W.Va. DNR Reports Results from Spring 2010 CWD Surveillance Efforts In Hampshire County; CWD Containment Area Expanded

Joe Manchin III, Governor Frank Jezioro, Director

News Release: June 28, 2010

Hoy Murphy, Public Information Officer (304) 558-2003 ext. 365 hoy.r.murphy@wv.gov Contact: Paul Johansen, Wildlife Resources Section 304-558-2771 dnr.wildlife@wv.gov

W.Va. DNR Reports Results from Spring 2010 CWD Surveillance Efforts In Hampshire County; CWD Containment Area Expanded

HAMPSHIRE COUNTY, W.Va. – With the cooperation of local landowners, the West Virginia Division of Natural Resources (DNR) tested 152 deer collected from within one to two miles of previously known locations of Chronic Wasting Disease (CWD) infected deer. Testing detected the CWD agent in a total of 12 white-tailed deer sampled during the 2010 spring collections in Hampshire County, according to the DNR.

The detection of 15 CWD positive deer during the fall 2009 hunting season, combined with this spring’s testing results, has required the expansion of the CWD Containment Area to include all of Hampshire County. Within the CWD Containment Area, supplemental feeding and baiting of deer is prohibited and there are transport restrictions for deer carcasses leaving the county.

The spring CWD monitoring of deer provides an incidence rate of infected CWD deer in the area of established infection and removes CWD positive deer from the landscape. In addition, wildlife biologists also use the information to monitor changes in age structure and reproduction in the deer herd within the established CWD infected area.

The first case of CWD in West Virginia was confirmed on September 2, 2005. Since that time, the DNR has been fully engaged in activities guided by its CWD Incident Response Plan, which is designed to accomplish the following objectives:

•Determine the distribution and prevalence of CWD through enhanced surveillance efforts. •Communicate and coordinate with the public and other appropriate agencies on issues relating to CWD and the steps being taken to respond to this disease. •Initiate appropriate management actions necessary to control the spread of this disease and prevent further introduction of the disease. To date, CWD surveillance efforts conducted by the DNR have resulted in a total of 74 deer being confirmed positive for CWD in Hampshire County. Ongoing and extensive surveillance efforts being conducted by Wildlife Resources Section personnel throughout West Virginia has not detected CWD outside of Hampshire County.

CWD is a neurological disease found in deer and elk and belongs to a family of diseases known as transmissible spongiform encephalopathies. The disease is currently accepted as being caused by abnormal, proteinaceous particles called prions that slowly attack the brain of infected deer and elk. Animals progressively become emaciated, display abnormal behavior and invariably die as a result of the disease. There is no known treatment for CWD and it is fatal for the infected deer or elk. It is important to note that currently, there is no evidence to suggest CWD poses a risk for humans or domestic animals.

“Landowner and hunter cooperation throughout this entire CWD response effort in Hampshire County continues to be excellent,” noted DNR Director Frank Jezioro. “As we strive to meet this wildlife disease challenge and implement appropriate management strategies, the support and involvement of landowners and hunters remains essential. The DNR is committed to keeping the public informed and involved in these wildlife disease management actions.”

**DNR**

http://www.wvdnr.gov/2010news/10news115.shtm



Friday, January 15, 2010

Sixteen Additional Deer Test Positive for Chronic Wasting Disease In Hampshire County, West Virginia West Virginia Division of Natural Resources

http://chronic-wasting-disease.blogspot.com/2010/01/sixteen-additional-deer-test-positive.html



Friday, May 29, 2009

Seven Deer Test Positive for Chronic Wasting Disease During 2009 Spring Collections in Hampshire County, West Virginia Joe Manchin III, Governor Frank Jezioro, Director News Release : May 29, 2009

http://chronic-wasting-disease.blogspot.com/2009/05/seven-deer-test-positive-for-chronic.html



Thursday, May 08, 2008

Eleven Deer Test Positive for Chronic Wasting Disease During Spring Collections in Hampshire County, West Virginia West Virginia Division of Natural Resources

http://chronic-wasting-disease.blogspot.com/2008/05/eleven-deer-test-positive-for-chronic.html



Monday, December 17, 2007

Five Additional Deer Test Positive for Chronic Wasting Disease In Hampshire County, West Virginia

http://chronic-wasting-disease.blogspot.com/2007/12/five-additional-deer-test-positive-for.html



Monday, June 14, 2010 A molecular switch controls interspecies prion disease transmission in mice J Clin Invest. doi:10.1172/JCI42051. Copyright © 2010, The American Society for Clinical Investigation.

Research Article

http://chronic-wasting-disease.blogspot.com/2010/06/molecular-switch-controls-interspecies.html



Thursday, June 03, 2010 Prion Strain Mutation and Selection John Collinge MEDICINE

John Collinge

http://chronic-wasting-disease.blogspot.com/2010/06/prion-strain-mutation-and-selection.html



CWD, GAME FARMS, BAITING, AND POLITICS

http://chronic-wasting-disease.blogspot.com/2009/01/cwd-game-farms-baiting-and-politics.html



ALSO, NOTE MINERAL LICKS A POSSIBLE SOURCE AND TRANSMISSION MODE FOR CWD ;

http://chronic-wasting-disease.blogspot.com/2009/08/third-international-cwd-symposium-july.html



http://www.cwd-info.org/pdf/3rd_CWD_Symposium_utah.pdf



2003D-0186 Guidance for Industry: Use of Material From Deer and Elk In Animal Feed

EMC 1 Terry S. Singeltary Sr. Vol #: 1

http://www.fda.gov/ohrms/dockets/dailys/03/Jun03/060903/060903.htm



http://www.fda.gov/ohrms/dockets/dailys/01/Oct01/101501/101501.htm



see my full text submission here ;

http://madcowfeed.blogspot.com/2008/07/docket-03d-0186-fda-issues-draft.html



Subject: MAD COW FEED RECALL AL AND FL VOLUME OF PRODUCT IN COMMERCE 125 TONS Products manufactured from 02/01/2005 until 06/06/2006

Date: August 6, 2006 at 6:16 pm PST

PRODUCT a) CO-OP 32% Sinking Catfish, Recall # V-100-6; Performance Sheep Pell W/Decox/A/N, medicated, net wt. 50 lbs, Recall # V-101-6; c) Pro 40% Swine Conc Meal -- 50 lb, Recall # V-102-6; d) CO-OP 32% Sinking Catfish Food Medicated,

Recall # V-103-6; e) "Big Jim's" BBB Deer Ration, Big Buck Blend,

Recall # V-104-6; f) CO-OP 40% Hog Supplement Medicated Pelleted, Tylosin 100 grams/ton, 50 lb. bag, Recall # V-105-6; g) Pig Starter Pell II, 18% W/MCDX Medicated 282020, Carbadox -- 0.0055%, Recall # V-106-6; h) CO-OP STARTER-GROWER CRUMBLES, Complete Feed for Chickens from Hatch to 20 Weeks, Medicated, Bacitracin Methylene Disalicylate, 25 and 50 Lbs, Recall # V-107-6; i) CO-OP LAYING PELLETS, Complete Feed for Laying Chickens, Recall # 108-6; j) CO-OP LAYING CRUMBLES, Recall # V-109-6; k) CO-OP QUAIL FLIGHT CONDITIONER MEDICATED, net wt 50 Lbs, Recall # V-110-6; l) CO-OP QUAIL STARTER MEDICATED, Net Wt. 50 Lbs, Recall # V-111-6; m) CO-OP QUAIL GROWER MEDICATED, 50 Lbs, Recall # V-112-6 CODE Product manufactured from 02/01/2005 until 06/06/2006 RECALLING FIRM/MANUFACTURER Alabama Farmers Cooperative, Inc., Decatur, AL, by telephone, fax, email and visit on June 9, 2006. FDA initiated recall is complete.

REASON Animal and fish feeds which were possibly contaminated with ruminant based protein not labeled as "Do not feed to ruminants".

VOLUME OF PRODUCT IN COMMERCE 125 tons DISTRIBUTION AL and FL

END OF ENFORCEMENT REPORT FOR AUGUST 2, 2006

###

http://www.fda.gov/bbs/topics/enforce/2006/ENF00963.html



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



NOW, let's look at oral transmission studies with CWD ;


Experimental oral transmission of chronic wasting disease to red deer (Cervus elaphus elaphus): Early detection and late stage distribution of protease-resistant prion protein

Aru Balachandran, Noel P. Harrington, James Algire, Andrei Soutyrine, Terry R. Spraker, Martin Jeffrey, Lorenzo González, Katherine I. O’Rourke

Abstract — Chronic wasting disease (CWD), an important emerging prion disease of cervids, is readily transmitted by intracerebral or oral inoculation from deer-to-deer and elk-to-elk, suggesting the latter is a natural route of exposure. Studies of host range susceptibility to oral infection, particularly of those species found in habitats where CWD currently exists are imperative. This report describes the experimental transmission of CWD to red deer following oral inoculation with infectious CWD material of elk origin. At 18 to 20 months post-inoculation, mild to moderate neurological signs and weight loss were observed and animals were euthanized and tested using 3 conventional immunological assays. The data indicate that red deer are susceptible to oral challenge and that tissues currently used for CWD diagnosis show strong abnormal prion (PrPCWD) accumulation. Widespread peripheral PrPCWD deposition involves lymphoreticular tissues, endocrine tissues, and cardiac muscle and suggests a potential source of prion infectivity, a means of horizontal transmission and carrier state.

Can Vet J 2010;51:169–178

http://canadianveterinarians.net/publications-journal-issue-abstracts.aspx



Chronic wasting disease (CWD), an important emerging prion disease of cervids, is readily transmitted by intracerebral or oral inoculation from deer-to-deer and elk-to-elk, suggesting the latter is a natural route of exposure.

http://canadianveterinarians.net/publications-journal-issue-abstracts.aspx


Potential Venison Exposure Among FoodNet Population Survey Respondents, 2006-2007

Ryan A. Maddox1*, Joseph Y. Abrams1, Robert C. Holman1, Lawrence B. Schonberger1, Ermias D. Belay1 Division of Viral and Rickettsial Diseases, National Center for Zoonotic, Vector-Borne, and Enteric Diseases, Centers for Disease Control and Prevention, Atlanta, GA *Corresponding author e-mail: rmaddox@cdc.gov

The foodborne transmission of bovine spongiform encephalopathy to humans, resulting in variant Creutzfeldt-Jakob disease, indicates that humans can be susceptible to animal prion diseases. However, it is not known whether foodborne exposure to the agent causing chronic wasting disease (CWD) in cervids can cause human disease. The United States Foodborne Diseases Active Surveillance Network (FoodNet) conducts surveillance for foodborne diseases through an extensive survey administered to respondents in selected states. To describe the frequency of deer and elk hunting and venison consumption, five questions were included in the 2006-2007 FoodNet survey. This survey included 17,372 respondents in ten states: California, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee. Of these respondents, 3,220 (18.5%) reported ever hunting deer or elk, with 217 (1.3%) reporting hunting in a CWD-endemic area (northeastern Colorado, southeastern Wyoming, and southwestern Nebraska). Of the 217 CWD-endemic area hunters, 74 (34.1%) were residents of Colorado. Respondents reporting hunting were significantly more likely to be male than female (prevalence ratio: 3.3, 95% confidence interval: 3.1-3.6) and, in general, older respondents were significantly more likely to report hunting than younger respondents. Venison consumption was reported by more than half (67.4%) of the study population, and most venison consumers (94.1%) reported that at least half of their venison came from the wild. However, more than half (59.1%) of the consumers reported eating venison only one to five times in their life or only once or twice a year. These findings indicate that a high percentage of the United States population engages in hunting and/or venison consumption. If CWD continues to spread to more areas across the country, a substantial number of people could potentially be exposed to the infectious agent.

http://www.cwd-info.org/pdf/3rd_CWD_Symposium_utah.pdf



Title: Experimental oral transmission of chronic wasting disease (CWD) to red deer (Cervus elaphus elaphus): early detection and late stage distribution of protease-resistant protein (PrP-res)

Balachandran, A - CANADIAN FOOD INSPCTN AG Harrington, Noel - CANADIAN FOOD INSPCTN AG Algire, James - CANADIAN FOOD INSPCTN AG Souyrine, Andre - CANADIAN FOOD INSPCTN AG Orourke, Katherine Spraker, Terry - COLORADO ST UNIV

Submitted to: Canadian Journal of Veterinary Research Publication Type: Peer Reviewed Journal Publication Acceptance Date: December 1, 2008 Publication Date: N/A

Interpretive Summary: Farmed cervids may be exposed to the prion disorder chronic wasting disease through contact with free ranging or farmed infected Rocky Mountain elk, white tailed deer, mule deer, or moose. This is the first report of experimental transmission of chronic wasting disease to red deer, an economically important agricultural commodity in parts of North America. Brain tissue from infected Rocky Mountain elk was administered by the oral route of red deer. Deer were examined at 18 months after infection for evidence of abnormal prion protein, the marker for the disease. The abnormal protein was found throughout the brain, spinal cord and lymphoid tissues, with variable distribution in other organ systems. This finding confirms the potential susceptibility of this species to disease under natural conditions and the reliability of the current testing format for identifying the abnormal protein in the tissues routinely collected in surveillance programs. The widespread distribution of the abnormal protein in red deer indicates the potential for shedding of the agent into the environment. Technical Abstract: Chronic wasting disease CWD is the transmissible spongiform encephalopathy or prion disease of wild and farmed cervid ruminants, including Rocky Mountain elk (Cervus elaphus nelsoni), white tailed deer (Odocoileus virginianus), mule deer (Odocoileus hemionus), or moose (Alces alces). Reliable data on the susceptibility of other farmed cervid species, the distribution of the abnormal prion protein marker in brain and lymphoid tissues collected in surveillance programs, and the role of prion genotype are necessary for design of control programs for CWD in farmed cervids. In this study, red deer (Cervus elaphus elaphus) were exposed to the prion agent by oral administration of brain homogenates from infected Rocky Mountain elk. Antemortem testing was performed at 7 months post infection and the deer were euthanized when clinical disease was observed at approximately 18 months after infection. The abnormal prion protein was assayed by immunohistochemistry, enzyme linked immunosorbent assay and western blot. Abnormal prion protein was found in the spinal cord, brainstem, cerebellum, midbrain, thalamus, and cerebrum in all 4 infected red deer. Most of the lymph nodes throughout the body were positive for abnormal prion proteins. Abnromal prion protein was observed in some additional peripheral tissues in some but not all of the deer. In particular, most areas of the gastrointestinal tract were positive for abnormal prions, although the salivary glands were rarely positive. This study demonstrates the potential for oral transmission of chronic wasting disease to red deer and confirms the usefulness of the current testing methods for post mortem diagnosis of the disease in this species.

http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=228787



Oral transmission and early lymphoid tropism of chronic wasting disease PrPres in mule deer fawns (Odocoileus hemionus )

Christina J. Sigurdson1, Elizabeth S. Williams2, Michael W. Miller3, Terry R. Spraker1,4, Katherine I. O'Rourke5 and Edward A. Hoover1

Mule deer fawns (Odocoileus hemionus) were inoculated orally with a brain homogenate prepared from mule deer with naturally occurring chronic wasting disease (CWD), a prion-induced transmissible spongiform encephalopathy. Fawns were necropsied and examined for PrP res, the abnormal prion protein isoform, at 10, 42, 53, 77, 78 and 80 days post-inoculation (p.i.) using an immunohistochemistry assay modified to enhance sensitivity. PrPres was detected in alimentary-tract-associated lymphoid tissues (one or more of the following: retropharyngeal lymph node, tonsil, Peyer's patch and ileocaecal lymph node) as early as 42 days p.i. and in all fawns examined thereafter (53 to 80 days p.i.). No PrPres staining was detected in lymphoid tissue of three control fawns receiving a control brain inoculum, nor was PrPres detectable in neural tissue of any fawn. PrPres-specific staining was markedly enhanced by sequential tissue treatment with formic acid, proteinase K and hydrated autoclaving prior to immunohistochemical staining with monoclonal antibody F89/160.1.5. These results indicate that CWD PrP res can be detected in lymphoid tissues draining the alimentary tract within a few weeks after oral exposure to infectious prions and may reflect the initial pathway of CWD infection in deer. The rapid infection of deer fawns following exposure by the most plausible natural route is consistent with the efficient horizontal transmission of CWD in nature and enables accelerated studies of transmission and pathogenesis in the native species.

snip...

These results indicate that mule deer fawns develop detectable PrP res after oral exposure to an inoculum containing CWD prions. In the earliest post-exposure period, CWD PrPres was traced to the lymphoid tissues draining the oral and intestinal mucosa (i.e. the retropharyngeal lymph nodes, tonsil, ileal Peyer's patches and ileocaecal lymph nodes), which probably received the highest initial exposure to the inoculum. Hadlow et al. (1982) demonstrated scrapie agent in the tonsil, retropharyngeal and mesenteric lymph nodes, ileum and spleen in a 10-month-old naturally infected lamb by mouse bioassay. Eight of nine sheep had infectivity in the retropharyngeal lymph node. He concluded that the tissue distribution suggested primary infection via the gastrointestinal tract. The tissue distribution of PrPres in the early stages of infection in the fawns is strikingly similar to that seen in naturally infected sheep with scrapie. These findings support oral exposure as a natural route of CWD infection in deer and support oral inoculation as a reasonable exposure route for experimental studies of CWD.

snip...

http://vir.sgmjournals.org/cgi/content/full/80/10/2757



see full text ;


http://chronic-wasting-disease.blogspot.com/2009/09/experimental-oral-transmission-of.html



Sunday, December 06, 2009

Detection of Sub-Clinical CWD Infection in Conventional Test-Negative Deer Long after Oral Exposure to Urine and Feces from CWD+ Deer

http://chronic-wasting-disease.blogspot.com/2009/12/detection-of-sub-clinical-cwd-infection.html



Wednesday, March 18, 2009

Detection of CWD Prions in Urine and Saliva of Deer by Transgenic Mouse Bioassay

http://chronic-wasting-disease.blogspot.com/2009/03/detection-of-cwd-prions-in-urine-and.html



Tuesday, June 16, 2009

Infectious Prions in Pre-Clinical Deer and Transmission of Chronic Wasting Disease Solely by Environmental Exposure

http://chronic-wasting-disease.blogspot.com/2009/06/infectious-prions-in-pre-clinical-deer.html



Wednesday, October 14, 2009

Detection of protease-resistant cervid prion protein in water from a CWD-endemic area

http://chronic-wasting-disease.blogspot.com/2009/10/detection-of-protease-resistant-cervid.html



AS THE CROW FLIES, SO DOES CWD

Sunday, November 01, 2009

American crows (Corvus brachyrhynchos) and potential spreading of CWD through feces of digested infectious carcases

http://chronic-wasting-disease.blogspot.com/2009/11/american-crows-corvus-brachyrhynchos.html



Wednesday, January 07, 2009

CWD to tighten taxidermy rules Hunters need to understand regulations

http://chronic-wasting-disease.blogspot.com/2009/01/cwd-to-tighten-taxidermy-rules-hunters.html



Friday, February 20, 2009

Both Sides of the Fence: A Strategic Review of Chronic Wasting Disease

http://chronic-wasting-disease.blogspot.com/2009/02/both-sides-of-fence-strategic-review-of.html



Saturday, September 06, 2008

Chronic wasting disease in a Wisconsin white-tailed deer farm 79% INFECTION RATE

Contents: September 1 2008, Volume 20, Issue 5

snip...see full text ;

http://chronic-wasting-disease.blogspot.com/2008/11/commentary-crimes-hurt-essence-of.html



Tuesday, February 09, 2010

Chronic Wasting Disease: Surveillance Update North America: February 2010

***

>>> In addition, we documented horizontal transmission of CWD from inoculated mice and to un-inoculated cohabitant cage-mates. <<<


http://ajp.amjpathol.org/cgi/content/abstract/ajpath.2010.090710v1



disturbing. ...TSS


http://chronic-wasting-disease.blogspot.com/2010/02/chronic-wasting-disease-surveillance.html



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



kind regards, terry


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

A molecular switch controls interspecies prion disease transmission in mice

J Clin Invest. doi:10.1172/JCI42051. Copyright © 2010, The American Society for Clinical Investigation.

Research Article

A molecular switch controls interspecies prion disease transmission in mice

Christina J. Sigurdson1,2,3, K. Peter R. Nilsson3, Simone Hornemann4, Giuseppe Manco3, Natalia Fernández-Borges5, Petra Schwarz3, Joaquín Castilla5,6, Kurt Wüthrich4,7 and Adriano Aguzzi3

1Department of Pathology and Department of Medicine, University of California, San Diego, La Jolla, California, USA. 2Department of Pathology, Immunology, and Microbiology, University of California, Davis, Davis, California, USA. 3UniversitätsSpital Zürich, Institute of Neuropathology, Zürich, Switzerland. 4Institut für Molekularbiologie und Biophysik, ETH Zürich, Zürich, Switzerland. 5CIC BioGUNE, Parque tecnológico de Bizkaia, Bizkaia, Spain. 6Ikerbasque, Basque Foundation for Science, Bizkaia, Spain. 7Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California, USA.

Address correspondence to: Adriano Aguzzi, UniversitätsSpital Zürich, Institute of Neuropathology, Department of Pathology, Schmelzbergstrasse 12, CH–8091 Zürich, Switzerland. Phone: 41.44.255.2107; Fax: 41.44.255.4402; E-mail: adriano.aguzzi@usz.ch. Or to: Christina Sigurdson, Department of Pathology, University of California, San Diego, 9500 Gilman Dr., La Jolla, California 92093, USA. Phone: 858.534.0978; Fax: 858.246.0523; E-mail: csigurdson@ucsd.edu.

Published June 14, 2010 Received for publication December 15, 2009, and accepted in revised form April 28, 2010.

Transmissible spongiform encephalopathies are lethal neurodegenerative disorders that present with aggregated forms of the cellular prion protein (PrPC), which are known as PrPSc. Prions from different species vary considerably in their transmissibility to xenogeneic hosts. The variable transmission barriers depend on sequence differences between incoming PrPSc and host PrPC and additionally, on strain-dependent conformational properties of PrPSc. The ß2-a2 loop region within PrPC varies substantially between species, with its structure being influenced by the residue types in the 2 amino acid sequence positions 170 (most commonly S or N) and 174 (N or T). In this study, we inoculated prions from 5 different species into transgenic mice expressing either disordered-loop or rigid-loop PrPC variants. Similar ß2-a2 loop structures correlated with efficient transmission, whereas dissimilar loops correlated with strong transmission barriers. We then classified literature data on cross-species transmission according to the 170S/N polymorphism. Transmission barriers were generally low between species with the same amino acid residue in position 170 and high between those with different residues. These findings point to a triggering role of the local ß2-a2 loop structure for prion transmissibility between different species.

snip...

Discussion 170 and 174 are positions that can modulate prion transmission. The S170N and N174T substitutions in the ß2-a2 loop of PrPC erected a complete barrier to TSEs derived from 2 different host species, cattle and sheep (Table 3). Conversely, the very strong barrier of mice against hamster prions was completely ablated, as hamster prions infected all mice expressing RL-PrPC (Table 3). The potent impact on species barriers caused by 2 amino acid substitutions indicates that prion species barriers may be profoundly altered in humans or animals expressing polymorphisms or mutant PrP molecules. Thus, human or animal TSEs may be replicated by mutant molecules, even when otherwise strong species barriers are known to exist.

TSE infection in the tg1020 mice. We have previously reported that tg1020 mice spontaneously develop a new strain of TSE (53). The resulting disease may confound the assessment of TSE transmission to prion-inoculated tg1020 mice. On the other hand, several traits allowed for unequivocal differentiation between transmitted and spontaneous prion disease. First, immunoblots showed the canonical “shift” in electrophoretic mobility in PrPSc recovered from TSE-infected tg1020 mice after PK digestion. This shift has never been detected in spontaneously sick tg1020 mice. Second, inoculated mice showed widespread deposition of PrPSc in the brain, which extended to regions, such as the thalamus, in which aggregates have never been observed in spontaneous disease. Third, the staining profiles of specific LCP dyes and their fluorescence emission spectra differed vastly between inoculated and spontaneously sick tg1020 mice. For example, PTAA failed to stain any brain sections of RL-RML2 and RL hamster strains in tg1020 mice, whereas it consistently labeled spontaneously appearing prion aggregates. Taken together, these features support that the instances of disease reported in this study represent bona fide transmission of TSE rather than spontaneous disease typical of noninoculated tg1020 mice.

tga20 mice express 2-fold more PrPC than the tg1020 mice and would therefore have been expected to develop prion disease after a shorter ip if there was no transmission barrier induced by the S170N and N174T substitutions. However, the tga20 mice only developed prion disease with a shorter ip after inoculation with RML prions and actually had a longer ip after inoculation with CWD prions. With RML infection, the tg1020 mice showed clear evidence of a transmission barrier, in that the ip exceeded that of lower expressing WT mice and shortened by 50% upon second passage. Together, the data clearly support that the differences in prion susceptibility are due to the S170N and N174T substitutions and not due to the differences in PrPC expression.

Consistency of in vivo and in vitro studies of species barriers. Two decades of published studies indicate that the penetrance of cross-species transmission is affected by the sequence similarity between the host PrPC and the incoming PrPSc (61). Even single–amino acid polymorphisms can radically alter the transmissibility profiles of individual prion strains (62–69). Scrapie infection of cells expressing variant sequences of PrPC has also revealed the striking effects of mutations on the efficiency of conversion of PrPC to PrPSc (70).

Hamster prions were successfully transmitted only to tg1020 mice and not to tga20 mice. The hamster PrP sequence is homologous to RL-PrP at position 170 and to WT-PrP at position 174, suggesting that homology at 170 was critical for transmission. Studies of prion transmission in bank voles and PMCA experiments with CWD in a panel of mammalian species also implicate residue 170 as a key position for influencing species barriers (37, 71). These results can be rationalized by classifying TSE hosts into 2 groups: 170S animals that include cattle, sheep, and mice and 170N animals that include elk, deer, hamsters, and RL mice.

Here, we show that susceptibility to a number of prion strains seemed to be driven by homology at position 170, although further experiments with single mutants would be necessary to fully clarify the relative contributions of residues at positions 170 and 174. tga20 mice could readily convert other 170S prions, such as cattle BSE and classical sheep scrapie, but not the 170N prions, such as hamster scrapie. While the overexpressing tga20 mice could convert 170N mule deer CWD prions after a long ip (59), WT mice are resistant to CWD (57, 58). Conversely, tg1020 mice could convert 170N hamster scrapie and mule deer CWD but completely resisted infection with 170S sheep scrapie and BSE (Table 3). While tg1020 mice may have developed spontaneous infectivity, which would have been detected on further passages, this possibility would not have interfered with the above interpretation.

The above results prompted us to reinterpret published prion transmission experiments and epidemiologic studies in the context of the 170S/170N transmission barrier. In accordance with our predictions, prions are readily transmitted within 170S mammals: sheep scrapie prions infect cattle (72–74) and mice (75, 76), and cattle BSE prions readily infect sheep (77–79) and mice (14, 80). BSE (170S) has also been transmitted to other 170S species, including greater kudu, nyala, eland, scimitar-horned oryx, bison, rhesus macaque, domestic cat, and mink (13, 16, 81, 82). Conversely, prions generated in 170S animals are poorly transmissible to 170N recipients and vice versa. Transgenic mice overexpressing bovine or ovine PrP completely resisted infection to 9 different CWD isolates (58), and WT mice do not develop clinical prion disease after infection with elk CWD or hamster 263K scrapie (57, 58, 60). Furthermore, cattle and sheep are poorly infectible with mule deer CWD, since few animals develop disease after prolonged ips of 6 years, and only after intracerebral inoculation (83, 84). Among 170N animals, prions are also transmissible, as elk CWD is infectious to hamsters (85), albeit not very efficiently. Collectively, most historical data from studies on species barriers support the model that similarity at the loop region, and particularly the 170S/N switch, impacts transmission barriers in a broad variety of species. As a possible exception to these observations, cattle may be susceptible to CWD from white-tailed deer (86). The latter finding suggests that specific prion strains can overrule the codon 170 homology requirement.

Does the ß2-a2 loop direct prion strain conformation? What are the structural consequences of the substitutions at residues 170 and 174, and how might they explain the important role of these substitutions in interspecies prion transmission? Crystallographic investigations of PrP peptides revealed that adjacent ß2-a2 loops can engage in a “dry steric zipper” interface, which was proposed to represent the elemental backbone of many amyloids. Peptide crystal structures encompassing the ß2-a2 loops bearing the 170S/174N and 170N/174T substitutions were arranged in a P1 or a P21 crystal space group, respectively (87). These observations suggest striking differences in the ß-sheet alignment of PrPSc aggregates between prion-infected 170S and 170N animals and may provide a plausible starting point for clarifying the structural basis of prion species barriers that are highly relevant to public health, including the potential transmissibility of bovine and cervid prions to humans.

snip...


see full text ;


http://www.jci.org/articles/view/42051?key=456180f4a34aad821c6f#B87



JCI online early table of contents: June 14, 2010 Featured In: Disease Research

By Eurek

Alert

Monday, June 14, 2010

EDITOR'S PICK: Sequence and structure key to prion disease transmission

Prion diseases are lethal neurodegenerative disorders that include Creutzfeldt-Jakob disease (CJD) in humans and bovine spongiform encephalopathy (BSE; commonly known as mad cow disease) in cows. A team of researchers, led by Adriano Aguzzi and Christina Sigurdson, at UniversitätsSpital Zürich, Switzerland, has generated data in mice that provides greater understanding of the factors that determine how easy it is for prion diseases to be transmitted to a new host species. This information provides new insight into a highly important food safety issue; dietary exposure to beef contaminated with the BSE agent is believed to have caused nearly 200 cases of variant CJD in humans.

The key infectious agent in prion diseases is PrPSc, a highly aggregated form of the cellular prion protein (PrPC). The ease with which prions from different species can be transmitted to a new host species varies dramatically. The team found that transmission between species with the same protein building block at position 170 in PrPC was relatively easy while it was relatively difficult between those species with different building blocks at that position. As this protein building block influences the structure of the PrPC protein, the authors suggest that local structure of PrPC affected by the protein building block at position 170 might have a triggering role in prion transmissibility between different species.

TITLE: A molecular switch controls interspecies prion disease transmission in mice

AUTHOR CONTACT: Adriano Aguzzi UniversitätsSpital Zürich, Zürich, Switzerland. Phone: 41.44.255.2107; Fax: 41.44.255.4402;E-mail: adriano.aguzzi@usz.ch.

Christina Sigurdson University of California at San Diego, La Jolla, California, USA. Phone: 858.534.0978; Fax: 858.246.0523; E-mail: csigurdson@ucsd.edu.



http://www.biosciencetechnology.com/News/Feeds/2010/06/disease-research-jci-online-early-table-of-contents-june-14-2010/




>>> These observations suggest striking differences in the ß-sheet alignment of PrPSc aggregates between prion-infected 170S and 170N animals and may provide a plausible starting point for clarifying the structural basis of prion species barriers that are highly relevant to public health, including the potential transmissibility of bovine and cervid prions to humans.<<<



snip...



>>> As a possible exception to these observations, cattle may be susceptible to CWD from white-tailed deer (86). The latter finding suggests that specific prion strains can overrule the codon 170 homology requirement. <<<



http://chronic-wasting-disease.blogspot.com/2010/05/prion-strain-mutation-determined-by.html



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



TSS

Prion Strain Mutation and Selection John Collinge

MEDICINE

John Collinge

Structural compatibility of infecting prion proteins with those of a new host determine whether they will be successfully transmitted. When the connection was made between bovine spongiform encephalopathy (BSE or “mad cow” disease) and human illnesses in the 1990s, it raised the public profile of the underlying prion diseases as the implications of animal and public health crises, and their economic impacts, became apparent. At the core of these concerns is how prions, the infectious agent, diversify and expand their host range. On page 1154 of this issue, Angers et al. ( 1) reveal how this occurs in chronic wasting disease (CWD), a contagious prion disease of wild deer and elk. Its prevalence in the United States raised fears that, like BSE, it might transmit to humans.

Prions cause fatal neurodegenerative diseases of humans and animals such as scrapie in sheep and goats, BSE in cattle, and Creutzfeldt-Jakob disease in humans ( 2). They consist of a rogue form of a protein produced by an infected animal, not by a foreign DNA or RNA genome, and pass from one species to another via dietary and other routes of transmission. Prions are thought to be composed principally or entirely of polymers of misfolded prion protein (known collectively as PrP scrapie or PrPSc). They propagate by recruiting the normal host prion protein (PrPC) via seeded protein fi brilization. In this process, fragmentation of elongating fi brils leads to an autocatalytic, exponential amplifi cation process that effectively mimics a conventional infectious agent in its ability to invade and colonize susceptible hosts. Despite the absence of a nucleic acid genome, prions exist as multiple strains that can be serially propagated in laboratory animals and differentiated by the patterns of disease they produce. Because multiple strains can be maintained in inbred mice with identical PrP genes, prions cannot be encoded by differences in PrP primary structure (its amino acid sequence). Rather, it is thought that they represent structurally different PrPSc seeds that recruit host PrPC into polymers of misfolded PrP. Thus, strains may be associated with biochemically distinct PrPSc types that can propagate on serial passage in susceptible hosts, including those from different species ( 3– 5) (see the figure).

PrPs have a highly conserved structure, which is presumably central to their ability to infect across species. Although differences in PrPC primary structure have been considered a barrier to cross-species infection, the “strain-ness” of a prion is fundamental to its ability to infect a new species. Thus, two prion types, or strains, that propagate in one species may have different abilities to cross a transmission barrier ( 6). Under the conformational selection model ( 7), of the possible PrPSc strains that can overcome natural clearance and propagate effectively in mammals, only a subset is compatible with a given host PrPC structure, and can thereby propagate in that host. Transmission barriers can be explained by the degree of overlap between strain types that are permissible in the two species concerned. Such effects may also be encountered within a species where there are PrP polymorphisms. A common human PrP polymorphism (at amino acid position 129) dramatically affects strain selection ( 4, 8) and has a powerful effect on human susceptibility to prion disease ( 9, 10). Important PrP polymorphisms are also seen in sheep and other species, and conformational selection occurs with yeast prions as well ( 11).

However, in some cases, prions do not maintain their identity in a new host but switch properties. Such strain “mutation” ( 12) may result from crossing between species, or intraspecies transmission due to PrP polymorphism or the effect of genetic background ( 13). The new strain generated may be more or less pathogenic in a second species than its progenitor, so mutation has potential public and animal health implications.

Although is has been argued that prion strains may be cloned ( 12), such material is heterogeneous when assessed by physical and biochemical methods. It may be that prion strains represent an ensemble of molecular species maintained under host selection ( 14). Such a quasispecies would have a dominant component with recognizable biochemical and biological properties, but also have lower-abundance subspecies. The preferential selection of the latter in an alternate host that is unable to propagate the dominant species could explain strain mutation ( 14), as observed in prion-infected cell cultures ( 15).

CWD is prevalent in wild cervids (deer and elk) in several U.S. states and has been recognized in Canada and South Korea. It spreads readily between wild animals, and urine, feces, and saliva are infectious ( 16). The occurrence of multiple strains of CWD is likely, given that multiple cervid species and different PrPC structures (including within-species PrP polymorphism) are involved, and the existence of at least two CWD strains (CWD 1 and 2) has now been demonstrated by Angers et al. The authors show that CWD prion strain selection and mutation are influenced by the amino acid at position 226 in PrP ( 4, 8), which differs between deer and elk. Although CWD 1 and 2 can be distinguished by biological strain typing methods, their biochemical characteristics are similar by the molecular strain typing methods used. Assuming that the “proteinonly” model of replication is correct, such differences in disease-associated PrP must exist. However, these differences may reside in protease- sensitive forms of abnormal PrP, which are important components of prion isolates.

What is the importance of the findings of Angers et al. for public health? One method to model human susceptibility, as done with BSE in the 1990s ( 2), is to determine the susceptibility of transgenic mice expressing human PrPC to CWD prion infection in comparison to susceptibility in human and other animal strains. Studies so far show that such mice are resistant ( 17, 18). However, it is necessary to repeat these studies with all CWD strains identified and to take account of permutations of PrP polymorphisms in CWD affected animals and humans. This further evidence for the role of PrP polymorphism on strain selection and mutation should highlight the potential for a new zoonotic prion strain to emerge from prion evolution in animal reservoirs, notably in worldwide endemic scrapie of sheep and goats as well as CWD in deer and elk.

Prion-like mechanisms may be relevant in common human neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Accumulation of misfolded host proteins occurs in these diseases, and seeded protein aggregation may be relevant to the etiology and spread of pathology ( 14). It will be of great interest to see if the phenomena of conformational and kinetic selection of strains and their mechanisms of neurotoxicity are also important in these and other diseases of protein misfolding.

Prion propagation. (A) A limited set of mammalian PrPSc conformations can propagate as prions using the PrPC present in susceptible host species. Prions transmit readily between hosts that express the same PrPC, and may do so in those with different PrPC if there is substantial overlap of permissible conformations (species I and II). If there is little or no overlap (species I and III), a major transmission barrier occurs. (B) A prion strain may be a molecular ensemble maintained under host selection. (a) A strain can propagate in the same species expressing identical PrPC; (b) strain mutation may occur when prions colonize the same species with a different PrPC, or (c) may propagate in a different species with compatible PrPC; (d) if not compatible in a new species, mutation may occur.

References

1. R. C. Angers et al., Science 328, 1154 (2010).

2. J. Collinge, Annu. Rev. Neurosci. 24, 519 (2001).

3. R. A. Bessen, R. F. Marsh, J. Virol. 68, 7859 (1994).

4. J. Collinge et al., Nature 383, 685 (1996).

5. G. C. Telling et al., Science 274, 2079 (1996).

6. A. F. Hill et al., Nature 389, 448, 526 (1997).

7. J. Collinge, Lancet 354, 317 (1999).

8. J. D. Wadsworth et al., Science 306, 1793 (2004).

9. M. S. Palmer et al., Nature 352, 340 (1991).

10. S. Mead et al., Science 300, 640 (2003).

11. R. B. Wickner et al., Annu. Rev. Genet. 38, 681 (2004).

12. M. E. Bruce, A. G. Dickinson, J. Gen. Virol. 68, 79 (1987).

13. S. E. Lloyd et al., J. Gen. Virol. 85, 2471 (2004).

14. J. Collinge, A. R. Clarke, Science 318, 930 (2007).

15. J. Li et al., Science 327, 869 (2010).

16. C. K. Mathiason et al., PLoS ONE 4, e5916 (2009).

17. G. Tamguney et al., J. Virol. 80, 9104 (2006).

18. Q. Kong et al., J. Neurosci. 25, 7944 (2005).


www.sciencemag.org

SCIENCE VOL 328 28 MAY 2010



Friday, May 14, 2010

Prion Strain Mutation Determined by Prion Protein Conformational Compatibility and Primary Structure

Published Online May 13, 2010 Science DOI: 10.1126/science.1187107 Science Express Index


http://www.sciencemag.org/cgi/content/abstract/science.1187107



see full text and more here ;


http://chronic-wasting-disease.blogspot.com/2010/05/prion-strain-mutation-determined-by.html




John Collinge wrote ;


>>> "They consist of a rogue form of a protein produced by an infected animal, not by a foreign DNA or RNA genome...Despite the absence of a nucleic acid genome, prions exist as multiple strains" <<<


SOME interesting findings and comments below ; Our laboratory continues to do fundamental research on infectious dementias and the causes of neurodegenerative disease. The transmission of variant Creutzfeldt-Jakob Disease (vCJD) to normal mice as well as to neuronal cultures here (PMID: 19097123) proves that the vCJD infectious agent is derived from epidemic “mad cow disease” (BSE) in the UK. This virus-like agent is a unique strain belonging to the group that causes Transmissible Spongiform Encephalopathies (TSEs). These agents affect many mammalian species. Our transmission of kuru, a human TSE in New Guinea, both to mice and to monotypic cultures (PMID: 19633190) shows kuru is another unique agent that is also geographically restricted. In addition, there are vast differences in the incubation time and regional brain lesions that distinguish the many distinct geographic human CJD and sheep scrapie isolates (dramatic brain differences in CJD strains isolated from the USA and Japan can be seen at


http://info.med.yale.edu/neurosci/faculty/manuelidis_main.html


http://www.ncbi.nlm.nih.gov/sites/entrez


http://www.pnas.org/content/106/32/13529.full


http://info.med.yale.edu/neurosci/faculty/manuelidis_files/tse/25_nm_virion.pdf



Our results emphasize an environmental origin of TSE infectious agents . Indeed, it is likely that environmental causes, infectious, toxic and traumatic, underlie more common dementias such as Alzheimer’s Disease. This line of approach deserves increased investigation, especially in view of major public health issues. Our stable tissue culture models of many different TSE strains, as well as the ability to rapidly assay infectivity in culture (PMID: 18989813; PMID: 18788938, and see below), offer exciting new avenues for direct molecular analysis of infectious TSE particles and rational approaches to prevent and cure these infections. We here point out some of the reasons why we think it likely that the infectious agent is a virus rather than a misfolded host protein.


The backwards evolution of the prion concept


Sometimes speculations leap so far ahead of evidence that they develop a detached life of their own. When popularized, unfounded beliefs can also be difficult to erase. Through much of the Middle Ages it was believed that plagues were a consequence of divine retribution. Yet most people in the USA today realize that plagues are caused by infectious organisms. Eradication of these organisms is both preventive and curative. Barrier experiments during the 1700s first proved that rats and other forms of visible life did not arise spontaneously. However, the idea of spontaneous generation of microscopic forms of life, such as bacteria and viruses, persisted until similar barrier and filtration experiments of Pasteur and others were undertaken. These showed a pre-existing “seed” or organism had to be present to generate new life. Furthermore, modern molecular genetics clearly shows infectious organisms all need nucleic acid for true replication (making many new copies), and viral and bacterial genomes can be propagated solely by using their nucleic acid (DNA or RNA) sequences. Moreover, simply modifying these sequences alters the strain-specific properties of infectious agents.


A hypothetical new form of life called a “prion” (an acronym for a protein infectious particle, later identified as the host protein “PrP”) is claimed to have remarkable features that are most reminiscent of ancient beliefs. Yet there is no direct evidence for many prion claims. These include the spontaneous generation of infectivity by a normal mammalian protein. Spontaneous conversion was a convenient belief (and legal cover) for governments dealing with practices that led to the epidemic outbreak of mad cow disease. Unlike spontaneous events that should occur with some type of mathematical frequency, the characteristics of the specific mad cow infectious agent had never been seen before. Additionally, the disease occurred only in places exposed to contaminated products (i.e., not spontaneously made by the host). Removing infected materials dramatically and abruptly diminished the UK cow epidemic. Similarly, new kuru infections disappeared after the cessation of ritual cannibalism in New Guinea Perhaps more disingenuous, in view of the experimental data, are the statements that TSE infectious agents, “because they are prions”, contain no nucleic acids (DNA or RNA). The prion concept was introduced in 1982 (PMID: 6801762) despite the fact that the preparations treated to abolish nucleic acids had enough DNA to code for a million human beings (reviewed in PMID: 12828865). In fact, the only two subsequent “peer-reviewed” experimental papers (from 1993 and 2005) to conclude that there are no nucleic acids of >50 bases in TSE infectious fractions are written by S. Prusiner’s prion group. Neither of these reports used modern sensitive end labeling, or established RT-PCR methods for nucleic acid detection (PMID: 16051871). Nor were controls such as enteroviral particles added to monitor nucleic acid extraction. Moreover, detailed RT-PCR methods published in 1994 (PMID: 8152913) had already demonstrated endogenous virus with >5,000 bases co-migrates with infectious TSE particles during purification. These TSE and viral particles were resistant to exhaustive nuclease digestion. It is also notable that both the R. Marsh (PMID: 1972202) and C. Weissmann groups independently uncovered nucleic acids of >300 bases in Prusiner’s purified prion preparations that were presumably free of nucleic acids. Several groups in France have also independently reported nucleic acids in their own infectious preparations (PMID: 18422484, and cited in


http://www.sciencemag.org/cgi/eletters/327/5967/869#12963



The belief that an infectious protein, rather than a covert nucleic acid, must code for the wellestablished different TSE agent strains (sporadic CJD, kuru, BSE and various scrapie isolates) excludes the objective evidence of nucleic acids in infectious preparations. Recent claims that prion protein mutates and evolves (PMID: 20044542), instead of a nucleic acid, also replays the discredited Tobacco Mosaic Virus story where a self-catalyzed crystalline protein was said to be the causal infectious agent. This Nobel Prize work simply ignored the viral nucleic acid present in the preparations that coded for the viral replication.


We continue to work on the more parsimonious concept that the fundamental infectious particle causing CJD, scrapie and other TSEs is a small virus of ~25nm, as determined experimentally by independent size, density and ultrastructural studies (PMID: 17044041; PMID: 17267596). PrP acts as a necessary host receptor or scaffold for this virus, and pathologic PrP amyloid is formed late in infection as a result of this interaction. Notably, microglia that have negligible PrP and no detectable PrP amyloid have shown very high levels of infectivity (PMID: 12368333). Thus we continue to do work on TSEs to understand this group of infectious agents and the ways they cause dementia. There are far more parts of this puzzle than the prion protein.


The following table lists essential prion claims that are contradicted by experimental data. The findings continue to implicate a 25nm diameter virus as the cause of TSEs.


CLAIM* Experiment COMMENT


1) “PrPSc (PrP amyloid, PrP-res) is proportional to titer” FALSE diverse data from many labs


2) “Procedures that modify or hydrolyze PrPSc inactivate prions” TRUE They also inactivate viruses


3) “No evidence exists for a virus-like particle” FALSE discrete ~25nm viral particle


4) “Transmissible particles are devoid of nucleic acid” FALSE all infectious preps contain long nucleic acids


5) “PrP gene mutations cause formation of PrPSc” FALSE toxic pathology, but no PrPSc


6) “PrP gene mutations cause transmissible disease” not reproducible Contamination with lab scrapie 263K


7) “Prion diversity is enciphered by PrPSc” conformation FALSE changing PrP-res folding has no effect on strain or titer


8) TSE “strains can be generated by passing through hosts with different PrP genes” rarely Strains typically keep their unique identity in different species (as BSE)


9) “No sign of an immune response to foreign agent” FALSE Early innate immune responses before detectable PrP-res


10) “Accumulation of PrPSc associated with pathology” TRUE PrPSc is a late response to infection


11) Protein X postulated to bind PrP for transmission X not found PrP itself not infectious; X is probably a virus


12) “Prions defy the rules of protein structure” TRUE possibly also of thermodynamics


13) CJD infectious agent arises spontaneously No evidence An idea predating evolution


TABLE I: Major arguments and the “wealth of data…for the fundamental principles of prion biology”. PrPsc the presumably “infectious scrapie or prion form” is revealed by limited protease digestion of tissue in a test tube and is equivalent to PrP amyloid, PrP-res, aggregated PrP.


Tissue culture studies have shown that altering the PrP profile does not change the strain properties. The bands are tissue and cell-type specific, and unlike the infectious agent do not breed true (e.g., PMID: 15161970). Below is a picture of infected neuronal cultures and they can also show the pathological prion protein (in red) unlike mock-infected cultures (inset). Notably, despite the high level of pathological PrP in these cells they show no toxic response. Thus PrP itself may not be the ultimate or sole cause of neurodegeneration. These cells give reliable, rapid assays of the agent.


The ultrastructural 25nm particles have been found in more purified infectious TSE preparations. They do not bind PrP antibodies, unlike isolated amyloid fibrils (PMID: 17044041). These virus-like particles can also be identified in intact cells with high levels of infectivity (PMID: 17267596), and can be seen in compact arrays, like many conventional virions. An array is depicted here inside the cell and shown in a corresponding 3-D projection from different angles. These particle arrays are unrelated to the PrP amyloid fibrils in the cytoplasm identified structurally and by PrP antibodies.



http://medicine.yale.edu/surgery/neuropathology/research/index.aspx



http://medicine.yale.edu/surgery/neuropathology/Images/lmwebresearch_tcm313-46643.pdf




I will quote what one of the leading scientist in the world on prion disease once said about CWD, and then post some data on this topic. Good question, one that should be addressed. I will attempt to address it. I am a meat eater, and I don't care what you and others eat, but on the topic of human and animal Transmissible Spongiform Encephalopathy, I can assure you that you have not been told the complete truth. This is a long post, take the information, and please look at the source of the data. I post this data on blogs, no advertisements, not making money doing this. The information is for your benefit, please use as you wish. ...kind regards, terry



A. Aguzzi - Chronic Wasting Disease (CWD) also needs to be addressed.

Most serious because of rapid horizontal spread and higher prevalence than BSE in UK, up to 15% in some populations.

Also may be a risk to humans - evidence that it is not dangerous to humans is thin. ...end



REMEMBER, there are over twenty strains of typical scrapie, and the atypical scrapie cases (Nor-98) are mounting, two documented strains of Transmissible Mink Encephalopathy, and 3 strains of BSE in cattle, all of which have been documented in North America, all have been shown to transmit to man via lab studies in mice, with the L-type atypical BSE being much more virulent. Also, now there are two strains of CWD. all these TSE in different animals have been rendered and put into feed for livestock producing animals for human and animal in the USA. This is fact.


can humans get a prion disease from deer or elk that have CWD ?

as someone else stated here, no one knows for sure to date, but the likelyhood of being exposed to CWD from eating a CWD deer or elk is high, and then years on down the road, regardless whether or not this person ever goes clinical, due to any medical surgical, or dental procedures, blood donations, the agent will continue to spread, more humans exposed. the fact that some of these atypical TSE are mutating and becoming more virulent is very troublesome. the incubation time is shortened.

I assure you that the FDA did not recall this CWD postive elk meat in commerce, for the well being of the dead CWD postive elk ;



Wednesday, March 18, 2009

Noah's Ark Holding, LLC, Dawson, MN RECALL Elk products contain meat derived from an elk confirmed to have CWD NV, CA, TX, CO, NY, UT, FL, OK RECALLS AND FIELD CORRECTIONS: FOODS CLASS II

please see ;

RECALLS AND FIELD CORRECTIONS: FOODS CLASS II

___________________________________

PRODUCT a) Elk Meat, Elk Tenderloin, Frozen in plastic vacuum packaging. Each package is approximately 2 lbs., and each case is approximately 16 lbs.; Item number 755125, Recall # F-129-9;

b) Elk Meat, Elk Trim, Frozen; Item number 755155, Recall # F-130-9;

c) Elk Meat, French Rack, Chilled. Item number 755132, Recall # F-131-9;

d) Elk Meat, Nude Denver Leg. Item number 755122, Recall # F-132-9;

e) Elk Meat, New York Strip Steak, Chilled. Item number 755128, Recall # F-133-9;

f) Elk Meat, Flank Steak Frozen. Item number 755131, Recall # F-134-9; CODE Elk Meats with production dates of December 29, 30, and 31 RECALLING FIRM/MANUFACTURER Recalling Firm: Sierra Meats, Reno, NV, by telephone on January 29, 2009 and press release on February 9, 2009. Manufacturer: Noah’s Ark Holding, LLC, Dawson, MN. Firm initiated recall is ongoing. REASON Elk products contain meat derived from an elk confirmed to have Chronic Wasting Disease (CWD). VOLUME OF PRODUCT IN COMMERCE Unknown DISTRIBUTION NV, CA, TX, CO, NY, UT, FL, OK

___________________________________

END OF ENFORCEMENT REPORT FOR March 18, 2009

###


http://www.fda.gov/Safety/Recalls/EnforcementReports/ucm154840.htm




http://chronic-wasting-disease.blogspot.com/2009/03/noahs-ark-holding-llc-dawson-mn-recall.html



http://chronic-wasting-disease.blogspot.com/2009/02/exotic-meats-usa-announces-urgent.html




Sunday, April 12, 2009

CWD UPDATE Infection Studies in Two Species of Non-Human Primates and one Environmental reservoir infectivity study and evidence of two strains

http://chronic-wasting-disease.blogspot.com/2009/04/cwd-update-infection-studies-in-two.html




Thursday, April 03, 2008

A prion disease of cervids: Chronic wasting disease

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

A prion disease of cervids: Chronic wasting disease

Sigurdson CJ.


snip...


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


snip...


full text ;


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




From: TSS (216-119-163-189.ipset45.wt.net)

Subject: CWD aka MAD DEER/ELK TO HUMANS ???

Date: September 30, 2002 at 7:06 am PST

From: "Belay, Ermias"

To:

Cc: "Race, Richard (NIH)" ; ; "Belay,

Ermias"

Sent: Monday, September 30, 2002 9:22 AM

Subject: RE: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG HUNTERS

Dear Sir/Madam,

In the Archives of Neurology you quoted (the abstract of which was

attached to your email), we did not say CWD in humans will present like

variant CJD.

That assumption would be wrong. I encourage you to read the whole

article and call me if you have questions or need more clarification

(phone: 404-639-3091). Also, we do not claim that "no-one has ever been

infected with prion disease from eating venison." Our conclusion stating

that we found no strong evidence of CWD transmission to humans in the

article you quoted or in any other forum is limited to the patients we

investigated.

Ermias Belay, M.D.

Centers for Disease Control and Prevention


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


From:

Sent: Sunday, September 29, 2002 10:15 AM

To: rr26k@nih.gov; rrace@niaid.nih.gov; ebb8@CDC.GOV

Subject: TO CDC AND NIH - PUB MED- 3 MORE DEATHS - CWD - YOUNG

HUNTERS

Sunday, November 10, 2002 6:26 PM ......snip........end..............TSS

SEE also ;

A. Aguzzi - Chronic Wasting Disease (CWD) also needs to be addressed. Most

serious because of rapid horizontal spread and higher prevalence than BSE in

UK, up to 15% in some populations. Also may be a risk to humans - evidence

that it is not dangerous to humans is thin.

http://www.tseandfoodsafety.org/activities/bse_conference_basel_april_02/2summar



SNIP...END...TSS

Chronic Wasting Disease and Potential Transmission to Humans

Ermias D. Belay,* Ryan A. Maddox,* Elizabeth S. Williams,? Michael W. Miller,? Pierluigi Gambetti,§ and Lawrence B. Schonberger*

*Centers for Disease Control and Prevention, Atlanta, Georgia, USA; ?University of Wyoming, Laramie, Wyoming, USA; ?Colorado Division of Wildlife, Fort Collins, Colorado, USA; and §Case Western Reserve University, Cleveland, Ohio, USA

Suggested citation for this article: Belay ED, Maddox RA, Williams ES, Miller MW, Gambetti P, Schonberger LB. Chronic wasting disease and potential transmission to humans. Emerg Infect Dis [serial on the Internet]. 2004 Jun [date cited]. Available from:

http://www.cdc.gov/ncidod/EID/vol10no6/03-1082.htm




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

Chronic wasting disease (CWD) of deer and elk is endemic in a tri-corner area of Colorado, Wyoming, and Nebraska, and new foci of CWD have been detected in other parts of the United States. Although detection in some areas may be related to increased surveillance, introduction of CWD due to translocation or natural migration of animals may account for some new foci of infection. Increasing spread of CWD has raised concerns about the potential for increasing human exposure to the CWD agent. The foodborne transmission of bovine spongiform encephalopathy to humans indicates that the species barrier may not completely protect humans from animal prion diseases. Conversion of human prion protein by CWD-associated prions has been demonstrated in an in vitro cell-free experiment, but limited investigations have not identified strong evidence for CWD transmission to humans. More epidemiologic and laboratory studies are needed to monitor the possibility of such transmissions.

snip...full text ;

http://www.cdc.gov/ncidod/EID/vol10no6/03-1082.htm




Volume 12, Number 10-October 2006

Research

Human Prion Disease and Relative Risk Associated with Chronic Wasting Disease

Samantha MaWhinney,* W. John Pape,? Jeri E. Forster,* C. Alan Anderson,?§ Patrick Bosque,?¶ and Michael W. Miller#

*University of Colorado at Denver and Health Sciences Center, Denver, Colorado, USA; ?Colorado Department of Public Health and Environment, Denver, Colorado, USA; ?University of Colorado School of Medicine, Denver, Colorado, USA; §Denver Veteran's Affairs Medical Center, Denver, Colorado, USA; ¶Denver Health Medical Center, Denver, Colorado, USA; and #Colorado Division of Wildlife, Fort Collins, Colorado, USA

Suggested citation for this article

The transmission of the prion disease bovine spongiform encephalopathy (BSE) to humans raises concern about chronic wasting disease (CWD), a prion disease of deer and elk. In 7 Colorado counties with high CWD prevalence, 75% of state hunting licenses are issued locally, which suggests that residents consume most regionally harvested game. We used Colorado death certificate data from 1979 through 2001 to evaluate rates of death from the human prion disease Creutzfeldt-Jakob disease (CJD). The relative risk (RR) of CJD for CWD-endemic county residents was not significantly increased (RR 0.81, 95% confidence interval [CI] 0.40-1.63), and the rate of CJD did not increase over time (5-year RR 0.92, 95% CI 0.73-1.16). In Colorado, human prion disease resulting from CWD exposure is rare or nonexistent. However, given uncertainties about the incubation period, exposure, and clinical presentation, the possibility that the CWD agent might cause human disease cannot be eliminated.

snip... full text ;


http://0-www.cdc.gov.mill1.sjlibrary.org/ncidod/EID/vol12no10/06-0019.htm




full text ;


http://chronic-wasting-disease.blogspot.com/2006_12_01_archive.html




(10) Transmission of Elk and Deer Prions to Transgenic Mice


http://jvi.asm.org/cgi/content/abstract/80/18/9104




(30) Neurobiology of Disease Chronic Wasting Disease of Elk: Transmissibility to Humans Examined by Transgenic Mouse Models


http://www.jneurosci.org/cgi/content/short/25/35/7944




(13) Prions in Skeletal Muscles of Deer with Chronic Wasting Disease


http://www.sciencemag.org/cgi/content/abstract/sci;311/5764/1117




(14) Volume 15, Number 5–May 2009 Research Chronic Wasting Disease Prions in Elk Antler Velvet


http://www.cdc.gov/eid/content/15/5/696.htm




Friday, May 14, 2010

Prion Strain Mutation Determined by Prion Protein Conformational Compatibility and Primary Structure

Published Online May 13, 2010 Science DOI: 10.1126/science.1187107 Science Express Index


http://chronic-wasting-disease.blogspot.com/2010/05/prion-strain-mutation-determined-by.html





P35

ADAPTATION OF CHRONIC WASTING DISEASE (CWD) INTO HAMSTERS, EVIDENCE OF A WISCONSIN STRAIN OF CWD

Chad Johnson1, Judd Aiken2,3,4 and Debbie McKenzie4,5 1 Department of Comparative Biosciences, University of Wisconsin, Madison WI, USA 53706 2 Department of Agriculture, Food and Nutritional Sciences, 3 Alberta Veterinary Research Institute, 4.Center for Prions and Protein Folding Diseases, 5 Department of Biological Sciences, University of Alberta, Edmonton AB, Canada T6G 2P5 The identification and characterization of prion strains is increasingly important for the diagnosis and biological definition of these infectious pathogens. Although well-established in scrapie and, more recently, in BSE, comparatively little is known about the possibility of prion strains in chronic wasting disease (CWD), a disease affecting free ranging and captive cervids, primarily in North America. We have identified prion protein variants in the white-tailed deer population and demonstrated that Prnp genotype affects the susceptibility/disease progression of white-tailed deer to CWD agent. The existence of cervid prion protein variants raises the likelihood of distinct CWD strains. Small rodent models are a useful means of identifying prion strains. We intracerebrally inoculated hamsters with brain homogenates and phosphotungstate concentrated preparations from CWD positive hunter-harvested (Wisconsin CWD endemic area) and experimentally infected deer of known Prnp genotypes. These transmission studies resulted in clinical presentation in primary passage of concentrated CWD prions. Subclinical infection was established with the other primary passages based on the detection of PrPCWD in the brains of hamsters and the successful disease transmission upon second passage. Second and third passage data, when compared to transmission studies using different CWD inocula (Raymond et al., 2007) indicate that the CWD agent present in the Wisconsin white-tailed deer population is different than the strain(s) present in elk, mule-deer and white-tailed deer from the western United States endemic region.


http://www.istitutoveneto.it/prion_09/Abstracts_09.pdf




Potential Venison Exposure Among FoodNet Population Survey Respondents, 2006-2007

Ryan A. Maddox1*, Joseph Y. Abrams1, Robert C. Holman1, Lawrence B. Schonberger1, Ermias D. Belay1 Division of Viral and Rickettsial Diseases, National Center for Zoonotic, Vector-Borne, and Enteric Diseases, Centers for Disease Control and Prevention, Atlanta, GA *Corresponding author e-mail: rmaddox@cdc.gov

The foodborne transmission of bovine spongiform encephalopathy to humans, resulting in variant Creutzfeldt-Jakob disease, indicates that humans can be susceptible to animal prion diseases. However, it is not known whether foodborne exposure to the agent causing chronic wasting disease (CWD) in cervids can cause human disease. The United States Foodborne Diseases Active Surveillance Network (FoodNet) conducts surveillance for foodborne diseases through an extensive survey administered to respondents in selected states. To describe the frequency of deer and elk hunting and venison consumption, five questions were included in the 2006-2007 FoodNet survey. This survey included 17,372 respondents in ten states: California, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee. Of these respondents, 3,220 (18.5%) reported ever hunting deer or elk, with 217 (1.3%) reporting hunting in a CWD-endemic area (northeastern Colorado, southeastern Wyoming, and southwestern Nebraska). Of the 217 CWD-endemic area hunters, 74 (34.1%) were residents of Colorado. Respondents reporting hunting were significantly more likely to be male than female (prevalence ratio: 3.3, 95% confidence interval: 3.1-3.6) and, in general, older respondents were significantly more likely to report hunting than younger respondents. Venison consumption was reported by more than half (67.4%) of the study population, and most venison consumers (94.1%) reported that at least half of their venison came from the wild. However, more than half (59.1%) of the consumers reported eating venison only one to five times in their life or only once or twice a year. These findings indicate that a high percentage of the United States population engages in hunting and/or venison consumption. If CWD continues to spread to more areas across the country, a substantial number of people could potentially be exposed to the infectious agent.


http://www.cwd-info.org/pdf/3rd_CWD_Symposium_utah.pdf





Sunday, April 12, 2009

CWD UPDATE Infection Studies in Two Species of Non-Human Primates and one Environmental reservoir infectivity study and evidence of two strains


http://chronic-wasting-disease.blogspot.com/2009/04/cwd-update-infection-studies-in-two.html




In Confidence - Perceptions of unconventional slow virus diseases of animals in the USA - APRIL-MAY 1989 - G A H Wells

3. Prof. A Robertson gave a brief account of BSE. The US approach was to accord it a very low profile indeed. Dr. A Thiermann showed the picture in the ''Independent'' with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs. BSE was not reported in the USA.

snip...

CWD occurred principally in two locations, this one at Sybille and in a similar faccility at Fort Collins, Colorado, some 120 miles southwest. It was estimated that in total probably 60-70 cases of CWD have occurred.

It was difficult to gain a clear account of incidence and temporal sequence of events (-this presumably is data awaiting publication - see below) but during the period 1981-1984, 10-15 cases occurred at the Sybille facility.

The moribidity amongst mule deer in the facilities ie. those of the natural potentially exposed group has been about 90% with 100% mortality.

snip...

Spraker suggested an interesting explanation for the occurrence of CWD. The deer pens at the Foot Hills Campus were built some 30-40 years ago by a Dr. Bob Davis. At or abut that time, allegedly, some scrapie work was conducted at this site. When deer were introduced to the pens they occupied ground that had previously been occupied by sheep.

see full text 33 pages ;


http://collections.europarchive.org/tna/20080102193705/http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf




CHRONIC WASTING DISEASE BLOG


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





*****URGENT NOTE HERE ABOUT OIE AND THEIR JUNK SCIENCE ABOUT ATYPICAL BSE*****



Wednesday, March 31, 2010

Atypical BSE in Cattle


http://bse-atypical.blogspot.com/2010/03/atypical-bse-in-cattle-position-post.html




To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.


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




Archive Number 20100405.1091 Published Date 05-APR-2010

Subject PRO/AH/EDR> Prion disease update 1010 (04)

snip...

[Terry S. Singeltary Sr. has added the following comment:

"According to the World Health Organisation, the future public health threat of vCJD in the UK and Europe and potentially the rest of the world is of concern and currently unquantifiable. However, the possibility of a significant and geographically diverse vCJD epidemic occurring over the next few decades cannot be dismissed

.

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?"

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



> Up until about 6 years ago, the pt worked at Tyson foods where she

> worked on the assembly line, slaughtering cattle and preparing them for

> packaging. She was exposed to brain and spinal cord matter when she

> would euthanize the cattle.



please see full text ;

Monday, March 29, 2010

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



http://creutzfeldt-jakob-disease.blogspot.com/2010/03/irma-linda-andablo-cjd-victim-she-died.html





14th International Congress on Infectious Diseases H-type and L-type Atypical BSE January 2010 (special pre-congress edition)

18.173 page 189

Experimental Challenge of Cattle with H-type and L-type Atypical BSE

A. Buschmann1, U. Ziegler1, M. Keller1, R. Rogers2, B. Hills3, M.H. Groschup1. 1Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany, 2Health Canada, Bureau of Microbial Hazards, Health Products & Food Branch, Ottawa, Canada, 3Health Canada, Transmissible Spongiform Encephalopathy Secretariat, Ottawa, Canada

Background: After the detection of two novel BSE forms designated H-type and L-type atypical BSE the question of the pathogenesis and the agent distribution of these two types in cattle was fully open. From initial studies of the brain pathology, it was already known that the anatomical distribution of L-type BSE differs from that of the classical type where the obex region in the brainstem always displays the highest PrPSc concentrations. In contrast in L-type BSE cases, the thalamus and frontal cortex regions showed the highest levels of the pathological prion protein, while the obex region was only weakly involved.

Methods:We performed intracranial inoculations of cattle (five and six per group) using 10%brainstemhomogenates of the two German H- and L-type atypical BSE isolates. The animals were inoculated under narcosis and then kept in a free-ranging stable under appropriate biosafety conditions.At least one animal per group was killed and sectioned in the preclinical stage and the remaining animals were kept until they developed clinical symptoms. The animals were examined for behavioural changes every four weeks throughout the experiment following a protocol that had been established during earlier BSE pathogenesis studies with classical BSE.

Results and Discussion: All animals of both groups developed clinical symptoms and had to be euthanized within 16 months. The clinical picture differed from that of classical BSE, as the earliest signs of illness were loss of body weight and depression. However, the animals later developed hind limb ataxia and hyperesthesia predominantly and the head. Analysis of brain samples from these animals confirmed the BSE infection and the atypical Western blot profile was maintained in all animals. Samples from these animals are now being examined in order to be able to describe the pathogenesis and agent distribution for these novel BSE types. Conclusions: A pilot study using a commercially avaialble BSE rapid test ELISA revealed an essential restriction of PrPSc to the central nervous system for both atypical BSE forms. A much more detailed analysis for PrPSc and infectivity is still ongoing.


http://www.isid.org/14th_icid/


http://ww2.isid.org/Downloads/IMED2009_AbstrAuth.pdf


http://www.isid.org/publications/ICID_Archive.shtml




14th ICID International Scientific Exchange Brochure -

Final Abstract Number: ISE.114

Session: International Scientific Exchange

Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America

update October 2009

T. Singeltary

Bacliff, TX, USA

Background:

An update on atypical BSE and other TSE in North America. Please remember, the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been documented in North America, along with the typical scrapie's, and atypical Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these TSE in different species have been rendered and fed to food producing animals for humans and animals in North America (TSE in cats and dogs ?), and that the trading of these TSEs via animals and products via the USA and Canada has been immense over the years, decades.

Methods:

12 years independent research of available data

Results:

I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc.

Conclusion:

I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena's. Restricting the reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route.


http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf




International Society for Infectious Diseases Web: http://www.isid.org




I ask Professor Kong ;



Thursday, December 04, 2008 3:37 PM Subject: RE: re--Chronic Wating Disease (CWD) and Bovine Spongiform Encephalopathies (BSE): Public Health Risk Assessment

''IS the h-BSE more virulent than typical BSE as well, or the same as cBSE, or less virulent than cBSE? just curious.....''

Professor Kong reply ;

.....snip

''As to the H-BSE, we do not have sufficient data to say one way or another, but we have found that H-BSE can infect humans. I hope we could publish these data once the study is complete.

Thanks for your interest.''

Best regards,

Qingzhong Kong, PhD Associate Professor Department of Pathology Case Western Reserve University Cleveland, OH 44106 USA

END...TSS




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.


http://www.neuroprion.com/pdf_docs/conferences/prion2007/abstract_book.pdf




Sunday, February 14, 2010

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


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




http://transmissiblespongiformencephalopathy.blogspot.com/2010/02/transmissible-spongiform-encephalopathy.html




2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006


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




TSE

Senate 'Down Under' link at bottom of the following url, my submission read out in the Hansard Senate recently by the ABA Chairman Brad Bellinger ;


http://transmissiblespongiformencephalopathy.blogspot.com/





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





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




2008 - 2010

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




Wednesday, June 02, 2010


CJD Annex H UPDATE AFTER DEATH PRECAUTIONS Published: 2 June 2003 Updated: May 2010


http://creutzfeldt-jakob-disease.blogspot.com/2010/06/cjd-annex-h-update-after-death.html




Tuesday, June 1, 2010


USA cases of dpCJD rising with 24 cases so far in 2010


http://cjdtexas.blogspot.com/2010/06/usa-cases-of-dpcjd-rising-with-24-cases.html




Friday, November 30, 2007

CJD QUESTIONNAIRE USA CWRU AND CJD FOUNDATION


http://cjdquestionnaire.blogspot.com/




Meeting of the Transmissible Spongiform Encephalopathies Committee On June 12, 2009 (TRANSCRIPT)


http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/TransmissibleSpongiformEncephalopathiesAdvisoryCommittee/UCM171810.pdf




Meeting of the Transmissible Spongiform Encephalopathies Committee On June 12, 2009 (Singeltary submission)


http://tseac.blogspot.com/2009/05/meeting-of-transmissible-spongiform.html




Saturday, June 13, 2009

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


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




Friday, February 05, 2010

New Variant Creutzfelt Jakob Disease case reports United States 2010 A Review


http://vcjd.blogspot.com/2010/02/new-variant-creutzfelt-jakob-disease.html




Saturday, January 2, 2010

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

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



my comments to PLosone here ;


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




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




USA DEAD STOCK DOWNER COWS


Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.

snip...

The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...


http://web.archive.org/web/20030516051623/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf





PLEASE be aware, for 4 years, the USDA fed our children all across the Nation dead stock downer cows, the most high risk cattle for BSE aka mad cow disease and other dangerous pathogens. who will watch our children for CJD for the next 5+ decades ???


SCHOOL LUNCH PROGRAM FROM DOWNER CATTLE UPDATE


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



http://downercattle.blogspot.com/




NOW, for the ones that think the Government will not lie to you, just to save the industry at all cost, I have two words for you.

Tobacco and Asbestos. how many thousands and thousands of humans died for decades, and are still dying today from these two products, and how many decades did the industry and government lie about this ? just something to ponder, then ponder this ;


Wednesday, April 14, 2010

Food Combination and Alzheimer Disease Risk A Protective Diet


http://betaamyloidcjd.blogspot.com/2010/04/food-combination-and-alzheimer-disease.html




Saturday, March 22, 2008

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


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




Monday, January 4, 2010

Rising Tide: The Impact of Dementia in Canada Huge wave of dementia cases coming, warns report


http://betaamyloidcjd.blogspot.com/2010/01/rising-tide-impact-of-dementia-in.html




Alzheimer's and CJD


http://betaamyloidcjd.blogspot.com/




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