Monday, September 13, 2010

atypical BSE strains and sporadic CJD strains, is there a connection and why shouldn't there be $

A Surprisingly High Number of the Plaque-Like VV sCJD Subtype Among the Polish sCJD-is There a Connection with BASE?


A Surprisingly High Number of the Plaque-Like VV sCJD Subtype Among the Polish sCJD—is There a Connection with BASE?

Beata Sikorska and Pawel P. Liberski Department of Molecular Pathology and Neuropathology; Medical University of Lodz; Lodz, Poland

Recently described bovine amyloidotic spongiform encephalopathy (BASE) or L type BSE—was is overrepresented in Poland (15% of all cases of BSE). Moreover, the number of BASE cases in Poland per million bovines is the highest in Europe. A potential human risk from BASE is evident from experimental transmission to “humanized” transgenic animals and primates. Taking into consideration that non-human primate inoculated with BASE had a shorter incubation period than monkeys infected with classical BSE, and that humanized Tg mice have been found to be highly susceptible to infection with atypical form of BSE, it seems probable that BASE may be more pathogenic for humans than BSE, but the transmitted disease may differ from BSE-derived vCJD. Among 47 cases which have been diagnosed as definite in our laboratory, in 19 cases complete histopathological examination and codon 129 status were available. On the basis of the histological pattern and codon 129 status the cases of sCJD were divided into subtypes according to the Parchi&Gambetti classification. The results are as follows: type 1 (MMorMV)- 42%, type 2 (VV)-32%, type 3 (MV)-10.5%, type 4c (MM)- 10.5% and type 5 (VV)-5 %. Although the number of cases is too low to conclude a significantly different distribution of sCJD subtypes in Polish population those data show surprisingly high number of the plaque-like VV sCJD subtype. Interestingly, it was shown before that Tg mice inoculated with BASE showed granular and plaque-like aggregates or PrPSc in brains resembling those observed in VV2 subtype of sCJD.


Transmission of Classical and Atypical (L-type) Bovine Spongiform Encephalopathy (BSE) Prions to Cynomolgus macaques

Fumiko Ono,1 Yoshio Yamakawa,2 Minoru Tobiume,3 Yuko Sato,3 Harutaka Katano,3 Kenichi Hagiwara,2 Iori Itagaki,1 Akio Hiyaoka,1 Katuhiko Komatuzaki,1 Yasunori Emoto,1 Hiroaki Shibata,4 Yuichi Murayama,5 Keiji Terao,4 Yasuhiro Yasutomi4 and Tetsutaro Sata3

1The Corporation for Production and Research of Laboratory Primates; Tsukuba City, Japan; 2Departments of Cell Biology and Biochemistry; and 3Pathology; National Institute of Infectious Diseases; Tokyo, Japan; 4Tsukuba Primate Research Center; National Institute of Biomedical Innovation; Tsukuba City, Japan; 5Prion Disease Research Team; National Institute of Animal Health; Tsukuba City, Japan

Key words: L-type BSE, cBSE, cynomolgus macaques, transmission

BSE prion derived from classical BSE (cBSE) or L-type BSE was characterized by inoculation into the brain of cynomolgus macaques. The neurologic manifestation was developed in all cynomolgus macaques at 27–43 months after intracerebral inoculation of brain homogenate from cBSE-affected cattle (BSE JP/6). Second transmission of cBSE from macaque to macaque shortened incubation period to 13–18 months. cBSE-affected macaques showed the similar clinical signs including hyperekplexia, tremor and paralysis in both primary and second transmission.

Two macaques were intracerebrally inoculated brain homogenate from the L-type BSE-affected cattle (BSE JP/24). The incubation periods were 19–20 months in primary transmission.

The clinical course of the L-type BSE-affected macaques differed from that in cBSE-affected macaques in the points of severe myoclonus without hyperekplexia. The glycoform profile of PrPSc detected in macaque CNS was consistent with original pattern of either cBSE or L-typeBSE PrPSc, respectively. Although severe spongiform change in the brain was remarkable in all BSE-affected macaques, severe spongiform spread widely in cerebral cortex in L-type BSE-affected macaques. Heavy accumulation of PrPSc surrounded by vacuola formed florid plaques in cerebral cortex of cBSE-affected macaques. Deposit of PrPSc in L-type BSE-affected macaque was weak and diffuse synaptic pattern in cerebrum, but large PrPSc plaques were evident at cerebellum. MRI analysis, T2, T1, DW and flair sequences, at the time of autopsy revealed that brain atrophy and dilatation of cerebral ventricles were significantly severe in L-type BSE-affected macaques. These results suggest that L-type BSE is more virulent strain to primates comparing to cBSE.


Evidence from Molecular Strain Typing

Gianluigi Zanusso Department of Neurological and Visual Sciences; Section of Clinical Neurology; University of Verona; Verona, Italy

Key words: molecular analysis, strain typing, atypical BSE, CJD

In 2001, active surveillance for bovine spongiform encephalopathy (BSE) led to the discovery of atypical BSE phenotypes in aged cattle distinct from classical BSE (C-type). These atypical BSE cases had been classified as low L-type (BASE) or high H-type BSE based on the molecular mass and the degree of glycosylation of of the pathological prion protein (PrPSc). Transmission studies in TgBov mice showed that H-type BSE, C-type BSE and BASE behave as distinct prion strains with different incubation periods, PrPSc molecular patterns and pathological phenotypes. A still unclear issue concerns the potential transmissibility and phenotypes of atypical BSEs in humans. We previously indicated that BASE was similar to a distinct subgroup of sporadic form of Creutzfeldt-Jakob disease (sCJD) MV2, based on molecular similarities and on neuropathological pattern of PrP deposition. To investigate a possible link between BASE and sCJD, Kong et al. and Comoy et al. experimentally inoculated TgHu mice (129MM) and a non-human primate respectively, showing in both models that BASE was more virulent compare to BSE. Further, non-human primate reproduced a clinical phenotype resembling to that of sCJD subtype MM2. Here, we presented a comparative analysis of the biochemical fingerprints of PrPSc between the different sCJD subtypes and animal TSEs and after experimental transmission to animals.

Opinion of the Scientific Steering Committee on the GEOGRAPHICAL RISK OF BOVINE SPONGIFORM ENCEPHALOPATHY (GBR) in POLAND Adopted on 30/03/2001

It is concluded that it is likely but not confirmed that one or several cattle that are (pre-clinically or clinically) infected with the BSE agent are currently present in the domestic herd of Poland (GBR III).

Number of reported cases of bovine spongiform encephalopathy (BSE) in farmed cattle worldwide*(excluding the United Kingdom)

Country/Year 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07 08 09 10

Poland 0 0 0 0 0 0 0 0 0 0 0 0 0 4f 5 11 19 10 9 5 4

Annual incidence rate* of bovine spongiform encephalopathy (BSE) in OIE Member Countries that have reported cases, excluding the United Kingdom

Bovine Spongiform Encephalopathy, Poland

Impact Worksheet, May 7, 2002

What is the level of passenger traffic arriving in the United States from Poland?

A total of 188,946 passengers arrived at US airports on direct flights from Poland in fiscal year 2000. An undetermined number of passengers arrived in the US from Poland via indirect flights.

Under APHIS-PPQ’s agricultural quarantine inspection monitoring, 451 air passengers from Poland were sampled for items of agricultural interest in fiscal year 2000. Thirteen (13) of these passengers, or 2.9 percent, carried a total of 26.2 kg of meat items that could potentially harbor the pathogen(s) that cause BSE. None of these passengers from whom meat items were confiscated reported plans to visit or work on a ranch or farm during their visit to the US.

Source: US Department of Transportation, and APHIS-PPQ Agricultural Quarantine Inspection data base

PLEASE NOTICE THAT SPORADIC CJD IN POLAND TRIPLED FROM THE YEAR 2008 TO 2009, FROM 10 TO 30 CASES. AS with sporadic CJD in the USA drastically increasing over the years. ...TSS

Ultrastructural study of florid plaques in variant Creutzfeldt–Jakob disease: a comparison with amyloid plaques in kuru, sporadic Creutzfeldt–Jakob disease and Gerstmann–Sträussler–Scheinker disease

B. Sikorska1, P. P. Liberski1, T. Sobów2, H. Budka3, J. W. Ironside4Article first published online: 30 MAY 2008

DOI: 10.1111/j.1365-2990.2008.00959.x

© 2008 Blackwell Publishing Ltd Issue Neuropathology and Applied Neurobiology Volume 35, Issue 1, pages 46–59, February 2009

Keywords:amyloid;Gerstmann–Sträussler–Scheinker disease;kuru;plaque;prion protein;sporadic Creutzfeldt–Jakob disease;variant Creutzfeldt–Jakob disease;ultrastructure

Background: Although the histological features of the amyloid plaques in variant Creutzfeldt–Jakob disease (vCJD) are distinct from those in other forms of prion disease [kuru, sporadic Creutzfeldt–Jakob disease (sCJD) and Gerstmann–Sträussler–Scheinker disease (GSS)], their ultrastructural features have only been described in a single case report. Aims: To study vCJD plaques systematically and compare them with plaques in kuru, sCJD, GSS and Alzheimer disease (AD).

Methods: Amyloid plaques were studied by transmission electron microscopy and image analysis in five cases of vCJD, three cases of GSS, two cases of sCJD, one case of kuru and five cases of AD. Immunohistochemistry was performed on paraffin sections from one case of vCJD, two cases of GSS, one case of kuru and two cases of sCJD.

Results: The florid plaques in vCJD were either compact or more diffuse; in both forms, the radiating fibrils were organized into thick ‘tongues’, in contrast to kuru plaques. Dystrophic neurites (DNs) containing lysosomal electron-dense bodies or vesicles surrounded florid plaques. Microglial cells were found within florid plaques; occasional amyloid fibrils were identified in membrane-bound pockets of microglial cells. In vCJD, there was significant tau immunoreactivity in DNs around florid plaques while, in sCJD, GSS and kuru, minimal tau immunoreactivity was observed around plaques.

Conclusions: The ultrastructure of the florid plaques and DNs in vCJD is more reminiscent of neuritic plaques in AD than kuru or multicentric plaques. These findings may reflect differences both in the strains of the transmissible agents responsible for these disorders and in host factors.

Docket Management Docket: 02N-0276 - Bioterrorism Preparedness; Registration of Food Facilities, Section 305 Comment Number: EC -254 Accepted - Volume 11

2003-04-08 10:36:55

Where has atypical BSE been found? ..

Although the greatest number of cases is in France(12), increasing numbers of cases have now been identified in other countries – Canada (1), Germany (2), Italy (2), Japan (2), Netherlands (4), Poland (7), Sweden (1), Switzerland (1), UK (1), and USA (2). In Sweden and the USA the atypical cases represent the only indigenous cases detected. In other words – typical BSE has not been detected in native cattle in these two countries (34). .. In France, Poland, Netherlands and Germany both H and L forms of atypical BSE have been reported(25).

June 2007

Journal of Clinical Microbiology, June 2007, p. 1821-1829, Vol. 45, No. 6 0095-1137/07/$08.00+0 doi:10.1128/JCM.00160-07 Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Molecular Discrimination of Atypical Bovine Spongiform Encephalopathy Strains from a Geographical Region Spanning a Wide Area in Europe

Jorg G. Jacobs,1 Jan P. M. Langeveld,1* Anne-Gaëlle Biacabe,2 Pier-Luigi Acutis,3 Miroslaw P. Polak,4 Dolores Gavier-Widen,5 Anne Buschmann,6 Maria Caramelli,3 Cristina Casalone,3 Maria Mazza,3 Martin Groschup,6 Jo H. F. Erkens,1 Aart Davidse,1 Fred G. van Zijderveld,1 and Thierry Baron2 Central Institute for Animal Disease Control (CIDC-Lelystad), 8203 AA 2004, Lelystad, The Netherlands,1 Agence Française de Sécurité Sanitaire des Aliments (AFSSA-Lyon Fr), Unité ATNC, 31 avenue Tony Garnier, 69342 Lyon cedex 07, France,2 Centro di Referenza per le Encefalopatie Animali (CEA), Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, Via Bologna 148, 10154 Turin, Italy,3 National Veterinary Research Institute (NVRI), Al. Partyzantow 57, 24-100 Pulawy, Poland,4 National Veterinary Institute (SVA), SE-751 89 Uppsala, Sweden,5 Friedrich-Loeffler-Institut, Boddenblick 5a, 17493 Greifswald-Insel Riems, Germany6

Received 22 January 2007/ Returned for modification 12 March 2007/ Accepted 6 April 2007


Transmissible spongiform encephalopathy strains can be differentiated by their behavior in bioassays and by molecular analyses of the disease-associated prion protein (PrP) in a posttranslationally transformed conformation (PrPSc). Until recently, isolates from cases of bovine spongiform encephalopathy (BSE) appeared to be very homogeneous. However, a limited number of atypical BSE isolates have recently been identified upon analyses of the disease-associated proteinase K (PK) resistance-associated moiety of PrPSc (PrPres), suggesting the existence of at least two additional BSE PrPres variants. These are defined here as the H type and the L type, according to the higher and lower positions of the nonglycosylated PrPres band in Western blots, respectively, compared to the position of the band in classical BSE (C-type) isolates. These molecular PrPres variants, which originated from six different European countries, were investigated together. In addition to the migration properties and glycosylation profiles (glycoprofiles), the H- and L-type isolates exhibited enhanced PK sensitivities at pH 8 compared to those of the C-type isolates. Moreover, H-type BSE isolates exhibited differences in the binding of antibodies specific for N- and more C-terminal PrP regions and principally contained two aglycosylated PrPres moieties which can both be glycosylated and which is thus indicative of the existence of two PrPres populations or intermediate cleavage sites. These properties appear to be consistent within each BSE type and independent of the geographical origin, suggesting the existence of different BSE strains in cattle. The choice of three antibodies and the application of two pHs during the digestion of brain homogenates provide practical and diverse tools for the discriminative detection of these three molecular BSE types and might assist with the recognition of other variants.


More than 180,000 cases of BSE have been reported within the United Kingdom by passive surveillance since the beginning of the epidemic. In the European Union, since the year 2001, all slaughter cattle aged 30 months or older and all fallen stock animals older than age 24 months must be rapidly tested for BSE (24). This has led to the detection of over 5,000 BSE cases outside the United Kingdom. On the basis of the results available from diagnostic and limited bioassay studies, the cases from this active surveillance are expected to be of the same BSE type as the type detected in the United Kingdom (16, 22, 37). However, rare variants of BSE have now also been detected as a consequence of this active surveillance in cattle (Bos taurus) (8, 14, 17, 23, 45, 49, 61) and in a miniature zebu (Bos indicus) (53). The isolates from these cases showed by Western blot (WB) analysis a PrPres profile that deviated from that of the classical BSE cases (named the C type), in which the PrPres bands migrated to a higher (H type) or a lower (L type) position (8, 17). Both atypical forms, but especially the L type, were further characterized by a smaller proportion of diglycosylated PrPres compared to the proportion in C-type BSE isolates. The histological features seen in the initial report of the two L-type cases were peculiar because of the prominent involvement of the forebrain; in contrast, in C-type BSE, the brain stem is primarily affected. Moreover, PrPSc was deposited in unusual amyloid plaques, which led to the name bovine amyloidotic spongiform encephalopathy (17). Other reports describing PrPres from cattle with atypical profiles have appeared; these include both an L-type case and an H-type case in Germany and single unclassified cases in each of Poland, the United States, Japan, and Belgium (10, 14, 23, 45, 49, 61). Recent reports have shown that such atypical H- and L-type isolates are transmissible to mice and clearly differ from C-type BSE isolates, with unique incubation periods, PrPres profiles, and histological lesions (3, 4, 7, 14).

This study analyzed together 17 aberrant BSE isolates from six European countries with the purpose of studying in depth the behavior, comparability, and homogeneity of their molecular properties by the use of WB analysis. All BSE isolates could be differentiated into three groups, i.e., the L, C, or H type, by using the previously published criteria of apparent molecular mass and glycoprofile, while other criteria for their discrimination were also defined, such as sensitivity to PK, whether an additional nonglycosylated PrPres band was present, and antibody-dependent molecular patterns.




Our data on the glycoprofiles of the three different BSE types yield some further interesting information. A prominent aspect in L-type isolates is the small proportion of diglycosyl-PrPres, especially compared to that in C-type isolates and, to a lesser degree, also compared to that in H-type isolates. In C-type and H-type isolates, this fraction reaches values well above 55%, while in L-type isolates it remains below 55%. These differences were observed when detection antibodies that bind to the core region of the PrP-like group A, antibodies 9A2, L42, and 6H4, were applied. For the H type, the glycoprofile appeared, surprisingly, to depend also on the detection antibody applied: while core-specific antibodies like L42, 6H4, and 9A2 yielded features quite similar to those of C-type BSE isolates, with group C antibody 94B4 the glycoprofile was intermediate between those of C- and L-type BSE isolates due to the relatively large amount of staining in the position of the monoglycosylated band (Fig. 5A). A plausible explanation for this might be that C-terminus-specific antibodies like 94B4 react with two triple-banded PrPres populations, of which the second population migrates to a position 5 to 10 kDa lower than that where the first population migrates so that its diglycosylated band merges into the position of the monoglycosylated band of the PrPres of the first population (7). In this concept of two populations, group A and B antibodies like 12B2, 9A2, L42, and 6H4 can bind only to the first population; group C antibodies bind to both populations. These data further support the idea of the existence of a mixture of glycosylated PrPres populations, one of which is 1.3 kDa larger than that of the C type and can be bound by N-terminus-, core-, and C-terminus-specific antibodies, while the other is unusually short and consists of the region from approximately positions 163 to 242 of PrP which can be bound only by group C antibodies like 94B4 and SAF84. If PK cleaves near residue 163, the occurrence of an 7-kDa band, such as that which is most prominently present in H type, could represent a PrPSc fragment that is located at the N terminus of this cleavage site (7).

A difference in the length of the PrPres molecules in H-type isolates compared to the lengths in C- and L-type isolates was also clearly confirmed by using group A antibody 12B2, which binds to the N terminus of PrPres and which overtly detects H-type BSE isolates. Interestingly, SAF32, whose epitope (the octarepeat region) is more N-terminally located, also displays a limited affinity for binding to H-type PrPres if digestion is performed at pH 6.5, while group B antibody 9A2, in comparison to 12B2, which binds only 9 amino acid residues farther toward the C terminus of PrP does, fully binds to the PrPress of all three types of BSE, which is very similar to the signal obtained with antibodies like 94B4, L42, and 6H4. The epitope data and grouping of these antibodies (see Materials and Methods and Results) and the differences in the apparent molecular masses of the PrPres types point to major cleavage sites at approximately position 92 of bovine PrP for the H type, position 103 for the C type, and position 108 for the L type (Fig. 6).

Cleavage of PrPSc by endoproteases like PK hydrolyzes the N terminus of PrPSc (6, 28, 32, 41, 42, 48). In C-type BSE isolates and under the conditions used here (50 µg PK/ml, 37°C, 10% brain homogenate in lysis buffer), this mainly occurs up to residue 109 of bovine PrP and, thus, between the epitopes of antibodies 12B2 and 9A2. This process, however, also depends on the pH during the reaction, the enzyme/substrate ratio, and also, possibly, the presence of denaturing agents (36, 40). For the BSE isolates studied here, it became clear that C-type BSE isolates are unusually resistant even under the harshest conditions of pH 8.0 and an enzyme concentration of 500 µg/ml. The H- and L-type isolates were more susceptible; however, some residual PrPres always remained, even under the most degradative conditions investigated. This resistance to PK and other subtilisin-like enzymes like keratinase has previously been noticed for scrapie isolate- and BSE isolate-infected brain homogenates, where only denaturation at temperatures well above 100°C allowed the full digestion of detectable PrP (36). For diagnostic purposes, even if the digestion conditions do not lead to a stable PrPres level, differences between BSE types can be reliably visualized by using two different PK cleavage conditions at 37°C: pH 6.5 with 50 µg PK/ml or pH 8.0 with 500 µg PK/ml.

This study serves the important goal of defining adequate tools for the discrimination of BSE types. Striking similarities in molecular properties were encountered for the samples of each BSE type when quite different treatments were applied before analysis by WB. The main features are summarized in Table 2. In practice, the following strategy for the determination of the BSE type (C, H, or L type) is proposed. A homogenate can be divided into two aliquots and titrated to obtain two conditions of digestion with PK: mild and stringent. After the PK digestion the digests are subjected to parallel electrophoresis and WB analysis with group A, B, and C antibodies (MAbs 12B2, L42, and 94B4, respectively) at established antibody concentrations and with similar film exposures. Under mild PK conditions, only the H type overtly binds to MAb 12B2 at an intensity similar to that at which it binds to MAbs L42 and 94B4. In the same blots, a stringent condition/mild condition signal ratio approximating 1 confirms the presence of the C type, while a much lower value is found for the L and H types. Simultaneously, the presence of the L type is confirmed under mild digestion conditions by its special glycoprofile, with approximately equal proportions of diglycosylated PrPres and monoglycosylated PrPres, while the C type shows a clearly higher proportion of the diglycosylated PrPres. The H-type character is further confirmed by subjecting PK digests (at pH 6.5 to 7.4) to digestion with PNGase F, which leads to the unique aspect of two deglycosylated PrPres bands when group C antibody is used.

The increasing number of recognized atypical BSE cases represents only a small fraction of the total BSE population. This might well reflect an increased awareness, since the early reports in 2004, of the existence of deviant phenotypes of BSE in laboratories involved in the identification of BSE isolates. In addition, this fraction occurs in older animals and might increase due to the increased age of animals with BSE at the time of detection as a result of the decrease in the level of the BSE epidemic linked to contaminated meat and bone meal. The high incidence of atypical cases in Poland might also have a relation to the higher numbers of aged animals under surveillance. Such cases, including C-type BSE, might also represent previously unnoticed sporadic forms of BSE. With this study and recent publications (8, 14, 17), better awareness and better possibilities for recognition are now available. Sporadic forms of BSE are likely to exist, since even countries with low levels of exposure or unlikely exposure to BSE, like Sweden, Austria, the United States, Japan, and Canada, have detected cases of BSE.

In routine BSE screening, atypical BSE cases (those of the H type and the L type) can, in theory, be missed if the PrPres signals are under the detection levels either due to the application of PK digestion conditions that are too harsh or due to the use of an unsuitable PrP N-terminus-specific antibody (L type). However, it is unlikely that many of these atypical cases have in fact been missed, since the isolates used in this study were detected or their presence was confirmed by the most frequently used commercial screening methods (Table 1). Another concern is the anatomical distribution of the PrPSc deposition in the brain if it differs from that of C-type BSE, in which the obex region is strongly involved in pathology and which is used for routine diagnosis (54). A recent description of an H-type isolate in a zebu showed that the distribution of lesions was similar to that observed in typical BSE (53). In contrast, the Italian L-type case studied here displayed only a comparably weak signal in the obex region, while the thalamus and olfactory bulb were the regions with the highest signals (17). This concern is supported by the fact that it still cannot be predicted whether these cases represent a risk to human health (10). If one or both of the atypical BSE types leads to a human health risk even higher than that presented by C-type BSE, it would be crucial to be able to reliably detect such cases in the bovine population and to differentiate them from C-type BSE.

These data, in any case, might contribute to our understanding of the origin of the BSE epidemic, which remains unresolved and which is also a concern for the future. It is possible that one of such atypical forms could have changed to C-type BSE and was the origin of BSE. It is just as possible that they could have coexisted with C-type BSE as sporadic forms while the epidemic was disguising sporadic cases.



>>>In addition, this fraction occurs in older animals and might increase due to the increased age of animals with BSE at the time of detection as a result of the decrease in the level of the BSE epidemic linked to contaminated meat and bone meal.<<<

SAME as with sporadic CJD in humans, except now, sporadic CJD is showing up in young, with kuru type-like plaques, of long duration from clinical onset of symptoms to death, and with nvCJD like psychiatric symptoms, in Country's with atypical BSE, and none of it is related to mad cow disease ??? why is it that the UKBSEnvCJD only theory cannot happen from any other strain of TSE in cattle, besides the UK c-BSE $ show me the transmission studies that prove atypical BSE cannot transmit just like the c-BSE did orally through feed to other cattle, and to humans there from ? or worse, via birth, or even possibly contagious like CWD and Scrapie ? there are documented cases of a man and his cat with sporadic CJD, husband and wife with sporadic CJD, and a husband and wife with Alzheimer's, coincedence ? what about atypical scrapie, how can it be that the OIE with the help of the USDA, how can it be that they systematically made atypical scrapie a disease that cannot be transmitted to humans or animals, and is not a risk there from, without any scientific testing to prove this hypothesis, but yet went ahead and made regulations on science that has not been proven $ in fact, more and more science is showing just the opposite, that in fact not only the atypical scrapie, but the typical scrapie as well transmits to primates by their NON-FORCED ORAL consumption of scrapie tainted feed, and is in fact a potential human health risk. IF UK c-BSE was from a certain strain or multiple strains of typical scrapie, why is it that another strain of scrapie cannot cause a different strain of BSE. spontaneous TSE has never been proven in the field. and in the lab, no field TSE has ever been proven to be spontaneous. what gives the USA this mad cow cloaking device $$$

Friday, August 27, 2010


Thursday, August 19, 2010

SCRAPIE CANADA UPDATE Current as of 2010-07-31 The following table lists sheep flocks and/or goat herds confirmed to be infected with scrapie in Canada in 2010. Current as of: 2010-07-31

the OIE and the USDA systematically changed the science with the BSE MRR policy, and put everyone around the globe at risk by taking us back to ground zero 1984-1985 kent bse cow.

Saturday, June 19, 2010


i explained it here recently ;

Terry S. Singeltary Sr. has added the following comment: "According to the World Health Organisation, the future public health threat of vCJD in the UK and Europe and potentially the rest of the world is of concern and currently unquantifiable. However, the possibility of a significant and geographically diverse vCJD epidemic occurring over the next few decades cannot be dismissed .

The key word here is diverse. What does diverse mean?

If USA scrapie transmitted to USA bovine does not produce pathology as the UK c-BSE, then why would CJD from there look like UK vCJD?"

SEE FULL TEXT ;,F2400_P1001_PUB_MAIL_ID:1000,82101

.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. 32 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. 33 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. 34 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.

32 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

33 YB88/10.00/1.1

34 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


Rural and Regional Affairs and Transport References Committee The possible impacts and consequences for public health, trade and agriculture of the Government’s decision to relax import restrictions on beef Final report June 2010

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

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

Sunday, September 6, 2009



don't believe me, ask stan the man, the prion man, the nobel prize winner for the prion ;


''they don't wanna know, the dont' care''


Title: Identification and characterization of two bovine spongiform encephalopathy cases diagnosed in the United States


Richt, Juergen Kunkle, Robert Alt, David Nicholson, Eric Hamir, Amirali Czub, Stefanie - NATL BSE REF LAB,MANITOBA Kluge, John - NVSL, APHIS, USDA, AMES, Davis, Arthur - NVSL, APHIS, USDA, AMES, Hall, S Mark - NVSL, APHIS, USDA, AMES,

Submitted to: Journal of Veterinary Diagnostic Investigation Publication Type: Peer Reviewed Journal Publication Acceptance Date: October 20, 2006 Publication Date: March 1, 2007 Citation: Richt, J.A., Kunkle, R.A., Alt, D., Nicholson, E.M., Hamir, A.N., Czub, S., Kluge, J., Davis, A.J., Hall, S.M. 2007. Identification and characterization of two bovine spongiform encephalopathy cases diagnosed in the United States. Journal of Veterinary Diagnostic Investigation. 19(2):142-154.

Interpretive Summary: Bovine spongiform encephalopathy (BSE), also known as "mad cow disease," is a transmissible spongiform encephalopathy of cattle, first detected in 1986 in the United Kingdom and subsequently in other countries. Here we report the identification and characterization the two cases of BSE diagnosed in the United States. BSE case 1 (12/2003) and BSE case 2 (11/2004) were identified and characterized using various diagnostic methods specific for BSE (rapid test, Western blot, immunohistochemistry). Sequencing of the prion protein gene of both BSE-positive animals revealed that the sequences of both cattle were similar as previously reported for cattle. These results confirm that two cases of BSE have been identified in the United States so far: one in a cow imported from Canada and one in a cow born and raised in Texas.

Technical Abstract: Bovine spongiform encephalopathy (BSE) is a transmissible spongiform encephalopathy of cattle, first detected in 1986 in the United Kingdom and subsequently in other countries. It is the most likely cause of variant Creutzfeldt-Jakob disease (vCJD) in humans, but the origin of BSE has not been elucidated so far. Here we report the identification and characterization of the two cases of BSE diagnosed in the United States. Case 1 (12/2003) revealed spongiform changes in the obex area of the brainstem and the presence of the abnormal form of the prion protein, PrP**Sc, in the same brain area, by immunohistochemistry and Western blot analysis. Initial suspect diagnosis of BSE for case 2 (11/2004) was made by a rapid ELISA-based BSE test. Case 2 did not reveal unambiguous spongiform changes in the obex area, but PrP**Sc was detected by immunohistochemistry and enrichment Western Blot analysis in the obex. Using Western blot analysis, PrP**Sc from case 1 showed molecular features similar to typical BSE isolates, whereas PrP**Sc from case 2 revealed an unusual molecular PrP**Sc pattern: molecular mass of the unglycosylated and monoglycosylated isoform was higher than that of typical BSE isolates and case 2 was strongly labeled with antibody P4, which is consistent with a higher molecular mass. Sequencing of the prion protein gene of both BSE-positive animals revealed that the sequences of both animals were within the range of the prion protein gene sequence diversity previously reported for cattle.

Research Project: Transmission, Differentiation, and Pathobiology of Transmissible Spongiform Encephalopathies Location: Virus and Prion Research Unit

Title: Frequencies of polymorphisms associated with BSE resistance differ significantly between Bos taurus, Bos indicus, and composite cattle


Brunelle, Brian Greenlee, Justin Seabury, Christopher - TEXAS A&M UNIVERSITY Brown Ii, Charles - ABS GLOBAL Nicholson, Eric

Submitted to: BioMed Central (BMC) Veterinary Research Publication Type: Peer Reviewed Journal Publication Acceptance Date: August 22, 2008 Publication Date: August 22, 2008 Publisher's URL: Citation: Brunelle, B.W., Greenlee, J.J., Seabury, C.M., Brown II, C.E., Nicholson, E.M. 2008. Frequencies of Polymorphisms Associated with BSE Resistance Differ Significantly Between Bos taurus, Bos indicus, and Composite Cattle. BioMed Central (BMC) Veterinary Research. 4(1):36. Available:

Interpretive Summary: Bovine spongiform encephalopathy (BSE) is a neurodegenerative prion disease of cattle. There are three host factors related to the host prion protein known to influence susceptibility or resistance to BSE: single amino acid changes in the prion protein, repeat regions within the prion protein, and expression levels of the prion protein. These factors have been well documented in breeds of Bos taurus cattle, but there is little-to-no data on these factors in Bos indicus purebred or Bos indicus x Bos taurus crossbred cattle. Since Bos indicus cattle contribute to the U.S. cattle population, we wanted to determine the frequency of the host factors associated with BSE susceptibility. We studied 58 Bos indicus purebred and 38 Bos indicus x Bos taurus crossbred cattle. The only differences between Bos indicus and Bos taurus cattle were in two factors associated with prion protein expression levels. It was observed that Bos indicus cattle had a much higher frequency of one factor associated with resistance to BSE compared to Bos taurus cattle, while the second factor associated with resistance to BSE was much lower in Bos indicus cattle compared to Bos taurus cattle. This data is useful in determining the relative risk of BSE in Bos indicus cattle based upon these factors. Technical Abstract: Transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases that affect several mammalian species. At least three factors related to the host prion protein are known to modulate susceptibility or resistance to a TSE: amino acid sequence, atypical number of octapeptide repeats, and expression level. These factors have been extensively studied in breeds of Bos taurus cattle in relation to bovine spongiform encephalopathy (BSE). However, little is currently known about these factors in Bos indicus purebred or B. indicus x B. taurus crossbred cattle. The goal of our study was to establish the frequency of markers associated with enhanced susceptibility or resistance to BSE in B. indicus purebred and crossbred cattle.


Molecular Features of the Protease-resistant Prion Protein (PrPres) in H-type BSE

Biacabe, A-G1; Jacobs, JG2; Gavier-Widén, D3; Vulin, J1; Langeveld, JPM2; Baron, TGM1 1AFSSA, France; 2CIDC-Lelystad, Netherlands; 3SVA, Sweden

Western blot analyses of PrPres accumulating in the brain of BSE-infected cattle have demonstrated 3 different molecular phenotypes regarding to the apparent molecular masses and glycoform ratios of PrPres bands. We initially described isolates (H-type BSE) essentially characterized by higher PrPres molecular mass and decreased levels of the diglycosylated PrPres band, in contrast to the classical type of BSE. This type is also distinct from another BSE phenotype named L-type BSE, or also BASE (for Bovine Amyloid Spongiform Encephalopathy), mainly characterized by a low representation of the diglycosylated PrPres band as well as a lower PrPres molecular mass. Retrospective molecular studies in France of all available BSE cases older than 8 years old and of part of the other cases identified since the beginning of the exhaustive surveillance of the disease in 20001 allowed to identify 7 H-type BSE cases, among 594 BSE cases that could be classified as classical, L- or H-type BSE. By Western blot analysis of H-type PrPres, we described a remarkable specific feature with antibodies raised against the C-terminal region of PrP that demonstrated the existence of a more C-terminal cleaved form of PrPres (named PrPres#2 ), in addition to the usual PrPres form (PrPres #1). In the unglycosylated form, PrPres #2 migrates at about 14 kDa, compared to 20 kDa for PrPres #1. The proportion of the PrPres#2 in cattle seems to by higher compared to the PrPres#1. Furthermore another PK-resistant fragment at about 7 kDa was detected by some more N-terminal antibodies and presumed to be the result of cleavages of both N- and C-terminal parts of PrP. These singular features were maintained after transmission of the disease to C57Bl/6 mice. The identification of these two additional PrPres fragments (PrPres #2 and 7kDa band) reminds features reported respectively in sporadic Creutzfeldt-Jakob disease and in Gerstmann-Sträussler-Scheinker (GSS) syndrome in humans.

Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle to a Primate

Emmanuel E. Comoy1*, Cristina Casalone2, Nathalie Lescoutra-Etchegaray1, Gianluigi Zanusso3, Sophie Freire1, Dominique Marcé1, Frédéric Auvré1, Marie-Magdeleine Ruchoux1, Sergio Ferrari3, Salvatore Monaco3, Nicole Salès4, Maria Caramelli2, Philippe Leboulch1,5, Paul Brown1, Corinne I. Lasmézas4, Jean-Philippe Deslys1

1 Institute of Emerging Diseases and Innovative Therapies, CEA, Fontenay-aux-Roses, France, 2 Istituto Zooprofilattico Sperimentale del Piemonte, Turin, Italy, 3 Policlinico G.B. Rossi, Verona, Italy, 4 Scripps Florida, Jupiter, Florida, United States of America, 5 Genetics Division, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America


Human variant Creutzfeldt-Jakob Disease (vCJD) results from foodborne transmission of prions from slaughtered cattle with classical Bovine Spongiform Encephalopathy (cBSE). Atypical forms of BSE, which remain mostly asymptomatic in aging cattle, were recently identified at slaughterhouses throughout Europe and North America, raising a question about human susceptibility to these new prion strains.

Methodology/Principal Findings

Brain homogenates from cattle with classical BSE and atypical (BASE) infections were inoculated intracerebrally into cynomolgus monkeys (Macacca fascicularis), a non-human primate model previously demonstrated to be susceptible to the original strain of cBSE. The resulting diseases were compared in terms of clinical signs, histology and biochemistry of the abnormal prion protein (PrPres). The single monkey infected with BASE had a shorter survival, and a different clinical evolution, histopathology, and prion protein (PrPres) pattern than was observed for either classical BSE or vCJD-inoculated animals. Also, the biochemical signature of PrPres in the BASE-inoculated animal was found to have a higher proteinase K sensitivity of the octa-repeat region. We found the same biochemical signature in three of four human patients with sporadic CJD and an MM type 2 PrP genotype who lived in the same country as the infected bovine.


Our results point to a possibly higher degree of pathogenicity of BASE than classical BSE in primates and also raise a question about a possible link to one uncommon subset of cases of apparently sporadic CJD. Thus, despite the waning epidemic of classical BSE, the occurrence of atypical strains should temper the urge to relax measures currently in place to protect public health from accidental contamination by BSE-contaminated products.

Citation: Comoy EE, Casalone C, Lescoutra-Etchegaray N, Zanusso G, Freire S, et al. (2008) Atypical BSE (BASE) Transmitted from Asymptomatic Aging Cattle to a Primate. PLoS ONE 3(8): e3017. doi:10.1371/journal.pone.0003017

Editor: Neil Mabbott, University of Edinburgh, United Kingdom

Received: April 24, 2008; Accepted: August 1, 2008; Published: August 20, 2008

Copyright: © 2008 Comoy et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This work has been supported by the Network of Excellence NeuroPrion.

Competing interests: CEA owns a patent covering the BSE diagnostic tests commercialized by the company Bio-Rad.

* E-mail: mhtml:%7B33B38F65-8D2E-434D-8F9B-8BDCD77D3066%7Dmid://00000110/!

I ask Professor Kong ;

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

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

Professor Kong reply ;


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

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




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

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



Transmission of atypical BSE in humanized mouse models

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

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

Objectives: To investigate these atypical BSE types in terms of their transmissibility and phenotypes in humanized mice.

Methods: Transgenic mice expressing human PrP were inoculated with several classical (C-type) and atypical (L-, H-, or Mtype) BSE isolates, and the transmission rate, incubation time, characteristics and distribution of PrPSc, symptoms, and histopathology were or will be examined and compared.

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

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

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

14th International Congress on Infectious Diseases

H-type and L-type Atypical BSE January 2010 (special pre-congress edition)

18.173 page 189

Experimental Challenge of Cattle with H-type and L-type Atypical BSE

A. Buschmann1, U. Ziegler1, M. Keller1, R. Rogers2, B. Hills3, M.H. Groschup1. 1Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany, 2Health Canada, Bureau of Microbial Hazards, Health Products & Food Branch, Ottawa, Canada, 3Health Canada, Transmissible Spongiform Encephalopathy Secretariat, Ottawa, Canada

Background: After the detection of two novel BSE forms designated H-type and L-type atypical BSE the question of the pathogenesis and the agent distribution of these two types in cattle was fully open. From initial studies of the brain pathology, it was already known that the anatomical distribution of L-type BSE differs from that of the classical type where the obex region in the brainstem always displays the highest PrPSc concentrations. In contrast in L-type BSE cases, the thalamus and frontal cortex regions showed the highest levels of the pathological prion protein, while the obex region was only weakly involved.

Methods:We performed intracranial inoculations of cattle (five and six per group) using 10%brainstemhomogenates of the two German H- and L-type atypical BSE isolates. The animals were inoculated under narcosis and then kept in a free-ranging stable under appropriate biosafety conditions.At least one animal per group was killed and sectioned in the preclinical stage and the remaining animals were kept until they developed clinical symptoms. The animals were examined for behavioural changes every four weeks throughout the experiment following a protocol that had been established during earlier BSE pathogenesis studies with classical BSE.

Results and Discussion: All animals of both groups developed clinical symptoms and had to be euthanized within 16 months. The clinical picture differed from that of classical BSE, as the earliest signs of illness were loss of body weight and depression. However, the animals later developed hind limb ataxia and hyperesthesia predominantly and the head. Analysis of brain samples from these animals confirmed the BSE infection and the atypical Western blot profile was maintained in all animals. Samples from these animals are now being examined in order to be able to describe the pathogenesis and agent distribution for these novel BSE types. Conclusions: A pilot study using a commercially avaialble BSE rapid test ELISA revealed an essential restriction of PrPSc to the central nervous system for both atypical BSE forms. A much more detailed analysis for PrPSc and infectivity is still ongoing.

14th ICID International Scientific Exchange Brochure -

Final Abstract Number: ISE.114

Session: International Scientific Exchange

Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America

update October 2009

T. Singeltary

Bacliff, TX, USA


An update on atypical BSE and other TSE in North America. Please remember, the typical U.K. c-BSE, the atypical l-BSE (BASE), and h-BSE have all been documented in North America, along with the typical scrapie's, and atypical Nor-98 Scrapie, and to date, 2 different strains of CWD, and also TME. All these TSE in different species have been rendered and fed to food producing animals for humans and animals in North America (TSE in cats and dogs ?), and that the trading of these TSEs via animals and products via the USA and Canada has been immense over the years, decades.


12 years independent research of available data


I propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2009. With all the science to date refuting it, to continue to validate this old myth, will only spread this TSE agent through a multitude of potential routes and sources i.e. consumption, medical i.e., surgical, blood, dental, endoscopy, optical, nutritional supplements, cosmetics etc.


I would like to submit a review of past CJD surveillance in the USA, and the urgent need to make all human TSE in the USA a reportable disease, in every state, of every age group, and to make this mandatory immediately without further delay. The ramifications of not doing so will only allow this agent to spread further in the medical, dental, surgical arena's. Restricting the reporting of CJD and or any human TSE is NOT scientific. Iatrogenic CJD knows NO age group, TSE knows no boundaries. I propose as with Aguzzi, Asante, Collinge, Caughey, Deslys, Dormont, Gibbs, Gajdusek, Ironside, Manuelidis, Marsh, et al and many more, that the world of TSE Transmissible Spongiform Encephalopathy is far from an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route.

page 114 ;

Wednesday, February 24, 2010

Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America 14th

ICID International Scientific Exchange Brochure -

To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE. In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.

Transmissible Spongiform Encephalopathy

Wednesday, March 31, 2010

Atypical BSE in Cattle

let's take a closer look at this new prionpathy or prionopathy, and then let's look at the g-h-BSEalabama mad cow.

This new prionopathy in humans? the genetic makeup is IDENTICAL to the g-h-BSEalabama mad cow, the only _documented_ mad cow in the world to date like this, ......wait, it get's better. this new prionpathy is killing young and old humans, with LONG DURATION from onset of symptoms to death, and the symptoms are very similar to nvCJD victims, OH, and the plaques are very similar in some cases too, bbbut, it's not related to the g-h-BSEalabama cow, WAIT NOW, it gets even better, the new human prionpathy that they claim is a genetic TSE, has no relation to any gene mutation in that family. daaa, ya think it could be related to that mad cow with the same genetic make-up ??? there were literally tons and tons of banned mad cow protein in Alabama in commerce, and none of it transmitted to cows, and the cows to humans there from ??? r i g h t $$$


In this study, we identified a novel mutation in the bovine prion protein gene (Prnp), called E211K, of a confirmed BSE positive cow from Alabama, United States of America. This mutation is identical to the E200K pathogenic mutation found in humans with a genetic form of CJD. This finding represents the first report of a confirmed case of BSE with a potential pathogenic mutation within the bovine Prnp gene. We hypothesize that the bovine Prnp E211K mutation most likely has caused BSE in "the approximately 10-year-old cow" carrying the E221K mutation.

Saturday, August 14, 2010

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

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

Tuesday, August 03, 2010

Variably protease-sensitive prionopathy: A new sporadic disease of the prion protein

Monday, August 9, 2010

Variably protease-sensitive prionopathy: A new sporadic disease of the prion protein or just more PRIONBALONEY ?

Thursday, July 10, 2008

A Novel Human Disease with Abnormal Prion Protein Sensitive to Protease update July 10, 2008 Friday, June 20, 2008

Wednesday, August 18, 2010

Incidence of CJD Deaths Reported by CJD-SS in Canada as of July 31, 2010

Monday, August 9, 2010

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

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

Thursday, August 12, 2010

USA Blood products, collected from a donor who was at risk for vCJD, were distributed July-August 2010

Rural and Regional Affairs and Transport References Committee The possible impacts and consequences for public health, trade and agriculture of the Government’s decision to relax import restrictions on beef Final report June 2010

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

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

Wednesday, July 28, 2010

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

Sunday, September 6, 2009



The EMBO Journal (2002) 21, 6358 - 6366 doi:10.1093/emboj/cdf653

BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein

Emmanuel A. Asante1, Jacqueline M. Linehan1, Melanie Desbruslais1, Susan Joiner1, Ian Gowland1, Andrew L. Wood1, Julie Welch1, Andrew F. Hill1, Sarah E. Lloyd1, Jonathan D.F. Wadsworth1 and John Collinge1

1.MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College, Queen Square, London WC1N 3BG, UK Correspondence to:

John Collinge, E-mail:

Received 1 August 2002; Accepted 17 October 2002; Revised 24 September 2002



Variant Creutzfeldt–Jakob disease (vCJD) has been recognized to date only in individuals homozygous for methionine at PRNP codon 129. Here we show that transgenic mice expressing human PrP methionine 129, inoculated with either bovine spongiform encephalopathy (BSE) or variant CJD prions, may develop the neuropathological and molecular phenotype of vCJD, consistent with these diseases being caused by the same prion strain. Surprisingly, however, BSE transmission to these transgenic mice, in addition to producing a vCJD-like phenotype, can also result in a distinct molecular phenotype that is indistinguishable from that of sporadic CJD with PrPSc type 2. These data suggest that more than one BSE-derived prion strain might infect humans; it is therefore possible that some patients with a phenotype consistent with sporadic CJD may have a disease arising from BSE exposure.

Keywords:BSE, Creutzfeldt–Jakob disease, prion, transgenic


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