RE-Hunters Should Not be Concerned with Eating Venison

oh my God ! maybe you should read up on the latest science, not the junk science, but sound science ;

From: "Terry S. Singeltary Sr." Subject: CWD UPDATE 88 AUGUST 31, 2007

http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0709&L=sanet-mg&T=0&P=450

Date: Wed, 29 Aug 2007 21:13:08 -0500 From: "Terry S. Singeltary Sr." Subject: CWD NEW MEXICO RECORDS IT'S 19 CASE (near Texas border again)

http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=26079

Monitoring the Potential Transmission of Chronic Wasting Disease to Humans Using a Hunter Registry Database in Wyoming (405 lines) From: Terry S. Singeltary Sr. Date: Thu, 30 Aug 2007 21:23:42 -0500

http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&F=&S=&P=27654

Subject: Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease creates a new prion strain

Date: August 25, 2007 at 12:42 pm PST

Subject: Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease creates a new prion strain Date: August 25, 2007 at 12:42 pm PST

J Biol Chem. 2007 Aug 20; : 17709374

Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease creates a new prion strain.

[My paper] Atsushi Kobayashi , Masahiro Asano , Shirou Mohri , Tetsuyuki Kitamoto

The genotype (methionine or valine) at polymorphic codon 129 of the human prion protein (PrP) gene and the type (type 1 or type 2) of abnormal isoform of PrP (PrP(Sc)) are major determinants of the clinicopathological phenotypes of sporadic Creutzfeldt-Jakob disease (sCJD). Here we found that transmission of sCJD prions from a patient with valine homozygosity (129V/V) and type 2 PrP(Sc) (sCJD-VV2 prions) to mice expressing human PrP with methionine homozygosity (129M/M) generated unusual PrP(Sc) intermediate in size between type 1 and type 2. The intermediate type PrP(Sc) was seen in all examined dura mater graft-associated CJD cases with 129M/M and plaque-type PrP deposits (p-dCJD). p-dCJD prions and sCJD-VV2 prions exhibited similar transmissibility and neuropathology, and the identical type of PrP(Sc) when inoculated into PrP-humanized mice with 129M/M or 129V/V. These findings suggest that p-dCJD could be caused by cross-sequence transmission of sCJD-VV2 prions.

snip...

In this study, the strain-dependent traits of sCJDMM1 prions were inherited through cross-sequence transmission without any modification. The humanized mice with 129V/V produced type 1 PrPres after inoculation with sCJD-MM1 prions. Because sCJD-VV1 cases are extremely rare (at most 1-2% of the total number of sCJD cases) and characterized by early onset (mean age at onset: 39.3 years) (5),

our results raise the possibility that CJD cases classified as VV1 may include cases caused by iatrogenic transmission of sCJD-MM1 prions or food-borne infection by type 1 prions from animals, e.g., chronic wasting disease prions in cervid. In fact, two CJD-VV1 patients who hunted deer or consumed venison have been reported (40, 41). The results of the present study emphasize the need for traceback studies and careful re-examination of the biochemical properties of sCJD-VV1 prions.

In conclusion, cross-sequence transmission of sCJD-VV2 prions generates a new prion strain with altered conformational properties and disease phenotypes as p-dCJD prions. Furthermore, the newly generated prions have unique transmissibility including the traceback phenomenon. In the future, if atypical prion strains emerge through cross-sequence transmission, especially from animals, traceback studies will enable us to identify the origin of the prions.

REFERENCES...snip...end

FULL TEXT ;

http://www.jbc.org/cgi/content/abstract/M704597200v1?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=Cross-sequence+transmission+of+sporadic+Creutzfeldt-Jakob+disease+creates+a+new+&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT

http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=21267

Re: Colorado Surveillance Program for Chronic Wasting Disease Transmission to Humans (TWO SUSPECT CASES)

http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0704&L=sanet-mg&T=0&P=1165

P04.01

Chronic Wasting Disease in a Captive White-Tailed Deer Farm

Keane, D1; Barr, D1; Bochsler, P1; Hall, M2; Gidlewski, T3; O’Rourke, K4; Spraker, T5 1University of Wisconsin, USA; 2US Department of Agriculture, USA; 3US Department of Agriculture, USA; 4USDA ARS-ADRU, Washington |State University, USA; 5Veterinary Diagnostic Laboratory, Colorado State University, USA

A white-tailed deer farm in Portage, Wisconsin, was depopulated in January 2006, after chronic wasting disease (CWD) had been initially discovered on the property in September 2002. Prior to the depopulation, a total of 22 positive animals had been removed from the property: one in 2002, six in 2003, ten in 2004, four in 2005 and one in 2006. At the time of depopulation a total of 76 animals remained: 47 females and 29 males. Age was assessed by visual examination of teeth at the time of death and revealed 26 adult, 8 fawn and 42 yearling animals. The following tissues were examined by immunohistochemistry for PrPCWD using Ab99/97.6.1: obex, tonsil, retropharyngeal, submandibular, parotid, prescapular, axillary, inguinal, prefemoral and popliteal lymph nodes, recto-anal mucosal tissue and eye. Seventy-nine percent of animals (sixty) were found to be positive in at least one tissue; 49 were obex positive, 58 retropharyngeal positive, 56 tonsil positive, 48 recto-anal mucosal associated lymphoid tissue positive and 4 animals were positive for PrPCWD in the retina. Prion genotype was determined for all animals.

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

P04.61

Survival of PrPSc during Simulated Wastewater Treatment Processes

Pedersen, J1; Hinckley, G1; McMahon, K2; McKenzie, D3; Aiken, JM3 1University of Wisconsin, Soil Science/Civil and Environmental Engineering, USA; 2University of Wisconsin, Civil and Environmental Engineering, USA; 3University of Wisconsin, Comparative Biosciences, USA

Concern has been expressed that prions could enter wastewater treatment systems through sewer and/or septic systems (e.g., necropsy laboratories, rural meat processors, private game dressing) or through leachate from landfills that have received TSE-contaminated material. Prions are highly resistant to degradation and many disinfection procedures raising concern that they could survive conventional wastewater treatment. Here, we report the results of experiments examining the partitioning and survival of PrPSc during simulated wastewater treatment processes including activated and mesophilic anaerobic sludge digestion. We establish that PrPSc can be efficiently extracted from activated and anaerobic digester sludges with 1% sodium dodecyl sulfate, 10% sodium undecyl sulfate, and 1% sodium N-lauryl sarcosinate. Activated sludge digestion does not result in significant degradation of PrPSc. The protein partitions strongly to the activated sludge solids and is expected to enter biosolids treatment processes. A large fraction of PrPSc survived simulated mesophilic anaerobic sludge digestion. Our results suggest that if prions were to enter municipal waste water treatment systems, most of the agent would partition to activated sludge solids, survive mesophilic anaerobic digestion, and be present in treated biosolids. Land application of biosolids containing prions could represent a route for their unintentional introduction into the environment. Our results argue for excluding inputs of prions to municipal wastewater treatment facilities that would result in unacceptable risk of prion disease transmission via contaminated biosolids.

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

Subject: Aspects of the Cerebellar Neuropathology in Nor98 Date: September 26, 2007 at 4:06 pm PST

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.

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

From: "Terry S. Singeltary Sr." Sent: Tuesday, August 21, 2007 9:50 AM Subject: TWO MORE Nor98 atypical Scrapie cases detected in USA bringing total to 3 cases to date

Infected and Source Flocks

As of June 30, 2007, there were .....

snip...

One field case and one validation case were consistent with Nor-98 scrapie.

http://www.aphis.usda.gov/animalhealth/animaldiseases/scrapie/downloads/monthlyscrapierpt.pps

IN the February 2007 Scrapie report it only mentions ;

''One case was consistent with Nor98 scrapie.''

http://www.aphis.usda.gov/animalhealth/animaldiseases/scrapie/

(please note flocks of origin were in WY, CO, AND CA. PERSONAL COMMUNCATIONS USDA, APHIS, VS ET AL. ...TSS)

NOR98 SHOWS MOLECULAR FEATURES REMINISCENT OF GSS

http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=14553

An evaluation of scrapie surveillance in the United States

http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=3427

FOIA REQUEST FOR ATYPICAL TSE INFORMATION ON VERMONT SHEEP

http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=10451

Subject: FSIS NOTICE SAMPLE COLLECTION FROM CATTLE UNDER THE BOVINE SPONGIFORM ENCEPHALOPATHY (BSE) ONGOING SURVEILLANCE PROGRAM From: "Terry S. Singeltary Sr." Reply-To: Sustainable Agriculture Network Discussion Group Date: Fri, 2 Feb 2007 17:32:58 -0600

http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0702&L=sanet-mg&P=720

ABSTRACTS SPORADIC CJD AND H BASE MAD COW ALABAMA AND TEXAS SEPTEMBER 2007

Date: Mon, 24 Sep 2007 21:31:55 -0500

I suggest that you all read the data out about h-BASE and sporadic CJD, GSS, blood, and some of the other abstracts from the PRION2007. ...

http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0709&L=sanet-mg&T=0&F=&S=&P=19744

USA BASE CASE, (ATYPICAL BSE), AND OR TSE (whatever they are calling it today), please note that both the ALABAMA COW, AND THE TEXAS COW, both were ''H-TYPE'', personal communication Detwiler et al Wednesday, August 22, 2007 11:52 PM. ...TSS

http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=19779

see full text 143 pages ;

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

SEE STEADY INCREASE IN SPORADIC CJD IN THE USA FROM 1997 TO 2006. SPORADIC CJD CASES TRIPLED, with phenotype of 'UNKNOWN' strain growing. ...

http://www.cjdsurveillance.com/resources-casereport.html

There is a growing number of human CJD cases, and they were presented last week in San Francisco by Luigi Gambatti(?) from his CJD surveillance collection.

He estimates that it may be up to 14 or 15 persons which display selectively SPRPSC and practically no detected RPRPSC proteins.

http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm

http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

Singeltary, Sr et al. JAMA.2001; 285: 733-734.

http://jama.ama-assn.org/http://www.neurology.org/cgi/eletters/60/2/176#535

JOURNAL OF NEUROLOGY

MARCH 26, 2003

RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob

disease in the United States

Email Terry S. Singeltary:

flounder@wt.net

I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to

comment on the CDC's attempts to monitor the occurrence of emerging

forms of CJD. Asante, Collinge et al [1] have reported that BSE

transmission to the 129-methionine genotype can lead to an alternate

phenotype that is indistinguishable from type 2 PrPSc, the commonest

sporadic CJD. However, CJD and all human TSEs are not reportable

nationally. CJD and all human TSEs must be made reportable in every

state and internationally. I hope that the CDC does not continue to

expect us to still believe that the 85%+ of all CJD cases which are

sporadic are all spontaneous, without route/source. We have many TSEs in

the USA in both animal and man. CWD in deer/elk is spreading rapidly and

CWD does transmit to mink, ferret, cattle, and squirrel monkey by

intracerebral inoculation. With the known incubation periods in other

TSEs, oral transmission studies of CWD may take much longer. Every

victim/family of CJD/TSEs should be asked about route and source of this

agent. To prolong this will only spread the agent and needlessly expose

others. In light of the findings of Asante and Collinge et al, there

should be drastic measures to safeguard the medical and surgical arena

from sporadic CJDs and all human TSEs. I only ponder how many sporadic

CJDs in the USA are type 2 PrPSc?

http://www.neurology.org/cgi/eletters/60/2/176#535

THE PATHOLOGICAL PROTEIN Hardcover, 304 pages plus photos and illustrations. ISBN 0-387-95508-9

June 2003

BY Philip Yam

CHAPTER 14 LAYING ODDS

Answering critics like Terry Singeltary, who feels that the U.S. under- counts CJD, Schonberger conceded that the current surveillance system has errors but stated that most of the errors will be confined to the older population.

http://www.thepathologicalprotein.com/

doi:10.1016/S1473-3099(03)00715-1 Copyright © 2003 Published by Elsevier Ltd. Newsdesk

Tracking spongiform encephalopathies in North America

Xavier Bosch

Available online 29 July 2003.

Volume 3, Issue 8, August 2003, Page 463

“My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever since. What I have found is that we have not been told the truth. CWD in deer and elk is a small portion of a much bigger problem.” ............................

http://www.thelancet.com/journals/laninf/article/PIIS1473309903007151/fulltext

http://download.thelancet.com/pdfs/journals/1473-3099/PIIS1473309903007151.pdf

see history of cjd questionnaire

http://brain.hastypastry.net/forums/showthread.php?t=2408

Sent: Monday May 28, 2007

Subject: THE BIG LIE SPORADIC CJD AND MAD COW DISEASEs i.e. TSE

http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0705&L=sanet-mg&T=0&P=25276

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. propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2007. 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 i.e. consumption, surgical, blood, medical, cosmetics etc. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, 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 that all the rest of human TSE are just one single strain i.e. sporadic CJD (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, 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. ...

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

CJD NEWS

http://disc.server.com/Indices/236650.html

CJD VOICE (voice for all victims of human TSE)

http://members.aol.com/larmstr853/cjdvoice/cjdvoice.htm

Chronic Wasting Disease (CWD) continues to spread Sports RONALD E. MCCALL | Thursday, September 27, 2007 at 12:30 am

http://savannahnow.com/node/366050

re-CHRONIC WASTING DISEASE SPREADING and USA MAD COW H-BASE and SPORADIC CJD

http://savannahnow.com/node/366082

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

Thursday, April 03, 2008

A prion disease of cervids: Chronic wasting disease

1: Vet Res. 2008 Apr 3;39(4):41

A prion disease of cervids: Chronic wasting disease

Sigurdson CJ.

The recent discovery of chronic wasting disease in cervids (CWD) beyond the borders of Colorado and Wyoming, as far east as New York and including two Canadian Provinces, has led to the emergence of CWD as a prion disease of domestic and international importance. The apparent ease of horizontal transmission, potentially via environmental contamination or by prion-containing saliva, creates enormous challenges for disease management. Ongoing studies of CWD interspecies transmission by exposure of domestic and non-domestic species directly or using transgenic mice have shed light on species barriers. Transgenic mice expressing cervid PrP have also proven useful for assessing the genetic influences of Prnp polymorphisms on CWD susceptibility. Accumulating evidence of CWD pathogenesis indicates that the misfolded prion protein, PrPSc, seems to be widely disseminated in many nonneural organs, and CWD infectivity has been recently detected in blood. This review highlights recent research findings in this disease of free-ranging wildlife.

snip...

1. CWD prion spread and target organs

Collectively, CWD pathogenesis studies have revealed extensive deposition of PrPSc in the central nervous system (CNS) and extraneural tissues (Fig. 1). The only other natural prion diseases that even approach this degree of systemic involvement are variant Creutzfeldt-Jakob disease (vCJD) in humans, sheep scrapie, and transmissible mink encephalopathy [22, 23, 30, 61, 62]. In mule deer, PrPSc is detectable in the retropharyngeal lymph node within only 6 weeks following an oral exposure [76]. In a further study of the kinetics of prion

1 http://www.aphis.usda.gov/vs/nahps/cwd/cwd-distribution.html

5

infection in mule deer, Fox et al. showed that PrPSc is widely distributed in lymphoid tissues by 3 months post-oral exposure when it is first detected in brain [17]. By 9 months, PrPSc was detected in the myenteric and submucosal plexi throughout the gastrointestinal tract and in the vagus nerve, and by 16 months, PrPSc deposits were detectable throughout the brain and spinal cord. The Prnp genotype seemed to impact the infection kinetics in that mule deer that were SF heterozygous at codon 225 showed a delay in PrPSc spread; PrPSc was not detectable in the brain until 16 months post-inoculation which was 13 months later than the 225SS deer. Perhaps the 225F allele confers a dominant negative effect on the kinetics of this CWD strain, as has been described in sheep, where the 171R allele has been shown to have a dominant negative effect on prion susceptibility [20, 33]. CWD pathogenesis seems to vary between deer and elk: PrPSc levels have been found to be lower in lymphoid tissues of elk compared to deer [66]. In a report of 226 CWD-infected elk, 28 had no PrPSc in lymphoid tissues despite having PrPSc in brain [81].

In addition to lymphoid tissues, PrPSc or infectivity has been detected in other non-CNS tissues, including pancreas [17, 77], adrenal gland [17, 77], and skeletal muscle [2]. Recently PrPSc was described in cardiac muscle from 7 of 16 (44%) white-tailed deer and from 12 of 17 (71%) elk [35]. This is the first report of PrPSc in cardiac muscle in any TSE. The cellular and molecular mechanisms of systemic prion spread are under investigation in many laboratories. A recent report showed that blood from CWD-infected deer contained infectivity and could transmit prion disease via a blood transfusion [50].

This finding recapitulates indirect findings of blood infectivity in vCJD affected humans [61] and experimental transfusion studies of scrapie sick sheep [32], and indicates that prion transport throughout the body may include the blood as a potential vehicle.

snip...

* Thus far,

8

twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center,*

however there have been no unusual or novel prion subtypes that might indicate the appearance of a new prion strain [7, 41].

snip...

1. Conclusion

CWD in cervids is efficiently transmitted, likely more than any other TSE in animals or humans. Therefore, it is unlikely that this TSE can be eradicated, but perhaps through an improved understanding of transmission routes, biological factors influencing pathogenesis, and the molecular basis of CWD prion conversion, a targeted strategy for interrupting disease spread may be developed.

Acknowledgements

I thank Drs. Michael Miller, Jason Bartz and Mathias Heikenwalder for critical review of the manuscript.

see full text ;

http://www.vetres.org/index.php?option=article&access=standard&Itemid=129&url=/articles/vetres/pdf/2008/04/v08092.pdf

* Thus far,

8

twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center,*

however there have been no unusual or novel prion subtypes that might indicate the appearance of a new prion strain [7, 41].

???

GAH WELLS (very important statement here...TSS)

HOUND STUDY

AS implied in the Inset 25 we must not ASSUME that transmission of BSE to other species will invariably present pathology typical of a scrapie-like disease.

snip...

http://www.bseinquiry.gov.uk/files/yb/1991/01/04004001.pdf

2005

DEFRA Department for Environment, Food & Rural Affairs

Area 307, London, SW1P 4PQ Telephone: 0207 904 6000 Direct line: 0207 904 6287 E-mail: h.mcdonagh.defra.gsi.gov.uk

GTN: FAX:

Mr T S Singeltary P.O. Box 42 Bacliff Texas USA 77518

21 November 2001

Dear Mr Singeltary TSE IN HOUNDS

Thank you for e-mail regarding the hounds survey. I am sorry for the long delay in responding.

As you note, the hound survey remains unpublished. However the Spongiform Encephalopathy Advisory Committee (SEAC), the UK Government's independent Advisory Committee on all aspects related to BSE-like disease, gave the hound study detailed consideration at their meeting in January 1994. As a summary of this meeting published in the BSE inquiry noted, the Committee were clearly concerned about the work that had been carried out, concluding that there had clearly been problems with it, particularly the control on the histology, and that it was more or less inconclusive. However was agreed that there should be a re-evaluation of the pathological material in the study.

Later, at their meeting in June 95, The Committee re-evaluated the hound study to see if any useful results could be gained from it. The Chairman concluded that there were varying opinions within the Committee on further work. It did not suggest any further transmission studies and thought that the lack of clinical data was a major weakness.

Overall, it is clear that SEAC had major concerns about the survey as conducted. As a result it is likely that the authors felt that it would not stand up to r~eer review and hence it was never published. As noted above, and in the detailed minutes of the SEAC meeting in June 95, SEAC considered whether additional work should be performed to examine dogs for evidence of TSE infection. Although the Committee had mixed views about the merits of conducting further work, the Chairman noted that when the Southwood Committee made their recommendation to complete an assessment of possible spongiform disease in dogs, no TSEs had been identified in other species and hence dogs were perceived as a high risk population and worthy of study. However subsequent to the original recommendation, made in 1990, a number of other species had been identified with TSE ( e.g. cats) so a study in hounds was less

critical. For more details see- http://www.bseinquiry, gov.uk/files/yb/1995/06/21005001 .pdf

As this study remains unpublished, my understanding is that the ownership of the data essentially remains with the original researchers. Thus unfortunately, I am unable to help with your request to supply information on the hound survey directly. My only suggestion is that you contact one of the researchers originally involved in the project, such as Gerald Wells. He can be contacted at the following address.

Dr Gerald Wells, Veterinary Laboratories Agency, New Haw, Addlestone, Surrey, KT 15 3NB, UK

You may also wish to be aware that since November 1994 all suspected cases of spongiform encephalopathy in animals and poultry were made notifiable. Hence since that date there has been a requirement for vets to report any suspect SE in dogs for further investigation. To date there has never been positive identification of a TSE in a dog.

I hope this is helpful

Yours sincerely 4

HUGH MCDONAGH BSE CORRESPONDENCE SECTION

FC5.5.2 Transmission of Italian BSE and BASE Isolates in Cattle Results into a Typical BSE Phenotype and a Muscle Wasting Disease

Zanusso, G1; Lombardi, G2; Casalone, C3; D'Angelo, A4; Gelmetti, D2; Torcoli, G2; Barbieri, I2; Corona, C3; Fasoli, E1; Farinazzo, A1; Fiorini, M1; Gelati, M1; Iulini, B3; Tagliavini, F5; Ferrari, S1; Monaco, S1; Caramelli, M3; Capucci, L2 1University of Verona, Neurological and Visual Sciences, Italy; 2IZSLER, Italy; 3IZSPLVA, Italy; 4University of Turin, Animal Pathology, Italy; 5Isituto Carlo Besta, Italy

The clinical phenotype of bovine spongiform encephalopathy has been extensively reported in early accounts of the disorder. Following the introduction of statutory active surveillance, almost all BSE cases have been diagnosed on a pathological/molecular basis, in a pre-symptomatic clinical stage. In recent years, the active surveillance system has uncovered atypical BSE cases, which are characterized by distinct conformers of the PrPSc, named high-type (BSE-H) and low-type (BSE-L), whose clinicopathological phenotypes remain unknown. We recently reported two Italian atypical cases with a PrPSc type similar to BSE-L, pathologically characterized by PrP amyloid plaques. Experimental transmission to TgBov mice has recently disclosed that BASE is caused by a distinct prion strain which is extremely virulent. A major limitation of transmission studies to mice is the lack of reliable information on clinical phenotype of BASE in its natural host. In the present study, we experimentally infected Fresian/Holstein and Alpine/Brown cattle with Italian BSE and BASE isolates by i.c. route. BASE infected cattle showed survival times significantly shorter than BSE, a finding more readily evident in Fresian/Holstein, and in keeping with previous observations in TgBov mice. Clinically, BSE-infected cattle developed a disease phenotype highly comparable with that described in field BSE cases and in experimentally challenged cattle. On the contrary, BASE-inoculated cattle developed an amyotrophic disorder accompanied by mental dullness. The molecular and neuropathological profiles, including PrP deposition pattern, closely matched those observed in the original cases. This study further confirms that BASE is caused by a distinct prion isolate and discloses a novel disease phenotype in cattle, closely resembling the phenotype previous reported in scrapie-inoculated cattle * and in some subtypes of inherited and sporadic Creutzfeldt-Jakob disease.

Oral Abstracts 14

P02.35 Molecular Features of the Protease-resistant Prion Protein (PrPres) in H- type BSE

Biacabe, A-G1; Jacobs, JG2; Gavier-Widén, D3; Vulin, J1; Langeveld, JPM2; Baron, TGM1 1AFSSA, France; 2CIDC-Lelystad, Netherlands; 3SVA, Sweden

Western blot analyses of PrPres accumulating in the brain of BSE- infected cattle have demonstrated 3 different molecular phenotypes regarding to the apparent molecular masses and glycoform ratios of PrPres bands. We initially described isolates (H-type BSE) essentially characterized by higher PrPres molecular mass and decreased levels of the diglycosylated PrPres band, in contrast to the classical type of BSE. This type is also distinct from another BSE phenotype named L-type BSE, or also BASE (for Bovine Amyloid Spongiform Encephalopathy), mainly characterized by a low representation of the diglycosylated PrPres band as well as a lower PrPres molecular mass. Retrospective molecular studies in France of all available BSE cases older than 8 years old and of part of the other cases identified since the beginning of the exhaustive surveillance of the disease in 20001 allowed to identify 7 H- type BSE cases, among 594 BSE cases that could be classified as classical, L- or H-type BSE. By Western blot analysis of H-type PrPres, we described a remarkable specific feature with antibodies raised against the C-terminal region of PrP that demonstrated the existence of a more C-terminal cleaved form of PrPres (named PrPres#2 ), in addition to the usual PrPres form (PrPres #1). In the unglycosylated form, PrPres #2 migrates at about 14 kDa, compared to 20 kDa for PrPres #1. The proportion of the PrPres#2 in cattle seems to by higher compared to the PrPres#1. Furthermore another PK-resistant fragment at about 7 kDa was detected by some more N-terminal antibodies and presumed to be the result of cleavages of both N- and C- terminal parts of PrP. These singular features were maintained after transmission of the disease to C57Bl/6 mice. The identification of these two additional PrPres fragments (PrPres #2 and 7kDa band) * reminds features reported respectively in sporadic Creutzfeldt-Jakob disease and in Gerstmann-Sträussler-Scheinker (GSS) syndrome in humans.

FC5.5.1 BASE Transmitted to Primates and MV2 sCJD Subtype Share PrP27-30 and PrPSc C-terminal Truncated Fragments

Zanusso, G1; Commoy, E2; Fasoli, E3; Fiorini, M3; Lescoutra, N4; Ruchoux, MM4; Casalone, C5; Caramelli, M5; Ferrari, S3; Lasmezas, C6; Deslys, J-P4; Monaco, S3 1University of Verona, of Neurological and Visual Sciences, Italy; 2CEA, IMETI/SEPIA, France; 3University of Verona, Neurological and Visual Sciences, Italy; 4IMETI/SEPIA, France; 5IZSPLVA, Italy; 6The Scripps Research Insitute, USA

The etiology of sporadic Creutzfeldt-Jakob disease (sCJD), the most frequent human prion disease, remains still unknown. The marked disease phenotype heterogeneity observed in sCJD is thought to be influenced by the type of proteinase K- resistant prion protein, or PrPSc (type 1 or type 2 according to the electrophoretic mobility of the unglycosylated backbone), and by the host polymorphic Methionine/Valine (M/V) codon 129 of the PRNP. By using a two-dimensional gel electrophoresis (2D-PAGE) and imunoblotting we previously showed that in sCJD, in addition to the PrPSc type, distinct PrPSc C-terminal truncated fragments (CTFs) correlated with different sCJD subtypes. Based on the combination of CTFs and PrPSc type, * we distinguished three PrPSc patterns: (i) the first was observed in sCJD with PrPSc type 1 of all genotypes,;

(ii) the second was found in M/M-2 (cortical form); (iii) the third in amyloidogenic M/V- 2 and V/V-2 subtypes (Zanusso et al., JBC 2004) . Recently, we showed that sCJD subtype M/V-2 shared molecular and pathological features with an atypical form of BSE, named BASE, thus suggesting a potential link between the two conditions. This connection was further confirmed after 2D-PAGE analysis, which showed an identical PrPSc signature, including the biochemical pattern of CTFs. To pursue this issue, we obtained brain homogenates from Cynomolgus macaques intracerebrally inoculated with brain homogenates from BASE. Samples were separated by using a twodimensional electrophoresis (2D-PAGE) followed by immunoblotting. We here show that the PrPSc pattern obtained in infected primates is identical to BASE and sCJD MV-2 subtype. * These data strongly support the link, or at least a common ancestry, between a sCJD subtype and BASE.

This work was supported by Neuroprion (FOOD-CT-2004-506579)

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

Sunday, March 16, 2008

MAD COW DISEASE terminology UK c-BSE (typical), atypical BSE H or L, and or Italian L-BASE

http://bse-atypical.blogspot.com/2008/03/mad-cow-disease-terminology-uk-c-bse.html

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

Singeltary, Sr et al. JAMA.2001; 285: 733-734.

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

Since this article does not have an abstract, we have provided the first 150 words of the full text and any section headings.

To the Editor:

In their Research Letter, Dr Gibbons and colleagues1 reported that the annual US death rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These estimates, however, are based only on reported cases, and do not include misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would drastically change these figures. An unknown number of persons with a diagnosis of Alzheimer disease in fact may have CJD, although only a small number of these patients receive the postmortem examination necessary to make this diagnosis. Furthermore, only a few states have made CJD reportable. Human and animal transmissible spongiform encephalopathies should be reportable nationwide and internationally.

Terry S. Singeltary, Sr Bacliff, Tex

1. Gibbons RV, Holman RC, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA. 2000;284:2322-2323. FREE FULL TEXT

http://jama.ama-assn.org/cgi/content/extract/285/6/733?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=singeltary&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT

JOURNAL OF NEUROLOGY

MARCH 26, 2003

In light of the findings of Asante and Collinge et al, there

should be drastic measures to safeguard the medical and surgical arena

from sporadic CJDs and all human TSEs. I only ponder how many sporadic

CJDs in the USA are type 2 PrPSc?

http://www.neurology.org/cgi/eletters/60/2/176#535

snip...see full text 19 pages and other relating data in full here ;

A prion disease of cervids: Chronic wasting disease 2008

http://chronic-wasting-disease.blogspot.com/2008/04/prion-disease-of-cervids-chronic.html

CWD Update 90 March 7, 2008

http://chronic-wasting-disease.blogspot.com/2008/03/cwd-update-90-march-7-2008.html

P.S. (off topic) for anyone that wants to know ;

USDA CERTIFIED DEAD STOCK DOWNER COW SCHOOL LUNCH PROGRAM LIST OF SCHOOLS AFFECTED STATE BY STATE (dead stock downers i.e. non-ambulatory, the most high risk for mad cow disease)

March 28, 2008, 12:10AM

FDA lists school districts that got recalled meat Lawmakers had demanded info be released

http://downercattle.blogspot.com/2008/03/usda-certified-dead-stock-downer-cow.html

snip...

see full text all schools Nationally receiving non-ambulatory dead stock downer cattle (high risk BSE typical or atypical mad cow) for there school lunch program in every state here ;

http://www.fns.usda.gov/fns/safety/Hallmark-Westland_byState.pdf

TSS

1. Human susceptibility to CWD

Millions of North Americans hunt deer and elk (U.S. Department of the Interior, Census Bureau), and there is no doubt that people have been exposed to CWD through venison consumption, particularly in light of recent data showing CWD prions in muscle [2]. Human susceptibility to CWD or to other newly emerging animal TSE [9, 14] is still unclear, although we can be somewhat reassured in that there have been no large scale outbreaks of human TSE cases in Colorado and Wyoming, where CWD has existed for decades [51]. Up until approximately 10 years ago, autopsies were not performed on suspect human TSE cases in many states due to biosafety concerns, therefore the diagnosis of potential new TSE strains has been hampered. This indicates that clinical TSE diagnoses in humans were not confirmed, nor was any strain typing done to look for the appearance of potentially subtle or unusual pathological or biochemical phenotypes of a new TSE strain. Fortunately, the autopsy rate for suspect cases is improving. At the National Prion Disease Pathology Surveillance Center at Case Western Reserve University (Cleveland, Ohio), Creutzfeldt-Jakob disease (CJD) suspect cases are studied and classified by CJD subtype. Thus far,

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* twenty-seven CJD patients who regularly consumed venison were reported to the Surveillance Center*,

however there have been no unusual or novel prion subtypes that might indicate the appearance of a new prion strain [7, 41]. Other indirect studies of human susceptibility to CWD also suggest that the risk is low. In biochemical conversion studies, Raymond et al. [68] showed that the efficiency of CWD to convert recombinant human PrP into amyloid fibrils was low, but similar to that of both BSE and scrapie fibrils to do the same. These results suggest that there is a molecular incompatibility in the conversion of human PrPC by CWD, sheep scrapie, or BSE, and that cross species infections in humans may be rare events. To determine whether common PrPSc strain features may link CWD and CJD, histopathology and the PrPSc biochemical characteristics from deer and elk were compared with that of humans with sporadic CJD (sCJD) cases that are methionine homozygous at codon 129 of the Prnp gene by Xie et al. [96], although strain features including histologic profile, target organs, and glycoform patterns will not necessarily remain the same upon crossing species barriers [6, 5, 8, 57]. The PrPSc form is cleaved by proteinase-K (PK) at different sites depending on the conformation of the protein and may aid determination of whether the PrPSc conformation is similar. By western blot (SDS-PAGE) of elk CWD, the unglycosylated PK-resistant PrPSc migrated at 21 kDa, similar to sCJD (MM1 subtype) and the PK cleavage site was the same, occurring at residues 78 and 82 as assessed by N-terminal sequencing. Conformational stability was evaluated by measuring the PrPSc stability under partially denaturing conditions and also showed no significant difference between elk CWD and sCJD MM1 PrPSc. However, elk CWD and human sCJD MM1 strains exhibited distinct glycoform patterns by two dimensional gel electrophoresis, suggesting that the strains differed. Future studies may utilize luminescent conjugated polymers, which were recently shown to distinguish naturally- and experimentally-derived prion strains [79]. To study elk-human prion species barriers, Kong et al. inoculated elk CWD into transgenic mice expressing either human PrP or elk PrP. Whereas the elk PrP expressing mice developed disease after only 118-142 days post-inoculation, human PrP expressing mice (129M) did not develop any features of TSE after more than 657 or more than 756 days [41]. In accordance with these results, Tamgüney et al. also reported that human PrP overexpressing mice were not susceptible to 9 CWD isolates from mule deer, white-tailed deer, and elk [84]. However, mice have a limited lifespan and further passages may be necessary to detect low levels of prion infectivity that may be present subclinically. Although indi rect evidence is accumulating that there may be a robust species barrier for CWD transmission to humans, one report indicates nonhuman primate susceptibility to CWD. Intracerebral inoculation of squirrel monkeys (Saimiri sciureus) demonstrated a positive CWD transmission [49]. Among non-human primates, however, the Prnp sequence of the new world monkeys are the most distant from humans [72], and therefore may not indicate that human prion conversion would occur by CWD.

snip...

1. Disease control challenges posed by CWD

Evidence is building that indicates efficient horizontal transmission occurs in CWD, indeed a complicating aspect in disease control [91]. Potential transmission mechanisms range from spread via direct contact among animals to environmental exposure through grazing in areas contaminated by prion-infected secretions, excretions (saliva, urine, feces), tissues (placenta), or decomposed carcasses. Recently, in a breakthrough finding, saliva from CWD infected deer was shown to transmit prion disease [50]. An additional experiment by Miller and colleagues showed that CWD-infected carcasses allowed to decay naturally in confined pastures can lead to CWD infections in captive deer, demonstrating the potential for environmental contamination to spread infection [55]. Modelling studies have provided further

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support that environmental contamination is likely playing a significant role in transmitting CWD [56, 53]. Additionally, infectious prions have been demonstrated to bind soil particles and remain infectious to animals by both intracerebral and oral exposure routes [38, 37]. Prion infectivity has been recovered from soil more than two years after experimental exposure to prions, suggesting the soil may serve as a reservoir for CWD prions [75]. Taken together, these results indicate that there may even be multiple sources for CWD exposure, perhaps through direct contact and environmental routes. Significant challenges to CWD eradication exist in free-ranging cervids. Infected deer and elk range over a broad geographic region, and even previously surmised geographic barriers such as the Continental Divide have proven passable by infected animals. Ridding the environment of CWD-contaminated soil or even CWD-infected carcasses is not possible. Moreover, the available ante-mortem diagnostic tests for surveillance are laborious and impractical for large numbers of free-ranging animals [74, 88, 95]. Therefore for a wildlife manager, this disease is costly to survey and difficult to control.

1. Conclusion

CWD in cervids is efficiently transmitted, likely more than any other TSE in animals or humans. Therefore, it is unlikely that this TSE can be eradicated, but perhaps through an improved understanding of transmission routes, biological factors influencing pathogenesis, and the molecular basis of CWD prion conversion, a targeted strategy for interrupting disease spread may be developed.

Acknowledgements

I thank Drs. Michael Miller, Jason Bartz and Mathias Heikenwalder for critical review of the manuscript.

snip...see full text 19 pages ;

http://www.vetres.org/index.php?option=article&access=standard&Itemid=129&url=/articles/vetres/pdf/2008/04/v08092.pdf

http://chronic-wasting disease.blogspot.com/

TSS