Saturday, September 19, 2015

An interview with Professor John Collinge: VIDEO Director of the MRC Prion Unit Part of the Hayward Gallery's History Is Now

Published on Apr 7, 2015

An interview with Professor John Collinge: Director of the MRC Prion Unit. Part of the Hayward Gallery's History Is Now.

culture of denial...SEE VIDEO ;

https://www.youtube.com/watch?v=i0aRe4wQX2g

Subject: BSE INQUIRY

BSE INQUIRY DFAs

http://bseinquiry.blogspot.com/

Sunday, May 18, 2008

BSE Inquiry DRAFT FACTUAL ACCOUNT DFA

BSE Inquiry DRAFT FACTUAL ACCOUNTS DFA's

http://bseinquiry.blogspot.com/2008/05/bse-inquiry-draft-factual-account-dfa.html

Sunday, May 18, 2008

BSE, CJD, and Baby foods (the great debate 1999 to 2005)

http://bseinquiry.blogspot.com/2008/05/bse-cjd-and-baby-foods-great-debate.html

Sunday, May 18, 2008

MAD COW DISEASE BSE CJD CHILDREN VACCINES

http://bseinquiry.blogspot.com/2008/05/mad-cow-disease-bse-cjd-children.html

PRION 2015 ORAL AND POSTER CONGRESSIONAL ABSTRACTS

THANK YOU PRION 2015 TAYLOR & FRANCIS, Professor Chernoff, and Professor Aguzzi et al, for making these PRION 2015 Congressional Poster and Oral Abstracts available freely to the public. ...Terry S. Singeltary Sr.

O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations

Emmanuel Comoy, Jacqueline Mikol, Val erie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France

Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases). Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods. ***We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period, with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold longe incubation than BSE. ***Scrapie, as recently evoked in humanized mice (Cassard, 2014), is the third potentially zoonotic PD (with BSE and L-type BSE), ***thus questioning the origin of human sporadic cases. We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.

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

***thus questioning the origin of human sporadic cases...

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

https://prion2015.files.wordpress.com/2015/05/programguide1.pdf

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

Subject: re-BSE prions propagate as either variant CJD-like or sporadic CJD

Date: Thu, 28 Nov 2002 10:23:43 -0000

From: "Asante, Emmanuel A" e.asante@ic.ac.uk

To: "'flounder@wt.net'" flounder@wt.net

Dear Terry,

I have been asked by Professor Collinge to respond to your request. I am a Senior Scientist in the MRC Prion Unit and the lead author on the paper. I have attached a pdf copy of the paper for your attention.

Thank you for your interest in the paper.

In respect of your first question, the simple answer is, ***yes. As you will find in the paper, we have managed to associate the alternate phenotype to type 2 PrPSc, the commonest sporadic CJD. It is too early to be able to claim any further sub-classification in respect of Heidenhain variant CJD or Vicky Rimmer's version. It will take further studies, which are on-going, to establish if there are sub-types to our initial finding which we are now reporting. The main point of the paper is that, as well as leading to the expected new variant CJD phenotype, BSE transmission to the 129-methionine genotype can lead to an alternate phenotype which is indistinguishable from type 2 PrPSc.

I hope reading the paper will enlighten you more on the subject. If I can be of any further assistance please to not hesitate to ask. Best wishes.

Emmanuel Asante

<>

____________________________________

Dr. Emmanuel A Asante MRC Prion Unit & Neurogenetics Dept. Imperial College School of Medicine (St. Mary's) Norfolk Place, LONDON W2 1PG Tel: +44 (0)20 7594 3794 Fax: +44 (0)20 7706 3272 email: e.asante@ic.ac.uk (until 9/12/02) New e-mail: e.asante@prion.ucl.ac.uk (active from now)

____________________________________

***Our study demonstrates susceptibility of adult cattle to oral transmission of classical BSE. ***

***our findings suggest that possible transmission risk of H-type BSE to sheep and human. ***

P.86: Estimating the risk of transmission of BSE and scrapie to ruminants and humans by protein misfolding cyclic amplification

Morikazu Imamura, Naoko Tabeta, Yoshifumi Iwamaru, and Yuichi Murayama National Institute of Animal Health; Tsukuba, Japan

To assess the risk of the transmission of ruminant prions to ruminants and humans at the molecular level, we investigated the ability of abnormal prion protein (PrPSc) of typical and atypical BSEs (L-type and H-type) and typical scrapie to convert normal prion protein (PrPC) from bovine, ovine, and human to proteinase K-resistant PrPSc-like form (PrPres) using serial protein misfolding cyclic amplification (PMCA).

Six rounds of serial PMCA was performed using 10% brain homogenates from transgenic mice expressing bovine, ovine or human PrPC in combination with PrPSc seed from typical and atypical BSE- or typical scrapie-infected brain homogenates from native host species. In the conventional PMCA, the conversion of PrPC to PrPres was observed only when the species of PrPC source and PrPSc seed matched. However, in the PMCA with supplements (digitonin, synthetic polyA and heparin), both bovine and ovine PrPC were converted by PrPSc from all tested prion strains. On the other hand, human PrPC was converted by PrPSc from typical and H-type BSE in this PMCA condition.

Although these results were not compatible with the previous reports describing the lack of transmissibility of H-type BSE to ovine and human transgenic mice, ***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.

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

***Our study demonstrates susceptibility of adult cattle to oral transmission of classical BSE. ***

P.86: Estimating the risk of transmission of BSE and scrapie to ruminants and humans by protein misfolding cyclic amplification

Morikazu Imamura, Naoko Tabeta, Yoshifumi Iwamaru, and Yuichi Murayama National Institute of Animal Health; Tsukuba, Japan

To assess the risk of the transmission of ruminant prions to ruminants and humans at the molecular level, we investigated the ability of abnormal prion protein (PrPSc) of typical and atypical BSEs (L-type and H-type) and typical scrapie to convert normal prion protein (PrPC) from bovine, ovine, and human to proteinase K-resistant PrPSc-like form (PrPres) using serial protein misfolding cyclic amplification (PMCA).

Six rounds of serial PMCA was performed using 10% brain homogenates from transgenic mice expressing bovine, ovine or human PrPC in combination with PrPSc seed from typical and atypical BSE- or typical scrapie-infected brain homogenates from native host species. In the conventional PMCA, the conversion of PrPC to PrPres was observed only when the species of PrPC source and PrPSc seed matched. However, in the PMCA with supplements (digitonin, synthetic polyA and heparin), both bovine and ovine PrPC were converted by PrPSc from all tested prion strains. On the other hand, human PrPC was converted by PrPSc from typical and H-type BSE in this PMCA condition.

Although these results were not compatible with the previous reports describing the lack of transmissibility of H-type BSE to ovine and human transgenic mice, ***our findings suggest that possible transmission risk of H-type BSE to sheep and human. Bioassay will be required to determine whether the PMCA products are infectious to these animals.

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

https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf

https://prion2015.files.wordpress.com/2015/05/programguide1.pdf

Saturday, May 30, 2015

PRION 2015 ORAL AND POSTER CONGRESSIONAL ABSTRACTS

https://prion2015.files.wordpress.com/2015/05/prion2015abstracts.pdf

http://transmissiblespongiformencephalopathy.blogspot.com/2015/05/prion-2015-oral-and-poster.html

PRION 2015 CONFERENCE FT. COLLINS CWD RISK FACTORS TO HUMANS

*** LATE-BREAKING ABSTRACTS PRION 2015 CONFERENCE ***

O18

Zoonotic Potential of CWD Prions

Liuting Qing1, Ignazio Cali1,2, Jue Yuan1, Shenghai Huang3, Diane Kofskey1, Pierluigi Gambetti1, Wenquan Zou1, Qingzhong Kong1 1Case Western Reserve University, Cleveland, Ohio, USA, 2Second University of Naples, Naples, Italy, 3Encore Health Resources, Houston, Texas, USA

*** These results indicate that the CWD prion has the potential to infect human CNS and peripheral lymphoid tissues and that there might be asymptomatic human carriers of CWD infection.

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

***These results indicate that the CWD prion has the potential to infect human CNS and peripheral lymphoid tissues and that there might be asymptomatic human carriers of CWD infection.***

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

P.105: RT-QuIC models trans-species prion transmission

Kristen Davenport, Davin Henderson, Candace Mathiason, and Edward Hoover Prion Research Center; Colorado State University; Fort Collins, CO USA

Conversely, FSE maintained sufficient BSE characteristics to more efficiently convert bovine rPrP than feline rPrP. Additionally, human rPrP was competent for conversion by CWD and fCWD.

***This insinuates that, at the level of protein:protein interactions, the barrier preventing transmission of CWD to humans is less robust than previously estimated.

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

***This insinuates that, at the level of protein:protein interactions, the barrier preventing transmission of CWD to humans is less robust than previously estimated.***

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

https://prion2015.files.wordpress.com/2015/05/programguide1.pdf

Evidence That Transmissible Mink Encephalopathy Results from Feeding Infected Cattle

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

snip...

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

http://collections.europarchive.org/tna/20090505194948/http://bseinquiry.gov.uk/files/mb/m09/tab05.pdf

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

3. Prof. A. Robertson gave a brief account of BSE. The US approach was to accord it a very low profile indeed. Dr. A Thiermann showed the picture in the ''Independent'' with cattle being incinerated and thought this was a fanatical incident to be avoided in the US at all costs. ...

http://web.archive.org/web/20060307063531/http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf

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

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

Tuesday, September 15, 2015

Texas TAHC Chronic Wasting Disease Confirmed in Lavaca County Captive White-tailed Deer; Linked to Index Herd

http://chronic-wasting-disease.blogspot.com/2015/09/texas-detects-more-deer-positive-for.html

Thursday, September 10, 2015

25th Meeting of the Transmissible Spongiform Encephalopathies Advisory Committee Food and Drug Administration Silver Spring, Maryland June 1, 2015

FDA TSE PRION MAD COW CIRCUS AND TRAVELING ROAD SHOW (their words)

http://tseac.blogspot.com/2015/09/25th-meeting-of-transmissible.html

Saturday, September 12, 2015

The Canadian Management of Bovine Spongiform Encephalopathy in Historical and Scientific Perspective, 1990-2014

>>>We propose that Canadian policies largely ignored the implicit medical nature of BSE, treating it as a purely agricultural and veterinary issue. In this way, policies to protect Canadians were often delayed and incomplete, in a manner disturbingly reminiscent of Britain’s failed management of BSE. Despite assurances to the contrary, it is premature to conclude that BSE (and with it the risk of variant Creutzfeldt-Jakob disease) is a thing of Canada’s past: BSE remains very much an issue in Canada’s present. <<<

http://bovineprp.blogspot.com/2015/09/the-canadian-management-of-bovine.html

Tuesday, August 4, 2015

*** FDA U.S. Measures to Protect Against BSE ***

http://bseusa.blogspot.com/2015/08/fda-us-measures-to-protect-against-bse.html


Alzheimer's, iatrogenic, transmissible, tse, prion, what if ?

 
Wednesday, September 9, 2015


*** Evidence for human transmission of amyloid-β pathology and cerebral amyloid angiopathy

 

 
Wednesday, September 2, 2015


*** Clinically Unsuspected Prion Disease Among Patients With Dementia Diagnoses in an Alzheimer’s Disease Database




Tuesday, September 1, 2015

 
*** Evidence for α-synuclein prions causing multiple system atrophy in humans with parkinsonism



 
Self-Propagative Replication of Ab Oligomers Suggests Potential Transmissibility in Alzheimer Disease

 
Received July 24, 2014; Accepted September 16, 2014; Published November 3, 2014

 
Singeltary comment ;

 


IBNC Tauopathy or TSE Prion disease, it appears, no one is sure

 
Singeltary et al


Posted by flounder on 03 Jul 2015 at 16:53 GMT

 

 

Monday, August 17, 2015

 
FDA Says Endoscope Makers Failed to Report Superbug Problems OLYMPUS

 
*** I told Olympus 15 years ago about these risk factors from endoscopy equipment, disinfection, even spoke with the Doctor at Olympus, this was back in 1999. I tried to tell them that they were exposing patients to dangerous pathogens such as the CJD TSE prion, because they could not properly clean them. even presented my concern to a peer review journal GUT, that was going to publish, but then it was pulled by Professor Michael Farthing et al... see ;

 


Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery.

 
Gibbs CJ Jr, Asher DM, Kobrine A, Amyx HL, Sulima MP, Gajdusek DC. Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.


Stereotactic multicontact electrodes used to probe the cerebral cortex of a middle aged woman with progressive dementia were previously implicated in the accidental transmission of Creutzfeldt-Jakob disease (CJD) to two younger patients. The diagnoses of CJD have been confirmed for all three cases. More than two years after their last use in humans, after three cleanings and repeated sterilisation in ethanol and formaldehyde vapour, the electrodes were implanted in the cortex of a chimpanzee. Eighteen months later the animal became ill with CJD. This finding serves to re-emphasise the potential danger posed by reuse of instruments contaminated with the agents of spongiform encephalopathies, even after scrupulous attempts to clean them.



 
IBNC Tauopathy or TSE Prion disease, it appears, no one is sure


Singeltary et al


Posted by flounder on 03 Jul 2015 at 16:53 GMT



 
Thursday, August 13, 2015

 
Iatrogenic CJD due to pituitary-derived growth hormone with genetically determined incubation times of up to 40 years

 


Terry S. Singeltary Sr.
 
Posted by at No comments:

Tuesday, September 1, 2015

Evidence for α-synuclein prions causing multiple system atrophy in humans with parkinsonism

 Evidence for α-synuclein prions causing multiple system atrophy in humans with parkinsonism


Stanley B. Prusinera,b,c,1, Amanda L. Woermana, Daniel A. Mordesd, Joel C. Wattsa,b,2, Ryan Rampersauda, David B. Berrya, Smita Patela, Abby Oehlere, Jennifer K. Lowef, Stephanie N. Kravitzf, Daniel H. Geschwindf,g, David V. Gliddenh, Glenda M. Hallidayi, Lefkos T. Middletonj, Steve M. Gentlemank, Lea T. Grinbergb,l, and Kurt Gilesa,b Author Affiliations

 
aInstitute for Neurodegenerative Diseases, University of California, San Francisco, CA 94143; bDepartment of Neurology, University of California, San Francisco, CA 94143; cDepartment of Biochemistry and Biophysics, University of California, San Francisco, CA 94143; dC. S. Kubik Laboratory for Neuropathology, Department of Pathology, Massachusetts General Hospital, Boston, MA 02114; eDepartment of Pathology, University of California, San Francisco, CA 94143; fCenter for Neurobehavioral Genetics, Center for Autism Research and Treatment, and Department of Neurology, University of California, Los Angeles, CA 90095; gDepartment of Human Genetics, University of California, Los Angeles, CA 90095; hDepartment of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143; iSchool of Medical Science, Faculty of Medicine, University of New South Wales, and Neuroscience Research Australia, Randwick, NSW 2031, Australia; jAgeing Research Unit, School of Public Health, Imperial College London, London SW7 2AZ, United Kingdom; kCentre for Neuroinflammation and Neurodegeneration, Department of Medicine, Imperial College London, London SW7 2AZ, United Kingdom; lMemory and Aging Center, University of California, San Francisco, CA 94143 Contributed by Stanley B. Prusiner, July 22, 2015 (sent for review May 19, 2015)

 
Abstract

 
Authors & Info SI Metrics Related Content PDF PDF + SI

 
Significance Prions are proteins that assume alternate shapes that become self-propagating, and while some prions perform normal physiological functions, others cause disease. Prions were discovered while studying the cause of rare neurodegenerative diseases of animals and humans called scrapie and Creutzfeldt–Jakob disease, respectively. We report here the discovery of α-synuclein prions that cause a more common neurodegenerative disease in humans called multiple system atrophy (MSA). In contrast to MSA, brain extracts from Parkinson’s disease (PD) patients were not transmissible to genetically engineered cells or mice, although much evidence argues that PD is also caused by α-synuclein, suggesting that this strain (or variant) is different from those that cause MSA.

 
snip...

 
Abstract

 
Prions are proteins that adopt alternative conformations that become self-propagating; the PrPSc prion causes the rare human disorder Creutzfeldt–Jakob disease (CJD). We report here that multiple system atrophy (MSA) is caused by a different human prion composed of the α-synuclein protein. MSA is a slowly evolving disorder characterized by progressive loss of autonomic nervous system function and often signs of parkinsonism; the neuropathological hallmark of MSA is glial cytoplasmic inclusions consisting of filaments of α-synuclein. To determine whether human α-synuclein forms prions, we examined 14 human brain homogenates for transmission to cultured human embryonic kidney (HEK) cells expressing full-length, mutant human α-synuclein fused to yellow fluorescent protein (α-syn140*A53T–YFP) and TgM83+/− mice expressing α-synuclein (A53T). The TgM83+/− mice that were hemizygous for the mutant transgene did not develop spontaneous illness; in contrast, the TgM83+/+ mice that were homozygous developed neurological dysfunction. Brain extracts from 14 MSA cases all transmitted neurodegeneration to TgM83+/− mice after incubation periods of ∼120 d, which was accompanied by deposition of α-synuclein within neuronal cell bodies and axons. All of the MSA extracts also induced aggregation of α-syn*A53T–YFP in cultured cells, whereas none of six Parkinson’s disease (PD) extracts or a control sample did so. Our findings argue that MSA is caused by a unique strain of α-synuclein prions, which is different from the putative prions causing PD and from those causing spontaneous neurodegeneration in TgM83+/+ mice. Remarkably, α-synuclein is the first new human prion to be identified, to our knowledge, since the discovery a half century ago that CJD was transmissible.

 
neurodegeneration Parkinson's disease synucleinopathies strains

 
snip...

 
http://www.pnas.org/content/early/2015/08/27/1514475112.abstract

 
Transmission of multiple system atrophy prions to transgenic mice

 
Joel C. Wattsa,b, Kurt Gilesa,b, Abby Oehlerc, Lefkos Middletond, David T. Dextere, Steve M. Gentlemane, Stephen J. DeArmonda,c, and Stanley B. Prusinera,b,1 Author Affiliations

 
aInstitute for Neurodegenerative Diseases, and Departments of bNeurology and cPathology, University of California, San Francisco, CA 94143; and dAgeing Research Unit, School of Public Health and eCentre for Neuroinflammation and Neurodegeneration, Department of Medicine, Imperial College, London SW7 2AZ, United Kingdom Contributed by Stanley B. Prusiner, September 30, 2013 (sent for review August 21, 2013)

 
Abstract

 
Free Full Text Authors & Info Figures SI Metrics Related Content In This Issue PDF PDF + SI

 
Significance Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by the accumulation of misfolded α-synuclein protein in glial cells within the brain. Transgenic mice expressing mutant α-synuclein that were inoculated with brain homogenate from MSA patients developed clinical, biochemical, and pathological signs of a neurodegenerative disease, indicating that MSA is transmissible under certain conditions. This transmissibility is reminiscent of the human prion disorders, such as Creutzfeldt–Jakob disease, and suggests that MSA is caused by the accumulation of toxic α-synuclein prions in the brain.

 
Next Section

Abstract

Prions are proteins that adopt alternative conformations, which become self-propagating. Increasing evidence argues that prions feature in the synucleinopathies that include Parkinson’s disease, Lewy body dementia, and multiple system atrophy (MSA). Although TgM83+/+ mice homozygous for a mutant A53T α-synuclein transgene begin developing CNS dysfunction spontaneously at ∼10 mo of age, uninoculated TgM83+/− mice (hemizygous for the transgene) remain healthy. To determine whether MSA brains contain α-synuclein prions, we inoculated the TgM83+/− mice with brain homogenates from two pathologically confirmed MSA cases. Inoculated TgM83+/− mice developed progressive signs of neurologic disease with an incubation period of ∼100 d, whereas the same mice inoculated with brain homogenates from spontaneously ill TgM83+/+ mice developed neurologic dysfunction in ∼210 d. Brains of MSA-inoculated mice exhibited prominent astrocytic gliosis and microglial activation as well as widespread deposits of phosphorylated α-synuclein that were proteinase K sensitive, detergent insoluble, and formic acid extractable. Our results provide compelling evidence that α-synuclein aggregates formed in the brains of MSA patients are transmissible and, as such, are prions. The MSA prion represents a unique human pathogen that is lethal upon transmission to Tg mice and as such, is reminiscent of the prion causing kuru, which was transmitted to chimpanzees nearly 5 decades ago.

 
neurodegeneration bioluminescence imaging seeding proteinopathies

 
snip...

 
Discussion

 
In the studies reported here, we demonstrate that a fatal synucleinopathy can be initiated in Tg(M83+/−:Gfap-luc) mice that do not spontaneously develop a neurologic illness, by intracerebral inoculation with brain homogenate from MSA patients. These results parallel recent reports describing the induction of α-synuclein deposits and dopaminergic neuron loss, but not overt clinical signs of neurologic dysfunction, in non-Tg mice following inoculation with recombinant α-synuclein fibrils (25, 26). Our study reveals that self-propagating, transmissible α-synuclein aggregates (i.e., α-synuclein prions) are formed not just in Tg mice that overexpress mutant α-synuclein, but also in the brains of individuals with a degenerative synucleinopathy such as MSA.

 
Despite the predilection for oligodendrocytic deposition of α-synuclein in MSA, we did not observe appreciable levels of phosphorylated α-synuclein deposition in oligodendrocytes within the brains of MSA-inoculated bigenic mice. This observation suggests that additional human brain-specific factors may be responsible for encoding the oligodendrocyte-specific tropism of α-synuclein aggregates in MSA. However, a more simple explanation is that the heterologous Prnp promoter that drives mutant α-synuclein expression in TgM83 mice does not engender a native spatial pattern of α-synuclein expression. This difference may preclude deposition in mature oligodendrocytes, which do not express α-synuclein mRNA (31). Inoculation of Tg mice expressing A53T mutant human α-synuclein under the control of the SNCA promoter or even non-Tg mice with MSA brain homogenate may help to resolve this issue.

 
Although some investigators prefer to use alternate terms to describe the recently recognized “prion” proteins involved in PD, Alzheimer’s disease, and the tauopathies, the shared features of these protein-mediated degenerative diseases are becoming progressively more apparent. Some terms suggested to distinguish self-propagating Aβ, tau, and α-synuclein aggregates from those composed of PrP include “prion-like protein aggregates,” “transmissible proteins,” “templated proteins,” “prionoids,” “proteopathic seeds,” “misfolded proteins,” and “protein pathogens” (32, 33). However, we believe that α-synuclein aggregates fulfill all of the criteria for being labeled a prion. First, brain homogenates prepared from MSA patients or spontaneously ill TgM83+/+ mice containing abundant α-synuclein deposits induce the deposition of insoluble α-synuclein in the brains of recipient Tg(M83+/−:Gfap-luc) mice following intracerebral inoculation [Figs. 3 and 4 (23, 24)], demonstrating that α-synuclein aggregates, like PrPSc, are self-propagating. Second, intracerebral inoculation with samples containing pathological α-synuclein aggregates causes not only seeding of protein aggregation in the brain, but also the induction of clinical signs of neurologic dysfunction, indicative of true disease transmission [Table 1 (23, 24)]. Third, disease can be initiated by recombinant α-synuclein that had been polymerized into fibrils (24), indicating that α-synuclein aggregates, like PrP (34), are sufficient to induce disease. Fourth, transmission of a degenerative synucleinopathy can occur in animals that do not develop spontaneous illness within their normal lifespan [Figs. 1 and 2 (25, 26)], ruling out disease acceleration as a mechanism of transmission. Together, these data mount a compelling case for α-synuclein aggregates in the brains of MSA patients as being prions.

 
Although α-synuclein aggregates are clearly capable of behaving like prions at the molecular level, there is currently no evidence to suggest that MSA or the other human synucleinopathies are transmissible between humans, in contrast to CJD, which can be transmitted through the use of PrPSc-infected dura mater grafts or growth hormone preparations (35) as well as the reuse of PrPSc-contaminated neurosurgical instruments (36). It is currently unknown whether α-synuclein prions can attach to surgical instruments and to what extent they may persist following sterilization. Although attempts to transmit PD to monkeys by intracerebral inoculation were unsuccessful (37), our transmission data suggest that caution should be exercised when reusing neurosurgical instruments that have been previously used on suspected cases of MSA or PD to minimize any risk for iatrogenic transmission of the disease. Although deep brain stimulation is not commonly used to treat MSA patients, its increasingly wide use to control dyskinesias often found in many patients with advanced PD requires surgical implantation (38) and, as such, may represent a potential risk for human-to-human transmission of α-synuclein prions.

 
The rapid transmission of the MSA inocula, compared with TgM83+/+ samples, in Tg(M83+/−:Gfap-luc) mice was surprising for two reasons. First, the MSA samples do not harbor α-synuclein with the A53T mutation, which is present in the TgM83 line. For PrPSc prions, even a single amino acid mismatch between PrPSc in the inoculum and PrPC in the host can dramatically prolong the disease incubation period (39). Thus, there does not appear to be a substantial “transmission barrier” between the WT α-synuclein aggregates present in the MSA inocula and the A53T mutant α-synuclein present in the mice. Second, the levels of insoluble phosphorylated α-synuclein were much lower in the MSA brains than in the brains of the spontaneously ill TgM83+/+ mice used as inocula. This observation could suggest that the most infectious α-synuclein species may consist of smaller, more soluble assemblies, as has been observed for PrPSc and Aβ prions (40, 41). However, a more likely explanation for the rapid transmission of MSA prions is that these α-synuclein aggregates constitute a distinct “strain” of prion from the aggregates found in spontaneously ill TgM83+/+ mice. In prion disease, distinct strains are believed to result from conformational differences in PrPSc (42, 43). Indeed, conformationally distinct “strains” of recombinant α-synuclein aggregates that possess varying ability to initiate tau aggregation have recently been identified (44). Thus, the α-synuclein aggregates found within oligodendrocytes in the brains of MSA patients may be conformationally distinct from those found in the brains of TgM83+/+ mice, engendering distinct transmission properties. The rapid transmissibility of the MSA strain of α-synuclein prions may reflect the fact that the α-synuclein aggregates are not sequestered in Lewy bodies, which may constitute a protective mechanism to limit the spread of a distinct group of strains of α-synuclein prions in PD and DLB.

 
The successful transmission of MSA prions to Tg(M83+/−:Gfap-luc) mice described herein represents a unique human neurodegenerative disease that demonstrates lethality upon transmission to animals and is reminiscent of the transmission of kuru, CJD, and related diseases to nonhuman primates (45, 46). Although Aβ and tau prions derived from the brains of Alzheimer’s disease or tauopathy patients, respectively, stimulate prion formation as detected by protein aggregation and deposition upon inoculation into susceptible Tg mice, neither induces overt signs of neurologic disease nor lethality in the recipient animals (12, 47). Importantly, MSA-inoculated bigenic mice may comprise a reliable system for assessing the therapeutic efficacy of drugs designed to target the formation of α-synuclein prions.

 
http://www.pnas.org/content/110/48/19555.long

 
Multiple System Atrophy (MSA)

 
What is Multiple System Atrophy (MSA)?

 
Multiple system atrophy (MSA) is a rare neurodegenerative disease marked by a combination of symptoms affecting movement, blood pressure, and other body functions; hence the label "multiple system" atrophy. According to the American Autonomic Society, Multiple System Atrophy (MSA) is a sporadic, progressive, adult-onset disorder characterized by autonomic dysfunction, parkinsonism and ataxia (a failure of muscular coordination) in any combination.

 
Symptoms of MSA include:

 
Orthostatic hypotension,or a significant fall in blood pressure when standing, causing dizziness, lightheadedness, fainting, or blurred vision urinary difficulties or constipation motor control symptoms, including tremor, rigidity, and loss of muscle coordination, loss of balance male impotence (inability to achieve or maintain an erection) speech or swallowing difficulties Who gets MSA?

 
MSA affects both men and women primarily in their 50s.

 
What causes MSA?

 
Multiple system atrophy is associated with deterioration and shrinkage (atrophy) of portions of the brain (cerebellum, basal ganglia and brainstem) that regulate internal body functions, digestion and motor control.

 
There is no known cause for brain changes in MSA.

 
How is MSA diagnosed?

 
Diagnosis of MSA can be challenging because there is no test that can make or confirm the diagnosis in a living patient. Certain signs and symptoms of MSA also occur with other disorders, such as Parkinson's disease, making the diagnosis more difficult.

 
If your doctor suspects multiple system atrophy, he or she will obtain a medical history and perform a physical examination. You may receive a referral to a neurologist or other specialist for specific evaluations that can help in making the diagnosis.

 
Tests that may be helpful in making a diagnosis include:

 
Tilt table test - In this procedure, your blood pressure is monitored while you are on a special table that will tilt you to an almost upright position. This allows the physician to record blood pressure irregularities, and information about whether they occur with a change in physical position. Blood tests A sweat test to evaluate perspiration Tests to assess your bladder and bowel function Electrocardiogram to track the electrical signals of your heart Brain-imaging tests, particularly a magnetic resonance imaging (MRI) scan, to determine if another condition might be triggering symptoms Pharmacological challenge tests (administering certain medications and observing the patient’s body’s reaction to them, in controlled clinical settings) For patients with sleep irregularities, particularly if they involve interrupted breathing or snoring, physicians may recommend an evaluation in a sleep laboratory to determine if there is an underlying and treatable sleep disorder, such as sleep apnea.

 
What is the treatment for MSA?

 
There is no known cure for MSA, so management of the disease focuses on treating the more disabling symptoms listed above.

 
A clinical trial of the drug Rifampicin is being conducted by the Autonomic Disorders Consortium.

 
http://www.rarediseasesnetwork.org/ARDCRC/patients/learnmore/MSA/index.htm

 
Tuesday, November 26, 2013

Transmission of multiple system atrophy prions to transgenic mice

http://proteinopathies.blogspot.com/2013/11/transmission-of-multiple-system-atrophy.html

 
Self-Propagative Replication of Ab Oligomers Suggests Potential Transmissibility in Alzheimer Disease

 
Received July 24, 2014; Accepted September 16, 2014; Published November 3, 2014

 
http://www.plosone.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0111492&representation=PDF

 
Singeltary comment ;

 
http://www.plosone.org/annotation/listThread.action?root=82860

 
Saturday, March 21, 2015

 
*** Canada and United States Creutzfeldt Jakob TSE Prion Disease Incidence Rates Increasing

 
http://creutzfeldt-jakob-disease.blogspot.com/2015/03/canada-and-united-states-creutzfeldt.html

 
*** HUMAN MAD COW DISEASE nvCJD TEXAS CASE NOT LINKED TO EUROPEAN TRAVEL CDC ***

 
Sunday, November 23, 2014

 
*** Confirmed Variant Creutzfeldt-Jakob Disease (variant CJD) Case in Texas in June 2014 confirmed as USA case NOT European ***

 
the patient had resided in Kuwait, Russia and Lebanon. The completed investigation did not support the patient's having had extended travel to European countries, including the United Kingdom, or travel to Saudi Arabia. The specific overseas country where this patient’s infection occurred is less clear largely because the investigation did not definitely link him to a country where other known vCJD cases likely had been infected.

 
http://vcjd.blogspot.com/2014/11/confirmed-variant-creutzfeldt-jakob.html

 
Sunday, December 14, 2014

 
*** ALERT new variant Creutzfeldt Jakob Disease nvCJD or vCJD, sporadic CJD strains, TSE prion aka Mad Cow Disease United States of America Update December 14, 2014 Report ***

 
http://transmissiblespongiformencephalopathy.blogspot.com/2014/12/alert-new-variant-creutzfeldt-jakob.html

 
Thursday, July 30, 2015

 
Professor Lacey believes sporadic CJD itself originates from a cattle infection number of cattle farmers falling victim to Creutzfeld-Jakob Disease is much too high to be mere chance

 
http://creutzfeldt-jakob-disease.blogspot.com/2015/07/professor-lacey-believes-sporadic-cjd.html

 
Tuesday, August 4, 2015

 
FDA U.S. Measures to Protect Against BSE

 
http://bseusa.blogspot.com/2015/08/fda-us-measures-to-protect-against-bse.html

 
PRION 2015 CONFERENCE FT. COLLINS CWD RISK FACTORS TO HUMANS

 

*** LATE-BREAKING ABSTRACTS PRION 2015 CONFERENCE ***

 

O18

 

Zoonotic Potential of CWD Prions

 

Liuting Qing1, Ignazio Cali1,2, Jue Yuan1, Shenghai Huang3, Diane Kofskey1, Pierluigi Gambetti1, Wenquan Zou1, Qingzhong Kong1 1Case Western Reserve University, Cleveland, Ohio, USA, 2Second University of Naples, Naples, Italy, 3Encore Health Resources, Houston, Texas, USA

 

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

 

***These results indicate that the CWD prion has the potential to infect human CNS and peripheral lymphoid tissues and that there might be asymptomatic human carriers of CWD infection.***

 

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

 

P.105: RT-QuIC models trans-species prion transmission

 

Kristen Davenport, Davin Henderson, Candace Mathiason, and Edward Hoover Prion Research Center; Colorado State University; Fort Collins, CO USA

 

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

 

***This insinuates that, at the level of protein:protein interactions, the barrier preventing transmission of CWD to humans is less robust than previously estimated.***

 

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

 


 

From: Terry S. Singeltary Sr.

 

Sent: Saturday, November 15, 2014 9:29 PM

 

To: Terry S. Singeltary Sr.

 

Subject: THE EPIDEMIOLOGY OF CREUTZFELDT-JAKOB DISEASE R. G. WILL 1984

 

THE EPIDEMIOLOGY OF CREUTZFELDT-JAKOB DISEASE

 

R. G. WILL

 

1984

 

*** The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04). (SEE LINK IN REPORT HERE...TSS) PLUS, THE CDC DID NOT PUT THIS WARNING OUT FOR THE WELL BEING OF THE DEER AND ELK ;

 

snip...

 


 

*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).***

 


 

*** The potential impact of prion diseases on human health was greatly magnified by the recognition that interspecies transfer of BSE to humans by beef ingestion resulted in vCJD. While changes in animal feed constituents and slaughter practices appear to have curtailed vCJD, there is concern that CWD of free-ranging deer and elk in the U.S. might also cross the species barrier. Thus, consuming venison could be a source of human prion disease. Whether BSE and CWD represent interspecies scrapie transfer or are newly arisen prion diseases is unknown. Therefore, the possibility of transmission of prion disease through other food animals cannot be ruled out. There is evidence that vCJD can be transmitted through blood transfusion. There is likely a pool of unknown size of asymptomatic individuals infected with vCJD, and there may be asymptomatic individuals infected with the CWD equivalent. These circumstances represent a potential threat to blood, blood products, and plasma supplies.

 


 

Tuesday, May 26, 2015

 

*** Minimise transmission risk of CJD and vCJD in healthcare settings ***

 

Last updated 15 May 2015

 


 

Monday, August 17, 2015

 

FDA Says Endoscope Makers Failed to Report Superbug Problems OLYMPUS

 

I told Olympus 15 years ago about these risk factors from endoscopy equipment, disinfection, even spoke with the Doctor at Olympus, this was back in 1999. I tried to tell them that they were exposing patients to dangerous pathogens such as the CJD TSE prion, because they could not properly clean them. even presented my concern to a peer review journal GUT, that was going to publish, but then it was pulled by Professor Michael Farthing et al... see ;

 


 

 *** now, from all the consumption and exposure above, now think iatrogenic cjd tse prion at a hospital near you, what if?

 

Thursday, August 13, 2015

 

Iatrogenic CJD due to pituitary-derived growth hormone with genetically determined incubation times of up to 40 years

 


 

Saturday, December 13, 2014

 

*** Terry S. Singeltary Sr. Publications TSE prion disease Peer Review ***

 

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

 

Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA

 

snip...

 


 

Terry S. Singeltary Sr.

 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 


 

 

iatrogenic, what if ???
Posted by at No comments:

Friday, August 21, 2015

Porcine prion protein amyloid or mad pig disease PSE Porcine Spongiform Encephalopathy ?

Prion

 

Volume 9, Issue 4, 2015

 

Porcine prion protein amyloid

 

DOI:10.1080/19336896.2015.1065373Per Hammarströma & Sofie Nyströma*

 

pages 266-277

 

Received: 1 Jun 2015 Accepted: 17 Jun 2015 Accepted author version posted online: 28 Jul 2015

 

© 2015 The Author(s). Published with license by Taylor & Francis Group, LLC Additional license information

 

 ABSTRACT

 

 Mammalian prions are composed of misfolded aggregated prion protein (PrP) with amyloid-like features. Prions are zoonotic disease agents that infect a wide variety of mammalian species including humans. Mammals and by-products thereof which are frequently encountered in daily life are most important for human health. It is established that bovine prions (BSE) can infect humans while there is no such evidence for any other prion susceptible species in the human food chain (sheep, goat, elk, deer) and largely prion resistant species (pig) or susceptible and resistant pets (cat and dogs, respectively). PrPs from these species have been characterized using biochemistry, biophysics and neurobiology. Recently we studied PrPs from several mammals in vitro and found evidence for generic amyloidogenicity as well as cross-seeding fibril formation activity of all PrPs on the human PrP sequence regardless if the original species was resistant or susceptible to prion disease. Porcine PrP amyloidogenicity was among the studied. Experimentally inoculated pigs as well as transgenic mouse lines overexpressing porcine PrP have, in the past, been used to investigate the possibility of prion transmission in pigs. The pig is a species with extraordinarily wide use within human daily life with over a billion pigs harvested for human consumption each year. Here we discuss the possibility that the largely prion disease resistant pig can be a clinically silent carrier of replicating prions.

 

SNIP...

 

CONCLUDING REMARKS Should the topic of porcine PrP amyloid be more of a worry than of mere academic interest? Well perhaps. Prions are particularly insidious pathogens. A recent outbreak of peripheral neuropathy in human, suggests that exposure to aerosolized porcine brain is deleterious for human health.43,44 Aerosolization is a known vector for prions at least under experimental conditions.45-47 where a mere single exposure was enough for transmission in transgenic mice. HuPrP is seedable with BoPrP seeds and even more so with PoPrP seed (Fig. 1), indicating that humans could be infected by porcine APrP prions while neurotoxicity associated with spongiform encephalopathy if such a disease existed is even less clear. Importantly transgenic mice over-expressing PoPrP are susceptible to BSE and BSE passaged through domestic pigs implicating that efficient downstream neurotoxicity pathways in the mouse, a susceptible host for prion disease neurotoxicity is augmenting the TSE phenotype.25,26 Prions in silent carrier hosts can be infectious to a third species. Data from Collinge and coworkers.21 propose that species considered to be prion free may be carriers of replicating prions. Especially this may be of concern for promiscuous prion strains such as BSE.19,48 It is rather established that prions can exist in both replicating and neurotoxic conformations.49,50 and this can alter the way in which new host organisms can react upon cross-species transmission.51 The na€ıve host can either be totally resistant to prion infection as well as remain non-infectious, become a silent non-symptomatic but infectious carrier of disease or be afflicted by disease with short or long incubation time. The host can harbor and/or propagate the donor strain or convert the strain conformation to adapt it to the na€ıve host species. The latter would facilitate infection and shorten the incubation time in a consecutive event of intra-species transmission. It may be advisable to avoid procedures and exposure without proper biosafety precautions as the knowledge of silence carrier species is poor. One case of iatrogenic CJD in recipient of porcine dura mater graft has been reported in the literature.52 The significance of this finding is still unknown. The low public awareness in this matter is exemplified by the practice of using proteolytic peptide mixtures prepared from porcine brains (Cerebrolysin) as a nootropic drug. While Cerebrolysin may be beneficial for treatment of severe diseases such as vascular dementia,53 a long term follow-up of such a product for recreational use is recommended.

 


 

The case for mad pigs in the US

 

From the Consumer Policy Institute and Consumers Union: March 24, 1997

 

Stephen F. Sundlof, D.V.M., Ph.D

 

Center for Veterinary Medicine Food and Drug Administration 7500 Standish Place, Room 482, HFV 1 RockvLIle, MD 20855

 

Dear Dr. Sundlof:

 

We are writing to you to submit information that has recently come to our attention which suggests that a TSE like disease (transmissible spongiform encephalopathy) might exist in pigs in the U.S. We believe this new informantion calls for intensive research and makes it urgent to ban the use of all mammalian proteins, including swine, in the feed of all food animals, until better answers are found.

 

The evidence for the potential PSE (porcine spongiform encephalopathy ) is as follows. In 1979, an FSQS veternarian, Dr. Masuo Doi, noticed some unusual central nervous system (CNS) symptoms in young (about 6 months old) hogs coming into a slaughter plant In Albany, New York. Since the plant received hogs from a wide variety of sources (New York, Canada, Indiana, Illinois, Ohio, and other Midwestern states) and was not a plant used to dealing with diseased animals, Dr. Doi thought that the problem might be affecting hogs slaughtered nationwide. So, he decided to conduct a detailed study on central nervous system (CNS) symptoms/disease in young hogs coming into that slaughter plant. The study ran for 15 months (January, 1979 to March, 1980) and consisted of extended observations of the behavior of animals with suspected CNS symptoms at the plant, followed by pathological, histopatholpgical, and microbiological work on tissues from various organs of particular animals after slaughter.

 

For his behavioral observational work, Dr. Doi extended the usual two day observation period to three to four days, during which he took careful notes on the animals' behavior and other vital signs. During the 15 month period of the study, some 106 animals exhibiting CNS symptoms were retained during antemortem inspection.

 

A 1980 paper that summarized Dr. Doi's findings on the clinical symptoms and incidence of the 'disease," contained descriptions of these symptoms that sound remarkably similar to the symptoms noted for bovine spongiform encephalopathy (BSE):

 

"Excitable or nervous temperament to external stimuli such as touch to the skin, handling and menacing approach to the animals is a common characteristic sign among swine affected with the disease.... In the advanced stage of the disease, manifestation of neurological signs are evidenced in the form of general ataxia . . . Many animals have been found to be "downers' at first observation; if the hindquarters of these downers are raised they may be able to walk one or two steps and then fall to the ground" (Doi et al., 1980: 2, 4). Indeed, a table of symptoms includes, for the early stage: "excitability and nervousness (squealing, smacking of lips, grinding of teath, chewing, gnawing ant foaming at mouth); stiffness of limbs . . . 'tic'; weakness of hindquarters; focal tremors of skeletal muscles"; and for the advanced stage: depression; ataxia; crossing over of limbs . . . kneeling posture . . . crawling". In addition to his clinical observations, Dr. Doi also made an 8 mm film of thirteen of the affected animals; film of two of the pigs was shown at the MPI National Pathology Meeting in Seattle, Washington on flay 20, 1979.

 

Dr. Doi sent tissue samples from suspect cases to the USDA's Eastern Laboratory in Athens, GA for pathological, histopathogical and microbiological work. Known infectious diseases were ruled out. As Dr. Doi points out, "Histopathological studies of tissue collected from the brain and spinal cord of these animals in the early stage of the disease show congestion, hemorrhage and neuronal degeneration. All animals in the advanced stage of the disease have been confined to have Encephalitis or Meningitis by MPI laboratory" (Doi et al., 1980: 5). Eventually some 60 animals were confirmed by the MPI Laboratory to have encephalitis or meningitis, with no ldentifiable cause. As pointed out in a paper presented at the 1979 MPI National Pathology Meetings,

 

"Since January, a number of hogs in this establishment have been found, in antemortem, to show what appears to be CNS. Sets of tissue samples were sent to the laboratory for examination, various tests were done which include histological study (E H stain), fluorescence antibody technique, virus neutralization and viral and bacteriological isolation. Differential diagnosis was also done to exclude vitamin B deficiency, post vaccination reaction, chlorinated hydrocarbon, arthritis, and transport stress" (Doi et al., 1979). The brains of the 60 animals were examined. The brain of one of these pigs, on histopathological analysis, exhibited signs reminiscent of a TSE. This histopathological work was performed by Dr. Karl Langheinrich, Pathologist-In-Charge at USDA's Eastern Laboratory in Athens, Georgia. According to the USDA FSQS laboratory report, dated early November, 1979, Dr. Langheinrich noted:

 

"Microscopic examination of the barrow tissues revealed a encephalopathy and diffuse gliosis characterized by vacuolated neurons, loss of neurons and gliosis in a confined region (nucleus) of the brain stem (anterior ventral midbrain). Only an empty sometimes divided vacuole was present instead of the normal morphology of a nerve cell. Occasionally a shriveled neuron was seen. According to . . . Pathology of Domestic Animals, . . . 'The degeneration of neurons, the reactivity of the glia .... are the classical hallmarks of viral infection of the central nervous system' .... Scrapie of sheep, and encephalopathy of mink, according to the literature, all produce focal vacuolation of the neurons similar to the kind as described for this pig. I was unable to locate any lead as to the cause of this interesting phenomenon in other species including swine'' (Langheinrich, 1979). Indeed, Dr. Langheinrich's main diagnosis was, " Encephalopathy and diffuse gliosis of undetermined etiology." Portions of the brain were sent for microbiological testing to a neurologist at the University of Georgia, where they came up negative for pseudo-rabies. The brain was unique enough that USDA scientists, such as Dr. Langheinrich and Or. Dot, mentioned it to student and scientific colleagues over the years.

 

In 1979-1980, BSE was completely unknown. However, both the behavior of the pigs, as well as the histopathology on at least one pig, both showed sign consistent with a porcine TSE. This raises particular concern became the affected animal was only 6 months old; in an animal this young, one would rust expect to see any physical signs of TSE in the brain. Histopathology of TSEs can be very variable, so that spongiform appearance (i.e. vacuolated neurons) are not always present. Behavioral changes can be seen in TSE-infected animals before any changes in brain morphology are visible. Dr. Clarence Gibbs, in testimony before a Congressional hearing on the TSE issue on January 29, 1997 made just this point:

 

''In the mid-1960s, we demonstrated with our French and English collaborators that during the early incubation of the TSEs, when the virus titer in the brain was very low, there were already marked functional changes, even though no pathology was yet detectable, even ultrastructurally. A month or hero later, polynucleation of neurons appeared in spider monkeys, incubating kuru, and somewhat later, microvacuolation and membrane changes visible only by electron microscopy. This preceded the pest appearance of astrogliosis and spongiform change. It was only much later that the classical scrapie TSE pathology appeared with virus titers in brain of 10 -5 or higher" (Gibbs, 1997; pg. 4). Given that TSEs can cause behavioral changes in infected animals before any physical changes in the brain can be seen, that the manifestation of TSE in the brain can be quite variable, and that changes in brain morphology are not usually seen in 6 month old animals, we are concerned that the brain of one pig actually showed physical evidence consistent with a TSE.

 

Following the announcement In March, 1996 of ten cases of new variant CJD (Creutzfeldt-Jakob Disease) in the United Kingdom and their possible connection to BSE, Drs. Doi, Langheinrich and others urged reinvestigation of this case.

 

In August, 1996, the USDA sent five slides, one of which was a histopathology slide, to Dr. Janice Miller of USDA's Agricultural Research Servicer . Dr. Miller stained four of the slides for prion protein (she didn't stain the H&E slide). Dr. Miller told Consumers Union that Dr. Patrick McCaskey, USDA/FSIS, in charge of the Research Center at Athens, GA, called her, told her that he had five slides that all showed "problems" and asked her to stain four of them. The H&E slide, which clearly show vacuoles in the neurons (one sign of TSE), wasn't stained because to stain for PrP entails removing the slide cover, baking the slide to destain it and then restaining it for PrP; they didn't want to risk destroying the H&E slide.

 

Dr. Doi had kept frozen samples of the brain and spinal chord of the suspect PSE pig in case the Eastern lab wanted more material for analysis. Unfortunately, these samples were discarded when the packing plant in Albany, NY closed in 1991. It appears that the brain material sent to the Univcrsity of Georgia may have been discarded. [pers com.. Dr. Doi 3/13/97]

 

Dr. Miller found that the PrP stained in the four pig slides was found only on the inside of neurons, while a positive control slide from a scrapie sheep showed massive amounts of extraneuronal staining. In a letter summarizing her results (copy attached), she concludes that the PrP stained in this pig was normal: "In the pig sections you will see a small particulate type of staining that is confined to neurons and as I indicated on the phone, I would interpret as normal PrP. It is in marked contrast to the massive amount of extraneuronal staining seen in the scrapie section" (Miller, 1996).

 

Unfortunately, Dr. Miller's finding toes not conclusively rule out a TSE. We are concerned that while British BSE and serapie create a massive amount of extraneuronal staining, there are TSEs where this isn't the case. Three experiments were done in He U.S. -- in Mission, TX (APHIS work), Pullman, Washington (ARS work), and Ames, Iowa (ARS work) -- to see whether sheep scrapie can possibly infect cows. In all the experiments, cattle were inoculated with tissue from scrapie -infected sheep primarily by intra-cranial injection, but in the case of the Texas and Iowa studies also by oral feeding -- to see if cattle were susceptible to scrapie at all. In all three experiments, the majority of cows injected in the brain with scrapie-infected sheep material (usually brains) also developed a fatal spongiform encephalopathy.

 

However, in all three examples, the symptoms of the spongifonn encephalopathy differed from "mad cow" disease ~ England, as did the appearances of slides from their brains. The brain lesions seen in ail these animals were more variable than those seen in England. When Dr. Miller did similar staining for PrP from these brains (what she called "bovine scrapie") she only found PrP stains on the inside of the neurons, not the massive extraneuronal staining seen in BSE (Miller, pers. comm., March 7, 1997). Thus, Dr. Miller's finding of PrP stains only inside the neurons in the suspect pigs is not particularly reassuring.

 

In November 1996, USDA sent the single histopathology slide to Dr. William Hadlow, one of the foremost spongiform encephalopathy pathologists in the world. (For unknown reasons, Dr. Hadlow was only sent the one slide; he was not told of the existence of the other slides, nor of Dr. Miller's findings, nor was he told or given the behavioral report from Dr. Doi or the morphology work by Dr. Langheinrich, or shown film of the affected pigs [Dr. Hadlow, pers. com., 3/13/97] From this single slide, Dr. Hadlow found some evidence consistent with TSEs but not enough for a conclusive diagnosis. He noted that the slide contained vacuoles inside neurons, one of the signs of a TSE (Dr. Langheinrich had noted this as well).

 

However, since such vacuoles occasionally occur normally in pigs, he thought that was not something special: "About twelve (12) neurons in the parasympathetic nucleus have unilocular optically empty vacuoles in the perikaryon. This is the site where such vacuolated neurons have been seen in the swine (as well as in cats and sheep) as an incidental finding. So I do not think such cells have any significance in this pig" (Hadlow, 1996). However, he did see evidence, Including changes in astrocytes, that suggested a TSE, but without examining other parts of the brain to look for other evidence of TSE, he couldn't be sure:

 

"I am impressed, though, with what seems to be an increase in the number of astrocytes in the section. Some astrocytes are in clusters, some are enlarged and vesicular. Where they are most numerous, a few rod cells (activated microglia) are seen. These findings suggest some perturbation of the nervous tissue. Although such a global response occurs in the transmissible spongifonn encephalopathies, I do no! know its significance in this case without examining other parts of the brain for changes characteristic of these diseases. Thus, from looking; at this one (1) section of brain, I cannot conclude that the pig was affected with a scrapie-like spongiform encephalopathy" (Hadlow, 1996). In sum, Dr. Hadlow~s letter does not rule out the possibility of a TSE. He says that there is suggestive evidence, but that he would need to look at other slides/sections of the brain, to make a conclusive diagnosis.

 

In our view, the implications of this data are extremely serious. Experiments in the United Kingdom have shown that pigs are susceptible to BSE. Pigs inoculated with BSE develop a TSE (Dawson et al., 1990). Feeding experiments are underway in the UK to see if BSE can be orally transmitted to pigs; as of March, 1997, some 6 years after the start of the experiment, none of the pigs fed BSE brain have come down with a TSE. Unfortunately the design of this experiment severely limits what we will learn from it, and will most likely not tell us conclusively if pigs can get BSE from feed. It turns out that the pigs were not fed BSE brain continuously. Rather, the pigs were only fed BSE brain material on three days, over a three week period (i.e.. one day each week). Following these three doses, the pigs were never fed contaminated material again. The total amount of infective material given to the pigs was therefore quite small. Thus, a negative finding would be hard to interpret and would not mean that BSE is not orally active in pigs.

 

We believe that as a top priority USDA should conduct follow-up studies to look for potential CNS/PSE cases in pigs (we plan to communicate about this to USDA separately). In brief, we feel that the following kinds of studies need to be done:

 

i) TSE pathology experts should examine all the slides from the suspect pig (2709). To our knowledge, at least 12 separate slides exist.

 

ii) Determine if any brain material from the suspect pig (2709) still exists at the Unlverslty of Georgia. If so, this material should be retrieved and used for transmission studies. In particular, suckling pigs should be inoculated with the material and then permitted to live unto they die of a disease or old age, at which point their brains should be examined for physical signs of a TSE as well as for immunchistochemical evidence (i.e. staining looking for the abnormal PrP).

 

iii) Increase antemortem inspection for CNS symptoms at hog facilities. Inspectors should be trained to detect the subtle CNS symptoms seen in the Doi et al. study. At a select number of slaughter facilities, animals exhibiting CNS symptoms should be removed and held for observation until they die, at which time their brains should be examined for evidence of a TSE.

 

iv) Research on CNS symptoms among Me 6,000 or so breeding sows which are permitted to live for 3+ years. Sows exhibiting CNS symptoms should be removed and held for observation until they die, at which time then brains should be exernined for evidence of a TSE.

 

While such work is underway, given the above inforrnabon, we believe that as a precutionary measure the FDA must expand the proposed ruminant plus mink-to-ruminnant feed ban to prevent protein from any material, including hogs, being fed to any food animal.

 

Sincerely,

 

Michael Hansen, Ph.D Research Associate

 

Jean Halloran Director

 

References

 

Dawson, M., Wells, G.A.H., Parker, B.N;J. and A.C Scott. 1990. Primary parental transmission of bovine spongiform encephalopathy to the pig. Veternary Record, pg. 338.

 

Doi, M., Matzner, N.D. and C. Rothaug. 1979. Observation of CNS disease in market hogs at Est. 893 Tobin Packing Co., Inc. Albany, New York. United States Department of Agriculture, Food Safety and Quality.Service, Meat and Poultry Inspection Service. 7pp.

 

Doi, M, Langheinrich, K. and F. Rellosa. 1980. Observations of CNS signs in hogs at Est. 893 Tobin Packing C:o., Inc. Presented by Dr. Lngheinrich at the MPI National Pathology Meeting in Seattle, Washington on July 20, 1979.

 

Gibbs, C. 1997. Statement to the Committee on Governnent Reform and Oversight, Subcommittee on Human Resources and Intergovernmental Relations, U.S. House of Representatives. January 29,1997.

 

Hadlow, WJ. 1996. Letter to Patrick McCaskey, USDA/FSIS/Eastem Lab, dated November 13, 1996.

 

Langheinrich, KA. 1979. USDA/FSQS Laboratory report on specimen 2709. Dated November 8, 1979

 

Miller, J. 1996. Letter to Patrick McCaskey, USDA/ESIS/Eastern Lab, dated September 6, 1996.

 

Dr. Janice Miller, ARS< USDA responds Mon, 31 Mar 1997 Correspondence My involvement in the "pig incident" (I refuse to say "mad pig disease" since no such disease has been recognized):

 

I was asked by Dr. Al Jenny at the National Veterinary Services Laboratory if I had ever done immunohistochemistry on slides that had already been stained by hematoxylin and eosin, the standard stain used for histopathology. I had done it on a few scrapie cases so he asked if I would do the procedure on some pig brain slides that he had received from Dr. Pat McCaskey, an FSIS pathologist in Athens, GA.

 

At the time I didn't know the history of the situation but Dr. Jenny said I should call Dr. McCaskey and discuss it with him before proceeding. Only then did I learn a little about the history of the case. We decided that I wouldn't try to stain all of the slides because I was afraid the procedure required to remove the cover slips might damage the sections and Dr. McCaskey was concerned about preserving the sections for other pathology consultations, if necessary.

 

We agreed that I would stain 4 of the 5 slides, leaving the slide with the best lesions untouched. I was also concerned that I didn't know whether the antiserum we use would stain pig PrP but decided it was worth a try. When I completed the staining procedure the only positive material I observed was a small amount of particulate staining within the cell body of some neurons. We have occasionally observed that kind of staining in brains from control cattle and sheep in our experiments and interpret it to be normal PrP. (A similar finding was reported by Dr. Haritani, who first described the technique for BSE).

 

That observation was reported in our 1994 paper and we stated that consequently we could not interpret intraneuronal staining as indicative of scrapie (although it may be present, the bulk of staining is in neuropil, around vessels and neurons, etc). In that study I think our interpretation was somewhat validated by the very close correlation we had between immunohistochemistry and western blot results. At any rate, I told Dr. McCaskey that my interpretation on the slides was that the only staining present was consistent with normal PrP. The good news was that the antiserum did in fact stain something and that it was in the correct location for normal PrP, indicating that the antiserum would have detected abnormal PrP, had it been present. Subsequently, I called Dr. Richard Rubenstein, who provided the antibody we use, and asked if he knew whether it would react with pig PrP and he said he didn't know. However, he said it reacted with almost all mammalian species, except ferret and mink, that he had tried so he would be surprised if it wasn't reactive with pig PrP.

 

So, having all of this information at hand, people can decide whether the immunohistochemical test means anything or not. The lack of a positive control pig tissue (positive sheep tissue is included in every test) may be viewed by some people as diminishing the value of a negative result, but feel we did the best we could under the circumstances.

 

The above recitation describes my experience with the case in question. I did not photograph the slides and returned all 5 to Dr. McCaskey. It was later that he had Dr. Hadlow look at the case for histopathologic interpretation. I did not examine the slides for that purpose because I do not have experience in scrapie diagnosis and would not consider my observations meaningful.

 

I appreciated the additional information about the original study done by Dr. Doi. Although I've heard bits and pieces of the story from different people, this was the first time I had heard that 60 of the pigs were diagnosed as having encephalitis or meningitis. I think that fact, plus the fact that the pigs were only about 6 months old, should certainly indicate that it's highly unlikey that a spongiform encephalopathy epidemic was causing the CNS signs observed. Whether the 1 pig with the questionable encephalopathy lesions was a TSE could be debated, I suppose. The age would seem to argue against it and the immunohistochemistry result would also (at least that's my opinion).

 

We disagree about the implications of age regarding the liklihood of TSE in a 6-month old pig. Certainly dose has an effect on incubation period in experimental transmissions and probably also in the "natural" acquired transmissions. However, regardless of the manner of transmission, I don't know of any first passage experimental interspecies transmission where the incubation period was as short as 6 months.

 

Early onset in mice were achieved only after adaptation through at least 1 intraspecies transfer. I believe the same is true for development of the hamster models. With regard to acquired transmissions, Linda Detwiler's review on scrapie cites research that indicated infectivity was found in CNS tissues of lambs as early as 4 months of age: however, they were not showing clinical signs. From what I can find in the literature, a clinical case of scrapie under 2 years of age would be exceptional, but with the amount of material published on that disease I wouldn't want to say it hasn't happened.

 

With TME the shortest incubation I've seen reported was 9 months. Elizabeth Williams has indicated that the youngest case of CWD observed in their wildlife facilities was 18 months old. You stated that in England calves were getting BSE by one year. In the experimental BSE transmissions cattle didn't develop clinical signs until the second year of observation and the earlest sign we observed in cattle inoculated with sheep scrapie was 14 months.

 

With respect to swine, the only model we have is the experimental transmission of BSE. The animal first developed signs about 17 months after inoculation. I think that it would be highly unlikely for a 6 month old pig to be showing CLINICAL signs of a TSE (the claim in this particular situation). One can never say never but it seems reasonable to at least examine what is known and make an educated estimate about what is likely.

 

A case-control study of CJD. Dietary risk factors. Am J Epidemiol 122 (3): 443-451 (1985) Davanipour Z, Alter M, Sobel E, Asher DM, Gajdusek DC The mode of natural transmission of Creutzfeldt-Jakob disease remains unknown. In a case-control study conducted in 1981-1983 to evaluate possible dietary and other sources of the disease, 26 cases were ascertained in the mid-Atlantic region of the United States, 23 of which were obtained from accumulated records of the Laboratory of Central Nervous System Studies of the National Institutes of Health. Controls included 18 family members and 22 hospital-matched individuals (total sample size, 66). An increased consumption among patients was found for roast pork, ham, hot dogs (p less than 0.05), roast lamb, pork chops, smoked pork, and scrapple (p less than 0.1). An excess consumption of rare meat (p less than 0.01) and raw oysters/clams (p less than 0.1) was also reported among the patients. Liver consumption, among organ foods, was greater (p less than 0.1) among the cases. If Creutzfeldt-Jakob disease is acquired through ingestion of foods containing the agent, then the food items identified may be among those which need to be evaluated more intensively. Larger case-control studies with more focused dietary questions are warranted.

 

Sundlof can't comment From: Dr. Stephen Sundlof D.V.M., Ph.D. Director, Center for Veterinary Medicine Food and Drug Administration :

 

At the present time FDA is in the process of developing a final rule which will regulate the feeding of certain animal-derived protein to other animals. In addition to studying the scientific literature pertaining to TSE's, we have received 700 comments relating the proposed rule that was published in the Federal Register on January 3, 1977. The information provided by Dr. Hansen and others will be considered in developing the final rule along with all of the other information and comments that have been officially submitted to FDA. Until the final rule is published, FDA is prohibited from commenting on information that might impact the final rule. Therefore, I am unable to respond to the documents in Dr. Hansen's letter.

 

I do not have access to the photomicrographs of the histopathology slides, and I was unaware of their existance until Dr. Hansen brought the issue to my attention. Furthermore, I do not have addresses or telephone numbers for Drs. Doi. Langheinrich, or Hadlow. Someone from the USDA would have this information but I am not sure who that would be.

 

Webmaster had written: " Do photomicrographs of any of the 12 slides exist? If you have any of them, I would like to scan a few of these and post them at high resolution on the internet so that pathologists world-wide could view and comment on them.

 

Primary parenteral transmission of bovine spongiform encephalopathy to the pig. Veterinary Record 1990 127 13 338 Dawson, M.; Wells, G. A. H.; Parker, B. N. J.; Scott, A. C. Ten, weaned one- to two-week old piglets from a specific pathogen free breeding herd were inoculated under halothane anaesthesia by simultaneous injections intracerebrally (0.5 ml) intravenously (1 to 2 ml) and intraperitoneally (8 to 9 ml) with an inoculum consisting of 10% saline suspension of pooled homogenised brainstem from 4 natural bovine spongiform encephalopathy cases. Control piglets were similarly inoculated with saline. After 69 weeks one challenged pig showed mild aggressive behaviour towards the animal attendants. Intermittent inappetence and depression were also noted. Within one week the behavioural changes included aimless biting activity and there was mild symmetrical ataxia. The ataxia progressed and 5 weeks after onset of signs the gait ataxia was generalised with hypermetria and wide-based stance. At this time the pig was killed. Histopathological examination of the brain revealed spongiosis of grey matter neuropil with greatest intensity in the medial geniculate body, superior colliculus and corpus striatum. There was sparse vacuolation of neuronal perikarya in the dorsal nucleus of the vagina nerve and widespread astrocytic reaction. Characteristic fibrils associated with transmissible spongiform encephalopathies were detected by electron microscopy.

 

One good question is what _pooled_ medical products do they make from pigs. The key issues for spread of this disease are the amplification cycle and distribution pooling. That is, one rotten apple by itself is less of a problem than if it is in a barrel. – webmaster

 


 

IN CONFIDENCE

 

EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY 1. CMO should be aware that a pig inoculated experimentally (ic, iv, and ip) with BSE brain suspension has after 15 months developed an illness, now confirmed as a spongiform encephalopathy. This is the first ever description of such a disease in a pig, although it seems there ar no previous attempts at experimental inoculation with animal material. The Southwood group had thought igs would not be susceptible. Most pigs are slaughtered when a few weeks old but there have been no reports of relevant neurological illness in breeding sows or other elderly pigs.

 

...see full text ;

 


 

IN CONFIDENCE

 

So it is plausible pigs could be preclinically affected with BSE but since so few are allowed to reach adulthood this has not been recognised through clinical disease. ...

 


 

snip...

 

CONFIDENTIAL EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY

 

PLEASE NOTE, these old BSE Inquiry links take a while to open with the wayback machine, so be patient. ...tss Title: Experimental Intracerebral and Oral Inoculation of Scrapie to Swine: Preliminary Report In the United States, feeding of ruminant by-products to ruminants is prohibited, but feeding of ruminant materials to swine and poultry still occurs. The potential for swine to have access to scrapie-contaminated feedstuffs exists, but the potential for swine to serve as a host for replication/accumulation of the agent of scrapie is unknown. The purpose of this study was to perform oral and intracerebral inoculation of the U.S. scrapie agent to determine the potential of swine as a host for the scrapie agent and their clinical susceptibility. snip... IN CONFIDENCE EXPERIMENTAL PORCINE SPONGIFORM ENCEPHALOPATHY 1. CMO should be aware that a pig inoculated experimentally (ic, iv, and ip) with BSE brain suspension has after 15 months developed an illness, now confirmed as a spongiform encephalopathy. This is the first ever description of such a disease in a pig, although it seems there ar no previous attempts at experimental inoculation with animal material. The Southwood group had thought igs would not be susceptible. Most pigs are slaughtered when a few weeks old but there have been no reports of relevant neurological illness in breeding sows or other elderly pigs. ...see full text ;

 


 

we cannot rule out the possibility that unrecognised subclinical spongiform encephalopathy could be present in British pigs though there is no evidence for this: only with parenteral/implantable pharmaceuticals/devices is the theoretical risk to humans of sufficient concern to consider any action.

 


 

May I, at the outset, reiterate that we should avoid dissemination of papers relating to this experimental finding to prevent premature release of the information. ...

 


 

3. It is particularly important that this information is not passed outside the Department, until Ministers have decided how they wish it to be handled. ...

 


 

But it would be easier for us if pharmaceuticals/devices are not directly mentioned at all. ...

 


 

Our records show that while some use is made of porcine materials in medicinal products, the only products which would appear to be in a hypothetically ''higher risk'' area are the adrenocorticotrophic hormone for which the source material comes from outside the United Kingdom, namely America China Sweden France and Germany. The products are manufactured by Ferring and Armour. A further product, ''Zenoderm Corium implant'' manufactured by Ethicon, makes use of porcine skin - which is not considered to be a ''high risk'' tissue, but one of its uses is described in the data sheet as ''in dural replacement''. This product is sourced from the United Kingdom.....

 


 

snip...

 

It was not until . . . August 1990, that the result from the pig persuaded both SEAC and us to change our view and to take out of pig rations any residual infectivity that might have arisen from the SBOs.

 


 

4.303 The minutes of the meeting record that: It was very difficult to draw conclusions from one experimental result for what may happen in the field. However it would be prudent to exclude specified bovine offals from the pig diet. Although any relationship between BSE and the finding of a spongiform encephalopathy in cats had yet to be demonstrated, the fact that this had occurred suggested that a cautious view should be taken of those species which might be susceptible. The 'specified offals' of bovines should therefore be excluded from the feed of all species. 17

 


 

7 OF 10 LITTLE PIGGIES WENT ON TO DEVELOP BSE;

 

1: J Comp Pathol. 2000 Feb-Apr; 122(2-3): 131-43. Related Articles, Links Click here to read

 

The neuropathology of experimental bovine spongiform encephalopathy in the pig.

 

Ryder SJ, Hawkins SA, Dawson M, Wells GA. Veterinary Laboratories Agency Weybridge, Woodham Lane, New Haw, Addlestone, Surrey, KT15 3NB, UK.

 

In an experimental study of the transmissibility of BSE to the pig, seven of 10 pigs, infected at 1-2 weeks of age by multiple-route parenteral inoculation with a homogenate of bovine brain from natural BSE cases developed lesions typical of spongiform encephalopathy. The lesions consisted principally of severe neuropil vacuolation affecting most areas of the brain, but mainly the forebrain. In addition, some vacuolar change was identified in the rostral colliculi and hypothalamic areas of normal control pigs. PrP accumulations were detected immunocytochemically in the brains of BSE-infected animals. PrP accumulation was sparse in many areas and its density was not obviously related to the degree of vacuolation. The patterns of PrP immunolabelling in control pigs differed strikingly from those in the infected animals. PMID: 10684682 [PubMed - indexed for MEDLINE]

 


 

Transgenic mice expressing porcine prion protein resistant to classical scrapie but susceptible to sheep bovine spongiform encephalopathy and atypical scrapie.

 

Emerg Infect Dis. 2009 Aug; [Epub ahead of print]

 


 

Wednesday, July 06, 2011

 

Swine Are Susceptible to Chronic Wasting Disease by Intracerebral Inoculation snip... In the US, feeding of ruminant by-products to ruminants is prohibited, but feeding of ruminant materials to swine, mink and poultry still occurs. Although unlikely, the potential for swine to have access to TSE-contaminated feedstuffs exists.

 

snip...

 


 

Wednesday, July 06, 2011

 

Swine Are Susceptible to Chronic Wasting Disease by Intracerebral Inoculation (see tonnage of mad cow feed in commerce USA...tss)

 


 

In an experimental study of the transmissibility of BSE to the pig, seven of 10 pigs, infected at 1-2 weeks of age by multiple-route parenteral inoculation with a homogenate of bovine brain from natural BSE cases developed lesions typical of spongiform encephalopathy.

 

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?holding=npg&cmd=Retrieve&db=PubMed&list_uids=10684682&dopt=Abstract Title: Experimental Intracerebral and Oral Inoculation of Scrapie to Swine: Preliminary Report

 

In the United States, feeding of ruminant by-products to ruminants is prohibited, but feeding of ruminant materials to swine and poultry still occurs. The potential for swine to have access to scrapie-contaminated feedstuffs exists, but the potential for swine to serve as a host for replication/accumulation of the agent of scrapie is unknown. The purpose of this study was to perform oral and intracerebral inoculation of the U.S. scrapie agent to determine the potential of swine as a host for the scrapie agent and their clinical susceptibility. snip... snip... In the United States, feeding of ruminant by-products to ruminants is prohibited, but feeding of ruminant materials to swine and poultry still occurs. The potential for swine to have access to scrapie-contaminated feedstuffs exists, but the potential for swine to serve as a host for replication/accumulation of the agent of scrapie is unknown. The purpose of this study was to perform oral and intracerebral inoculation of the U.S. scrapie agent to determine the potential of swine as a host for the scrapie agent and their clinical susceptibility.

 

see full text and more transmission studies here ;

 


 

snip... see full text ;

 

Thursday, November 10, 2011

 

National Meat Association v. Harris Docket No., 10-224 DEADSTOCK DOWNER PIGS AND PORCINE SPONGIFORM ENCEPHALOPATHY PSE Court Likely to Overturn Calif. Law on Livestock

 


 

Friday, April 20, 2012

 

Ultrastructural findings in pigs experimentally infected with bovine spongiform encephalopathy agent

 


 

Wednesday, July 29, 2015

 

Porcine Prion Protein Amyloid or mad pig disease PSE

 


 

Monday, August 10, 2015

 

Detection and Quantification of beta-Amyloid, Pyroglutamyl A beta, and Tau in Aged Canines

 


 

Friday, August 7, 2015

 

Transgenic Mouse Bioassay: Evidence That Rabbits Are Susceptible to a Variety of Prion Isolates

 


 

PRION 2015 CONFERENCE FT. COLLINS CWD RISK FACTORS TO HUMANS

 

*** LATE-BREAKING ABSTRACTS PRION 2015 CONFERENCE ***

 

O18

 

Zoonotic Potential of CWD Prions

 

Liuting Qing1, Ignazio Cali1,2, Jue Yuan1, Shenghai Huang3, Diane Kofskey1, Pierluigi Gambetti1, Wenquan Zou1, Qingzhong Kong1 1Case Western Reserve University, Cleveland, Ohio, USA, 2Second University of Naples, Naples, Italy, 3Encore Health Resources, Houston, Texas, USA

 

***These results indicate that the CWD prion has the potential to infect human CNS and peripheral lymphoid tissues and that there might be asymptomatic human carriers of CWD infection.***

 

P.105: RT-QuIC models trans-species prion transmission

 

Kristen Davenport, Davin Henderson, Candace Mathiason, and Edward Hoover Prion Research Center; Colorado State University; Fort Collins, CO USA

 

Additionally, human rPrP was competent for conversion by CWD and fCWD.

 

***This insinuates that, at the level of protein:protein interactions, the barrier preventing transmission of CWD to humans is less robust than previously estimated.***

 


 

From: Terry S. Singeltary Sr.

 

Sent: Saturday, November 15, 2014 9:29 PM

 

To: Terry S. Singeltary Sr.

 

Subject: THE EPIDEMIOLOGY OF CREUTZFELDT-JAKOB DISEASE R. G. WILL 1984

 

THE EPIDEMIOLOGY OF CREUTZFELDT-JAKOB DISEASE

 

R. G. WILL

 

1984

 

*** The association between venison eating and risk of CJD shows similar pattern, with regular venison eating associated with a 9 FOLD INCREASE IN RISK OF CJD (p = 0.04). (SEE LINK IN REPORT HERE...TSS) PLUS, THE CDC DID NOT PUT THIS WARNING OUT FOR THE WELL BEING OF THE DEER AND ELK ;

 

snip...

 


 

*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).***

 


 

*** The potential impact of prion diseases on human health was greatly magnified by the recognition that interspecies transfer of BSE to humans by beef ingestion resulted in vCJD. While changes in animal feed constituents and slaughter practices appear to have curtailed vCJD, there is concern that CWD of free-ranging deer and elk in the U.S. might also cross the species barrier. Thus, consuming venison could be a source of human prion disease. Whether BSE and CWD represent interspecies scrapie transfer or are newly arisen prion diseases is unknown. Therefore, the possibility of transmission of prion disease through other food animals cannot be ruled out. There is evidence that vCJD can be transmitted through blood transfusion. There is likely a pool of unknown size of asymptomatic individuals infected with vCJD, and there may be asymptomatic individuals infected with the CWD equivalent. These circumstances represent a potential threat to blood, blood products, and plasma supplies.

 


 

O.05: Transmission of prions to primates after extended silent incubation periods: Implications for BSE and scrapie risk assessment in human populations

 

Emmanuel Comoy, Jacqueline Mikol, Val erie Durand, Sophie Luccantoni, Evelyne Correia, Nathalie Lescoutra, Capucine Dehen, and Jean-Philippe Deslys Atomic Energy Commission; Fontenay-aux-Roses, France

 

Prion diseases (PD) are the unique neurodegenerative proteinopathies reputed to be transmissible under field conditions since decades. The transmission of Bovine Spongiform Encephalopathy (BSE) to humans evidenced that an animal PD might be zoonotic under appropriate conditions. Contrarily, in the absence of obvious (epidemiological or experimental) elements supporting a transmission or genetic predispositions, PD, like the other proteinopathies, are reputed to occur spontaneously (atpical animal prion strains, sporadic CJD summing 80% of human prion cases). Non-human primate models provided the first evidences supporting the transmissibiity of human prion strains and the zoonotic potential of BSE. Among them, cynomolgus macaques brought major information for BSE risk assessment for human health (Chen, 2014), according to their phylogenetic proximity to humans and extended lifetime. We used this model to assess the zoonotic potential of other animal PD from bovine, ovine and cervid origins even after very long silent incubation periods. *** We recently observed the direct transmission of a natural classical scrapie isolate to macaque after a 10-year silent incubation period, ***with features similar to some reported for human cases of sporadic CJD, albeit requiring fourfold longe incubation than BSE. Scrapie, as recently evoked in humanized mice (Cassard, 2014), ***is the third potentially zoonotic PD (with BSE and L-type BSE), ***thus questioning the origin of human sporadic cases. We will present an updated panorama of our different transmission studies and discuss the implications of such extended incubation periods on risk assessment of animal PD for human health.

 

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

 

***thus questioning the origin of human sporadic cases...TSS

 

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

 


 

O35

 

J. Mikol1, S. Luccantoni-Freire1, E. Correia1, N. Lescoutra-Etchegaray1, V. Durand1, C. Dehen1, J.P. Deslys1, E. Comoy1

 

1Institute of Emerging Diseases and Innovative Therapies, Service of Prion Diseases, Atomic Energy Commission, 18 Route du Panorama 92265 Fontenayaux- Roses, France

 

E-mail: jacqueline.mikol@wanadoo.fr

 

Uncommon prion disease induced in macaque ten years after scrapie inoculation

 

Introduction: Bovine Spongiform Encephalopathy (BSE) is the single animal prion disease reputed to be zoonotic, inducing variant of Creutzfeldt-Jakob Disease (vCJD) in man, and therefore strongly conditioned the protective measures. Among different sources of animal prion diseases, we show here that after more than ten years of incubation, intracerebral injection of a sheep scrapie isolate can induce a prion disease in cynomolgus macaque, a relevant model of human situation towards several prion strains. Neuropathological studies showed classical and uncommon data.

 

Material and method: The cynomolgus macaque was intracerebrally exposed to a classical scrapie isolate issued from a naturally infected sheep flock. Upon onset of clinical signs, euthanasia was performed for ethical reasons. Classical methods of biochemistry and neuropathology were used.

 

Results: The three elements of the triad were present:

 

spongiosis was predominant in the cortex, the striatum, the cerebellum. Neuronal loss and gliosis were moderate.

 

The notable data were the following

 

(i) the brain was small, the atrophy involved mostly the temporal lobe in which axonal loss was histologically demonstrated

 

(ii) the spongiosis of the Purkinje cells was so intense that most of them were destroyed

 

(iii) there was a neuronal loss and a massive gliosis of the dorsomedialis nucleus of the thalamus

 

(iv) iron deposits were present in the lenticular nucleus. PrPres heavily distributed in the cortex, the basal ganglia and the cerebellum consisted in synaptic deposits and aggregates. Western Blot exhibited a type 1 PrPres in all parts of the brain.

 

Conclusion: We described here the successful transmission of a scrapie prion disease to a non-human primate after an extended incubation period, leading to a fatal, non-relapsing neurological disease with all the features of a prion disease. The cerebral lesional profile we observed was original in comparison to other animal prion diseases (c-BSE, L-type BSE, TME) we previously experimentally transmitted in this model.

 


 

Tuesday, December 16, 2014

 

Evidence for zoonotic potential of ovine scrapie prions

 

Hervé Cassard,1, n1 Juan-Maria Torres,2, n1 Caroline Lacroux,1, Jean-Yves Douet,1, Sylvie L. Benestad,3, Frédéric Lantier,4, Séverine Lugan,1, Isabelle Lantier,4, Pierrette Costes,1, Naima Aron,1, Fabienne Reine,5, Laetitia Herzog,5, Juan-Carlos Espinosa,2, Vincent Beringue5, & Olivier Andréoletti1, Affiliations Contributions Corresponding author Journal name: Nature Communications Volume: 5, Article number: 5821 DOI: doi:10.1038/ncomms6821 Received 07 August 2014 Accepted 10 November 2014 Published 16 December 2014 Article tools Citation Reprints Rights & permissions Article metrics

 

Abstract

 

Although Bovine Spongiform Encephalopathy (BSE) is the cause of variant Creutzfeldt Jakob disease (vCJD) in humans, the zoonotic potential of scrapie prions remains unknown. Mice genetically engineered to overexpress the human ​prion protein (tgHu) have emerged as highly relevant models for gauging the capacity of prions to transmit to humans. These models can propagate human prions without any apparent transmission barrier and have been used used to confirm the zoonotic ability of BSE. Here we show that a panel of sheep scrapie prions transmit to several tgHu mice models with an efficiency comparable to that of cattle BSE. The serial transmission of different scrapie isolates in these mice led to the propagation of prions that are phenotypically identical to those causing sporadic CJD (sCJD) in humans. These results demonstrate that scrapie prions have a zoonotic potential and raise new questions about the possible link between animal and human prions.

 

Subject terms: Biological sciences• Medical research At a glance

 


 

why do we not want to do TSE transmission studies on chimpanzees $

 

5. A positive result from a chimpanzee challenged severly would likely create alarm in some circles even if the result could not be interpreted for man. I have a view that all these agents could be transmitted provided a large enough dose by appropriate routes was given and the animals kept long enough. Until the mechanisms of the species barrier are more clearly understood it might be best to retain that hypothesis.

 

snip...

 

R. BRADLEY

 


 

1: J Infect Dis 1980 Aug;142(2):205-8

 

Oral transmission of kuru, Creutzfeldt-Jakob disease, and scrapie to nonhuman primates.

 

Gibbs CJ Jr, Amyx HL, Bacote A, Masters CL, Gajdusek DC.

 

Kuru and Creutzfeldt-Jakob disease of humans and scrapie disease of sheep and goats were transmitted to squirrel monkeys (Saimiri sciureus) that were exposed to the infectious agents only by their nonforced consumption of known infectious tissues. The asymptomatic incubation period in the one monkey exposed to the virus of kuru was 36 months; that in the two monkeys exposed to the virus of Creutzfeldt-Jakob disease was 23 and 27 months, respectively; and that in the two monkeys exposed to the virus of scrapie was 25 and 32 months, respectively. Careful physical examination of the buccal cavities of all of the monkeys failed to reveal signs or oral lesions. One additional monkey similarly exposed to kuru has remained asymptomatic during the 39 months that it has been under observation.

 

snip...

 

The successful transmission of kuru, Creutzfeldt-Jakob disease, and scrapie by natural feeding to squirrel monkeys that we have reported provides further grounds for concern that scrapie-infected meat may occasionally give rise in humans to Creutzfeldt-Jakob disease.

 

PMID: 6997404

 


 

Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasized by the finding that some strains of scrapie produce lesions identical to the once which characterize the human dementias"

 

Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the scrapie problem urgent if the sheep industry is not to suffer grievously.

 

snip...

 

76/10.12/4.6

 


 

Nature. 1972 Mar 10;236(5341):73-4.

 

Transmission of scrapie to the cynomolgus monkey (Macaca fascicularis).

 

Gibbs CJ Jr, Gajdusek DC.

 

Nature 236, 73 - 74 (10 March 1972); doi:10.1038/236073a0

 

Transmission of Scrapie to the Cynomolgus Monkey (Macaca fascicularis)

 

C. J. GIBBS jun. & D. C. GAJDUSEK

 

National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland

 

SCRAPIE has been transmitted to the cynomolgus, or crab-eating, monkey (Macaca fascicularis) with an incubation period of more than 5 yr from the time of intracerebral inoculation of scrapie-infected mouse brain. The animal developed a chronic central nervous system degeneration, with ataxia, tremor and myoclonus with associated severe scrapie-like pathology of intensive astroglial hypertrophy and proliferation, neuronal vacuolation and status spongiosus of grey matter. The strain of scrapie virus used was the eighth passage in Swiss mice (NIH) of a Compton strain of scrapie obtained as ninth intracerebral passage of the agent in goat brain, from Dr R. L. Chandler (ARC, Compton, Berkshire).

 


 


 


 


 

Friday, January 30, 2015

 

*** Scrapie: a particularly persistent pathogen ***

 


 

Thursday, March 26, 2015

 

Increased Infectivity of Anchorless Mouse Scrapie Prions in Transgenic Mice Overexpressing Human Prion Protein

 


 

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

 

J. Virol. doi:10.1128/JVI.01578-10 Copyright (c) 2010, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

 

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

 

Chris Plinston, Patricia Hart, Angela Chong, Nora Hunter, James Foster, Pedro Piccardo, Jean C. Manson, and Rona M Barron* Neuropathogenesis Division, The Roslin Institute and R(D)SVS, University of Edinburgh, Roslin, Midlothian, UK; Laboratory of Bacterial and TSE Agents, Food and Drug Administration, Rockville, MD, USA

 

* To whom correspondence should be addressed. Email: rona.barron@roslin.ed.ac.uk .

 

Abstract

 

The risk of transmission of ruminant transmissible spongiform encephalopathy (TSE) to humans was thought to be low due to the lack of association between sheep scrapie and incidence of human TSE. However a single TSE agent strain has been shown to cause both bovine spongiform encephalopathy (BSE) and human vCJD, indicating that some ruminant TSEs may be transmissible to humans. While the transmission of cattle BSE to humans in transgenic mouse models has been inefficient, indicating the presence of a significant transmission barrier between cattle and humans, BSE has been transmitted to a number of other species. Here we aimed to further investigate the human transmission barrier following passage of BSE in a sheep. Following inoculation with cattle BSE, gene targeted transgenic mice expressing human PrP showed no clinical or pathological signs of TSE disease. However following inoculation with an isolate of BSE that had been passaged through a sheep, TSE associated vacuolation and proteinase-K resistant PrP deposition were observed in mice homozygous for the codon 129-methionine PRNP gene. This observation may be due to higher titres of the BSE agent in sheep, or an increased susceptibility of humans to BSE prions following passage through a sheep. ***However these data confirm that, contrary to previous predictions, it is possible that a sheep prion may be transmissible to humans and that BSE from other species may be a public health risk.

 


 


 

BSE: TIME TO TAKE H.B. PARRY SERIOUSLY

 

If the scrapie agent is generated from ovine DNA and thence causes disease in other species, then perhaps, bearing in mind the possible role of scrapie in CJD of humans (Davinpour et al, 1985), scrapie and not BSE should be the notifiable disease. ...

 


 

Tuesday, August 4, 2015

 

FDA U.S. Measures to Protect Against BSE

 


 

Thursday, August 20, 2015 Doctor William J. Hadlow RIP

 

William J. Hadlow Dr. Hadlow (Ohio State ’48), 94, Hamilton, Montana, died June 20, 2015.

 


 


 

 

Terry S. Singeltary Sr.

 

 
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