Sunday, February 2, 2014

The Presence of Disease-Associated Prion Protein in Skeletal Muscle of Cattle Infected with Classical Bovine Spongiform Encephalopathy

NOTE Pathology

 

The Presence of Disease-Associated Prion Protein in Skeletal Muscle of Cattle Infected with Classical Bovine Spongiform Encephalopathy

 

Hiroyuki OKADA1)*, Kohtaro MIYAZAWA1), Shigeo FUKUDA2), Yoshifumi IWAMARU1), Morikazu IMAMURA1), Kentaro MASUJIN1), Yuichi MATSUURA1), Takashi FUJII2), Kei FUJII2), Soichi KAGEYAMA2), Miyako YOSHIOKA1), Yuichi MURAYAMA1) and Takashi YOKOYAMA1)

 

1)National Institute of Animal Health, National Agriculture and Food Research Organization, Tsukuba, Ibaraki 305–0856, Japan 2)Hokkaido Animal Research Center, Hokkaido Research Organization, Shintoku, Hokkaido 081–0038, Japan (Received 16 July 2013/Accepted 13 August 2013/Published online in J-STAGE 27 August 2013)

 

ABSTRACT. The aim of this study was to investigate the presence of disease-associated prion protein (PrPSc) in the skeletal muscle of cattle infected with classical bovine spongiform encephalopathy (C-BSE). The study was carried out systematically in 12 different muscle samples from 43 (3 field and 40 experimental) cases of C-BSE; however, muscle spindles were not available in many of these cases. Therefore, analysis became restricted to a total of 31 muscles in 23 cattle. Even after this restriction, low levels of PrPSc were detected in the muscle spindles of the masseter, intercostal, triceps brachii, psoas major, quadriceps femoris and semitendinosus muscles from 3 field and 6 experimental clinical-stage cases. The present data indicate that small amounts of PrPSc are detectable by immunohistochemistry in the skeletal muscles of animals terminally affected with C-BSE.

 

SNIP...

 

31. No muscle spindles were detected in the gluteus medius muscle, diaphragm or tongue. Even after this restriction, the global frequency of immunolabeled PrPSc detection was 9 (3 natural and 6 experimental) of 23 cases. Positive immunolabeling was detected in 16 of the 31 muscle samples containing spindles, including the masseter muscle (4/9; number of positive samples/number of detected samples), intercostal muscle (2/5), triceps brachii muscle (4/4), psoas major muscle (1/2), quadriceps femoris muscle (1/1) and semitendinosus muscle (3/3). In experimentally challenged animals, PrPSc detection was associated with clinical symptoms, but not with preclinical status. No positive spindles were observed in the 14 preclinical and 4 control animals. By WB analysis, a very weak signal for PrPSc was detected in 2 different muscle samples from naturally (masseter muscle from BSE/JP17) and experimentally (intercostal muscle from ID#5413) C-BSE-infected animals (Fig. 2). However, a detectable PrPSc signal was obtained from only 1 of 3 tissue pieces; adjacent locations were used for PrPSc immunohistochemistry within the same tissue in each case.

 

The results of this study indicate that low amounts of PrPSc are deposited in the muscle spindles of C-BSE-infected cattle. To the best of our knowledge, this is the first, or at least the most comprehensive, report on the localization of PrPSc by IHC in skeletal muscles of C-BSE affected cattle. Localization of PrPSc in the muscle spindles of skeletal muscles in the study was consistent with that of atypical BSE in cattle [8] and natural scrapie in sheep [1]. In addition, immunolabeled PrPSc localized at the terminal nerve endings of myofibrils has been reported in hamsters with scrapie and [16] in rodent and primate models with C-BSE and CJD, respectively [6, 9, 17].

 

PrPC is primarily expressed in neural tissues, but is also distributed in non-neural organs and tissues, such as the spleen, lymph node, heart, skeletal muscle, kidney, uterus, adrenal gland, intestine and mammary gland [7]. In muscle tissues, PrPC is located primarily at the neuromuscular junction [5]. Somatic motor neurons known as efferent nerve fibers arise from the ventral horn of the spinal cord and innervate skeletal muscle tissues at the neuromuscular junction via alpha motor neurons or intrafusal muscle fibers of the muscle spindles via gamma motor neurons. In addition, type Ia afferent sensory fibers connect to the muscle spindles. However, there are no precedents for a primary role for sensory neural pathways in the pathogenesis of BSE [10]. PrPSc accumulation in the peripheral nervous tissues may be attributed to a high degree of neurotropism in C-BSE [3, 10]. Our results indicate the centrifugal spread of the infectious agent from central nervous tissues through the somatic motor and/or sensory pathways to the muscle spindles of various muscle tissues during the clinical stage of the disease in both naturally occurring and experimentally-induced C-BSE animals.

 

Although we did not attempt a mouse bioassay to demonstrate infectivity in skeletal muscles, small amounts of PrPSc were detected in the skeletal muscles of C-BSE cattle in the clinical stage of the disease. The study suggests that it is important to investigate the presence of PrPSc in muscle tissues of C-BSE-affected cattle using immunohistochemical analysis.

 

This study was supported by Grants-in-Aid from the BSE and other Prion Disease Control Project of the Ministry of Agriculture, Forestry and Fisheries of Japan and from the TSE research of the Ministry of Health, Labor and Welfare of Japan.

 

SNIP...

 

REFERENCES

 

KEY WORDS: BSE, muscle spindle, prion, skeletal muscle.

 

doi: 10.1292/jvms.13-0363; J. Vet. Med. Sci. 76(1): 103–107, 2014

 


 

Envt.07:

 

Pathological Prion Protein (PrPTSE) in Skeletal Muscles of Farmed and Free Ranging White-Tailed Deer Infected with Chronic Wasting Disease

 

Martin L. Daus,1,† Johanna Breyer,2 Katjs Wagenfuehr,1 Wiebke Wemheuer,2 Achim Thomzig,1 Walter Schulz-Schaeffer2 and Michael Beekes1 1Robert Koch Institut; P24 TSE; Berlin, Germany; 2Department of Neuropathology, Prion and Dementia Research Unit, University Medical Center Göttingen; Göttingen, Germany †Presenting author; Email: dausm@rki.de

 

Chronic wasting disease (CWD) is a contagious, rapidly spreading transmissible spongiform encephalopathy (TSE) occurring in cervids in North America. Despite efficient horizontal transmission of CWD among cervids natural transmission of the disease to other species has not yet been observed. Here, we report a direct biochemical demonstration of pathological prion protein PrPTSE and of PrPTSE-associated seeding activity in skeletal muscles of CWD-infected cervids. The presence of PrPTSE was detected by Western- and postfixed frozen tissue blotting, while the seeding activity of PrPTSE was revealed by protein misfolding cyclic amplification (PMCA). The concentration of PrPTSE in skeletal muscles of CWD-infected WTD was estimated to be approximately 2000- to 10000-fold lower than in brain tissue. Tissue-blot-analyses revealed that PrPTSE was located in muscle- associated nerve fascicles but not, in detectable amounts, in myocytes. The presence and seeding activity of PrPTSE in skeletal muscle from CWD-infected cervids suggests prevention of such tissue in the human diet as a precautionary measure for food safety, pending on further clarification of whether CWD may be transmissible to humans.

 


 

Monday, August 26, 2013

 

***The Presence of Disease-Associated Prion Protein in Skeletal Muscle of Cattle Infected with Classical Bovine Spongiform Encephalopathy

 


 

 CDC DR. PAUL BROWN TSE EXPERT COMMENTS 2006

 

The U.S. Department of Agriculture was quick to assure the public earlier this week that the third case of mad cow disease did not pose a risk to them, but what federal officials have not acknowledged is that this latest case indicates the deadly disease has been circulating in U.S. herds for at least a decade.

 

The second case, which was detected last year in a Texas cow and which USDA officials were reluctant to verify, was approximately 12 years old.

 

These two cases (the latest was detected in an Alabama cow) present a picture of the disease having been here for 10 years or so, since it is thought that cows usually contract the disease from contaminated feed they consume as calves. The concern is that humans can contract a fatal, incurable, brain-wasting illness from consuming beef products contaminated with the mad cow pathogen.

 

"The fact the Texas cow showed up fairly clearly implied the existence of other undetected cases," Dr. Paul Brown, former medical director of the National Institutes of Health's Laboratory for Central Nervous System Studies and an expert on mad cow-like diseases, told United Press International. "The question was, 'How many?' and we still can't answer that."

 

Brown, who is preparing a scientific paper based on the latest two mad cow cases to estimate the maximum number of infected cows that occurred in the United States, said he has "absolutely no confidence in USDA tests before one year ago" because of the agency's reluctance to retest the Texas cow that initially tested positive.

 

USDA officials finally retested the cow and confirmed it was infected seven months later, but only at the insistence of the agency's inspector general.

 

"Everything they did on the Texas cow makes everything USDA did before 2005 suspect," Brown said. ...snip...end

 


 

 PAUL BROWN COMMENT TO ME ON THIS ISSUE

 

Tuesday, September 12, 2006 11:10 AM

 

"Actually, Terry, I have been critical of the USDA handling of the mad cow issue for some years, and with Linda Detwiler and others sent lengthy detailed critiques and recommendations to both the USDA and the Canadian Food Agency."

 

OR, what the Honorable Phyllis Fong of the OIG found ;

 

Audit Report

 

Animal and Plant Health Inspection Service

 

Bovine Spongiform Encephalopathy (BSE) Surveillance Program – Phase II

 

and

 

Food Safety and Inspection Service

 

Controls Over BSE Sampling, Specified Risk Materials, and Advanced Meat Recovery Products - Phase III

 

Report No. 50601-10-KC January 2006

 

Finding 2 Inherent Challenges in Identifying and Testing High-Risk Cattle Still Remain

 


 

"These 9,200 cases were different because brain tissue samples were preserved with formalin, which makes them suitable for only one type of test--immunohistochemistry, or IHC."

 

THIS WAS DONE FOR A REASON!

 

THE IHC test has been proven to be the LEAST LIKELY to detect BSE/TSE in the bovine, and these were probably from the most high risk cattle pool, the ones the USDA et al, SHOULD have been testing. ...TSS

 

USDA 2003

 

snip...see

 


 

FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED VIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE DECEMBER

 

2013 UPDATE

 

 OAI 2012-2013

 

OAI (Official Action Indicated) when inspectors find significant objectionable conditions or practices and believe that regulatory sanctions are warranted to address the establishment’s lack of compliance with the regulation. An example of an OAI classification would be findings of manufacturing procedures insufficient to ensure that ruminant feed is not contaminated with prohibited material. Inspectors will promptly re-inspect facilities classified OAI after regulatory sanctions have been applied to determine whether the corrective actions are adequate to address the objectionable conditions.

 

 ATL-DO 1035703 Newberry Feed & Farm Ctr, Inc. 2431 Vincent St. Newberry SC 29108-0714 OPR DR, FL, FR, TH HP 9/9/2013 OAI Y

 

DET-DO 1824979 Hubbard Feeds, Inc. 135 Main, P.O. Box 156 Shipshewana IN 46565-0156 OPR DR, FL, OF DP 8/29/2013 OAI Y

 

ATL-DO 3001460882 Talley Farms Feed Mill Inc 6309 Talley Rd Stanfield NC 28163-7617 OPR FL, TH NP 7/17/2013 OAI N

 

NYK-DO 3010260624 Sherry Sammons 612 Stoner Trail Rd Fonda NY 12068-5007 OPR FR, OF NP 7/16/2013 OAI Y

 

DEN-DO 3008575486 Rocky Ford Pet Foods 21693 Highway 50 East Rocky Ford CO 81067 OPR RE, TH HP 2/27/2013 OAI N

 

CHI-DO 3007091297 Rancho Cantera 2866 N Sunnyside Rd Kent IL 61044-9605 OPR FR, OF HP 11/26/2012 OAI Y

 

*** DEN-DO 1713202 Weld County Bi Products, Inc. 1138 N 11th Ave Greeley CO 80631-9501 OPR RE, TH HP 10/12/2012 OAI N

 

Ruminant Feed Inspections Firms Inventory (excel format)

 


 

PLEASE NOTE, the VAI violations were so numerous, and unorganized in dates posted, as in numerical order, you will have to sift through them for yourselves. ...tss

 

Tuesday, June 11, 2013

 

*** Weld County Bi-Products dba Fort Morgan Pet Foods 6/1/12 significant deviations from requirements in FDA regulations that are intended to reduce the risk of bovine spongiform encephalopathy (BSE) within the United States

 


 

 Thursday, June 6, 2013

 

BSE TSE PRION USDA FDA MAD COW FEED COMPLIANCE REPORT and NAI, OAI, and VAI ratings as at June 5, 2013

 

Greetings,

 

since our fine federal friends have decided not to give out any more reports on the USA breaches of the feed ban and surveillance etc. for the BSE TSE prion mad cow type disease in the USDA livestock, I thought I might attempt it. I swear, I just don’t understand the logic of the SSS policy, and that includes all of it. I assure you, it would be much easier, and probably better for the FDA and the USDA INC., if they would simply put some kind of report out for Pete’s sake, instead of me doing it after I get mad, because I am going to put it all out there. the truth.

 

PLEASE BE ADVISED, any breach of any of the above classifications OAI, VAI, RTS, CAN lead to breaches into the feed BSE TSE prion protocols, and CAN lead to the eventual suspect tainted feed reaching livestock. please, if any USDA official out there disputes this, please explain then how they could not. paperwork errors can eventually lead to breaches of the BSE TSE prion mad cow feed ban reaching livestock, or contamination and exposure there from, as well.

 

I would sure like to see the full reports of just these ;

 

 4018 CHI-DO 3007091297 Rancho Cantera 2866 N Sunnyside Rd Kent IL 61044-9605 OPR FR, OF HP 11/26/2012 OAI Y

 

9367 3008575486 Rocky Ford Pet Foods 21693 Highway 50 East Rocky Ford CO 81067 OPR RE, TH HP 2/27/2013 OAI N

 

9446 DEN-DO 1713202 Weld County Bi Products, Inc. 1138 N 11th Ave Greeley CO 80631-9501 OPR RE, TH HP 10/12/2012 OAI N

 

9447 DEN-DO 3002857110 Weld County Bi-Products dba Fort Morgan Pet Foods 13553 County Road 19 Fort Morgan CO 80701-7506 OPR RE HP 12/7/2011 OAI N

 

 see full list of the fda mad cow bse feed follies, toward the bottom, after a short brief update on the mad cow bse follies, and our good friend Lester Crawford that was at the FDA.

 

ALSO, I would kindly like to comment on this FDA BSE/Ruminant Feed Inspections Firms Inventory (excel format)4 format, for reporting these breaches of BSE TSE prion protocols, from the extensive mad cow feed ban warning letters the fda use to put out for each violations. simply put, this excel format sucks, and the FDA et al intentionally made it this difficult to follow the usda fda mad cow follies. this is an intentional format to make it as difficult as possible to follow these breaches of the mad cow TSE prion safety feed protocols. to have absolutely no chronological or numerical order, and to format such violations in a way that they are almost impossible to find, says a lot about just how far the FDA and our fine federal friends will go through to hide these continued violations of the BSE TSE prion mad cow feed ban, and any breaches of protocols there from. once again, the wolf guarding the henhouse $$$

 

 NAI = NO ACTION INDICATED

 

OAI = OFFICIAL ACTION INDICATED

 

VAI = VOLUNTARY ACTION INDICATED

 

RTS = REFERRED TO STATE

 

Inspections conducted by State and FDA investigators are classified to reflect the compliance status at the time of the inspection, based upon whether objectionable conditions were documented. Based on the conditions found, inspection results are recorded in one of three classifications:

 

OAI (Official Action Indicated) when inspectors find significant objectionable conditions or practices and believe that regulatory sanctions are warranted to address the establishment’s lack of compliance with the regulation. An example of an OAI classification would be findings of manufacturing procedures insufficient to ensure that ruminant feed is not contaminated with prohibited material. Inspectors will promptly re-inspect facilities classified OAI after regulatory sanctions have been applied to determine whether the corrective actions are adequate to address the objectionable conditions.

 

VAI (Voluntary Action Indicated) when inspectors find objectionable conditions or practices that do not meet the threshold of regulatory significance, but warrant an advisory to inform the establishment that inspectors found conditions or practices that should be voluntarily corrected. VAI violations are typically technical violations of the 1997 BSE Feed Rule. These violations include minor recordkeeping lapses or conditions involving non-ruminant feeds.

 

NAI (No Action Indicated) when inspectors find no objectionable conditions or practices or, if they find objectionable conditions, those conditions are of a minor nature and do not justify further actions.

 


 

when sound science was bought off by junk science, in regards to the BSE TSE prion mad cow type disease, by the USDA, CFIA, WHO, OIE, et al. $$$

 

when the infamous, and fraudulently USDA, FSIS, APHIS, FDA, gold card was taken away that infamous day in December of 2003, all cards were off the table, it was time to change the science, and change they did. ...tss

 

snip. ...please see full text ;

 

Thursday, June 6, 2013

 

BSE TSE PRION USDA FDA MAD COW FEED COMPLIANCE REPORT and NAI, OAI, and VAI ratings as at June 5, 2013

 


 

IN A NUT SHELL ;

 

(Adopted by the International Committee of the OIE on 23 May 2006)

 

11. Information published by the OIE is derived from appropriate declarations made by the official Veterinary Services of Member Countries. The OIE is not responsible for inaccurate publication of country disease status based on inaccurate information or changes in epidemiological status or other significant events that were not promptly reported to the Central Bureau,

 


 

 Sunday, December 15, 2013

 

*** FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED VIOLATIONS OFFICIAL ACTION INDICATED OAI UPDATE DECEMBER 2013 UPDATE

 


 

 Saturday, December 21, 2013

 

**** Complementary studies detecting classical bovine spongiform encephalopathy infectivity in jejunum, ileum and ileocaecal junction in incubating cattle ****

 


 

Saturday, December 15, 2012

 

*** Bovine spongiform encephalopathy: the effect of oral exposure dose on attack rate and incubation period in cattle -- an update 5 December 2012

 


 

***Oral Transmission of L-type Bovine Spongiform Encephalopathy in Primate Model

 


 

***Infectivity in skeletal muscle of BASE-infected cattle

 


 

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

 


 

***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans.

 


 

full text ; atypical L-type BASE BSE

 


 

However, a BSE expert said that consumption of infected material is the only known way that cattle get the disease under natural conditons.

 

*** “In view of what we know about BSE after almost 20 years experience, contaminated feed has been the source of the epidemic,” said Paul Brown, a scientist retired from the National Institute of Neurological Diseases and Stroke. BSE is not caused by a microbe. It is caused by the misfolding of the so-called “prion protein” that is a normal constituent of brain and other tissues. If a diseased version of the protein enters the brain somehow, it can slowly cause all the normal versions to become misfolded. It is possible the disease could arise spontaneously, though such an event has never been recorded, Brown said.

 


 

*** What irks many scientists is the USDA’s April 25 statement that the rare disease is “not generally associated with an animal consuming infected feed.” The USDA’s conclusion is a “gross oversimplification,” said Dr. Paul Brown, one of the world’s experts on this type of disease who retired recently from the National Institutes of Health. "(The agency) has no foundation on which to base that statement.”

 


 

2012 ATYPICAL L-TYPE BSE BASE CALIFORNIA ‘confirmed’ Saturday, August 4, 2012

 

*** Final Feed Investigation Summary - California BSE Case - July 2012

 


 

Saturday, August 14, 2010

 

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

 

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

 


 

Friday, January 17, 2014

 

*** Annual report of the Scientific Network on BSE-TSE EFSA, Question No EFSA-Q-2013-01004, approved on 11 December 2013

 


 

Wednesday, December 4, 2013

 

*** Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products; Final Rule Federal Register / Vol. 78 , No. 233 / Wednesday, December 4, 2013

 

TO ALL IMPORTING COUNTRIES THAT IMPORTS FROM THE USA, BE WARNED, NEW MAD COW BSE REGULATIONS USDA, AND OIE, not worth the paper the regulations were wrote on, kind of like the mad cow feed ban of August 1997, nothing but ink on paper $$$

 

full text ;

 


 

Wednesday, May 2, 2012

 

ARS FLIP FLOPS ON SRM REMOVAL FOR ATYPICAL L-TYPE BASE BSE RISK HUMAN AND ANIMAL HEALTH

 


 

 Saturday, June 12, 2010

 

PUBLICATION REQUEST AND FOIA REQUEST Project Number: 3625-32000-086-05 Study of Atypical Bse

 


 

 Wednesday, July 28, 2010

 

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

 


 

Tuesday, June 11, 2013

 

*** Weld County Bi-Products dba Fort Morgan Pet Foods 6/1/12 significant deviations from requirements in FDA regulations that are intended to reduce the risk of bovine spongiform encephalopathy (BSE) within the United States

 


 

Monday, March 8, 2010

 

UPDATE 429,128 lbs. feed for ruminant animals may have been contaminated with prohibited material Recall # V-258-2009

 


 

Friday, September 4, 2009

 

FOIA REQUEST ON FEED RECALL PRODUCT 429,128 lbs. feed for ruminant animals may have been contaminated with prohibited material Recall # V-258-2009

 


 

Tuesday, November 3, 2009

 

re-FOIA REQUEST ON FEED RECALL PRODUCT contaminated with prohibited material Recall # V-258-2009 and Recall # V-256-2009

 


 

Friday, March 8, 2013

 

Dogs may have been used to make Petfood and animal feed

 


 

Monday, March 26, 2012

 

CANINE SPONGIFORM ENCEPHALOPATHY: A NEW FORM OF ANIMAL PRION DISEASE

 


 


 

FELINE SPONGIFORM ENCEPHALOPATHY FSE

 


 


 


 

Saturday, November 2, 2013

 

APHIS Finalizes Bovine Import Regulations in Line with International Animal Health Standards while enhancing the spread of BSE TSE prion mad cow type disease around the Globe

 


 

Monday, March 19, 2012

 

Infectivity in Skeletal Muscle of Cattle with Atypical Bovine Spongiform Encephalopathy

 

PLoS One. 2012; 7(2): e31449.

 


 

Saturday, June 25, 2011

 

Transmissibility of BSE-L and Cattle-Adapted TME Prion Strain to Cynomolgus Macaque

 

"BSE-L in North America may have existed for decades"

 


 

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...

 


 

EFSA Journal 2011 The European Response to BSE: A Success Story

 

snip...

 

EFSA and the European Centre for Disease Prevention and Control (ECDC) recently delivered a scientific opinion on any possible epidemiological or molecular association between TSEs in animals and humans (EFSA Panel on Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical BSE prions as the only TSE agents demonstrated to be zoonotic so far but the possibility that a small proportion of human cases so far classified as "sporadic" CJD are of zoonotic origin could not be excluded. Moreover, transmission experiments to non-human primates suggest that some TSE agents in addition to Classical BSE prions in cattle (namely L-type Atypical BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic wasting disease (CWD) agents) might have zoonotic potential.

 

snip...

 


 


 

see follow-up here about North America BSE Mad Cow TSE prion risk factors, and the ever emerging strains of Transmissible Spongiform Encephalopathy in many species here in the USA, including humans ;

 


 

Thursday, August 12, 2010

 

Seven main threats for the future linked to prions

 

First threat

 

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

 

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

 

Second threat

 

snip...

 


 

Rural and Regional Affairs and Transport References Committee

 

The possible impacts and consequences for public health, trade and agriculture of the Government's decision to relax import restrictions on beef Final report June 2010

 

2.65 At its hearing on 14 May 2010, the committee heard evidence from Dr Alan Fahey who has recently submitted a thesis on the clinical neuropsychiatric, epidemiological and diagnostic features of Creutzfeldt-Jakob disease.48 Dr Fahey told the committee of his concerns regarding the lengthy incubation period for transmissible spongiform encephalopathies, the inadequacy of current tests and the limited nature of our current understanding of this group of diseases.49

 

2.66 Dr Fahey also told the committee that in the last two years a link has been established between forms of atypical CJD and atypical BSE. Dr Fahey said that: They now believe that those atypical BSEs overseas are in fact causing sporadic Creutzfeldt-Jakob disease. They were not sure if it was due to mad sheep disease or a different form. If you look in the textbooks it looks like this is just arising by itself. But in my research I have a summary of a document which states that there has never been any proof that sporadic Creutzfeldt-Jakob disease has arisen de novo-has arisen of itself. There is no proof of that. The recent research is that in fact it is due to atypical forms of mad cow disease which have been found across Europe, have been found in America and have been found in Asia. These atypical forms of mad cow disease typically have even longer incubation periods than the classical mad cow disease.50

 


 

Atypical BSE in Cattle

 

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

 

In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

 

This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.

 


 

When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

 

This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.

 


 

P.4.23

 

Transmission of atypical BSE in humanized mouse models

 

Liuting Qing1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5, Qingzhong Kong1 1Case Western Reserve University, USA; 2Instituto Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research Institute, Poland; 5Kansas State University (Previously at USDA National Animal Disease Center), USA

 

Background: Classical BSE is a world-wide prion disease in cattle, and the classical BSE strain (BSE-C) has led to over 200 cases of clinical human infection (variant CJD). Atypical BSE cases have been discovered in three continents since 2004; they include the L-type (also named BASE), the H-type, and the first reported case of naturally occurring BSE with mutated bovine PRNP (termed BSE-M). The public health risks posed by atypical BSE were largely undefined.

 

Objectives: To investigate these atypical BSE types in terms of their transmissibility and phenotypes in humanized mice. Methods: Transgenic mice expressing human PrP were inoculated with several classical (C-type) and atypical (L-, H-, or Mtype) BSE isolates, and the transmission rate, incubation time, characteristics and distribution of PrPSc, symptoms, and histopathology were or will be examined and compared.

 

Results: Sixty percent of BASE-inoculated humanized mice became infected with minimal spongiosis and an average incubation time of 20-22 months, whereas only one of the C-type BSE-inoculated mice developed prion disease after more than 2 years. Protease-resistant PrPSc in BASE-infected humanized Tg mouse brains was biochemically different from bovine BASE or sCJD. PrPSc was also detected in the spleen of 22% of BASE-infected humanized mice, but not in those infected with sCJD. Secondary transmission of BASE in the humanized mice led to a small reduction in incubation time.*** The atypical BSE-H strain is also transmissible with distinct phenotypes in the humanized mice, but no BSE-M transmission has been observed so far.

 

Discussion: Our results demonstrate that BASE is more virulent than classical BSE, has a lymphotropic phenotype, and displays a modest transmission barrier in our humanized mice. BSE-H is also transmissible in our humanized Tg mice. The possibility of more than two atypical BSE strains will be discussed.

 

Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.

 


 

P26 TRANSMISSION OF ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY (BSE) IN HUMANIZED MOUSE MODELS

 

Liuting Qing1, Fusong Chen1, Michael Payne1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5*, and Qingzhong Kong1 1Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA; 2CEA, Istituto Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research Institute, Poland; 5Kansas State University, Diagnostic Medicine/Pathobiology Department, Manhattan, KS 66506, USA. *Previous address: USDA National Animal Disease Center, Ames, IA 50010, USA

 

Classical BSE is a world-wide prion disease in cattle, and the classical BSE strain (BSE-C) has led to over 200 cases of clinical human infection (variant CJD). Two atypical BSE strains, BSE-L (also named BASE) and BSE-H, have been discovered in three continents since 2004. The first case of naturally occurring BSE with mutated bovine PrP gene (termed BSE-M) was also found in 2006 in the USA. The transmissibility and phenotypes of these atypical BSE strains/isolates in humans were unknown. We have inoculated humanized transgenic mice with classical and atypical BSE strains (BSE-C, BSE-L, BSE-H) and the BSE-M isolate. We have found that the atypical BSE-L strain is much more virulent than the classical BSE-C.*** The atypical BSE-H strain is also transmissible in the humanized transgenic mice with distinct phenotype, but no transmission has been observed for the BSE-M isolate so far.

 

III International Symposium on THE NEW PRION BIOLOGY: BASIC SCIENCE, DIAGNOSIS AND THERAPY 2 - 4 APRIL 2009, VENEZIA (ITALY)

 


 

I ask Professor Kong ;

 

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

 

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

 

Professor Kong reply ;

 

.....snip

 

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

 

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

 

END...TSS

 

Thursday, December 04, 2008 2:37 PM

 

"we have found that H-BSE can infect humans."

 

personal communication with Professor Kong. ...TSS

 

BSE-H is also transmissible in our humanized Tg mice.

 

The possibility of more than two atypical BSE strains will be discussed.

 

Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.

 


 


 

 Tuesday, July 14, 2009 U.S.

 

Emergency Bovine Spongiform Encephalopathy Response Plan Summary and BSE Red Book

 

Date: February 14, 2000 at 8:56 am PST

 

WHERE did we go wrong $$$

 


 

 LET'S take a closer look at this new prionpathy or prionopathy, and then let's look at the g-h-BSEalabama mad cow. This new prionopathy in humans? the genetic makeup is IDENTICAL to the g-h-BSEalabama mad cow, the only _documented_ mad cow in the world to date like this, ......wait, it get's better. this new prionpathy is killing young and old humans, with LONG DURATION from onset of symptoms to death, and the symptoms are very similar to nvCJD victims, OH, and the plaques are very similar in some cases too, bbbut, it's not related to the g-h-BSEalabama cow, WAIT NOW, it gets even better, the new human prionpathy that they claim is a genetic TSE, has no relation to any gene mutation in that family. daaa, ya think it could be related to that mad cow with the same genetic make-up ??? there were literally tons and tons of banned mad cow protein in Alabama in commerce, and none of it transmitted to cows, and the cows to humans there from ??? r i g h t $$$ ALABAMA MAD COW g-h-BSEalabama In this study, we identified a novel mutation in the bovine prion protein gene (Prnp), called E211K, of a confirmed BSE positive cow from Alabama, United States of America. This mutation is identical to the E200K pathogenic mutation found in humans with a genetic form of CJD. This finding represents the first report of a confirmed case of BSE with a potential pathogenic mutation within the bovine Prnp gene. We hypothesize that the bovine Prnp E211K mutation most likely has caused BSE in "the approximately 10-year-old cow" carrying the E221K mutation.

 


 


 

Saturday, August 14, 2010

 

BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and VPSPr PRIONPATHY (see mad cow feed in COMMERCE IN ALABAMA...TSS)

 


 

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

 

This raises the possibility that the disease could occasionally be genetic in origin. Indeed, the report of the UK BSE Inquiry in 2000 suggested that the UK epidemic had most likely originated from such a mutation and argued against the scrapierelated assumption. Such rare potential pathogenic PRNP mutations could occur in countries at present considered to be free of BSE, such as Australia and New Zealand. So it is important to maintain strict surveillance for BSE in cattle, with rigorous enforcement of the ruminant feed ban (many countries still feed ruminant proteins to pigs). Removal of specified risk material, such as brain and spinal cord, from cattle at slaughter prevents infected material from entering the human food chain. Routine genetic screening of cattle for PRNP mutations, which is now available, could provide additional data on the risk to the public. Because the point mutation identified in the Alabama animals is identical to that responsible for the commonest type of familial (genetic) CJD in humans, it is possible that the resulting infective prion protein might cross the bovine-human species barrier more easily. Patients with vCJD continue to be identified. The fact that this is happening less often should not lead to relaxation of the controls necessary to prevent future outbreaks. Malcolm A. Ferguson-Smith Cambridge University Department of Veterinary Medicine, Madingley Road, Cambridge CB3 0ES, UK e-mail: maf12@cam.ac.uk Jürgen A. Richt College of Veterinary Medicine, Kansas State University, K224B Mosier Hall, Manhattan, Kansas 66506-5601, USA NATURE|Vol 457|26 February 2009

 


 

 SEE FULL TEXT OF ALL THIS HERE ;

 

2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006

 


 

 Friday, December 23, 2011

 

Oral Transmission of L-type Bovine Spongiform Encephalopathy in Primate Model

 

Volume 18, Number 1—January 2012 Dispatch

 


 

 Friday, March 09, 2012

 

Experimental H-type and L-type bovine spongiform encephalopathy in cattle: observation of two clinical syndromes and diagnostic challenges

 

Research article

 


 

Sunday, February 5, 2012

 

February 2012 Update on Feed Enforcement Activities to Limit the Spread of BSE

 


 

Wednesday, March 7, 2012

 

Case-control study of cases of bovine spongiform encephalopathy born after July 31, 1996 (BARB cases) in Great Britain Veterinary Record doi:10.1136/vr.100097

 


 

Wednesday, March 7, 2012

 

The epidemiology of bovine spongiform encephalopathy in the Republic of Ireland before and after the reinforced feed ban

 


 

Thursday, February 23, 2012

 

EIGHT FORMER SECRETARIES OF AGRICULTURE SPEAKING AT USDA'S 2012 AGRICULTURE OUTLOOK FORUM INDUCTED INTO USA MAD COW HALL OF SHAME

 


 

Thursday, February 16, 2012

 

Bovine Spongiform Encephalopathy BSE

 

31 USA SENATORS ASK PRESIDENT OBAMA TO HELP SPREAD MAD COW DISEASE 2012

 


 

Tuesday, February 14, 2012

 

White House budget proposes cuts to ag programs including TSE PRION disease aka mad cow type disease

 


 

Saturday, July 23, 2011

 

CATTLE HEADS WITH TONSILS, BEEF TONGUES, SPINAL CORD, SPECIFIED RISK MATERIALS (SRM's) AND PRIONS, AKA MAD COW DISEASE

 


 

Saturday, November 6, 2010

 

TAFS1 Position Paper on Position Paper on Relaxation of the Feed Ban in the EU

 

Berne, 2010 TAFS INTERNATIONAL FORUM FOR TRANSMISSIBLE ANIMAL DISEASES AND FOOD SAFETY a non-profit Swiss Foundation

 


 

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

 

Prion disease update 2010 (11) PRION DISEASE UPDATE 2010 (11)

 


 

P.9.21 Molecular characterization of BSE in Canada

 

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

 

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

 

Objectives: This study was conducted to further characterize the 16 Canadian BSE cases based on the biochemical properties of there associated PrPres.

 

Methods: Immuno-reactivity, molecular weight, glycoform profiles and relative proteinase K sensitivity of the PrPres from each of the 16 confirmed Canadian BSE cases was determined using modified Western blot analysis. Results: Fourteen of the 16 Canadian BSE cases were C type, 1 was H type and 1 was L type. The Canadian H and L-type BSE cases exhibited size shifts and changes in glycosylation similar to other atypical BSE cases. PK digestion under mild and stringent conditions revealed a reduced protease resistance of the atypical cases compared to the C-type cases. N terminal- specific antibodies bound to PrPres from H type but not from C or L type. The C-terminal-specific antibodies resulted in a shift in the glycoform profile and detected a fourth band in the Canadian H-type BSE.

 

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

 


 

October 2009 O.11.3 Infectivity in skeletal muscle of BASE-infected cattle

 

Silvia Suardi1, Chiara Vimercati1, Fabio Moda1, Ruggerone Margherita1, Ilaria Campagnani1, Guerino Lombardi2, Daniela Gelmetti2, Martin H. Groschup3, Anne Buschmann3, Cristina Casalone4, Maria Caramelli4, Salvatore Monaco5, Gianluigi Zanusso5, Fabrizio Tagliavini1 1Carlo Besta" Neurological Institute,Italy; 2IZS Brescia, Italy; 33FLI Insel Riems, D, Germany; 4CEA-IZS Torino, Italy; 5University of Verona, Italy

 

Background: BASE is an atypical form of bovine spongiform encephalopathy caused by a prion strain distinct from that of BSE. Upon experimental transmission to cattle, BASE induces a previously unrecognized disease phenotype marked by mental dullness and progressive atrophy of hind limb musculature. Whether affected muscles contain infectivity is unknown. This is a critical issue since the BASE strain is readily transmissible to a variety of hosts including primates, suggesting that humans may be susceptible.

 

Objectives: To investigate the distribution of infectivity in peripheral tissues of cattle experimentally infected with BASE. Methods: Groups of Tg mice expressing bovine PrP (Tgbov XV, n= 7-15/group) were inoculated both i.c. and i.p. with 10% homogenates of a variety of tissues including brain, spleen, cervical lymph node, kidney and skeletal muscle (m. longissimus dorsi) from cattle intracerebrally infected with BASE. No PrPres was detectable in the peripheral tissues used for inoculation either by immunohistochemistry or Western blot.

 

Results: Mice inoculated with BASE-brain homogenates showed clinical signs of disease with incubation and survival times of 175±15 and 207±12 days. Five out of seven mice challenged with skeletal muscle developed a similar neurological disorder, with incubation and survival times of 380±11 and 410±12 days. At present (700 days after inoculation) mice challenged with the other peripheral tissues are still healthy. The neuropathological phenotype and PrPres type of the affected mice inoculated either with brain or muscle were indistinguishable and matched those of Tgbov XV mice infected with natural BASE.

 

Discussion: Our data indicate that the skeletal muscle of cattle experimentally infected with BASE contains significant amount of infectivity, at variance with BSE-affected cattle, raising the issue of intraspecies transmission and the potential risk for humans. Experiments are in progress to assess the presence of infectivity in skeletal muscles of natural BASE.

 


 

 

 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

 


 

 

WHAT about the sporadic CJD TSE proteins ?

 

WE now know that some cases of sporadic CJD are linked to atypical BSE and atypical Scrapie, so why are not MORE concerned about the sporadic CJD, and all it’s sub-types $$$

 

Creutzfeldt-Jakob Disease CJD cases rising North America updated report August 2013

 

*** Creutzfeldt-Jakob Disease CJD cases rising North America with Canada seeing an extreme increase of 48% between 2008 and 2010 ***

 


 

Sunday, October 13, 2013

 

*** CJD TSE Prion Disease Cases in Texas by Year, 2003-2012

 


 

 Thursday, January 2, 2014

 

*** CWD TSE Prion in cervids to hTGmice, Heidenhain Variant Creutzfeldt-Jacob Disease MM1 genotype, and iatrogenic CJD ???

 


 

 Friday, January 10, 2014

 

*** vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ???

 


 

 Monday, January 13, 2014

 

*** Prions in Variably Protease-Sensitive Prionopathy: An Update Pathogens 2013

 

Pathogens 2013, 2, 457-471; doi:10.3390/pathogens2030457

 


 

Wednesday, January 15, 2014

 

*** INFECTION PREVENTION AND CONTROL OF CJD, VCJD AND OTHER HUMAN PRION DISEASES IN HEALTHCARE AND COMMUNITY SETTINGS Variably Protease-Sensitive Prionopathy (VPSPr) January 15, 2014

 


 

Sunday, January 19, 2014

 

*** National Prion Disease Pathology Surveillance Center Cases Examined1 as of January 8, 2014 ***

 


 

Thursday, January 23, 2014

 

Medical Devices Containing Materials Derived from Animal Sources (Except for In Vitro Diagnostic Devices) [Docket No. FDA–2013–D–1574]

 


 

 

 Saturday, February 01, 2014

 

vCJD With Extremely Low Lymphoreticular Deposition of Prion Protein MAY NOT HAVE BEEN DETECTABLE

 


 

 

 Terry S. Singeltary Sr. Bacliff, Texas USA 77518 flounder9@verizon.net

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