 2011 ;
http://www.prion2011.ca/files/PRION_2011_-_Posters_(May_5-11).pdf
exactly !
please see September 29, 2000 ;
From: Terry S. Singeltary Sr.
To:
Sent: Friday, September 29, 2000 9:15 AM
Subject: vCJD (aka madcow disease) or vaccineCJD???
snip...
just speaking of human TSE's; "different strains (of same disease), different routes of infection (of same disease), different infectivity levels (dose rate) of the (same disease) = different symptoms, different lengths of illness from 1st onset of illness to death, (of the same disease) + different cultures = different geographical locations = different strains (of same disease)...TSS"
snip...
p.s. (on the old lyman links, remove the word lyman in the url link, and add the word madcow, the link should then work... tss)
http://www.whale.to/v/cjd2.html
January 08,200l 3:03 PM
Freas, William
From: Terry S. Singeltary Sr. [flounder@wt.net]
Sent: Monday, January 08,200l 3:03 PM
To: freas@CBS5055530.CBER.FDA.GOV
Subject: CJD/BSE (aka madcow) Human/Animal TSE’s--U.S.--Submission To Scientific Advisors and Consultants Staff January 2001 Meeting (short version)
AND PLEASE FOR GODS SAKE, STOP saying vCJD victims are the only ones tied to this environmental death sentence. "PROVE IT". It's just not true. The 'CHOSEN ONES' are not the only ones dying because of this man-made death sentence. When making regulations for human health from human/animal TSEs, you had better include ALL human TSE's, not just vCJD. Do NOT underestimate sporadic CJD with the 'prehistoric' testing available to date. This could be a deadly mistake. Remember, sCJD kills much faster from 1st onset.of symptoms to death, and hvCJD is the fastest. Could it just be a higher titre of infectivity, or route or source, or all three?
Last, but not least. The illegal/legal harvesting of body parts and tissues will come back to haunt you. Maybe not morally, but due to NO background checks and human TSEs, again it i will continue to spread. Stupidity, Ignorance and Greed is what fuels this disease. You must stop all of this, and ACT AT ONCE...
http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2_09.pdf
2003
"so my quesion is, how low is 'low' in quantifing the infectious dose in vCJD, comparing to _all_ sporadic CJDs, from the different potential routes, sources, and infectivity dose?"
Greetings List Members,
This is _very_ disturbing to me:
snip...
The distribution of PrPSc in the body is different in sporadic and variant CJD, reflecting the different pathogenesis of the two forms. In the case ot sporadic CJD, prion infectivity is largely limited to the CNS (including the retina) and only operations involving the brain and eye have resulted in iatrogenic transmission of the disease. Gastro-intestinal endoscopy is unlikely to be a vector for the transmission of sporadic CJD as infected tissue is not encountered during the procedure. No special precautions are necessary during or after the procedure and the endoscope should be cleaned and disinfected in the normal thorough way.4
snip...
i personally believe it is irresponsible for anyone to state in this day and time, that sporadic CJDs (now at 6 variants) will not transmit the disease by this route. considering infective dose cannot be quantified, only speculated, such a statement is thus, irresponsible. to hypothosize that sporadic CJD just happens spontaneously (with no scientific proof), that the PrPSc distribution in tissues of all sporadic CJDs is entirely different than that of vCJD, without being able to quantify the titre of infection, or even confirm all the different variants yet, again is _not_ based on all scientific data, then it's only a hypothosis. who is to say that some of these variants of sporadic CJD were not obtained _orally_?
also stated:
snip...
Although thorough cleaning of flexible endoscopes ensures patient safety for ''normal'' pathogens, the same process may not be adequate for the PrPSc.
snip...
The sporadic form of CJD affects approximately one person per mil-lion per annum in the population on a worldwide basis.
who is to say how much infectivity are in some of these variants of sporadic CJDs, without confirming this? if we look at the 6 different variants of sporadic CJDs, has the infective dose for all 6 _documented_ variants been quantified, and documented as being 'measurable'?
will there be more variants of sporadic CJDs, and what of the ramifications from them?
what of other strains/variants of TSE in cattle, BSE in sheep, CWD in cattle, or any of the 20+ strains of Scrapies in deer/elk? i get dizzy thinking of the different scenerio's. what would the human TSEs from these species look like and how can anyone quantify any tissue infectivity from these potential TSE transmissions to humans, and the risk scenerio described here from this potential route? could not some of these sporadic CJDs have derived directly or indirectly from one of these species, and if so, pose a risk by the route described here?
something else to consider, in the recent finding of the incubation period of 38 years from a _small_ dose of human growth hormone;
snip...
We describe the second patient with hGH related CJD in the Netherlands. The patient developed the disease 38 years after hGH injections. To our knowledge, this is the longest incubation period described for any form of iatrogentic CJD. Furthermore, our patient was _not_ treated with hGH, but only received a _low_ dose as part of a diagnostic procedure. (see full text below).
snip...
so my quesion is, how low is 'low' in quantifing the infectious dose in vCJD, comparing to _all_ sporadic CJDs, from the different potential routes, sources, and infectivity dose?
will the titre of infectivity in every tissue and organ of all sporadic CJDs stay exact or constant, no matter what the infective dose, route and species may be? this is considering you don't buy the fact that sporadic CJDs 85%+ of _all_ CJDs, are a happen stance of bad luck, happen spontaneously without cause, and are one-in-a-million world wide, with no substantial surveillance to confirm this.
see gut link bramble et al on blogspot...tss
http://creutzfeldt-jakob-disease.blogspot.com/2010/01/evidence-for-cjd-tse-transmission-via.html
2009
Could it just be a higher titre of infectivity, or route or source, or all three? ...
http://tseac.blogspot.com/2009/05/meeting-of-transmissible-spongiform.html
Thursday, June 23, 2011
Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/experimental-h-type-bovine-spongiform.html
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"
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/transmissibility-of-bse-l-and-cattle.html
Sunday, May 01, 2011
STUDY OF ATYPICAL BSE 2010 Annual Report May 2011
http://bse-atypical.blogspot.com/2011/05/study-of-atypical-bse-2010-annual.html
Saturday, January 29, 2011
Atypical L-Type Bovine Spongiform Encephalopathy (L-BSE) Transmission to Cynomolgus Macaques, a Non-Human Primate Jpn. J. Infect. Dis., 64 (1), 81-84, 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/atypical-l-type-bovine-spongiform.html
Wednesday, July 28, 2010
Atypical prion proteins and IBNC in cattle DEFRA project code SE1796 FOIA Final report
http://bse-atypical.blogspot.com/2010/07/atypical-prion-proteins-and-ibnc-in.html
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
http://transmissible-mink-encephalopathy.blogspot.com/2007/12/phenotypic-similarity-of-transmissible.html
Wednesday, June 15, 2011
Galveston, Texas - Isle port moves through thousands of heifers headed to Russia, none from Texas, Alabama, or Washington, due to BSE risk factor
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/galveston-texas-isle-port-moves-through.html
What is the potential cost of pre- and post-slaughter testing? The estimated cost of post-mortem testing is $40 per head. This amount is comprised almost entirely of the cost of the test kit and sample analysis. It is expected that ante-mortem tests (live animal), if a test is developed, will reduce BSE testing costs to approximately $15 per head.
http://www.prionetcanada.ca/detail.aspx?menu=12&dt=293720&app=70&cat1=211&tp=12&lk=no
Thursday, August 12, 2010
Seven main threats for the future linked to prions
First threat
The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed.
***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.
Second threat
snip...
http://www.neuroprion.org/en/np-neuroprion.html
Rural and Regional Affairs and Transport References Committee
The possible impacts and consequences for public health, trade and agriculture of the Government’s decision to relax import restrictions on beef Final report June 2010
2.66 Dr Fahey also told the committee that in the last two years a link has been established between forms of atypical CJD and atypical BSE. Dr Fahey said that: They now believe that those atypical BSEs overseas are in fact causing sporadic Creutzfeldt-Jakob disease. They were not sure if it was due to mad sheep disease or a different form. If you look in the textbooks it looks like this is just arising by itself. But in my research I have a summary of a document which states that there has never been any proof that sporadic Creutzfeldt-Jakob disease has arisen de novo—has arisen of itself. There is no proof of that. The recent research is that in fact it is due to atypical forms of mad cow disease which have been found across Europe, have been found in America and have been found in Asia. These atypical forms of mad cow disease typically have even longer incubation periods than the classical mad cow disease.50
http://www.aph.gov.au/senate/committee/rrat_ctte/mad_cows/report/report.pdf
Monday, May 23, 2011
Atypical Prion Diseases in Humans and Animals 2011
Top Curr Chem (2011)
DOI: 10.1007/128_2011_161
# Springer-Verlag Berlin Heidelberg 2011
Michael A. Tranulis, Sylvie L. Benestad, Thierry Baron, and Hans Kretzschmar
http://bse-atypical.blogspot.com/2011/05/atypical-prion-diseases-in-humans-and.html
14th ICID International Scientific Exchange Brochure -
Final Abstract Number: ISE.114
Session: International Scientific Exchange
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America update October 2009
T. Singeltary
Bacliff, TX, USA
Background:
An update on atypical BSE and other TSE in North America. Please remember, the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been documented in North America, along with the typical scrapie's, and atypical Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these TSE in different species have been rendered and fed to food producing animals for humans and animals in North America (TSE in cats and dogs ?), and that the trading of these TSEs via animals and products via the USA and Canada has been immense over the years, decades.
Methods:
12 years independent research of available data
Results:
I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc.
Conclusion:
I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena's. Restricting the reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route.
http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf
Saturday, March 5, 2011
MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html
Tuesday, June 14, 2011
Clinical research in CJD at a U.S. clinical prion research center: CJD Quinacrine Study results and improved diagnosis of prion disease
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/clinical-research-in-cjd-at-us-clinical.html
Tuesday, April 26, 2011
sporadic CJD RISING Text and figures of the latest annual report of the NCJDRSU covering the period 1990-2009 (published 11th March 2011)
http://creutzfeldt-jakob-disease.blogspot.com/2011/04/sporadic-cjd-rising-text-and-figures-of.html
Tuesday, March 29, 2011
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY EXPOSURE SPREADING VIA HOSPITALS AND SURGICAL PROCEDURES AROUND THE GLOBE
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/transmissible-spongiform-encephalopathy.html
TSE & HOUNDS
GAH WELLS (very important statement here...TSS)
HOUND STUDY
AS implied in the Inset 25 we must not _ASSUME_ that transmission of BSE to other species will invariably present pathology typical of a scrapie-like disease.
http://web.archive.org/web/20010305222642/www.bseinquiry.gov.uk/files/yb/1991/01/04004001.pdf
http://caninespongiformencephalopathy.blogspot.com/
PLEASE NOTE *
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...
http://web.archive.org/web/20030516051623/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf
TSS
Emmanuel Comoy,1,† Nina Jaffre,1 Jacqueline Mikol,1 Valérie Durand,1 Sophie Freire,1 Evelyne Correia,1 Maurizio Pocchiari,2 Bob Hills,3 Paul Brown1 and Jean-Philippe Deslys1
1 Atomic Energy Commission; Fontenay-aux-Roses, France; 2 Istituto Superiore di Sanita; Roma, Italy; 3 Health Canada; Ottawa, ON Canada†Presenting author; Email: emmanuel.comoy@cea.fr
On the basis of 200,000 clinical BSE cases recorded in UK, it has been estimated that nearly 2,000,000 infected but undiagnosed cattle would have entered the human food chain. To date, only 171 clinical cases of vCJD have been reported, suggesting a high species barrier between cattle and humans. However, transmission experiments in primates would instead suggest a low cattle-to-primate species barrier.
This apparent paradox could be partly explained by a very heterogeneous exposure of consumers; either a low number of people exposed to a high amount of infectivity, or a high number of people (10,000- to 100,000-fold more) exposed to a very low amount of infectivity. The existence of subclinical or preclinical cases with extended periods of incubation in individuals exposed to low doses of infectivity remains to be answered, and bears heavily on the issue of potential secondary exposures through surgical procedures and blood (and tissue) donations
We inoculated cynomolgus macaques with serial dilutions of BSE-infected material. High dose-inoculated animals developed typical clinical disease with all the pathognomonic hallmarks, and incubation periods ranging from 3–8 years. Among low-dosed animals, some developed clinical signs with atypical patterns after extensive incubation periods, exhibiting lesion and biochemical profiles that differed sharply from the typical disease picture. Despite the presence of neurological signs and neuronal lesions, classical lesions of spongiosis and presence of cerebral PrPres were inconstant, or even absent. These observations suggest that low-dose exposure, which would have been the most frequent occurrence during the period of risk, could induce a non-typical pathology that may not be recognized as "prion disease."
link url not available, please see PRION 2011 ;
http://www.prion2011.ca/files/PRION_2011_-_Posters_(May_5-11).pdf
exactly !
please see September 29, 2000 ;
From: Terry S. Singeltary Sr.
To:
Sent: Friday, September 29, 2000 9:15 AM
Subject: vCJD (aka madcow disease) or vaccineCJD???
snip...
just speaking of human TSE's; "different strains (of same disease), different routes of infection (of same disease), different infectivity levels (dose rate) of the (same disease) = different symptoms, different lengths of illness from 1st onset of illness to death, (of the same disease) + different cultures = different geographical locations = different strains (of same disease)...TSS"
snip...
p.s. (on the old lyman links, remove the word lyman in the url link, and add the word madcow, the link should then work... tss)
http://www.whale.to/v/cjd2.html
January 08,200l 3:03 PM
Freas, William
From: Terry S. Singeltary Sr. [flounder@wt.net]
Sent: Monday, January 08,200l 3:03 PM
To: freas@CBS5055530.CBER.FDA.GOV
Subject: CJD/BSE (aka madcow) Human/Animal TSE’s--U.S.--Submission To Scientific Advisors and Consultants Staff January 2001 Meeting (short version)
AND PLEASE FOR GODS SAKE, STOP saying vCJD victims are the only ones tied to this environmental death sentence. "PROVE IT". It's just not true. The 'CHOSEN ONES' are not the only ones dying because of this man-made death sentence. When making regulations for human health from human/animal TSEs, you had better include ALL human TSE's, not just vCJD. Do NOT underestimate sporadic CJD with the 'prehistoric' testing available to date. This could be a deadly mistake. Remember, sCJD kills much faster from 1st onset.of symptoms to death, and hvCJD is the fastest. Could it just be a higher titre of infectivity, or route or source, or all three?
Last, but not least. The illegal/legal harvesting of body parts and tissues will come back to haunt you. Maybe not morally, but due to NO background checks and human TSEs, again it i will continue to spread. Stupidity, Ignorance and Greed is what fuels this disease. You must stop all of this, and ACT AT ONCE...
http://www.fda.gov/ohrms/dockets/ac/01/slides/3681s2_09.pdf
2003
"so my quesion is, how low is 'low' in quantifing the infectious dose in vCJD, comparing to _all_ sporadic CJDs, from the different potential routes, sources, and infectivity dose?"
Greetings List Members,
This is _very_ disturbing to me:
snip...
The distribution of PrPSc in the body is different in sporadic and variant CJD, reflecting the different pathogenesis of the two forms. In the case ot sporadic CJD, prion infectivity is largely limited to the CNS (including the retina) and only operations involving the brain and eye have resulted in iatrogenic transmission of the disease. Gastro-intestinal endoscopy is unlikely to be a vector for the transmission of sporadic CJD as infected tissue is not encountered during the procedure. No special precautions are necessary during or after the procedure and the endoscope should be cleaned and disinfected in the normal thorough way.4
snip...
i personally believe it is irresponsible for anyone to state in this day and time, that sporadic CJDs (now at 6 variants) will not transmit the disease by this route. considering infective dose cannot be quantified, only speculated, such a statement is thus, irresponsible. to hypothosize that sporadic CJD just happens spontaneously (with no scientific proof), that the PrPSc distribution in tissues of all sporadic CJDs is entirely different than that of vCJD, without being able to quantify the titre of infection, or even confirm all the different variants yet, again is _not_ based on all scientific data, then it's only a hypothosis. who is to say that some of these variants of sporadic CJD were not obtained _orally_?
also stated:
snip...
Although thorough cleaning of flexible endoscopes ensures patient safety for ''normal'' pathogens, the same process may not be adequate for the PrPSc.
snip...
The sporadic form of CJD affects approximately one person per mil-lion per annum in the population on a worldwide basis.
who is to say how much infectivity are in some of these variants of sporadic CJDs, without confirming this? if we look at the 6 different variants of sporadic CJDs, has the infective dose for all 6 _documented_ variants been quantified, and documented as being 'measurable'?
will there be more variants of sporadic CJDs, and what of the ramifications from them?
what of other strains/variants of TSE in cattle, BSE in sheep, CWD in cattle, or any of the 20+ strains of Scrapies in deer/elk? i get dizzy thinking of the different scenerio's. what would the human TSEs from these species look like and how can anyone quantify any tissue infectivity from these potential TSE transmissions to humans, and the risk scenerio described here from this potential route? could not some of these sporadic CJDs have derived directly or indirectly from one of these species, and if so, pose a risk by the route described here?
something else to consider, in the recent finding of the incubation period of 38 years from a _small_ dose of human growth hormone;
snip...
We describe the second patient with hGH related CJD in the Netherlands. The patient developed the disease 38 years after hGH injections. To our knowledge, this is the longest incubation period described for any form of iatrogentic CJD. Furthermore, our patient was _not_ treated with hGH, but only received a _low_ dose as part of a diagnostic procedure. (see full text below).
snip...
so my quesion is, how low is 'low' in quantifing the infectious dose in vCJD, comparing to _all_ sporadic CJDs, from the different potential routes, sources, and infectivity dose?
will the titre of infectivity in every tissue and organ of all sporadic CJDs stay exact or constant, no matter what the infective dose, route and species may be? this is considering you don't buy the fact that sporadic CJDs 85%+ of _all_ CJDs, are a happen stance of bad luck, happen spontaneously without cause, and are one-in-a-million world wide, with no substantial surveillance to confirm this.
see gut link bramble et al on blogspot...tss
http://creutzfeldt-jakob-disease.blogspot.com/2010/01/evidence-for-cjd-tse-transmission-via.html
2009
Could it just be a higher titre of infectivity, or route or source, or all three? ...
http://tseac.blogspot.com/2009/05/meeting-of-transmissible-spongiform.html
Thursday, June 23, 2011
Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/experimental-h-type-bovine-spongiform.html
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"
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/transmissibility-of-bse-l-and-cattle.html
Sunday, May 01, 2011
STUDY OF ATYPICAL BSE 2010 Annual Report May 2011
http://bse-atypical.blogspot.com/2011/05/study-of-atypical-bse-2010-annual.html
Saturday, January 29, 2011
Atypical L-Type Bovine Spongiform Encephalopathy (L-BSE) Transmission to Cynomolgus Macaques, a Non-Human Primate Jpn. J. Infect. Dis., 64 (1), 81-84, 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/atypical-l-type-bovine-spongiform.html
Wednesday, July 28, 2010
Atypical prion proteins and IBNC in cattle DEFRA project code SE1796 FOIA Final report
http://bse-atypical.blogspot.com/2010/07/atypical-prion-proteins-and-ibnc-in.html
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
http://transmissible-mink-encephalopathy.blogspot.com/2007/12/phenotypic-similarity-of-transmissible.html
Wednesday, June 15, 2011
Galveston, Texas - Isle port moves through thousands of heifers headed to Russia, none from Texas, Alabama, or Washington, due to BSE risk factor
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/galveston-texas-isle-port-moves-through.html
What is the potential cost of pre- and post-slaughter testing? The estimated cost of post-mortem testing is $40 per head. This amount is comprised almost entirely of the cost of the test kit and sample analysis. It is expected that ante-mortem tests (live animal), if a test is developed, will reduce BSE testing costs to approximately $15 per head.
http://www.prionetcanada.ca/detail.aspx?menu=12&dt=293720&app=70&cat1=211&tp=12&lk=no
Thursday, August 12, 2010
Seven main threats for the future linked to prions
First threat
The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed.
***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.
Second threat
snip...
http://www.neuroprion.org/en/np-neuroprion.html
Rural and Regional Affairs and Transport References Committee
The possible impacts and consequences for public health, trade and agriculture of the Government’s decision to relax import restrictions on beef Final report June 2010
2.66 Dr Fahey also told the committee that in the last two years a link has been established between forms of atypical CJD and atypical BSE. Dr Fahey said that: They now believe that those atypical BSEs overseas are in fact causing sporadic Creutzfeldt-Jakob disease. They were not sure if it was due to mad sheep disease or a different form. If you look in the textbooks it looks like this is just arising by itself. But in my research I have a summary of a document which states that there has never been any proof that sporadic Creutzfeldt-Jakob disease has arisen de novo—has arisen of itself. There is no proof of that. The recent research is that in fact it is due to atypical forms of mad cow disease which have been found across Europe, have been found in America and have been found in Asia. These atypical forms of mad cow disease typically have even longer incubation periods than the classical mad cow disease.50
http://www.aph.gov.au/senate/committee/rrat_ctte/mad_cows/report/report.pdf
Monday, May 23, 2011
Atypical Prion Diseases in Humans and Animals 2011
Top Curr Chem (2011)
DOI: 10.1007/128_2011_161
# Springer-Verlag Berlin Heidelberg 2011
Michael A. Tranulis, Sylvie L. Benestad, Thierry Baron, and Hans Kretzschmar
http://bse-atypical.blogspot.com/2011/05/atypical-prion-diseases-in-humans-and.html
14th ICID International Scientific Exchange Brochure -
Final Abstract Number: ISE.114
Session: International Scientific Exchange
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America update October 2009
T. Singeltary
Bacliff, TX, USA
Background:
An update on atypical BSE and other TSE in North America. Please remember, the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been documented in North America, along with the typical scrapie's, and atypical Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these TSE in different species have been rendered and fed to food producing animals for humans and animals in North America (TSE in cats and dogs ?), and that the trading of these TSEs via animals and products via the USA and Canada has been immense over the years, decades.
Methods:
12 years independent research of available data
Results:
I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc.
Conclusion:
I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena's. Restricting the reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route.
http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf
Saturday, March 5, 2011
MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html
Tuesday, June 14, 2011
Clinical research in CJD at a U.S. clinical prion research center: CJD Quinacrine Study results and improved diagnosis of prion disease
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/clinical-research-in-cjd-at-us-clinical.html
Tuesday, April 26, 2011
sporadic CJD RISING Text and figures of the latest annual report of the NCJDRSU covering the period 1990-2009 (published 11th March 2011)
http://creutzfeldt-jakob-disease.blogspot.com/2011/04/sporadic-cjd-rising-text-and-figures-of.html
Tuesday, March 29, 2011
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY EXPOSURE SPREADING VIA HOSPITALS AND SURGICAL PROCEDURES AROUND THE GLOBE
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/transmissible-spongiform-encephalopathy.html
TSE & HOUNDS
GAH WELLS (very important statement here...TSS)
HOUND STUDY
AS implied in the Inset 25 we must not _ASSUME_ that transmission of BSE to other species will invariably present pathology typical of a scrapie-like disease.
http://web.archive.org/web/20010305222642/www.bseinquiry.gov.uk/files/yb/1991/01/04004001.pdf
http://caninespongiformencephalopathy.blogspot.com/
PLEASE NOTE *
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...
http://web.archive.org/web/20030516051623/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf
TSS
Tuesday, June 7, 2011
Protein aggregate spreading in neurodegenerative diseases: Problems and perspectives
Protein aggregate spreading in neurodegenerative diseases: Problems and perspectives
doi:10.1016/j.neures.2011.05.008 | How to Cite or Link Using DOI Permissions & Reprints
Review article Protein aggregate spreading in neurodegenerative diseases: Problems and perspectives Purchase $ 31.50
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Seung-Jae Leea, c, , , Hee-Sun Lima, c, Eliezer Masliahd and He-Jin Leeb, c
a Department of Biomedical Science and Technology, Konkuk University, Seoul 143-701, Republic of Korea
b Department of Anatomy School of Medicine, Konkuk University, Seoul 143-701, Republic of Korea
c Institute of Biomedical Science and Technology, Konkuk University, Seoul 143-701, Republic of Korea
d Department of Neurosciences and Pathology, School of Medicine, University of California San Diego, La Jolla, CA 92093-0624, USA
Received 4 March 2011; revised 13 May 2011; accepted 16 May 2011. Available online 20 May 2011.
Abstract
Progressive accumulation of specific protein aggregates is a defining feature of many major neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, fronto-temporal dementia, Huntington's disease, and Creutzfeldt–Jakob disease (CJD). Findings from several recent studies have suggested that aggregation-prone proteins, such as tau, a-synuclein, polyglutamine-containing proteins, and amyloid-ß, can spread to other cells and brain regions, a phenomenon considered unique to prion disorders, such as CJD and bovine spongiform encephalopathy. Cell-to-cell propagation of protein aggregates may be the general underlying principle for progressive deterioration of neurodegenerative diseases. This may also have significant implications in cell replacement therapies, as evidenced by the propagation of a-synuclein aggregates from host to grafted cells in long-term transplants in Parkinson's patients. Here, we review recent progress in protein aggregate propagation in experimental model systems and discuss outstanding questions and future perspectives. Understanding the mechanisms of this pathological spreading may open the way to unique opportunities for development of diagnostic techniques and novel therapies for protein misfolding-associated neurodegenerative diseases.
Keywords: Protein aggregation; Alzheimer's disease; Parkinson's disease; Huntington's disease; Prion
Abbreviations: CJD, Creutzfeldt–Jakob disease; AD, Alzheimer's disease; PD, Parkinson's disease; HD, Huntington's disease; Aß, amyloid-ß; polyQ, polyglutamine; CNS, central nervous system; NFTs, neurofibrillary tangles; NTs, neuropil threads; APP, amyloid precursor protein
http://www.sciencedirect.com/science/article/pii/S0168010211001325
Saturday, January 22, 2011
Alzheimer's, Prion, and Neurological disease, and the misdiagnosis there of, a review 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/alzheimers-prion-and-neurological.html
Saturday, March 5, 2011
MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html
Tuesday, April 26, 2011
sporadic CJD RISING Text and figures of the latest annual report of the NCJDRSU covering the period 1990-2009 (published 11th March 2011)
http://creutzfeldt-jakob-disease.blogspot.com/2011/04/sporadic-cjd-rising-text-and-figures-of.html
PLEASE REMEMBER ;
The Akron, Ohio-based CJD Foundation said the Center for Disease Control revised that number in October of 2004 to about one in 9,000 CJD cases per year in the population group age 55 and older.
HAVE YOU GOT YOUR CJD QUESTIONNAIRE ASKING REAL QUESTIONS PERTAINING TO ROUTE AND SOURCE OF THE TSE AGENT THAT KILLED YOUR LOVED ONE ???
Friday, November 30, 2007
CJD QUESTIONNAIRE USA CWRU AND CJD FOUNDATION
http://cjdquestionnaire.blogspot.com/2007/11/cjd-questionnaire.html
http://cjdquestionnaire.blogspot.com/
USA PRION FUNDING
"which includes the ___elimination___ of Prion activities ($5,473,000),"
All Other Emerging and Zoonotic Infectious Diseases CDC's FY 2012 request of $52,658,000 for all other emerging and zoonotic infectious disease activities is a decrease of $13,607,000 below the FY 2010 level, which includes the elimination of Prion activities ($5,473,000), a reduction for other cross-cutting infectious disease activities, and administrative savings. These funds support a range of critical emerging and zoonotic infectious disease programs such Lyme Disease, Chronic Fatigue Syndrome, and Special Pathogens, as well as other activities described below.
http://www.cdc.gov/fmo/topic/Budget%20Information/appropriations_budget_form_pdf/FY2012_CDC_CJ_Final.pdf
Sunday, June 5, 2011
PRION TSE FUNDING, WHAT ARE THE PRIORITIES of APHCA, ASEAN, OIE, Korea, and USA ?
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/prion-tse-funding-what-are-priorities.html
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518
doi:10.1016/j.neures.2011.05.008 | How to Cite or Link Using DOI Permissions & Reprints
Review article Protein aggregate spreading in neurodegenerative diseases: Problems and perspectives Purchase $ 31.50
References and further reading may be available for this article. To view references and further reading you must purchase this article.
Seung-Jae Leea, c, , , Hee-Sun Lima, c, Eliezer Masliahd and He-Jin Leeb, c
a Department of Biomedical Science and Technology, Konkuk University, Seoul 143-701, Republic of Korea
b Department of Anatomy School of Medicine, Konkuk University, Seoul 143-701, Republic of Korea
c Institute of Biomedical Science and Technology, Konkuk University, Seoul 143-701, Republic of Korea
d Department of Neurosciences and Pathology, School of Medicine, University of California San Diego, La Jolla, CA 92093-0624, USA
Received 4 March 2011; revised 13 May 2011; accepted 16 May 2011. Available online 20 May 2011.
Abstract
Progressive accumulation of specific protein aggregates is a defining feature of many major neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, fronto-temporal dementia, Huntington's disease, and Creutzfeldt–Jakob disease (CJD). Findings from several recent studies have suggested that aggregation-prone proteins, such as tau, a-synuclein, polyglutamine-containing proteins, and amyloid-ß, can spread to other cells and brain regions, a phenomenon considered unique to prion disorders, such as CJD and bovine spongiform encephalopathy. Cell-to-cell propagation of protein aggregates may be the general underlying principle for progressive deterioration of neurodegenerative diseases. This may also have significant implications in cell replacement therapies, as evidenced by the propagation of a-synuclein aggregates from host to grafted cells in long-term transplants in Parkinson's patients. Here, we review recent progress in protein aggregate propagation in experimental model systems and discuss outstanding questions and future perspectives. Understanding the mechanisms of this pathological spreading may open the way to unique opportunities for development of diagnostic techniques and novel therapies for protein misfolding-associated neurodegenerative diseases.
Keywords: Protein aggregation; Alzheimer's disease; Parkinson's disease; Huntington's disease; Prion
Abbreviations: CJD, Creutzfeldt–Jakob disease; AD, Alzheimer's disease; PD, Parkinson's disease; HD, Huntington's disease; Aß, amyloid-ß; polyQ, polyglutamine; CNS, central nervous system; NFTs, neurofibrillary tangles; NTs, neuropil threads; APP, amyloid precursor protein
http://www.sciencedirect.com/science/article/pii/S0168010211001325
Saturday, January 22, 2011
Alzheimer's, Prion, and Neurological disease, and the misdiagnosis there of, a review 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/alzheimers-prion-and-neurological.html
Saturday, March 5, 2011
MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html
Tuesday, April 26, 2011
sporadic CJD RISING Text and figures of the latest annual report of the NCJDRSU covering the period 1990-2009 (published 11th March 2011)
http://creutzfeldt-jakob-disease.blogspot.com/2011/04/sporadic-cjd-rising-text-and-figures-of.html
PLEASE REMEMBER ;
The Akron, Ohio-based CJD Foundation said the Center for Disease Control revised that number in October of 2004 to about one in 9,000 CJD cases per year in the population group age 55 and older.
HAVE YOU GOT YOUR CJD QUESTIONNAIRE ASKING REAL QUESTIONS PERTAINING TO ROUTE AND SOURCE OF THE TSE AGENT THAT KILLED YOUR LOVED ONE ???
Friday, November 30, 2007
CJD QUESTIONNAIRE USA CWRU AND CJD FOUNDATION
http://cjdquestionnaire.blogspot.com/2007/11/cjd-questionnaire.html
http://cjdquestionnaire.blogspot.com/
USA PRION FUNDING
"which includes the ___elimination___ of Prion activities ($5,473,000),"
All Other Emerging and Zoonotic Infectious Diseases CDC's FY 2012 request of $52,658,000 for all other emerging and zoonotic infectious disease activities is a decrease of $13,607,000 below the FY 2010 level, which includes the elimination of Prion activities ($5,473,000), a reduction for other cross-cutting infectious disease activities, and administrative savings. These funds support a range of critical emerging and zoonotic infectious disease programs such Lyme Disease, Chronic Fatigue Syndrome, and Special Pathogens, as well as other activities described below.
http://www.cdc.gov/fmo/topic/Budget%20Information/appropriations_budget_form_pdf/FY2012_CDC_CJ_Final.pdf
Sunday, June 5, 2011
PRION TSE FUNDING, WHAT ARE THE PRIORITIES of APHCA, ASEAN, OIE, Korea, and USA ?
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/prion-tse-funding-what-are-priorities.html
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518
Thursday, December 23, 2010
Molecular Typing of Protease-Resistant Prion Protein in Transmissible Spongiform Encephalopathies of Small Ruminants, France, 2002–2009
Volume 17, Number 1–January 2011
Research
Molecular Typing of Protease-Resistant Prion Protein in Transmissible Spongiform Encephalopathies of Small Ruminants, France, 2002–2009
Johann Vulin, Anne-Gaëlle Biacabe, Géraldine Cazeau, Didier Calavas, and Thierry Baron Author affiliation: Agence Nationale de Sécurité Sanitaire, Lyon, France
Suggested citation for this article
Abstract The agent that causes bovine spongiform encephalopathy (BSE) may be infecting small ruminants, which could have serious implications for human health. To distinguish BSE from scrapie and to examine the molecular characteristics of the protease-resistant prion protein (PrPres), we used a specifically designed Western blot method to test isolates from 648 sheep and 53 goats. During 2002–2009, classical non-Nor98 transmissible spongiform encephalopathy had been confirmed among ˜1.7 million small ruminants in France. Five sheep and 2 goats that showed a PrPres pattern consistent with BSE, or with the CH1641 experimental scrapie source, were identified. Later, bioassays confirmed infection by the BSE agent in 1 of the 2 goats. Western blot testing of the 6 other isolates showed an additional C-terminally cleaved PrPres product, with an unglycosylated band at ˜14 kDa, similar to that found in the CH1641 experimental scrapie isolate and different from the BSE isolate.
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Discussion We investigated the PrPres molecular features of one of the largest series of natural TSE isolates from sheep and goats analyzed so far in Europe. Approximately 1.7 million small ruminants were subjected to a rapid test; among these, 1,153 sheep and 78 goats originating from 992 flocks were confirmed as TSE-positive on the basis of identification of PrPres in the brain stem. Another large study using 1,247 sheep originating from 450 flocks in Great Britain has been reported (24). Similar studies have been conducted in other European countries such as Germany (34), the Netherlands (14), and Italy (23), but fewer TSE-positive animals were reported. In our series, animals with classical cases represented 53% of the TSE-affected animals.
The molecular features of most of these isolates (99%) were comparable to those previously described for most scrapie cases, in studies in Europe or France (21). In all of these cases, PrPres from sheep and goats showed clearly distinct features from BSE, based on the identification of a higher molecular mass of unglycosylated PrPres, associated with strong labeling by the P4 antibody that recognizes the N terminal end of the protein. However, our observation of large individual variations in this PrPres molecular mass implies that a possible relationship with the biologic diversity of TSE agents, which has been described after transmission of scrapie to inbred wild-type mice (35), would be questionable. Only a few animals (5 sheep and 2 goats) in this large series of TSE-affected animals showed molecular characteristics that, in comparison with the usual features of scrapie, could be consistent with the known BSE signature in small ruminants. These samples represented all the suspected isolates that were identified by official surveillance in France during 2002–2009.
An essential molecular criterion defined from the observation of PrPres BSE compared with scrapie was the low molecular mass of the unglycosylated band in PrPres BSE, associated with a decreased PrPres signal lower with an N terminal antibody than with a core antibody (13,22,36). After identification of these molecular features in a few small ruminants, only 1 (CH636) of the 2 cases here described in goats, identified as TSE positive in 2002, has been shown to be infected by the BSE agent after bioassays in mice (37). Another goat in the United Kingdom identified by an immunohistochemical discriminatory method as TSE-positive in 1990 showed characteristics that were indistinguishable from BSE (18). These results clearly indicate that in a situation characterized by a decrease in the number of cases in cattle in all countries in Europe, the possibility of finding BSE in small ruminants is now remote.
The other unusual isolates showed molecular characteristics that were partly similar, not only to BSE in small ruminants with a low molecular mass of PrPres and faint labeling with P4 antibody, but also to the CH1641 experimental scrapie isolate. However, detailed immunohistochemical investigations of CH1641 showed subtle differences in the cleavage site of the protein compared with BSE in sheep (38). As previously described, after transmission in ovine transgenic mice (17), the slightly lower PrPres molecular mass in CH1641-like isolates, as recognized in the CH1641 experimental isolate (13) was confirmed by Western blot, at least in sheep (Figure 2, panel B). However, these differences in molecular mass are more easily identified on the diglycosylated band. Compared with BSE in small ruminants, lower proportions of this diglycosylated band were found in sheep, whereas the 08-357 goat sample showed very high levels of this diglycosylated band, which would be consistent with BSE. Experimental transmissions of BSE in sheep have shown that, to a certain extent, the PrPres molecular features could be influenced by different factors, such as serial passages in sheep (39) or sheep genotypes (36), although slight variability did not compromise the discrimination with scrapie. Furthermore, all these CH1641-like natural isolates in sheep and goats clearly differed from BSE by the presence of an additional, C-terminally cleaved, PrPres product specifically recognized by a C-terminal antibody (SAF84), as previously described for the CH1641 experimental scrapie isolate (17). Baron et al. described bioassays of 3 of 20 CH1641-like sheep isolates (17), which are also being conducted for the other isolates.
These 6 CH1641-like isolates were identified among 1,153 sheep and 78 goats with confirmed TSE, and the goat case represents, to our knowledge, a spreading of the known species range for natural CH1641 infection. At least in sheep, for which 4.34 cases per million sheep tested were identified in this study, the frequency of CH1641-like scrapie was notably higher compared with other rare TSEs in ruminants such as atypical BSEs, which showed a frequency of 0.76 per million cattle tested during 2001–2007 (40). Thus, large-scale testing of animals would be required to identify these rare TSE isolates. Similar isolates were only identified in sheep in the other large series reported from 450 flocks in Great Britain (2 cases in 1 flock) (23) and in a previous study of 214 TSE-infected sheep in France (2 cases in 1 flock) (27). However, an underestimation of the frequency of such cases cannot be fully excluded. PrPres features are assessed by analyzing a single homogenate prepared from a brain fragment from the animal. Stack et al. described a case in sheep that appeared as CH1641-like after repeated Western blot analysis of a brain stem sample, whereas previous analysis of the caudal medulla at the time of submission had shown the usual scrapie profile (24). Immunohistochemical testing of 2 CH1641-like cases in sheep showed, that unlike BSE, PrPd could be clearly identified by using P4 antibody in some of the brain stem nuclei and in lymphoid tissues (27). Finally, on the basis of identification of low levels of C-terminal PrPres product in ovine transgenic mice infected with usual scrapie isolates, we hypothesized that a CH1641-like component might be present as a minor component in these scrapie cases that showed usual molecular features (17). All these data raise the question of the existence of possible mixtures of TSE agents in these particular CH1641-like isolates.
please see full text ;
http://www.cdc.gov/eid/content/17/1/55.htm
Sunday, December 12, 2010
EFSA reviews BSE/TSE infectivity in small ruminant tissues News Story 2 December 2010
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One of these isolates (TR316211) behaved like the CH1641 isolate, with PrPres features in mice similar to those in the sheep brain. From two other isolates (O100 and O104), two distinct PrPres phenotypes were identified in mouse brains, with either high (h-type) or low (l-type) apparent molecular masses of unglycosylated PrPres, the latter being similar to that observed with CH1641, TR316211, or BSE. Both phenotypes could be found in variable proportions in the brains of the individual mice. In contrast with BSE, l-type PrPres from "CH1641-like" isolates showed lower levels of diglycosylated PrPres. From one of these cases (O104), a second passage in mice was performed for two mice with distinct PrPres profiles. This showed a partial selection of the l-type phenotype in mice infected with a mouse brain with predominant l-type PrPres, and it was accompanied by a significant increase in the proportions of the diglycosylated band. These results are discussed in relation to the diversity of scrapie and BSE strains.
http://jvi.asm.org/cgi/content/full/81/13/7230?view=long&pmid=17442721
In the US, scrapie is reported primarily in sheep homozygous for 136A/171Q (AAQQ) and the disease phenotype is similar to that seen with experimental strain CH1641.
http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=182469
4.2.9 A further hypothesis to explain the occurrence of BSE is the emergence or selection of a strain or strains of the scrapie agent pathogenic for cattle. Mutations of the scrapie agent. which can occur after a single passage in mice. have been well documented (9). This phenomenon cannot be dismissed for BSE. but given the form of the epidemic and the geographically widespread occurrence of BSE, such a hypothesis" would require the emergence of a mutant scrapie strain simultaneously in a large . number of sheep flocks, or cattle. throughout the country. Also. if it resulted "from a localised chance transmission of the scrapie strain from sheep to cattle giving rise , . to a mutant. a different pattern of disease would have been expected: its range would '. have increased with time. Thus the evidence from Britain is against the disease being due to a new strain of the agent, but we note that in the United States from 1984 to 1988 outbreaks of scrapie in sheep flocks are reported to have Increased markedly. now being nearly 3 times as high as during any previous period (18).
http://collections.europarchive.org/tna/20080102132706/http://www.bseinquiry.gov.uk/files/ib/ibd1/tab02.pdf
If the scrapie agent is generated from ovine DNA and thence causes disease in other species, then perhaps, bearing in mind the possible role of scrapie in CJD of humans (Davinpour et al, 1985), scrapie and not BSE should be the notifiable disease. ...
http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1988/06/08004001.pdf
http://scrapie-usa.blogspot.com/2007/12/scrapie-hb-parry-seriously-yb886841.html
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. ........
http://web.archive.org/web/20010305222246/www.bseinquiry.gov.uk/files/yb/1994/02/07002001.pdf
RISK OF BSE TO SHEEP VIA FEED
http://collections.europarchive.org/tna/20090114022605/http://www.bseinquiry.gov.uk/files/sc/seac31/tab01.pdf
Marion Simmons communicated surprising evidence for oral transmissibility of Nor98/atypical scrapie in neonatal sheep and although bioassay is ongoing, infectivity of the distal ileum of 12 and 24 month infected sheep is positive in Tg338 mice.
http://www.goatbse.eu/site/index.php?option=com_content&view=article&id=94:minutes-workshop-2010&catid=9:popular&Itemid=22
SUMMARY REPORTS OF MAFF BSE TRANSMISSION STUDIES AT THE CVL ;
http://collections.europarchive.org/tna/20090114023010/http://www.bseinquiry.gov.uk/files/sc/seac18/tab02b.pdf
THE RISK TO HUMANS FROM SHEEP;
http://collections.europarchive.org/tna/20090114022915/http://www.bseinquiry.gov.uk/files/sc/seac24/tab03.pdf
EXPERIMENTAL TRANSMISSION OF BSE TO SHEEP
http://collections.europarchive.org/tna/20090114023211/http://www.bseinquiry.gov.uk/files/sc/seac25/tab05.pdf
SHEEP AND BSE
PERSONAL AND CONFIDENTIAL
SHEEP AND BSE
A. The experimental transmission of BSE to sheep.
Studies have shown that the ''negative'' line NPU flock of Cheviots can be experimentally infected with BSE by intracerebral (ic) or oral challenge (the latter being equivalent to 0.5 gram of a pool of four cow brains from animals confirmed to have BSE).
http://collections.europarchive.org/tna/20090506010048/http://www.bseinquiry.gov.uk/files/sc/seac33/tab02.pdf
RB264
BSE - TRANSMISSION STUDIES
http://collections.europarchive.org/tna/20090113230127/http://www.bseinquiry.gov.uk/files/sc/Seac06/tab06.pdf
1: J Infect Dis 1980 Aug;142(2):205-8
Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.
Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.
Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.
snip...
The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.
PMID: 6997404
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract
12/10/76 AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE Office Note CHAIRMAN: PROFESSOR PETER WILDY
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A The Present Position with respect to Scrapie A] The Problem Scrapie is a natural disease of sheep and goats. It is a slow and inexorably progressive degenerative disorder of the nervous system and it ia fatal. It is enzootic in the United Kingdom but not in all countries. The field problem has been reviewed by a MAFF working group (ARC 35/77). It is difficult to assess the incidence in Britain for a variety of reasons but the disease causes serious financial loss; it is estimated that it cost Swaledale breeders alone $l.7 M during the five years 1971-1975. A further inestimable loss arises from the closure of certain export markets, in particular those of the United States, to British sheep. It is clear that scrapie in sheep is important commercially and for that reason alone effective measures to control it should be devised as quickly as possible. Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates.
One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias" Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.
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76/10.12/4.6
http://web.archive.org/web/20010305223125/www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf
Nature. 1972 Mar 10;236(5341):73-4.
Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).
Gibbs CJ Jr, Gajdusek DC. Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0
Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)
C. J. GIBBS jun. & D. C. GAJDUSEK National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland
SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey (Macaca fascicularis) with an incubation period of more than 5 yr from the time of intracerebral inoculation of scrapie-infected mouse brain. The animal developed a chronic central nervous system degeneration, with ataxia, tremor and myoclonus with associated severe scrapie-like pathology of intensive astroglial hypertrophy and proliferation, neuronal vacuolation and status spongiosus of grey matter. The strain of scrapie virus used was the eighth passage in Swiss mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton, Berkshire).
http://www.nature.com/nature/journal/v236/n5341/abs/236073a0.html
Epidemiology of Scrapie in the United States 1977
http://web.archive.org/web/20030513212324/http://www.bseinquiry.gov.uk/files/mb/m08b/tab64.pdf
Sunday, April 18, 2010
SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010
http://scrapie-usa.blogspot.com/2010/04/scrapie-and-atypical-scrapie.html
One of these isolates (TR316211) behaved like the CH1641 isolate, with PrPres features in mice similar to those in the sheep brain. From two other isolates (O100 and O104), two distinct PrPres phenotypes were identified in mouse brains, with either high (h-type) or low (l-type) apparent molecular masses of unglycosylated PrPres, the latter being similar to that observed with CH1641, TR316211, or BSE. Both phenotypes could be found in variable proportions in the brains of the individual mice. In contrast with BSE, l-type PrPres from "CH1641-like" isolates showed lower levels of diglycosylated PrPres. From one of these cases (O104), a second passage in mice was performed for two mice with distinct PrPres profiles. This showed a partial selection of the l-type phenotype in mice infected with a mouse brain with predominant l-type PrPres, and it was accompanied by a significant increase in the proportions of the diglycosylated band. These results are discussed in relation to the diversity of scrapie and BSE strains.
http://jvi.asm.org/cgi/content/full/81/13/7230?view=long&pmid=17442721
In the US, scrapie is reported primarily in sheep homozygous for 136A/171Q (AAQQ) and the disease phenotype is similar to that seen with experimental strain CH1641.
http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=182469
snip...
please see full text ;
Sunday, December 12, 2010
EFSA reviews BSE/TSE infectivity in small ruminant tissues News Story 2 December 2010
http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/efsa-reviews-bsetse-infectivity-in.html
Monday, November 22, 2010
Atypical transmissible spongiform encephalopathies in ruminants: a challenge for disease surveillance and control
REVIEW ARTICLES
http://transmissiblespongiformencephalopathy.blogspot.com/2010/11/atypical-transmissible-spongiform.html
Thursday, November 18, 2010
Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy following passage in sheep
http://bse-atypical.blogspot.com/2010/11/increased-susceptibility-of-human-prp.html
Saturday, December 18, 2010
OIE Global Conference on Wildlife Animal Health and Biodiversity - Preparing for the Future (TSE AND PRIONS) Paris (France), 23-25 February 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/oie-global-conference-on-wildlife.html
Scrapie
The two Commissions discussed the issue of ‘atypical’ scrapie in terms of notification requirements and the issue of the host genetic resistance. In response to questions of Members, the Code Commission clarified that ‘classical’ scrapie is reportable to the OIE but that ‘atypical’ scrapie is not reportable (in accordance with the recommendations made by the ad hoc Group on Atypical Scrapie and Atypical BSE, which met in November 2007). However, the sharing of scientific information on ‘atypical’ scrapie is encouraged. At this time, the Code Commission considered that more scientific information would be needed to fully address the issues associated with host genotype.
EU comment
4
OIE Terrestrial Animal Health Standards Commission / September 2010
The EU takes note of the fact that atypical scrapie is not an OIE listed disease. Nevertheless, it will remain notifiable in the EU. Moreover it must be stressed that any emergence of this disease should be notified to the OIE by Members and that scientific data should continue to be gathered.
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Zoonotic Potential
Has transmission to humans been proven? (with the exception of artificial
circumstances) AND
Is human infection associated with severe consequences? (death or prolonged illness)
http://ec.europa.eu/food/international/organisations/docs/EU_comments_OIE_terrestrial_animal_health_code_en.pdf
Tuesday, November 02, 2010
BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only) diagnostic criteria CVL 1992
http://bse-atypical.blogspot.com/2010/11/bse-atypical-lesion-distribution-rbse.html
Friday, August 29, 2008
A C-Terminal Protease-Resistant Prion Fragment Distinguishes Ovine "CH1641-Like" Scrapie from Bovine Classical and L-Type BSE in Ovine Transgenic Mice
http://bse-atypical.blogspot.com/2008/08/c-terminal-protease-resistant-prion.html
Seven main threats for the future linked to prions
The NeuroPrion network has identified 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.
http://www.neuroprion.org/en/np-neuroprion.html
Thursday, August 12, 2010
Seven main threats for the future linked to prions
http://prionpathy.blogspot.com/2010/08/seven-main-threats-for-future-linked-to.html
http://prionpathy.blogspot.com/
AS implied in the Inset 25 we must not _ASSUME_ that transmission of BSE to other species will invariably present pathology typical of a scrapie-like disease.
snip...
http://collections.europarchive.org/tna/20080102185948/http://www.bseinquiry.gov.uk/files/yb/1991/01/04004001.pdf
TSS
Research
Molecular Typing of Protease-Resistant Prion Protein in Transmissible Spongiform Encephalopathies of Small Ruminants, France, 2002–2009
Johann Vulin, Anne-Gaëlle Biacabe, Géraldine Cazeau, Didier Calavas, and Thierry Baron Author affiliation: Agence Nationale de Sécurité Sanitaire, Lyon, France
Suggested citation for this article
Abstract The agent that causes bovine spongiform encephalopathy (BSE) may be infecting small ruminants, which could have serious implications for human health. To distinguish BSE from scrapie and to examine the molecular characteristics of the protease-resistant prion protein (PrPres), we used a specifically designed Western blot method to test isolates from 648 sheep and 53 goats. During 2002–2009, classical non-Nor98 transmissible spongiform encephalopathy had been confirmed among ˜1.7 million small ruminants in France. Five sheep and 2 goats that showed a PrPres pattern consistent with BSE, or with the CH1641 experimental scrapie source, were identified. Later, bioassays confirmed infection by the BSE agent in 1 of the 2 goats. Western blot testing of the 6 other isolates showed an additional C-terminally cleaved PrPres product, with an unglycosylated band at ˜14 kDa, similar to that found in the CH1641 experimental scrapie isolate and different from the BSE isolate.
snip...
Discussion We investigated the PrPres molecular features of one of the largest series of natural TSE isolates from sheep and goats analyzed so far in Europe. Approximately 1.7 million small ruminants were subjected to a rapid test; among these, 1,153 sheep and 78 goats originating from 992 flocks were confirmed as TSE-positive on the basis of identification of PrPres in the brain stem. Another large study using 1,247 sheep originating from 450 flocks in Great Britain has been reported (24). Similar studies have been conducted in other European countries such as Germany (34), the Netherlands (14), and Italy (23), but fewer TSE-positive animals were reported. In our series, animals with classical cases represented 53% of the TSE-affected animals.
The molecular features of most of these isolates (99%) were comparable to those previously described for most scrapie cases, in studies in Europe or France (21). In all of these cases, PrPres from sheep and goats showed clearly distinct features from BSE, based on the identification of a higher molecular mass of unglycosylated PrPres, associated with strong labeling by the P4 antibody that recognizes the N terminal end of the protein. However, our observation of large individual variations in this PrPres molecular mass implies that a possible relationship with the biologic diversity of TSE agents, which has been described after transmission of scrapie to inbred wild-type mice (35), would be questionable. Only a few animals (5 sheep and 2 goats) in this large series of TSE-affected animals showed molecular characteristics that, in comparison with the usual features of scrapie, could be consistent with the known BSE signature in small ruminants. These samples represented all the suspected isolates that were identified by official surveillance in France during 2002–2009.
An essential molecular criterion defined from the observation of PrPres BSE compared with scrapie was the low molecular mass of the unglycosylated band in PrPres BSE, associated with a decreased PrPres signal lower with an N terminal antibody than with a core antibody (13,22,36). After identification of these molecular features in a few small ruminants, only 1 (CH636) of the 2 cases here described in goats, identified as TSE positive in 2002, has been shown to be infected by the BSE agent after bioassays in mice (37). Another goat in the United Kingdom identified by an immunohistochemical discriminatory method as TSE-positive in 1990 showed characteristics that were indistinguishable from BSE (18). These results clearly indicate that in a situation characterized by a decrease in the number of cases in cattle in all countries in Europe, the possibility of finding BSE in small ruminants is now remote.
The other unusual isolates showed molecular characteristics that were partly similar, not only to BSE in small ruminants with a low molecular mass of PrPres and faint labeling with P4 antibody, but also to the CH1641 experimental scrapie isolate. However, detailed immunohistochemical investigations of CH1641 showed subtle differences in the cleavage site of the protein compared with BSE in sheep (38). As previously described, after transmission in ovine transgenic mice (17), the slightly lower PrPres molecular mass in CH1641-like isolates, as recognized in the CH1641 experimental isolate (13) was confirmed by Western blot, at least in sheep (Figure 2, panel B). However, these differences in molecular mass are more easily identified on the diglycosylated band. Compared with BSE in small ruminants, lower proportions of this diglycosylated band were found in sheep, whereas the 08-357 goat sample showed very high levels of this diglycosylated band, which would be consistent with BSE. Experimental transmissions of BSE in sheep have shown that, to a certain extent, the PrPres molecular features could be influenced by different factors, such as serial passages in sheep (39) or sheep genotypes (36), although slight variability did not compromise the discrimination with scrapie. Furthermore, all these CH1641-like natural isolates in sheep and goats clearly differed from BSE by the presence of an additional, C-terminally cleaved, PrPres product specifically recognized by a C-terminal antibody (SAF84), as previously described for the CH1641 experimental scrapie isolate (17). Baron et al. described bioassays of 3 of 20 CH1641-like sheep isolates (17), which are also being conducted for the other isolates.
These 6 CH1641-like isolates were identified among 1,153 sheep and 78 goats with confirmed TSE, and the goat case represents, to our knowledge, a spreading of the known species range for natural CH1641 infection. At least in sheep, for which 4.34 cases per million sheep tested were identified in this study, the frequency of CH1641-like scrapie was notably higher compared with other rare TSEs in ruminants such as atypical BSEs, which showed a frequency of 0.76 per million cattle tested during 2001–2007 (40). Thus, large-scale testing of animals would be required to identify these rare TSE isolates. Similar isolates were only identified in sheep in the other large series reported from 450 flocks in Great Britain (2 cases in 1 flock) (23) and in a previous study of 214 TSE-infected sheep in France (2 cases in 1 flock) (27). However, an underestimation of the frequency of such cases cannot be fully excluded. PrPres features are assessed by analyzing a single homogenate prepared from a brain fragment from the animal. Stack et al. described a case in sheep that appeared as CH1641-like after repeated Western blot analysis of a brain stem sample, whereas previous analysis of the caudal medulla at the time of submission had shown the usual scrapie profile (24). Immunohistochemical testing of 2 CH1641-like cases in sheep showed, that unlike BSE, PrPd could be clearly identified by using P4 antibody in some of the brain stem nuclei and in lymphoid tissues (27). Finally, on the basis of identification of low levels of C-terminal PrPres product in ovine transgenic mice infected with usual scrapie isolates, we hypothesized that a CH1641-like component might be present as a minor component in these scrapie cases that showed usual molecular features (17). All these data raise the question of the existence of possible mixtures of TSE agents in these particular CH1641-like isolates.
please see full text ;
http://www.cdc.gov/eid/content/17/1/55.htm
Sunday, December 12, 2010
EFSA reviews BSE/TSE infectivity in small ruminant tissues News Story 2 December 2010
snip...
One of these isolates (TR316211) behaved like the CH1641 isolate, with PrPres features in mice similar to those in the sheep brain. From two other isolates (O100 and O104), two distinct PrPres phenotypes were identified in mouse brains, with either high (h-type) or low (l-type) apparent molecular masses of unglycosylated PrPres, the latter being similar to that observed with CH1641, TR316211, or BSE. Both phenotypes could be found in variable proportions in the brains of the individual mice. In contrast with BSE, l-type PrPres from "CH1641-like" isolates showed lower levels of diglycosylated PrPres. From one of these cases (O104), a second passage in mice was performed for two mice with distinct PrPres profiles. This showed a partial selection of the l-type phenotype in mice infected with a mouse brain with predominant l-type PrPres, and it was accompanied by a significant increase in the proportions of the diglycosylated band. These results are discussed in relation to the diversity of scrapie and BSE strains.
http://jvi.asm.org/cgi/content/full/81/13/7230?view=long&pmid=17442721
In the US, scrapie is reported primarily in sheep homozygous for 136A/171Q (AAQQ) and the disease phenotype is similar to that seen with experimental strain CH1641.
http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=182469
4.2.9 A further hypothesis to explain the occurrence of BSE is the emergence or selection of a strain or strains of the scrapie agent pathogenic for cattle. Mutations of the scrapie agent. which can occur after a single passage in mice. have been well documented (9). This phenomenon cannot be dismissed for BSE. but given the form of the epidemic and the geographically widespread occurrence of BSE, such a hypothesis" would require the emergence of a mutant scrapie strain simultaneously in a large . number of sheep flocks, or cattle. throughout the country. Also. if it resulted "from a localised chance transmission of the scrapie strain from sheep to cattle giving rise , . to a mutant. a different pattern of disease would have been expected: its range would '. have increased with time. Thus the evidence from Britain is against the disease being due to a new strain of the agent, but we note that in the United States from 1984 to 1988 outbreaks of scrapie in sheep flocks are reported to have Increased markedly. now being nearly 3 times as high as during any previous period (18).
http://collections.europarchive.org/tna/20080102132706/http://www.bseinquiry.gov.uk/files/ib/ibd1/tab02.pdf
If the scrapie agent is generated from ovine DNA and thence causes disease in other species, then perhaps, bearing in mind the possible role of scrapie in CJD of humans (Davinpour et al, 1985), scrapie and not BSE should be the notifiable disease. ...
http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/yb/1988/06/08004001.pdf
http://scrapie-usa.blogspot.com/2007/12/scrapie-hb-parry-seriously-yb886841.html
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. ........
http://web.archive.org/web/20010305222246/www.bseinquiry.gov.uk/files/yb/1994/02/07002001.pdf
RISK OF BSE TO SHEEP VIA FEED
http://collections.europarchive.org/tna/20090114022605/http://www.bseinquiry.gov.uk/files/sc/seac31/tab01.pdf
Marion Simmons communicated surprising evidence for oral transmissibility of Nor98/atypical scrapie in neonatal sheep and although bioassay is ongoing, infectivity of the distal ileum of 12 and 24 month infected sheep is positive in Tg338 mice.
http://www.goatbse.eu/site/index.php?option=com_content&view=article&id=94:minutes-workshop-2010&catid=9:popular&Itemid=22
SUMMARY REPORTS OF MAFF BSE TRANSMISSION STUDIES AT THE CVL ;
http://collections.europarchive.org/tna/20090114023010/http://www.bseinquiry.gov.uk/files/sc/seac18/tab02b.pdf
THE RISK TO HUMANS FROM SHEEP;
http://collections.europarchive.org/tna/20090114022915/http://www.bseinquiry.gov.uk/files/sc/seac24/tab03.pdf
EXPERIMENTAL TRANSMISSION OF BSE TO SHEEP
http://collections.europarchive.org/tna/20090114023211/http://www.bseinquiry.gov.uk/files/sc/seac25/tab05.pdf
SHEEP AND BSE
PERSONAL AND CONFIDENTIAL
SHEEP AND BSE
A. The experimental transmission of BSE to sheep.
Studies have shown that the ''negative'' line NPU flock of Cheviots can be experimentally infected with BSE by intracerebral (ic) or oral challenge (the latter being equivalent to 0.5 gram of a pool of four cow brains from animals confirmed to have BSE).
http://collections.europarchive.org/tna/20090506010048/http://www.bseinquiry.gov.uk/files/sc/seac33/tab02.pdf
RB264
BSE - TRANSMISSION STUDIES
http://collections.europarchive.org/tna/20090113230127/http://www.bseinquiry.gov.uk/files/sc/Seac06/tab06.pdf
1: J Infect Dis 1980 Aug;142(2):205-8
Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.
Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.
Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.
snip...
The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.
PMID: 6997404
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract
12/10/76 AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE Office Note CHAIRMAN: PROFESSOR PETER WILDY
snip...
A The Present Position with respect to Scrapie A] The Problem Scrapie is a natural disease of sheep and goats. It is a slow and inexorably progressive degenerative disorder of the nervous system and it ia fatal. It is enzootic in the United Kingdom but not in all countries. The field problem has been reviewed by a MAFF working group (ARC 35/77). It is difficult to assess the incidence in Britain for a variety of reasons but the disease causes serious financial loss; it is estimated that it cost Swaledale breeders alone $l.7 M during the five years 1971-1975. A further inestimable loss arises from the closure of certain export markets, in particular those of the United States, to British sheep. It is clear that scrapie in sheep is important commercially and for that reason alone effective measures to control it should be devised as quickly as possible. Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates.
One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias" Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.
snip...
76/10.12/4.6
http://web.archive.org/web/20010305223125/www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf
Nature. 1972 Mar 10;236(5341):73-4.
Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).
Gibbs CJ Jr, Gajdusek DC. Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0
Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)
C. J. GIBBS jun. & D. C. GAJDUSEK National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland
SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey (Macaca fascicularis) with an incubation period of more than 5 yr from the time of intracerebral inoculation of scrapie-infected mouse brain. The animal developed a chronic central nervous system degeneration, with ataxia, tremor and myoclonus with associated severe scrapie-like pathology of intensive astroglial hypertrophy and proliferation, neuronal vacuolation and status spongiosus of grey matter. The strain of scrapie virus used was the eighth passage in Swiss mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton, Berkshire).
http://www.nature.com/nature/journal/v236/n5341/abs/236073a0.html
Epidemiology of Scrapie in the United States 1977
http://web.archive.org/web/20030513212324/http://www.bseinquiry.gov.uk/files/mb/m08b/tab64.pdf
Sunday, April 18, 2010
SCRAPIE AND ATYPICAL SCRAPIE TRANSMISSION STUDIES A REVIEW 2010
http://scrapie-usa.blogspot.com/2010/04/scrapie-and-atypical-scrapie.html
One of these isolates (TR316211) behaved like the CH1641 isolate, with PrPres features in mice similar to those in the sheep brain. From two other isolates (O100 and O104), two distinct PrPres phenotypes were identified in mouse brains, with either high (h-type) or low (l-type) apparent molecular masses of unglycosylated PrPres, the latter being similar to that observed with CH1641, TR316211, or BSE. Both phenotypes could be found in variable proportions in the brains of the individual mice. In contrast with BSE, l-type PrPres from "CH1641-like" isolates showed lower levels of diglycosylated PrPres. From one of these cases (O104), a second passage in mice was performed for two mice with distinct PrPres profiles. This showed a partial selection of the l-type phenotype in mice infected with a mouse brain with predominant l-type PrPres, and it was accompanied by a significant increase in the proportions of the diglycosylated band. These results are discussed in relation to the diversity of scrapie and BSE strains.
http://jvi.asm.org/cgi/content/full/81/13/7230?view=long&pmid=17442721
In the US, scrapie is reported primarily in sheep homozygous for 136A/171Q (AAQQ) and the disease phenotype is similar to that seen with experimental strain CH1641.
http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=182469
snip...
please see full text ;
Sunday, December 12, 2010
EFSA reviews BSE/TSE infectivity in small ruminant tissues News Story 2 December 2010
http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/efsa-reviews-bsetse-infectivity-in.html
Monday, November 22, 2010
Atypical transmissible spongiform encephalopathies in ruminants: a challenge for disease surveillance and control
REVIEW ARTICLES
http://transmissiblespongiformencephalopathy.blogspot.com/2010/11/atypical-transmissible-spongiform.html
Thursday, November 18, 2010
Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy following passage in sheep
http://bse-atypical.blogspot.com/2010/11/increased-susceptibility-of-human-prp.html
Saturday, December 18, 2010
OIE Global Conference on Wildlife Animal Health and Biodiversity - Preparing for the Future (TSE AND PRIONS) Paris (France), 23-25 February 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/oie-global-conference-on-wildlife.html
Scrapie
The two Commissions discussed the issue of ‘atypical’ scrapie in terms of notification requirements and the issue of the host genetic resistance. In response to questions of Members, the Code Commission clarified that ‘classical’ scrapie is reportable to the OIE but that ‘atypical’ scrapie is not reportable (in accordance with the recommendations made by the ad hoc Group on Atypical Scrapie and Atypical BSE, which met in November 2007). However, the sharing of scientific information on ‘atypical’ scrapie is encouraged. At this time, the Code Commission considered that more scientific information would be needed to fully address the issues associated with host genotype.
EU comment
4
OIE Terrestrial Animal Health Standards Commission / September 2010
The EU takes note of the fact that atypical scrapie is not an OIE listed disease. Nevertheless, it will remain notifiable in the EU. Moreover it must be stressed that any emergence of this disease should be notified to the OIE by Members and that scientific data should continue to be gathered.
snip...
Zoonotic Potential
Has transmission to humans been proven? (with the exception of artificial
circumstances) AND
Is human infection associated with severe consequences? (death or prolonged illness)
http://ec.europa.eu/food/international/organisations/docs/EU_comments_OIE_terrestrial_animal_health_code_en.pdf
Tuesday, November 02, 2010
BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only) diagnostic criteria CVL 1992
http://bse-atypical.blogspot.com/2010/11/bse-atypical-lesion-distribution-rbse.html
Friday, August 29, 2008
A C-Terminal Protease-Resistant Prion Fragment Distinguishes Ovine "CH1641-Like" Scrapie from Bovine Classical and L-Type BSE in Ovine Transgenic Mice
http://bse-atypical.blogspot.com/2008/08/c-terminal-protease-resistant-prion.html
Seven main threats for the future linked to prions
The NeuroPrion network has identified 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.
http://www.neuroprion.org/en/np-neuroprion.html
Thursday, August 12, 2010
Seven main threats for the future linked to prions
http://prionpathy.blogspot.com/2010/08/seven-main-threats-for-future-linked-to.html
http://prionpathy.blogspot.com/
AS implied in the Inset 25 we must not _ASSUME_ that transmission of BSE to other species will invariably present pathology typical of a scrapie-like disease.
snip...
http://collections.europarchive.org/tna/20080102185948/http://www.bseinquiry.gov.uk/files/yb/1991/01/04004001.pdf
TSS
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