Biochemical typing of pathological prion protein in aging cattle with BSE

Biochemical typing of pathological prion protein in aging cattle with BSE

Virology Journal 2009, 6:64 doi:10.1186/1743-422X-6-64 Seraina Tester (mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000056/!x-usc:mailto:seraina.tester@itn.unibe.ch) Valerie Juillerat (mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000056/!x-usc:mailto:valerie.juillerat@itn.unibe.ch) Marcus G Doherr (mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000056/!x-usc:mailto:marcus.doherr@itn.unibe.ch) Bianca Haase (mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000056/!x-usc:mailto:bianca.haase@itz.unibe.ch) Miroslaw Polak (mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000056/!x-usc:mailto:ppolak@piwet.pulawy.pl) Felix Ehrensperger (mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000056/!x-usc:mailto:f.ehrensperger@vetpath.uzh.ch) Tosso Leeb (mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000056/!x-usc:mailto:tosso.leeb@itz.unibe.ch) Andreas Zurbriggen (mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000056/!x-usc:mailto:andreas.zurbriggen@itn.unibe.ch) Torsten Seuberlich (mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000056/!x-usc:mailto:torsten.seuberlich@itn.unibe.ch) ISSN 1743-422X Article type Research Submission date 23 March 2009 Acceptance date 26 May 2009 Publication date 26 May 2009 Article URL http://www.virologyj.com/content/6/1/64 This peer-reviewed article was published immediately upon acceptance. It can be downloaded, printed and distributed freely for any purposes (see copyright notice below). Articles in Virology Journal are listed in PubMed and archived at PubMed Central. For information about publishing your research in Virology Journal or any BioMed Central journal, go to http://www.virologyj.com/info/instructions/ For information about other BioMed Central publications go to http://www.biomedcentral.com/ Virology Journal © 2009 Tester et al. , licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 1

Biochemical typing of pathological prion protein in aging cattle with BSE

Seraina Tester1, Valerie Juillerat1, Marcus G. Doherr1, Bianca Haase2, Miroslaw Polak3, Felix Ehrensperger4, Tosso Leeb2, Andreas Zurbriggen1 and Torsten Seuberlich1* 1 NeuroCenter, Reference Laboratory for TSE in animals, Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Berne, Switzerland 2 Institute of Genetics, Vetsuisse Faculty, University of Berne, Switzerland 3 National Veterinary Research Institute, Pulawy, Poland 4 Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zürich, Switzerland ST: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000056/!x-usc:mailto:seraina.tester@itn.unibe.ch VJ: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000056/!x-usc:mailto:vallerie.juillerat@itn.unibe.ch MGD: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000056/!x-usc:mailto:marcus.doherr@itn.unibe.ch BH: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000056/!x-usc:mailto:bianca.haase@itz.unibe.ch MP: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000056/!x-usc:mailto:ppolak@piwet.pulawy.pl FE: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000056/!x-usc:mailto:f.ehrensperger@vetpath.uzh.ch TL: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000056/!x-usc:mailto:tosso.leeb@itz.unibe.ch AZ: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000056/!x-usc:mailto:andreas.zurbriggen@itn.unibe.ch *Corresponding author: Dr. med. vet. Torsten Seuberlich NeuroCenter - Reference Laboratory for TSE in animals Department of Clinical Research and VPH Vetsuisse Faculty University of Berne Bremgartenstrasse 109a CH- 3001 Berne Switzerland Email: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000056/!x-usc:mailto:torsten.seuberlich@itn.unibe.ch Phone: +41 31 631 2206 Fax: +41 31 631 2538 2

Abstract:

Background

The broad enforcement of active surveillance for bovine spongiform encephalopathy (BSE) in 2000 led to the discovery of previously unnoticed, atypical BSE phenotypes in aged cattle that differed from classical BSE (C-type) in biochemical properties of the pathological prion protein. Depending on the molecular mass and the degree of glycosylation of its proteinase K resistant core fragment (PrPres), mainly determined in samples derived from the medulla oblongata, these atypical cases are currently classified into low (L)-type or high (H)-type BSE. In the present study we address the question to what extent such atypical BSE cases are part of the BSE epidemic in Switzerland.

Results

To this end we analyzed the biochemical PrPres type by Western blot in a total of 33 BSE cases in cattle with a minimum age of eight years, targeting up to ten different brain regions. Our work confirmed H-type BSE in a zebu but classified all other cases as C-type BSE; indicating a very low incidence of H- and L-type BSE in Switzerland. It was documented for the first time that the biochemical PrPres type was consistent across different brain regions of aging animals with C-type and H-type BSE, i.e. independent of the neuroanatomical structure investigated.

Conclusions

Taken together this study provides further characteristics of the BSE epidemic in Switzerland and generates new baseline data for the definition of C- and H-type BSE phenotypes, thereby underpinning the notion that they indeed represent distinct prion disease entities.

snip...

Conclusions

Taken together these results indicate that the prevalence of H- and L-type BSE in Switzerland remains under the detection limit of the Swiss active surveillance program. However one H-type BSE case was identified by passive BSE surveillance and proves in principle the capacity to identify such cases in the population. Hence, the overall prevalence of atypical BSE in Switzerland appears very low and similar to what has been reported from other countries. It has been speculated and strengthened by experimental data [53,54] that atypical BSE once recycled in the cattle population was the origin of the worldwide BSE epidemic in the last 20 years. If this holds true and such cases occur spontaneously in the population, then BSE might never be completely eradicated. Furthermore, in these circumstances, it would be hazardous to relieve certain disease control measures, including the total prohibition of MBM in ruminant feed.



http://www.virologyj.com/content/pdf/1743-422X-6-64.pdf





Greetings,


O.K., let me get this straight, we have typical, U.K. c-BSE, we have now a spontaneous atypical h-BSE and l-BSE, of which they are now just calling an 'old cow disease', which happens spontaneously without any route or source, just happens.

OH, and then we have the new/old ibncBSE, of which is just another 'old cow prion disease', another one of those spontaneous events $$$

IT SEEMS there is a pattern here to make all Transmissible Spongiform Encephalopathies a spontaneous event, even though there is no such evidence what so ever.

WITH all the sub-types of TSE showing up now in the Scrapie, BSE, CWD, (all of which has been rendered and fed back to livestock producing animals for human and animal feed), and even in humans i.e. CJD, there is no way, they know for a fact that all are of a spontaneous, sporadic event, that just happened due to a twisted up protein that folded the wrong way by itself, from no route and no source. they do NOT know if any of these atypical TSE are of a spontaneous old cows prion disease or not, but yet they preach it like it's the gospel $$$

I don't believe them today, and i will never believe that 85%+ of all human sporadic CJD, just happens without any route and source from anything. ...


kind regards, terry



Absence of spontaneous disease and comparative prion susceptibility of transgenic mice expressing mutant human prion proteins

Emmanuel A. Asante, Ian Gowland, Andrew Grimshaw, Jacqueline M. Linehan, Michelle Smidak, Richard Houghton, Olufunmilayo Osiguwa, Andrew Tomlinson, Susan Joiner, Sebastian Brandner, Jonathan D. F. Wadsworth and John Collinge Correspondence John Collinge mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000056/!x-usc:mailto:j.collinge@prion.ucl.ac.uk MRC Prion Unit and Department of Neurodegenerative Disease, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK Received 15 October 2008 Accepted 2 December 2008

Approximately 15% of human prion disease is associated with autosomal-dominant pathogenic mutations in the prion protein (PrP) gene. Previous attempts to model these diseases in mice have expressed human PrP mutations in murine PrP, but this may have different structural consequences. Here, we describe transgenic mice expressing human PrP with P102L or E200K mutations and methionine (M) at the polymorphic residue 129. Although no spontaneous disease developed in aged animals, these mice were readily susceptible to prion infection from patients with the homotypic pathogenic mutation. However, while variant Creutzfeldt-Jakob disease (CJD) prions transmitted infection efficiently to both lines of mice, markedly different susceptibilities to classical (sporadic and iatrogenic) CJD prions were observed. Prions from E200K and classical CJD M129 homozygous patients, transmitted disease with equivalent efficiencies and short incubation periods in human PrP 200K, 129M transgenic mice. However, mismatch at residue 129 between inoculum and host dramatically increased the incubation period. In human PrP 102L, 129M transgenic mice, short disease incubation periods were only observed with transmissions of prions from P102L patients, whereas classical CJD prions showed prolonged and variable incubation periods irrespective of the codon 129 genotype. Analysis of diseaserelated PrP (PrPSc) showed marked alteration in the PrPSc glycoform ratio propagated after transmission of classical CJD prions, consistent with the PrP point mutations directly influencing PrPSc assembly. These data indicate that P102L or E200K mutations of human PrP have differing effects on prion propagation that depend upon prion strain type and can be significantly influenced by mismatch at the polymorphic residue 129.

snip...

Transgenic mice expressing high levels of mouse PrP 101L (equivalent to 102L in human PrP) spontaneously developed neurological dysfunction at 166 days of age (Hsiao et al., 1990). PrPSc levels were low or undetectable, and brain extracts from affected mice did not transmit CNS degeneration to wild-type mice, but transmission to hamsters and Tg(GSSPrP)196 mice, expressing lower levels of the same mutant transgene product, was reported (Hsiao et al., 1994; Telling et al., 1996a). These Tg(GSSPrP)196 mice have subsequently been reported to develop spontaneous disease at advanced age (Tremblay et al., 2004; Nazor et al., 2005). It therefore remains debateable as to whether prions had been generated in these transgenic mice or this simply represents acceleration of a spontaneous neurodegenerative disease already poised to occur in these mice (Nazor et al., 2005). Others generated transgenic mice expressing endogenous levels of mouse PrP 101L by the gene knock-in approach (Manson et al., 1999). These mice did not develop spontaneous neurodegeneration but were reported to show greater susceptibility to human P102L prions than wildtype mice (Barron et al., 2001).

However, we consider it essential to study this and other human pathogenic mutations in human PrP, rather than in mouse PrP where the mutation may have different structural consequences. With respect to such models it is important to demonstrate that human PrP is functionally active and can participate in prion propagation and pathogenesis in mouse cells. Human PrP can rescue a PrP null phenotype in mice (Whittington et al., 1995), confirming it is functionally active and human prions can replicate in transgenic mice expressing only human PrP, which develop spongiform neurodegeneration (Collinge et al., 1995).

snip...see full text ;



http://vir.sgmjournals.org/cgi/reprint/90/3/546



****** [2] Correction Date: Tue 5 Sep 2006 From: "Terry S Singeltary Sr" <mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000056/!x-usc:mailto:flounder9@verizon.net>

Characterization of atypical BSE in Germany:


correction -------------------------------------------------------


[In the Moderator's comment accompanying the abstract of the paper entitled "Atypical BSE in Germany-Proof of transmissibility and biochemical characterization'" by A Buschmannaet et al, (see part [2] of CJD (new var.) update 2006 (09) 20060904.2519) it was wrongly implied that Terry S Singeltary Sr endorsed the conclusions of the paper, whereas his comments were intended merely to highlight the conclusions of the paper. Namely that the atypical cases suggested the possible existence of sporadic BSE cases in bovines and perhaps the BSE epidemic in the UK could have also been initiated by an intraspecies transmission from a sporadic BSE case. I apologize for inadvertently misrepresenting Terry's views. - Mod.CP]

Terry S Singeltary Sr has written the following. "In fact I disagree with the spontaneous/sporadic BSE/TSE theory, IF this is what the authors of this paper meant by 'sporadic BSE' to mean. For one thing, it has never been proven. IF atypical BSE i.e. BASE is so similar to some sporadic CJDs, then how did they all of a sudden become spontaneous? Could it not be so simple as an atypical BSE i.e. BASE was transmitted the same way most of all of the other BSE cattle were i.e. feed of just an atypical source, thus causing atypical strain? Why would these animals not develop an atypical BSE i.e. BASE from the same oral route? WHAT about an atypical strain mutating to become infectious via a lateral or horizontal mode in the bovine, as with CWD and scrapie? Also, please explain to me how a distinct synthetic prion, of a strain that is supposedly unlike any other we have ever seen, how can this explain 6 different documented phenotypes of sporadic CJD to date?

It's like trying to explain away all the 6 phenotypes of sporadic CJD with the spontaneous theory, it's just not scientific. OR, if you render an atypical TSE of what ever phenotype, in what ever species, of the atypical strain and feed it to another whatever species, nothing happens x 1 x 2 x 3 x 4 etc passage? This all has been proven?

Please show me these transmission studies? What Prusiner and Soto produced in vitro did not look like any natural field TSE, and as far as this in vitro TSE being infectious, well this was questionable too. If this was the case, then why does CWD not spontaneously happen in geographical areas where it has never been documented, OR with scrapie, as in scrapie free New Zealand? If TSE were to arise spontaneously, I don't see how the scientific arena can dictate which animal TSE can arise spontaneously, and which ones cannot, without any scientific evidence to support this to date, and by even suggesting this in this study, was not scientific. The words sporadic and spontaneous are very confusing in the world literature of human and animal TSE and, in my opinion, should not be used as terminology of any TSE."

-- Terry S Singeltary Sr <mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000056/!x-usc:mailto:flounder9@verizon.net>



http://apex.oracle.com/pls/otn/f?p=2400:1202:17822992441545446841::NO::F2400_P1202_CHECK_DISPLAY,F2400_P1202_PUB_MAIL_ID:X,34659




Saturday, February 28, 2009

NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS "All of the 15 cattle tested showed that the brains had abnormally accumulated PrP" 2009 SEAC 102/2



http://bse-atypical.blogspot.com/2009/02/new-results-on-idiopathic-brainstem.html




Sunday, May 17, 2009

De Novo Generation of Infectious Prions In Vitro Produces a New Disease Phenotype



http://bse-atypical.blogspot.com/2009/05/de-novo-generation-of-infectious-prions.html




Monday, May 11, 2009

Rare BSE mutation raises concerns over risks to public health



http://bse-atypical.blogspot.com/2009/05/rare-bse-mutation-raises-concerns-over.html





Sunday, April 12, 2009


BSE MAD COW TESTING USA 2009 FIGURES Month Number of Tests


Feb 2009 -- 1,891

Jan 2009 -- 4,620



http://www.aphis.usda.gov/newsroom/hot_issues/bse/surveillance/ongoing_surv_results.shtml




SEE FULL TEXT ;



http://madcowtesting.blogspot.com/2009/04/bse-mad-cow-testing-usa-2009-figures.html




Monday, May 4, 2009

Back to the Past With New TSE Testing Agricultural Research/May-June 2009



http://madcowtesting.blogspot.com/2009/05/back-to-past-with-new-tse-testing.html




Sunday, May 10, 2009

Identification and characterization of bovine spongiform encephalopathy cases diagnosed and NOT diagnosed in the United States



http://bse-atypical.blogspot.com/2009/05/identification-and-characterization-of.html




Friday, May 29, 2009

Characterization of a U.S. Sheep Scrapie Isolate with Short Incubation Time




http://scrapie-usa.blogspot.com/2009/05/characterization-of-us-sheep-scrapie.html




Friday, May 29, 2009

Seven Deer Test Positive for Chronic Wasting Disease During 2009 Spring Collections in Hampshire County, West Virginia




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




O.K. confusious asks, IF all these new atypical BSEs i.e. new strains of mad cow disease is just an 'OLD COW PRION DISEASE', why then can not the 'old human prion disease' such as the sporadic CJD, be from an 'old cow prion disease', same as the nvCJD 'young people mad cow disease' (which also happens in 74 year old), but why cannot the 'old cow prion diseases', i.e. l-BSE, h-BSE, and ibncBSE, cause the 'old people prion disease', which looks like sporadic CJD. seems that is what some of the pathology is showing ???


OH, that probably makes too much sense, and that the only answer could be that it's all just a happenstance of bad luck and or a spontaneous event, that just happens out of the clear blue sky $$$


IF this is the case, then where are all the SPONTANEOUS BSE CASES OF MAD COW DISEASE IN THE U.S.A., AND WHERE HAVE THEY BEEN BURIED IN THE USA OVER THE LAST 25 YEARS ???


Atypical BSE North America Update February 2009



http://bse-atypical.blogspot.com/2009/02/atypical-bse-north-america-update.html




Sunday, December 28, 2008

MAD COW DISEASE USA DECEMBER 28, 2008 an 8 year review of a failed and flawed policy



http://bse-atypical.blogspot.com/2008/12/mad-cow-disease-usa-december-28-2008-8.html




Wednesday, August 20, 2008

Bovine Spongiform Encephalopathy Mad Cow Disease typical and atypical strains, was there a cover-up ?



http://bse-atypical.blogspot.com/2008/08/bovine-spongiform-encephalopathy-mad.html





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

NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS "All of the 15 cattle tested showed that the brains had abnormally accumulated PrP" 2009

SEAC 102/2

NEW RESULTS ON IDIOPATHIC BRAINSTEM NEURONAL CHROMATOLYSIS FROM THE VETERINARY LABORATORIES AGENCY

ISSUE

1. The Department for Environment, Food and Rural Affairs (Defra) has asked SEAC to consider a research article (Annex A) entitled “Idiopathic Brainstem Neuronal Chromatolysis (IBNC): a novel prion protein related disorder of cattle?” produced by the Veterinary Laboratories Agency.

2. Martin Jeffrey, the lead author of the article, will be present at the meeting to present an overview and answer questions.

BACKGROUND

3. IBNC is a rare1 neurodegenerative disease of adult cattle. This disorder has some clinical similarity to BSE and was initially recognised from histological examination of cattle brains submitted as part of the UK surveillance for BSE diagnosis in 1989. However, the brains of IBNC-affected cattle have pathological features which are clearly different from those seen in BSE. Most cases have been detected in Scotland, but it is not known if this is a true distribution or primarily because Scottish scientists have examined BSE negative cases in more detail. The last reported case of IBNC in an animal presented as a BSE suspect was in 2005, in an animal born in 1992.

PREVIOUS CONSIDERATION BY SEAC

4. SEAC first considered IBNC at its 14th meeting (April 1993) and emphasised the importance of defining the new condition in detail with

1 Between the years 1988 and 1991 IBNC occurred in Scotland with an incidence of 7 cases per 100,000 beef suckler cattle over the age of 6 years (from Annex A).

transmission studies and PrP examination. The next discussion was at the 19th meeting (June 1995), when the committee reflected on results of transmission studies in mice (VM, RIII, C57 and C57xVM mice) from brains of two cattle with IBNC. Some mice had shown signs of TSE disease, but it was suggested this could have been due to low level BSE contamination of the samples. The committee recommended that further investigations should be carried out on isolates from brains of IBNC cases with removal of the brain and subsequent handling under conditions that would prevent contamination.

5. At the 49th meeting (March 1998) the committee considered a further IBNC transmission study in which the brain from an IBNC case was removed under aseptic conditions. The mouse strains challenged were RIII, VM, C57BL, C57BL x VM and IM. These experiments ran for between 577 and 631 days and no clinical signs of transmission were evident. The Committee stated2 it was content that, although little was known about IBNC, it did not constitute a health risk to man because suspect IBNC cases would be taken as BSE suspects or caught by the Over Thirty Months (OTM) Scheme.

6. Annex B contains the minutes of the discussions on IBNC at previous SEAC meetings.

NEW RESULTS

7. The research article “Idiopathic Brainstem Neuronal Chromatolysis (IBNC): a novel prion protein related disorder of cattle?” was published in September 2008. The cases studied concerned brains from cattle killed between 1993 and 2005 when they were between 5 and 15 years of age. All of the 15 cattle tested showed that the brains had abnormally accumulated prion protein.

8. Defra has asked that SEAC considers the VLA paper in order to confirm or revise its previous views on this disorder as:

• This is the first time IBNC has been shown to be associated with abnormal expression or accumulation of the prion protein.

• The previous transmission studies conducted in the 1990s were inconclusive and repeat studies are planned.

• IBNC is thought to be rare but the exact prevalence of the disorder is unknown, as IBNC would not be picked up through the

2 At 49th SEAC meeting (9th March 1998), paragraph 52, see Annex B.

active surveillance programme for BSE which uses rapid post-mortem tests to detect proteinase-K resistant PrPSc.

9. Additionally, TSE controls on older cattle have changed since the previous SEAC advice in 1998. For example the OTM Scheme, which was in operation then, has now been replaced with testing of cattle slaughtered for human consumption aged over 48 months. Other controls remain, such as compulsory notification of suspected BSE, ante-mortem inspection, specified risk for cattle slaughtered for human consumption and a ban on cattle born or reared in UK before 1st August 1996 entering the food chain.

FUTURE RESEARCH

10. VLA are hoping to carry out further mouse transmission studies of IBNC cases as part of a larger project, on TSE molecular sciences, about which Defra is currently in advanced negotiations with VLA. If new cases of IBNC occur, it is planned that the brains from 2 cases of IBNC will be obtained and bioassayed in transgenic mouse lines, expressing bovine PrP or ovine PrP (PrP genotype AHQ), developed by the VLA.

ADVICE SOUGHT

11. The committee is asked to consider:

• if the paper changes the previous opinion of SEAC in 1998?

• if members have any comments on the further research planned?

SEAC SECRETARIAT

FEBRUARY 2009

ANNEX A

A copy of the paper “Idiopathic Brainstem Neuronal

snip...

full text ;



http://www.seac.gov.uk/papers/102-2.pdf





>>>All of the 15 cattle tested showed that the brains had abnormally accumulated prion protein.<<<>>>



Considering that Mad Cow disease of all documented phenotypes, either the c-BSE, or the atypical h-BSE and or the l-BSE, ALL of which have been documented in North America, how many more, who knows, but they seem to be throwing all there marbles in the pot now by calling the h-type BSE 'familial'. what happens if we come up with another strain ?



http://creutzfeldt-jakob-disease.blogspot.com/2009/02/case-control-study-of-sporadic.html





Wednesday, October 08, 2008 Idiopathic Brainstem Neuronal Chromatolysis (IBNC): a novel prion protein related disorder of cattle?



http://bse-atypical.blogspot.com/2008/10/idiopathic-brainstem-neuronal.html



''THE LINE TO TAKE'' ON IBNC $$$ 1995 $$$



1995


page 9 of 14 ;


30. The Committee noted that the results were unusual. the questioned whether there could be coincidental BSE infection or contamination with scrapie. Dr. Tyrell noted that the feeling of the committee was that this did not represent a new agent but it was important to be prepared to say something publicly about these findings. A suggested line to take was that these were scientifically unpublishable results but in line with the policy of openness they would be made publicly available and further work done to test their validity. Since the BSE precautions were applied to IBNC cases, human health was protected. Further investigations should be carried out on isolations from brains of IBNC cases with removal of the brain and subsequent handling under strict conditions to avoid the risk of any contamination.


31. Mr. Bradley informed the Committee that the CVO had informed the CMO about the IBNC results and the transmission from retina and he, like the Committee was satisfied that the controls already in place or proposed were adequate. ...


snip... see full text



http://web.archive.org/web/20010305223122/www.bseinquiry.gov.uk/files/yb/1995/06/21005001.pdf



(page 8, bottom paragraph first, then top paragraph at bottom...TSS)


DRAFT


SPONGIFORM ENCEPHALOPATHY ADVISORY COMMITTEE MINUTES OF THE 19TH MEETING HELD ON 21 JUNE 1995 AT THE CENTRAL VETERINARY LABORATORY


Idiopathic Brain Stem Neuronal Chromatolysis (IBNC)

29. Mr. Bradley described the results of transmission studies in mice from brains of two cows with IBNC (paper SEAC 19/8). At the previous meeting of SEAC, and at the review of R&D, it had been announced that there was no clinical observation of a scrapie-like disease in mice: this information had proved to be INCORRECT for a number of reasons. Of the mice inoculated with brain tissue from the first cow, there had been mild transient clinical signs, one had shown equivocal lesions of SE but PrP studies had proved negative. From the second cow there were two definite cases of SE though the lesion distribution and incubation period were not the same as seen in mice inoculated with brain from BSE cases or any characterized strain of scrapie. The lesions in these two mice were PrP positive. There was no obvious evidence of any mix up though one possible area of cross-contamination was during the necropsy in the Perth VIC. More evidence would be needed and further transmission studies to validate the results and proposals were put forward for further study.

30. The Committee noted that the results were unusual. They questioned whether there could be coincidental BSE infection or contamination with scrapie. Dr Tyrrell noted that the feeling of the Committee was that this did not represent a new agent but it was important to be prepared to say something publicly about these findings. A suggested line to take was that these were scientifically unpublishable results but in line with the policy of openness they would be made publicly available and further work done to test their validity. Since the BSE precautions were applied to IBNC cases, human health was protected. Further investigations should be carried out on isolations from brains of IBNC cases with removal of the brain and subsequent handling under strict conditions to avoid the risk of any contamination.

31. Mr Bradley informed the Committee that the CVO had informed the CMO about the IBNC results and the transmission from retina and he, like the Committee was satisfied that the controls already in place or proposed were adequate.

Agenda Item 7 - Any Other Business: the Hounds Survey

26. Paper SEAC 19/7 responded to a request from the Committee for a re-evaluation of the pathology material in the hounds survey to determine whether anything further could be derived from the available data.

27. In discussion of the options for further work set out in the paper most members felt that the study had been badly carried out and there would be little value in spending more money to try and improve the interpretation of the data. It was particularly significant that no clinical data were available, although the Committee were reminded that most of the hounds were clinically normal culls. Dr Kimberlin was concerned about the lack of results from the study. Any further work would require a control but this could be obtained by exposing hounds to BSE which would also help to answer questions about species sensitivity, thereby serving more than one purpose. The use of immunocytochemistry was fairly robust and would enable the work to be brought to a satisfactory conclusion. Dr Kimberlin's view that this would be necessary was confirmed by an article, circulated at the meeting, showing that the predictive protein sequence was the same in dogs as in cattle. Mr Eddy noted that such an experiment could be expensive and it would be necessary to know what questions were to be addressed.

28. Concluding, Dr Tyrrell said that there was a range of opinions in the Committee from those who thought further work a waste of time to those who wished to do limited further experiments using immunocytochemistry. The Committee did not suggest transmission studies and thought that the lack of clinical data was a major weakness. Hounds were initially studied on the recommendation of the Southwood Committee because they were perceived as a ''high risk'' population exposed to large quantities of potentially infective bovine tissues. SINCE THEN, HOWEVER, A RANGE OF OTHER SPECIES HAD BEEN IDENTIFIED WITH TSEs, AND THE STUDY OF HOUNDS WAS THEREFORE LESS CRITICAL. ...

snip...end




http://web.archive.org/web/20010305223122/www.bseinquiry.gov.uk/files/yb/1995/06/21005001.pdf





for the life of me i do not understand that last sentence???


you can see DEFRA comment to me about the Hound Study here, but if anyone claims BSE and or TSE will not transmit to hounds, well, i would beg to differ. ... they don't know, but evidence to date sure looks like something transmitted to the hounds. so why did they halt all scientific investigations of this $$$ same as with the INBC BSE cover-up. they don't want to know, and they don't want you to know. old deep throat warned me about Mr. Ray Bradley 10 years ago. ...TSS






http://felinespongiformencephalopathyfse.blogspot.com/2009/04/immunohistochemical-study-of-prpsc.html






update ;


2009 31 March 2009 - A summary of the 102nd SEAC meeting (35 KB) held on 4th March 2009


snip...

SEAC noted that IBNC appeared to be a rare disease that occurred in older cattle, predominantly as single cases, although it is possible that surveillance may not detect all cases. Biochemical studies suggested that the prion protein may play a role in the disease. However, it is unclear whether the normal form of the protein or an abnormal form is involved. Studies are required to determine whether IBNC is transmissible or not. SEAC concluded, noting that specified risk material controls are in place to prevent cattle brain from entering the food supply, that current data on IBNC do not suggest it presents a risk to human health.




http://www.seac.gov.uk/summaries/seac102_summary.pdf





>>> All of the 15 cattle tested showed that the brains had abnormally accumulated prion protein. <<<




http://bse-atypical.blogspot.com/2009/02/new-results-on-idiopathic-brainstem.html






http://bse-atypical.blogspot.com/2009/02/new-results-on-idiopathic-brainstem.html







???


TSS




Sunday, December 28, 2008

MAD COW DISEASE USA DECEMBER 28, 2008 an 8 year review of a failed and flawed policy




http://bse-atypical.blogspot.com/2008/12/mad-cow-disease-usa-december-28-2008-8.html




Saturday, January 24, 2009

Bovine Spongiform Encephalopathy h-BSE ATYPICAL USA 2008 Annual Report Research Project: Study of Atypical Bse

Location: Virus and Prion Diseases of Livestock

2008 Annual Report



http://bse-atypical.blogspot.com/2009/01/bovine-spongiform-encephalopathy-h-bse.html




Wednesday, January 28, 2009

TAFS1 Position Paper on BSE in small ruminants (January 2009)



http://scrapie-usa.blogspot.com/2009/01/tafs1-position-paper-on-bse-in-small.html



10,000,000+ LBS. of PROHIBITED BANNED MAD COW FEED I.E. MBM IN COMMERCE USA 2007

Date: March 21, 2007 at 2:27 pm PST REASON Blood meal used to make cattle feed was recalled because it was cross-contaminated with prohibited bovine meat and bone meal that had been manufactured on common equipment and labeling did not bear cautionary BSE statement. VOLUME OF PRODUCT IN COMMERCE 42,090 lbs. DISTRIBUTION WI

REASON Products manufactured from bulk feed containing blood meal that was cross contaminated with prohibited meat and bone meal and the labeling did not bear cautionary BSE statement. VOLUME OF PRODUCT IN COMMERCE 9,997,976 lbs. DISTRIBUTION ID and NV

END OF ENFORCEMENT REPORT FOR MARCH 21, 2007



http://www.fda.gov/bbs/topics/enforce/2007/ENF00996.html



Wednesday, January 28, 2009

TAFS1 Position Paper on Specified Risk Materials (January, 2009)

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

(January 2009)

TAFS1 Position Paper on Specified Risk Materials



http://madcowspontaneousnot.blogspot.com/2009/01/tafs1-position-paper-on-specified-risk.html



TAFS1 Position Paper on Testing of Cattle for BSE (Revision January 2009)



http://madcowtesting.blogspot.com/2009/02/tafs1-position-paper-on-testing-of.html



Tuesday, November 11, 2008

Transmission of atypical bovine prions to mice transgenic for human prion protein

DOI: 10.3201/eid1412.080941



http://bse-atypical.blogspot.com/2008/11/transmission-of-atypical-bovine-prions.html



Wednesday, August 20, 2008

Bovine Spongiform Encephalopathy Mad Cow Disease typical and atypical strains, was there a cover-up ?



http://bse-atypical.blogspot.com/2008/08/bovine-spongiform-encephalopathy-mad.html




In this context, a word is in order about the US testing program. After the discovery of the first (imported) cow in 2003, the magnitude of testing was much increased, reaching a level of >400,000 tests in 2005 (Figure 4). Neither of the 2 more recently indigenously infected older animals with nonspecific clinical features would have been detected without such testing, and neither would have been identified as atypical without confirmatory Western blots. Despite these facts, surveillance has now been decimated to 40,000 annual tests (USDA news release no. 0255.06, July 20, 2006) and invites the accusation that the United States will never know the true status of its involvement with BSE.

In short, a great deal of further work will need to be done before the phenotypic features and prevalence of atypical BSE are understood. More than a single strain may have been present from the beginning of the epidemic, but this possibility has been overlooked by virtue of the absence of widespread Western blot confirmatory testing of positive screening test results; or these new phenotypes may be found, at least in part, to result from infections at an older age by a typical BSE agent, rather than neonatal infections with new "strains" of BSE. Neither alternative has yet been investigated.



http://www.cdc.gov/ncidod/EID/vol12no12/06-0965.htm



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

http://www.upi.com/

CDC - Bovine Spongiform Encephalopathy and Variant Creutzfeldt ... Dr. Paul Brown is Senior Research Scientist in the Laboratory of Central Nervous System ... Address for correspondence: Paul Brown, Building 36, Room 4A-05, ...



http://www.cdc.gov/ncidod/eid/vol7no1/brown.htm



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."



http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0703&L=sanet-mg&T=0&P=8125



A New Prionopathy OR more of the same old BSe and sporadic CJD



http://creutzfeldt-jakob-disease.blogspot.com/2008/08/new-prionopathy-or-more-of-same-old-bse.html



Communicated by: Terry S. Singeltary Sr.

[In submitting these data, Terry S. Singeltary Sr. draws attention to the steady increase in the "type unknown" category, which, according to their definition, comprises cases in which vCJD could be excluded. The total of 26 cases for the current year (2007) is disturbing, possibly symptomatic of the circulation of novel agents. Characterization of these agents should be given a high priority. - Mod.CP]



http://pro-med.blogspot.com/2007/11/proahedr-prion-disease-update-2007-07.html



http://www.promedmail.org/pls/askus/f?p=2400:1001:6833194127530602005::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1010,39963



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

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



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



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



sporadic Fatal Familial Insomnia



http://sporadicffi.blogspot.com/



THE PATHOLOGICAL PROTEIN

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

June 2003

BY Philip Yam

CHAPTER 14 LAYING ODDS

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



http://www.thepathologicalprotein.com/



The Lancet Infectious Diseases, Volume 3, Issue 8, Page 463, August 2003

doi:10.1016/S1473-3099(03)00715-1Cite or Link Using DOI

Tracking spongiform encephalopathies in North America

Original TextXavier Bosch

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



http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(03)00715-1/fulltext



http://www.thelancet.com/journals/laninf/article/PIIS1473309903007151/%20fulltext



http://www.ncbi.nlm.nih.gov/pubmed/12906010



http://infection.thelancet.com/journal/journal.isa




JOURNAL OF NEUROLOGY

MARCH 26, 2003

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

disease in the United States

Email Terry S. Singeltary:

mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000116/!x-usc:mailto:flounder@wt.net

I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment on the CDC's attempts to monitor the occurrence of emerging forms of CJD. Asante, Collinge et al [1] have reported that BSE transmission to the 129-methionine genotype can lead to an alternate phenotype that is indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD and all human TSEs are not reportable nationally. CJD and all human TSEs must be made reportable in every state and internationally. I hope that the CDC does not continue to expect us to still believe that the 85%+ of all CJD cases which are sporadic are all spontaneous, without route/source. We have many TSEs in the USA in both animal and man. CWD in deer/elk is spreading rapidly and CWD does transmit to mink, ferret, cattle, and squirrel monkey by intracerebral inoculation. With the known incubation periods in other TSEs, oral transmission studies of CWD may take much longer. Every victim/family of CJD/TSEs should be asked about route and source of this agent. To prolong this will only spread the agent and needlessly expose others. In light of the findings of Asante and Collinge et al, there should be drastic measures to safeguard the medical and surgical arena from sporadic CJDs and all human TSEs. I only ponder how many sporadic CJDs in the USA are type 2 PrPSc?



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



Diagnosis and Reporting of Creutzfeldt-Jakob Disease Singeltary, Sr et al. JAMA.2001; 285: 733-734. Vol. 285 No. 6, February 14, 2001 JAMA

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

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

Terry S. Singeltary, Sr Bacliff, Tex

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



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



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




2 January 2000


British Medical Journal U.S. Scientist should be concerned with a CJD epidemic in the U.S., as well




http://www.bmj.com/cgi/eletters/320/7226/8/b#6117




15 November 1999


British Medical Journal vCJD in the USA * BSE in U.S.




http://www.bmj.com/cgi/eletters/319/7220/1312/b#5406




Creutzfeldt Jakob Disease




http://creutzfeldt-jakob-disease.blogspot.com/




***Atypical forms of BSE have emerged which, although rare, appear to be more virulent than the classical BSE that causes vCJD.***

Progress Report from the National Prion Disease Pathology Surveillance Center

An Update from Stephen M. Sergay, MB, BCh & Pierluigi Gambetti, MD

April 3, 2008



http://www.aan.com/news/?event=read&article_id=4397&page=72.45.45




USA PRION UNIT BLOG



http://prionunitusaupdate2008.blogspot.com/



Sunday, April 20, 2008 Progress Report from the National Prion Disease Pathology Surveillance Center April 3, 2008

Atypical forms of BSE have emerged which, although rare, appear to be more virulent than the classical BSE that causes vCJD.

see full text ;



http://prionunitusaupdate2008.blogspot.com/2008/04/progress-report-from-national-prion.html



CJD TEXAS (cjd clusters)



http://cjdtexas.blogspot.com/



USA WRITTEN CJD QUESTIONNAIRE ???



http://cjdquestionnaire.blogspot.com/



The statistical incidence of CJD cases in the United States has been revised to reflect that there is one case per 9000 in adults age 55 and older. Eighty-five percent of the cases are sporadic, meaning there is no known cause at present.



http://www.cjdfoundation.org/fact.html



Attending Dr.: Date / Time Admitted : 12/14/97 1228

UTMB University of Texas Medical Branch Galveston, Texas 77555-0543 (409) 772-1238 Fax (409) 772-5683 Pathology Report

FINAL AUTOPSY DIAGNOSIS Autopsy' Office (409)772-2858

FINAL AUTOPSY DIAGNOSIS

I. Brain: Creutzfeldt-Jakob disease, Heidenhain variant.



http://creutzfeldt-jakob-disease.blogspot.com/2008/07/heidenhain-variant-creutzfeldt-jakob.html



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