ENLARGING SPECTRUM OF PRION-LIKE DISEASES Prusiner Colby et al 2011

Prions

David W. Colby1,* and Stanley B. Prusiner1,2

+ Author Affiliations

1Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, California 94143 2Department of Neurology, University of California, San Francisco, San Francisco, California 94143 Correspondence: stanley@ind.ucsf.edu


Abstract


The discovery of infectious proteins, denoted prions, was unexpected. After much debate over the chemical basis of heredity, resolution of this issue began with the discovery that DNA, not protein, from pneumococcus was capable of genetically transforming bacteria ( Avery et al. 1944). Four decades later, the discovery that a protein could mimic viral and bacterial pathogens with respect to the transmission of some nervous system diseases ( Prusiner 1982) met with great resistance. Overwhelming evidence now shows that Creutzfeldt–Jakob disease (CJD) and related disorders are caused by prions. The prion diseases are characterized by neurodegeneration and lethality. In mammals, prions reproduce by recruiting the normal, cellular isoform of the prion protein (PrPC) and stimulating its conversion into the disease-causing isoform (PrPSc). PrPC and PrPSc have distinct conformations: PrPC is rich in a-helical content and has little ß-sheet structure, whereas PrPSc has less a-helical content and is rich in ß-sheet structure ( Pan et al. 1993). The conformational conversion of PrPC to PrPSc is the fundamental event underlying prion diseases. In this article, we provide an introduction to prions and the diseases they cause.


snip...


HUMAN PRION DISEASES


Prion diseases occur as sporadic, genetic, and transmissible disease in humans (Table 1). Although infectious forms of prion disease are most well known to the general public, sporadic and heritable forms of the disease occur much more frequently in humans, with sporadic (s) CJD accounting for approximately 85% of cases. sCJD has no known cause although spontaneous misfolding of PrPC into PrPSc is a leading hypothesis (Prusiner 1989; Hsiao et al. 1991a). Alternate hypotheses include somatic mutation of PRNP, undetected horizontal transmission (Gajdusek 1977), and infrequent amplification of low levels of PrPSc that are part of “normal” protein homeostasis. The brains of sCJD patients harbor infectious prions that are transmissible to experimental animals (Gibbs et al. 1968; Brown et al. 1994). In humans, virtually all forms of prion disease feature neuropathological changes including vacuolation (resulting in the spongiform appearance of brain tissue), astrocytic gliosis, and PrP deposition. The morphology of vacuoles and PrP deposits varies depending on the prion strain and host, as do the regions of the brain affected.


Prion diseases in humans and animals.


To date, over 40 different mutations of the PrP gene have been shown to segregate with the heritable human prion diseases (Fig. 2). The resulting diseases have been classified as Gerstmann–Sträussler–Scheinker syndrome (GSS), familial (f) CJD, or fatal familial insomnia (FFI) according to the clinical symptoms, although all result from PRNP mutations. At the time when the discoveries were reported that fCJD and GSS could be transmitted to apes and monkeys, many still thought that scrapie, CJD, and related disorders were caused by slow viruses (Roos et al. 1973; Masters et al. 1981). Only the discovery that a proline-to-leucine mutation at codon 102 of the human PrP gene was genetically linked to some GSS pedigrees permitted the unprecedented conclusion that prion disease can have both genetic and infectious etiologies (Hsiao et al. 1989; Prusiner 1989). This mutation has been found in unrelated families from several countries (Doh-ura et al. 1989; Goldgaber et al. 1989; Kretzschmar et al. 1991), and other mutations causing GSS have since been identified (Dlouhy et al. 1992; Petersen et al. 1992; Poulter et al. 1992; Rosenmann et al. 1998).


Likewise, several different mutations have also been discovered to cause fCJD. A repeat expansion in the amino-terminal region of PrP, which in the healthy population contains five repetitive sequences of eight residues each (octarepeats), has been genetically linked to fCJD. Insertions of two to nine additional octarepeats have been found in individuals within fCJD pedigrees (Owen et al. 1989; Goldfarb et al. 1991a). Molecular genetic investigations have revealed that Libyan and Tunisian Jews with fCJD have a PrP gene point mutation at codon 200, resulting in a glutamic acid-to-lysine substitution (Goldfarb et al. 1990a; Hsiao et al. 1991b), a mutation that has since been identified in fCJD pedigrees in many locations (Goldfarb et al. 1990a; Goldfarb et al. 1990b; Bertoni et al. 1992).


The D178N mutation can cause either fCJD or FFI, depending on the polymorphism present at codon 129, where both methionine and valine are commonly found. D178N coupled with V129 produces fCJD, in which patients present with dementia and widespread deposition of PrPSc (Goldfarb et al. 1991c). If the disease mutation is coupled with M129, however, FFI results and patients present with a progressive sleep disorder that is ultimately fatal. Postmortem analysis of FFI brains revealed deposition of PrPSc confined largely to specific regions of the thalamus (Lugaresi et al. 1986; Gambetti et al. 1995).


Infectious forms of prion diseases include kuru, iatrogenic (i) CJD, and variant (v) CJD. Kuru in the highlands of New Guinea was transmitted by ritualistic cannibalism, as people in the region ate the brains of their dead relatives in an attempt to immortalize them (Glasse 1967; Alpers 1968; Gajdusek 1977). Iatrogenic transmissions include prion-tainted human growth hormone and gonadotropin, dura mater grafts, and transplants of corneas obtained from people who died of CJD (Koch et al. 1985; PHS 1997). In addition, CJD cases have been recorded after neurosurgical procedures in which ineffectively sterilized depth electrodes or instruments were used.


More than 200 teenagers and young adults have died of vCJD, mostly in Britain (Spencer et al. 2002; Will 2003). Both epidemiologic and experimental studies have built a convincing case that vCJD resulted from prions being transmitted from cattle with bovine spongiform encephalopathy (BSE, or “mad cow” disease) to humans through consumption of contaminated beef products (Chazot et al. 1996; Will et al. 1996; Cousens et al. 1997). Until recently, all of the vCJD-affected individuals were identified to express methionine homozygously at codon 129. A single case of vCJD in a patient heterozygous at codon 129 has been reported, raising the possibility of a second wave of “mad cow”–related deaths (Kaski et al. 2009).


PRION DISEASES OF ANIMALS


Prion diseases occur naturally in many mammals, including scrapie of sheep and goats, BSE, transmissible mink encephalopathy (TME), chronic wasting disease (CWD) of mule deer and elk, feline spongiform encephalopathy, and exotic ungulate encephalopathy (Table 1). Unlike in humans, prion diseases in animals mainly occur as infectious disorders. As in humans, prion disease in animals is characterized by neuropathologic changes, including vacuolation, astrocytic gliosis, and PrP deposition.


Scrapie of sheep has been documented in Europe for hundreds of years. Despite efforts attempting to link scrapie to CJD, no evidence exists to establish a relationship (Chatelain et al. 1981). Polymorphisms in sheep PrP modulate susceptibility to scrapie, rendering some breeds more resistant to infection than others (Goldmann et al. 1991). As scrapie prions can persist in soil for years (Palsson 1979; Brown and Gajdusek 1991), selective breeding programs may be the most effective means to eradicate scrapie. In part because scrapie is not infectious for humans, hamster- and mouse-adapted scrapie strains, such as Sc237 and RML, are important laboratory tools for studying prions.


During the BSE epidemic in Britain, it was estimated that nearly one million cattle were infected with prions (Anderson et al. 1996; Nathanson et al. 1997). The mean incubation time for BSE is approximately 5 years. Most cattle were slaughtered between 2 and 3 years of age, and therefore, in a presymptomatic phase of infection (Stekel et al. 1996). BSE is a massive common-source epidemic caused by meat and bone meal (MBM) fed primarily to dairy cows (Wilesmith et al. 1991; Nathanson et al. 1997). MBM was prepared from the offal of sheep, cattle, pigs, and chickens as a high-protein nutritional supplement. In the late 1970s, the hydrocarbon-solvent extraction method used in the rendering of offal began to be abandoned, resulting in MBM with a much higher fat content (Wilesmith et al. 1991; Muller et al. 2007). It is now thought that this change allowed scrapie prions from sheep or low levels of bovine prions generated sporadically to survive the rendering process, resulting in the widespread infection of cattle. Changes in the methods used for feeding cattle have since eliminated the epidemic, although sporadic BSE cases arise occasionally.


Mule deer, white-tailed deer, and elk have been reported to develop CWD. As the only prion disease identified in free-ranging animals, CWD appears to be far more communicable than other forms of prion disease. CWD was first described in 1967 and was reported to be a spongiform encephalopathy in 1978 on the basis of histopathology of the brain. Originally detected in the American West, CWD has spread across much of North America and has been reported also in South Korea. In captive populations, up to 90% of mule deer have been reported to be positive for prions (Williams and Young 1980). The incidence of CWD in cervids living in the wild has been estimated to be as high as 15% (Miller et al. 2000). The development of transgenic (Tg) mice expressing cervid PrP, and thus susceptible to CWD, has enhanced detection of CWD and the estimation of prion titers (Browning et al. 2004; Tamgüney et al. 2006). Shedding of prions in the feces, even in presymptomatic deer, has been identified as a likely source of infection for these grazing animals (Williams and Miller 2002; Tamgüney et al. 2009b). CWD has been transmitted to cattle after intracerebral inoculation, although the infection rate was low (4 of 13 animals [Hamir et al. 2001]). This finding raised concerns that CWD prions might be transmitted to cattle grazing in contaminated pastures.


snip...


PRION STRAINS


Naturally occurring prion strains have been isolated, each with a distinct incubation period and characteristic pathology; these traits are often conserved on serial transmission (Dickinson and Meikle 1969; Fraser and Dickinson 1973). Because prions are composed only of protein and replicate using the PrP substrate present in the host, differences in prion strains cannot be attributed to genetic variability, which accounts for the existence of viral strains. Rather, prion strains arise from conformational variability—that is, PrP can assume several different, self-propagating conformations, each of which enciphers a distinct prion strain. Biochemical evidence (Bessen and Marsh 1994; Collinge et al. 1996; Telling et al. 1996; Peretz et al. 2001a) and recent studies with synthetic prions support this theory (Colby et al. 2009).


Studies with synthetic prions showed that the mouse synthetic prion (MoSP) strain 1 gradually adopted properties associated with naturally occurring prion strains such as RML, including short incubation times and low conformational stabilities (Ghaemmaghami et al., in prep.). These changes were accompanied by a structural transformation, as indicated by a shift in the molecular mass of the protease-resistant core of MoSP1 from approximately 19 kDa [MoSP1(2)] to 21 kDa [MoSP1(1)]. We found that MoSP1(1) and MoSP1(2) could be bred with fidelity when cloned in N2a cells but when present as a mixture, MoSP1(1) propagation led to the disappearance of MoSP1(2). In culture, the rate of this transformation could be modified by the culture media and the presence of polyamidoamines. These findings showed that prions exist as conformationally diverse populations and each strain can replicate with high fidelity. Competition and selection among the pool of strains provide a mechanism for prion transformation and adaptation (Li et al. 2010).


Yeast also show multiple prion strains. A recombinant Sup35 protein fragment refolded into two different conformations was shown to initiate two distinct [PSI+] strain phenotypes on transduction into yeast (King and Diaz-Avalos 2004; Tanaka et al. 2004). The propagation rates for these synthetic yeast prion strains were coupled to their conformational stability (Tanaka et al. 2004), a finding that was later extended to mammalian prion strains (Legname et al. 2006; Colby et al. 2009).


ENLARGING SPECTRUM OF PRION-LIKE DISEASES


The discovery that prions form amyloid prompted one of us to suggest that the common neurodegenerative diseases are also caused by prions (Prusiner 1984; Prusiner 2001) despite the inability to transmit such illnesses to monkeys and apes (Goudsmit et al. 1980). Brain extracts from either Alzheimer's patients or aged Tg mice expressing mutant APP injected into the brains of Tg mice expressing the amyloid precursor protein (APP) carrying the Swedish point mutation (Haass et al. 1995) accelerated the formation of Aß amyloid plaques (Meyer-Luehmann et al. 2006; Eisele et al. 2009). Brain extracts from Tg mice expressing mutant tau injected into the brains of Tg mice expressing human wt tau produced aggregates of human tau (Clavaguera et al. 2009). Similar results were found for aggregated tau protein added to cultured cells, which induced the aggregation of nascent tau (Frost et al. 2009). These findings suggest that the tauopathies result from a prion-like process that induces hyperphosphorylation of tau followed by polymerization into filamentous aggregates. The production of hyperphosphorylated tau also appears to be stimulated by oligomers of the Aß peptide, whereas amyloid fibrils comprised of Aß are a much less efficient stimulus (Lambert et al. 1998). An expanded 44-mer polyglutamine repeat of a truncated huntingtin protein was found to stimulate aggregation of a “normal” 25 mer; this aggregated state could be maintained in cell culture over many generations, arguing for prion-like propagation of huntingtin aggregates (Ren et al. 2009). Patients suffering from Parkinson's disease who received fetal grafts of substantia nigral cells later showed aberrantly folded a-synuclein in Lewy bodies within the transplanted grafts, arguing that a-synuclein acted like a prion (Kordower et al. 2008; Li et al. 2008; Olanow and Prusiner 2009). Taken together, these findings argue that prion-like, self-propagating states feature in many different, if not all, neurodegenerative diseases.


A general model of propagation of mammalian prion-like conformational states should include the following considerations (Table 2): First, when the precursor protein is converted to a prion, it undergoes posttranslational modification. Such changes generally result in the acquisition of a high ß-sheet content. Proteolytic cleavage features in Alzheimer's disease (AD) (Glenner and Wong 1984; Masters et al. 1985) and hyperphosphorylation occurs in both AD and the tauopathies (Grundke-Iqbal et al. 1986; Lee et al. 1991). Second, the ß-sheet–rich conformers form oligomers that are toxic to cells (Walsh and Selkoe 2007). Third, such oligomers are generally rendered less toxic when they polymerize into amyloid fibrils. Fourth, amyloid fibrils are sequestered into biological wastebaskets in the CNS where they are designated “plaques” in the extracellular space, and “tangles” or “bodies” within the cytoplasm of neurons. Inert PrP amyloid fibrils coalesce to form plaques in prion diseases whereas fibrils composed of the Aß peptide form plaques in AD. Paired-helical filaments composed of hyperphosphorylated tau form neurofibrillary tangles in AD, whereas tau fibrils coalesce into deposits called Pick bodies in one of the frontotemporal dementias generally labeled Pick's disease. In other tauopathies, less well-formed tau aggregates have been identified inside cells. After a-synuclein acquires a high ß-sheet content, it polymerizes into amyloid fibrils that coalesce in neurons to form Lewy bodies. Fifth, mutations in the corresponding proteins cause familial neurodegenerative diseases and facilitate conversion of the protein to its prion state. For example, over 40 mutations in PrP have been identified that cause GGS, fCJD, and FFI (Hsiao et al. 1989; Goldfarb et al. 1991b; Medori et al. 1992). Mutations in APP or presenilin (?-secretase) that cleaves APP into Aß cause familial AD (Goate et al. 1991), and duplication of the APP gene in Down's syndrome invariably causes AD (Goldgaber et al. 1987). Mutations in tau cause tauopathies (Hutton et al. 1998). Mutations in a-synuclein cause familial Parkinson's disease (Polymeropoulos et al. 1997); duplication or triplication of the a-synuclein gene also causes Parkinson's disease (Singleton et al. 2003).


Prions need not cause disease but may function as regulators of cell metabolism. In yeast, all of the prion proteins found to date have a CG-rich domain that adopts a ß-sheet–rich conformation that polymerizes into amyloid. The Sup35 protein in the prion state causes a reduction in the fidelity of polypeptide chain termination during protein synthesis (Wickner et al. 2007). The Aplysia prion comprised of the cytoplasmic polyadenylation element binding (CPEB) protein appears to facilitate polyadenylation within limited regions of neuronal cells, such as dendrites, and has been suggested to function in long-term memory (Si et al. 2010).


snip...


TOWARD THERAPEUTICS FOR PRION DISEASES


Despite these advances in understanding prions and many of the neurodegenerative diseases, no treatment is currently available to halt the progression of any of these illnesses. Studies of prions in mice have elucidated several aspects of neurodegeneration that may prove useful in developing effective therapeutics. First, reduction of the precursor protein PrPC prolongs the incubation time (Büeler et al. 1993; Prusiner et al. 1993; Safar et al. 2005). Second, slowing prion formation by inhibiting of the formation of nascent PrPSc prolongs the incubation time (Kawasaki et al. 2007). Third, reducing the availability of PrPC in cells or mice where prion infection has already been established allows for existing prions to be cleared (Enari et al. 2001; Peretz et al. 2001b; Safar et al. 2005). Fourth, enhancing the clearance of PrPSc provides an alternative route of action for therapeutic intervention (Supattapone et al. 1999b; Supattapone et al. 2001).


Blocking conversion of PrPC to PrPSc would seem to be the most practical therapeutic approach, as the cellular pathogenesis of prion disease is downstream of this event and not well understood. Many compounds that inhibit conversion have been identified, including polysulfated anions, dextrans, Congo red dye, oligonucleotides, and cyclic tetrapyrroles (for reviews, see Trevitt and Collinge [2006]; Sim and Caughey [2009]; Silber [2010]). Effective treatment for prion disease is hampered by the difficulty of these and other putative therapeutics to access the CNS, and by the difficulty of identifying small molecules that can prevent the protein–protein interactions that result in propagation of alternatively folded protein isoforms. Studies with a phenylhydrazone revealed restricted efficacy for specific prion strains (Kawasaki et al. 2007) whereas studies with the drug quinacrine revealed the development of drug-resistant prions (Ghaemmaghami et al. 2009).


It seems likely that studies on therapeutics for prion diseases will inform the development of drugs that halt AD, the frontotemporal dementias, or Parkinson's disease; moreover, the lack of success in treating such diseases argues for new paradigms. Work on the prion diseases suggests that treatment for a limited time that reduces or interrupts the formation of nascent prions may be sufficient for the normal cellular clearance mechanisms to overtake the synthesis of new prions. Such an approach would argue for the development of drugs that can be administered for a short period of time instead of many years, which is the commonly held supposition.


snip...please see full text here ;



http://cshperspectives.cshlp.org/content/3/1/a006833.full.html#ref-24




CWD to cattle figures CORRECTION


Greetings,


I believe the statement and quote below is incorrect ;



"CWD has been transmitted to cattle after intracerebral inoculation, although the infection rate was low (4 of 13 animals [Hamir et al. 2001]). This finding raised concerns that CWD prions might be transmitted to cattle grazing in contaminated pastures."



Please see ;




Within 26 months post inoculation, 12 inoculated animals had lost weight, revealed abnormal clinical signs, and were euthanatized. Laboratory tests revealed the presence of a unique pattern of the disease agent in tissues of these animals. These findings demonstrate that when CWD is directly inoculated into the brain of cattle, 86% of inoculated cattle develop clinical signs of the disease.



http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=194089





" although the infection rate was low (4 of 13 animals [Hamir et al. 2001]). "




shouldn't this be corrected, 86% is NOT a low rate. ...




kindest regards,


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




Thank you!

Thanks so much for your updates/comments. We intend to publish as rapidly as possible all updates/comments that contribute substantially to the topic under discussion.



http://cshperspectives.cshlp.org/letters/submit




re-Prions David W. Colby1,* and Stanley B. Prusiner1,2 + Author Affiliations

1Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, California 94143 2Department of Neurology, University of California, San Francisco, San Francisco, California 94143 Correspondence: stanley@ind.ucsf.edu


http://cshperspectives.cshlp.org/content/3/1/a006833.full.pdf+html




Mule deer, white-tailed deer, and elk have been reported to develop CWD. As the only prion disease identified in free-ranging animals, CWD appears to be far more communicable than other forms of prion disease. CWD was first described in 1967 and was reported to be a spongiform encephalopathy in 1978 on the basis of histopathology of the brain. Originally detected in the American West, CWD has spread across much of North America and has been reported also in South Korea. In captive populations, up to 90% of mule deer have been reported to be positive for prions (Williams and Young 1980). The incidence of CWD in cervids living in the wild has been estimated to be as high as 15% (Miller et al. 2000). The development of transgenic (Tg) mice expressing cervid PrP, and thus susceptible to CWD, has enhanced detection of CWD and the estimation of prion titers (Browning et al. 2004; Tamgüney et al. 2006). Shedding of prions in the feces, even in presymptomatic deer, has been identified as a likely source of infection for these grazing animals (Williams and Miller 2002; Tamgüney et al. 2009b). CWD has been transmitted to cattle after intracerebral inoculation, although the infection rate was low (4 of 13 animals [Hamir et al. 2001]). This finding raised concerns that CWD prions might be transmitted to cattle grazing in contaminated pastures.


snip...


http://cshperspectives.cshlp.org/content/3/1/a006833.full.pdf+html




please see CWD potential to humans here ;


http://betaamyloidcjd.blogspot.com/2011/01/enlarging-spectrum-of-prion-like.html




Greetings,


I believe the statement and quote below is incorrect ;



"CWD has been transmitted to cattle after intracerebral inoculation, although the infection rate was low (4 of 13 animals [Hamir et al. 2001]). This finding raised concerns that CWD prions might be transmitted to cattle grazing in contaminated pastures."



Please see ;




Within 26 months post inoculation, 12 inoculated animals had lost weight, revealed abnormal clinical signs, and were euthanatized. Laboratory tests revealed the presence of a unique pattern of the disease agent in tissues of these animals. These findings demonstrate that when CWD is directly inoculated into the brain of cattle, 86% of inoculated cattle develop clinical signs of the disease.



http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=194089




"although the infection rate was low (4 of 13 animals [Hamir et al. 2001])."



shouldn't this be corrected, 86% is NOT a low rate. ...




kindest regards,

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



MARCH 1, 2011

UPDATED CORRESPONDENCE FROM AUTHORS OF THIS STUDY I.E. COLBY, PRUSINER ET AL, ABOUT MY CONCERNS OF THE DISCREPANCY BETWEEN THEIR FIGURES AND MY FIGURES OF THE STUDIES ON CWD TRANSMISSION TO CATTLE ;



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

From: David Colby

To: flounder9@verizon.net

Cc: stanley@XXXXXXXX

Sent: Tuesday, March 01, 2011 8:25 AM

Subject: Re: FW: re-Prions David W. Colby1,* and Stanley B. Prusiner1,2 + Author Affiliations



Dear Terry Singeltary,

Thank you for your correspondence regarding the review article Stanley Prusiner and I recently wrote for Cold Spring Harbor Perspectives. Dr. Prusiner asked that I reply to your message due to his busy schedule. We agree that the transmission of CWD prions to beef livestock would be a troubling development and assessing that risk is important. In our article, we cite a peer-reviewed publication reporting confirmed cases of laboratory transmission based on stringent criteria. The less stringent criteria for transmission described in the abstract you refer to lead to the discrepancy between your numbers and ours and thus the interpretation of the transmission rate. We stand by our assessment of the literature--namely that the transmission rate of CWD to bovines appears relatively low, but we recognize that even a low transmission rate could have important implications for public health and we thank you for bringing attention to this matter.

Warm Regards,
David Colby

--

David Colby, PhDAssistant ProfessorDepartment of Chemical EngineeringUniversity of Delaware



====================END...TSS==============




re-ENLARGING SPECTRUM OF PRION-LIKE DISEASES Prusiner Colby et al 2011 Prions




CWD to cattle figures CORRECTION


Greetings,


I believe the statement and quote below is incorrect ;



"CWD has been transmitted to cattle after intracerebral inoculation, although the infection rate was low (4 of 13 animals [Hamir et al. 2001]). This finding raised concerns that CWD prions might be transmitted to cattle grazing in contaminated pastures."



Please see ;




Within 26 months post inoculation, 12 inoculated animals had lost weight, revealed abnormal clinical signs, and were euthanatized. Laboratory tests revealed the presence of a unique pattern of the disease agent in tissues of these animals. These findings demonstrate that when CWD is directly inoculated into the brain of cattle, 86% of inoculated cattle develop clinical signs of the disease.



http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=194089



"although the infection rate was low (4 of 13 animals [Hamir et al. 2001])."



shouldn't this be corrected, 86% is NOT a low rate. ...




kindest regards,

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




Thank you!

Thanks so much for your updates/comments. We intend to publish as rapidly as possible all updates/comments that contribute substantially to the topic under discussion.



http://cshperspectives.cshlp.org/letters/submit





re-Prions David W. Colby1,* and Stanley B. Prusiner1,2 + Author Affiliations

1Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, California 94143 2Department of Neurology, University of California, San Francisco, San Francisco, California 94143 Correspondence: stanley@ind.ucsf.edu


http://cshperspectives.cshlp.org/content/3/1/a006833.full.pdf+html





snip...full text ;





Wednesday, January 5, 2011

ENLARGING SPECTRUM OF PRION-LIKE DISEASES Prusiner Colby et al 2011 Prions

David W. Colby1,* and Stanley B. Prusiner1,2



http://cshperspectives.cshlp.org/content/3/1/a006833.full.html#ref-24





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


Subject: Re: CWD TO CATTLE by inoculation (ok,is it three or four OR NOW FIVE???)

Date: Mon, 23 Jun 2003 12:36:59 -0500

From: "Janice M. Miller"

Reply-To: Bovine Spongiform Encephalopathy

To: BSE-L@uni-karlsruhe.de

######## Bovine Spongiform Encephalopathy #########

I am happy to provide an update on the experimental inoculation of cattle and sheep with CWD. These are ongoing experiments and updates are normally provided via presentations at meetings. Dr. Hamir has prepared a poster of the following information that will be displayed at 4 upcoming meetings this summer and fall.

Experimental Transmission of Chronic Wasting Disease (CWD) to Cattle and Sheep Progress report - June 23, 2003

Experimental Transmission to Cattle

Background:

In 1997, 13 calves were inoculated intracerebrally with brain suspension from mule deer naturally affected with CWD. During the first 3 years, 3 animals were euthanized 23, 24, and 28 months after inoculation because of weight loss (2) or sudden death (1). Although microscopic examination of the brains did not show classical lesions of transmissible spongiform encephalopathy (TSE), a specific TSE marker protein, PrPres, was detected by immunohistochemistry (IHC) and western blot. Detailed information on these animals has been published previously (A Hamir et al., J Vet Diagn Invest 13: 91-96, 2001).

Update:

During the 3rd, 4th and 6th years of observation, 7 additional animals have been euthanized due to a variety of health concerns (primarily chronic joint and foot problems). IHC and western blot results indicate that 2 of these animals, necropsied 59 and 63 months after inoculation, were positive for PrPres. One animal (# 1746) had not been eating well for approximately 1 week prior to being found recumbent. At necropsy, significant gross lesions consisted of an oblique fracture of L1 vertebral arch with extension into the body, and moderate multifocal hemorrhagic ulceration in the abomasum. Microscopic examination of brain revealed a few isolated neurons with single or multiple vacuoles, but neither neuronal degeneration nor gliosis was observed. IHC revealed the presence of PrPres in sections from several areas of the brain. The other PrPres positive animal (#1742) was euthanized after being found in lateral recumbency with a body temperature of 104.6 F. It had not shown prior clinical signs except for some decreased appetite for 2 days. Necropsy revealed only moderate hepatitis and a small renal infarct due to intravascular thrombosis.

Summary of findings on all necropsied animals to date:

Ear tag Date of Survival Disease Clinical

Histo- IHC WB

no. necropsy period course signs

pathology

__________________________________________________

1745 8/18/99 23m 2m + ± + + 1768 9/22/99 24m 3m + ± + + 1744 1/29/00 28m 3d ± - + + 1749 5/20/01 44m NA - - - - 1748 6/27/01 45m NA - - - - 1743 8/21/02 59m NA - - - - 1741 8/22/02 59m NA - - - - 1746 8/27/02 59m 7d ± ± + + 1765 11/27/02 62m 1d ± ± - - 1742 12/28/02 63m 2d ± - + +

NT = not tested; IHC = immunohistochemistry for PrPres; SAF = scrapie associated fibrils; NA = not applicable; WB = Western blot (Prionics-Check); + = lesions or antigen present; - = lesions or antigen absent; ± = signs/lesions equivocal; i/c = intracerebral; m = months; d = days.

Summary:

After 5.75 years of observation we have 5 CWD transmissions to cattle from a group of 13 inoculates. These animals, which were necropsied 23, 24, 28, 59, and 63 months after inoculation, did not show the clinical signs or histopathologic lesions typical of a TSE, but PrPres was detected in brain samples by both immunohistochemistry and western blot.

Five other animals necropsied during the 4th, 5th and 6th years of observation have not shown evidence of PrPres and the remaining 3 cattle are apparently healthy. Note that this study involved direct intracerebral inoculation of cattle with the CWD agent, which is an unnatural route of exposure. Likely, it would be more difficult to infect cattle by the oral route. Cattle have been inoculated orally at the University of Wyoming with the same inoculum used in this experiment, and 5.75 years into the study the animals remain healthy (personal communication, Dr. Beth Williams).

Experimental Transmission of CWD to sheep

Eight Suffolk sheep from the NADC scrapie-free flock were inoculated intracerebrally with the CWD brain suspension used to inoculate cattle. PRNP genotyping showed that 4 of the sheep were QQ at codon 171 and the other four were QR. Two of the QQ sheep were euthanized during the 3rd year of observation. At necropsy one of these animals had a urethral obstruction and PrPres was not detected in brain or lymphoid tissues. The other sheep, necropsied 35 months after inoculation, showed clinical signs and histopathologic lesions that were indistinguishable from scrapie. IHC tests showed typical PrPres accumulations in brain, tonsil, and some lymph nodes. The 2 remaining QQ sheep and all 4 QR sheep are apparently healthy 47 months after inoculation.

Summary:

After 4 years of observation we have 1 transmission of CWD to a 171 QQ sheep. This animal, which was necropsied 35 months after inoculation, showed clinical signs and histopathologic lesions that were indistinguishable from scrapie. Another QQ sheep that was necropsied during the 3rd year showed no evidence of prion disease and all remaining sheep (2 QQ and 4 QR) are apparently healthy.


########### http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############



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


Subject: Re: CWD TO CATTLE by inoculation (ok, is it three or four OR NOW FIVE???)

Date: Mon, 23 Jun 2003 09:25:27 -0500

From: "Terry S. Singeltary Sr."

Reply-To: Bovine Spongiform Encephalopathy

To: BSE-L@uni-karlsruhe.de


######## Bovine Spongiform Encephalopathy #########


Greetings List Members,

i hear now that a 5th cow has gone done with CWD from the studies of Amir Hamir et al. will Dr. Miller please confirm or deny this please, and possibly explain why this has not made the news, if in fact this is the case?

seems these cows infected with CWD/TSE did not display the usual BSE symptoms. i wonder how many more are out there in the field? course, we will never know unless someone starts rapid TSE/BSE testing in sufficient numbers to find...

thank you, kind regards, terry

Date: Sat, 23 Nov 2002 18:54:49 -0600

Reply-To: BSE

Sender: BSE

From: "Terry S. Singeltary Sr."

Subject: CWD TO CATTLE by inoculation (ok, is it three or four???)

1: J Vet Diagn Invest 2001 Jan;13(1):91-6

Preliminary findings on the experimental transmission of chronic wasting disease agent of mule deer to cattle.

Hamir AN, Cutlip RC, Miller JM, Williams ES, Stack MJ, Miller MW, O'Rourke KI, Chaplin MJ.

National Animal Disease Center, ARS, USDA, Ames, IA 50010, USA.

To determine the transmissibility of chronic wasting disease (CWD) to cattle and to provide information about clinical course, lesions, and suitability of currently used diagnostic procedures for detection of CWD in cattle, 13 calves were inoculated intracerebrally with brain suspension from mule deer naturally affected with CWD. Between 24 and 27 months postinoculation, 3 animals became recumbent and were euthanized.

Gross necropsies revealed emaciation in 2 animals and a large pulmonary abscess in the third. Brains were examined for protease-resistant prion protein (PrP(res)) by immunohistochemistry and Western blotting and for scrapie-associated fibrils (SAFs) by negative-stain electron microscopy. Microscopic lesions in the brain were subtle in 2 animals and absent in the third case. However, all 3 animals were positive for PrP(res) by immunohistochemistry and Western blot, and SAFs were detected in 2 of the animals. An uninoculated control animal euthanized during the same period did not have PrP(res) in its brain. These are preliminary observations from a currently in-progress experiment. Three years after the CWD challenge, the 10 remaining inoculated cattle are alive and apparently healthy. These preliminary findings demonstrate that diagnostic techniques currently used for bovine spongiform encephalopathy (BSE) surveillance would also detect CWD in cattle should it occur naturally.

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


Sat, Nov 23, 2002

Scientists unsure if CWD can jump species

By Jessica Bock Wausau Daily Herald jbock@wdhprint.com

snip...

Janice Miller, a veterinarian in charge of the experiment, said she believes previous research shows it is hard for the disease to be transmitted naturally from whitetail deer to dairy cattle. "Our study says nothing of how it could be transmitted in natural surroundings," she said.

Miller has been studying the transmission of CWD from mule deer to cattle since 1997. Since then, chronic wasting disease was transmitted to four out of 13 cattle injected with brain tissue from naturally infected mule deer, she said.

In Wyoming, Williams has been studying cattle that were given a concoction of diseased brain tissue orally, and five years into the study the animals remain healthy, Miller said. No one knows if chronic wasting disease could ever spread to another species through natural surroundings.

"Our experience is that it's pretty hard to predict," Miller said.

http://www.wausaudailyherald.com/



greetings list,

Since then, chronic wasting disease was

transmitted to four out of 13 cattle

is this a typo by the media or has another cow gone down with CWD since the preliminary findings were found?

TSS

########### http://mailhost.rz.uni-karlsruhe.de/warc/bse-l.html ############







Title: Susceptibility of cattle to first-passage intracerebral inoculation with chronic wasting disease agent from white-tailed deer

Authors

Hamir, Amirali Miller, Janice - ARS RETIRED Kunkle, Robert Hall, S - USDA, APHIS, NVSL, PL Richt, Juergen

Submitted to: Veterinary Pathology Publication Type: Peer Reviewed Journal Publication

Acceptance Date: February 20, 2007

Publication Date: July 1, 2007

Citation: Hamir, A.N., Miller, J.M., Kunkle, R.A., Hall, S.M., Richt, J.A. 2007.

Susceptibility of cattle to first-passage intracerebral inoculation with chronic wasting disease agent from white-tailed deer.

Veterinary Pathology. 44:487-493.

Interpretive Summary: This study reports findings assessing susceptibility of cattle to infection following direct surgical inoculation of the transmissible spongiform encephalopathy (TSE), chronic wasting disease (CWD, from white tailed deer) into the brain of 14 cattle. Three-month-old calves were inoculated with the CWD agent from white tailed deer. Two non-inoculated calves served as controls. Within 26 months post inoculation, 12 inoculated animals had lost weight, revealed abnormal clinical signs, and were euthanatized. Laboratory tests revealed the presence of a unique pattern of the disease agent in tissues of these animals. These findings demonstrate that when CWD is directly inoculated into the brain of cattle, 86% of inoculated cattle develop clinical signs of the disease. The findings also indicate that diagnostic techniques currently used for detection of bovine spongiform encephalopathy (BSE) would detect CWD in cattle should it ever cross the species barrier. Moreover, these findings confirm our earlier findings with CWD from mule deer, thus demonstrating a unique pattern of the CWD disease agent from deer when experimentally inoculated into cattle, further validating our ability to distinguish this form of cross-species TSE transmission from BSE in cattle.


Technical Abstract: To compare clinicopathological findings of chronic wasting disease (CWD) from white-tailed deer (CWD**wtd) with other transmissible spongiform encephalopathies [transmissible spongiform encephalopathy (TSE), prion diseases) that have been shown to be experimentally transmissible to cattle [sheep scrapie, CWD of mule deer (CWD**md) and transmissible mink encephalopathy (TME)], 14 three-month-old calves were intracerebrally inoculated with the CWD**wtd agent. Two uninoculated calves served as controls. Within 26 months post inoculation (MPI), 12 inoculated animals had lost considerable weight and eventually became recumbent. Eleven of these had clinical signs of central nervous system (CNS) abnormality and all 12 were euthanized. Although microscopic lesions of spongiform encephalopathy (SE) were not seen in CNS tissues, PrP**res was detected by immunohistochemistry (IHC) and Western blot (WB). These findings demonstrate that when CWD**wtd is intracerebrally inoculated in cattle, 86% of inoculated cattle develop abnormal clinical signs and amplify PrP**res in their CNS tissues without evidence of morphologic lesions of SE. The latter has also been shown with other TSE agents (scrapie and CWD**md) similarly inoculated into cattle. These findings suggest that the diagnostic techniques currently used for confirmation of bovine spongiform encephalopathy (BSE) would detect CWD**wtd in cattle should it occur naturally. The absence of microscopic morphologic lesions and a unique IHC pattern of CWD**wtd in cattle, suggests that it should be possible to distinguish this form of cross-species transmission from BSE in cattle.



http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=194089




TSS





***

Thursday, December 23, 2010

Alimentary prion infections: Touch-down in the intestine, Alzheimer, Parkinson disease and TSE mad cow diseases $ The Center for Consumer Freedom


http://betaamyloidcjd.blogspot.com/2010/12/alimentary-prion-infections-touch-down.html



BSE101/1 0136

IN CONFIDENCE

CMO

From: Dr J S Metters DCMO

4 November 1992

TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES

http://collections.europarchive.org/tna/20081106170650/http://www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf



CJD1/9 0185

Ref: 1M51A

IN STRICT CONFIDENCE

From: Dr. A Wight

Date: 5 January 1993

Copies:

Dr Metters

Dr Skinner

Dr Pickles

Dr Morris

Mr Murray

TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES

http://collections.europarchive.org/tna/20080102191246/http://www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf



Friday, September 3, 2010

Alzheimer's, Autism, Amyotrophic Lateral Sclerosis, Parkinson's, Prionoids, Prionpathy, Prionopathy, TSE


http://betaamyloidcjd.blogspot.com/2010/09/alzheimers-autism-amyotrophic-lateral.html



http://betaamyloidcjd.blogspot.com/



2010 PRION UPDATE

Thursday, August 12, 2010

Seven main threats for the future linked to prions


http://prionpathy.blogspot.com/2010/08/seven-main-threats-for-future-linked-to.html



http://prionpathy.blogspot.com/




Friday, October 22, 2010

Peripherally Applied Aß-Containing Inoculates Induce Cerebral ß-Amyloidosis


http://betaamyloidcjd.blogspot.com/2010/10/peripherally-applied-containing.html



Saturday, March 22, 2008

10 Million Baby Boomers to have Alzheimer's in the coming decades


http://betaamyloidcjd.blogspot.com/2008/03/10-million-baby-boomers-to-have.html



see full text Alzheimer's and CJD i.e. TSE, aka mad cow disease


http://betaamyloidcjd.blogspot.com/



Wednesday, December 29, 2010

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY PRION END OF YEAR REPORT DECEMBER 29, 2010


http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/transmissible-spongiform-encephalopathy.html



Wednesday, December 29, 2010

CWD Update 99 December 13, 2010


http://chronic-wasting-disease.blogspot.com/2010/12/cwd-update-99-december-13-2010.html




TSS

Alimentary prion infections: Touch-down in the intestine, Alzheimer, Parkinson disease and TSE mad cow diseases $ The Center for Consumer Freedom

Commentary

Alimentary prion infections: Touch-down in the intestine

Volume 5, Issue 1 January/February/March 2011 Bianca Da Costa Dias, Katarina Jovanovic and Stefan F.T. Weiss View affiliations Hide affiliations Bianca Da Costa DiasSchool of Molecular and Cell Biology; University of the Witwatersrand; Johannesburg, Republic of South Africa Katarina JovanovicSchool of Molecular and Cell Biology; University of the Witwatersrand; Johannesburg, Republic of South Africa Stefan F.T. WeissCorresponding author: stefan.weiss@wits.ac.za School of Molecular and Cell Biology; University of the Witwatersrand; Johannesburg, Republic of South Africa

Neurodegenerative diseases are caused by proteinaceous aggregates, usually consisting of misfolded proteins which are often typified by a high proportion of ß-sheets, which accumulate in the Central Nervous System. These diseases, including Morbus Alzheimer, Parkinson disease and Transmissible Spongiform Encephalopathies (TSEs) also termed prion disorders, afflict a substantial proportion of the human population and as such the etiology and pathogenesis of these diseases has been the focus of mounting research. Although many of these diseases arise from genetic mutations or are sporadic in nature, the possible horizontal transmissibility of neurodegenerative diseases poses a great threat to population health. In this article we discuss recent studies which suggest that the “non-transmissible” status bestowed upon Alzheimer and Parkinson diseases may need to be revised as these diseases have been successfully induced through tissue transplants. Furthermore, we highlight the importance of investigating the “natural” mechanism of prion transmission including peroral and perenteral transmission, proposed routes of gastrointestinal uptake and neuroinvasion of ingested infectious prion proteins. We examine the multitude of factors which may influence oral transmissibility and discuss the zoonotic threats which Chronic Wasting Disease (CWD), Bovine Spongiform Encephalopathy (BSE) and Scrapie may pose resulting in vCJD or related disorders. In addition, we suggest that the 37 kDa/67 kDa laminin receptor on the cell surface of enterocytes, a major cell population in the intestine, may play an important role in the intestinal pathophysiology of alimentary prion infections.

http://www.landesbioscience.com/journals/prion/article/14283



Commentary ß-amyloid oligomers and prion protein: Fatal attraction?

Volume 5, Issue 1 January/February/March 2011 Gianluigi Forloni and Claudia Balducci

Gianluigi Forloni Corresponding author: forloni@marionegri.it

Claudia Balducci Biology of Neurodegenerative Diseases Lab; Department of Neuroscience; “Mario Negri” Institute for Pharmacological Research; Milano, Italy

The relationship between Alzheimer disease (AD) and prion-related encephalopathies (TSE) has been proposed by different points of view. Recently, the scientific attention has been attracted by the results proposing the possibility that PrPc, the protein whose pathologic form is responsible of TSE, can mediated the toxic effect of ß amyloid (Aß) oligomers. The oligomers are considered the culprit of the neurodegenerative process associated to AD, although the pathogenic mechanism activated by these small aggregates remain to be elucidated. In the initial study based on the binding screening PrPc was identified as ligand /receptor of Aß oligomers, while long term potentiation (LTP) analysis in vitro and behavioural studies in vivo, demonstrated that the absence of PrPc abolished the damage induced by Aß oligomers. The high affinity binding Aß oligomers-PrPc has been confirmed, whereas a functional role of this association has been excluded by three different studies. We approached this issue by the direct application of Aß oligomers in the brain followed by the behavioural examination of memory deficits. Our data using PrP knock-out mice suggest that Aß 1-42 oligomers are responsible for cognitive impairment in AD but PrPc is not required for their effect. Similarly, in two other studies the LTP alterations induced by Aß 1-42 oligomers was not influenced by the absence of PrP. Possible explanations of these contradictory results are discussed.



http://www.landesbioscience.com/journals/prion/article/14367/



http://www.landesbioscience.com/journals/prion/toc/volume/5/issue/1/




BSE101/1 0136

IN CONFIDENCE

CMO

From: Dr J S Metters DCMO

4 November 1992

TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES



http://collections.europarchive.org/tna/20081106170650/http://www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf



CJD1/9 0185

Ref: 1M51A

IN STRICT CONFIDENCE

From: Dr. A Wight

Date: 5 January 1993

Copies:

Dr Metters

Dr Skinner

Dr Pickles

Dr Morris

Mr Murray


TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES


http://collections.europarchive.org/tna/20080102191246/http://www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf


Friday, October 22, 2010


Peripherally Applied Aß-Containing Inoculates Induce Cerebral ß-Amyloidosis


http://betaamyloidcjd.blogspot.com/2010/10/peripherally-applied-containing.html




Friday, September 3, 2010

Alzheimer's, Autism, Amyotrophic Lateral Sclerosis, Parkinson's, Prionoids, Prionpathy, Prionopathy, TSE


http://betaamyloidcjd.blogspot.com/2010/09/alzheimers-autism-amyotrophic-lateral.html




http://betaamyloidcjd.blogspot.com/




Posted On December 20, 2003 AFTER THE FIRST CASE OF MAD COW DISEASE IN THE USA WAS DOCUMENTED


" Like many activists, Singletary ignores overwhelming epidemiological and laboratory evidence that rules out a connection between sporadic CJD and beef. Relying entirely on shallow circumstantial evidence and frequent repetition of claims which have been publicly refuted as false, he also blindly insists upon a mad-cow with Alzheimer’s, Parkinson’s, and Lou Gehrig’s disease. "


http://www.consumerfreedom.com/article_detail.cfm/a/138-mad-cow-scaremongers




SO, just who are The Center for Consumer Freedom ;

http://www.consumerfreedom.com/index.cfm



let's take a closer look shall we ;

The Center for Consumer Freedom (CCF) (formerly called the "Guest Choice Network (GCN)") is a front group for the restaurant, alcohol and tobacco industries. It runs media campaigns which oppose the efforts of scientists, doctors, health advocates, environmentalists and groups like Mothers Against Drunk Driving, calling them "the Nanny Culture -- the growing fraternity of food cops, health care enforcers, anti-meat activists, and meddling bureaucrats who 'know what's best for you.'"

CCF is registered as a tax-exempt, non-profit organization under the IRS code 501(c)(3). Its advisory board is comprised mainly of representatives from the restaurant, meat and alcoholic beverage industries.

http://www.sourcewatch.org/index.php?title=Center_for_Consumer_Freedom


http://en.wikipedia.org/wiki/Center_for_Consumer_Freedom



What Is the Center for Consumer Freedom, and Why Is It Attacking PETA?

The Center for Consumer Freedom is a nonprofit corporation run by lobbyist Richard Berman through his Washington, D.C.-based for-profit public relations company, Berman & Co. The Center for Consumer Freedom, formerly known as the Guest Choice Network, was set up by Berman with a $600,000 “donation” from tobacco company Philip Morris.

Berman arranges for large sums of corporate money to find its way into nonprofit societies of which he is the executive director. He then hires his own company as a consultant to these nonprofit groups. Of the millions of dollars “donated” by Philip Morris between the years 1995 and 1998, 49 percent to 79 percent went directly to Berman or Berman & Co.

Richard Berman is an influence peddler. He has worked out a scheme to funnel charitable donations from wealthy corporations into his own pocket. In exchange, he provides a flurry of disinformation, flawed studies, op-ed pieces, letters to the editor, and trade-industry articles, as well as access to his high-level government contacts, who are servants of the industries he represents.

Berman’s name might sound familiar. In 1995, Berman and Norm Brinker, his former boss at Steak and Ale Restaurants, were identified as the special-interest lobbyists who donated the $25,000 that disgraced then-House Speaker Newt Gingrich, who was hauled before the House Ethics Committee for influence-peddling over the money. Berman and Brinker were lobbying against raising the minimum wage.

Richard Berman is a spin doctor. For example, he has argued against a Mothers Against Drunk Driving (MADD) initiative to lower the blood alcohol content (BAC) limit for drivers by claiming that the stricter limits would punish responsible social drinkers. He has claimed that U.S. Centers for Disease Control and Prevention (CDC) warnings about salmonella-related food poisoning are just “whipping up fear over food.”

Here’s how an internal Philip Morris memo described Berman’s spin: “His proposed solution would broaden the focus of the ‘smoking issue,’ and expand into the bigger picture of over-regulation.” Smoking won’t kill you; over-regulation will.

Berman is “a one-man wrecking crew on important issues.” His approach has been described as “misleading” and “despicable.” Berman has been called “a tobacco company whore,” but he’s branched out since then.

Using “freedom of choice” as his battle cry, Berman has now taken on PETA and a number of other groups and organizations whose points of view could have an impact on the profits of his clients by waking consumers up. Berman’s Guest Choice Network has an “advisory panel” whose members in 1998 included officials representing companies ranging from Cargill Processed Meat Products and Outback Steakhouse to Minnesota Licensed Beverage Association and Sutter Home Winery. Berman’s clients are companies with vested interests in low employee wages; cheap, unhealthy restaurant-chain food, particularly meat; and tobacco, soft drink, and alcohol consumption—companies like Ruth’s Chris Steakhouse, Armour Swift, and Philip Morris, whose product line includes Kraft Foods and everything from Marlboro cigarettes to Oscar Meyer wieners and which is a major shareholder in its former subsidiary Miller Brewing, now known as SABMiller.

PETA’s recent successes in gaining fast-food industry concessions for more humane conditions for farm animals have sent ripples of fear through the food and beverage service industry. About the same time that McDonald’s buckled to PETA’s demands, Richard Berman changed his front group’s name and stepped up his attacks.

The key to Berman’s aggressive strategy is, in his own words, “to shoot the messenger ... we’ve got to attack their credibility as spokespersons,”—an interesting remark from someone whose background and funding so severely challenge his own credibility.

http://www.consumerdeception.com/index.asp



NOW, what about that Journal of Neurology article published by Singeltary ;


JOURNAL OF NEUROLOGY

MARCH 26, 2003

Send Post-Publication Peer Review to journal:

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

disease in the United States

Email Terry S. Singeltary:

flounder@wt.net flounder9@verizon.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



about sporadic CJD and BSE ;

CJD RISING SWITZERLAND

CJD is a predominantly sporadic disorder but can also occur as a dominantly inherited or infective condition. Only one of the 26 most recent confirmed cases was identified as carrying a disease related mutation of the PRNP gene, none had identifiable iatrogenic exposure, and none resembled variant CJD. Thus 25 of the 26 cases appear to be sporadic cases. Sporadic CJD is distributed worldwide with a reported incidence of about one in a million per year. Raised awareness of the disease in recent years could account for an increase in reported cases of CJD, although neither an increase in the average age of patients nor more frequent recognition of CJD amongst residents of nursing homes (where dementing illness is prevalent and misdiagnosis might be expected) were seen in the Swiss cases. Moreover, improved ascertainment as an explanation for the observed increase would imply levels of under-reporting in countries other than Switzerland, which appear implausible. The authors of the Lancet report suggest that the rise in cases might be due to some form of unidentified iatrogenic transmission or to exposure to a zoonotic source of infection, though cases do not resemble variant Creutzfeldt-Jakob disease (vCJD). The ongoing surveillance of CJD in Switzerland and the rest of Europe is essential to monitor the situation to see if this rise is sustained in Switzerland, and if a similar rise occurs in other countries (see http://www.eurocjd.ed.ac.uk).

http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=1921



Prion data suggest BSE link to sporadic CJD Declan Butler

Predicting the number of cases of Creutzfeldt-Jakob disease (CJD) in people as a result of transmission of bovine spongiform encephalopathy (BSE) has just got more difficult.Whereas it was thought that BSE only caused a new form of the disease called variant CJD (vCJD), a study in mice from a team led by John Collinge at University College London suggests that it may also cause a disease indistinguishable from the commonest form of classical, or 'sporadic', CJD...

http://www.nature.com/nature/journal/v420/n6915/full/420450a.html




Sent: Saturday, December 11, 2010 3:17 PM

Subject: Species-barrier-independent prion replication in apparently resistant species

Species-barrier-independent prion replication in apparently resistant species

Pertenece a: UCL University College London Eprints

Descripción: Transmission of prions between mammalian species is thought to be limited by a "species barrier," which depends on differences in the primary structure of prion proteins in the infecting inoculum and the host, Here we demonstrate that a strain of hamster prions thought to be nonpathogenic for conventional mice leads to prion replication to high levels in such mice but without causing clinical disease. Prions pathogenic in both mice and hamsters are produced. These results demonstrate the existence of subclinical forms of prion infection with important public health implications, both with respect to iatrogenic transmission from apparently healthy humans and dietary exposure to cattle and other species exposed to bovine spongiform encephalopathy prions, Current definitions of the species barrier, which have been based on clinical endpoints, need to be fundamentally reassessed.


Autor(es): Hill, AF - Joiner, S - Linehan, J - Desbruslais, M - Lantos, PL - Collinge, J -

Id.: 52395313

Versión: 1.0

Estado: Final

Palabras clave: TRANSMISSIBLE MINK ENCEPHALOPATHY, CREUTZFELDT - JAKOB - DISEASE, FATAL FAMILIAL INSOMNIA, STRAIN VARIATION, TRANSGENIC MICE, SCRAPIE INFECTIVITY, HAMSTER SCRAPIE, VARIANT CJD, BSE AGENT, PROTEIN -

Tipo de recurso: Article -

Tipo de Interactividad: Expositivo

Nivel de Interactividad: muy bajo

Audiencia: Estudiante - Profesor - Autor -

Estructura: Atomic

Coste: no

Copyright: sí

Requerimientos técnicos: Browser: Any -

Fecha de contribución: 10-dic-2010

Contacto:

http://biblioteca.universia.net/html_bura/ficha/params/id/52395313.html



for those interested, see more here with comments........


Saturday, December 11, 2010

Species-barrier-independent prion replication in apparently resistant species

http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/species-barrier-independent-prion.html



Thursday, November 18, 2010

UNITED STATES OF AMERICA VS GALEN J. NIEHUES FAKED MAD COW FEED TEST ON 92 BSE INSPECTION REPORTS FOR APPROXIMATELY 100 CATTLE OPERATIONS

http://bse-atypical.blogspot.com/2010/11/united-states-of-america-vs-galen-j.html




Wednesday, December 22, 2010

Manitoba veterinarian has been fined $10,000 for falsifying certification documents for U.S. bound cattle and what about mad cow disease ?

http://usdameatexport.blogspot.com/2010/12/manitoba-veterinarian-has-been-fined.html




Tuesday, November 02, 2010

BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only) diagnostic criteria CVL 1992

http://bse-atypical.blogspot.com/2010/11/bse-atypical-lesion-distribution-rbse.html




Monday, November 22, 2010

Atypical transmissible spongiform encephalopathies in ruminants: a challenge for disease surveillance and control

REVIEW ARTICLES

http://transmissiblespongiformencephalopathy.blogspot.com/2010/11/atypical-transmissible-spongiform.html



Thursday, November 18, 2010

Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy following passage in sheep

http://bse-atypical.blogspot.com/2010/11/increased-susceptibility-of-human-prp.html



Seven main threats for the future linked to prions

The NeuroPrion network has identified seven main threats for the future linked to prions.

First threat

The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed.

*** Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.


http://www.neuroprion.org/en/np-neuroprion.html



Thursday, August 12, 2010

Seven main threats for the future linked to prions


http://prionpathy.blogspot.com/2010/08/seven-main-threats-for-future-linked-to.html



http://prionpathy.blogspot.com/



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://collections.europarchive.org/tna/20080102185948/http://www.bseinquiry.gov.uk/files/yb/1991/01/04004001.pdf



Sunday, November 28, 2010

Variably protease-sensitive prionopathy in a PRNP codon 129 heterozygous UK patient with co-existing tau, a synuclein and AB pathology


http://prionopathy.blogspot.com/2010/11/variably-protease-sensitive-prionopathy.html



what about that sheep scrapie, and how the feds so freely said that sheep scrapie has and would never transmit to humans......well, think again. ...terry

Thursday, November 18, 2010

Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy following passage in sheep

http://bse-atypical.blogspot.com/2010/11/increased-susceptibility-of-human-prp.html



Sunday, December 12, 2010

EFSA reviews BSE/TSE infectivity in small ruminant tissues News Story 2 December 2010

http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/efsa-reviews-bsetse-infectivity-in.html



Tuesday, March 16, 2010

COMMONWEALTH OF AUSTRALIA Hansard Import restrictions on beef FRIDAY, 5 FEBRUARY 2010 AUSTRALIA

COMMONWEALTH OF AUSTRALIA

Proof Committee Hansard

RRA&T 2 Senate Friday, 5 February 2010

RURAL AND REGIONAL AFFAIRS AND TRANSPORT

[9.03 am]

BELLINGER, Mr Brad, Chairman, Australian Beef Association

CARTER, Mr John Edward, Director, Australian Beef Association

CHAIR—Welcome. Would you like to make an opening statement?

Mr Bellinger—Thank you. The ABA stands by its submission, which we made on 14 December last year, that the decision made by the government to allow the importation of beef from BSE affected countries is politically based, not science based. During this hearing we will bring forward compelling new evidence to back up this statement. When I returned to my property after the December hearing I received a note from an American citizen. I will read a small excerpt from the mail he sent me in order to reinforce the dangers of allowing the importation of beef from BSE affected countries. I have done a number of press releases on this topic, and this fellow has obviously picked my details up from the internet. His name is Terry Singeltary and he is from Bacliff, Texas. He states, and rightfully so:

You should be worried. Please let me explain. I’ve kept up with the mad cow saga for 12 years today, on December 14th 1997, some four months post voluntary and partial mad cow feed ban in the USA, I lost my mother to the Heidenhain variant Creutzfeldt-Jakob disease (CJD). I know this is just another phenotype of the infamous sporadic CJDs. Here in the USA, when USA sheep scrapie was transmitted to USA bovine, the agent was not UK BSE—it was a different strain. So why then would human TSE from USA cattle look like UK CJD from UK BSE? It would not. So this accentuates that the science is inconclusive still on this devastating disease. He goes on to state:

The OIE— the International Organisation of Epizootics, the arm of the WTO— is a failed global agent that in my opinion is bought off via bogus regulations for global trade and industry reps. I have done this all these years for nothing but the truth. I am a consumer, I eat meat, but I do not have to sit idly by and see the ignorance and greed of it all while countless numbers of humans and animals are being exposed to the TSE agents. All the USA is interested in is trade, nothing else matters.

Even Dr Stanley Prusiner, who incidentally won the Nobel Health Prize in 1997 for his work on the prion—he invented the word ‘prion’, or it came from him—states:

snip...see full text 110 pages ;

http://www.aph.gov.au/hansard/senate/commttee/S12742.pdf



for those interested, please see much more here ;


http://docket-aphis-2006-0041.blogspot.com/2010/03/commonwealth-of-australia-hansard.html



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



Tuesday, July 13, 2010


(SEE BEEF PRODUCTS EXPORTED TO AUSTRALIA FROM USA...TSS)


AUSTRALIAN QUESTIONNAIRE TO ASSESS BSE RISK (OIE) Terrestrial Animal Health Code, 2009 and USA export risk factor for BSE to Australia

http://usdameatexport.blogspot.com/2010/07/australian-questionnaire-to-assess-bse.html



Saturday, August 14, 2010

USA NON-SPECIES CODING SYSTEM (BEEF IMPORT EXPORT BSE RISK THERE FROM)

US denies it's illegally sending beef to Australia ?

Friday, 13/08/2010

http://usdameatexport.blogspot.com/2010/08/usa-non-species-coding-system-beef.html



Saturday, June 19, 2010

U.S. DENIED UPGRADED BSE STATUS FROM OIE

http://usdameatexport.blogspot.com/2010/06/us-denied-upgraded-bse-status-from-oie.html



Sunday, August 15, 2010

ATYPICAL BSE NOW LINKED TO CAUSING SPORADIC CJD OVERSEAS Commonwealth of Australia

http://bse-atypical.blogspot.com/2010/08/atypical-bse-now-linked-to-causing.html



Tuesday, January 5, 2010

JOINT STATEMENT FROM USTR, USDA ON TAIWAN'S ACTIONS TO UNJUSTIFIABLY RESTRICT U.S. BEEF IMPORTS IN VIOLATION OF OUR BILATERAL AGREEMENT Release No. 0002.10 Contact: USTR, Nefeterius McPherson (202) 395-3230 USDA, Caleb Weaver (202) 720-4623

http://usdavskorea.blogspot.com/2010/01/joint-statement-from-ustr-usda-on.html


2010


Dear Mr Singeltary,

We would very much like to interview you about the 7 main threats for the future linked to prions for our program series !

is an internet and satellite television station broadcasting globally all news positive and constructive to the world 24 hours/day 7 days /week

It broadcasts in 40+ languages and has a potential viewing audience of 4 billion + world wide

If you are agreeable, would you be available the afternoon of Sunday October 3rd ? We would be driving from Houston. It takes 1 hour for the camera men to set up and then the interview lasts approximately 1 and 1/2 hours.

snip...

"Dear Houston center,

Would you please contact this person for an interview?

Guest : Terry Singeltary

"My mother was murdered by what I call corporate and political homicide i.e. FOR PROFIT! she died from a rare phenotype of CJD i.e. the Heidenhain Variant of Creutzfeldt Jakob Disease i.e. sporadic, simply meaning from unknown route and source. I have simply been trying to validate her death DOD 12/14/97 with the truth."


http://prionpathy.blogspot.com/2010/08/seven-main-threats-for-future-linked-to.html



http://www.blogger.com/profile/06986622967539963260



So the interview is to raise the awareness of the general public to this very real risk of prion disease.

The interview would be from the angle of your own personal experience /personal research and advocacy.

Wishing you all the very best with your upcoming surgery!

snip...Taiwan...end...TSS



Friday, April 02, 2010 U.S.

beef trade talks to continue but curbs to remain: Japan

http://bse-atypical.blogspot.com/2010/04/us-beef-trade-talks-to-continue-but.html



Even McDonald’s, an international business symbolic of American culture, advertises that it uses only “pure Australian beef” in South Korea. Burger King announced that it only uses beef from Australia and New Zealand. Why? Even famous brands like McDonald’s cannot survive if they are perceived as using unsafe ingredients. They know that Koreans still do not trust the safety of American beef and must distance their brands from American beef.

Therefore the U.S. should aim to export only the best quality beef to Korea and regain the Korean people’s trust. Regaining Koreans’ confidence in U.S. beef will be a long-term gain for many American industries seeking to access the 12th largest economy in the world.

How will we know that U.S. beef has regained trust in South Korea? When McDonald’s in South Korea announces it uses “pure American beef.”

Kwon Seung-woo, a professor at Korea University Business School


http://joongangdaily.joins.com/article/view.asp?aid=2928098



hmmmm, let's see just what the BIG MAC himself had to say ;


Wednesday, November 10, 2010

McDonald's and USA BSE aka mad cow disease McDonald's AND Seriologicals USA NOT PROTECTED FROM MAD COW

http://bse-atypical.blogspot.com/2010/11/mcdonalds-and-usa-bse-aka-mad-cow.html



Atypical BSE in Cattle

BSE has been linked to the human disease variant Creutzfeldt Jakob Disease (vCJD). The known exposure pathways for humans contracting vCJD are through the consumption of beef and beef products contaminated by the BSE agent and through blood transfusions. However, recent scientific evidence suggests that the BSE agent may play a role in the development of other forms of human prion diseases as well. These studies suggest that classical type of BSE may cause type 2 sporadic CJD and that H-type atypical BSE is connected with a familial form of CJD.

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.

snip...see full text ;

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



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.

page 114 ;

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



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



Wednesday, March 31, 2010

Atypical BSE in Cattle

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



UPDATED DATA ON 2ND CWD STRAIN

Wednesday, September 08, 2010

CWD PRION CONGRESS SEPTEMBER 8-11 2010

http://chronic-wasting-disease.blogspot.com/2010/09/cwd-prion-2010.html



PRION 2010 Meeting Report International Prion Congress: From agent to disease; September 8–11, 2010; Salzburg, Austria Volume 4, Issue 3 July/August/September 2010

http://www.landesbioscience.com/journals/prion/article/12764/



THIS FDA recall for CWD positive product in commerce, was NOT done for the welfare of the dead CWD postive elk. ...TSS

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

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

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



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

snip...

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: [log in to unmask]">[log in to unmask]; [log in to unmask]">[log in to unmask]; [log in to unmask]">[log in to unmask]

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

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

snip...

full text ;

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



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



see full text ;

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



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



There are now two documented strains of CWD, and science is showing that indeed CWD could transmit to humans via transmission studies ;

PPo3-7:

Prion Transmission from Cervids to Humans is Strain-dependent

Qingzhong Kong, Shenghai Huang,*Fusong Chen, Michael Payne, Pierluigi Gambetti and Liuting Qing Department of Pathology; Case western Reserve University; Cleveland, OH USA *Current address: Nursing Informatics; Memorial Sloan-Kettering Cancer Center; New York, NY USA

Key words: CWD, strain, human transmission

Chronic wasting disease (CWD) is a widespread prion disease in cervids (deer and elk) in North America where significant human exposure to CWD is likely and zoonotic transmission of CWD is a concern. Current evidence indicates a strong barrier for transmission of the classical CWD strain to humans with the PrP-129MM genotype. A few recent reports suggest the presence of two or more CWD strains. What remain unknown is whether individuals with the PrP-129VV/MV genotypes are also resistant to the classical CWD strain and whether humans are resistant to all natural or adapted cervid prion strains. Here we report that a human prion strain that had adopted the cervid prion protein (PrP) sequence through passage in cervidized transgenic mice efficiently infected transgenic mice expressing human PrP, indicating that the species barrier from cervid to humans is prion strain-dependent and humans can be vulnerable to novel cervid prion strains. Preliminary results on CWD transmission in transgenic mice expressing human PrP-129V will also be discussed.

Acknowledgement Supported by NINDS NS052319 and NIA AG14359.



PPo2-27:

Generation of a Novel form of Human PrPSc by Inter-species Transmission of Cervid Prions

Marcelo A. Barria,1 Glenn C. Telling,2 Pierluigi Gambetti,3 James A. Mastrianni4 and Claudio Soto1 1Mitchell Center for Alzheimer's disease and related Brain disorders; Dept of Neurology; University of Texas Houston Medical School; Houston, TX USA; 2Dept of Microbiology, Immunology & Molecular Genetics and Neurology; Sanders Brown Center on Aging; University of Kentucky Medical Center; Lexington, KY USA; 3Institute of Pathology; Case western Reserve University; Cleveland, OH USA; 4Dept of Neurology; University of Chicago; Chicago, IL USA

Prion diseases are infectious neurodegenerative disorders affecting humans and animals that result from the conversion of normal prion protein (PrPC) into the misfolded and infectious prion (PrPSc). Chronic wasting disease (CWD) of cervids is a prion disorder of increasing prevalence within the United States that affects a large population of wild and captive deer and elk. CWD is highly contagious and its origin, mechanism of transmission and exact prevalence are currently unclear. The risk of transmission of CWD to humans is unknown. Defining that risk is of utmost importance, considering that people have been infected by animal prions, resulting in new fatal diseases. To study the possibility that human PrPC can be converted into the infectious form by CWD PrPSc we performed experiments using the Protein Misfolding Cyclic Amplification (PMCA) technique, which mimic in vitro the process of prion replication. Our results show that cervid PrPSc can induce the pathological conversion of human PrPC, but only after the CWD prion strain has been stabilized by successive passages in vitro or in vivo. Interestingly, this newly generated human PrPSc exhibits a distinct biochemical pattern that differs from any of the currently known forms of human PrPSc, indicating that it corresponds to a novel human prion strain. Our findings suggest that CWD prions have the capability to infect humans, and that this ability depends on CWD strain adaptation, implying that the risk for human health progressively increases with the spread of CWD among cervids.



PPo2-7:

Biochemical and Biophysical Characterization of Different CWD Isolates

Martin L. Daus and Michael Beekes Robert Koch Institute; Berlin, Germany

Key words: CWD, strains, FT-IR, AFM

Chronic wasting disease (CWD) is one of three naturally occurring forms of prion disease. The other two are Creutzfeldt-Jakob disease in humans and scrapie in sheep. CWD is contagious and affects captive as well as free ranging cervids. As long as there is no definite answer of whether CWD can breach the species barrier to humans precautionary measures especially for the protection of consumers need to be considered. In principle, different strains of CWD may be associated with different risks of transmission to humans. Sophisticated strain differentiation as accomplished for other prion diseases has not yet been established for CWD. However, several different findings indicate that there exists more than one strain of CWD agent in cervids. We have analysed a set of CWD isolates from white-tailed deer and could detect at least two biochemically different forms of disease-associated prion protein PrPTSE. Limited proteolysis with different concentrations of proteinase K and/or after exposure of PrPTSE to different pH-values or concentrations of Guanidinium hydrochloride resulted in distinct isolate-specific digestion patterns. Our CWD isolates were also examined in protein misfolding cyclic amplification studies. This showed different conversion activities for those isolates that had displayed significantly different sensitivities to limited proteolysis by PK in the biochemical experiments described above. We further applied Fourier transform infrared spectroscopy in combination with atomic force microscopy. This confirmed structural differences in the PrPTSE of at least two disinct CWD isolates. The data presented here substantiate and expand previous reports on the existence of different CWD strains.



http://www.prion2010.org/bilder/prion_2010_program_latest_w_posters_4_.pdf?139&PHPSESSID=a30a38202cfec579000b77af81be3099



UPDATED DATA ON 2ND CWD STRAIN

Wednesday, September 08, 2010

CWD PRION CONGRESS SEPTEMBER 8-11 2010


http://chronic-wasting-disease.blogspot.com/2010/09/cwd-prion-2010.html


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




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



Wednesday, November 17, 2010

CWD Update 98 November 10, 2010


http://chronic-wasting-disease.blogspot.com/2010/11/cwd-update-98-november-10-2010.html



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



yep, but the SECOND passage was especially a doozy, and remember, oral transmission will take much longer than intracerebral route, and we now have two documented strains of cwd i.e. the regular strain of cwd (whatever the hell that means), and the Wisconsin strain, with probably more in the pipeline. NOW, THE MILLION DOLLAR QUESTION, WAS THE WISCONSIN CWD STRAIN INCLUDED IN THE ORAL TRANSMISSION STUDY ?

also, cwd has been transmitted to deer mice (Peromyscus maniculatus), white-footed mice (P. leucopus), meadow voles (Microtus pennsylvanicus), and red-backed voles (Myodes gapperi).

considering scrapie, over 20 regular strains, with the atypical NOR-98, TWO documented TME strains i.e. hyper and drowsy, c-BSE, h-BSE, l-BSE, all in North America, all of which have been rendered and fed to animals for human and animal food..............terry

Title: Experimental Second Passage of Chronic Wasting Disease (Cwd(mule Deer)) Agent to Cattle

Authors

Hamir, Amirali Kunkle, Robert Miller, Janice - ARS RETIRED Greenlee, Justin Richt, Juergen

Submitted to: Journal of Comparative Pathology Publication Type: Peer Reviewed Journal Publication Acceptance Date: July 25, 2005 Publication Date: January 1, 2006 Citation: Hamir, A.N., Kunkle, R.A., Miller, J.M., Greenlee, J.J., Richt, J.A. 2006. Experimental second passage of chronic wasting disease (CWD(mule deer)) agent to cattle. Journal of Comparative Pathology. 134(1):63-69.

Interpretive Summary: To compare the findings of experimental first and second passage of chronic wasting disease (CWD) in cattle, 6 calves were inoculated into the brain with CWD-mule deer agent previously (first) passaged in cattle. Two other uninoculated calves served as controls. Beginning 10-12 months post inoculation (PI), all inoculates lost appetite and weight. Five animals subsequently developed clinical signs of central nervous system (CNS) abnormality. By 16.5 months PI, all cattle had been euthanized because of poor prognosis. None of the animals showed microscopic lesions of spongiform encephalopathy (SE) but the CWD agent was detected in their CNS tissues by 2 laboratory techniques (IHC and WB). These findings demonstrate that inoculated cattle amplify CWD agent but also develop clinical CNS signs without manifestation of microscopic lesions of SE. This situation has also been shown to occur following inoculation of cattle with another TSE agent, namely, sheep scrapie. The current study confirms previous work that indicates that the diagnostic tests currently used for confirmation of bovine spongiform encephalopathy (BSE) in the U.S. would detect CWD in cattle, should it occur naturally. Furthermore, it raises the possibility of distinguishing CWD from BSE in cattle due to the absence of microscopic lesions and a unique multifocal distribution of PrPres, as demonstrated by IHC, which in this study, appears to be more sensitive than the WB. Technical Abstract: To compare clinicopathological findings of first and second passage of chronic wasting disease (CWD) in cattle, a group of calves (n=6) were intracerebrally inoculated with CWD-mule deer agent previously (first) passaged in cattle. Two other uninoculated calves served as controls. Beginning 10-12 months post inoculation (PI), all inoculates lost appetite and lost weight. Five animals subsequently developed clinical signs of central nervous system (CNS) abnormality. By 16.5 months PI, all cattle had been euthanized because of poor prognosis. None of the animals showed microscopic lesions of spongiform encephalopathy (SE) but PrPres was detected in their CNS tissues by immunohistochemistry (IHC) and Western blot (WB) techniques. These findings demonstrate that intracerebrally inoculated cattle not only amplify CWD PrPres but also develop clinical CNS signs without manifestation of morphologic lesions of SE. This situation has also been shown to occur following inoculation of cattle with another TSE agent, scrapie. The current study confirms previous work that indicates the diagnostic techniques currently used for confirmation of bovine spongiform encephalopathy (BSE) in the U.S. would detect CWD in cattle, should it occur naturally. Furthermore, it raises the possibility of distinguishing CWD from BSE in cattle due to the absence of neuropathologic lesions and a unique multifocal distribution of PrPres, as demonstrated by IHC, which in this study, appears to be more sensitive than the WB.


http://www.ars.usda.gov/research/publications/publications.htm?SEQ_NO_115=178318



PLUS, oral transmission between cervids, either infected carcases AND ESPECIALLY FEED THAT HAS ANIMAL PROTEIN, PLEASE SEE ;

PRODUCT Custom deer feed made for a Wisconsin farm. The product was in bags holding about 40 pounds each. Recall # V-122-4. CODE 1-30-04 on the product invoice and mixing record. RECALLING FIRM/MANUFACTURER Crivitz Feed Mill, Crivitz, WI, by telephone on February 20, 2004. Wisconsin State initiated recall is complete. REASON The recalled deer feed contained steamed bone meal which is prohibited material in feed for ruminants.

VOLUME OF PRODUCT IN COMMERCE 515 pounds.

DISTRIBUTION WI.

END OF ENFORCEMENT REPORT FOR APRIL 7, 2004

###

http://www.fda.gov/bbs/topics/enforce/2004/ENF00842.html



Monday, August 9, 2010

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

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

SEE where sporadic cjd in the USA went from 59 cases in 1997, to 216 cases in 2009. a steady increase since 1997. ...TSS

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

Year Total Referrals2 Prion Disease Sporadic Familial Iatrogenic vCJD

1997 114 68 59 9 0 0

to

2009 425 259 216 43 0 0

http://www.cjdsurveillance.com/pdf/case-table.pdf



see full text ;

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



2010

PLEASE NOTE REFERENCE LINES 5. AND 6. AT BOTTOM ;

Monday, August 9, 2010

National Prion Disease Pathology Surveillance Center Cases Examined (July 31, 2010) Year Total Referrals2 Prion Disease Sporadic Familial Iatrogenic vCJD

1996 & earlier 51 33 28 5 0 0

1997 114 68 59 9 0 0

1998 88 52 44 7 1 0

1999 120 72 64 8 0 0

2000 146 103 89 14 0 0

2001 209 119 109 10 0 0

2002 248 149 125 22 2 0

2003 274 176 137 39 0 0

2004 325 186 164 21 0 1(3)

2005 344 194 157 36 1 0

2006 383 197 166 29 0 2(4)

2007 377 214 187 27 0 0

2008 394 231 204 25 0 0

2009 425 259 216 43 0 0

2010 204 124 85 20 0 0

TOTAL 3702(5) 2177(6) 1834 315 4 3

1 Listed based on the year of death or, if not available, on year of referral;

2 Cases with suspected prion disease for which brain tissue and/or blood (in familial cases) were submitted;

3 Disease acquired in the United Kingdom;

4 Disease was acquired in the United Kingdom in one case and in Saudi Arabia in the other case;

5 Includes 16 cases in which the diagnosis is pending, and 18 inconclusive cases;

6 Includes 21 (19 from 2010) cases with type determination pending in which the diagnosis of vCJD has been excluded.

http://www.cjdsurveillance.com/pdf/case-table.pdf



Tuesday, December 14, 2010

Infection control of CJD, vCJD and other human prion diseases in healthcare and community settings part 4, Annex A1, Annex J, UPDATE DECEMBER 2010

http://creutzfeldt-jakob-disease.blogspot.com/2010/12/infection-control-of-cjd-vcjd-and-other.html



Tuesday, December 14, 2010 TAFS1

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

http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/tafs1-position-paper-on-relaxation-of.html



Saturday, December 18, 2010

OIE Global Conference on Wildlife Animal Health and Biodiversity - Preparing for the Future (TSE AND PRIONS) Paris (France), 23-25 February 2011

http://transmissiblespongiformencephalopathy.blogspot.com/2010/12/oie-global-conference-on-wildlife.html




Merry Christmas..............PEACE !

kindest regards, terry

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