Isolation of two distinct prion strains from a scrapie-affected sheep
Isolation of two distinct prion strains from a scrapie-affected sheep
Kentaro Masujin • Yujing Shu • Hiroyuki Okada • Yuichi Matsuura • Yoshifumi Iwamaru • Morikazu Imamura • Shirou Mohri • Takashi Yokoyama Received: 27 July 2009 / Accepted: 29 September 2009 / Published online: 30 October 2009 The Author(s) 2009.
This article is published with open access at Springerlink.com Abstract
We performed a transmission study using mice to clarify the characteristics of the most recent case of scrapie in Japan. The mice that were inoculated with the brain homogenate from a scrapie-affected sheep developed progressive neurological disease, and one of the scrapieaffected mice showed unique clinical signs during primary transmission. This mouse developed obesity, polydipsia, and polyuria. In contrast, the other affected mice exhibited weight loss and hypokinesia. In subsequent passages, the mice showed distinct characteristic scrapie phenotypes. This finding may prove that different prion strains coexist in a naturally affected sheep with scrapie.
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Different types of PrPSc (types 1 and 2) were reported to co-exist in a case of sporadic Creutzfeldt–Jacob disease (sCJD) [15]. Scrapie in sheep is also proposed to be caused by mixed populations of different prion strains [16, 17]. In the present study, different prion strains were isolated from the brain of a scrapie-affected sheep during the primary transmission studies. In the previously reported CJD case, the PrPcore sizes of the two strains were different. In contrast, in the case reported in this study, although their PrPcore sizes were not different, the prions of the two strains showed distinct biological characteristics. In addition, this result showed that a transmission study using experimental animals is a useful approach for the isolation and characterization of prion strains. New TSE strains are believed to emerge due to mutations caused by differences in the primary PrP sequences of the host and the inoculum [17]. We observed that 3 out of 31 mice showed the characteristic clinical signs of the Ka/O strain in repeat trials of Ka/scrapie transmission (data not shown). This data indicates that the Ka/O strain shows a constant occurrence rate of 6–9%. Therefore, our findings may indicate that mixed prion populations exist in a strain in the brain of Ka/scrapie-affected sheep, while the Ka/O strain seemed to be the less dominant strain, which may have been inefficiently selected during interspecies transmission.
In this study, we examined the biological characteristics of prions in the most recent case of scrapie in Japan. On the basis of our results, we conclude that multiple prion strains coexist in a scrapie-affected sheep. To elucidate the molecular epidemiology of prion diseases, further studies should be conducted to clarify the mechanism underlying the emergence of new prion strains.
http://www.springerlink.com/content/f172377214414353/fulltext.pdf
Design and construction of diverse mammalian prion strains
David W. Colbya, Kurt Gilesa,b, Giuseppe Legnamea,b,1, Holger Willea,b, Ilia V. Baskakova,2, Stephen J. DeArmonda,c and Stanley B. Prusinera,b,3 + Author Affiliations
aInstitute for Neurodegenerative Diseases and Departments of bNeurology and cPathology, University of California, San Francisco, CA 94143 •?1Present address: Neurobiology Sector, Scuola Internazionale Superiore di Studi Avanzati, Trieste 34151, Italy.
•?2Present address: Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, MD 21201.
Contributed by Stanley B. Prusiner, September 11, 2009 (sent for review September 2, 2009)
Abstract
Prions are infectious proteins that encipher biological information within their conformations; variations in these conformations dictate different prion strains. Toward elucidating the molecular language of prion protein (PrP) conformations, we produced an array of recombinant PrP amyloids with varying conformational stabilities. In mice, the most stable amyloids produced the most stable prion strains that exhibited the longest incubation times, whereas more labile amyloids generated less stable strains and shorter incubation times. The direct relationship between stability and incubation time of prion strains suggests that labile prions are more fit, in that they accumulate more rapidly and thus kill the host faster. Although incubation times can be changed by altering the PrP expression level, PrP sequence, prion dose, or route of inoculation, we report here the ability to modify the incubation time predictably in mice by modulating the prion conformation.
synthetic prions stability amyloid neurodegeneration conformation Footnotes 3
To whom correspondence should be addressed. E-mail: stanley@ind.ucsf.eduAuthor contributions: D.W.C., G.L., and S.B.P. designed research; D.W.C., K.G., H.W., I.V.B., and S.J.D. performed research; D.W.C., K.G., H.W., S.J.D., and S.B.P. analyzed data; and D.W.C., S.J.D., and S.B.P. wrote the paper. The authors declare no conflict of interest.
http://www.pnas.org/content/early/2009/11/12/0910350106.abstract?etoc=
Scientific Opinion on genetic TSE resistance in goats in all European Union Member States Question number: EFSA-Q-2009-00448
Adopted: 21 October 2009 Summary (0.1Mb)
Opinion (0.3Mb)
Summary
Following a request from the European Commission, the Panel on Biological Hazards (BIOHAZ) was asked to deliver a scientific opinion on genetic resistance to Transmissible Spongiform Encephalopathies (TSE) in goats.
For a first part of that request, the BIOHAZ Panel adopted on 5th March 2009 a scientific opinion on the scientific validity of a study carried out by the Cypriot authorities under the auspices of the Community Reference Laboratory (CRL) for TSEs. That scientific opinion also indicated to what extent the information contained in the study could be used as relevant tools to control Classical scrapie in Cyprus.
In the current scientific opinion the BIOHAZ Panel addresses genetic resistance as a relevant tool for breeding for resistance to all TSEs of goats (including Atypical scrapie and BSE) in all the Member States (MSs) (except for Classical scrapie in Cyprus).
To carry out this task, available scientific knowledge on genetic TSE resistance in goats in the EU is reviewed, addressing those PRNP polymorphisms for which a capacity to provide resistance to TSEs in goats has been (or is being) investigated. Details tailored to the different TSEs found in this small ruminants (i.e. Classical scrapie, Atypical scrapie and BSE) are also considered and presented.
Further on, the feasibility of a large-scale breeding program in animal populations would need to be supported by a sound logistical and technical infrastructure in any given territory. In order to collect preliminary data that could help to evaluate the specific situation in the different EU MSs, a questionnaire was developed and circulated among the EFSA BSE-TSE Network. The results of the analysis of the replies received are also presented herewith.
The BIOHAZ Panel concluded that there are encouraging but as yet incomplete data to consider supporting a breeding programme for resistance in goats against Classical scrapie in all EU MSs, and ongoing studies are expected to provide a more robust scientific background in the coming years. On the other hand, at this moment there are not enough data available to consider supporting a breeding programme for resistance against Atypical scrapie and BSE in goats in all EU MSs. Experiments are ongoing on BSE in goats and results will be available in the next years. Furthermore, there are limited data suggesting that an allele (H154) might confer resistance to Classical scrapie but increase susceptibility to Atypical scrapie.
The frequency of the wild type allele, which is known to confer susceptibility to Classical scrapie, is high in all goat breeds considered. Thus, selection for putative resistance alleles will be slow, complicated and highly dependent on breeding structure.
It is acknowledged that any large scale breeding programme for TSE resistance in goats must take into consideration key elements related to the current dissemination of potentially TSE protective polymorphisms in the goat population of each EU MS and the characterisation of the real protection provided by those polymorphisms. At present, only a few EU MSs seem to have in place the necessary elements to introduce a breeding for resistance programme for Classical scrapie in goats.
The BIOHAZ Panel makes a series of recommendations on new investigations in order to assess the efficacy of breeding for the candidate PRNP alleles as a mean to control TSEs in goats. Furthermore, research on the possible adverse effects of the candidate PRNP polymorphisms on other production traits should be encouraged. In addition, it is recommended that a breeding for resistance programme for TSE in goats is first implemented in the seven EU MSs with the largest goat population as this would have the most impact.
Published: 9 November 2009
http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1211903027156.htm?WT.mc_id=EFSAHL01&emt=1
OPINION
http://www.efsa.europa.eu/EFSA/Scientific_Opinion/1371,0.pdf?ssbinary=true
Tuesday, November 10, 2009
A retrospective immunohistochemical study reveals atypical scrapie has existed in the United Kingdom since at least 1987
Brief Research Reports
http://nor-98.blogspot.com/2009/11/retrospective-immunohistochemical-study.html
Coexistence of multiple PrPSc types in individuals with Creutzfeldt-Jakob disease
Magdalini Polymenidou, Katharina Stoeck, Markus Glatzel, Martin Vey, Anne Bellon, and Adriano Aguzzi
Summary
Background The molecular typing of sporadic Creutzfeldt-Jakob disease (CJD) is based on the size and glycoform ratio of protease-resistant prion protein (PrPSc), and on PRNP haplotype. On digestion with proteinase K, type 1 and type 2 PrPSc display unglycosylated core fragments of 21 kDa and 19 kDa, resulting from cleavage around amino acids 82 and 97, respectively.
Methods
We generated anti-PrP monoclonal antibodies to epitopes immediately preceding the differential proteinase K cleavage sites. These antibodies, which were designated POM2 and POM12, recognise type 1, but not type 2, PrPSc.
Findings
We studied 114 brain samples from 70 patients with sporadic CJD and three patients with variant CJD. Every patient classified as CJD type 2, and all variant CJD patients, showed POM2/POM12 reactivity in the cerebellum and other PrPSc-rich brain areas, with a typical PrPSc type 1 migration pattern.
Interpretation
The regular coexistence of multiple PrPSc types in patients with CJD casts doubts on the validity of electrophoretic PrPSc mobilities as surrogates for prion strains, and questions the rational basis of current CJD classifications.
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The above results set the existing CJD classifications into debate and introduce interesting questions about human CJD types. For example, do human prion types exist in a dynamic equilibrium in the brains of affected individuals? Do they coexist in most or even all CJD cases? Is the biochemically identified PrPSc type simply the dominant type, and not the only PrPSc species?
Published online October 31, 2005
http://neurology.thelancet.com/
Detection of Type 1 Prion Protein in Variant Creutzfeldt-Jakob Disease
Helen M. Yull,* Diane L. Ritchie,* Jan P.M. Langeveld,? Fred G. van Zijderveld,? Moira E. Bruce,? James W. Ironside,* and Mark W. Head*
From the National CJD Surveillance Unit,* School of Molecular and Clinical Medicine, University of Edinburgh, Edinburgh, United Kingdom; Central Institute for Animal Disease Control (CIDC)-Lelystad, ? Lelystad, The Netherlands; Institute for Animal Health, Neuropathogenesis Unit, ? Edinburgh, United Kingdom
Molecular typing of the abnormal form of the prion protein (PrPSc) has come to be regarded as a powerful tool in the investigation of the prion diseases. All evidence thus far presented indicates a single PrPSc molecular type in variant Creutzfeldt-Jakob disease (termed type 2B), presumably resulting from infection with a single strain of the agent (bovine spongiform encephalopathy).
Here we show for the first time that the PrPSc that accumulates in the brain in variant Creutzfeldt- Jakob disease also contains a minority type 1 component. This minority type 1 PrPSc was found in all 21 cases of variant Creutzfeldt-Jakob disease tested, irrespective of brain region examined, and was also present in the variant Creutzfeldt-Jakob disease tonsil. The quantitative balance between PrPSc types was maintained when variant Creutzfeldt-Jakob disease was transmitted to wild-type mice and was also found in bovine spongiform encephalopathy cattle brain, indicating that the agent rather than the host specifies their relative representation. These results indicate that PrPSc molecular typing is based on quantitative rather than qualitative phenomena and point to a complex relationship between prion protein biochemistry, disease phenotype and agent strain. (Am J Pathol 2006, 168:151-157; DOI: 10.2353/ajpath.2006.050766)
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Discussion
Irrespective of whether this proves to be the case, the results shown here point to further complexities in the relationship between the physico-chemical properties of the prion protein, human disease phenotype, and prion agent strain.
Acknowledgments
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Type 1 PrPSc in Variant Creutzfeldt-Jakob Disease 157 AJP January 2006, Vol. 168, No. 1 ...TSS
http://ajp.amjpathol.org/
snip...see full text ;
Elsevier Editorial System(tm) for The Lancet Infectious Diseases Manuscript Draft Manuscript Number: Title: HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory Article Type: Personal View Corresponding Author: Mr. Terry S. Singeltary, Corresponding Author's Institution: na First Author: Terry S Singeltary, none Order of Authors: Terry S Singeltary, none; Terry S. Singeltary
http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648027c28e&disposition=attachment&contentType=pdf
Thursday, November 05, 2009
Incidence and spectrum of sporadic Creutzfeldt-Jakob disease variants with mixed phenotype and co-occurrence of PrPSc types: an updated classification
http://creutzfeldt-jakob-disease.blogspot.com/2009/11/incidence-and-spectrum-of-sporadic.html
ALSO, SEE Scrapie Mission, Texas, did not produce _typical_ BSE....
3.57 The experiment which might have determined whether BSE and scrapie were caused by the same agent (ie, the feeding of natural scrapie to cattle) was never undertaken in the UK. It was, however, performed in the USA in 1979, when it was shown that cattle inoculated with the scrapie agent endemic in the flock of Suffolk sheep at the United States Department of Agriculture in Mission, Texas, developed a TSE quite unlike BSE.339 The findings of the initial transmission, though not of the clinical or neurohistological examination, were communicated in October 1988 to Dr Watson, Director of the CVL, following a visit by Dr Wrathall, one of the project leaders in the Pathology Department of the CVL, to the United States Department of Agriculture.340 The results were not published at this point, since the attempted transmission to mice from the experimental cow brain had been inconclusive. The results of the clinical and histological differences between scrapie-affected sheep and cattle were published in 1995. Similar studies in which cattle were inoculated intracerebrally with scrapie inocula derived from a number of scrapie-affected sheep of different breeds and from different States, were carried out at the US National Animal Disease Centre.341 The results, published in 1994, showed that this source of scrapie agent, though pathogenic for cattle,
*** did not produce the same clinical signs of brain lesions characteristic of BSE. ***
3.58 There are several possible reasons why the experiment was not performed in the UK. It had been recommended by Sir Richard Southwood (Chairman of the Working Party on Bovine Spongiform Encephalopathy) in his letter to the Permanent Secretary of MAFF, Mr (now Sir) Derek Andrews, on 21 June 1988,342 though it was not specifically recommended in the Working Party Report or indeed in the Tyrrell Committee Report (details of the Southwood Working Party and the Tyrell Committee can be found in vol. 4: The Southwood Working Party, 1988–89 and vol. 11: Scientists after Southwood respectively). The direct inoculation of scrapie into calves was given low priority, because of its high cost and because it was known that it had already taken place in the USA.343 It was also felt that the results of such an experiment would be hard to interpret. While a negative result 337 Fraser, H., Bruce, M., Chree, A., McConnell, I. and Wells, G. (1992) Transmission of Bovine Spongiform Encephalopathy and Scrapie to Mice, Journal of General Virology, 73, 1891–7; Bruce, M., Chree, A., McConnell, I., Foster, J., Pearson, G. and Fraser, H. (1994) Transmission of Bovine Spongiform Encephalopathy and Scrapie to Mice: Strain Variation and the Species Barrier, Philosophical Transactions of the Royal Society of London, Series B, Biological Sciences, 343, 405–11 338 Bruce, M., Will, R., Ironside, J., McConell, I., Drummond, D., Suttie, A., McCordie, L., Chree, A., Hope, J., Birkett, C., Cousens, S., Fraser, H. and Bostock, C. (1997) Transmissions to Mice Indicate that ‘New Variant’ CJD is Caused by the BSE Agent, Nature, 389, 498–501 339 Clark, W., Hourrigan, J. and Hadlow, W. (1995) Encephalopathy in Cattle Experimentally Infected with the Scrapie Agent, American Journal of Veterinary Research, 56, 606–12 340 YB88/10.00/1.1 341 Cutlip, R., Miller, J., Race, R., Jenny, A., Katz, J., Lehmkuhl, H., Debey, B. and Robinson, M. (1994) Intracerebral Transmission of Scrapie to Cattle, Journal of Infectious Diseases, 169, 814–20 342 YB88/6.21/1.2 343 YB88/11.17/2.4 SCIENCE 84 would be informative, a positive result would need to demonstrate that when scrapie was transmitted to cattle, the disease which developed in cattle was the same as BSE.344 Given the large number of strains of scrapie and the possibility that BSE was one of them, it would be necessary to transmit every scrapie strain to cattle separately, to test the hypothesis properly. Such an experiment would be expensive. Secondly, as measures to control the epidemic took hold, the need for the experiment from the policy viewpoint was not considered so urgent. It was felt that the results would be mainly of academic interest.345 3.59 Nevertheless, from the first demonstration of transmissibility of BSE in 1988, the possibility of differences in the transmission properties of BSE and scrapie was clear. Scrapie was transmissible to hamsters, but by 1988 attempts to transmit BSE to hamsters had failed. Subsequent findings increased that possibility.
http://www.bseinquiry.gov.uk/pdf/volume2/chapter3.pdf
http://bse-atypical.blogspot.com/2009/06/l-type-bse-h-type-bse-c-type-bse-ibnc.html
NOR-98 ATYPICAL SCRAPIE 5 cases documented in USA in 5 different states USA 2007
http://nor-98.blogspot.com/2008/04/seac-spongiform-encephalopathy-advisory.html
Tuesday, June 3, 2008 SCRAPIE USA UPDATE JUNE 2008 NOR-98 REPORTED PA
http://nor-98.blogspot.com/2008/06/scrapie-usa-update-june-2008-nor-98.html
http://nor-98.blogspot.com/
Monday, September 1, 2008
RE-FOIA OF DECLARATION OF EXTRAORDINARY EMERGENCY BECAUSE OF AN ATYPICAL T.S.E. (PRION DISEASE) OF FOREIGN ORIGIN IN THE UNITED STATES [No. 00-072-1] September 1, 2008
http://foiamadsheepmadrivervalley.blogspot.com/2008/09/re-foia-of-declaration-of-extraordinary.html
experimental transmission of 171RR Nor98 brain to 5 RR recipients (Jan 2008)
http://www.sheepusa.org/index.phtml?page=site/get_file&print=1&file_id=f4d1b2a4739ab82d903cf042526bd9ee
http://www.eradicatescrapie.org/Educational%20Resources/PDFs%20&%20PPTs/Genotyping%20PPT/Slide%20Notes%20for%20Genotyping.pdf
http://www.eradicatescrapie.org/Educational%20Resources/PDFs%20&%20PPTs/Genotyping%20PPT/Genotyping%20A%20Tool%20for%20Controlling%20Classical%20Scrapie.ppt
P7.12 Co-existence of classical and atypical scrapie strains in a sheep from an Italian outbreak
Results: IHC revealed the simultaneous presence in the brain of pathological features characteristic of Nor98 and classical scrapie. This was confirmed by WB: PrPres fragments characteristic of Nor98 and scrapie were simultaneously present in all areas investigated, although in different proportions, with Nor98 being more abundant in the cortex and classical scrapie in the brainstem. The lymph node showed the presence of PrPsc with a molecular pattern referable only to classical scrapie, while the tongue resulted negative. Genetic analysis showed the following genotype: A136L141R154Q171/A136F141R154Q171.
Discussion: Our results suggest either the co-existence of Nor98 and classical scrapie in this sheep or the presence of a new scrapie phenotype. The presence of classical scrapie in the outbreak and the genotype of the animal support the first event, which might be explained by the different genetic and cellular targets of the two strains. The bioassay analysis in bank voles and Tg338 mice, at the moment in progress, will help to confirm this hypothesis.
also see ;
P9.18 First Report of Classical Scrapie in Portugal, including co-existence with atypical scrapie in the same flock
also see ;
P9.37 Sporadic Creutzfeldt-Jakob Disease in the Basque Country: Coexistence of prion protein strains in the same and different brain regions
Discussion: The Basque Country presents one of the highest annual incidences of confirmed sCJD in Spain and in Europe (1.87 per million inhabitants per annum). It also suffers the highest frequency of FFI (43.12%). Regarding regional pattern distribution, our results show a predominance of PrPsc type 1 in sCJD. Surprisingly, a high frequency of cases with both types of prion protein was observed, indicating that the coexistence of two different molecular patterns in the same individual is more common than expected.
http://www.neuroprion.org/resources/pdf_docs/conferences/prion2008/abstract-book-prion2008.pdf
Saturday, May 2, 2009
APHIS AND WHO PLAN TO EXEMPT THE ATYPICAL SCRAPIE NOR-98 FROM REGULATIONS AT MEETING THIS MONTH
http://nor-98.blogspot.com/2009/05/aphis-and-who-plan-to-exempt-atypical.html
SCRAPIE DETECTED IN ANOTHER GOAT USA UPDATE MARCH 2009
http://scrapie-usa.blogspot.com/2009/04/scrapie-detected-in-another-goat-usa.html
Full Scientific Reports
Experimental oral transmission of United States origin scrapie to neonatal sheep
Amir N. Hamir1, Robert A. Kunkle, Justin J. Greenlee and Juergen A. Richt Correspondence: 1Corresponding Author: Amir N. Hamir, National Animal Disease Center, ARS, USDA, 2300 Dayton Avenue, PO Box 70, Ames, IA 50010. amir.hamir@ars.usda.gov
Scrapie, a transmissible spongiform encephalopathy (TSE), is a naturally occurring fatal neurodegenerative disease of sheep and goats. The current study documents incubation periods, pathologic findings, and distribution of abnormal prion proteins (PrPSc) by immunohistochemistry and Western blot in tissues of genetically susceptible and resistant neonatal lambs inoculated with pooled brain homogenates from 13 U.S. origin scrapie-affected ewes. Nine Suffolk lambs with genotypes AA/RR/QQ (n = 5) and AA/RR/QR (n = 4) at codons 136, 154, and 171, respectively) were orally inoculated, within 12 hr of birth, with 1 ml of a 10% (w/v) brain homogenate prepared from scrapie-affected sheep brains. Inoculated animals were euthanized when advanced clinical signs of scrapie were observed. All QQ sheep developed clinical signs of scrapie, with a mean survival time of 24 months. Spongiform lesions in the brains and PrPSc deposits in the central nervous system and lymphoid tissues were present in these sheep. None of the QR sheep succumbed to the disease. A previous study that used a larger volume (30 ml of 10% brain suspension) of the same inoculum in 4-month-old Suffolk lambs of susceptible genotype documented longer survival periods (average 32 months), and only 5 of 9 inoculated sheep developed scrapie. Findings of this study suggest that orally exposed neonatal lambs of a susceptible (QQ) genotype exhibit a higher attack rate and shorter incubation period than older (4-month-old) lambs exposed to a larger dose (30x) of the same inoculum.
Key Words: Immunohistochemistry . neonatal sheep . scrapie . spongiform encephalopathy . Western blot
http://jvdi.org/cgi/content/abstract/21/1/64?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=prion&searchid=1&FIRSTINDEX=0&volume=21&issue=1&resourcetype=HWCIT
EVIDENCE OF SCRAPIE IN SHEEP AS A RESULT OF FOOD BORNE EXPOSURE
This is provided by the statistically significant increase in the incidence of sheep scrape from 1985, as determined from analyses of the submissions made to VI Centres, and from individual case and flock incident studies. ........
http://web.archive.org/web/20010305222246/www.bseinquiry.gov.uk/files/yb/1994/02/07002001.pdf
Title: Characterization of a U.S. Sheep Scrapie Isolate with Short Incubation Time
Authors
Hamir, Amirali Richt, Juergen Kunkle, Robert Greenlee, Justin Bulgin, M - UNIVERSITY OF IDAHO Gregori, L - VA MEDICAL CENTER, MD Rohwer, R - VA MEDICAL CENTER, MD
Submitted to: Veterinary Pathology Publication Type: Peer Reviewed Journal Publication Acceptance Date: April 16, 2009 Publication Date: N/A
Interpretive Summary: Scrapie is a naturally occurring fatal disease of sheep and goats. In a previous study it was shown that sheep inoculated with US scrapie inoculum (No. 13-7) induced terminal disease within an average of 19 months. We have since produced an inoculum, No. X124 from pooled brains of US origin sheep scrapie, that results in incubations nearly 3 fold shorter. The present study documents laboratory findings in tissues of sheep inoculated with No. X124. All inoculated sheep developed clinical disease and were euthanized within an average of 7.7 months post inoculation (MPI). Sheep that were genetically susceptible developed the disease faster (within 6 months). Also, the inoculum was able to induce disease in a short time (7 MPI) in a sheep that was supposed to be highly resistant to scrapie. This indicates that inoculum No. X124 appears to be more virulent than inoculum No. 13-7. Importantly this strain of scrapie represents a significant development in that it provides a natural model that requires less than 25 percent of the time for the disease to develop, thus enabling a faster pace for research investigating prion disease pathogenesis and inactivation. Technical Abstract: Scrapie is a naturally occurring fatal neurodegenerative disease of sheep and goats. Susceptibility to the disease is partly dependent upon the genetic makeup of the host. In a previous study it was shown that sheep intracerebrally inoculated with US scrapie inoculum (No. 13-7) developed terminal disease within an average of 19 months. We have since produced an inoculum, No. x124 from pooled brains of US origin sheep scrapie, that results in incubations nearly 3 fold shorter. The present study documents clinicopathological findings and the distribution of abnormal prion proteins (PrP**Sc) by immunohistochemical (IHC) and Western blot (WB) techniques, in tissues of sheep inoculated with No. x124. All inoculated sheep developed clinical disease and were euthanized within an average of 7.7 months post-inoculation (MPI). Sheep that had VV or AV at codon 136 of prion protein (PRNP) gene developed the disease faster and were euthanized at an average of 4.3 and 5.6 MPI, respectively. Also, the inoculum was able to induce disease in a short time (7 MPI) in a sheep that was relatively resistant (QR at codon 171) to scrapie. This indicates that inoculum No. x124 appears to induce scrapie in shorter time than inoculum No. 13-7, especially in sheep homozygous or heterozygous for valine at codon 136.
http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=230885
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.
PMID: 6997404
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract
12/10/76 AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE Office Note CHAIRMAN: PROFESSOR PETER WILDY
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A The Present Position with respect to Scrapie
A1 The Problem
Scrapie is a natural disease of sheep and goats. It is a slow and inexorably progressive degenerative disorder of the nervous system and it ia fatal. It is enzootic in the United Kingdom but not in all countries.
The field problem has been reviewed by a MAFF working group (ARC 35/77). It is difficult to assess the incidence in Britain for a variety of reasons but the disease causes serious financial loss; it is estimated that it cost Swaledale breeders alone $l.7 M during the five years 1971-1975. A further inestimable loss arises from the closure of certain export markets, in particular those of the United States, to British sheep.
It is clear that scrapie in sheep is important commercially and for that reason alone effective measures to control it should be devised as quickly as possible.
Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias"
Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.
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76/10.12/4.6
http://web.archive.org/web/20010305223125/www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf
Epidemiology of Scrapie in the United States 1977
http://www.bseinquiry.gov.uk/files/mb/m08b/tab64.pdf
http://scrapie-usa.blogspot.com/
Like lambs to the slaughter 31 March 2001 by Debora MacKenzie Magazine issue 2284
FOUR years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.
Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.
Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in ...
http://www.newscientist.com/article/mg16922840.300-like-lambs-to-the-slaughter.html
http://nor-98.blogspot.com/
http://scrapie-usa.blogspot.com/
Wednesday, July 1, 2009
Nor98 scrapie identified in the United States J Vet Diagn Invest 21:454-463 (2009)
http://nor-98.blogspot.com/2009/07/nor98-scrapie-identified-in-united.html
Thursday, November 12, 2009
BSE FEED RECALL Misbranding of product by partial label removal to hide original source of materials 2009
http://madcowfeed.blogspot.com/2009/11/bse-feed-recall-misbranding-of-product.html
Tuesday, November 10, 2009
Surveillance On the Bovine Spongiform Encephalopathy and rabies in Taiwan
http://usdavskorea.blogspot.com/2009/11/surveillance-on-bovine-spongiform.html
Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518
Kentaro Masujin • Yujing Shu • Hiroyuki Okada • Yuichi Matsuura • Yoshifumi Iwamaru • Morikazu Imamura • Shirou Mohri • Takashi Yokoyama Received: 27 July 2009 / Accepted: 29 September 2009 / Published online: 30 October 2009 The Author(s) 2009.
This article is published with open access at Springerlink.com Abstract
We performed a transmission study using mice to clarify the characteristics of the most recent case of scrapie in Japan. The mice that were inoculated with the brain homogenate from a scrapie-affected sheep developed progressive neurological disease, and one of the scrapieaffected mice showed unique clinical signs during primary transmission. This mouse developed obesity, polydipsia, and polyuria. In contrast, the other affected mice exhibited weight loss and hypokinesia. In subsequent passages, the mice showed distinct characteristic scrapie phenotypes. This finding may prove that different prion strains coexist in a naturally affected sheep with scrapie.
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Different types of PrPSc (types 1 and 2) were reported to co-exist in a case of sporadic Creutzfeldt–Jacob disease (sCJD) [15]. Scrapie in sheep is also proposed to be caused by mixed populations of different prion strains [16, 17]. In the present study, different prion strains were isolated from the brain of a scrapie-affected sheep during the primary transmission studies. In the previously reported CJD case, the PrPcore sizes of the two strains were different. In contrast, in the case reported in this study, although their PrPcore sizes were not different, the prions of the two strains showed distinct biological characteristics. In addition, this result showed that a transmission study using experimental animals is a useful approach for the isolation and characterization of prion strains. New TSE strains are believed to emerge due to mutations caused by differences in the primary PrP sequences of the host and the inoculum [17]. We observed that 3 out of 31 mice showed the characteristic clinical signs of the Ka/O strain in repeat trials of Ka/scrapie transmission (data not shown). This data indicates that the Ka/O strain shows a constant occurrence rate of 6–9%. Therefore, our findings may indicate that mixed prion populations exist in a strain in the brain of Ka/scrapie-affected sheep, while the Ka/O strain seemed to be the less dominant strain, which may have been inefficiently selected during interspecies transmission.
In this study, we examined the biological characteristics of prions in the most recent case of scrapie in Japan. On the basis of our results, we conclude that multiple prion strains coexist in a scrapie-affected sheep. To elucidate the molecular epidemiology of prion diseases, further studies should be conducted to clarify the mechanism underlying the emergence of new prion strains.
http://www.springerlink.com/content/f172377214414353/fulltext.pdf
Design and construction of diverse mammalian prion strains
David W. Colbya, Kurt Gilesa,b, Giuseppe Legnamea,b,1, Holger Willea,b, Ilia V. Baskakova,2, Stephen J. DeArmonda,c and Stanley B. Prusinera,b,3 + Author Affiliations
aInstitute for Neurodegenerative Diseases and Departments of bNeurology and cPathology, University of California, San Francisco, CA 94143 •?1Present address: Neurobiology Sector, Scuola Internazionale Superiore di Studi Avanzati, Trieste 34151, Italy.
•?2Present address: Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, MD 21201.
Contributed by Stanley B. Prusiner, September 11, 2009 (sent for review September 2, 2009)
Abstract
Prions are infectious proteins that encipher biological information within their conformations; variations in these conformations dictate different prion strains. Toward elucidating the molecular language of prion protein (PrP) conformations, we produced an array of recombinant PrP amyloids with varying conformational stabilities. In mice, the most stable amyloids produced the most stable prion strains that exhibited the longest incubation times, whereas more labile amyloids generated less stable strains and shorter incubation times. The direct relationship between stability and incubation time of prion strains suggests that labile prions are more fit, in that they accumulate more rapidly and thus kill the host faster. Although incubation times can be changed by altering the PrP expression level, PrP sequence, prion dose, or route of inoculation, we report here the ability to modify the incubation time predictably in mice by modulating the prion conformation.
synthetic prions stability amyloid neurodegeneration conformation Footnotes 3
To whom correspondence should be addressed. E-mail: stanley@ind.ucsf.eduAuthor contributions: D.W.C., G.L., and S.B.P. designed research; D.W.C., K.G., H.W., I.V.B., and S.J.D. performed research; D.W.C., K.G., H.W., S.J.D., and S.B.P. analyzed data; and D.W.C., S.J.D., and S.B.P. wrote the paper. The authors declare no conflict of interest.
http://www.pnas.org/content/early/2009/11/12/0910350106.abstract?etoc=
Scientific Opinion on genetic TSE resistance in goats in all European Union Member States Question number: EFSA-Q-2009-00448
Adopted: 21 October 2009 Summary (0.1Mb)
Opinion (0.3Mb)
Summary
Following a request from the European Commission, the Panel on Biological Hazards (BIOHAZ) was asked to deliver a scientific opinion on genetic resistance to Transmissible Spongiform Encephalopathies (TSE) in goats.
For a first part of that request, the BIOHAZ Panel adopted on 5th March 2009 a scientific opinion on the scientific validity of a study carried out by the Cypriot authorities under the auspices of the Community Reference Laboratory (CRL) for TSEs. That scientific opinion also indicated to what extent the information contained in the study could be used as relevant tools to control Classical scrapie in Cyprus.
In the current scientific opinion the BIOHAZ Panel addresses genetic resistance as a relevant tool for breeding for resistance to all TSEs of goats (including Atypical scrapie and BSE) in all the Member States (MSs) (except for Classical scrapie in Cyprus).
To carry out this task, available scientific knowledge on genetic TSE resistance in goats in the EU is reviewed, addressing those PRNP polymorphisms for which a capacity to provide resistance to TSEs in goats has been (or is being) investigated. Details tailored to the different TSEs found in this small ruminants (i.e. Classical scrapie, Atypical scrapie and BSE) are also considered and presented.
Further on, the feasibility of a large-scale breeding program in animal populations would need to be supported by a sound logistical and technical infrastructure in any given territory. In order to collect preliminary data that could help to evaluate the specific situation in the different EU MSs, a questionnaire was developed and circulated among the EFSA BSE-TSE Network. The results of the analysis of the replies received are also presented herewith.
The BIOHAZ Panel concluded that there are encouraging but as yet incomplete data to consider supporting a breeding programme for resistance in goats against Classical scrapie in all EU MSs, and ongoing studies are expected to provide a more robust scientific background in the coming years. On the other hand, at this moment there are not enough data available to consider supporting a breeding programme for resistance against Atypical scrapie and BSE in goats in all EU MSs. Experiments are ongoing on BSE in goats and results will be available in the next years. Furthermore, there are limited data suggesting that an allele (H154) might confer resistance to Classical scrapie but increase susceptibility to Atypical scrapie.
The frequency of the wild type allele, which is known to confer susceptibility to Classical scrapie, is high in all goat breeds considered. Thus, selection for putative resistance alleles will be slow, complicated and highly dependent on breeding structure.
It is acknowledged that any large scale breeding programme for TSE resistance in goats must take into consideration key elements related to the current dissemination of potentially TSE protective polymorphisms in the goat population of each EU MS and the characterisation of the real protection provided by those polymorphisms. At present, only a few EU MSs seem to have in place the necessary elements to introduce a breeding for resistance programme for Classical scrapie in goats.
The BIOHAZ Panel makes a series of recommendations on new investigations in order to assess the efficacy of breeding for the candidate PRNP alleles as a mean to control TSEs in goats. Furthermore, research on the possible adverse effects of the candidate PRNP polymorphisms on other production traits should be encouraged. In addition, it is recommended that a breeding for resistance programme for TSE in goats is first implemented in the seven EU MSs with the largest goat population as this would have the most impact.
Published: 9 November 2009
http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1211903027156.htm?WT.mc_id=EFSAHL01&emt=1
OPINION
http://www.efsa.europa.eu/EFSA/Scientific_Opinion/1371,0.pdf?ssbinary=true
Tuesday, November 10, 2009
A retrospective immunohistochemical study reveals atypical scrapie has existed in the United Kingdom since at least 1987
Brief Research Reports
http://nor-98.blogspot.com/2009/11/retrospective-immunohistochemical-study.html
Coexistence of multiple PrPSc types in individuals with Creutzfeldt-Jakob disease
Magdalini Polymenidou, Katharina Stoeck, Markus Glatzel, Martin Vey, Anne Bellon, and Adriano Aguzzi
Summary
Background The molecular typing of sporadic Creutzfeldt-Jakob disease (CJD) is based on the size and glycoform ratio of protease-resistant prion protein (PrPSc), and on PRNP haplotype. On digestion with proteinase K, type 1 and type 2 PrPSc display unglycosylated core fragments of 21 kDa and 19 kDa, resulting from cleavage around amino acids 82 and 97, respectively.
Methods
We generated anti-PrP monoclonal antibodies to epitopes immediately preceding the differential proteinase K cleavage sites. These antibodies, which were designated POM2 and POM12, recognise type 1, but not type 2, PrPSc.
Findings
We studied 114 brain samples from 70 patients with sporadic CJD and three patients with variant CJD. Every patient classified as CJD type 2, and all variant CJD patients, showed POM2/POM12 reactivity in the cerebellum and other PrPSc-rich brain areas, with a typical PrPSc type 1 migration pattern.
Interpretation
The regular coexistence of multiple PrPSc types in patients with CJD casts doubts on the validity of electrophoretic PrPSc mobilities as surrogates for prion strains, and questions the rational basis of current CJD classifications.
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The above results set the existing CJD classifications into debate and introduce interesting questions about human CJD types. For example, do human prion types exist in a dynamic equilibrium in the brains of affected individuals? Do they coexist in most or even all CJD cases? Is the biochemically identified PrPSc type simply the dominant type, and not the only PrPSc species?
Published online October 31, 2005
http://neurology.thelancet.com/
Detection of Type 1 Prion Protein in Variant Creutzfeldt-Jakob Disease
Helen M. Yull,* Diane L. Ritchie,* Jan P.M. Langeveld,? Fred G. van Zijderveld,? Moira E. Bruce,? James W. Ironside,* and Mark W. Head*
From the National CJD Surveillance Unit,* School of Molecular and Clinical Medicine, University of Edinburgh, Edinburgh, United Kingdom; Central Institute for Animal Disease Control (CIDC)-Lelystad, ? Lelystad, The Netherlands; Institute for Animal Health, Neuropathogenesis Unit, ? Edinburgh, United Kingdom
Molecular typing of the abnormal form of the prion protein (PrPSc) has come to be regarded as a powerful tool in the investigation of the prion diseases. All evidence thus far presented indicates a single PrPSc molecular type in variant Creutzfeldt-Jakob disease (termed type 2B), presumably resulting from infection with a single strain of the agent (bovine spongiform encephalopathy).
Here we show for the first time that the PrPSc that accumulates in the brain in variant Creutzfeldt- Jakob disease also contains a minority type 1 component. This minority type 1 PrPSc was found in all 21 cases of variant Creutzfeldt-Jakob disease tested, irrespective of brain region examined, and was also present in the variant Creutzfeldt-Jakob disease tonsil. The quantitative balance between PrPSc types was maintained when variant Creutzfeldt-Jakob disease was transmitted to wild-type mice and was also found in bovine spongiform encephalopathy cattle brain, indicating that the agent rather than the host specifies their relative representation. These results indicate that PrPSc molecular typing is based on quantitative rather than qualitative phenomena and point to a complex relationship between prion protein biochemistry, disease phenotype and agent strain. (Am J Pathol 2006, 168:151-157; DOI: 10.2353/ajpath.2006.050766)
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Discussion
Irrespective of whether this proves to be the case, the results shown here point to further complexities in the relationship between the physico-chemical properties of the prion protein, human disease phenotype, and prion agent strain.
Acknowledgments
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Type 1 PrPSc in Variant Creutzfeldt-Jakob Disease 157 AJP January 2006, Vol. 168, No. 1 ...TSS
http://ajp.amjpathol.org/
snip...see full text ;
Elsevier Editorial System(tm) for The Lancet Infectious Diseases Manuscript Draft Manuscript Number: Title: HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory Article Type: Personal View Corresponding Author: Mr. Terry S. Singeltary, Corresponding Author's Institution: na First Author: Terry S Singeltary, none Order of Authors: Terry S Singeltary, none; Terry S. Singeltary
http://www.regulations.gov/search/Regs/contentStreamer?objectId=090000648027c28e&disposition=attachment&contentType=pdf
Thursday, November 05, 2009
Incidence and spectrum of sporadic Creutzfeldt-Jakob disease variants with mixed phenotype and co-occurrence of PrPSc types: an updated classification
http://creutzfeldt-jakob-disease.blogspot.com/2009/11/incidence-and-spectrum-of-sporadic.html
ALSO, SEE Scrapie Mission, Texas, did not produce _typical_ BSE....
3.57 The experiment which might have determined whether BSE and scrapie were caused by the same agent (ie, the feeding of natural scrapie to cattle) was never undertaken in the UK. It was, however, performed in the USA in 1979, when it was shown that cattle inoculated with the scrapie agent endemic in the flock of Suffolk sheep at the United States Department of Agriculture in Mission, Texas, developed a TSE quite unlike BSE.339 The findings of the initial transmission, though not of the clinical or neurohistological examination, were communicated in October 1988 to Dr Watson, Director of the CVL, following a visit by Dr Wrathall, one of the project leaders in the Pathology Department of the CVL, to the United States Department of Agriculture.340 The results were not published at this point, since the attempted transmission to mice from the experimental cow brain had been inconclusive. The results of the clinical and histological differences between scrapie-affected sheep and cattle were published in 1995. Similar studies in which cattle were inoculated intracerebrally with scrapie inocula derived from a number of scrapie-affected sheep of different breeds and from different States, were carried out at the US National Animal Disease Centre.341 The results, published in 1994, showed that this source of scrapie agent, though pathogenic for cattle,
*** did not produce the same clinical signs of brain lesions characteristic of BSE. ***
3.58 There are several possible reasons why the experiment was not performed in the UK. It had been recommended by Sir Richard Southwood (Chairman of the Working Party on Bovine Spongiform Encephalopathy) in his letter to the Permanent Secretary of MAFF, Mr (now Sir) Derek Andrews, on 21 June 1988,342 though it was not specifically recommended in the Working Party Report or indeed in the Tyrrell Committee Report (details of the Southwood Working Party and the Tyrell Committee can be found in vol. 4: The Southwood Working Party, 1988–89 and vol. 11: Scientists after Southwood respectively). The direct inoculation of scrapie into calves was given low priority, because of its high cost and because it was known that it had already taken place in the USA.343 It was also felt that the results of such an experiment would be hard to interpret. While a negative result 337 Fraser, H., Bruce, M., Chree, A., McConnell, I. and Wells, G. (1992) Transmission of Bovine Spongiform Encephalopathy and Scrapie to Mice, Journal of General Virology, 73, 1891–7; Bruce, M., Chree, A., McConnell, I., Foster, J., Pearson, G. and Fraser, H. (1994) Transmission of Bovine Spongiform Encephalopathy and Scrapie to Mice: Strain Variation and the Species Barrier, Philosophical Transactions of the Royal Society of London, Series B, Biological Sciences, 343, 405–11 338 Bruce, M., Will, R., Ironside, J., McConell, I., Drummond, D., Suttie, A., McCordie, L., Chree, A., Hope, J., Birkett, C., Cousens, S., Fraser, H. and Bostock, C. (1997) Transmissions to Mice Indicate that ‘New Variant’ CJD is Caused by the BSE Agent, Nature, 389, 498–501 339 Clark, W., Hourrigan, J. and Hadlow, W. (1995) Encephalopathy in Cattle Experimentally Infected with the Scrapie Agent, American Journal of Veterinary Research, 56, 606–12 340 YB88/10.00/1.1 341 Cutlip, R., Miller, J., Race, R., Jenny, A., Katz, J., Lehmkuhl, H., Debey, B. and Robinson, M. (1994) Intracerebral Transmission of Scrapie to Cattle, Journal of Infectious Diseases, 169, 814–20 342 YB88/6.21/1.2 343 YB88/11.17/2.4 SCIENCE 84 would be informative, a positive result would need to demonstrate that when scrapie was transmitted to cattle, the disease which developed in cattle was the same as BSE.344 Given the large number of strains of scrapie and the possibility that BSE was one of them, it would be necessary to transmit every scrapie strain to cattle separately, to test the hypothesis properly. Such an experiment would be expensive. Secondly, as measures to control the epidemic took hold, the need for the experiment from the policy viewpoint was not considered so urgent. It was felt that the results would be mainly of academic interest.345 3.59 Nevertheless, from the first demonstration of transmissibility of BSE in 1988, the possibility of differences in the transmission properties of BSE and scrapie was clear. Scrapie was transmissible to hamsters, but by 1988 attempts to transmit BSE to hamsters had failed. Subsequent findings increased that possibility.
http://www.bseinquiry.gov.uk/pdf/volume2/chapter3.pdf
http://bse-atypical.blogspot.com/2009/06/l-type-bse-h-type-bse-c-type-bse-ibnc.html
NOR-98 ATYPICAL SCRAPIE 5 cases documented in USA in 5 different states USA 2007
http://nor-98.blogspot.com/2008/04/seac-spongiform-encephalopathy-advisory.html
Tuesday, June 3, 2008 SCRAPIE USA UPDATE JUNE 2008 NOR-98 REPORTED PA
http://nor-98.blogspot.com/2008/06/scrapie-usa-update-june-2008-nor-98.html
http://nor-98.blogspot.com/
Monday, September 1, 2008
RE-FOIA OF DECLARATION OF EXTRAORDINARY EMERGENCY BECAUSE OF AN ATYPICAL T.S.E. (PRION DISEASE) OF FOREIGN ORIGIN IN THE UNITED STATES [No. 00-072-1] September 1, 2008
http://foiamadsheepmadrivervalley.blogspot.com/2008/09/re-foia-of-declaration-of-extraordinary.html
experimental transmission of 171RR Nor98 brain to 5 RR recipients (Jan 2008)
http://www.sheepusa.org/index.phtml?page=site/get_file&print=1&file_id=f4d1b2a4739ab82d903cf042526bd9ee
http://www.eradicatescrapie.org/Educational%20Resources/PDFs%20&%20PPTs/Genotyping%20PPT/Slide%20Notes%20for%20Genotyping.pdf
http://www.eradicatescrapie.org/Educational%20Resources/PDFs%20&%20PPTs/Genotyping%20PPT/Genotyping%20A%20Tool%20for%20Controlling%20Classical%20Scrapie.ppt
P7.12 Co-existence of classical and atypical scrapie strains in a sheep from an Italian outbreak
Results: IHC revealed the simultaneous presence in the brain of pathological features characteristic of Nor98 and classical scrapie. This was confirmed by WB: PrPres fragments characteristic of Nor98 and scrapie were simultaneously present in all areas investigated, although in different proportions, with Nor98 being more abundant in the cortex and classical scrapie in the brainstem. The lymph node showed the presence of PrPsc with a molecular pattern referable only to classical scrapie, while the tongue resulted negative. Genetic analysis showed the following genotype: A136L141R154Q171/A136F141R154Q171.
Discussion: Our results suggest either the co-existence of Nor98 and classical scrapie in this sheep or the presence of a new scrapie phenotype. The presence of classical scrapie in the outbreak and the genotype of the animal support the first event, which might be explained by the different genetic and cellular targets of the two strains. The bioassay analysis in bank voles and Tg338 mice, at the moment in progress, will help to confirm this hypothesis.
also see ;
P9.18 First Report of Classical Scrapie in Portugal, including co-existence with atypical scrapie in the same flock
also see ;
P9.37 Sporadic Creutzfeldt-Jakob Disease in the Basque Country: Coexistence of prion protein strains in the same and different brain regions
Discussion: The Basque Country presents one of the highest annual incidences of confirmed sCJD in Spain and in Europe (1.87 per million inhabitants per annum). It also suffers the highest frequency of FFI (43.12%). Regarding regional pattern distribution, our results show a predominance of PrPsc type 1 in sCJD. Surprisingly, a high frequency of cases with both types of prion protein was observed, indicating that the coexistence of two different molecular patterns in the same individual is more common than expected.
http://www.neuroprion.org/resources/pdf_docs/conferences/prion2008/abstract-book-prion2008.pdf
Saturday, May 2, 2009
APHIS AND WHO PLAN TO EXEMPT THE ATYPICAL SCRAPIE NOR-98 FROM REGULATIONS AT MEETING THIS MONTH
http://nor-98.blogspot.com/2009/05/aphis-and-who-plan-to-exempt-atypical.html
SCRAPIE DETECTED IN ANOTHER GOAT USA UPDATE MARCH 2009
http://scrapie-usa.blogspot.com/2009/04/scrapie-detected-in-another-goat-usa.html
Full Scientific Reports
Experimental oral transmission of United States origin scrapie to neonatal sheep
Amir N. Hamir1, Robert A. Kunkle, Justin J. Greenlee and Juergen A. Richt Correspondence: 1Corresponding Author: Amir N. Hamir, National Animal Disease Center, ARS, USDA, 2300 Dayton Avenue, PO Box 70, Ames, IA 50010. amir.hamir@ars.usda.gov
Scrapie, a transmissible spongiform encephalopathy (TSE), is a naturally occurring fatal neurodegenerative disease of sheep and goats. The current study documents incubation periods, pathologic findings, and distribution of abnormal prion proteins (PrPSc) by immunohistochemistry and Western blot in tissues of genetically susceptible and resistant neonatal lambs inoculated with pooled brain homogenates from 13 U.S. origin scrapie-affected ewes. Nine Suffolk lambs with genotypes AA/RR/QQ (n = 5) and AA/RR/QR (n = 4) at codons 136, 154, and 171, respectively) were orally inoculated, within 12 hr of birth, with 1 ml of a 10% (w/v) brain homogenate prepared from scrapie-affected sheep brains. Inoculated animals were euthanized when advanced clinical signs of scrapie were observed. All QQ sheep developed clinical signs of scrapie, with a mean survival time of 24 months. Spongiform lesions in the brains and PrPSc deposits in the central nervous system and lymphoid tissues were present in these sheep. None of the QR sheep succumbed to the disease. A previous study that used a larger volume (30 ml of 10% brain suspension) of the same inoculum in 4-month-old Suffolk lambs of susceptible genotype documented longer survival periods (average 32 months), and only 5 of 9 inoculated sheep developed scrapie. Findings of this study suggest that orally exposed neonatal lambs of a susceptible (QQ) genotype exhibit a higher attack rate and shorter incubation period than older (4-month-old) lambs exposed to a larger dose (30x) of the same inoculum.
Key Words: Immunohistochemistry . neonatal sheep . scrapie . spongiform encephalopathy . Western blot
http://jvdi.org/cgi/content/abstract/21/1/64?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=prion&searchid=1&FIRSTINDEX=0&volume=21&issue=1&resourcetype=HWCIT
EVIDENCE OF SCRAPIE IN SHEEP AS A RESULT OF FOOD BORNE EXPOSURE
This is provided by the statistically significant increase in the incidence of sheep scrape from 1985, as determined from analyses of the submissions made to VI Centres, and from individual case and flock incident studies. ........
http://web.archive.org/web/20010305222246/www.bseinquiry.gov.uk/files/yb/1994/02/07002001.pdf
Title: Characterization of a U.S. Sheep Scrapie Isolate with Short Incubation Time
Authors
Hamir, Amirali Richt, Juergen Kunkle, Robert Greenlee, Justin Bulgin, M - UNIVERSITY OF IDAHO Gregori, L - VA MEDICAL CENTER, MD Rohwer, R - VA MEDICAL CENTER, MD
Submitted to: Veterinary Pathology Publication Type: Peer Reviewed Journal Publication Acceptance Date: April 16, 2009 Publication Date: N/A
Interpretive Summary: Scrapie is a naturally occurring fatal disease of sheep and goats. In a previous study it was shown that sheep inoculated with US scrapie inoculum (No. 13-7) induced terminal disease within an average of 19 months. We have since produced an inoculum, No. X124 from pooled brains of US origin sheep scrapie, that results in incubations nearly 3 fold shorter. The present study documents laboratory findings in tissues of sheep inoculated with No. X124. All inoculated sheep developed clinical disease and were euthanized within an average of 7.7 months post inoculation (MPI). Sheep that were genetically susceptible developed the disease faster (within 6 months). Also, the inoculum was able to induce disease in a short time (7 MPI) in a sheep that was supposed to be highly resistant to scrapie. This indicates that inoculum No. X124 appears to be more virulent than inoculum No. 13-7. Importantly this strain of scrapie represents a significant development in that it provides a natural model that requires less than 25 percent of the time for the disease to develop, thus enabling a faster pace for research investigating prion disease pathogenesis and inactivation. Technical Abstract: Scrapie is a naturally occurring fatal neurodegenerative disease of sheep and goats. Susceptibility to the disease is partly dependent upon the genetic makeup of the host. In a previous study it was shown that sheep intracerebrally inoculated with US scrapie inoculum (No. 13-7) developed terminal disease within an average of 19 months. We have since produced an inoculum, No. x124 from pooled brains of US origin sheep scrapie, that results in incubations nearly 3 fold shorter. The present study documents clinicopathological findings and the distribution of abnormal prion proteins (PrP**Sc) by immunohistochemical (IHC) and Western blot (WB) techniques, in tissues of sheep inoculated with No. x124. All inoculated sheep developed clinical disease and were euthanized within an average of 7.7 months post-inoculation (MPI). Sheep that had VV or AV at codon 136 of prion protein (PRNP) gene developed the disease faster and were euthanized at an average of 4.3 and 5.6 MPI, respectively. Also, the inoculum was able to induce disease in a short time (7 MPI) in a sheep that was relatively resistant (QR at codon 171) to scrapie. This indicates that inoculum No. x124 appears to induce scrapie in shorter time than inoculum No. 13-7, especially in sheep homozygous or heterozygous for valine at codon 136.
http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=230885
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.
PMID: 6997404
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=6997404&dopt=Abstract
12/10/76 AGRICULTURAL RESEARCH COUNCIL REPORT OF THE ADVISORY COMMITTE ON SCRAPIE Office Note CHAIRMAN: PROFESSOR PETER WILDY
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A The Present Position with respect to Scrapie
A1 The Problem
Scrapie is a natural disease of sheep and goats. It is a slow and inexorably progressive degenerative disorder of the nervous system and it ia fatal. It is enzootic in the United Kingdom but not in all countries.
The field problem has been reviewed by a MAFF working group (ARC 35/77). It is difficult to assess the incidence in Britain for a variety of reasons but the disease causes serious financial loss; it is estimated that it cost Swaledale breeders alone $l.7 M during the five years 1971-1975. A further inestimable loss arises from the closure of certain export markets, in particular those of the United States, to British sheep.
It is clear that scrapie in sheep is important commercially and for that reason alone effective measures to control it should be devised as quickly as possible.
Recently the question has again been brought up as to whether scrapie is transmissible to man. This has followed reports that the disease has been transmitted to primates. One particularly lurid speculation (Gajdusek 1977) conjectures that the agents of scrapie, kuru, Creutzfeldt-Jakob disease and transmissible encephalopathy of mink are varieties of a single "virus". The U.S. Department of Agriculture concluded that it could "no longer justify or permit scrapie-blood line and scrapie-exposed sheep and goats to be processed for human or animal food at slaughter or rendering plants" (ARC 84/77)" The problem is emphasised by the finding that some strains of scrapie produce lesions identical to the once which characterise the human dementias"
Whether true or not. the hypothesis that these agents might be transmissible to man raises two considerations. First, the safety of laboratory personnel requires prompt attention. Second, action such as the "scorched meat" policy of USDA makes the solution of the acrapie problem urgent if the sheep industry is not to suffer grievously.
snip...
76/10.12/4.6
http://web.archive.org/web/20010305223125/www.bseinquiry.gov.uk/files/yb/1976/10/12004001.pdf
Epidemiology of Scrapie in the United States 1977
http://www.bseinquiry.gov.uk/files/mb/m08b/tab64.pdf
http://scrapie-usa.blogspot.com/
Like lambs to the slaughter 31 March 2001 by Debora MacKenzie Magazine issue 2284
FOUR years ago, Terry Singeltary watched his mother die horribly from a degenerative brain disease. Doctors told him it was Alzheimer's, but Singeltary was suspicious. The diagnosis didn't fit her violent symptoms, and he demanded an autopsy. It showed she had died of sporadic Creutzfeldt-Jakob disease.
Most doctors believe that sCJD is caused by a prion protein deforming by chance into a killer. But Singeltary thinks otherwise. He is one of a number of campaigners who say that some sCJD, like the variant CJD related to BSE, is caused by eating meat from infected animals. Their suspicions have focused on sheep carrying scrapie, a BSE-like disease that is widespread in flocks across Europe and North America.
Now scientists in France have stumbled across new evidence that adds weight to the campaigners' fears. To their complete surprise, the researchers found that one strain of scrapie causes the same brain damage in ...
http://www.newscientist.com/article/mg16922840.300-like-lambs-to-the-slaughter.html
http://nor-98.blogspot.com/
http://scrapie-usa.blogspot.com/
Wednesday, July 1, 2009
Nor98 scrapie identified in the United States J Vet Diagn Invest 21:454-463 (2009)
http://nor-98.blogspot.com/2009/07/nor98-scrapie-identified-in-united.html
Thursday, November 12, 2009
BSE FEED RECALL Misbranding of product by partial label removal to hide original source of materials 2009
http://madcowfeed.blogspot.com/2009/11/bse-feed-recall-misbranding-of-product.html
Tuesday, November 10, 2009
Surveillance On the Bovine Spongiform Encephalopathy and rabies in Taiwan
http://usdavskorea.blogspot.com/2009/11/surveillance-on-bovine-spongiform.html
Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518
Labels: bse, cjd, coexist, multiple prion strains, scrapie
posted by Terry S. Singeltary Sr. | 10:58 AM
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