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The contribution of different prion protein types and host polymorphisms to clinicopathological variations in Creutzfeldt–

Posted Mar 03 2012 10:46pm
Review



The contribution of different prion protein types and host polymorphisms to clinicopathological variations in Creutzfeldt–Jakob disease



Mark W. Head*, James W. Ironside Article first published online: 28 FEB 2012

DOI: 10.1002/rmv.725

Copyright © 2012 John Wiley & Sons, Ltd.





Head, M. W. and Ironside, J. W. (2012), The contribution of different prion protein types and host polymorphisms to clinicopathological variations in Creutzfeldt–Jakob disease. Rev. Med. Virol.. doi: 10.1002/rmv.725

Author Information

The National CJD Research & Surveillance Unit, School of Molecular & Clinical Medicine, University of Edinburgh, Edinburgh, UK

Email: Mark W. Head (m.w.head@ed.ac.uk)

*Dr M. W. Head, The National CJD Research & Surveillance Unit, Bryan Matthews Building, Western General Hospital, Edinburgh, EH4 2XU, UK. E-mail: m.w.head@ed.ac.uk



Publication History

Article first published online: 28 FEB 2012 Manuscript Revised: 21 OCT 2011 Manuscript Accepted: 21 OCT 2011 Manuscript Received: 22 AUG 2011



SUMMARY

Creutzfeldt–Jakob disease is a fatal neurodegenerative disease that primarily affects the central nervous system. In this respect, it can be considered alongside the more frequently occurring neurodegenerative diseases, such as Alzheimer's disease. Creutzfeldt–Jakob disease is perhaps the paradigmatic protein misfolding disorder, so comparisons between the mechanisms involved in Creutzfeldt–Jakob disease and other neurodegenerative diseases associated with protein misfolding (such as the tauopathies and synucleinopathies) may also be informative. Like many of these diseases, Creutzfeldt–Jakob disease occurs sporadically or can, more rarely, be associated with mutations. However, Creutzfeldt–Jakob disease can also be acquired and is experimentally transmissible. These properties have had profound public health implications and made the disease of interest to virologists, in addition to those interested in protein misfolding disorders and neurodegeneration. The possible causes for the pronounced phenotypic variation among different forms of Creutzfeldt–Jakob disease are beginning to become understood, and these appear to depend in large measure on the genetics of the host (specifically the sequence of the prion protein gene, PRNP) and the epigenetic aspects of the agent (thought to be a misfolded and aggregated form of the PRNP gene product, termed a prion). This review will examine whether this model in its present form has sufficient complexity and subtlety to account for the clinicopathological variation evident in Creutzfeldt–Jakob disease and will outline the ways in which a more complete and informative molecular definition of human prions are currently being sought. Copyright © 2012 John Wiley & Sons, Ltd.



http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1099-1654/homepage/Advertise.html






Monday, October 10, 2011


EFSA Journal 2011 The European Response to BSE: A Success Story

snip...

EFSA and the European Centre for Disease Prevention and Control (ECDC) recently delivered a scientific opinion on any possible epidemiological or molecular association between TSEs in animals and humans (EFSA Panel on Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical BSE prions as the only TSE agents demonstrated to be zoonotic so far but the possibility that a small proportion of human cases so far classified as "sporadic" CJD are of zoonotic origin could not be excluded. Moreover, transmission experiments to non-human primates suggest that some TSE agents in addition to Classical BSE prions in cattle (namely L-type Atypical BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic wasting disease (CWD) agents) might have zoonotic potential.

snip...



http://www.efsa.europa.eu/en/efsajournal/pub/e991.htm?emt=1





http://www.efsa.europa.eu/en/efsajournal/doc/e991.pdf






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



http://transmissiblespongiformencephalopathy.blogspot.com/2011/10/efsa-journal-2011-european-response-to.html







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






Atypical BSE in Cattle

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

In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.




http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2







When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.



http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2







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, February 5, 2012


February 2012 Update on Feed Enforcement Activities to Limit the Spread of BSE


http://transmissiblespongiformencephalopathy.blogspot.com/2012/02/february-2012-update-on-feed.html








Thursday, March 01, 2012


Variant Creutzfeldt-Jakob disease Fact sheet N°180 Revised February 2012 W.H.O.


http://vcjd.blogspot.com/2012/03/variant-creutzfeldt-jakob-disease-fact.html






Sunday, February 12, 2012


National Prion Disease Pathology Surveillance Center Cases Examined1 (August 19, 2011) including Texas




SNIP...




Monday, March 29, 2010

Irma Linda Andablo CJD Victim, she died at 38 years old on February 6, 2010 in Mesquite Texas


Irma Linda Andablo CJD Victim, she died at 38 years old on February 6, 2010 in Mesquite Texas.She left 6 Kids and a Husband.The Purpose of this web is to give information in Spanish to the Hispanic community, and to all the community who want's information about this terrible disease.-

Physician Discharge Summary, Parkland Hospital, Dallas Texas

Admit Date: 12/29/2009 Discharge Date: 1/20/2010 Attending Provider: Greenberg, Benjamin Morris; General Neurology Team: General Neurology Team

Linda was a Hispanic female with no past medical history presents with 14 months of incresing/progressive altered mental status, generalized weakness, inability to walk, loss of appetite, inability to speak, tremor and bowel/blader incontinence.She was, in her usual state of health up until February, 2009, when her husbans notes that she began forgetting things like names and short term memories. He also noticed mild/vague personality changes such as increased aggression. In March, she was involved in a hit and run MVA,although she was not injured. The police tracked her down and ticketed her. At that time, her son deployed to Iraq with the Army and her husband assumed her mentation changes were due to stress over these two events. Also in March, she began to have weakness in her legs, making it difficult to walk. Over the next few months, her mentation and personality changes worsened, getting to a point where she could no longer recognized her children. She was eating less and less. She was losing more weight. In the last 2-3 months, she reached the point where she could not walk without an assist, then 1 month ago, she stopped talking, only making grunting/aggressive sounds when anyone came near her. She also became both bowel and bladder incontinent, having to wear diapers. Her '"tremor'" and body jerks worsened and her hands assumed a sort of permanent grip position, leading her family to put tennis balls in her hands to protect her fingers.

The husband says that they have lived in Nebraska for the past 21 years. They had seen a doctor there during the summer time who prescribed her Seroquel and Lexapro, Thinking these were sx of a mood disorder. However, the medications did not help and she continued to deteriorate clinically. Up until about 6 years ago, the pt worked at Tyson foods where she worked on the assembly line, slaughtering cattle and preparing them for packaging. She was exposed to brain and spinal cord matter when she would euthanize the cattle. The husband says that he does not know any fellow workers with a similar illness. He also says that she did not have any preceeding illness or travel.


http://www.recordandoalinda.com/index.php?option=com_content&view=article&id=19:cjd-english-info&catid=9:cjd-ingles&Itemid=8







SNIP...




see full text and more here ;





Sunday, February 12, 2012



National Prion Disease Pathology Surveillance Center Cases Examined1 (August 19, 2011) including Texas




http://transmissiblespongiformencephalopathy.blogspot.com/2012/02/national-prion-disease-pathology.html








Saturday, June 13, 2009


Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States 2003 revisited 2009




http://cjdusa.blogspot.com/2009/06/monitoring-occurrence-of-emerging-forms.html







Sunday, August 09, 2009


CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009


http://creutzfeldt-jakob-disease.blogspot.com/2009/08/cjdstraight-talk-withjames.html






Tuesday, August 18, 2009



BSE-The Untold Story - joe gibbs and singeltary 1999 - 2009



http://madcowusda.blogspot.com/2009/08/bse-untold-story-joe-gibbs-and.html






re-Human Prion Diseases in the United States

Posted by flounder on 01 Jan 2010 at 18:11 GMT

I kindly disagree with your synopsis for the following reasons ;




http://www.plosone.org/annotation/listThread.action?inReplyTo=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd&root=info%3Adoi%2F10.1371%2Fannotation%2F04ce2b24-613d-46e6-9802-4131e2bfa6fd







Saturday, January 2, 2010


Human Prion Diseases in the United States January 1, 2010 ***FINAL***


http://prionunitusaupdate2008.blogspot.com/2010/01/human-prion-diseases-in-united-states.html





GOVERNMENT REMOVED MY SUBMISSION RECENTLY ;

Manuscript Draft Manuscript Number: Title: HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory Article Type: Personal View Corresponding Author: Mr. Terry S. Singeltary, Corresponding Author's Institution: na First Author: Terry S Singeltary, none Order of Authors: Terry S Singeltary, none; Terry S. Singeltary Abstract: TSEs have been rampant in the USA for decades in many species, and they all have been rendered and fed back to animals for human/animal consumption. 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 2007.



http://www.regulations.gov/fdmspublic/ContentViewer?objectId=090000648027c28e&disposition=attachment&contentType=pdf





http://cjdusa.blogspot.com/2009/06/monitoring-occurrence-of-emerging-forms.html






Owens, Julie

From: Terry S. Singeltary Sr. [flounder9@verizon.net]

Sent: Monday, July 24, 2006 1:09 PM To: FSIS RegulationsComments

Subject: [Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE) Page 1 of 98 8/3/2006


Greetings FSIS, I would kindly like to comment on the following ;


http://www.fsis.usda.gov/OPPDE/Comments/2006-0011/2006-0011-1.pdf




http://www.scribd.com/doc/1490709/USDA-200600111






Response to Public Comments on the Harvard Risk Assessment of Bovine Spongiform Encephalopathy Update, October 31, 2005


INTRODUCTION


The United States Department of Agriculture’s Food Safety and Inspection Service (FSIS) held a public meeting on July 25, 2006 in Washington, D.C. to present findings from the Harvard Risk Assessment of Bovine Spongiform Encephalopathy Update, October 31, 2005 (report and model located on the FSIS website: http://www.fsis.usda.gov/Science/Risk_Assessments/index.asp).


Comments on technical aspects of the risk assessment were then submitted to FSIS.


Comments were received from Food and Water Watch, Food Animal Concerns Trust (FACT), Farm Sanctuary, R-CALF USA, Linda A Detwiler, and Terry S. Singeltary.


This document provides itemized replies to the public comments received on the 2005 updated Harvard BSE risk assessment. Please bear the following points in mind:



http://www.fsis.usda.gov/PDF/BSE_Risk_Assess_Response_Public_Comments.pdf






Suppressed peer review of Harvard study October 31, 2002.


October 31, 2002 Review of the Evaluation of the Potential for Bovine Spongiform Encephalopathy in the United States Conducted by the Harvard Center for Risk Analysis, Harvard School of Public Health and Center for Computational Epidemiology, College of Veterinary Medicine, Tuskegee University Final Report Prepared for U.S. Department of Agriculture Food Safety and Inspection Service Office of Public Health and Science Prepared by RTI Health, Social, and Economics Research Research Triangle Park, NC 27709 RTI Project Number 07182.024



http://www.fsis.usda.gov/oa/topics/BSE_Peer_Review.pdf





Sunday, February 14, 2010


[Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of Bovine Spongiform Encephalopathy (BSE)



http://bseusa.blogspot.com/2010/02/docket-no-fsis-2006-0011-fsis-harvard.html






http://www.scribd.com/doc/1490059/USDA-03025IFA2






http://docket-aphis-2006-0041.blogspot.com/









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






Sunday, August 21, 2011


The British disease, or a disease gone global, The TSE Prion Disease


(see video here)


http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/british-disease-or-disease-gone-global.html





U.S.A. HIDING MAD COW DISEASE VICTIMS AS SPORADIC CJD ?


(see video at bottom)


http://creutzfeldt-jakob-disease.blogspot.com/2009/07/usa-hiding-mad-cow-disease-victims-as.html





Sunday, September 6, 2009


MAD COW USA 1997


(SEE SECRET VIDEO)


http://madcowusda.blogspot.com/2009/09/mad-cow-usa-1997-video.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









Tuesday, November 08, 2011

Can Mortality Data Provide Reliable Indicators for Creutzfeldt-Jakob Disease Surveillance? A Study in France from 2000 to 2008 Vol. 37, No. 3-4, 2011

Original Paper

Conclusions:These findings raise doubt about the possibility of a reliable CJD surveillance only based on mortality data.


http://creutzfeldt-jakob-disease.blogspot.com/2011/11/can-mortality-data-provide-reliable.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 ??

if not, why not...




Friday, November 30, 2007



CJD QUESTIONNAIRE USA CWRU AND CJD FOUNDATION



http://cjdquestionnaire.blogspot.com/2007/11/cjd-questionnaire.html







http://cjdquestionnaire.blogspot.com/








Terry S. Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis




http://www.youtube.com/watch?v=zf3lfz9NrT4





http://www.youtube.com/watch?v=c0tWkNvhO4g





http://www.youtube.com/watch?v=zf3lfz9NrT4&feature=results_main&playnext=1&list=PL780BE2AF0B62A944







full text with source references ;



http://transmissiblespongiformencephalopathy.blogspot.com/2011/08/terry-singeltary-sr-on-creutzfeldt.html








TSS




layperson




Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518
flounder9@verizon.net
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