Monday, October 12, 2009

SEAC Science and Technology Committee's investigation of research funding priorities on behalf of the Advisory Committee on Dangerous Pathogens TSE

8 October 2009

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House of Lords Science and Technology Committee

Setting science and technology research funding priorities Evidence from the UK Government’s Spongiform Encephalopathy Advisory Committees:

1. Advisory Committee on Dangerous Pathogens Transmissible Spongiform Encephalopathy Working Group (ACDP TSE WG),

2. CJD Incidents Panel,

3. Engineering and Science Advisory Committee into the decontamination of surgical instruments including Prion Removal (ESAC Pr)

4. Spongiform Encephalopathy Advisory Committee (SEAC)

1. The handling of transmissible spongiform encephalopathies (TSEs) has important lessons for the work that the House of Lords Science and Technology Committee intends to focus on, specifically:

• How decisions are made to fund research to meet societal needs

• The balance of funding for targeted versus unsolicited response-mode curiosity-driven research, and

• How research is commissioned in Government departments and agencies

2. The transmissible spongiform encephalopathies (TSEs), also known as prion diseases, are a group of fatal transmissible neurodegenerative disorders of man and animals, characterized by the “spongy” microscopic appearance of the brain in affected animals and by a link with a ubiquitous protein, the prion protein (PrP), a misfolded form of which is widely believed (though never unequivocally proved) to be the infectious agent or prion. The most widely known examples of these diseases are bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep and goats and Creutzfeldt-Jakob disease (CJD) in humans. BSE emerged in the UK in the 1980s, has been reported in many other countries and is responsible for the human disease, variant CJD (vCJD).

3. TSEs are thus a group of diseases that, in a short space of time, gave rise to significant health effects in animals and humans and resulted in massive economic loss. In identifying the solutions that were required, science and scientific research, both basic and applied, were critical. The recent history of the diseases and the research into them therefore merits careful consideration by the House of Lords Science and Technology Committee, as many of the specific aspects of that history are relevant to the general principles that the Committee is looking into.

4. SEAC is the government’s overarching committee for advising on the science of TSEs and thereby assessing risk to the public. ACDP TSE WG, CJDIP and ESAC Pr are in their different ways involved in developing practical advice to reduce the spread of TSEs (risk management), most notably spread of CJD/vCJD from person to person via contaminated surgical instruments or via blood transfusion.

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What is the overall objective of publicly-funded science and technology research?

5. The overall objective of publicly-funded science and technology research, the public good, has to be considered in a broader and longer term context than that of policy, as the latter is often understood within government. This policy, in practice, is, inevitably, strongly influenced by electoral and media cycles whereas effective scientific policy has to be constructed around a much longer term administrative cycle. This is particularly aptly illustrated by TSEs, in which the slow progression of the diseases can make developing reliable answers to scientific questions, necessarily, a long term undertaking.

6. Publicly funded TSE research in the UK was stimulated by substantial public funding in the late 1980s/ early 1990s, initially in response to the threat that the emerging BSE epidemic in cattle posed to animal health and later following the recognition, in 1996, that BSE was linked to vCJD and posed a public health risk.. The need to limit the damage to health and wellbeing from BSE gave rise to a number of intensely practical questions such as the nature of the infection and the infectious agent, the distribution of the agent in different animal species and whether barriers to transmission existed between certain species. These questions could not be answered without an investment in basic science. Equally some of the key techniques for characterising the diseases, such as biological and molecular strain typing of the responsible agents had been developed in the 1970s and 1980s to distinguish different isolates of scrapie. This latter work had taken place at a time when the policy community put so little emphasis on TSEs that these developments were seen, at the time, as of little practical application. How are science and technology research priorities co-ordinated across government and between government and the relevant funding organizations? Who is responsible for ensuring that research gaps are filled?

7. Balancing curiosity driven research with research driven by departmental and policy needs requires that both research councils and the departments themselves are in a position to commission meaningful research and that this research can be effectively co-ordinated.

8. The model by which research funding priorities has been co-ordinated between government departments and the research councils has been the TSE Joint Funders Advisory Group which has been sufficiently successful to be emulated for novel H1N1 influenza A virus (“swine flu”) research. However, the decline of the BSE and vCJD epidemics has led to a recent disinvestment in the field. This is premature. Those of us who are members of the three risk-management committees, particularly, are aware of questions that, if answered, would facilitate disease control, by allowing potentially the relaxation of certain expensive contemporary control measures as well as those answers having implications for other more widespread diseases. There are equally other widespread TSEs such as Chronic Wasting Disease (CWD) of mule deer and elk in the United States and Canada that may yet show the potential to infect man, as well as newly identified TSEs such as bovine amyloid spongiform encephalopathy (BASE), and atypical scrapie, whose potential to be a human

3

health problem is not yet fully understood. In humans there is a recently discovered ‘new’ TSE called protease sensitive prionopathy (PSP), the significance of which is, as yet, unclear.

9. More specific examples of unanswered questions with health implications are:

• Will the eventual elimination of classical scrapie in the EU leave an ecological niche for other TSEs such as BSE or atypical scrapie?

• Is CWD transmissible to humans?

• Can a reliable ante mortem diagnostic blood test for vCJD be developed?

• What is the true prevalence of v CJD infection (as opposed to overt disease) in the UK?

• Are some commoner types of neurodegenerative disease (including Alzheimer's disease and Parkinson's disease) also transmissible? Some recent scientific research has suggested this possibility

• Could cases of protease sensitive prionopathy (PSP) be missed by conventional tests which, in all other TSEs, rely on the resistance of the prion protein in the nervous system that accompanies disease to digestion by protease enzymes?

• Can we develop reliable methods for removing and detecting protein on re-usable surgical instruments?

10. These are frequently highly practical questions impacting on very expensive policy options but needing to be informed by scientific work that may more appropriately be described as basic rather than applied. The cost of funding such work could well be trivial compared to the precautionary measures that are currently being put in place to mitigate such possible but unproven risks. To what extent should publicly-funded science and technology research be focussed on areas of potential economic importance? How should these areas be identified?

11. We would argue that the evaluation of the economic importance of science and technology research needs to be based on a model that is sufficiently sophisticated to acknowledge adequately longer term economic benefit. For example, DEFRA have developed a prioritization tool which ranks animal diseases according to a number of variables – for example impact on public health, animal welfare, international trade and wider society.

12. Thus any method for evaluating the economic importance of research should be able to recognize that TSE research in the UK remains a vibrant field in which there are a number of young researchers making real progress with implications for a variety of diseases and disease processes. The TSEs themselves retain the capacity to surprise and although BSE and vCJD appear to be declining, other

4

health questions that give rise to circumstances that lead to human illness, economic loss and political embarrassment, seem likely. Further, we have now also arrived at the point where a research infrastructure (laboratories, animal facilities, cell lines, animal lines, reagents, trained personnel) with strong international links within the European Union and to Japan and North America, has been established in the UK that can allow complicated questions to be answered efficiently. There would be a considerable opportunity cost to losing this resource.

24 September 2009

The Secretariat on behalf of:

• Advisory Committee on Dangerous Pathogens Transmissible Spongiform Encephalopathy Working Group (ACDP TSE WG),

• CJD Incidents Panel,

• Engineering and Science Advisory Committee into the decontamination of surgical instruments including Prion Removal (ESAC Pr)

• Spongiform Encephalopathy Advisory Committee (SEAC)


http://www.seac.gov.uk/pdf/hol-response091008.pdf




Sunday, May 17, 2009

WHO WILL WATCH THE CHILDREN ? SCHOOL LUNCH PROGRAM FROM DOWNER CATTLE UPDATE


http://downercattle.blogspot.com/2009/05/who-will-watch-children.html




http://downercattle.blogspot.com/




Sunday, September 6, 2009

MAD COW USA 1997 SECRET VIDEO


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




DAMNING TESTIMONY FROM STANLEY PRUSINER THE NOBEL PEACE PRIZE WINNER ON PRIONS SPEAKING ABOUT ANN VENEMAN
SEE VIDEO


http://maddeer.org/video/embedded/prusinerclip.html





2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006


http://bse-atypical.blogspot.com/2006/08/bse-atypical-texas-and-alabama-update.html




http://creutzfeldt-jakob-disease.blogspot.com/2009/08/characteristics-of-established-and.html




Office of Inspector General Semiannual Report to Congress FY 2007 - 2nd Half

Two Texas Companies Sentenced and Fined for Misbranding Meat Products In April 2007, two closely held and related Texas companies pled guilty in Federal court and were sentenced to 12 months of probation and ordered to pay $10,250 in fines for misbranding meat products. One of the companies sold adulterated meat products to a retail store in New Mexico. Additionally, portions of the invoices failed to properly and consistently identify the meat products as being from cattle more than 30 months old at time of slaughter. This information is required to be disclosed because of bovine spongiform encephalopathy (BSE, or "mad cow disease") concerns. No adulterated meat reached consumers.


http://www.usda.gov/oig/webdocs/sarc071212.pdf




Tuesday, July 14, 2009

U.S. Emergency Bovine Spongiform Encephalopathy Response Plan Summary and BSE Red Book Date: February 14, 2000 at 8:56 am PST

WHERE did we go wrong $$$


http://madcowtesting.blogspot.com/2009/07/us-emergency-bovine-spongiform.html




Sunday, December 28, 2008

MAD COW DISEASE USA DECEMBER 28, 2008 an 8 year review of a failed and flawed policy


http://bse-atypical.blogspot.com/2008/12/mad-cow-disease-usa-december-28-2008-8.html




Wednesday, August 20, 2008

Bovine Spongiform Encephalopathy Mad Cow Disease typical and atypical strains, was there a cover-up ? August 20, 2008


http://bse-atypical.blogspot.com/2008/08/bovine-spongiform-encephalopathy-mad.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




Tuesday, August 11, 2009

Characteristics of Established and Proposed Sporadic Creutzfeldt-Jakob Disease Variants

Brian S. Appleby, MD; Kristin K. Appleby, MD; Barbara J. Crain, MD, PhD; Chiadi U. Onyike, MD, MHS; Mitchell T. Wallin, MD, MPH; Peter V. Rabins, MD, MPH

Background: The classic Creutzfeldt-Jakob disease (CJD), Heidenhain, and Oppenheimer-Brownell variants are sporadic CJD (sCJD) phenotypes frequently described in the literature, but many cases present with neuropsychiatric symptoms, suggesting that there may be additional sCJD phenotypes.

Objective: To characterize clinical, diagnostic, and molecular features of 5 sCJD variants.

Design: Retrospective analysis.

Setting: The Johns Hopkins and Veterans Administration health care systems.

Participants: Eighty-eight patients with definite or probable sCJD.

Main Outcome Measures: Differences in age at onset, illness progression, diagnostic test results, and molecular subtype.

Results: The age at onset differed among sCJD variants (P=.03); the affective variant had the youngest mean age at onset (59.7 years). Survival time (P.001) and the time to clinical presentation (P=.003) differed among groups. Patients with the classic CJD phenotype had the shortest median survival time from symptom onset (66 days) and those who met criteria for the affective sCJD variant had the longest (421 days) and presented to clinicians significantly later (median time from onset to presentation, 92 days; P=.004). Cerebrospinal fluid analyses were positive for 14-3-3 protein in all of the affective variants, regardless of illness duration. Periodic sharp-wave complexes were not detected on any of the electroencephalography tracings in the Oppenheimer-Brownell group; basal ganglia hyperintensity was not detected on brain magnetic resonance imaging in this group either. All of the Heidenhain variants were of the methionine/ methionine type 1 molecular subtype.

Conclusions: The classic CJD phenotype and the Heidenhain, Oppenheimer-Brownell, cognitive, and affective sCJD variants differ by age at disease onset, survival time, and diagnostic test results. Characteristics of these 5 phenotypes are provided to facilitate further clinicopathologic investigation that may lead to more reliable and timely diagnoses of sCJD.

Arch Neurol. 2009;66(2):208-215

snip...

COMMENT

snip...see full text ;


http://creutzfeldt-jakob-disease.blogspot.com/2009/08/characteristics-of-established-and.html




Office of Inspector General Semiannual Report to Congress FY 2007 - 2nd Half

Two Texas Companies Sentenced and Fined for Misbranding Meat Products In April 2007, two closely held and related Texas companies pled guilty in Federal court and were sentenced to 12 months of probation and ordered to pay $10,250 in fines for misbranding meat products. One of the companies sold adulterated meat products to a retail store in New Mexico. Additionally, portions of the invoices failed to properly and consistently identify the meat products as being from cattle more than 30 months old at time of slaughter. This information is required to be disclosed because of bovine spongiform encephalopathy (BSE, or "mad cow disease") concerns. No adulterated meat reached consumers.


http://www.usda.gov/oig/webdocs/sarc071212.pdf




Saturday, August 29, 2009

FOIA REQUEST FEED RECALL 2009 Product may have contained prohibited materials Bulk Whole Barley, Recall # V-256-2009


http://madcowfeed.blogspot.com/2009/08/foia-request-feed-recall-2009-product.html




Friday, September 4, 2009

FOIA REQUEST ON FEED RECALL PRODUCT 429,128 lbs. feed for ruminant animals may have been contaminated with prohibited material Recall # V-258-2009


http://madcowfeed.blogspot.com/2009/09/foia-request-on-feed-recall-product.html




THIS recall is not confusing ;

10,000,000+ LBS. of PROHIBITED BANNED MAD COW FEED I.E. BLOOD LACED MBM IN COMMERCE USA 2007

Date: March 21, 2007 at 2:27 pm PST

RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II

___________________________________

PRODUCT

Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash Dried, Recall # V-024-2007

CODE

Cattle feed delivered between 01/12/2007 and 01/26/2007

RECALLING FIRM/MANUFACTURER

Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007.

Firm initiated recall is ongoing.

REASON

Blood meal used to make cattle feed was recalled because it was cross- contaminated with prohibited bovine meat and bone meal that had been manufactured on common equipment and labeling did not bear cautionary BSE statement.

VOLUME OF PRODUCT IN COMMERCE

42,090 lbs.

DISTRIBUTION

WI

___________________________________

PRODUCT

Custom dairy premix products: MNM ALL PURPOSE Pellet, HILLSIDE/CDL Prot- Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal, TATARKA, M CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN Meal, COPPINI - 8# SPECIAL DAIRY Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J - PROTEIN/LACTATION, ROCK CREEK/GHC MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR, V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A- BYPASS ML W/SMARTA, Recall # V-025-2007

CODE

The firm does not utilize a code - only shipping documentation with commodity and weights identified.

RECALLING FIRM/MANUFACTURER

Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm initiated recall is complete.

REASON

Products manufactured from bulk feed containing blood meal that was cross contaminated with prohibited meat and bone meal and the labeling did not bear cautionary BSE statement.

VOLUME OF PRODUCT IN COMMERCE

9,997,976 lbs.

DISTRIBUTION

ID and NV

END OF ENFORCEMENT REPORT FOR MARCH 21, 2007

http://www.fda.gov/bbs/topics/enforce/2007/ENF00996.html


NEW URL


http://www.fda.gov/Safety/Recalls/EnforcementReports/2007/ucm120446.htm




Thursday, March 19, 2009

MILLIONS AND MILLIONS OF POUNDS OF MAD COW FEED IN COMMERCE USA WITH ONGOING 12 YEARS OF DENIAL


http://madcowfeed.blogspot.com/2009/03/millions-and-millions-of-pounds-of-mad.html






Monday, May 11, 2009

Rare BSE mutation raises concerns over risks to public health


http://bse-atypical.blogspot.com/2009/05/rare-bse-mutation-raises-concerns-over.html





Sunday, June 07, 2009

L-TYPE-BSE, H-TYPE-BSE, C-TYPE-BSE, IBNC-TYPE-BSE, TME, CWD, SCRAPIE, CJD, NORTH AMERICA


http://bse-atypical.blogspot.com/2009/06/l-type-bse-h-type-bse-c-type-bse-ibnc.html




Sunday, May 10, 2009

Identification and characterization of bovine spongiform encephalopathy cases diagnosed and NOT diagnosed in the United States


http://bse-atypical.blogspot.com/2009/05/identification-and-characterization-of.html




Docket APHIS-2006-0026 Docket Title Bovine Spongiform Encephalopathy; Animal Identification and Importation of Commodities Docket Type Rulemaking Document APHIS-2006-0026-0001 Document Title Bovine Spongiform Encephalopathy; Minimal-Risk Regions, Identification of Ruminants and Processing and Importation of Commodities Public Submission APHIS-2006-0026-0012 Public Submission Title Comment from Terry S Singletary


http://www.regulations.gov/fdmspublic/component/main?main=DocumentDetail&o=09000064801e47e1




Docket APHIS-2006-0041 Docket Title Bovine Spongiform Encephalopathy; Minimal-Risk Regions; Importation of Live Bovines and Products Derived from Bovines Commodities Docket Type Rulemaking Document APHIS-2006-0041-0001 Document Title Bovine Spongiform Encephalopathy; Minimal-Risk Regions; Importation of Live Bovines and Products Derived From Bovines Public Submission APHIS-2006-0041-0028 Public Submission Title Comment from Terry S Singletary

Comment 2006-2007 USA AND OIE POISONING GLOBE WITH BSE MRR POLICY

THE USA is in a most unique situation, one of unknown circumstances with human and animal TSE. THE USA has the most documented TSE in different species to date, with substrains growing in those species (BSE/BASE in cattle and CWD in deer and elk, there is evidence here with different strains), and we know that sheep scrapie has over 20 strains of the typical scrapie with atypical scrapie documented and also BSE is very likely to have passed to sheep. all of which have been rendered and fed back to animals for human and animal consumption, a frightening scenario. WE do not know the outcome, and to play with human life around the globe with the very likely TSE tainted products from the USA, in my opinion is like playing Russian roulette, of long duration, with potential long and enduring consequences, of which once done, cannot be undone. These are the facts as I have come to know through daily and extensive research of TSE over 9 years, since 12/14/97. I do not pretend to have all the answers, but i do know to continue to believe in the ukbsenvcjd only theory of transmission to humans of only this one strain from only this one TSE from only this one part of the globe, will only lead to further failures, and needless exposure to humans from all strains of TSE, and possibly many more needless deaths from TSE via a multitude of proven routes and sources via many studies with primates and rodents and other species.

MY personal belief, since you ask, is that not only the Canadian border, but the USA border, and the Mexican border should be sealed up tighter than a drum for exporting there TSE tainted products, until a validated, 100% sensitive test is available, and all animals for human and animal consumption are tested. all we are doing is the exact same thing the UK did with there mad cow poisoning when they exported it all over the globe, all the while knowing what they were doing. this BSE MRR policy is nothing more than a legal tool to do just exactly what the UK did, thanks to the OIE and GW, it's legal now. and they executed Saddam for poisoning ???

go figure. ...


http://www.regulations.gov/fdmspublic/component/main?main=DocumentDetail&o=09000064801f8151




Docket APHIS-2006-0041 Docket Title Bovine Spongiform Encephalopathy; Minimal-Risk Regions; Importation of Live Bovines and Products Derived from Bovines Commodities Docket Type Rulemaking Document APHIS-2006-0041-0001 Document Title Bovine Spongiform Encephalopathy; Minimal-Risk Regions; Importation of Live Bovines and Products Derived From Bovines Public Submission APHIS-2006-0041-0028.1 Public Submission Title Attachment to Singletary comment

January 28, 2007

Greetings APHIS,

I would kindly like to submit the following to ;

BSE; MRR; IMPORTATION OF LIVE BOVINES AND PRODUCTS DERIVED FROM BOVINES [Docket No. APHIS-2006-0041] RIN 0579-AC01


http://www.regulations.gov/fdmspublic/ContentViewer?objectId=09000064801f8152&disposition=attachment&contentType=msw8




Sunday, August 10, 2008

A New Prionopathy OR more of the same old BSe and sporadic CJD


http://creutzfeldt-jakob-disease.blogspot.com/2008/08/new-prionopathy-or-more-of-same-old-bse.html




SEAC OCTOBER 2009

• Are some commoner types of neurodegenerative disease (including Alzheimer's disease and Parkinson's disease) also transmissible? Some recent scientific research has suggested this possibility


http://www.seac.gov.uk/pdf/hol-response091008.pdf




Thursday, February 26, 2009

'Harmless' prion protein linked to Alzheimer's disease Non-infectious form of prion protein could cause brain degeneration ???


http://betaamyloidcjd.blogspot.com/2009/02/harmless-prion-protein-linked-to.html




CJD1/9 0185

Ref: 1M51A

IN STRICT CONFIDENCE

TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES

1. CMO will wish to be aware that a meeting was held at DH yesterday, 4 January, to discuss the above findings. It was chaired by Professor Murray (Chairman of the MRC Co-ordinating Committee on Research in the Spongiform Encephalopathies in Man), and attended by relevant experts in the fields of Neurology, Neuropathology, molecular biology, amyloid biochemistry, and the spongiform encephalopathies, and by representatives of the MRC and AFRC.

2. Briefly, the meeting agreed that:

i) Dr Ridley et als findings of experimental induction of p amyloid in primates were valid, interesting and a significant advance in the understanding of neurodegeneradve disorders;

ii) there were no immediate implications for the public health, and no further safeguards were thought to be necessary at present; and

iii) additional research was desirable, both epidemiological and at the molecular level. Possible avenues are being followed up by DH and the MRC, but the details will require further discussion.

93/01.05/4.1tss


http://www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf




Regarding Alzheimer's disease

(note the substantial increase on a yearly basis)


http://www.bseinquiry.gov.uk/files/yb/1988/07/08014001.pdf




snip...

The pathogenesis of these diseases was compared to Alzheimer's disease at a molecular level...

snip...


http://www.bseinquiry.gov.uk/files/yb/1990/03/12003001.pdf




And NONE of this is relevant to BSE?

There is also the matter whether the spectrum of ''prion disease'' is wider than that recognized at present.


http://www.bseinquiry.gov.uk/files/yb/1990/07/06005001.pdf




http://www.bseinquiry.gov.uk/files/yb/1990/07/09001001.pdf





BSE101/1 0136

IN CONFIDENCE

5 NOV 1992

CMO From: Dr J S Metters DCMO 4 November 1992

TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES


http://www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf




also, see the increase of Alzheimer's from 1981 to 1986


http://www.bseinquiry.gov.uk/files/yb/1988/07/08014001.pdf




Tuesday, August 26, 2008

Alzheimer's Transmission of AA-amyloidosis: Similarities with Prion Disorders NEUROPRION 2007 FC4.3


http://betaamyloidcjd.blogspot.com/2008/08/alzheimers-transmission-of-aa.html




see full text ;


http://betaamyloidcjd.blogspot.com/2009/02/harmless-prion-protein-linked-to.html




Alzheimer's and CJD


http://betaamyloidcjd.blogspot.com/




Saturday, March 22, 2008

10 Million Baby Boomers to have Alzheimer's in the coming decades 2008 Alzheimer's disease facts and figures


http://betaamyloidcjd.blogspot.com/2008/03/association-between-deposition-of-beta.html




re-Association between Deposition of Beta-Amyloid and Pathological Prion Protein in Sporadic Creutzfeldt-Jakob Disease


http://betaamyloidcjd.blogspot.com/2008/04/re-association-between-deposition-of.html




Thursday, December 04, 2008 2:37 PM

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

personal communication with Professor Kong. ...TSS

see full text ;


http://bse-atypical.blogspot.com/2009/02/atypical-bse-north-america-update.html




PR-26

NOR98 SHOWS MOLECULAR FEATURES REMINISCENT OF GSS

R. Nonno1, E. Esposito1, G. Vaccari1, E. Bandino2, M. Conte1, B. Chiappini1, S. Marcon1, M. Di Bari1, S.L. Benestad3, U. Agrimi1 1 Istituto Superiore di Sanità, Department of Food Safety and Veterinary Public Health, Rome, Italy (romolo.nonno@iss.it); 2 Istituto Zooprofilattico della Sardegna, Sassari, Italy; 3 National Veterinary Institute, Department of Pathology, Oslo, Norway

Molecular variants of PrPSc are being increasingly investigated in sheep scrapie and are generally referred to as “atypical” scrapie, as opposed to “classical scrapie”. Among the atypical group, Nor98 seems to be the best identified. We studied the molecular properties of Italian and Norwegian Nor98 samples by WB analysis of brain homogenates, either untreated, digested with different concentrations of proteinase K, or subjected to enzymatic deglycosylation. The identity of PrP fragments was inferred by means of antibodies spanning the full PrP sequence. We found that undigested brain homogenates contain a Nor98-specific PrP fragment migrating at 11 kDa (PrP11), truncated at both the C-terminus and the N-terminus, and not N-glycosylated. After mild PK digestion, Nor98 displayed full-length PrP (FL-PrP) and N-glycosylated C-terminal fragments (CTF), along with increased levels of PrP11. Proteinase K digestion curves (0,006-6,4 mg/ml) showed that FL-PrP and CTF are mainly digested above 0,01 mg/ml, while PrP11 is not entirely digested even at the highest concentrations, similarly to PrP27-30 associated with classical scrapie. Above 0,2 mg/ml PK, most Nor98 samples showed only PrP11 and a fragment of 17 kDa with the same properties of PrP11, that was tentatively identified as a dimer of PrP11. Detergent solubility studies showed that PrP11 is insoluble in 2% sodium laurylsorcosine and is mainly produced from detergentsoluble, full-length PrPSc. Furthermore, among Italian scrapie isolates, we found that a sample with molecular and pathological properties consistent with Nor98 showed plaque-like deposits of PrPSc in the thalamus when the brain was analysed by PrPSc immunohistochemistry. Taken together, our results show that the distinctive pathological feature of Nor98 is a PrP fragment spanning amino acids ~ 90-155. This fragment is produced by successive N-terminal and C-terminal cleavages from a full-length and largely detergent-soluble PrPSc, is produced in vivo and is extremely resistant to PK digestion. Intriguingly, these conclusions suggest that some pathological features of Nor98 are reminiscent of Gerstmann-Sträussler-Scheinker disease.

119


http://www.neuroprion.com/pdf_docs/conferences/prion2006/abstract_book.pdf




When Atypical Scrapie cross species barriers

Authors

Andreoletti O., Herva M. H., Cassard H., Espinosa J. C., Lacroux C., Simon S., Padilla D., Benestad S. L., Lantier F., Schelcher F., Grassi J., Torres, J. M., UMR INRA ENVT 1225, Ecole Nationale Veterinaire de Toulouse.France; ICISA-INlA, Madrid, Spain; CEA, IBiTec-5, DSV, CEA/Saclay, Gif sur Yvette cedex, France; National Veterinary Institute, Postboks 750 Sentrum, 0106 Oslo, Norway, INRA IASP, Centre INRA de Tours, 3738O Nouzilly, France.

Content

Atypical scrapie is a TSE occurring in small ruminants and harbouring peculiar clinical, epidemiological and biochemical properties. Currently this form of disease is identified in a large number of countries. In this study we report the transmission of an atypical scrapie isolate through different species barriers as modeled by transgenic mice (Tg) expressing different species PRP sequence.

The donor isolate was collected in 1995 in a French commercial sheep flock. inoculation into AHQ/AHQ sheep induced a disease which had all neuro-pathological and biochemical characteristics of atypical scrapie. Transmitted into Transgenic mice expressing either ovine or PrPc, the isolate retained all the described characteristics of atypical scrapie.

Surprisingly the TSE agent characteristics were dramatically different v/hen passaged into Tg bovine mice. The recovered TSE agent had biological and biochemical characteristics similar to those of atypical BSE L in the same mouse model. Moreover, whereas no other TSE agent than BSE were shown to transmit into Tg porcine mice, atypical scrapie was able to develop into this model, albeit with low attack rate on first passage.

Furthermore, after adaptation in the porcine mouse model this prion showed similar biological and biochemical characteristics than BSE adapted to this porcine mouse model. Altogether these data indicate.

(i) the unsuspected potential abilities of atypical scrapie to cross species barriers

(ii) the possible capacity of this agent to acquire new characteristics when crossing species barrier

These findings raise some interrogation on the concept of TSE strain and on the origin of the diversity of the TSE agents and could have consequences on field TSE control measures.


http://www.neuroprion.org/resources/pdf_docs/conferences/prion2008/abstract-book-prion2008.pdf




P03.141

Aspects of the Cerebellar Neuropathology in Nor98

Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E1 1National Veterinary Insitute, Sweden; 2National Veterinary Institute,

Norway Nor98 is a prion disease of old sheep and goats. This atypical form of scrapie was first described in Norway in 1998. Several features of Nor98 were shown to be different from classical scrapie including the distribution of disease associated prion protein (PrPd) accumulation in the brain. The cerebellum is generally the most affected brain area in Nor98. The study here presented aimed at adding information on the neuropathology in the cerebellum of Nor98 naturally affected sheep of various genotypes in Sweden and Norway. A panel of histochemical and immunohistochemical (IHC) stainings such as IHC for PrPd, synaptophysin, glial fibrillary acidic protein, amyloid, and cell markers for phagocytic cells were conducted. The type of histological lesions and tissue reactions were evaluated. The types of PrPd deposition were characterized. The cerebellar cortex was regularly affected, even though there was a variation in the severity of the lesions from case to case. Neuropil vacuolation was more marked in the molecular layer, but affected also the granular cell layer. There was a loss of granule cells. Punctate deposition of PrPd was characteristic. It was morphologically and in distribution identical with that of synaptophysin, suggesting that PrPd accumulates in the synaptic structures. PrPd was also observed in the granule cell layer and in the white matter. The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.

***The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.


http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf




Here we report that both Nor98 and discordant cases, including three sheep homozygous for the resistant PrPARR allele (A136R154R171), efficiently transmitted the disease to transgenic mice expressing ovine PrP, and that they shared unique biological and biochemical features upon propagation in mice. These observations support the view that a truly infectious TSE agent, unrecognized until recently, infects sheep and goat flocks and may have important implications in terms of scrapie control and public health.

Edited by Stanley B. Prusiner, University of California, San Francisco, CA, and approved September 12, 2005 (received for review March 21, 2005)


http://www.pnas.org/cgi/content/abstract/0502296102v1




NOR-98 ATYPICAL SCRAPIE 5 cases documented in USA in 5 different states USA 2007


http://nor-98.blogspot.com/2008/04/seac-spongiform-encephalopathy-advisory.html




Tuesday, June 3, 2008 SCRAPIE USA UPDATE JUNE 2008 NOR-98 REPORTED PA


http://nor-98.blogspot.com/2008/06/scrapie-usa-update-june-2008-nor-98.html




http://nor-98.blogspot.com/




Monday, September 1, 2008

RE-FOIA OF DECLARATION OF EXTRAORDINARY EMERGENCY BECAUSE OF AN ATYPICAL T.S.E. (PRION DISEASE) OF FOREIGN ORIGIN IN THE UNITED STATES [No. 00-072-1]

September 1, 2008


http://foiamadsheepmadrivervalley.blogspot.com/2008/09/re-foia-of-declaration-of-extraordinary.html




Monday, December 1, 2008

When Atypical Scrapie cross species barriers


http://nor-98.blogspot.com/2008/12/when-atypical-scrapie-cross-species.html



Tuesday, August 04, 2009

Susceptibilities of Nonhuman Primates to Chronic Wasting Disease


http://chronic-wasting-disease.blogspot.com/2009/08/susceptibilities-of-nonhuman-primates.html




Terry S. Singeltary Sr.

P.O. Box 42

Bacliff, Texas USA 77518

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