Clinical Heidenhain Variant Of Sporadic Creutzfeldt-Jakob Disease (CJD) With Co-occurrence Of Prion Protein Types 1 and 2

Poster 52

Clinical Heidenhain Variant Of Sporadic Creutzfeldt-Jakob Disease (CJD) With Co-occurrence Of Prion Protein Types 1 and 2

Adeela Alizai1, Gianfranco Puoti2, Pierluigi Gambetti2, Ignazio Cali21Temple University Hospital, Philadelphia, PA, United States, 2Case Western University, Cleveland, OH, United States

Background:

Sporadic Creutzfeldt-Jacob disease (sCJD) is a rare neurodegenerative illness comprising five phenotypically distinct subtypes based on the methionine(M)/valine(V) polymorphism at codon 129 of the prion protein (PrP) gene and presence of either one of the two protease-resistant PrP (PrPres), referred to as PrPres type 1 and type 2.1, 2 The most common of these five subtypes includes the sCJDMM(MV)1 that matches the .classic. sCJD and comprises the so-called Heidenhain variant (HsCJD) characterized by early and prominent visual symptoms. Recently, an additional subtype of sCJD has been described and identified as sCJDMM1-2 in which both types 1 and 2 histopathological changes are found in the same brain.3 The clinical Heidenhain phenotype in association with histopathological sCJDMM1-2 subtype has not been described.

Methods:

Clinical, neuroimaging, EEG findings, histopathological and immunostaining as well as PrPres characterization of 20 cases of sCJDMM1-2 were reviewed.

Results:

Two cases (10%) of HsCJD with ages at onset of 51 and 66 years and disease durations of 4 and 12 months were identified. Immunohistopathology and PrPres type determination were consistent with the features of the sCJDMM1-2 subtype.3 The visual cortex was more severely affected than the frontal cortex and was found to carry both PrPres types.4 The study of the quantitative distribution of PrPres types, expressed as mean percentage of total PrPres types 1 and 2 (1:2), was 79%:21% for the sCJDMM1-2 with 4 month and 45%:55% for the case with 12 months disease duration respectively. The cerebellum showed both PrPres types and PrP immunohistochemical patterns of the sCJDMM1-2.

Conclusion:

To our knowledge, this is the first histopathological finding of sCJDMM1-2 in Heidenhain variant of sporadic CJD. Also, the amount of PrPres type 2 and to a lesser extent that of the MM2-like immunohistochemical features increase with the disease duration, as seen for the sCJDMM1-2.

References:

1. Parchi P, Giese A, Capellari S et al. Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects. Ann Neurol 1999; 46: 224-233.

2. Gambetti P, Kong Q, Zou W, Parchi P, Chen SG. Sporadic and familial CJD: classification and characterization. Br Med Bull 2003; 66: 213.39.

3. Cali I, Castellani R, Alshekhlee A et al. Co-existence of scrapie prion protein types 1 and 2 in sporadic Creutzfeldt.Jakob disease: its effect on the phenotype and prion-type characteristics. Brain. 2009 Sep 4. [Epub ahead of print]

4. Kropp S, Schulz-Schaeffer WJ, Finkenstaedt M, Riedemann C, Windl O, Steinhoff BJ, Zerr I, Kretzschmar HA, Poser S. The Heidenhain variant of Creutzfeldt-Jakob disease. Arch Neurol. 1999 Jan; 56(1):55-61.

Key Words: Heidenhain variant of sporadic CJD disease duration, co-existence of Prion proteins types 1 and 2, disease duration

Financial Disclosure: NONE

http://content.lib.utah.edu/cgi-bin/showfile.exe?CISOROOT=/ehsl-nam&CISOPTR=229&filename=230.pdf


88


Heidenhain Variant of Sporadic Creutzfeldt-Jakob Disease With the Co-Occurrence of Two Different Types of Prion Protein

Ignazio Cali1, Gianfranco Puoti1, Janis Blevins1, Adeela Alizai2, Pierluigi Gambetti1. 1Case Western Reserve University; 2Temple University Hospital

Sporadic Creutzfeldt-Jacob disease (sCJD) is a rare neurodegenerative disorder classified into five distinct phenotypes based on i) the polymorphic methionine (M)/valine (V) genotype at codon 129, and ii) detection of either type 1 or type 2 of the protease-resistant prion protein (PrPres) (Parchi et al., Ann Neurol 1999; Gambetti et al., Br Med Bull 2003). Sporadic CJDMM1, the most common CJD subtype, is the only CJD subtype that includes the Heidenhain variant (HsCJD), a condition characterized by early and prominent visual deficits associated with the preferential involvement of the occipital cortex (Kropp et al., Arch Neurol 1999). The histopathological phenotype of HsCJD is indistinguishable from that of sCJDMM1. Recently, we described a group of sCJD cases identified as sCJDMM1-2 in which both PrPres types were found to co-exist in the same brain (Cali et al., Brain 2009). In the present study, we investigated whether the Heidenhain clinical phenotype is present in sCJDMM1-2. To date, the screening of clinical histories from 59 sCJDMM1-2 patients that were received at the National Prion Disease Pathology Surveillance Center between 1998 and 2009 has led to the identification of 8 (14%) HsCJDMM1-2 subjects. The detailed study of two HsCJDMM1-2 cases shows that the immunohistopathological features as well as PrPres type determined in different brain locations are consistent with the features of the sCJDMM1-2 subtype (Cali et al., Brain 2009). The visual cortex is severely affected in both cases and is found to carry both PrPres types (Kropp et al., Arch Neurol 1999). To our knowledge, this is the first finding of HsCJD in sCJDMM1-2 and indicates that the presence of even relatively large amounts of PrPres type 2 does not impede the expression of HsCJD.

(Supported by, NIH AG-14359, CDC UR8/CCU515004 and Charles S. Britton Foundation; the CDC Foundation).

http://journals.lww.com/jneuropath/Fulltext/2010/05000/American_Association_of_Neuropathologists,_Inc__.9.aspx



Friday, August 20, 2010

Heidenhain Variant of Sporadic Creutzfeldt-Jakob Disease With the Co-Occurrence of Two Different Types of Prion Protein

http://creutzfeldt-jakob-disease.blogspot.com/2010/08/heidenhain-variant-of-sporadic.html



Tuesday, July 29, 2008

Heidenhain Variant Creutzfeldt Jakob Disease Case Report

FINAL AUTOPSY DIAGNOSIS

I. Brain: Creutzfeldt-Jakob disease, Heidenhain variant.

http://creutzfeldt-jakob-disease.blogspot.com/2008/07/heidenhain-variant-creutzfeldt-jakob.html


WHAT ABOUT those old studies at Mission, Texas, where USA scrapie was transmitted to USA cattle, but the results was not c-BSE. IT was a different TSE.

WHAT ABOUT atypical Nor-98 Scrapie in the USA, and TSE there from to other species ???

The key word here is diverse. What does diverse mean?

If USA scrapie transmitted to USA bovine does not produce pathology as the UK c-BSE, then why would CJD from there look like UK vCJD?"

SEE FULL TEXT ;

http://www.promedmail.org/pls/apex/f?p=2400:1001:568933508083034::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,82101



.57 The experiment which might have determined whether BSE and scrapie were caused by the same agent (ie, the feeding of natural scrapie to cattle) was never undertaken in the UK. It was, however, performed in the USA in 1979, when it was shown that cattle inoculated with the scrapie agent endemic in the flock of Suffolk sheep at the United States Department of Agriculture in Mission, Texas, developed a TSE quite unlike BSE. 32 The findings of the initial transmission, though not of the clinical or neurohistological examination, were communicated in October 1988 to Dr Watson, Director of the CVL, following a visit by Dr Wrathall, one of the project leaders in the Pathology Department of the CVL, to the United States Department of Agriculture. 33 The results were not published at this point, since the attempted transmission to mice from the experimental cow brain had been inconclusive. The results of the clinical and histological differences between scrapie-affected sheep and cattle were published in 1995. Similar studies in which cattle were inoculated intracerebrally with scrapie inocula derived from a number of scrapie-affected sheep of different breeds and from different States, were carried out at the US National Animal Disease Centre. 34 The results, published in 1994, showed that this source of scrapie agent, though pathogenic for cattle, did not produce the same clinical signs of brain lesions characteristic of BSE.

32 Clark, W., Hourrigan, J. and Hadlow, W. (1995) Encephalopathy in Cattle Experimentally Infected with the Scrapie Agent, American Journal of Veterinary Research, 56, 606-12

33 YB88/10.00/1.1

http://web.archive.org/web/20040823105233/www.bseinquiry.gov.uk/files/yb/1988/10/00001001.pdf



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, 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, 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


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 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


BSE: TIME TO TAKE H.B. PARRY SERIOUSLY

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



Suspect symptoms

What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?

28 Mar 01

Like lambs to the slaughter 31 March 2001 by Debora MacKenzie Magazine issue 2284. Subscribe and get 4 free issues. FOUR years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.

Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.

Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in mice as sCJD.

"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb.

Scrapie has been around for centuries and until now there has been no evidence that it poses a risk to human health. But if the French finding means that scrapie can cause sCJD in people, countries around the world may have overlooked a CJD crisis to rival that caused by BSE.

Deslys and colleagues were originally studying vCJD, not sCJD. They injected the brains of macaque monkeys with brain from BSE cattle, and from French and British vCJD patients. The brain damage and clinical symptoms in the monkeys were the same for all three. Mice injected with the original sets of brain tissue or with infected monkey brain also developed the same symptoms.

As a control experiment, the team also injected mice with brain tissue from people and animals with other prion diseases: a French case of sCJD; a French patient who caught sCJD from human-derived growth hormone; sheep with a French strain of scrapie; and mice carrying a prion derived from an American scrapie strain. As expected, they all affected the brain in a different way from BSE and vCJD. But while the American strain of scrapie caused different damage from sCJD, the French strain produced exactly the same pathology.

"The main evidence that scrapie does not affect humans has been epidemiology," says Moira Bruce of the neuropathogenesis unit of the Institute for Animal Health in Edinburgh, who was a member of the same team as Deslys. "You see about the same incidence of the disease everywhere, whether or not there are many sheep, and in countries such as New Zealand with no scrapie." In the only previous comparisons of sCJD and scrapie in mice, Bruce found they were dissimilar.

But there are more than 20 strains of scrapie, and six of sCJD. "You would not necessarily see a relationship between the two with epidemiology if only some strains affect only some people," says Deslys. Bruce is cautious about the mouse results, but agrees they require further investigation. Other trials of scrapie and sCJD in mice, she says, are in progress.

People can have three different genetic variations of the human prion protein, and each type of protein can fold up two different ways. Kretschmar has found that these six combinations correspond to six clinical types of sCJD: each type of normal prion produces a particular pathology when it spontaneously deforms to produce sCJD.

But if these proteins deform because of infection with a disease-causing prion, the relationship between pathology and prion type should be different, as it is in vCJD. "If we look at brain samples from sporadic CJD cases and find some that do not fit the pattern," says Kretschmar, "that could mean they were caused by infection."

There are 250 deaths per year from sCJD in the US, and a similar incidence elsewhere. Singeltary and other US activists think that some of these people died after eating contaminated meat or "nutritional" pills containing dried animal brain. Governments will have a hard time facing activists like Singeltary if it turns out that some sCJD isn't as spontaneous as doctors have insisted.

Deslys's work on macaques also provides further proof that the human disease vCJD is caused by BSE. And the experiments showed that vCJD is much more virulent to primates than BSE, even when injected into the bloodstream rather than the brain. This, says Deslys, means that there is an even bigger risk than we thought that vCJD can be passed from one patient to another through contaminated blood transfusions and surgical instruments.

http://www.newscientist.com/article/mg16922840.300-like-lambs-to-the-slaughter.html


Monday, December 14, 2009

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types

(hmmm, this is getting interesting now...TSS)

Sporadic CJD type 1 and atypical/ Nor98 scrapie are characterized by fine (reticular) deposits,

see also ;

All of the Heidenhain variants were of the methionine/ methionine type 1 molecular subtype.

http://cjdusa.blogspot.com/2009/09/co-existence-of-scrapie-prion-protein.html


see full text ;

Monday, December 14, 2009

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types

http://nor-98.blogspot.com/2009/12/similarities-between-forms-of-sheep.html


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


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


A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes

Annick Le Dur*,?, Vincent Béringue*,?, Olivier Andréoletti?, Fabienne Reine*, Thanh Lan Laï*, Thierry Baron§, Bjørn Bratberg¶, Jean-Luc Vilotte?, Pierre Sarradin**, Sylvie L. Benestad¶, and Hubert Laude*,?? +Author Affiliations

*Virologie Immunologie Moléculaires and ?Génétique Biochimique et Cytogénétique, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France; ?Unité Mixte de Recherche, Institut National de la Recherche Agronomique-Ecole Nationale Vétérinaire de Toulouse, Interactions Hôte Agent Pathogène, 31066 Toulouse, France; §Agence Française de Sécurité Sanitaire des Aliments, Unité Agents Transmissibles Non Conventionnels, 69364 Lyon, France; **Pathologie Infectieuse et Immunologie, Institut National de la Recherche Agronomique, 37380 Nouzilly, France; and ¶Department of Pathology, National Veterinary Institute, 0033 Oslo, Norway

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

Abstract Scrapie in small ruminants belongs to transmissible spongiform encephalopathies (TSEs), or prion diseases, a family of fatal neurodegenerative disorders that affect humans and animals and can transmit within and between species by ingestion or inoculation. Conversion of the host-encoded prion protein (PrP), normal cellular PrP (PrPc), into a misfolded form, abnormal PrP (PrPSc), plays a key role in TSE transmission and pathogenesis. The intensified surveillance of scrapie in the European Union, together with the improvement of PrPSc detection techniques, has led to the discovery of a growing number of so-called atypical scrapie cases. These include clinical Nor98 cases first identified in Norwegian sheep on the basis of unusual pathological and PrPSc molecular features and "cases" that produced discordant responses in the rapid tests currently applied to the large-scale random screening of slaughtered or fallen animals. Worryingly, a substantial proportion of such cases involved sheep with PrP genotypes known until now to confer natural resistance to conventional scrapie. 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.

http://www.pnas.org/content/102/44/16031.abstract


Monday, December 1, 2008

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



Tuesday, April 28, 2009

Nor98-like Scrapie in the United States of America

http://nor-98.blogspot.com/2009/04/nor98-like-scrapie-in-united-states-of.html


Heidenhain Variant Creutzfeldt Jakob Disease autopsy case report 'MOM'

DIVISION OF NEUROPATHOLOGY University of Texas Medical Branch 114 McCullough Bldg. Galveston, Texas 77555-0785

FAX COVER SHEET

DATE: 4-23-98

TO: Mr. Terry Singeltary @ -------

FROM: Gerald Campbell

FAX: (409) 772-5315 PHONE: (409) 772-2881

Number of Pages (including cover sheet):

Message:

*CONFIDENTIALITY NOTICE*

This document accompanying this transmission contains confidential information belonging to the sender that is legally privileged. This information is intended only for the use of the individual or entry names above. If you are not the intended recipient, you are hereby notified that any disclosure, copying distribution, or the taking of any action in reliances on the contents of this telefaxed information is strictly prohibited. If you received this telefax in error, please notify us by telephone immediately to arrange for return of the original documents. -------------------------- Patient Account: 90000014-518 Med. Rec. No.: (0160)118511Q Patient Name: POULTER, BARBARA Age: 63 YRS DOB: 10/17/34 Sex: F Admitting Race: C

Attending Dr.: Date / Time Admitted : 12/14/97 1228 Copies to:

UTMB University of Texas Medical Branch Galveston, Texas 77555-0543 (409) 772-1238 Fax (409) 772-5683 Pathology Report

FINAL AUTOPSY DIAGNOSIS Autopsy' Office (409)772-2858

Autopsy NO.: AU-97-00435

AUTOPSY INFORMATION: Occupation: Unknown Birthplace: Unknown Residence: Crystal Beach Date/Time of Death: 12/14/97 13:30 Date/Time of Autopsy: 12/15/97 15:00 Pathologist/Resident: Pencil/Fernandez Service: Private Restriction: Brain only

FINAL AUTOPSY DIAGNOSIS

I. Brain: Creutzfeldt-Jakob disease, Heidenhain variant.

http://creutzfeldt-jakob-disease.blogspot.com/2008/07/heidenhain-variant-creutzfeldt-jakob.html


P.9.21

Molecular characterization of BSE in Canada

Jianmin Yang1, Sandor Dudas2, Catherine Graham2, Markus Czub3, Tim McAllister1, Stefanie Czub1 1Agriculture and Agri-Food Canada Research Centre, Canada; 2National and OIE BSE Reference Laboratory, Canada; 3University of Calgary, Canada

Background: Three BSE types (classical and two atypical) have been identified on the basis of molecular characteristics of the misfolded protein associated with the disease. To date, each of these three types have been detected in Canadian cattle.

Objectives: This study was conducted to further characterize the 16 Canadian BSE cases based on the biochemical properties of there associated PrPres. Methods: Immuno-reactivity, molecular weight, glycoform profiles and relative proteinase K sensitivity of the PrPres from each of the 16 confirmed Canadian BSE cases was determined using modified Western blot analysis.

Results: Fourteen of the 16 Canadian BSE cases were C type, 1 was H type and 1 was L type. The Canadian H and L-type BSE cases exhibited size shifts and changes in glycosylation similar to other atypical BSE cases. PK digestion under mild and stringent conditions revealed a reduced protease resistance of the atypical cases compared to the C-type cases. N terminal- specific antibodies bound to PrPres from H type but not from C or L type. The C-terminal-specific antibodies resulted in a shift in the glycoform profile and detected a fourth band in the Canadian H-type BSE.

Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan. This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada.

*** It also suggests a similar cause or source for atypical BSE in these countries.

http://www.prion2009.com/sites/default/files/Prion2009_Book_of_Abstracts.pdf


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


Saturday, November 6, 2010

TAFS1 Position Paper on Position Paper on Relaxation of the Feed Ban in the EU Berne, 2010 TAFS

INTERNATIONAL FORUM FOR TRANSMISSIBLE ANIMAL DISEASES AND FOOD SAFETY a non-profit Swiss Foundation

http://madcowfeed.blogspot.com/2010/11/tafs1-position-paper-on-position-paper.html


Archive Number 20101206.4364 Published Date 06-DEC-2010 Subject PRO/AH/EDR

Prion disease update 2010 (11)

PRION DISEASE UPDATE 2010 (11)



http://www.promedmail.org/pls/apex/f?p=2400:1001:5492868805159684::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,86129




Identifying Variation in the U.S. Bovine Prion Gene

Bovine spongiform encephalopathy—BSE, or mad cow disease—is a serious threat to the U.S. beef industry.

While the first confirmed case of BSE on U.S. soil in December 2003 had little effect on domestic consumption, it carved into our international beef sales. According to USDA’s Economic Research Service, the United States exported only $552 million worth of beef in 2004—down from $2.6 billion in 2002 and $3.1 billion in 2003—a reduction due, in part, to the BSE case.

Are some cattle more susceptible to BSE? Is there a genetic component involved?

To address these and other questions, ARS scientists at the U.S. Meat Animal Research Center (USMARC) at Clay Center, Nebraska, have sequenced the bovine prion gene, PRNP, in 192 cattle representing 16 beef and 5 dairy breeds common in the United States. This work was partially funded by a grant from USDA’s Cooperative State Research, Education, and Extension Service.

Prions are proteins that occur naturally in mammals. BSE is a fatal neurological disorder characterized by irregularly folded prions. Much is unknown about the disease, but scientists recognize a correlation between variations in the PRNP gene in some mammals and susceptibility to transmissible spongiform encephalopathies, such as scrapie in sheep.

“Evidence indicates that this could also be true in cattle,” says molecular biologist Mike Clawson. He is among the USMARC scientists examining PRNP variation to learn if and how different forms, or alleles, of the prion gene correlate with BSE susceptibility.

A thorough characterization of PRNP variation in a U.S. cattle population will provide a reference framework for researchers to use in analyzing PRNP sequences from cattle afflicted with BSE.

From the 192 PRNP genes sequenced, Clawson and his colleagues have identified 388 variations, or polymorphisms, of which 287 were previously unknown. Some of these polymorphisms may influence BSE susceptibility in cattle, he says. Ongoing studies with European collaborators are testing the newly identified variants for association with BSE. If these studies show some cattle to be genetically less susceptible to the disease, this information could shed light on BSE’s transmission and development.

The United States has had only three confirmed cases of BSE. Laboratory tests showed that the second and third of these appear to differ significantly from the first case, says Clawson.

“By comparing the PRNP sequence from BSE-infected cattle to healthy cattle, we may be able to identify genetic markers in the prion gene that predict BSE susceptibility,” he says.

In addition to PRNP, the team is currently sequencing several genes closely related to it. These too will be tested for their association with BSE.

“The prevalence of BSE in the United States is extremely low and is declining worldwide,” Clawson says. “Well-characterized genetic markers that correlate to resistance could improve our understanding of the disease and prepare the cattle industry to respond if another prion disease arises in the future.”—By Laura McGinnis, Agricultural Research Service Information Staff.

This research is part of Animal Health, an ARS National Program (#103) described on the World Wide Web at www.nps.ars.usda.gov.

Michael L. Clawson is at the USDA-ARS Roman L. Hruska U.S. Meat Animal Research Center, P.O. Box 166, Clay Center, NE 68933; phone (402) 762-4342, fax (402) 762-4375.

"Identifying Variation in the U.S. Bovine Prion Gene" was published in the January 2007 issue of Agricultural Research magazine.

http://seprl.ars.usda.gov/is/AR/archive/jan07/bovine0107.htm?pf=1


Research Project: Susceptibility of Cattle with the E211k Prnp Allele to Bse

Location: Virus and Prion Research Unit

Project Number: 3625-32000-086-14 Project Type: Specific Cooperative Agreement

Start Date: Aug 14, 2008 End Date: Jul 31, 2013

Objective:

The objective of this cooperative research project is to investigate the influence of the bovine Prnp gene polymorphisms, E211K, on the susceptibility to BSE. Specifically, the research project will provide 134 embryos that will be used to generate approximately 62 animals, 31 of which will contain the rare allele for the purposes BSE research. This ongoing SCA with Iowa State University to produce cattle with the E211K Prnp allele for BSE research has resulted in an E211/K211 heterozygous bull. We are now in the unique position to extend our research on this allele to include animals homozygous for K at position 211. Based upon our understanding of this novel polymorphism one would predict homozygotes would have a more rapid onset of clinical signs associated with genetic BSE than heterozygotes.

Approach:

To achieve the research goals it is imperative to increase the number of animals available to study this Prnp polymorphism. One female calf of the 2006 BSE case was identified and carries the E211K allele. The specific objectives are to be accomplished through the production of multiple offspring from this E211K heifer through superovulation and embryo transfer. Approximately 50% of the offspring will be heterozygous for the E211K polymorphism while the others will serve as genetically matched non-E211K controls. Collection of semen from an E211K heterozygous bull will allow creation of E211K homozygotes. To protect this unique resource immediate collection of embryos is necessary. The initial goal is to harvest 134 embryos that should result in approximately 62 pregnancies (half of which will carry the E211K polymorphism) for immediate use in the studies to amplify the E211K material, test for genetic susceptibility to TSE, and develop a breeding group to produce calves for transmissibility studies. To achieve the goal of understanding the role of the E211K polymorphism with regard to genetic BSE we have utilized superovulation and embryo transfer obtaining a E211/K211 containing bull. We are now in a position to collect semen from the E211/K211 heterozygous bull to create K211/K211 homozygotes. To accomplish this goal we plan to collect semen from this bull and through artificial insemination using semen from the E211/K211 bull with superovulation and embryo transplantation using other E211/K211 heterzygotes generate 30-40 embryos resulting in 15-20 pregnancies yielding approximately 5 K211/K211 homozygous animals and 10 E211/K211 heterozyous animals as well as 5 E211/E211 homozygous controls.

http://www.ars.usda.gov/research/projects/projects.htm?accn_no=413249


http://www.cdc.gov/eid/content/15/12/pdfs/2013.pdf



Subject: Identifying Variation in the U.S. Bovine Prion Gene Date: January 22, 2007 at 8:32 am PST

Identifying Variation in the U.S. Bovine Prion Gene By Laura McGinnis January 22, 2007 Do genes affect bovine spongiform encephalopathy?also known as BSE, or "mad cow" disease? Are some cattle more susceptible than others?

To address these and other questions, Agricultural Research Service (ARS) scientists at the U.S. Meat Animal Research Center in Clay Center, Neb., have sequenced the bovine prion gene (PRNP) in 192 cattle that represent 16 beef and five dairy breeds common in the United States.

This work, partially funded by a grant from the U.S. Department of Agriculture's Cooperative State Research, Education and Extension Service, is expanding the understanding of how the disease works.

BSE is a fatal neurological disorder characterized by prions?proteins that occur naturally in mammals?that fold irregularly. Molecular biologist Mike Clawson and his Clay Center colleagues are examining PRNP variation in order to learn if and how prions correlate with BSE susceptibility.

From the 192 PRNP sequences, Clawson and his colleagues have identified 388 variations, or polymorphisms, 287 of which were previously unknown. Some of these polymorphisms may influence BSE susceptibility in cattle.

Comparing PRNP sequences from infected and healthy cattle may enable researchers to identify genetic markers in the prion gene that predict BSE susceptibility. In addition to PRNP, the team is currently sequencing several closely related genes, which will also be tested for their association with BSE.

The prevalence of BSE in the United States is extremely low, but this research could improve understanding of the disease and prepare the cattle industry to respond if another prion disease should arise in the future.

http://www.ars.usda.gov/is/pr/2007/070122.htm


Identifying Variation in the U.S. Bovine Prion Gene

Bovine spongiform encephalopathy (BSE, or mad cow disease) is a serious threat to the U.S. beef industry.

While the first confirmed case of BSE on U.S. soil in December 2003 had little effect on domestic consumption, it carved into our international beef sales. According to USDAs Economic Research Service, the United States exported only $552 million worth of beef in 2004 down from $2.6 billion in 2002 and $3.1 billion in 2003 a reduction due, in part, to the BSE case.

Are some cattle more susceptible to BSE? Is there a genetic component involved?

To address these and other questions, ARS scientists at the U.S. Meat Animal Research Center (USMARC) at Clay Center, Nebraska, have sequenced the bovine prion gene, PRNP, in 192 cattle representing 16 beef and 5 dairy breeds common in the United States. This work was partially funded by a grant from USDA?s Cooperative State Research, Education, and Extension Service.

Prions are proteins that occur naturally in mammals. BSE is a fatal neurological disorder characterized by irregularly folded prions. Much is unknown about the disease, but scientists recognize a correlation between variations in the PRNP gene in some mammals and susceptibility to transmissible spongiform encephalopathies, such as scrapie in sheep.

Evidence indicates that this could also be true in cattle, says molecular biologist Mike Clawson. He is among the USMARC scientists examining PRNP variation to learn if and how different forms, or alleles, of the prion gene correlate with BSE susceptibility.

A thorough characterization of PRNP variation in a U.S. cattle population will provide a reference framework for researchers to use in analyzing PRNP sequences from cattle afflicted with BSE.

From the 192 PRNP genes sequenced, Clawson and his colleagues have identified 388 variations, or polymorphisms, of which 287 were previously unknown. Some of these polymorphisms may influence BSE susceptibility in cattle, he says. Ongoing studies with European collaborators are testing the newly identified variants for association with BSE. If these studies show some cattle to be genetically less susceptible to the disease, this information could shed light on BSEs transmission and development.

The United States has had only three confirmed cases of BSE. Laboratory tests showed that the second and third of these appear to differ significantly from the first case, says Clawson.

By comparing the PRNP sequence from BSE-infected cattle to healthy cattle, we may be able to identify genetic markers in the prion gene that predict BSE susceptibility, he says.

In addition to PRNP, the team is currently sequencing several genes closely related to it. These too will be tested for their association with BSE.

The prevalence of BSE in the United States is extremely low and is declining worldwide, Clawson says. Well-characterized genetic markers that correlate to resistance could improve our understanding of the disease and prepare the cattle industry to respond if another prion disease arises in the future. By Laura McGinnis, Agricultural Research Service Information Staff.

This research is part of Animal Health, an ARS National Program (#103) described on the World Wide Web at www.nps.ars.usda.gov.

Michael L. Clawson is at the USDA-ARS Roman L. Hruska U.S. Meat Animal Research Center, P.O. Box 166, Clay Center, NE 68933; phone (402) 762-4342, fax (402) 762-4375.

http://www.ars.usda.gov/is/AR/archive/jan07/bovine0107.htm


http://www.ars.usda.gov/is/AR/archive/jan07/bovine0107.pdf


Title: Prion gene haplotypes of U.S. cattle

Authors

Clawson, Michael - mike Heaton, Michael - mike Keele, John Smith, Timothy - tim Harhay, Gregory Laegreid, William - will

Submitted to: BioMed Central (BMC) Genetics Publication Type: Peer Reviewed Journal Publication Acceptance Date: October 24, 2006 Publication Date: November 8, 2006 Reprint URL: http://www.biomedcentral.com/1471-2156/7/51 Citation: Clawson, M.L., Heaton, M.P., Keele, J.W., Smith, T.P., Harhay, G.P., Laegreid, W.W. 2006. Prion gene haplotypes of U.S. cattle. BioMed Central (BMC) Genetics. 7:51.

Interpretive Summary: Transmissible spongiform encephalopathies (TSEs) are fatal neurological disorders that are characterized by abnormal deposits of the prion protein. TSEs have been identified in cats, cattle, deer, elk, humans, mink, moose, and sheep. The cattle TSE, bovine spongiform encephalopathy (BSE) is also known as mad cow disease. BSE is the probable cause of the human TSE variant Creutzfeldt-Jakob disease, transmitted from cattle to people via the food chain. Sequence variation in the prion gene correlates with TSE progression in humans, sheep, and mice. Additionally, there is evidence that bovine PRNP variation correlates with BSE progression. In this study, 25.2 kb of PRNP was sequenced from the promoter region through the three prime untranslated region in 192 U.S. cattle (16 beef, five dairy breeds). Three hundred and eighty eight polymorphisms were observed, of which 287 have not been previously reported. A subset of polymorphisms that efficiently tag genetic variation in U.S. cattle was identified. The results of this study provide a reference framework for accurate and comprehensive evaluation of prion gene variation and its relationship to BSE. Technical Abstract: Background: Bovine spongiform encephalopathy (BSE) is a fatal neurological disorder characterized by abnormal deposits of a protease-resistant isoform of the prion protein. Characterizing linkage disequilibrium (LD) and haplotype networks within the bovine prion gene (PRNP) is important for 1) testing rare or common PRNP variation for an association with BSE and 2) interpreting any association of PRNP alleles with BSE susceptibility. The objective of this study was to identify polymorphisms and haplotypes within PRNP from the promoter region through the 3'UTR in a diverse sample of U.S. cattle genomes. Results: A 25.2-kb genomic region containing PRNP was sequenced from 192 diverse U.S. beef and dairy cattle. Sequence analyses identified 388 total polymorphisms, of which 287 have not previously been reported. The polymorphism alleles define PRNP by regions of high and low LD. High LD is present between alleles in the promoter region through exon 2 (6.7 kb). PRNP alleles within the majority of intron 2, the entire coding sequence and the untranslated region of exon 3 are in low LD (18.0 kb). Two haplotype networks, one representing the region of high LD and the other the region of low LD yielded nineteen different combinations that represent haplotypes spanning PRNP. The haplotype combinations are tagged by 19 polymorphisms (htSNPS) which characterize variation within and across PRNP.

Conclusion: The number of polymorphisms in the prion gene region of U.S. cattle is nearly four times greater than previously described. These polymorphisms define PRNP haplotypes that may influence BSE susceptibility in cattle.

http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=195487


Title: Frequencies of polymorphisms associated with BSE resistance differ significantly between Bos taurus, Bos indicus, and composite cattle

Authors

BRUNELLE, BRIAN GREENLEE, JUSTIN Seabury, Christopher - TEXAS A&M UNIVERSITY Brown Ii, Charles - ABS GLOBAL NICHOLSON, ERIC

Submitted to: BioMed Central (BMC) Veterinary Research Publication Type: Peer Reviewed Journal Publication Acceptance Date: August 22, 2008 Publication Date: August 22, 2008 Citation: Brunelle, B.W., Greenlee, J.J., Seabury, C.M., Brown II, C.E., Nicholson, E.M. 2008. Frequencies of Polymorphisms Associated with BSE Resistance Differ Significantly Between Bos taurus, Bos indicus, and Composite Cattle. BioMed Central (BMC) Veterinary Research. 4(1):36. Available: http://www.biomedcentral.com/1746-6148/4/36.

Interpretive Summary: Bovine spongiform encephalopathy (BSE) is a neurodegenerative prion disease of cattle. There are three host factors related to the host prion protein known to influence susceptibility or resistance to BSE: single amino acid changes in the prion protein, repeat regions within the prion protein, and expression levels of the prion protein. These factors have been well documented in breeds of Bos taurus cattle, but there is little-to-no data on these factors in Bos indicus purebred or Bos indicus x Bos taurus crossbred cattle. Since Bos indicus cattle contribute to the U.S. cattle population, we wanted to determine the frequency of the host factors associated with BSE susceptibility. We studied 58 Bos indicus purebred and 38 Bos indicus x Bos taurus crossbred cattle. The only differences between Bos indicus and Bos taurus cattle were in two factors associated with prion protein expression levels. It was observed that Bos indicus cattle had a much higher frequency of one factor associated with resistance to BSE compared to Bos taurus cattle, while the second factor associated with resistance to BSE was much lower in Bos indicus cattle compared to Bos taurus cattle. This data is useful in determining the relative risk of BSE in Bos indicus cattle based upon these factors. Technical Abstract: Transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases that affect several mammalian species. At least three factors related to the host prion protein are known to modulate susceptibility or resistance to a TSE: amino acid sequence, atypical number of octapeptide repeats, and expression level. These factors have been extensively studied in breeds of Bos taurus cattle in relation to bovine spongiform encephalopathy (BSE). However, little is currently known about these factors in Bos indicus purebred or B. indicus x B. taurus crossbred cattle. The goal of our study was to establish the frequency of markers associated with enhanced susceptibility or resistance to BSE in B. indicus purebred and crossbred cattle.

http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=224736


18 January 2007 - Draft minutes of the SEAC 95 meeting (426 KB) held on 7 December 2006 are now available.

snip...

ITEM 9 - ANY OTHER BUSINESS

snip...

+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

64. A member noted that at the recent Neuroprion meeting, a study was presented showing that in transgenic mice BSE passaged in sheep may be more virulent and infectious to a wider range of species than bovine derived BSE. Other work presented suggested that BSE and bovine amyloidotic spongiform encephalopathy (BASE) MAY BE RELATED. A mutation had been identified in the prion protein gene in an AMERICAN BASE CASE THAT WAS SIMILAR IN NATURE TO A MUTATION FOUND IN CASES OF SPORADIC CJD. A study also demonstrated that in a mouse model it was possible to alleviate the pathological changes of prion disease by suppressing expression of the prion protein gene after infection.

++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

NOW PLEASE GO BACK AND READ THAT SECOND PARAGRAPH AGAIN.....TSS

http://www.seac.gov.uk/minutes/95.pdf


PLEASE READ FULL TEXT ;

http://www.cdc.gov/ncidod/EID/vol12no12/06-0965.htm?s_cid=eid06_0965_e


Discussion

This study assessed the prevalence of specific BSE-associated factors in B. indicus purebred and composite cattle, which were then compared to frequencies observed in B. taurus cattle. Through PRNP sequence analysis, we surveyed cattle for the presence of an E211K amino acid replacement, as well as the presence of 7 or more octapeptide repeats. In addition, we determined the frequencies of the 23-bp and 12-bp indel regions associated with bovine PRNP transcriptional regulation.

None of the PRNP alleles for the B. indicus samples evaluated in this study exhibited an E211K amino acid replacement or any novel coding region polymorphism. To date, the E211K change has been reported in only two bovine samples, the 2006 Alabama atypical BSE case [7] and its only known living offspring [8]. The affected animal was a composite (B. taurus × B. indicus), but because no parental information is currently available, it is unknown whether the corresponding nucleotide change was inherited or the result of spontaneous mutation. If it was inherited, then the E211K allele may have originated in either a B. taurus ancestor or a B. indicus ancestor. Unfortunately, the data presented here cannot facilitate a species level assignment, as the PRNP coding sequence of the 2006 Alabama case did not possess any species-specific polymorphisms. This particular animal was determined to possess one haplotype with a 23 and 12-bp insertion, and the other with a 23 and 12-bp deletion [27]. These 2 haplotypes occur in 92% of B. taurus, but only in 25% B. indicus cattle (Table ?(Table1),1), as estimated by our analyses. Unless more information becomes available, it cannot be determined where the E211K replacement may have originated.

No B. indicus sample had an octapeptide region containing more than 6 repeats. Notably, humans are the only TSE-susceptible mammal besides the Brown Swiss breed of B. taurus cattle for which additional octapeptide repeats have been observed. Interestingly, a transgenic mouse model expressing bovine PrPC with 1 extra repeat was more susceptible to BSE challenge than a transgenic mouse with the normal number of repeats, but did not develop a spontaneous prion disease [14]. However, a transgenic mouse expressing a bovine PRNP gene encoding 4 additional repeats did in fact develop a spontaneous prion disease [15]. While cattle with 1 additional octapeptide repeat may have an enhanced risk for classical BSE only if exposed to infected material, the appearance of PRNP genes encoding extra octapeptide repeats in any cattle breed may be cause for concern.

The incidence of E211K as well as octapeptide regions with 7 repeats among cattle does not provide a species-level explanation for potential differences in susceptibility to BSE among B. taurus and B. indicus cattle. Therefore, only the 23-bp and 12-bp indel regions seem pertinent in these populations because both of these bovine PRNP sequence regions have been shown to influence transcription levels of PrPC. The B. indicus purebred and composite cattle had a very low frequency of the 23-bp insertion as compared to B. taurus, while only B. indicus purebred cattle had a high frequency of the 12-bp insertion. To date, no consensus has emerged regarding whether one of these bovine PRNP regions is more influential than the other with respect to classical BSE resistance in cattle. Originally, only the 23-bp region was found to be significantly associated with (classical) BSE resistance [26]. Using a reporter gene assay, it was later concluded that the 23-bp indel region was the most relevant locus, as the only constructs that lowered expression levels were those containing the 23-bp insertion [25]. In contrast, other reports indicate the 12-bp indel is more relevant both statistically [24] and in a reporter gene assay [30]. The discrepancy between the significance of these two regions with respect to resistance or susceptibility to classical BSE may be influenced by 3 or more factors. First, the 23-bp and 12-bp regions are physically linked (~2-Kbp apart). Therefore, recombination is most likely rare given the small distance separating the two indel polymorphisms. Moreover, high levels of linkage disequilibrium have been detected for genetic variation within the bovine PRNP promoter and intron 1 [31]. Secondarily, the 23-bp insertion and 12-bp deletion haplotype is absent among cattle surveyed to date, thereby creating an equal-to-greater overall frequency of 12-bp insertions as compared to the frequency spectrum of 23-bp insertions. More specifically, twice as many haplotypes (n = 12) contribute to the overall frequency of the 12-bp intron 1 insertion as those contributing to the frequency of the 23-bp insertion (n = 6; Table ?Table2).2). This may inevitably bias indel association studies. Lastly, species specific allelic variation associated with the genetic backgrounds of B. taurus and B. indicus may differentially interact with the 23-bp promoter and 12-bp intron 1 PRNP polymorphisms, perhaps making each polymorphism more or less relevant in a particular bovine species. On the basis of indel genotype alone, if it is ultimately concluded that the 23-bp insertion has a greater influence than the 12-bp insertion with respect to resistance to classical BSE in cattle following exposure to infected material, B. indicus purebred and composite cattle would be at greater risk than B. taurus cattle. Conversely, if the 12-bp insertion were to modulate a greater level of resistance to BSE, then B. indicus cattle would be at a lower risk than B. taurus and composite cattle.

Other Sections?

Conclusion

We determined the frequencies of known genetic factors associated with differential susceptibility to BSE in B. indicus purebred and B. indicus × B. taurus composite cattle, as compared to B. taurus purebred cattle. No deviations from the expected numbers of octapeptide repeats were detected for B. indicus purebred and composite cattle. Likewise, the E211K substitution was not detected within the PRNP coding sequences for cattle investigated herein. However, a significant difference was detected for a comparison of the 23-bp and 12-bp indel genotype frequencies between B. indicus and B. taurus cattle. The origin of this result could be attributed to significant differences in haplotype frequencies among B. indicus, B. taurus, and composite cattle. Currently, it is unknown which bovine PRNP region (23-bp promoter; 12-bp intron 1), if either, may be more important with respect to differential susceptibility to classical BSE in cattle following exposure to the etiologic agent. Should either the 23-bp promoter region or the 12-bp intron 1 region of the bovine PRNP prove more biologically relevant to the manifestation of disease, substantial heritable differences in overall susceptibility or resistance to classical BSE may exist between B. indicus and B. taurus cattle.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2569919/


let's take a closer look at this new prionpathy or prionopathy, and then let's look at the g-h-BSEalabama mad cow.

This new prionopathy in humans? the genetic makeup is IDENTICAL to the g-h-BSEalabama mad cow, the only _documented_ mad cow in the world to date like this, ......wait, it get's better. this new prionpathy is killing young and old humans, with LONG DURATION from onset of symptoms to death, and the symptoms are very similar to nvCJD victims, OH, and the plaques are very similar in some cases too, bbbut, it's not related to the g-h-BSEalabama cow, WAIT NOW, it gets even better, the new human prionpathy that they claim is a genetic TSE, has no relation to any gene mutation in that family. daaa, ya think it could be related to that mad cow with the same genetic make-up ??? there were literally tons and tons of banned mad cow protein in Alabama in commerce, and none of it transmitted to cows, and the cows to humans there from ??? r i g h t $$$

ALABAMA MAD COW g-h-BSEalabama

In this study, we identified a novel mutation in the bovine prion protein gene (Prnp), called E211K, of a confirmed BSE positive cow from Alabama, United States of America. This mutation is identical to the E200K pathogenic mutation found in humans with a genetic form of CJD. This finding represents the first report of a confirmed case of BSE with a potential pathogenic mutation within the bovine Prnp gene. We hypothesize that the bovine Prnp E211K mutation most likely has caused BSE in "the approximately 10-year-old cow" carrying the E221K mutation.

http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000156


http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.ppat.1000156&representation=PDF


her healthy calf also carried the mutation (J. A. Richt and S. M. Hall PLoS Pathog. 4, e1000156; 2008).

This raises the possibility that the disease could occasionally be genetic in origin. Indeed, the report of the UK BSE Inquiry in 2000 suggested that the UK epidemic had most likely originated from such a mutation and argued against the scrapierelated assumption. Such rare potential pathogenic PRNP mutations could occur in countries at present considered to be free of BSE, such as Australia and New Zealand. So it is important to maintain strict surveillance for BSE in cattle, with rigorous enforcement of the ruminant feed ban (many countries still feed ruminant proteins to pigs). Removal of specified risk material, such as brain and spinal cord, from cattle at slaughter prevents infected material from entering the human food chain. Routine genetic screening of cattle for PRNP mutations, which is now available, could provide additional data on the risk to the public. Because the point mutation identified in the Alabama animals is identical to that responsible for the commonest type of familial (genetic) CJD in humans, it is possible that the resulting infective prion protein might cross the bovine–human species barrier more easily. Patients with vCJD continue to be identified. The fact that this is happening less often should not lead to relaxation of the controls necessary to prevent future outbreaks.

Malcolm A. Ferguson-Smith Cambridge University Department of Veterinary Medicine, Madingley Road, Cambridge CB3 0ES, UK e-mail: maf12@cam.ac.uk Jürgen A. Richt College of Veterinary Medicine, Kansas State University, K224B Mosier Hall, Manhattan, Kansas 66506-5601, USA

NATURE|Vol 457|26 February 2009

http://www.nature.com/nature/journal/v457/n7233/full/4571079b.html


Friday, September 23, 2011

Bovine spongiform encephalopathy associated insertion/deletion polymorphisms of the prion protein gene in the four beef cattle breeds from North China

http://transmissiblespongiformencephalopathy.blogspot.com/2011/09/bovine-spongiform-encephalopathy.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


I am sure that most of you are aware of the Texas mad cow cases that were covered up. the 1st documented cover-up was successful, the second documented case of mad cow in Texas would have been successful, but after literally, an act of Congress to override Austin, Texas officials (rick perry), only after the Honorable Fong of the OIG, and scientist all over the world, and a few others, including myself wrote to the OIG about said cover-up, and 7 months later, did they finally retest that covered-up highly suspect mad cow, and said covered up mad cow was finally _confirmed_ by Weybridge as a confirmed Texas BSE mad cow case. this 7 months after the fact on a Government BSE REDBOOK regulations of a 48 turn around on said test. over course this was all done for a reason, the BSE MRR policy was being put into place while all this was going on, and Heaven forbid if rick perry would have had a confirmed BSE mad cow case while those regulations were over riding the BSE GBR risk assessments. however, during all this political science on mad cow disease, it was nothing more than a crap shoot, and 15 years later, we now know that some of the sporadic CJD cases are indeed tied to the atypical BSE cases here in North America. How many people during the Bush/Perry era, how many did they needlessly expose to mad cow disease? how many will go clinical and die in the decades to come? Whether or not you dare care, during the Bush/Perry era, they exposed our kids to mad cow disease, by feeding them dead stock downer cows via the NSLP, for over 4 years. DEAD STOCK DOWNER COWS ARE THE MOST HIGH RISK COW FOR MAD COW DISEASE. WHO will watch the children for the next 5 decades for CJD ???

http://www.organicconsumers.org/articles/article_23850.cfm



Thursday, July 21, 2011

A Second Case of Gerstmann-Sträussler-Scheinker Disease Linked to the G131V Mutation in the Prion Protein Gene in a Dutch Patient Journal of Neuropathology & Experimental Neurology:

August 2011 - Volume 70 - Issue 8 - pp 698-702

http://transmissiblespongiformencephalopathy.blogspot.com/2011/07/second-case-of-gerstmann-straussler.html


Saturday, August 14, 2010

BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and VPSPr PRIONPATHY

(see mad cow feed in COMMERCE IN ALABAMA...TSS)

http://prionpathy.blogspot.com/2010/08/bse-case-associated-with-prion-protein.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, 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


Thursday, August 4, 2011

Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011

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


Wednesday, September 21, 2011

PrioNet Canada researchers in Vancouver confirm prion-like properties in Amyotrophic Lateral Sclerosis (ALS)

http://transmissiblespongiformencephalopathy.blogspot.com/2011/09/prionet-canada-researchers-in-vancouver.html


see TSE prion updates ;

http://transmissiblespongiformencephalopathy.blogspot.com/




TSS

Heidenhain Variant of Sporadic Creutzfeldt-Jakob Disease With the Co-Occurrence of Two Different Types of Prion Protein

88 Heidenhain Variant of Sporadic Creutzfeldt-Jakob Disease With the Co-Occurrence of Two Different Types of Prion Protein

Ignazio Cali1, Gianfranco Puoti1, Janis Blevins1, Adeela Alizai2, Pierluigi Gambetti1. 1Case Western Reserve University; 2Temple University Hospital

Sporadic Creutzfeldt-Jacob disease (sCJD) is a rare neurodegenerative disorder classified into five distinct phenotypes based on i) the polymorphic methionine (M)/valine (V) genotype at codon 129, and ii) detection of either type 1 or type 2 of the protease-resistant prion protein (PrPres) (Parchi et al., Ann Neurol 1999; Gambetti et al., Br Med Bull 2003). Sporadic CJDMM1, the most common CJD subtype, is the only CJD subtype that includes the Heidenhain variant (HsCJD), a condition characterized by early and prominent visual deficits associated with the preferential involvement of the occipital cortex (Kropp et al., Arch Neurol 1999). The histopathological phenotype of HsCJD is indistinguishable from that of sCJDMM1. Recently, we described a group of sCJD cases identified as sCJDMM1-2 in which both PrPres types were found to co-exist in the same brain (Cali et al., Brain 2009). In the present study, we investigated whether the Heidenhain clinical phenotype is present in sCJDMM1-2. To date, the screening of clinical histories from 59 sCJDMM1-2 patients that were received at the National Prion Disease Pathology Surveillance Center between 1998 and 2009 has led to the identification of 8 (14%) HsCJDMM1-2 subjects. The detailed study of two HsCJDMM1-2 cases shows that the immunohistopathological features as well as PrPres type determined in different brain locations are consistent with the features of the sCJDMM1-2 subtype (Cali et al., Brain 2009). The visual cortex is severely affected in both cases and is found to carry both PrPres types (Kropp et al., Arch Neurol 1999). To our knowledge, this is the first finding of HsCJD in sCJDMM1-2 and indicates that the presence of even relatively large amounts of PrPres type 2 does not impede the expression of HsCJD.

(Supported by, NIH AG-14359, CDC UR8/CCU515004 and Charles S. Britton Foundation; the CDC Foundation).

http://journals.lww.com/jneuropath/Fulltext/2010/05000/American_Association_of_Neuropathologists,_Inc__.9.aspx




Monday, December 14, 2009


Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types



(hmmm, this is getting interesting now...TSS)



> Sporadic CJD type 1 and atypical/ Nor98 scrapie are characterized by fine (reticular) deposits,


see also ;


> All of the Heidenhain variants were of the methionine/ methionine type 1 molecular subtype.


http://cjdusa.blogspot.com/2009/09/co-existence-of-scrapie-prion-protein.html



see full text ;


Monday, December 14, 2009

Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types


http://nor-98.blogspot.com/2009/12/similarities-between-forms-of-sheep.html




Tuesday, April 28, 2009

Nor98-like Scrapie in the United States of America


http://nor-98.blogspot.com/2009/04/nor98-like-scrapie-in-united-states-of.html




Wednesday, March 3, 2010

NOR-98 ATYPICAL SCRAPIE USA 4 CASES DETECTED JANUARY 2010


http://nor-98.blogspot.com/2010/03/nor-98-atypical-scrapie-usa-4-cases.html




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



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



A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes

Annick Le Dur*,?, Vincent Béringue*,?, Olivier Andréoletti?, Fabienne Reine*, Thanh Lan Laï*, Thierry Baron§, Bjørn Bratberg¶, Jean-Luc Vilotte?, Pierre Sarradin**, Sylvie L. Benestad¶, and Hubert Laude*,?? +Author Affiliations

*Virologie Immunologie Moléculaires and ?Génétique Biochimique et Cytogénétique, Institut National de la Recherche Agronomique, 78350 Jouy-en-Josas, France; ?Unité Mixte de Recherche, Institut National de la Recherche Agronomique-Ecole Nationale Vétérinaire de Toulouse, Interactions Hôte Agent Pathogène, 31066 Toulouse, France; §Agence Française de Sécurité Sanitaire des Aliments, Unité Agents Transmissibles Non Conventionnels, 69364 Lyon, France; **Pathologie Infectieuse et Immunologie, Institut National de la Recherche Agronomique, 37380 Nouzilly, France; and ¶Department of Pathology, National Veterinary Institute, 0033 Oslo, Norway

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

Abstract Scrapie in small ruminants belongs to transmissible spongiform encephalopathies (TSEs), or prion diseases, a family of fatal neurodegenerative disorders that affect humans and animals and can transmit within and between species by ingestion or inoculation. Conversion of the host-encoded prion protein (PrP), normal cellular PrP (PrPc), into a misfolded form, abnormal PrP (PrPSc), plays a key role in TSE transmission and pathogenesis. The intensified surveillance of scrapie in the European Union, together with the improvement of PrPSc detection techniques, has led to the discovery of a growing number of so-called atypical scrapie cases. These include clinical Nor98 cases first identified in Norwegian sheep on the basis of unusual pathological and PrPSc molecular features and "cases" that produced discordant responses in the rapid tests currently applied to the large-scale random screening of slaughtered or fallen animals. Worryingly, a substantial proportion of such cases involved sheep with PrP genotypes known until now to confer natural resistance to conventional scrapie. 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.

http://www.pnas.org/content/102/44/16031.abstract



Monday, December 1, 2008

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



Tuesday, April 28, 2009

Nor98-like Scrapie in the United States of America


http://nor-98.blogspot.com/2009/04/nor98-like-scrapie-in-united-states-of.html



Heidenhain Variant Creutzfeldt Jakob Disease autopsy case report 'MOM'

DIVISION OF NEUROPATHOLOGY University of Texas Medical Branch 114 McCullough Bldg. Galveston, Texas 77555-0785

FAX COVER SHEET

DATE: 4-23-98

TO: Mr. Terry Singeltary @ -------

FROM: Gerald Campbell

FAX: (409) 772-5315 PHONE: (409) 772-2881

Number of Pages (including cover sheet):

Message:

*CONFIDENTIALITY NOTICE*

This document accompanying this transmission contains confidential information belonging to the sender that is legally privileged. This information is intended only for the use of the individual or entry names above. If you are not the intended recipient, you are hereby notified that any disclosure, copying distribution, or the taking of any action in reliances on the contents of this telefaxed information is strictly prohibited. If you received this telefax in error, please notify us by telephone immediately to arrange for return of the original documents. -------------------------- Patient Account: 90000014-518 Med. Rec. No.: (0160)118511Q Patient Name: POULTER, BARBARA Age: 63 YRS DOB: 10/17/34 Sex: F Admitting Race: C

Attending Dr.: Date / Time Admitted : 12/14/97 1228 Copies to:

UTMB University of Texas Medical Branch Galveston, Texas 77555-0543 (409) 772-1238 Fax (409) 772-5683 Pathology Report

FINAL AUTOPSY DIAGNOSIS Autopsy' Office (409)772-2858

Autopsy NO.: AU-97-00435

AUTOPSY INFORMATION: Occupation: Unknown Birthplace: Unknown Residence: Crystal Beach Date/Time of Death: 12/14/97 13:30 Date/Time of Autopsy: 12/15/97 15:00 Pathologist/Resident: Pencil/Fernandez Service: Private Restriction: Brain only

FINAL AUTOPSY DIAGNOSIS

I. Brain: Creutzfeldt-Jakob disease, Heidenhain variant.


http://creutzfeldt-jakob-disease.blogspot.com/2008/07/heidenhain-variant-creutzfeldt-jakob.html




Thursday, August 19, 2010

SCRAPIE CANADA UPDATE Current as of 2010-07-31 The following table lists sheep flocks and/or goat herds confirmed to be infected with scrapie in Canada in 2010.

Current as of: 2010-07-31

http://nor-98.blogspot.com/2010/08/scrapie-canada-update-current-as-of.html



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




Scrapie USA

http://scrapie-usa.blogspot.com/



Like lambs to the slaughter 31 March 2001 by Debora MacKenzie Magazine issue 2284

FOUR years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.

Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.

Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in ...


http://www.newscientist.com/article/mg16922840.300-like-lambs-to-the-slaughter.html




Wednesday, August 18, 2010

Incidence of CJD Deaths Reported by CJD-SS in Canada as of July 31, 2010

http://creutzfeldt-jakob-disease.blogspot.com/2010/08/incidence-of-cjd-deaths-reported-by-cjd.html



Monday, August 9, 2010

National Prion Disease Pathology Surveillance Center Cases Examined (July 31, 2010)

(please watch and listen to the video and the scientist speaking about atypical BSE and sporadic CJD and listen to Professor Aguzzi)


http://prionunitusaupdate2008.blogspot.com/2010/08/national-prion-disease-pathology.html




ALABAMA MAD COW g-h-BSEalabama

In this study, we identified a novel mutation in the bovine prion protein gene (Prnp), called E211K, of a confirmed BSE positive cow from Alabama, United States of America. This mutation is identical to the E200K pathogenic mutation found in humans with a genetic form of CJD. This finding represents the first report of a confirmed case of BSE with a potential pathogenic mutation within the bovine Prnp gene. We hypothesize that the bovine Prnp E211K mutation most likely has caused BSE in "the approximately 10-year-old cow" carrying the E221K mutation.


http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000156



http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.ppat.1000156&representation=PDF



Saturday, August 14, 2010

BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and VPSPr PRIONPATHY

(see mad cow feed in COMMERCE IN ALABAMA...TSS)

http://prionpathy.blogspot.com/2010/08/bse-case-associated-with-prion-protein.html



g-h-BSE-alabama E211K mad cows USA how many would that be annually ???


if our ciphering is correct (?), that would be about 35 g-h-BSE-alabama E211K mad cows going into the food chain a year.

an incidence of less than 1 in 2000.

let's see, that's 500 such per million.

or 50,000 cows per 100 million (US herd size).

even at less than 1 in a million, with 35 million slaughtered, that's 35 infected cows going into the food chain each year.

hmmm, friendly fire there from ???



Wednesday, July 28, 2010

re-Freedom of Information Act Project Number 3625-32000-086-05, Study of Atypical BSE UPDATE July 28, 2010

http://bse-atypical.blogspot.com/2010/07/re-freedom-of-information-act-project.html



Tuesday, August 03, 2010

Variably protease-sensitive prionopathy: A new sporadic disease of the prion protein

http://creutzfeldt-jakob-disease.blogspot.com/2010/08/variably-protease-sensitive-prionopathy.html



Monday, August 9, 2010

Variably protease-sensitive prionopathy: A new sporadic disease of the prion protein or just more PRIONBALONEY ?

http://prionunitusaupdate2008.blogspot.com/2010/08/variably-protease-sensitive-prionopathy.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/




TSS

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

News abstract

--------------------------------------------------------------------------------

Nature Medicine 15, 834 - 835 (2009) doi:10.1038/nm0809-834

Straight talk with...James Ironside

--------------------------------------------------------------------------------

Abstract

Would you entrust your brain to a bank? Well, many people do after they die, and such brain banks—often funded by government agencies or disease charities—are essential for neuroscience research. They collect and store the healthy and diseased brain specimens that neuroscientists need to explore neurological disorders such as Alzheimer's disease, schizophrenia and autism. Each brain bank typically has a limited supply of samples and tends to operate fairly independently. This means that researchers often have to trawl through numerous brain banks to find their desired specimens. Furthermore, there is a general shortage of brain samples. To help resolve these issues in the UK, James Ironside, professor of clinical neuropathology at the University of Edinburgh, was appointed in June as the director of the new UK Brain Banks Network. An expert in human prion diseases, particularly Creutzfeldt-Jakob disease (CJD), Ironside knows all about brain banks. He established the Brain and Tissue Bank at the UK's National CJD Surveillance Unit and is involved in the Sudden Death Brain and Tissue Bank at the University of Edinburgh. Jon Evans recently caught up with Ironside to discuss his new leadership position and how the brain network will benefit neuroscience research.


http://www.nature.com/nm/journal/v15/n8/abs/nm0809-834.html



straight talk with Terry Singeltary ;


Dr. James Ironside ask ;


> Would you entrust your brain to a bank?


WE all did here in the USA, and see what almost happened below ;


NIH may destroy human brain collection

By Steve Mitchell Medical Correspondent

Washington, DC, Mar. 24 (UPI) -- The National Institutes of Health may discard part or all of a rare collection that includes hundreds of human brain samples from patients that suffered from a disorder similar to mad cow disease -- unless another researcher or institution takes them on, United Press International has learned.

Several scientists said the collection, which is held by the NIH's National Institute for Neurological Disorders and Stroke in Bethesda, Md. -- and includes brains and other tissue samples from people afflicted with the brain-wasting illness Creutzfeldt Jakob disease -- is irreplaceable and could even provide insight into treatments for the fatal disorder. Currently, there is no cure for CJD and patients typically die within a year after symptoms begin.

However, NIH officials in control of the collection's fate told UPI the remaining samples are of little scientific value and may be disposed of if researchers outside the agency do not claim it. That position stands in sharp contrast with CJD experts who thought the collection should be preserved.

"It's invaluable," said Dr. Paul Brown, former medical director of the NIH's Laboratory for Central Nervous System Studies, whose expertise is in CJD and mad cow disease (also known as bovine spongiform encephalopathy, or BSE).

The collection is badly in need of organization and no one is certain how many brains or other tissue samples it contains, said Brown, who worked with the collection since its inception in the 1960's until his retirement last year. There could be brains, blood, spinal fluid and various other tissues from 1,000 people or more, he said. Some of the specimens would be of scientific use today, he said.

"This collection has the unique value of stretching back to the beginning of when these diseases were discovered," Brown told UPI, noting that the first samples were obtained in 1963. "It would be as though you had in your hands the possibility of finding out when AIDS started."

Bruce Johnson, a former technician at the CNSS lab who worked extensively with the collection before he retired in 2003, told UPI he was told "in two years they (NIH officials)are going to destroy it, if nobody wants it."

Eugene Major, acting director of the basic neuroscience program at the NIH, said no specific timeframe had been established.

"We have not set a firm deadline date," Major told UPI. "We are working very hard with investigators that we know in order to be able to make sure that whatever we deem is valuable is potentially kept here." Some samples already have been determined not to have any research value and have been "removed and disposed of," he said.

Others samples have been given out to Dr. David Asher at the Food and Drug Administration and Pierluigi Gambetti at the National Prion Disease Pathology Surveillance Center in Cleveland, Ohio.

Major maintained the remaining collection was not particularly valuable for research. "Whatever had been collected here that has not already been distributed to responsible investigators who could use them really has very little remaining value," he said.

Neither Asher nor Gambetti returned phone calls from UPI, but Brown said he thought Asher had received only a dozen or two samples at most and Gambetti had not received much at all.

Neil Cashman, a brain-disease researcher at the University of Toronto's Center for Research in Neurodegenerative Diseases -- who has tried to obtain the collection from the NIH -- said it was priceless.

"It would be like destroying an art museum," Cashman told UPI. "There's all this information and insight that's locked up in these tissues and if it's destroyed it will be lost forever."

The Memorial Institute for Neurodegenerative Diseases Inc., a non-profit organization consisting of more than 40 university and institute researchers from the United States, Canada, United Kingdom and France, also thinks the brain collection is invaluable.

"It is the opinion of the Board of Directors ... of The MIND Inc., that the ... brain bank should not be broken up nor destroyed," said Harry E. Peery, MIND's executive director, in a letter to UPI. "We believe that this collection is of inestimable research value and should be kept intact."

The institute, at the University of Saskatchewan in Saskatoon, applied for possession of the collection in early 2004, but received a letter from the NINDS indicating the fate of the collection had not yet been determined.

"We have heard nothing further since that time" and continue to be interested in acquiring the complete collection, Peery said.

CJD belongs to a group of rare, brain-wasting disorders that are little understood, incurable and fatal. This includes mad cow disease in cows, chronic wasting disease in deer and elk. The most infamous of these illnesses in humans is variant CJD, which people can contract from eating beef products infected with the mad-cow pathogen.

Although vCJD has infected more than 154 people worldwide, only one case has ever been detected in the United States -- in a Florida woman who is thought to have contracted the disease while living in the United Kingdom. However, the NIH brain samples have never been screened for vCJD -- something Johnson thinks is critically important.

"No one has ever looked to see if any American (in the collection) in the past had variant CJD," Johnson said. "You think it would be required that they do that. You think it would be a Congressional mandate that they test these brains: 'Let's see if we've got this disease in our country.'"

Johnson noted at least one brain in the collection he personally had examined -- from a French woman collected in 1971 -- showed evidence of possible vCJD infection, but the sample needed further study to be sure.

Other samples in the collection include the brains of patients who were only 16 years old when they were diagnosed with CJD. This would be unusual for sporadic CJD, because generally it strikes those over age 60. Variant CJD, on the other hand, typically occurs in patients in their 20s or younger.

"I thought it was absolutely vital (to test these brains)," Johnson said. "Maybe there's a dozen cases in there of variant CJD."

Major disagreed. "There's really no reason to do that," he said. "The effort it would take to screen those samples ... would not give us any new insights into variant CJD beyond what it is we already know."

Johnson said he was frustrated with the NIH administration's lack of interest in preserving the collection or testing for vCJD. "They don't understand," he said, "they honest-to-god don't understand what it's all about."

Patient advocates also objected to the possible destruction of the brains.

Terry Singeltary, whose mother died of a type of CJD called Heidenhain variant in 1997, said he is outraged and families of other CJD victims probably will be, too.

"A lot of these families went through a lot of heartache and a lot of trouble to get these brain samples to the NIH," Singeltary told UPI. "Now they're just going to discard them because they're not of scientific use? That's just asinine. That stuff is valuable information."

Graham Steel, vice-chair of the Human BSE Foundation in the United Kingdom, told UPI, "The potential loss of such important tissue samples would be a massive blow for TSE (the group of diseases that includes CJD and BSE) research in the United States. This should not be allowed to happen."

Singeltary noted there currently is no cure for these diseases. "If you don't have any answers yet, why would you throw these specimens away?" he asked.

He added that more sensitive tests are just becoming available and could help determine the origin of some of the CJD cases. "We've all been sitting around waiting for more sensitive tests to get validated because we want answers," he said.

"You know, it must be an embarrassment," Johnson said. "Some Senator is going to eventually say 'What is NIH doing about mad cow disease?' And people are going to scratch their heads and say 'not much'." He added, "What's going to happen (is) one of these senators or their wife is going to develop spontaneous CJD one day and ... there's going to be hell raised and they're going to ask, 'Why isn't NIH working on this?'"

--

http://www.washtimes.com/upi-breaking/20050323-053919-8481r.htm



http://www.accessmylibrary.com/coms2/summary_0286-8492054_ITM



http://www.promedmail.org/pls/otn/f?p=2400:1202:9557296506089968094::NO::F2400_P1202_CHECK_DISPLAY,F2400_P1202_PUB_MAIL_ID:X,28585



SCIENCE NEWS

Groups seek to save NIH brain collection

Published: April 1, 2005 at 4:48 PM By STEVE MITCHELL, Medical Correspondent

WASHINGTON, April 1 (UPI) -- Scientists, consumer groups and patient-advocates have embarked upon efforts -- including petitioning members of Congress and seeking storage space at a Canadian university -- to prevent the National Institutes of Health from destroying an irreplaceable collection of human brains from patients afflicted with a condition similar to mad cow disease.

As United Press International reported last week, the NIH has begun shopping for a new home for its collection of brains, spinal fluid and other tissues from hundreds of patients around the world who died from Creutzfeldt Jakob disease -- an incurable, fatal, brain-wasting illness. The collection dates back to 1963 and the consensus among scientists in this field is it is invaluable for research and could provide insights that might aid in developing diagnostic tests, treatments or cures for CJD.

NIH officials, however, maintain the remaining samples in the collection -- stored in some 30 freezers by the National Institute for Neurological Disorders and Stroke in Bethesda, Md. -- are of little value and may be disposed of if researchers or institutions do not come forward to claim them.

Families of patients who died of CJD have reacted with outrage, concerned that the effort mounted to collect the brains in the first place has been all for naught. Several have contacted their respective members of Congress and urged them to step in.

"The brains and brain tissue were sent to NIH in good faith for future research and destroying them is an outrage," Terry Singeltary, a patient advocate in Bacliff, Texas, wrote in a letter to Sen. Kay Bailey Hutchinson, R-Texas, and several other members of the state's congressional delegation. Singeltary's mother died of a type of CJD called Heidenhain variant in 1997.

Hutchinson's office did not return a call from UPI.

Eugene Major, who serves as acting director of the NINDS and is responsible for the fate of the brain collection, did not return a call from UPI.

"The patients these brains were taken from suffered greatly before they died of CJD," Heather Larson of Phoenix, whose mother succumbed to CJD last year at the age of 56, wrote in a letter to Arizona Republican Sens. John McCain and Jon Kyl, and Republican Rep. John Shadegg. "Their brains hold answers that can save human lives. Destroying the brains at Bethesda would greatly hinder the research being done to fight this disease and would cost many their lives."

The offices of McCain and Kyl did not return UPI's calls.

"The ravages of this disease, and the toll it takes not only on its victims but on family and loved ones, cannot easily be described to someone who has not witnessed it personally," Patty Cook of Kansas City, Kan., wrote in a letter to Kansas Republican Sens. Sam Brownback and Pat Roberts, and Democratic Rep. Dennis Moore.

"I urge you to do whatever you can to ensure these brains are not destroyed," added Cook, whose mother died of CJD in 1982.

Brownback's office did not return a call from UPI.

CJD belongs to a group of diseases -- called transmissible spongiform encephalopathies or TSEs -- that includes mad cow disease, chronic wasting disease in deer and elk, scrapie in sheep and several types of CJD in humans. There is no cure for CJD and it typically results in death within a year after the onset of symptoms.

Consumer groups also are concerned and are considering taking steps to ensure the brain collection will be preserved.

"This is outrageous," Michael Hansen, a biologist and senior research associate with Consumers Union in Yonkers, N.Y., told UPI. "Those brains are a critical resource for CJD science and they must be at a research facility."

Hansen added that his late friend, Joe Gibbs, the former chief of NINDS's Laboratory of Central Nervous System Studies, told him the brain of famed choreographer George Balanchine, who died of CJD in 1983, resides in the collection.

"How can we claim to be a scientific country if we're going to be throwing away an irreplaceable repository of the first evidence of these diseases?" asked Felicia Nestor, who serves as a consultant to Public Citizen.

There may be hope yet for the collection, however.

Neil Cashman, an expert on TSEs at the University of Toronto's Center for Research in Neurodegenerative Diseases, told UPI he has been attempting to drum up support for acquiring the collection with his colleagues at the University of British Columbia in Vancouver -- where he plans to move this summer.

"I'm trying to organize support for an official letter from UBC to NIH to request the collection," Cashman said.

The letter will probably go out in about a month, he said.

"The goal would be to make it a resource for the world and make the tissues available to scientists who had a reasonable request," he added.

Singeltary said he has heard from at least one other prominent scientist in this field who said they planned to contact the NIH and urge it to reconsider the fate of the collection.

One brain in the collection, that of a French woman who died in 1971, may help provide clues about the origins of variant CJD -- a condition similar to CJD that humans can contract from eating beef products contaminated with the mad-cow pathogen. The first recognized case of vCJD occurred in 1995 in the United Kingdom, but an NIH scientist said he tested the French woman's brain in 2000 and found signs consistent with vCJD -- not CJD.

French researchers currently are re-examining specimens from the case to determine if the woman was indeed infected with vCJD. If she was, it would suggest the disease began infecting people more than 20 years earlier than previously thought.

Cashman said the case underscores the value of the NIH brain collection.

"There is information locked up in these freezers that will be lost forever if this collection is destroyed," he said.

--

E-mail: sciencemail@upi.com

© 2005 United Press International, Inc. All Rights Reserved.


http://www.upi.com/Science_News/2005/04/01/Groups-seek-to-save-NIH-brain-collection/UPI-72961112392131/



NIH sends mixed signals on CJD brains

By Steve Mitchell Medical Correspondent

Washington, DC, Apr. 7 (UPI) -- A National Institutes of Health official who told United Press International the agency might destroy its collection of brains from human patients afflicted with a condition similar to mad cow disease reportedly has told the head of a patient-advocate group the collection would be preserved.

The official, Eugene Major, acting director of the basic neuroscience program at the NIH, has not responded to e-mail or a phone call from UPI seeking clarification of his remarks, and the official status of the collection remains unknown.

As reported by UPI on March 24, the collection is stored in freezers by the NIH's National Institute for Neurological Disorders and Stroke in Bethesda, Md. It contains brains and other tissue samples from hundreds of people who died from the brain-wasting illness Creutzfeldt Jakob disease, as well as tissues from an untold number of experimental animals.

The consensus of scientists in this field is the collection, which dates back to 1963, is invaluable for research and could even provide insight into treatments for the fatal disorder. Currently, there is no cure for CJD and patients typically die within a year after symptoms begin.

Florence Kranitz, president of the non-profit advocacy group CJD Foundation, told UPI she had "a very long conversation" with Major, in which he told her the remaining tissues in the collection would not be destroyed.

"He reassured me in no uncertain terms," Kranitz said, noting constituents of the foundation and other CJD advocacy groups had been expressing concerns to her the tissues would be destroyed.

Kranitz, who has personal reasons for wanting the collection preserved -- her husband died of CJD in 2000 -- said she plans to meet with Major at the end of April to discuss the issue further.

CJD belongs to a group of diseases collectively known as transmissible spongiform encephalopathies, or TSEs, that includes mad cow disease in cows, chronic wasting disease in deer and elk, and scrapie in sheep. All TSEs are incurable and fatal.

Major previously told UPI some samples already have been destroyed and others have been given to researchers at the Food and Drug Administration and the National Prion Disease Pathology Surveillance Center in Cleveland.

Major said the remaining collection "has very little remaining value" and could be destroyed if another entity does not claim them.

Bruce Johnson, a former NIH scientist who retired at the end of 2003, said he had been told the collection would be destroyed in two years if no one took the samples from the NIH.

In response to hearing that Major had failed to confirm to UPI the brain collection would not be destroyed, Patricia Ewanitz, who lives in Port Jefferson Station, N.Y., and is founder of the advocacy group CJD Voice, said, "The brain tissue might not be indispensable to the National Institutes of Health but it is absolutely necessary to the families who thought enough of science to donate the brains, brain tissue and blood in hopes of someday finding an answer to why their loved one died."

Ewanitz, whose husband died of CJD in 1997, added, "It now seems like such a joke."

Terry Singeltary, whose mother passed away from a type of CJD in 1997, said the NIH should use the samples for scientific research, not just store them in freezers.

Both Singeltary and Ewanitz said they would feel more reassured if Major verified in writing the collection will not be destroyed.

"I would go further and ask Major what he plans to do with them," Singeltary said. "If the samples are just going to sit up there and go bad, then they should give them out to researchers looking for cause and cure."

The revelation the NIH might destroy part or all of the collection sparked an outcry from patient advocates, consumer groups and scientists.

Advocates have been contacting their members of Congress, urging them to investigate and prevent the NIH from destroying the brains. Consumer groups also have gotten involved and scientists have taken steps to obtain the collection or have urged Major not to destroy the samples.

Felicia Nestor, who serves as a consultant to Public Citizen, told UPI she had contacted certain legislators and at least one was considering looking into the situation. Nestor asked the legislator's name be withheld.

Kranitz said Major also told her he plans "to advertise in professional neurological journals and by whatever means necessary to make it known" to researchers in the field the tissues are available.

Major previously said, however, that efforts to inform researchers of the availability of the collection were already underway and included informing NIH grantees. He added he had personally notified researchers at scientific meetings, but no TSE researcher contacted by UPI was aware of this.

"I was never informed," said Laura Manuelidis, an expert on these diseases and section chief of surgery in the neuropathology department at Yale University. She said the first she had heard of the situation was in UPI's March 24 report.

Manuelidis also said she contacted Major, expressing interest in the specimens, but so far has not received a response.

"I sent a letter to (Major) on (March 25) about our interest in these specimens, but he has not replied," she told UPI in an e-mail.

Neil Cashman, a TSE expert at the University of Toronto, who said he was not aware the samples might be destroyed, has lobbied colleagues at the University of British Columbia -- where Cashman is scheduled to move to this summer -- to help draft a letter requesting the collection.

The Memorial Institute for Neurodegenerative Diseases Inc., a non-profit organization consisting of more than 40 university and institute researchers from the United States, Canada, the United Kingdom and France, requested the collection in January, 2004. So far, the institute has not been informed of a decision by the NIH.

Asked if Major had told him whether the collection would be preserved, MIND Executive Director Harry Peery said, "We have heard nothing further from Eugene Major or anyone else at the NIH regarding the brain collection."

--

http://www.upi.com/Science_News/2005/04/07/NIH-sends-mixed-signals-on-CJD-brains/UPI-25701112902231/





my letter to Government Officials begging for help ;



-------- Original Message --------

Subject: NIH to destroy our loved ones brain tissues, WE NEED YOUR HELP PLEASE
Date: Fri, 25 Mar 2005 16:04:57 -0600
From: "Terry S. Singeltary Sr."

To: senator@hutchison.senate.gov

CC: Judith.Zaffirini@senate.state.tx.us, Bob.Deuell@senate.state.tx.us, District98.Truitt@house.state.tx.us, District115.Jackson@house.state.tx.us, Jane.Nelson@senate.state.tx.us, District96.Zedler@house.state.tx.us, Jon.Lindsay@senate.state.tx.us, f-gilstrap@tamu.edu, ka-phillips@tamu.edu


References: <422CA640.3030108@wt.net>


Greetings again Honorable Senator Hutchison and other Honorable Members of Texas Office,


My name is Terry S. Singeltary Sr. I lost my Mother to hvCJD aka mad cow.THE Heidenhain Variant of Creutzfeldt Jakob Disease. (there is more than one strain of mad cow disease and i will reference last)

I am once again writing to you on a matter of extreme importance. I would appreciate your assistance in writing to the National Institutes of Health requesting that the brain tissue collected over the years at NINDS from family members of Creutzfeldt-Jakob Disease victims be preserved and recorded and not discarded.

[See attached articles]

THE WASHINGTON TIMES UNITED PRESS INTERNATIONAL

NIH may destroy human brain collection

By Steve Mitchell Medical CorrespondentWashington, DC, Mar. 24 (UPI) -- ...


SNIP...END...TSS



FINALLY ONE, and only one Senator, did reply to my concerns, and help us with preserving the brain tissue bank at NIH. I had sent a hard copy via US postal to the Honorable Senator John Cornyn (see below), but none of the (above) Senators and other officials ever bothered to reply.


See The Honorable John Cornyn Reply below ;




JOHN CORNYN TEXAS UNITED STATES SENATE WASHINGTON, DC 20510-4305 April 26,2005

Mr. Terry Singeltary

P.O. Box 42

Bacliff, Texas 77518

Dear Mr. Singeltary:

In response to your recent request for my assistance, I have contacted the National Institutes ofHealth. I will write you again as soon as I receive a reply. I appreciate having the opportunity to represent you in the United States Senate and to be ofservice in this matter.

Sincerely,

JOHN CORNYN United States Senator JC:djl


===============


JOHN CORNYN TEXAS UNITED STATES SENATE WASHINGTON, DC 20510-4305

May 18,2005

Mr. Terry Singeltary

P.O. Box 42

Bacliff, Texas 77518

Dear Mr. Singeltary:

Enclosed is the reply I received from the Department of Health and Human Services in response to my earlier inquiry on your behalf. I hope this will be useful to you. I appreciate having the opportunity to represent you in the United States Senate. Thank you for taking time to contact me. Sincerely,

JOHN CORNYN United States Senate JC:djl Enclosure

DEPARTMENT OF HEALTH & HUMAN SERVICES National Institutes of HealthNational Institute of NeurologicalDisorders and Stroke NINDS Building 31, Room 8A52 31 Center Dr., MSC 2540 Bethesda, Maryland 20892-2540 Phone: 301-496-9746 Fax: 301-496-0296 Email: [log in to unmask]

May 10, 2005

The Honorable John CornynUnited States SenatorOccidental Tower5005 LBJ Freeway, Suite 1150Dallas, Texas 75244-6199

Dear Senator Cornyn:

Your letter to the National Institutes of Health (NIH) forwarding correspondence from Mr. Terry S. Singeltary, Sr., has been forwarded to me for reply. Mr. Singeltary is concerned about thepreservation of Creutzfeldt-Jakob disease (CJD) brain samples that have been maintained by theNational Institute of Neurological Disorders and Stroke (NINDS) Intramural Research programfor many years. I am sorry to learn that Mr. Singeltary's mother died of CJD and can certainly understand hisdesire that any tissues that could help investigators unravel the puzzle of this deadly disease arepreserved. I hope he will be pleased to learn that all the brains and other tissues with potential tohelp scientists learn about CJD are, and will continue to be, conserved. (The tissues that arediscarded are those that have either decayed to an extent that renders them no longer appropriatefor research or those for which we do not have sufficient identification.) The purpose of gathering these brains and tissues is to help scientists learn about CJD. To that end, some of the NINDS-held samples are distributed to investigators who can demonstrate thatthey have a compelling research or public health need for such materials. For example, sampleshave been transferred to NIH grantee Dr. Pierluigi Gambetti, who heads the National PrionDiseases Pathology Surveillance Center at Case Western Reserve University in Ohio and workswith the Centers for Disease Control and Prevention to monitor all cases of CJD in the UnitedStates. Dr. Gambetti studies the tissues to learn about the formation, physical and chemicalproperties, and pathogenic mechanisms of prion proteins, which are believed to be involved inthe cause of CJD. Samples have also been transferred to Dr. David Asher, at the U.S. Food andDrug Administration, for use in assessing a potential diagnostic test for CJD.

Page 2 - The Honorable John Cornyn

in closing, we know that donating organs and tissue from loved ones is a very difficult andpersonal choice that must often be made at the most stressful of times. We at the NINDS aregrateful to those stalwart family members who make this choice in the selfless hope that it willhelp others afflicted with CJD. We also know the invaluable contribution such donations maketo the advancement of medical science, and we are dedicated to the preservation of all of thetissue samples that can help in our efforts to overcome CJD.

I hope this information is helpful to you in responding to Mr. Singeltary. Sincerely,

Story C. Landis, Ph.D. Director, National Institute ofNeurological Disorders and Stroke


==================================


NIH says it will preserve CJD brains

By STEVE MITCHELL

WASHINGTON, May 31 (UPI) -- The National Institutes of Health apparently has reversed its position on the fate of an invaluable collection of brains from people afflicted with a condition similar to mad cow disease, saying in a letter to a U.S. senator it will not destroy the collection.

An NIH official had told United Press International previously that the brain collection, which consists of samples from hundreds of people who died from the brain-wasting illness called Creutzfeldt Jakob disease, could be discarded if another entity does not claim them.

That sparked an outcry from patient-advocacy groups, consumer watchdogs and scientists, and the agency now appears to have backed away from that course.

"All the brains and other tissues with potential to help scientists learn about CJD are, and will continue to be, conserved," Story Landis, director of the National Institute of Neurological Disorders and Stroke, which oversees the brain collection, wrote in a May 10 letter to Sen. John Cornyn, R-Texas.

Cornyn had inquired about the status of the collection in April.

Last March, Eugene Major, acting director of the basic neuroscience program at the NIH, told UPI the useful portions of the collection had been doled out to scientists and the remaining samples had "very little remaining value" and could be destroyed.

Landis could not be reached for comment Tuesday. NINDS spokesman Paul Girolami told UPI he had been unable to locate her.

Scientists think the collection, which dates back to 1963, is invaluable for research on CJD and similar diseases and could even provide insight into treatments. There is no cure for CJD and patients typically die within a year after symptoms begin.

"Absolutely, the collection is worth keeping," Bruce Johnson, a former NIH scientist who said he had been told the collection would be destroyed in two years if no one took the samples from the agency, told UPI.

The Memorial Institute for Neurodegenerative Diseases Inc., a non-profit organization consisting of more than 40 researchers from several countries, offered to take the collection off of NIH's hands more than a year ago and so far has not heard anything from the agency, Harry Peery, MIND's executive director, told UPI.

CJD belongs to a group of incurable and fatal diseases collectively known as transmissible spongiform encephalopathies, or TSEs, that includes mad cow disease in cows, chronic wasting disease in deer and elk, and scrapie in sheep.

Variant CJD, or vCJD, is a relatively new TSE, which people can contract from consuming beef products infected with the mad cow pathogen.

Despite Landis' assurance the collection will be preserved, some family members of the patients who donated their brains to the NIH are still skeptical. This is because the wording Landis used in the letter leaves open the possibility that some brain samples are being destroyed.

"The tissues that are discarded are those that have either decayed to an extent that renders them no longer appropriate for research or those for which we do not have sufficient identification," Landis wrote.

"Which ones" are being destroyed? asked Terry Singeltary, who is involved with several CJD patient groups.

"With a system like this, they could destroy whatever and whenever they wanted, for whatever reason they wanted," Singeltary, whose mother died of CJD in 1997, told UPI.

"It's a perfect excuse to discard some suspicious tissue resembling vCJD or some atypical TSE related to animal TSEs in the USA," he added.

Although the collection includes samples from CJD patients as young as 16 that could make them candidates for possible vCJD, the brains have never been screened for evidence of the disease. The only confirmed vCJD case in the United States occurred in a Florida woman who is thought to have contracted the disease in England.

Johnson said he along with renowned CJD expert Paul Brown were in the process of sorting through the samples to match them up with patient identification documents until they both retired. Some of the samples may prove impossible to identify, he said, but he and Brown are the only ones familiar enough with the collection to organize it and neither has been asked back by the agency to aid in the identification process.

Steve Mitchell is UPI's Medical Correspondent. E-mail: [log in to unmask]

Copyright 2005 by United Press International. All Rights Reserved.


http://www.upi.com/Science_News/2005/05/31/NIH-says-it-will-preserve-CJD-brains/UPI-67711117574761/




=====================


US scientist accused of selling tissue samples Deal said to earn $285,000 for vials that cost millions By Diedtra Henderson, Globe Staff June 14, 2006

WASHINGTON -- A senior government scientist pocketed hundreds of thousands of dollars as a drug company consultant in exchange for human tissue samples that cost the federal government millions to acquire, congressional investigators said yesterday .

The House Energy and Commerce Committee report, the culmination of a one-year inquiry, was released hours before a two-day hearing began to explore the government's practices for procuring human tissue samples. According to congressional investigators, the National Institutes of Health's Dr. Trey Sunderland agreed to collaborate with Pfizer Inc. , the world's largest drug company. Sunderland, chief of the geriatric psychiatry branch of the National Institute for Mental Health , sent Pfizer 3,200 tubes of spinal fluid and 388 tubes of plasma collected for Alzheimer's research.

The government spent $6.4 million to obtain the 3,500 samples that showed how Alzheimer's disease progressed in 538 subjects.

Pfizer paid Sunderland $285,000 in consulting fees related to the samples, investigators said. In total, Pfizer paid him more than $600,000 from 1998 to 2004 for outside consulting and speaking fees. Sunderland is scheduled to testify today at the hearing.

``Contrary to the House committee report, Dr. Sunderland did not receive any payments from Pfizer for human tissue samples," said Robert F. Muse, the scientist's Washington, D.C., attorney. ``He acted properly, ethically, and legally in his relationship with Pfizer."

Pfizer spokeswoman Kate Robins said the company had a transfer agreement endorsed by the NIH that permitted Sunderland to send cerebrospinal fluid from research participants with Alzheimer's, the participant's relatives who were at higher risk of developing the neurological disease, and elderly adults with normal Alzheimer's risk.

Sunderland's consulting role tapped his Alzheimer's disease expertise to look for signals in the samples that could help identify and diagnose the disease.

``The payments over a six-year period were reasonable and customary for an expert of Dr. Sunderland's stature, and reflect the fair-market value of his consulting services," Robins said.

The report said the tissue transfers, reported by a government whistleblower, raised serious questions about how the government ensures its scientists do not abuse their positions and about the agency's ability to track the valuable samples.

``NIH tells us it has no centralized inventory system that could tell the NIH director how many vials of tissues are in freezers at a particular institute," said Representative Joe Barton , Republican of Texas and House Energy and Commerce Committee chairman . ``It would really be a shame if we find out that the National Institutes of Health has more control over its paper clips and trash cans than it has over its human tissue samples."

John T. Burklow , a NIH spokesman, said the agency shares ``the committee's concerns in regard to the ethical management of human tissue samples."

Sunderland's arrangement with the drug maker -- made without NIH knowledge, according to Burklow -- occurred after the agency relaxed its ethics policy covering scientists' outside activities and ended before the agency enacted more stringent rules.

The NIH, pressured by Barton's committee, on Aug. 25 curbed outside consulting deals between its scientists and pharmaceutical and biotechnology companies.

Diedtra Henderson can be reached at [log in to unmask]

© Copyright 2006 Globe Newspaper Company.


http://www.boston.com/business/globe/articles/2006/06/14/us_scientist_accused_of_selling_tissue_samples/



NIH Scientist Exploited Human Tissue Samples For Personal Gain, Report Finds

Academic Shipped 3,500 Tubes to Pfizer; Pocketed $285,000

WASHINGTON - A senior scientist at the National Institutes of Health (NIH) shared thousands of valuable human tissue samples with the drug giant Pfizer, netting himself at least $285,000 and raising serious questions about existing government safeguards against abuse, a new House Energy and Commerce Committee staff report has found.

The report was released today in conjunction with a two-day Subcommittee on Oversight and Investigations hearing entitled "Human Tissue Samples: NIH Research Policies and Practices."

According to the committee's investigation, Dr. Trey Sunderland, chief of the Geriatric Psychiatry Branch of the National Institute for Mental Health, shipped 3,200 tubes of spinal fluid and 388 tubes of plasma collected for Alzheimer's research. As a result, Dr. Sunderland was paid $285,000 by Pfizer for consulting work related to the samples. All told, Dr. Sunderland received more than $600,000 in payments from Pfizer from 1998 to 2004 for outside consulting and speaking with any record of prior approval or disclosure in his government financial report filings.

Scientists considered the 3,500 samples, chronicling the progression of Alzheimer's disease on the same subjects over several years, to be priceless. An analysis by committee staff determined that simply procuring the samples from 538 subjects cost U.S. taxpayers $6.4 million. "It was unlikely that anywhere but at the clinics of NIH could this unique historical collection of human tissue samples be assembled," the report reads.

Committee investigators concluded that there were "reasonable grounds to believe" that obtaining the samples was a "primary reason for Pfizer's interest in collaborating with Dr. Sunderland."

The NIH's Office of Management Assessment has found that Dr. Sunderland's misconduct violated ethics rules as well as federal law and regulation. Yet, years after the transactions, he has not been prosecuted or disciplined to any measurable degree. He remains an employee at NIH and a member of the Public Health Service Corps.

The committee's year-long inquiry into the collections, storage, tracking and use of human tissue samples in the NIH's intramural research program was prompted in part by concerns raised by a former NIH scientist, Dr. Susan Molchan, in April 2005.

Human tissues include everything from DNA to organs to blood and they play a critical role in modern scientific research. According to the RAND Corporation, there are more than 307 million tissue samples from more than 178 million people stored in the United States .

Among the report's other findings:

The National Institutes of Health have "no uniform, centralized, and mandatory authority regulating the handling of human tissue samples. Some NIH laboratories kept a written record on the maintenance of these samples, but other NIH laboratories did not." NIH had "no formal inventory control or tracking system. ... Moreover, the lack of accountability left NIH wholly vulnerable to theft and diversion of valuable human tissue samples. These preliminary inquiries raised serious concerns over what was described to committee staff by NIH officials of a fairly loose, ad-hoc approach to controlling human tissue samples." http://energycommerce.house.gov/108/News/06132006_1941.htm

Barton: NIH Must Regain Control of Tissue Samples, Ethical Lapses 'It would really be a shame if we find out that the National Institute of Health has more control over its paper clips and trash cans than it has over its human tissue samples.' - Chairman Joe Barton

WASHINGTON - U.S. Rep. Joe Barton, R-Texas, chairman of the House Energy and Commerce Committee, issued the following statement today as part of an Oversight and Investigations Subcommittee hearing entitled "Human Tissue Samples: NIH Research Policies And Practices:"

"As I said, at the last set of oversight hearings on NIH, the hallmark of this committee has always been its oversight responsibility and its willingness and ability to hold agencies responsible under its jurisdiction and that produce results in better government and better services for the American people.

"Two years ago, we found that there were weaknesses in the system at that time and that those weaknesses were more severe than had been previously recognized. To his credit, Dr. Zerhouni, had a ringside seat at these hearings and took the facts of the hearings seriously and changed and reformed the NIH ethics system.

"Today we are going to take a look at how NIH protects its most precious assets -- the material that is at the core of the NIH research mission: human tissue samples. Once again, after extensive investigation on a bipartisan basis, we have found deeper concerns regarding human tissue samples at NIH than we first believed. We have found a lack of a centralized database and a lack of oversight at NIH that could, and probably does, leave NIH laboratory vulnerable to the risks of theft and abuse. We know from previous investigations that NIH has an inventory system, but NIH tells us it has no centralized inventory system that could tell the NIH director how many vials of tissues are in freezers at a particular institute. It would really be a shame if we find out that the National Institute of Health has more control over its paper clips and trash cans than it has over its human tissue samples.

"The committee has investigated a case and found evidence of a serious breach of trust. This case has focused on Dr. Trey Sunderland, who is supposed to be a witness later in this hearing. He's a very noted and respected researcher in the field of Alzheimer's disease. I wish we were here to discuss some great discovery he made to cure, or at least alleviate, the hazards of Alzheimer's. Instead, we are discussing the ways he used his position to use NIH spinal fluid samples to further his undisclosed, personal consulting. The information provided to the committee shows that Pfizer paid Dr. Sunderland $285,000 during the 1998-2003 time period to consult on two projects involving spinal fluid samples that Dr. Sunderland sent to Pfizer. During this same time period, Pfizer also paid Dr. Sunderland approximately $300,000 for lectures. These figures don't even count almost $200,000 additional for undisclosed activities with other companies. There is also evidence that he advised his subordinate to conceal these consulting activities involving the samples. This is from an official who for 10 years chaired a committee that reviews the ethics of conducting mental health research on human beings. This certainly appears to be a betrayal of the public trust that NIH stands for.

"These hearings underscore the need to enact NIH reauthorization and reform legislation. The NIH director must have some baseline of information about NIH assets. If we are going to gain new efficiencies and hopefully more effective ways to translate research into better healthcare, enacting NIH reauthorization legislation is of the highest importance.

"Out of this investigation of disturbing questions and concerns, we can use these hearings to make NIH stronger and better. The National Institute of Health is indeed a national treasure. It must be cherished, protected, nourished and allowed to flourish. Today's hearings are a first step toward strengthening public trust in NIH research and preserving confidence in its integrity.

"I thank you, Mr. Chairman, and Mr. Stupak for the bipartisan nature of this investigation. I also thank Mr. Dingell for his support of this investigation. Finally, I look forward to working with Dr. Zerhouni and the leadership of NIH on this matter and helping NIH become better managed -- and thus deliver the results for the health of America that we so depend on NIH to do."

####

--------------------------------------------------------------------------------


http://energycommerce.house.gov/108/News/06132006_1949.htm



FOR IMMEDIATE RELEASE Tuesday, June 13, 2006

CONTACT: OD Office of Communications and Public Liaison 301-496-5787

NIH Statement Regarding House Hearing on Human Tissue Samples

Attribution: John Burklow, NIH spokesman

NIH’s position on ethics is clear: any conflict of interest resulting in an individual personally profiting from official government research activities cannot be tolerated. We are committed to maintaining the public’s trust in NIH and its scientists as an unbiased source of biomedical research guidance and advice. The case under consideration concerns events that began in 1998 — after the NIH ethics rules concerning outside activities were relaxed — and that ended before the new rules were put in place. NIH has previously referred this case to the relevant authorities for appropriate action.

It is important to note that the specific consulting arrangements in question, had they been known to NIH, would not have been approved under the present or previous ethics regulations. Outside consulting connected to an NIH employee’s official government duties has always been prohibited at NIH.

NIH has undertaken a comprehensive review of its activities and conflict of interest policies in the last few years. As a result of that process, on August 25, 2005, NIH implemented comprehensive ethics rules that make it clear what NIH scientists can and cannot do in regard to outside activities. These new rules removed any ambiguity about what is allowed or not allowed. Here are two important points:

Under new NIH regulations, all NIH employees are now prohibited from engaging in outside employment with pharmaceutical companies and biotechnology companies in their private capacities — period. Collaboration and partnership with industry can nonetheless be very valuable in scientific pursuits and NIH rules allow such activities, as long as they are undertaken through an officially approved Cooperative Research and Development Agreement (CRADA). Although we cannot discuss this particular case because it remains under investigation, we can speak to the relevant issues that it raises.

Collaborations among scientists that involve human tissue samples are common and essential for science. There are, however, stringent rules in place to protect the participants who donated their samples, and to ensure that there is full informed consent.

We share the Committee’s concerns in regard to the ethical management of human tissue samples and the development of rigorous and uniform policies to protect the public’s trust and interests, while advancing science to address important public health problems. The thousands of scientists who work at NIH have always been and remain committed to these principles.

The Office of the Director, the central office at NIH, is responsible for setting policy for NIH, which includes 27 Institutes and Centers. This involves planning, managing, and coordinating the programs and activities of all NIH components. The Office of the Director also includes program offices which are responsible for stimulating specific areas of research throughout NIH. Additional information is available at http://www.nih.gov/icd/od/.

The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.


http://www.nih.gov/news/pr/jun2006/od-13.htm



THE LEGALITY OF STEALING ORGAN/TISSUE...TEXAS STATUTES


http://creutzfeldt-jakob-disease.blogspot.com/2008/01/cjd-hgh-body-snatchers.html



Friday, August 07, 2009

CJD Human Cornea Tissue, Recall END OF ENFORCEMENT REPORT FOR AUGUST 5, 2009


http://creutzfeldt-jakob-disease.blogspot.com/2009/08/cjd-human-cornea-tissue-recall-end-of.html





NATIONAL CREUTZFELDT-JAKOB DISEASE SURVEILLANCE UNITSCIENTIFIC REPORT2007/08


NCJDSU Scientific Report 2008

SPORADIC CJD

Question 7. What is the cause of sporadic CJD (sCJD) ? What are the risks of secondary transmission of sCJD?

Case control studies

Risk factor information has been collected for cases of sporadic CJD since before the Unit was established in 1990. Over the years various control groups have been recruited; the method chosen depending on the resources available and anticipated validity. These have been detailed in various previous NCJDSU Annual Reports.

Since 1990 there have been five papers published examining risk factors for sCJD that the Unit has either led or collaborated in:-

1) Wientjens et al, Neurology 1996. A meta analysis of three case control studies (178 CJD cases and 333 controls). The results showed an elevated risk of CJD for those with a family history of dementia, a history of poliomyelitis, those employed as health professionals and those exposed to cows and sheep. There was no association with consumption of animal organs, including brain.

2) van Duijn et al, Lancet 1998- this compared 405 CJD cases and 405 hospital controls recruited as part of the 1993-95 EU collaborative studies of CJD in Europe. The findings suggested that genetic factors other than CJD mutations may play an important part in CJD. Iatrogenic transmission seemed rare in the population studied. There was little evidence of association between the risk of CJD and animal exposure or consumption of processed bovine meat or milk products for the period studied.

3) Zerr I et al, J Clin Epid 2000- medical risk factors were examined using the 405 CJD cases and 405 hospital controls recruited as part of the 1993-95 EU collaborative studies of CJD in Europe. The study failed to identify any common medical risk factor for CJD.

4) Ward et al, Neurology 2002- Surgical risk factors from 326 sCJD cases recruited as part of the 1993-95 EU collaborative studies of CJD in Europe were compared with 326 community controls recruited by telephone in 2000. A history of surgery was associated with risk of sCJD and the results supported the hypothesis that sCJD may result from hitherto unrecognised surgical contamination events.

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5) Ward et al, Annals of Neurology 2007- Medical risk factors for 431 sCJD cases resident in the UK and referred to NCJDSU between 1998-2006 were compared with 454 general population control subjects recruited 2002-2003 (see NatCen controls in Appendix 6). This study found some evidence for a link between increased risk of sCJD and surgery, however there was no convincing evidence of temporal-geographical links between cases undergoing neurosurgery or gynaecological surgery. It concluded that it was unlikely that a high proportion of UK sCJD cases were the result of surgical transmission, but the possibility of such transmission cannot be excluded.

As for vCJD (see Questions 2 and 5 above), further work examining data from general practitioner records of cases and controls needs to be carried out in order to accurately determine risk for sCJD associated with medical or surgical procedures. This is on-going, though the priority has been given to vCJD at present.

Blood transfusion

An analysis of the potential for blood transfusion to be a risk factor for the development of sporadic CJD has been undertaken collaboratively by the major EU countries (coordinator M Pocchiari). A prospective study is under consideration.

Genetic factors

Possible genetic factors related to sCJD are being investigated by the Unit, both internally and through external collaboration (see Question 8 below).

Geographical distribution

The investigation of the geographical distribution of sporadic CJD by genetic and molecular subtype is on-going in the Unit.

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NCJDSU Scientific Report 2008

Question 8: What are the clinico-pathological, genetic & molecular features of sporadic CJD and how are they related?

While this is an interesting question in its own right, it has an extremely important bearing on the Unit’s core surveillance function, particularly in relation to vCJD. This is because the most important and potentially difficult differential diagnosis of vCJD is sCJD; many initial reports of suspect cases of vCJD in the UK and elsewhere, have been found to be atypical cases of sCJD. A full characterisation of the clinico- pathological, epidemiological and molecular phenotypes of sCJD is therefore clearly essential, which the Unit has continued to carry out within the UK.

Atypical clinical presentations, disease courses and pathological findings are found in only a small percentage of sCJD cases and so are difficult to characterise, even in the UK population of 50-60 million. This is of particular importance in relation to any attempt to recognise new clinical disease phenotypes either related to BSE or, potentially, to other animal diseases. Therefore, our international collaborations have contributed greatly to the analysis of clinical, epidemiological and pathological data. For example, within the NEUROCJD collaboration, a detailed study was undertaken of particular presentations of sporadic CJD, such as pure cerebellar ataxia and Heidenhain’s syndrome (currently being prepared for publication). Studies of atypical forms and cases with young age of onset are in progress (Murray et al, J Neurol Neurosurg Psychiatry 2008). The large number of cases of sCJD accumulated within the system allowed a detailed study of the factors that separately influence disease duration (Pocchiari et al, Brain 2004).
It is well established that the clinico-pathological features of sCJD vary with PRNP-129 genotype and PrP protein type. Both the Unit’s Molecular Genetic and Protein Laboratories contribute to the full clinico-pathological-molecular characterisation of sCJD cases and research is being undertaken into these correlations. Research into possible genetic factors that affect susceptibility and disease phenotype in sCJD has been described above in Question 3.
The differentiation of atypical sCJD from vCJD is potentially aided by prion protein molecular data. However, the relationship between PrP protein type and CJD strain is not as straightforward as it initially seemed and, in particular, the Unit has been active in research into the phenomenon of the co-occurrence of prion types in individual cases of

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CJD. Work carried out by the Prion Protein Laboratory used a type 1 specific antibody (12B2) to show that type 1 PrPres is a minor component in brains of sporadic CJD cases previously classified as type 2 and also that a minority type 1 component is present in BSE brain, in all tested cases of vCJD and in vCJD transmitted to wild-type mice (Yull et al, Am J Pathol 2006). Whilst this work provoked interest and a study with similar conclusions was published by the Aguzzi laboratory (University Hospital, Zurich), the findings are somewhat controversial. To address this, the Unit has conducted a detailed study of the WHO CJD standard reference materials (available from the UK National Institute for Biological Standards and Control) to compare the PrPres mixtures in cases of sporadic CJD that are acknowledged to be genuine mixtures, to those of vCJD where antibodies such as 12B2 are needed to detect the type 1 component. A paper is in preparation for publication. The distribution of disease-related prion protein in extra-neural tissues (such as skeletal muscle and pituitary) in cases of sCJD is an area of developing interest (Peden et al, Am J Pathol 2006; J Gen Virol 2007), which the Prion Protein Laboratory plans to continue to pursue in the future.

The protein laboratory studies have also included work on other forms of CJD. The study of iatrogenic CJD shows the presence of types 1 and/or type 2 PrPres, similar to those found in sporadic CJD, but with a very different protein type and codon 129 genotype distribution. These data, and that on panencephalopathic CJD, have been correlated with clinico-pathological data and are currently being prepared for publication and provide valuable comparisons with the sporadic and variant forms of CJD.

The relationship between PrPres type and agent strain is being investigated by ongoing analysis of transmission to wild-type mice in collaboration with the Neuropathogenesis Division, Roslin Institute. Studies of the transmission characteristics of subtypes of sporadic CJD in a human transgenic model have also been completed (J Manson) and provide important information on the extent of strain variation in sCJD and the influence of codon 129 genotype and prion protein type. This later project is harmonised with the EU funded HUMTRANS project which aims at identifying strain variation in all forms of human prion disease, including ’atypical’ cases (J Manson).

Complementing animal transmission studies the Prion Protein Laboratory aims to model the transmission of human prions, and prion protein conversion, by comparing the

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results of mouse transmission studies with the infection of cell cultures (including human stem cells) and the cell-free protein misfolding cyclic amplification (PMCA) method. The results of initial studies using PMCA indicate that amplification depends on both host and agent factors and that PrPres types are amplified with fidelity from sCJD brain (Jones & Head, unpublished observation). ...


snip...


http://www.cjd.ed.ac.uk/scientificreport.pdf




also see ;





Further characterisation of the prion protein molecular types detectable in the NIBSC CreutzfeldteJakob disease brain reference materials


1.4. Mixed PrP types The co-occurrence of types 1 and 2 in cases of sCJD is now a well recognised phenomenon [5,10,11,12] and several independent studies have each concluded that when an extensive brain sampling protocol is employed 20-50% of sCJD cases can be seen to contain both type 1 and type 2 PrPres [7,10,13,14,15].


AMAZING !!!

terry




Further characterisation of the prion protein molecular types detectable in the NIBSC CreutzfeldteJakob disease brain reference materials

Helen M. Yull, James W. Ironside, Mark W. Head* National CJD Surveillance Unit, School of Molecular & Clinical Medicine (Pathology), University of Edinburgh, Edinburgh, United Kingdom

Received 17 November 2008; revised 29 December 2008; accepted 23 January 2009

Abstract

Sporadic and variant CreutzfeldteJakob disease brain reference materials available from the UK National Institute for Biological Standards and Control have been subjected to further characterisation by Western blot analysis, with particular reference to the co-occurrence of different abnormal disease-associated prion protein (PrPSc) types. The results confirm the presence of genuine type 1 and type 2 protease-resistant PrP (PrPres) in each of the three sporadic CreutzfeldteJakob disease reagents, and provide evidence supporting the lower level presence of type 1 PrPres in the variant CreutzfeldteJakob disease reagents. We conclude that these reagents provide a valuable resource for future research and development.


snip...


1.4. Mixed PrP types The co-occurrence of types 1 and 2 in cases of sCJD is now a well recognised phenomenon [5,10,11,12] and several independent studies have each concluded that when an extensive brain sampling protocol is employed 20-50% of sCJD cases can be seen to contain both type 1 and type 2 PrPres [7,10,13,14,15].

snip...


On a superficial level the presence of more than one PrPSc type in individual CJD brains may seem at variance with the molecular strain typing hypothesis, which proposes that individual prion strains are enciphered by unique and self-perpetuating conformations and glycosylation states. However, this is not necessarily the case. It has long been known that multiple strains may be derived in mice from individual scrapie isolates, and cross-species transmission can, on occasion lead to an abrupt change in apparent strain characteristics.


snip...see full text ;


2009 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved. Keywords: CreutzfeldteJakob disease; Standards; Prion protein; Molecular typing; Co-occurrence



http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WBS-4VRWNKF-3&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=5a0c2f13b5476b0ddfea5bf9882300df




Beyond PrPres Type 1/Type 2 Dichotomy in Creutzfeldt-Jakob Disease

ArticleRelated ContentComments: 0.Formal Correction: This article has been formally corrected to address the following errors.

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Abstract Author Summary Introduction Materials and Methods Results Discussion Author Contributions References Emmanuelle Uro-Coste1#, Hervé Cassard2#, Stéphanie Simon3, Séverine Lugan2, Jean-Marc Bilheude4, Armand Perret-Liaudet5, James W. Ironside6, Stéphane Haik7,8, Christelle Basset-Leobon1, Caroline Lacroux2, Katell Peoch'9, Nathalie Streichenberger5, Jan Langeveld10, Mark W. Head6, Jacques Grassi3, Jean-Jacques Hauw8, Francois Schelcher2, Marie Bernadette Delisle1, Olivier Andréoletti2*

1 INSERM U858, Institut de Médecine Moléculaire de Rangueil and Service d'Anatomie Pathologique et Histologie-Cytologie, C.H.U. Rangueil, Toulouse, France, 2 UMR Institut National de la Recherche Agronomique (INRA)/Ecole Nationale Vétérinaire de Toulouse (ENVT) 1225, Interactions Hôtes Agents Pathogènes, ENVT, Toulouse, France, 3 Commissariat à l'Energie Atomique (CEA), Service de Pharmacologie et d'Immunologie, DRM, CEA/Saclay, Gif sur Yvette, France, 4 Bio-Rad, Research and Development Department, Marnes-la-Coquette, France, 5 Hôpital Neurologique, Services de Neurochimie et de Pathologie, Bron, France, 6 National Creutzfeldt-Jakob Disease Surveillance Unit, Division of Pathology, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom, 7 INSERM, Equipe Avenir, Maladies à Prions chez l'Homme, Paris, France, 8 Neuropathology Laboratory, Salpêtrière Hospital, AP-HP, Paris, France, 9 Service de Biochimie et Biologie Moléculaire, Hôpital Lariboisière, Paris (Laboratoire associé au CNR “ATNC”) et EA 3621 Faculté de Pharmacie, Paris, France, 10 Central Institute for Animal Disease Control CIDC-Lelystad, Lelystad, The Netherlands

Abstract Top Sporadic Creutzfeldt-Jakob disease (sCJD) cases are currently subclassified according to the methionine/valine polymorphism at codon 129 of the PRNP gene and the proteinase K (PK) digested abnormal prion protein (PrPres) identified on Western blotting (type 1 or type 2). These biochemically distinct PrPres types have been considered to represent potential distinct prion strains. However, since cases of CJD show co-occurrence of type 1 and type 2 PrPres in the brain, the basis of this classification system and its relationship to agent strain are under discussion. Different brain areas from 41 sCJD and 12 iatrogenic CJD (iCJD) cases were investigated, using Western blotting for PrPres and two other biochemical assays reflecting the behaviour of the disease-associated form of the prion protein (PrPSc) under variable PK digestion conditions. In 30% of cases, both type 1 and type 2 PrPres were identified. Despite this, the other two biochemical assays found that PrPSc from an individual patient demonstrated uniform biochemical properties. Moreover, in sCJD, four distinct biochemical PrPSc subgroups were identified that correlated with the current sCJD clinico-pathological classification. In iCJD, four similar biochemical clusters were observed, but these did not correlate to any particular PRNP 129 polymorphism or western blot PrPres pattern. The identification of four different PrPSc biochemical subgroups in sCJD and iCJD, irrespective of the PRNP polymorphism at codon 129 and the PrPres isoform provides an alternative biochemical definition of PrPSc diversity and new insight in the perception of Human TSE agents variability.

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Discussion Top Coexistence of Different PrPres Types in the Same Subject In this study, detection, by WB, of the coexistence of two PrPres types in about 30% (13/41) of cases is consistent with already published data [12],[14]. This observation could suggest the existence in brain from a single patient of different abnormal PrP species. Although two main PK cleavage sites are associated with PrPres type 1 and type 2 (respectively amino acid 82 and 97), N-terminal sequencing revealed in all investigated cases the presence of a whole spectrum of overlapping cleavage sites. Moreover in a part of investigated cases this technique demonstrated the presence (i) of variable but consistent level of type 1 PrPres in patients classified type 2 using WB and (ii) in some patient classified type 1, of low amount of type 2 PrPres [10]. These observations could suggest that, rather than a pure type 1 or type 2 PrPres, PK digestion of a PrPSc specific conformer generate variable mixture of PrPres fragments (with presence of dominant or sub dominant type 1 or type 2 PrPres), which WB usually failed to reveal accurately because its intrinsic technical limits [14]. Antibodies either harbouring higher affinity to PrP (like Sha31) [18] or probing specifically type 1 PrPres (like 12B2) [20], now allow a better perception of such mixture. However, investigations carried out using artificial mixture of type 1 and type 2 brain homogenate, even using high affinity anti-PrP antibodies, clearly indicate the current limits of WB discriminative power [14]. Together, these data suggest that WB analysis of PrPres on its own could be misleading for adequate discrimination between PrPSc variants in CJD.

Both PrPSc PK resistance ELISA and strain typing ELISA are based on the characterization the N terminal part of the PrPSc PK digestion either by increasing PK amount or modifying detergent conditions. While WB profile could be compared to a snapshot picture of PrPres fragments generated by PK digestion process, these assays reflect the dynamics of the PK cleavage rather than its final result (different forms of PrPres). Consequently they could provide different but also more accurate perception of the PrPSc conformers.

Our findings from the PrPSc capture immunoassays clearly indicate that in a single patient, irrespective of brain area, sCJD associated PrPSc displays uniform biochemical properties, regardless of the regional variation of type 1 and type 2 isoforms determined by WB. Such findings support the idea of the presence of a specific TSE agent in each brain and the accumulation of a single associated PrPSc conformer.

sCJD Classification Because the limited size of our cohort of cases, an in depth comparison between the PrPSc signature (as established in this study) and the Parchi classification system is not possible.

However, despite this limitation, two major groups were identified in our panel according to the PrPSc properties. The first major group was constituted with patients harbouring a highly PK resistant PrPSc (MM1 and MV1 patients). The second group included patients harboring a PK labile PrPSc (VV2 and MV2 patients). Using both lesion profile and clinical parameters [2], two major forms of sCJD are commonly recognized. The first sCJD form, named “classical”, is characterized by a “rapid evolution” (usually around 4 months), and affects most of the MM1 and MV1 patients. The second sCJD form, named “atypical”, affects VV2 and MV2 with a longer symptomatic evolution (usually longer than 6 months) and a late dementia. Despite inter-individual variations, sCJD Groups 1 and 2, as we defined them on biochemical criteria were consistent with this classification.

Both VV1 and MM2 sCJD cases are extremely rare; they respectively represent 1% and 4% of the identified sCJD cases. According to the literature, these patients have clinical features and lesion profiles that are very different from other sCJD patients [2]. However, in our study as in previously published studies, WB did not identify any distinct biochemical difference from other type 1 and type 2 cases. In contrast, both the strain typing ELISA and PrPSc resistance assays clearly differentiated these cases from Group 1 and Group 2 cases. This finding, which is consistent with clinico/pathological observations carried out in patients, could indicate that there are indeed differences in PrPSc that distinguish these VV1 and MM2 cases from other sCJD groups.

Prion Strains and PrPSc Phenotype Although prion strains can only be identified definitively by bioassay, molecular in vitro tools to characterize PrPSc are more and more widely used for the rapid identification of particular agents, such as BSE in cattle, sheep, rodent and humans (vCJD) [20],[21]. This has come to be termed “molecular strain typing” and although widely employed, the exact relationship between PrPSc biochemistry and the biological properties of the agents responsible remain to be determined. In sCJD, the presence of four distinct PrPSc biochemical forms apparently correlated to clinico-pathological phenotypes as defined by Parchi et al. [2] could be an indication of the involvement of different TSE agents.

iCJD cases are a consequence of accidental human to human TSE transmission, most likely representing transmission of sCJD. The identification in iCJD cases of the four PrPSc signatures identified in sCJD is consistent with the existence of distinct prions associated with these biochemical forms.

Three examples of human-to-human transmission of variant CJD through blood transfusion have now been identified. While all blood donors were MM at codon 129 PRNP, the recipients had either a MM (n = 2) or a MV genotype (n = 1). Despite this genotype difference there appears to have been conservation of the disease phenotype and PrPres type in all “secondary” vCJD cases [22]–[25]. These observations could suggest that in case of inter-human transmission, difference in donor/recipient genotype could result in un-altered abnormal PrP signature.

Our identification of MM GH iCJD cases harbouring similar PrPSc signature as a VV1 sCJD case or of a VV dura mater iCJD case similar to MM2 sCJD might indicate preservation of a specific PrPSc biochemical signature after human to human transmission between individuals of different codon 129 genotypes.

Treatment with extracts of GH contaminated by CJD has lead to a high number of iCJD cases in France and the UK. The codon 129 genotypes of the affected individuals in the two countries differ, with the French cohort predominantly MM and MV and the British cohort MV and VV [26]. In the absence of any clear explanation for this finding, it was suggested that it might be due to contamination of different batches of GH with different prion strains from individuals of differing PRNP codon 129 genotypes. Our identification of different biochemical forms of PrPSc in GH French patients and in UK patients is consistent with this hypothesis. The variability observed within the French GH cases could signify involvement of different prion strains, consistent with multiple contaminated GH batches in the French epidemic.

Conclusion The identification in this study of different PrPSc species in CJD patients with the same PRNP polymorphism at codon 129 and WB PrPres profile offers a new perspective on our understanding of the relationship between PrP biochemistry, prion disease phenotype and agent strain. We highlight two novel approaches to analysing PrPSc in sCJD and iCJD and offer evidence that these analyses provide potentially-strain associated information, which appears to be lacking from the conventional WB assay.



http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1000029




Saturday, April 04, 2009 An unusually presenting case of sCJD—The VV1 subtype Volume 111, Issue 3, Pages 282-291 (April 2009)

An unusually presenting case of sCJD—The VV1 subtype

Kaloyan S. Taneva, Mimi Yilmab

Received 16 November 2007; received in revised form 4 September 2008; accepted 12 September 2008.

Abstract Creutzfeldt–Jakob disease (CJD) is a rapidly progressive neurodegenerative disease caused by prions. Typically CJD presents with a triad of rapidly progressive dementia, abnormal movements (e.g., myoclonus) and electroencephalographic (EEG) changes. Recently, CJD has been subdivided into subtypes based on host genetic polymorphisms and the characteristics of the pathological prion protein. Different subtypes likely have different clinical and laboratory presentations. We describe a case of sporadic CJD of the VV1 subtype. We describe our patient's clinical symptoms, time course, laboratory workup, structural and functional neuroimaging data, EEG data and CJD biomarkers. Our patient presented with clinical symptoms atypical for CJD. Because of that, her clinical symptoms were initially attributed to psychiatric reasons. After extensive clinical and laboratory investigation, we concluded that the patient probably had CJD. Postmortem neuropathological results confirmed this clinical hypothesis. We compare our patient's clinical, laboratory and neuroimaging data to the data on typical CJD as well as the data on the few CJD VV1 cases described in the literature. We discuss our case's relevance to the diagnosis of CJD.

Keywords: Creutzfeldt–Jakob disease, Dementia, Neuroimaging, Magnetic resonance imaging, Electroencephalography, Biomarkers, Prion diseases a Department of Psychiatry, Massachusetts General Hospital, 55 Fruit Street, Warren 1220/Blake 11, Boston, MA 02114, United States

b University of Connecticut Health Center, Farmington, CT, United States

Corresponding author. Tel.: +1 617 726 7511; fax: +1 617 724 9155.

PII: S0303-8467(08)00320-X

doi:10.1016/j.clineuro.2008.09.017

© 2008 Elsevier B.V. All rights reserved.

http://www.clineu-journal.com/article/S0303-8467(08)00320-X/abstract


rare atypical strain of sporadic cjd ??? seems these rare strains are increasing ???


Wednesday, February 04, 2009

Creutzfeldt-Jacob disease presenting as severe depression: a case report

http://creutzfeldt-jakob-disease.blogspot.com/2009/02/creutzfeldt-jacob-disease-presenting-as.html


A case-control study of sporadic Creutzfeldt-Jakob disease in Switzerland: analysis of potential risk factors with regard to an increased CJD incidence in the years 2001-2004

http://creutzfeldt-jakob-disease.blogspot.com/2009/02/case-control-study-of-sporadic.html


Thursday, July 10, 2008

A New Prionopathy update July 10, 2008

snip...

DOES ANYONE BESIDES ME SEE A PATTERN YET ???

Vickey Rimmer, 16, DID NOT DIE FROM nvCJD, she died from a form of sporadic CJD, whatever the hell that is. and there have been 16 year old die from sporadic CJD in the USA as well.

SIMPLY PUT, the ukbsenvcjd only theory was wrong from day one. the elderly are expendable, pets and kids are not.

Science was dictated by 'big buisness' after the Vickey Rimmer case with the ukbsenvcjd only myth.

snip...

Sporadic creutzfeldt-jakob disease in two adolescents

http://jnnp.bmj.com/cgi/content/abstract/jnnp.2006.104570v1


see full text sporadic CJD the big lie;

snip...

IT seems we have come full circle from the 'ORIGINAL 10' i.e. the 1st 10 adolescents in the UKBSEnvCJD only theory. and now we find us at the 1st 10 in USA, or is it the first 10, or the tip of the iceburg, many that went undocumented ???

lets look at the full circle, to date ;

http://cjdmadcowbaseoct2007.blogspot.com/2008/07/new-prionopathy-update-july-10-2008.html


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



full text ;


http://creutzfeldt-jakob-disease.blogspot.com/2009/04/unusually-presenting-case-of-scjdthe.html




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

Saturday, July, 18, 2009

Greetings,

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. North America seems to have the most species with documented Transmissible Spongiform Encephalopathy's, most all of which have been rendered and fed back to food producing animals and to humans for years. If you look at the statistics, sporadic CJD seems to be rising in the USA, and has been, with atypical cases of the sCJD. I find deeply disturbing in the year of 2009, that Human Transmissible Spongiform Encephalopathy of any strain and or phenotype, of all age groups, and I stress all age groups, because human TSE's do not know age, and they do not know borders. someone 56 years old, that has a human TSE, that has surgery, can pass this TSE agent on i.e. friendly fire, and or passing it forward, and there have been documented nvCJD in a 74 year old. Remembering also that only sporadic CJD has been documented to transmit via iatrogenic routes, until recently with the 4 cases of blood related transmission, of which the origin is thought to be nvCJD donors. However most Iatrogenic CJD cases are nothing more than sporadic CJD, until the source is proven, then it becomes Iatrogenic. An oxymoron of sorts, because all sporadic CJD is, are multiple forms, or strains, or phenotypes of Creutzfeldt Jakob Disease, that the route and source and species have not been confirmed and or documented. When will the myth of the UKBSEnvCJD only theory be put to bed for good. This theory in my opinion, and the following there from, as the GOLD STANDARD, has done nothing more than help spread this agent around the globe. Politics and money have caused the terrible consequences to date, and the fact that TSEs are a slow incubating death, but a death that is 100% certain for those that are exposed and live long enough to go clinical. once clinical, there is no recourse, to date. But, while sub-clinical, how many can one exposed human infect? Can humans exposed to CWD and scrapie strains pass it forward as some form of sporadic CJD in the surgical and medical arenas? why must we wait decades and decades to prove this point, only to expose millions needlessly, only for the sake of the industries involved? would it not have been prudent from the beginning to just include all TSE's, and rule them out from there with transmission studies and change policies there from, as opposed to doing just the opposite? The science of TSE's have been nothing more than a political circus since the beginning, and for anyone to still believe in this one strain, one group of bovines, in one geographical location, with only one age group of human TSE i.e. nvCJD myth, for anyone to believe this today only enhances to spreading of these human and animal TSE's. This is exactly why we have been in this quagmire.

The ones that believe that there is a spontaneous CJD in 85%+ of all cases of human TSE, and the ones that do not believe that cattle can have this same phenomenon, are two of the same, the industry, and so goes the political science aspect of this tobacco and or asbestos scenario i.e. follow the money. I could go into all angles of this man made nightmare, the real facts and science, for instance, the continuing rendering technology and slow cooking with low temps that brewed this stew up, and the fact that THE USA HAD THIS TECHNOLOGY FIRST AND SHIPPED IT TO THE U.K. SOME 5 YEARS BEFORE THE U.S. STARTED USING THE SAME TECHNOLOGY, to save on fuel cost. This is what supposedly amplified the TSE agent via sheep scrapie, and spread via feed in the U.K. bovine, and other countries exporting the tainted product. BUT most everyone ignores this fact, and the fact that the U.S. has been recycling more TSE, from more species with TSEs, than any other country documented, but yet, it's all spontaneous, and the rise in sporadic CJD in the U.S. is a happenstance of bad luck ??? I respectfully disagree. To top that all off, the infamous BSE-FIREWALL that the USDA always brags about was nothing more than ink on paper, and I can prove this. YOU can ignore it, but this is FACT (see source, as late as 2007, in one recall alone, some 10,000,000 MILLION POUNDS OF BANNED MAD COW FEED WENT OUT INTO COMMERCE TO BE FED OUT, and most was never recovered. This was banned blood laced, meat and bone meal. 2006 was a banner year for banned mad cow protein going into commerce in the U.S. (see source of FDA feed ban warning letter below). I stress that the August 4, 1997 USA mad cow feed ban and this infamous BSE firewall, was nothing more than ink on paper, it was never enforceable.

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. 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. This would further have to be broken down to strain of species and then the route of transmission would further have to be broken down. Accumulation and Transmission are key to the threshold from sub-clinical to clinical disease, and key to all this, is to stop the amplification and transmission of this agent, the spreading of, no matter what strain. In my opinion, to continue with this myth that the U.K. strain of BSE one strain TSE in cows, and the nv/v CJD one strain TSE humans, and the one geographical location source i.e. U.K., and that all the rest of human TSE are just one single strain i.e. sporadic CJD, a happenstance of bad luck that just happens due to a twisted protein that just twisted the wrong way, IN 85%+ OF ALL HUMAN TSEs, when to date there are 6 different phenotypes of sCJD, and growing per Gambetti et al, and that no other animal TSE transmits to humans ??? With all due respect to all Scientist that believe this, I beg to differ. To continue with this masquerade will only continue to spread, expose, and kill, who knows how many more in the years and decades to come. ONE was enough for me, My Mom, hvCJD i.e. Heidenhain Variant CJD, DOD 12/14/97 confirmed, which is nothing more than another mans name added to CJD, like CJD itself, Jakob and Creutzfeldt, or Gerstmann-Straussler-Scheinker syndrome, just another CJD or human TSE, named after another human. WE are only kidding ourselves with the current diagnostic criteria for human and animal TSE, especially differentiating between the nvCJD vs the sporadic CJD strains and then the GSS strains and also the FFI fatal familial insomnia strains or the ones that mimics one or the other of those TSE? Tissue infectivity and strain typing of the many variants of the human and animal TSEs are paramount in all variants of all TSE. There must be a proper classification that will differentiate between all these human TSE in order to do this. With the CDI and other more sensitive testing coming about, I only hope that my proposal will some day be taken seriously. ...

please see history, and the ever evolving TSE science to date ;

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


SEE THE DAMNING VIDEO NOW AT THE BOTTOM OF THE BLOG BELOW ;

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



Saturday, August 01, 2009

Cases of Early-Onset Sporadic Creutzfeld-Jakob Disease in Michigan

http://creutzfeldt-jakob-disease.blogspot.com/2009/08/cases-of-early-onset-sporadic.html




2006


From: TSS
Subject: HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory
Date: January 29, 2006 at 9:03 am PST
In Reply to: Tracking Spongiform Encephalopathies in North America (Lancet Infectious Disease Volume 3, Number 8 01 August 2003)
posted by TSS on August 14, 2003 at 6:56 pm:
------------------------------------------------------------
Comments sent via JAMA Feedback Page
------------------------------------------------------------
NAME: Terry S. Singeltary Sr.
E-MAIL: flounder9@verizon.net
PREVIOUS PAGE: http://jama.ama-assn.org/


Comments sent via JAMA Feedback Page

NAME: Terry S. Singeltary Sr. E-MAIL: flounder9@verizon.net




COMMENTS: I wish to submit the following ;

HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory

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 2005. With all the science to date refuting it, to continue to validate this myth, will only spread this TSE agent through a multitude of potential routes and sources...snip...end...TSS



Monday, April 20, 2009

National Prion Disease Pathology Surveillance Center Cases Examined1 (December 31, 2008)

http://prionunitusaupdate2008.blogspot.com/2009/04/national-prion-disease-pathology.html




CJD TEXAS (cjd clusters)

http://cjdtexas.blogspot.com/



USA WRITTEN CJD QUESTIONNAIRE ???

http://cjdquestionnaire.blogspot.com/


The statistical incidence of CJD cases in the United States has been revised to reflect that there is one case per 9000 in adults age 55 and older. Eighty-five percent of the cases are sporadic, meaning there is no known cause at present.

http://www.cjdfoundation.org/fact.html


Attending Dr.: Date / Time Admitted : 12/14/97 1228

UTMB University of Texas Medical Branch Galveston, Texas 77555-0543 (409) 772-1238 Fax (409) 772-5683 Pathology Report

FINAL AUTOPSY DIAGNOSIS Autopsy' Office (409)772-2858

FINAL AUTOPSY DIAGNOSIS

I. Brain: Creutzfeldt-Jakob disease, Heidenhain variant.

http://creutzfeldt-jakob-disease.blogspot.com/2008/07/heidenhain-variant-creutzfeldt-jakob.html







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


Transgenic mice expressing porcine prion protein resistant to classical scrapie but susceptible to sheep bovine spongiform encephalopathy and atypical scrapie. Emerg Infect Dis. 2009 Aug; [Epub ahead of print]

http://nor-98.blogspot.com/2009/07/transgenic-mice-expressing-porcine.html


Transmissible mink encephalopathy - review of the etiology

http://transmissible-mink-encephalopathy.blogspot.com/2009/07/transmissible-mink-encephalopathy.html


Wednesday, July 1, 2009

Nor98 scrapie identified in the United States J Vet Diagn Invest 21:454-463 (2009)

http://nor-98.blogspot.com/2009/07/nor98-scrapie-identified-in-united.html


Monday, June 01, 2009 Biochemical typing of pathological prion protein in aging cattle with BSE

SOMETHING TO PONDER ???

O.K. confusious asks, IF all these new atypical BSEs i.e. new strains of mad cow disease is just an 'OLD COW PRION DISEASE', why then can not the 'old human prion disease' such as the sporadic CJD, be from an 'old cow prion disease', same as the nvCJD 'young people mad cow disease' (which also happens in 74 year old), but why cannot the 'old cow prion diseases', i.e. l-BSE, h-BSE, and ibncBSE, cause the 'old people prion disease', which looks like sporadic CJD. seems that is what some of the pathology is showing ???

OH, that probably makes too much sense, and that the only answer could be that it's all just a happenstance of bad luck and or a spontaneous event, that just happens out of the clear blue sky $$$

IF this is the case, then where are all the SPONTANEOUS BSE CASES OF MAD COW DISEASE IN THE U.S.A., AND WHERE HAVE THEY BEEN BURIED IN THE USA OVER THE LAST 25 YEARS ???

http://bse-atypical.blogspot.com/2009/06/biochemical-typing-of-pathological.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


Thursday, July 23, 2009

UW Hospital warning 53 patients about possible exposure to rare brain disease

http://creutzfeldt-jakob-disease.blogspot.com/2009/07/uw-hospital-warning-53-patients-about.html


Wednesday, August 05, 2009 Rate of CWD infection increases in core area WISCONSIN

http://chronic-wasting-disease.blogspot.com/2009/08/rate-of-cwd-infection-increases-in-core.html


Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518