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Evaluation of the Human Transmission Risk of an Atypical Bovine Spongiform Encephalopathy Prion Strain

Posted Apr 09 2009 7:13pm
Thursday, January 31, 2008

Evaluation of the Human Transmission Risk of an Atypical Bovine Spongiform Encephalopathy Prion Strain

J. Virol. doi:10.1128/JVI.02561-07Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Thursday, January 31, 2008Evaluation of the Human Transmission Risk of an Atypical Bovine Spongiform Encephalopathy Prion Strain J. Virol. doi:10.1128/JVI.02561-07Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Evaluation of the Human Transmission Risk of an Atypical Bovine Spongiform Encephalopathy Prion Strain

Qingzhong Kong*, Mengjie Zheng, Cristina Casalone, Liuting Qing, Shenghai Huang, Bikram Chakraborty, Ping Wang, Fusong Chen, Ignazio Cali, Cristiano Corona, Francesca Martucci, Barbara Iulini, Pierluigi Acutis, Lan Wang, Jingjing Liang, Meiling Wang, Xinyi Li, Salvatore Monaco, Gianluigi Zanusso, Wen-Quan Zou, Maria Caramelli, and Pierluigi Gambetti*Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA; CEA, Istituto Zooprofilattico Sperimentale, 10154 Torino, Italy; Department of Neurological and Visual Sciences, University of Verona, 37134 Verona, Italy

* To whom correspondence should be addressed. Email: . .


Bovine spongiform encephalopathy (BSE), the prion disease in cattle, was widely believed to have only one strain (BSE-C). BSE-C causes the fatal prion disease named new variant Creutzfeldt-Jacob disease in humans. Two atypical BSE strains, BASE (or BSE-L) and BSE-H, have been discovered in several countries since 2004; their transmissibility and phenotypes in humans are unknown. We investigated the infectivity and human phenotype of BASE by inoculating transgenic (Tg) mice expressing the human prion protein with brain homogenates from two BASE-affected cattle. Sixty percent of the inoculated Tg mice became infected after 20-22 months incubation, a transmission rate higher than those reported for BSE-C. A quarter of BASE-infected Tg mice, but none of the Tg mice infected with a sporadic human prion disease, showed presence of pathogenic prion protein isoforms in the spleen, indicating that the BASE prion is intrinsically lymphotropic. The pathological prion protein isoforms in BASE-infected humanized Tg mouse brains are different from those of the original cattle BASE or sporadic human prion disease. Minimal brain spongiosis and long incubation time are observed in the BASE-infected Tg mice. These results suggest that, in humans, BASE is a more virulent BSE strain and likely lymphotropic.

for those interested, further into this study ;


Overwhelming evidence indicates that BSE, a prion disease that has been detected in several hundred thousand cattle in the UK and many other countries since the 1980s, has been transmitted to humans through the consumption of prion contaminated beef, causing a prion disease named variant Creutzfeldt-Jakob disease (vCJD) (5, 20). Over 200 cases of vCJD have been reported around the world (19). In 2004 two types of bovine prion disease that differ from the original BSE, now named classical BSE (BSE-C), were reported (4, 8). The two atypical BSE were associated with prion protein (PrP) scrapie isoforms (PrPSc) that, after protease digestion, displayed distinct electrophoretic mobility or ratios of the PrPSc glycoforms different from those of BSE-C (4, 8). Currently, a total of at least 36 cases of these two atypical BSE have been reported in cattle older than eight years (5; Caramelli, M., unpublished data). The two atypical BSE are identified as BASE (bovine amyloidotic spongiform encephalopathy) or L-type and H- type, respectively; the “L” and “H” identify the higher and lower electrophoretic positions of their protease-resistant PrPSc isoforms (7). The bovine phenotype and the PrPSc molecular features of BASE have been described in detail (8). The histopathology and PrP immunostaining pattern of BASE are characterized by the presence of prion amyloid plaques, and a more rostral distribution of the PrPSc, which, at variance with BSE-C, is present in the cerebral cortex including the hippocampus but is underrepresented in the brain stem (8). These phenotypic features and PrPSc characteristics resemble a subtype of sporadic Creutzfeldt-Jakob disease (sCJD) named sCJDMV2, which affects subjects who are methionine (M)/valine (V) heterozygous at codon 129 of the PrP gene, and it is associated with PrPSc identified as type 2 (15). This similarity has raised the question as of whether sCJDMV2 is not sporadic but acquired from the consumption of BASE-contaminated meat (5, 8). To begin to investigate the transmissibility to humans and the “human” disease phenotype of BASE, including the involvement of the lymphoreticular system, we have inoculated brain homogenates from BASE- affected cattle to Tg mice expressing normal human PrP with Met at codon 129 (HuPrP-129M) in a mouse PrP ablated background [Tg(HuPrP)] (13). The inoculated Tg mice were examined for attack rate and the disease phenotype, including the presence and characteristics of protease- resistant PrPSc in the brain and spleen, the histopathology, along with the PrPSc topography and pattern of deposition in the brain.


To assess the transmissibility of BASE in humans, two BASE isolates (8) were used to intracerebrally inoculate 30 Tg40 mice that express normal level of human PrP-129M. More than half of the inoculated mice (18/30) became infected, as determined by the presence of protease-resistant PrPSc, with an average incubation time of 649±34 days for BASE isolate 1 and 595±28 days for BASE isolate 2, respectively (Table 1). Ten of the 18 infected mice that could be examined showed clear clinical signs of disease (Table 1), including hunched back, ruffled fur, lethargy, occasional wobbling and rigid tail. These signs were best detected in the younger mice because in mice older than 24 months they became difficult to distinguish from aging- related changes.

All the Tg40 mice were examined for the presence of proteinase K (PK)-resistant PrPSc in the brain by immunoblot analysis both directly and after enrichment with sodium phosphotungstate (NaPTA) precipitation. Such immunoblot analysis with three monoclonal antibodies (3F4, 6H4, 8H4) to various PrP regions (12, 14, 25) showed that all 18 BASE-infected Tg40 mice accumulated comparable amounts of proteinase K (PK)-resistant PrPSc in the brain (Figure 1A, Table 1, and data not shown). The electrophoretic mobility of PK-resistant PrPSc fragments from all the BASE-infected Tg40 mice was indistinguishable from that of the PK- resistant PrPSc present in either the BASE inoculum or sCJDMM2 that contains PrPSc type 2 (Figure 1A). The PK-resistant PrPSc fragments associated with both the BASE-infected Tg40 mice and the BASE isolates migrated slightly faster than those of BSE-C as originally reported (8). Measurements with software that automatically calculates the mid-point of the bands revealed a difference of 0.29±0.12 kDa in gel mobility between the unglycosylated PK-resistant PrPSc bands of BASE (native as well as from the Tg40 mice) and BSE-C.

The glycoform ratio of PrPSc in the BASE-infected Tg40 mice was slightly different from that of the BASE isolates (Figure 1B), and both were quite different from that of BSE-C (Figure 1B). The monoglycosylated form (the middle band) was the most prominent species in the BASE inocula where the glycoform ratio (diglycosylated : monoglycosylated : unglycosylated) is 32:41:27, whereas the diglycosylated form (the top band) was slightly more intense than the monoglycosylated form in BASE-infected Tg40 mice where the glycoform ratio is 44:39:17 (Figure 1B). In contrast, the diglycosylated form accounted for over 70% of the total PrPSc in BSE-C (glycoform ratio 72:20:8).

PrPSc in the spleen was also examined after NaPTA enrichment for all 30 BASE- inoculated Tg40 mice. PK-resistant PrPSc was readily detected in the spleen of 4 mice (Figure 1C), all of which also contained PK-resistant PrPSc in the brain. The electrophoretic mobility of the spleen PrPSc was similar to that of the brain PrPSc. The glycoform ratio of the spleen PrPSc was different from that of the brain and was characterized by the prominence of the monoglycosylated and unglycosylated forms (Figure 1C), but the glycoform ratio may have been affected by the NaPTA enrichment. In contrast, none of the 9 Tg40 mice inoculated with sCJDMM1 had detectable PK-resistant PrPSc in the spleen after NaPTA enrichment (data not shown).

None of the 12 BASE-infected Tg40 mice examined showed prominent and consistent histopathological changes related to prion diseases (Figure 2A). Focal, ambiguous spongiform degeneration was observed in 2 mice. No PrP amyloid plaques were observed in BASE-infected Tg40 mice. Histoblot analysis with mAb 3F4 showed a very distinct and selective distribution of PrPSc (Figure 3A-D). Particular nuclei or group of adjacent peri-ventricular nuclei in the thalamus, hypothalamus and brain stem were intensely immunostained for PrPSc (Figure 3B-D). In contrast, PrPSc appeared to be overall less intense in the cerebral and cerebellar cortices (Figure 3A-D). Immunohistochemical staining of paraffin-embedded brain tissue with 3F4 revealed PrP deposits in five of the 11 BASE-infected Tg40 mice examined. PrPSc deposits that stained intensely in the histoblots consisted of relatively large and well circumscribed granules (Figure 3E and G). Fine granular or small plaque-like aggregate patterns were occasionally seen in inferior regions of the cerebral cortex and in the thalamus (Figure 3I and data not shown). In contrast, widespread mostly fine granular staining was detected in the cerebral cortex of symptomatic Tg40 mice inoculated with sCJDMM1 brain homogenate (Figure 3J).

The histopathological features of the BASE-inoculated Tg40 mice were quite different from those observed following inoculation with brain homogenates from the two forms of sporadic CJD, sCJDMM1 and sCJDMM2. The sCJDMM1-inoculated Tg40 mice had widespread spongiform degeneration in the cerebrum (Figure 2B) and moderate apoptosis of neuronal cells without spongiform degeneration in the cerebellum (13). Widespread spongiform degeneration was also seen in Tg40 mice inoculated with sCJDMM2 brain homogenate (Data not shown).


We have shown that 60% of our Tg40 mice (in inbred FVB background) that express normal level of human PrP-129M became infected 20-22 months after intracerebral (i.c.) inoculation with 0.3mg of brain tissue from the two BASE isolates, suggesting a titer of approximately 3 ID50 units per mg of brain tissue in the Tg40 line. A ~20% attack rate has been reported in the Tg650 line (in a mixed 129/Sv x C57BL/6 background) after i.c. inoculation with 2mg brain tissues from BSE-C affected cattle (2). It is noteworthy that the Tg650 mice express human PrP-129M at 5-8x normal level, and high PrP levels are known to increase prion transmissibility (9, 17, 22). Inefficient BSE-C transmissions (0-30%) in Tg mouse lines of other genetic backgrounds expressing human PrP-129M at 1x or 2x normal levels have also been reported by different groups (1, 3). Although it is difficult to compare results from different mouse lines, these findings suggest that BASE has higher transmissibility than that of BSE-C to humanized transgenic mice with PrP-129M and possibly to humans with PrP-129MM. BASE also appears to be more virulent than BSE-C in bovinized Tg mice since the incubation time for BASE is 185±12 days whereas that for BSE-C is 230±7 days (7). Nevertheless, when compared with the 100% attack rate and incubation times of ~9 months for sCJDMM1 and sCJDMM2 in the Tg40 line (Table 1), the 60% attack rate and unusually long incubation times (20-22 months) for BASE in the same Tg line suggest that the transmission barrier from BASE to humans with PrP-129MM is still quite significant.

PK-resistant PrPSc was also detected in the spleen in 4 out of 18 BASE-infected Tg40 mice. In contrast, no spleen involvement could be demonstrated in the Tg40 mice following i.c. inoculation with human PrPSc from sCJDMM1. This is the first report of the presence of PrPSc in the spleen of humanized Tg mice after i.c. inoculation with a BSE strain, suggesting that the BASE strain, like BSE-C where at least in vCJD affected subjects PrPSc and prion infectivity have been detected in spleen and tonsil (6, 11), is intrinsically lymphotropic. Therefore, lymphoid tissues of BASE-infected individuals might also carry prion infectivity.

The gel mobility of the PK-resistant PrPSc recovered from the BASE-inoculated Tg40 mice was consistently slightly faster than that of BSE-C as originally reported for BASE (8). The computed difference in gel mobility between BASE and BSE-C PrPSc is 0.29 ± 0.12 kDa, corresponding to 2-4 amino acid residues. In contrast, the gel mobility of the PK-resistant PrPSc species from BASE, BASE-infected Tg40 mice, and sCJDMM2 that was used as representative of human PrPSc type 2, was indistinguishable. This finding suggests that the PK-resistant PrPSc electrophoretic heterogeneity between BASE and BSE-C falls well within the seven amino acid variability of the N-terminus (92-99) that is consistently found in PK-resistant PrPSc type 2 (16). Therefore, despite their minor but distinct variability in gel mobility, both BASE and BSE-C PrPSc species appear to belong to the PrPSc type 2. However, the PrPSc glycoform ratios of BASE-infected Tg40 mice and the BASE inocula display a small but statistically significant difference (Figure 1). Therefore, PrPSc in BASE-infected human subjects may be expected to display a different glycoform ratio from that of BASE. It is worth noting that the electrophoretic characteristics of the PK-resistant PrPSc of some human prion strains has been faithfully reproduced by our Tg40 line as well as by other humanized mouse lines (10, 13, 21).

Two distinct histopathological and PrP immunohistochemical phenotypes have been reported following BSE-C inoculation: one reproduced the distinctive features of vCJD with the “florid” plaques which intensely immunostained for PrP, and the other was reminiscent of sCJDMM1 with prominent spongiform degeneration and no plaque PrP immunostaining (1, 23).

The brain histopathology, the PrPSc distribution and the PrP immunostaining pattern of BASE- inoculated Tg40 mice were definitely distinct from such features described above (1, 23), further supporting the notion that BASE and BSE-C are associated with two distinct prion strains (8).

The relatively easy transmission of BASE to humanized Tg mice indicates that effective cattle prion surveillance should be maintained until the extent and origin of this and other atypical forms of BSE are fully understood.




P02.35 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.

FC5.5.1 BASE Transmitted to Primates and MV2 sCJD Subtype Share PrP27-30 and PrPSc C-terminal Truncated Fragments

Zanusso, G1; Commoy, E2; Fasoli, E3; Fiorini, M3; Lescoutra, N4; Ruchoux, MM4; Casalone, C5; Caramelli, M5; Ferrari, S3; Lasmezas, C6; Deslys, J-P4; Monaco, S3 1University of Verona, of Neurological and Visual Sciences, Italy; 2CEA, IMETI/SEPIA, France; 3University of Verona, Neurological and Visual Sciences, Italy; 4IMETI/SEPIA, France; 5IZSPLVA, Italy; 6The Scripps Research Insitute, USA

The etiology of sporadic Creutzfeldt-Jakob disease (sCJD), the most frequent human prion disease, remains still unknown. The marked disease phenotype heterogeneity observed in sCJD is thought to be influenced by the type of proteinase K- resistant prion protein, or PrPSc (type 1 or type 2 according to the electrophoretic mobility of the unglycosylated backbone), and by the host polymorphic Methionine/Valine (M/V) codon 129 of the PRNP. By using a two-dimensional gel electrophoresis (2D-PAGE) and imunoblotting we previously showed that in sCJD, in addition to the PrPSc type, distinct PrPSc C-terminal truncated fragments (CTFs) correlated with different sCJD subtypes. Based on the combination of CTFs and PrPSc type, we distinguished three PrPSc patterns: (i) the first was observed in sCJD with PrPSc type 1 of all genotypes,;

(ii) the second was found in M/M-2 (cortical form); (iii) the third in amyloidogenic M/V- 2 and V/V-2 subtypes (Zanusso et al., JBC 2004) . Recently, we showed that sCJD subtype M/V-2 shared molecular and pathological features with an atypical form of BSE, named BASE, thus suggesting a potential link between the two conditions. This connection was further confirmed after 2D-PAGE analysis, which showed an identical PrPSc signature, including the biochemical pattern of CTFs. To pursue this issue, we obtained brain homogenates from Cynomolgus macaques intracerebrally inoculated with brain homogenates from BASE. Samples were separated by using a twodimensional electrophoresis (2D-PAGE) followed by immunoblotting. We here show that the PrPSc pattern obtained in infected primates is identical to BASE and sCJD MV-2 subtype.
*** These data strongly support the link, or at least a common ancestry, between a sCJD subtype and BASE.

This work was supported by Neuroprion (FOOD-CT-2004-506579)

************************************************** *****



USA BASE CASE, (ATYPICAL BSE), AND OR TSE (whatever they are calling it today), please note that both the ALABAMA COW, AND THE TEXAS COW,both were ''H-TYPE'', personal communication Detwiler et al Wednesday, August 22, 2007 11:52 PM. ...TSS

************************************************** *****

FC5.5.2 Transmission of Italian BSE and BASE Isolates in Cattle Results into a Typical BSE Phenotype and a Muscle Wasting Disease

Zanusso, G1; Lombardi, G2; Casalone, C3; D’Angelo, A4; Gelmetti, D2; Torcoli, G2; Barbieri, I2; Corona, C3; Fasoli, E1; Farinazzo, A1; Fiorini, M1; Gelati, M1; Iulini, B3; Tagliavini, F5; Ferrari, S1; Monaco, S1; Caramelli, M3; Capucci, L2 1University of Verona, Neurological and Visual Sciences, Italy; 2IZSLER, Italy; 3IZSPLVA, Italy; 4University of Turin, Animal Pathology, Italy; 5Isituto Carlo Besta, Italy

The clinical phenotype of bovine spongiform encephalopathy has been extensively reported in early accounts of the disorder. Following the introduction of statutory active surveillance, almost all BSE cases have been diagnosed on a pathological/molecular basis, in a pre-symptomatic clinical stage. In recent years, the active surveillance system has uncovered atypical BSE cases, which are characterized by distinct conformers of the PrPSc, named high-type (BSE-H) and low-type (BSE-L), whose clinicopathological phenotypes remain unknown. We recently reported two Italian atypical cases with a PrPSc type similar to BSE-L, pathologically characterized by PrP amyloid plaques. Experimental transmission to TgBov mice has recently disclosed that BASE is caused by a distinct prion strain which is extremely virulent. A major limitation of transmission studies to mice is the lack of reliable information on clinical phenotype of BASE in its natural host. In the present study, we experimentally infected Fresian/Holstein and Alpine/Brown cattle with Italian BSE and BASE isolates by i.c. route. BASE infected cattle showed survival times significantly shorter than BSE, a finding more readily evident in Fresian/Holstein, and in keeping with previous observations in TgBov mice. Clinically, BSE-infected cattle developed a disease phenotype highly comparable with that described in field BSE cases and in experimentally challenged cattle. On the contrary, BASE-inoculated cattle developed an amyotrophic disorder accompanied by mental dullness. The molecular and neuropathological profiles, including PrP deposition pattern, closely matched those observed in the original cases. This study further confirms that BASE is caused by a distinct prion isolate and discloses a novel disease phenotype in cattle, closely resembling the phenotype previous reported in scrapie-inoculated cattle
*** and in some subtypes of inherited and sporadic Creutzfeldt-Jakob disease.

Oral Abstracts 14



Experimental BSE Infection of Non-human Primates: Efficacy of the Oral Route

Holznagel, E1; Yutzy, B1; Deslys, J-P2; Lasmézas, C2; Pocchiari, M3; Ingrosso, L3; Bierke, P4; Schulz-Schaeffer, W5; Motzkus, D6; Hunsmann, G6; Löwer, J1 1Paul-Ehrlich-Institut, Germany; 2Commissariat à l´Energie Atomique, France; 3Instituto Superiore di Sanità, Italy; 4Swedish Institute for Infectious Disease control, Sweden; 5Georg August University, Germany; 6German Primate Center, Germany

In 2001, a study was initiated in primates to assess the risk for humans to contract BSE through contaminated food. For this purpose, BSE brain was titrated in cynomolgus monkeys.

The primary objective is the determination of the minimal infectious dose (MID50) for oral exposure to BSE in a simian model, and, by in doing this, to assess the risk for humans. Secondly, we aimed at examining the course of the disease to identify possible biomarkers.

Groups with six monkeys each were orally dosed with lowering amounts of BSE brain: 16g, 5g, 0.5g, 0.05g, and 0.005g. In a second titration study, animals were intracerebrally (i.c.) dosed (50, 5, 0.5, 0.05, and 0.005 mg).

In an ongoing study, a considerable number of high-dosed macaques already developed simian vCJD upon oral or intracerebral exposure or are at the onset of the clinical phase. However, there are differences in the clinical course between orally and intracerebrally infected animals that may influence the detection of biomarkers.

Simian vCJD can be easily triggered in cynomolgus monkeys on the oral route using less than 5 g BSE brain homogenate. The difference in the incubation period between 5 g oral and 5 mg i.c. is only 1 year (5 years versus 4 years). However, there are rapid progressors among orally dosed monkeys that develop simian v CJD as fast as intracerebrally inoculated animals.

The work referenced was performed in partial fulfilment of the study “BSE in primates“ supported by the EU (QLK1-2002-01096).

Subject: Aspects of the Cerebellar Neuropathology in Nor98

Date: September 26, 2007 at 4:06 pm PST


Aspects of the Cerebellar Neuropathology in Nor98

Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E1 1National Veterinary Insitute, Sweden; 2National Veterinary Institute, Norway

Nor98 is a prion disease of old sheep and goats. This atypical form of scrapie was first described in Norway in 1998. Several features of Nor98 were shown to be different from classical scrapie including the distribution of disease associated prion protein (PrPd) accumulation in the brain. The cerebellum is generally the most affected brain area in Nor98. The study here presented aimed at adding information on the neuropathology in the cerebellum of Nor98 naturally affected sheep of various genotypes in Sweden and Norway. A panel of histochemical and immunohistochemical (IHC) stainings such as IHC for PrPd, synaptophysin, glial fibrillary acidic protein, amyloid, and cell markers for phagocytic cells were conducted. The type of histological lesions and tissue reactions were evaluated. The types of PrPd deposition were characterized. The cerebellar cortex was regularly affected, even though there was a variation in the severity of the lesions from case to case. Neuropil vacuolation was more marked in the molecular layer, but affected also the granular cell layer. There was a loss of granule cells. Punctate deposition of PrPd was characteristic. It was morphologically and in distribution identical with that of synaptophysin, suggesting that PrPd accumulates in the synaptic structures. PrPd was also observed in the granule cell layer and in the white matter.
*** The pathology features of Nor98 in the cerebellum of the affected sheep showed similarities with those of sporadic Creutzfeldt-Jakob disease in humans.


Creutzfeldt Jakob Disease Delaware UPDATE

Creutzfeldt Jakob Disease Texas




USA BASE CASE, (ATYPICAL BSE), AND OR TSE (whatever they are calling it today), please note that both the ALABAMA COW, AND THE TEXAS COW,both were ''H-TYPE'', personal communication Detwiler et al Wednesday, August 22, 2007 11:52 PM. ...TSS


[Docket No. FSIS-2006-0011] FSIS Harvard Risk Assessment of BovineSpongiform Encephalopathy (BSE)

APHIS-2006-0041-0006 TSE advisory committee for the meeting December 15,2006

Attachment to Singletary
January 28, 2007

Greetings APHIS,

I would kindly like to submit the following to ;

BSE; MRR; IMPORTATION OF LIVE BOVINES AND PRODUCTS DERIVED FROM BOVINES[Docket No. APHIS-2006-0041] RIN 0579-AC01[Federal Register: January 9, 2007 (Volume 72, Number 5)][Proposed Rules][Page 1101-1129]From the Federal Register Online via GPO Access [][DOCID:fr09ja07-21]




[Docket No. 03-025IFA] FSIS Prohibition of the Use of Specified Risk Materials for Human Food and Requirement for the Disposition of Non-Ambulatory Disabled Cattle


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