Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits
Hiroyuki Okada1*, Yoshifumi Iwamaru1, Morikazu Imamura1, Kentaro Masujin1, Yuichi Matsuura1, Yoshihisa Shimizu1, Kazuo Kasai1, Shirou Mohri1, Takashi Yokoyama1 and Stefanie Czub2
1Prion Disease Research Center, National Institute of Animal Health, 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0856, Japan 2Canadian and OIE Reference Laboratories for BSE, Canadian Food Inspection Agency Lethbridge Laboratory, Lethbridge, Alberta, Canada
- 1 -
Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits
Hiroyuki Okada1*, Yoshifumi Iwamaru1, Morikazu Imamura1, Kentaro Masujin1, Yuichi Matsuura1, Yoshihisa Shimizu1, Kazuo Kasai1, Shirou Mohri1, Takashi Yokoyama1 and Stefanie Czub2 1Prion Disease Research Center, National Institute of Animal Health, 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0856, Japan 2Canadian and OIE Reference Laboratories for BSE, Canadian Food Inspection Agency Lethbridge Laboratory, Lethbridge, Alberta, Canada *Corresponding author E-mail addresses: HO: okadahi@affrc.go.jp YI: gan@affrc.go.jp KM: masujin@affrc.go.jp MI: imamuram@affrc.go.jp YM: zrxmatsu@affrc.go.jp YS: zenzo@affrc.go.jp KK: kakasai@affrc.go.jp SM: shirou@affrc.go.jp TY: tyoko@affrc.go.jp SC: Stefanie.Czub@inspection.gc.ca
ABSTRACT
Atypical bovine spongiform encephalopathy (BSE) has recently been identified in Europe, North America, and Japan. It is classified as H-type and L-type BSE according to the molecular mass of the disease-associated prion protein (PrPSc). To investigate the topographical distribution and deposition patterns of immunolabeled PrPSc, H-type BSE isolate was inoculated intracerebrally into cattle. H-type BSE was successfully transmitted to 3 calves, with incubation periods between 500 and 600 days. Moderate to severe spongiform changes were detected in the cerebral and cerebellar cortices, basal ganglia, thalamus, and brainstem. H-type BSE was characterized by the presence of PrP-immunopositive amyloid plaques in the white matter of the cerebrum, basal ganglia, and thalamus. Moreover, intraglial-type immunolabeled PrPSc was prominent throughout the brain. Stellate-type immunolabeled PrPSc was conspicuous in the gray matter of the cerebral cortex, basal ganglia, and thalamus, but not in the brainstem. In addition, PrPSc accumulation was detected in the peripheral nervous tissues, such as trigeminal ganglia, dorsal root ganglia, optic nerve, retina, and neurohypophysis. Cattle are susceptible to H-type BSE with a shorter incubation period, showing distinct and distinguishable phenotypes of PrPSc accumulation.
SNIP$$$
Unfortunately, a detailed and all-encompassing analysis of neuropathology and topographical distribution of immunolabeled PrPSc in H-type BSE-affected cattle could not be performed, since only the obex region is routinely sampled for BSE surveillance testing and the remaining brain as well as the carcasses are not available in most countries [3, 10, 12, 13, 24-27]. Recently, clinical signs and biochemical properties of experimental German H-type BSE cases have been reported [20]. The primary objective of this study was to investigate the transmissibility of H-type BSE, using a field isolate detected in the active surveillance program in Canada [12]. The secondary objective was to extend the knowledge of the topographical distribution and deposition patterns of immunolabeled PrPSc in H-type BSE.
SNIP$$$
DISCUSSION
This study demonstrated successful intraspecies transmission of H-type BSE characterized by a shorter incubation period as compared with C-type BSE [19]. To the best of our knowledge, thus far, neuropathological and immunohistochemical data for H-type BSE have only been reported from the medulla oblongata at the obex in German, United States, and Swedish field cases [10, 13, 24]. This is related to the fact that only the obex region is sampled for BSE rapid tests and other brain regions are often unavailable due to marked autolysis, limitations in collection infrastructure, or freezing artifacts [10, 13, 24, 25]. This is the first presentation of H-type lesion profiles involving the whole CNS and additional nervous tissues, although of experimentally infected animals.
Incubation periods in the cattle challenged with the Canadian H-type BSE (mean period, 18 months) were two months longer than those reported in cattle challenged with German H-type BSE [20]. This difference in incubation periods has several potential explanations, which include differences in agents tested, inoculum titers, and breeding conditions. Infectivity titer issues might be resolved by comparing secondpassage infection experiment results.
Spongy changes were generally present in the gray matter throughout the brain and spinal cord, but were more conspicuous in the cerebral cortices, thalamus, hypothalamus, and midbrain. In most brain areas, vacuoles were generally detected in the neuropil and only occasionally in the neurons. The spatial distribution pattern of spongiform changes and immunolabeled PrPSc in the brain of an H-type BSE-infected Zebu, analyzed with N-terminal-specific mAb P4 and C-terminal-specific mAb F99/97.6.1, was similar to that in C-type BSE cases [38]. In natural and experimental C- 15 - type BSE cases, spongiform lesions are consistently distributed throughout the brain, but overall, the lesions in the thalamus and brainstem including the midbrain and medulla oblongata at the obex are more severe than those in the cerebral cortices [29, 39]. The results of the present study indicate that the vacuolar lesion score of the H-type BSE-challenged cattle was higher than that of C-type BSE-affected cattle [19, 29, 40, 41]. Moreover, the topographical distribution of PrPSc in the brain of BSE-infected sheep is similar irrespective of the different challenge routes such as intracerebral, intravascular, or intraperitoneal route [42], suggesting common patterns of neuroinvasion and CNS spread [43]. On the contrary, the minor differences detected in the distribution of PrPSc in the brain between deer that are orally and intracerebrally infected with BSE may be due to differences in the routes of infection [44].
The immunolabeling patterns of PrPSc in the cattle affected with H-type BSE were characterized by the presence of both PrPSc-positive plaques and intraglial- and stellate-type PrPSc accumulations in the brain. Severe intraneuronal- and intraglial-type PrPSc accumulations as well as plaque-like PrPSc aggregates with the absence of stellatetype PrPSc deposition have been reported in the obex region of H-type BSE-affected animals [10, 13]. These immunohistochemical features were detected in the obex region and coincided with those observed in the present study. However, neither amyloid plaques nor stellate-type PrPSc depositions have been reported in H-type BSE-affected cattle, most likely due to their limitation to the medulla oblongata at the obex [8, 10, 13, 24].
Two different types of plaques were found in this study: unicentric and multicentric PrP plaques. Most of these plaques were uniformly immunopositive for PrP, with a dense non-Congophilic core. The plaques that had a pale central core with a Congophilic reaction were less frequent. It has been suggested that Congophilic plaques - 16 - may correspond with the late stage of plaque formation, whereas non-Congophilic plaques coincide with the early stage of CJD and Gerstmann-Sträussler-Scheinker syndrome [45]. The 2 types of PrPSc-positive plaques—unicentric and multicentric— have been described in L-type BSE [5, 19, 46]. Our results indicate that the presence of PrPSc plaques in the forebrain but not in the brainstem is one of the neuropathological features in cattle affected with atypical BSE. In addition, glial-type PrPSc deposition in the white matter throughout the brain seems to be a characteristic feature of H-type BSE in cattle, as supported by identical findings in German and Swedish H-type BSE field cases [10, 13].
Extracellular PrPSc was immunolabeled with N-terminal-, core-, and C-terminalspecific antibodies, but intracellular PrPSc did not show immunoreactivity to the Nterminal- specific anti-PrP antibodies [47, 48]. Intracellular PrPSc has markedly diminished immunoreactivity to N-terminal-specific anti-PrP antibodies [47]. However, N-terminal-specific mAb P4, which recognizes an epitope at bovine PrP residues 101– 107, showed intraneuronal PrPSc immunolabeling in sheep affected with C-type BSE [47] and in Zebu affected with H-type BSE [38]. These results indicate that the epitope region for either mAb P4 or core-specific anti-PrP antibodies is located upstream of an intracellular truncation site [38, 48]. The differences in intracellular PrPSc truncation sites between sheep scrapie and ovine BSE [47] as well as between C-type BSE and Htype BSE [38] most probably depend on the strain and the tissues and cells [47]. The intensity and patterns of PrPSc immunolabeling varied with the different anti-PrP antibodies used, and the difference in the PrPSc immunohistochemical labeling results might be related to the application of different technical protocols, especially antigen retrieval methods [49-51].
The western blot profiles of PrPres for the H-type BSE-challenged cattle and the Canadian H-type BSE-infected brain homogenate used as inoculum were indistinguishable. Results of previous studies prove that H-type BSE isolates have distinct biological and biochemical properties compared with C-type and L-type BSE isolates [3, 52, 53]. The PrPres in H-type BSE, as detected by mAb SAF84 recognizing the C-terminus of PrP, was thought to be composed of 2 fragments with molecular masses of 19 kDa and 10–12 kDa, possessing a different cleavage site in the N-terminal region with PK digestion [53]. The higher molecular mass of the unglycosylated PrPres molecules, which included an additional 10–12 kDa fragment, in the Canadian H-type BSE case was maintained in the challenged animals. These unique molecular features of PrP in H-type BSE are also well preserved in transgenic and wild type mice [16, 53]. In addition, a distinct 10–12 kDa fragment detected with C-terminal-specific antibodies in H-type BSE might be associated with the presence of PrP plaques [53].
Although PrPC glycosylation seems to play a critical role in the maintenance of strain-dependent prion neurotropism [54, 55], a recent study has demonstrated that PrPSc glycosylation is not required for the maintenance of strain-specific neurotropisms [56]. Strain-dependent prion neurotropism is currently unknown, but several possibilities have been indicated [56]. Moreover, a local difference in the PrPSc replication rate may be attributed to a high degree of neurotropism in H-type BSE similar to that observed in C-type BSE [57].
Since 2003, sporadic and discontinuous occurrence of atypical BSE has been detected in Europe, North America, and Japan. Although, till date, the origin and frequency of atypical BSE is unknown, a high prevalence is found in older cattle over the age of eight years. This is the result of the active surveillance programs using rapid screening tests, with the exception of a Zebu case [38]. It has been reported that H-type - 18 - BSE can be the result of a naturally occurring, heritable variant caused by glutamic acid/lysine polymorphism at codon 211 of the bovine PRNP gene (E211K) [11, 58]. However, our cases, although experimentally challenged via the intracranial route, and the original Canadian H-type BSE field case [11, 58] developed the disease without the novel mutation E211K within PRNP. Therefore, atypical BSE seemed to be sporadic rather than inherited with a higher risk in fallen stock than in healthy slaughtered cattle [8, 13, 25], suggesting that young adult cattle affected with atypical BSE might be dormant carriers. Further studies are required to determine the epidemiological significance and origin of atypical BSE.
The present study demonstrated successful intraspecies transmission of H-type BSE to cattle and the distribution and immunolabeling patterns of PrPSc in the brain of the Htype BSE-challenged cattle. TSE agent virulence can be minimally defined by oral transmission of different TSE agents (C-type, L-type, and H-type BSE agents) [59]. Oral transmission studies with H-type BSE-infected cattle have been initiated and are underway to provide information regarding the extent of similarity in the immunohistochemical and molecular features before and after transmission. In addition, the present data will support risk assessments in some peripheral tissues derived from cattle affected with H-type BSE.
SNIP...
SEE FULL TEXT ;
http://www.veterinaryresearch.org/content/pdf/1297-9716-42-79.pdf
NOW, compare the pathology h-BSE to hvCJD ;
The Heidenhain Variant of Creutzfeldt-Jakob Disease
Stefan Kropp, MD; Walter J. Schulz-Schaeffer, MD; Michael Finkenstaedt, MD; Christian Riedemann, MD; Otto Windl, PhD; Bernhard J. Steinhoff, MD; Inga Zerr, MD; Hans A. Kretzschmar, MD; Sigrid Poser, MD
Arch Neurol. 1999;56:55-61.
snip...
NEUROPATHOLOGICAL EXAMINATION
As complete neuropathological samples were not obtained from all referred patients by the Reference Center for Spongiform Encephalopathies, different parts of cortical regions, basal ganglia, and cerebellum obtained at autopsy from 14 patients with Heidenhain variant were analyzed in a standardized neuropathological examination. For comparison, brain tissue from 14 patients with pathologically proved CJD with ataxia at onset was examined neuropathologically.
Formalin-fixed tissue was decontaminated for 1 hour in concentrated formic acid according to the instructions of Brown et al28 and embedded in paraffin. Microtome sections were cut at 2 µm and mounted on silanized slides. Immunohistochemical staining was performed after deparaffinization and pretreatement of the mounted sections by hydrolytic autoclaving in 2-mmol/L hydrochloric acid for 30 minutes at 121°C.29
A monoclonal antibody against a synthetic peptide corresponding to amino acids 138 to 152 of the human PrP (Gö138) was used.30 After 18 hours of incubation with the primary antibody at 4°C, a standard alkaline phosphatase anti-alkaline phosphatase (APAAP) technique was used for detection. The slides were counterstained with hemalum. Histological examination was performed by 2 investigators (S.K. and W.J.S.-S.) who were blinded to the clinical data. The degree of spongiform change of the molecular layer, astrocytic gliosis, and loss of granular cells were estimated semiquantitatively on a scale ranging from 0 to 4 in hematoxylin-eosin–stained sections. The pattern of immunohistochemical PrP staining was classified according to Kitamoto et al29 in a diffuse fine and coarse granular pattern ("synaptic type"), a plaquelike pattern, and plaques visible on hematoxylin-eosin staining.
Spongiform changes, gliosis, and nerve cell loss were classified semiquantitatively for each section (0-4 points, assigned for no change or mild, moderate, severe, or maximal changes [status spongiosus], respectively). The average of semiquantitatively measured pathological changes in 14 cases compared with controls was calculated for each section. A mean of spongiform changes, gliosis, and nerve cell loss was calculated in each case. A lesion profile was drawn, placing the location of the section at the x-axis and the average value of pathological changes along the y-axis of a 2-axis graph.
http://archneur.ama-assn.org/cgi/content/full/56/1/55
compare to the h-BSE case in this paper ;
Neuropathology
Scores for the distribution and severity of vacuolation in the brain were similar among the 3 challenged calves. Vacuolar changes were generally observed in all the brain areas. In general, the vacuoles varied in size. The highest mean lesion scores appeared in the thalamic nuclei and neuropil of the central gray matter of the midbrain, and the lowest scores were found in the caudal cerebral and cerebellar cortices. In the vestibular and pontine nuclei, spongy changes were not as prominent as in the other brainstem nuclei. In the spinal cord of the animals with clinical disease, mild vacuolation was - 10 - present in the neuropil of the gray matter. The detailed vacuolar lesion profile is shown in Figure 1. Lesion scores for C-type BSE in cattle have been previously described [21].
PrPSc immunohistochemistry
Initially, immunohistochemistry was performed with the C-terminus PrP specific antibody F99/97.6.1. Large amounts of PrPSc were deposited diffusely in the cerebral cortex, basal ganglia, thalamus, hypothalamus, brainstem, and spinal cord of all three challenged animals (Figure 2). The most conspicuous type of PrPSc deposition was fine or coarse particulate-type deposition in the neuropil of the gray matter throughout the brain and spinal cord of all the animals (Figures 3a and 3b). Linear, perineuronal, and intraneuronal types of PrPSc staining, usually detected in C-type BSE-affected cattle, were observed in the cerebral cortex, basal ganglia, thalamus, and brainstem of the Htype BSE-challenged cattle (Figure 3). The deposition pattern of PrPSc was characterized by the presence of stellate, intraglial, and plaque forms in the brain of the H-type BSE-challenged cattle (Figure 3). Stellate-type PrPSc deposition was predominantly identified in the cerebral cortex, basal ganglia, thalamus, hypothalamus, and hippocampus and often in the cerebellar cortex, but was not visible in the brainstem and spinal cord (Figure 3e). Intraglial-type PrPSc deposition was very consistent throughout the white matter of the central nervous system (CNS) and spinal cord (Figures 3h and 4e–h).
PrPSc-positive plaques were scattered throughout the cerebral white matter (Figure 4). Some PrPSc-positive were also detected in the deep cortical layer of the cerebrum, internal capsule of the corpus striatum and thalamic white matter, and cerebellum (Figures 3f and 4), but were absent from the brainstem and spinal cord. On the basis of the morphology of the cores, as revealed after application of immunohistochemistry, the plaques were classified into unicentric and multicentric types (Figure 4). Unicentric plaques had a single core and were up to 25 ìm in diameter (Figures 4a and 4e). Multicentric plaques were composed of multiple smaller cores clustered together or a central core surrounded by even smaller plaques or aggregates, varied in shape and could extend up to 40 ìm in diameter (Figures 4b-4d and 4f-4h). Both types of plaques were subdivided into two subtypes, that is, those with a dense compact core and others with a pale central core. The dense compact core plaques were less than 20 ìm in diameter and smaller than the plaques with a pale central core; they were uniformly immunolabeled and were difficult to detect in HE or Congo red-stained sections (Figures 4c and 4g). Furthermore, plaques with a pale central core were generally larger than that with a dense compact core and stained pale basophilic or amphophilic with HE and positively with Congo red under polarized light (Figure 4e). The periphery of these plaques looked like a halo unstained with HE and Congo red but well immunolabeled with PrP-specific antibodies. In addition, the granular form of plaque-like deposits, was rarely detected in the deep cerebral cortex, basal ganglia, and thalamic nuclei and not detected in the white matter (Figures 4d and 4h). These deposits were not stained with Congo red and were composed of aggregates about 5 ìm in diameter.
SEE FULL TEXT ;
http://www.veterinaryresearch.org/content/pdf/1297-9716-42-79.pdf
SNIP$$$
Unfortunately, a detailed and all-encompassing analysis of neuropathology and topographical distribution of immunolabeled PrPSc in H-type BSE-affected cattle could not be performed, since only the obex region is routinely sampled for BSE surveillance testing and the remaining brain as well as the carcasses are not available in most countries [3, 10, 12, 13, 24-27]. Recently, clinical signs and biochemical properties of experimental German H-type BSE cases have been reported [20]. The primary objective of this study was to investigate the transmissibility of H-type BSE, using a field isolate detected in the active surveillance program in Canada [12]. The secondary objective was to extend the knowledge of the topographical distribution and deposition patterns of immunolabeled PrPSc in H-type BSE.
SNIP$$$
SEE FULL TEXT ;
http://www.veterinaryresearch.org/content/pdf/1297-9716-42-79.pdf
WHY IS THIS $$$
maybe ask the USDA and the OIE ?
BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only) diagnostic criteria CVL 1992
http://bse-atypical.blogspot.com/2010/11/bse-atypical-lesion-distribution-rbse.html
Thursday, November 18, 2010
UNITED STATES OF AMERICA VS GALEN J. NIEHUES FAKED MAD COW FEED TEST ON 92 BSE INSPECTION REPORTS FOR APPROXIMATELY 100 CATTLE OPERATIONS
http://bse-atypical.blogspot.com/2010/11/united-states-of-america-vs-galen-j.html
Tuesday, May 24, 2011 2:24 PM
O.I.E. Terrestrial Animal Health Standards Commission and prion (TSE) disease reporting 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/oie-terrestrial-animal-health-standards.html
----- Original Message -----
From: Terry S. Singeltary Sr.
To: Debra.Beasley@aphis.usda.gov
Sent: Tuesday, November 24, 2009 11:01 AM
Subject: OIE has recently published its proposed animal welfare guidelines for public comment
Greetings USDA/APHIS et al,
I would kindly like to comment on OIE proposed guidelines.
AS I said before, OIE should hang up there jock strap now, since it appears they will buckle every time a country makes some political hay about trade protocol, commodities and futures. IF they are not going to be science based, they should do everyone a favor and dissolve there organization. THE reason most every country around the globe came down with BSE/TSE in their cattle, were due to the failed and flawed BSE/TSE testing and surveillance policy of the O.I.E. NOW, they don't even acknowledge atypical scrapie it seems, as one for concern $
Monday, November 23, 2009
BSE GBR RISK ASSESSMENTS UPDATE NOVEMBER 23, 2009 COMMISSION OF THE EUROPEAN COMMUNITIES AND O.I.E.
http://docket-aphis-2006-0041.blogspot.com/2009/11/bse-gbr-risk-assessments-update.html
Tuesday, May 24, 2011 2:24 PM
O.I.E. Terrestrial Animal Health Standards Commission and prion (TSE) disease reporting 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/oie-terrestrial-animal-health-standards.html
Saturday, June 19, 2010 U.S.
DENIED UPGRADED BSE STATUS FROM OIE
http://usdameatexport.blogspot.com/2010/06/us-denied-upgraded-bse-status-from-oie.html
IN A NUT SHELL ; $$$
(Adopted by the International Committee of the OIE on 23 May 2006)
11. Information published by the OIE is derived from appropriate declarations made by the official Veterinary Services of Member Countries.The OIE is not responsible for inaccurate publication of country disease status based on inaccurate information or changes in epidemiological status or other significant events that were not promptly reported to then Central Bureau............
http://www.oie.int/eng/Session2007/RF2006.pdf
2009 UPDATE ON ALABAMA AND TEXAS MAD COWS 2005 and 2006
http://bse-atypical.blogspot.com/2006/08/bse-atypical-texas-and-alabama-update.html
http://madcowtesting.blogspot.com/2007/10/bse-base-mad-cow-testing-texas-usa-and.html
http://madcowtesting.blogspot.com/
let's take a closer look at this new prionpathy or prionopathy, and then let's look at the g-h-BSEalabama mad cow.
This new prionopathy in humans? the genetic makeup is IDENTICAL to the g-h-BSEalabama mad cow, the only _documented_ mad cow in the world to date like this, ......wait, it get's better. this new prionpathy is killing young and old humans, with LONG DURATION from onset of symptoms to death, and the symptoms are very similar to nvCJD victims, OH, and the plaques are very similar in some cases too, bbbut, it's not related to the g-h-BSEalabama cow, WAIT NOW, it gets even better, the new human prionpathy that they claim is a genetic TSE, has no relation to any gene mutation in that family. daaa, ya think it could be related to that mad cow with the same genetic make-up ??? there were literally tons and tons of banned mad cow protein in Alabama in commerce, and none of it transmitted to cows, and the cows to humans there from ??? r i g h t $$$
ALABAMA MAD COW g-h-BSEalabama
In this study, we identified a novel mutation in the bovine prion protein gene (Prnp), called E211K, of a confirmed BSE positive cow from Alabama, United States of America. This mutation is identical to the E200K pathogenic mutation found in humans with a genetic form of CJD. This finding represents the first report of a confirmed case of BSE with a potential pathogenic mutation within the bovine Prnp gene. We hypothesize that the bovine Prnp E211K mutation most likely has caused BSE in "the approximately 10-year-old cow" carrying the E221K mutation.
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000156
http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.ppat.1000156&representation=PDF
her healthy calf also carried the mutation (J. A. Richt and S. M. Hall PLoS Pathog. 4, e1000156; 2008).
This raises the possibility that the disease could occasionally be genetic in origin. Indeed, the report of the UK BSE Inquiry in 2000 suggested that the UK epidemic had most likely originated from such a mutation and argued against the scrapierelated assumption. Such rare potential pathogenic PRNP mutations could occur in countries at present considered to be free of BSE, such as Australia and New Zealand. So it is important to maintain strict surveillance for BSE in cattle, with rigorous enforcement of the ruminant feed ban (many countries still feed ruminant proteins to pigs). Removal of specified risk material, such as brain and spinal cord, from cattle at slaughter prevents infected material from entering the human food chain. Routine genetic screening of cattle for PRNP mutations, which is now available, could provide additional data on the risk to the public. Because the point mutation identified in the Alabama animals is identical to that responsible for the commonest type of familial (genetic) CJD in humans, it is possible that the resulting infective prion protein might cross the bovine–human species barrier more easily. Patients with vCJD continue to be identified. The fact that this is happening less often should not lead to relaxation of the controls necessary to prevent future outbreaks.
Malcolm A. Ferguson-Smith Cambridge University Department of Veterinary Medicine, Madingley Road, Cambridge CB3 0ES, UK e-mail: maf12@cam.ac.uk Jürgen A. Richt College of Veterinary Medicine, Kansas State University, K224B Mosier Hall, Manhattan, Kansas 66506-5601, USA
NATURE|Vol 457|26 February 2009
http://www.nature.com/nature/journal/v457/n7233/full/4571079b.html
Monday, May 11, 2009
Rare BSE mutation raises concerns over risks to public health
http://bse-atypical.blogspot.com/2009/05/rare-bse-mutation-raises-concerns-over.html
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)
http://prionpathy.blogspot.com/2010/08/bse-case-associated-with-prion-protein.html
PLEASE NOTE *
Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.
snip...
The rancher was a ''dead stock'' feeder using mostly (> 95 %) downer or dead dairy cattle...
http://web.archive.org/web/20030516051623/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf
NOW, what about that mad cow feed from atypical BSE in commerce and SRM regulations ???
Research Project: Study of Atypical Bse Location: Virus and Prion Research Unit
Project Number: 3625-32000-086-05 Project Type: Specific Cooperative Agreement
Start Date: Sep 15, 2004 End Date: Sep 14, 2009
Objective: The objective of this cooperative research project with Dr. Maria Caramelli from the Italian BSE Reference Laboratory in Turin, Italy, is to conduct comparative studies with the U.S. bovine spongiform encephalopathy (BSE) isolate and the atypical BSE isolates identified in Italy. The studies will cover the following areas: 1. Evaluation of present diagnostics tools used in the U.S. for the detection of atypical BSE cases. 2. Molecular comparison of the U.S. BSE isolate and other typical BSE isolates with atypical BSE cases. 3. Studies on transmissibility and tissue distribution of atypical BSE isolates in cattle and other species.
Approach: This project will be done as a Specific Cooperative Agreement with the Italian BSE Reference Laboratory, Istituto Zooprofilattico Sperimentale del Piemonte, in Turin, Italy. It is essential for the U.S. BSE surveillance program to analyze the effectiveness of the U.S diagnostic tools for detection of atypical cases of BSE. Molecular comparisons of the U.S. BSE isolate with atypical BSE isolates will provide further characterization of the U.S. BSE isolate. Transmission studies are already underway using brain homogenates from atypical BSE cases into mice, cattle and sheep. It will be critical to see whether the atypical BSE isolates behave similarly to typical BSE isolates in terms of transmissibility and disease pathogenesis. If transmission occurs, tissue distribution comparisons will be made between cattle infected with the atypical BSE isolate and the U.S. BSE isolate. Differences in tissue distribution could require new regulations regarding specific risk material (SRM) removal.
http://www.ushrl.saa.ars.usda.gov/research/projects/projects.htm?accn_no=408490
Saturday, June 12, 2010
PUBLICATION REQUEST AND FOIA REQUEST Project Number: 3625-32000-086-05 Study of Atypical Bse
http://bse-atypical.blogspot.com/2010/06/publication-request-and-foia-request.html
Wednesday, July 28, 2010
re-Freedom of Information Act Project Number 3625-32000-086-05, Study of Atypical BSE UPDATE July 28, 2010
http://bse-atypical.blogspot.com/2010/07/re-freedom-of-information-act-project.html
Friday, October 8, 2010
Scientific reasons for a feed ban of meat-and-bone meal, applicable to all farmed animals including cattle, pigs, poultry, farmed fish and pet food
http://madcowfeed.blogspot.com/2010/10/scientific-reasons-for-feed-ban-of-meat.html
P.9.21
Molecular characterization of BSE in Canada
Jianmin Yang1, Sandor Dudas2, Catherine Graham2, Markus Czub3, Tim McAllister1, Stefanie Czub1 1Agriculture and Agri-Food Canada Research Centre, Canada; 2National and OIE BSE Reference Laboratory, Canada; 3University of Calgary, Canada
Background: Three BSE types (classical and two atypical) have been identified on the basis of molecular characteristics of the misfolded protein associated with the disease. To date, each of these three types have been detected in Canadian cattle.
Objectives: This study was conducted to further characterize the 16 Canadian BSE cases based on the biochemical properties of there associated PrPres. Methods: Immuno-reactivity, molecular weight, glycoform profiles and relative proteinase K sensitivity of the PrPres from each of the 16 confirmed Canadian BSE cases was determined using modified Western blot analysis.
Results: Fourteen of the 16 Canadian BSE cases were C type, 1 was H type and 1 was L type. The Canadian H and L-type BSE cases exhibited size shifts and changes in glycosylation similar to other atypical BSE cases. PK digestion under mild and stringent conditions revealed a reduced protease resistance of the atypical cases compared to the C-type cases. N terminal- specific antibodies bound to PrPres from H type but not from C or L type. The C-terminal-specific antibodies resulted in a shift in the glycoform profile and detected a fourth band in the Canadian H-type BSE.
Discussion: The C, L and H type BSE cases in Canada exhibit molecular characteristics similar to those described for classical and atypical BSE cases from Europe and Japan. This supports the theory that the importation of BSE contaminated feedstuff is the source of C-type BSE in Canada.
*** It also suggests a similar cause or source for atypical BSE in these countries.
http://www.prion2009.com/sites/default/files/Prion2009_Book_of_Abstracts.pdf
100S OF MILLIONS OF POUNDS OF BANNED SUSPECT MAD COW FEED IN COMMERCE IN THE USA A DECADE POST AUGUST 4, 1997 PARTIAL AND VOLUNTARY FEED BAN WAS INKED ON PAPER. now that that science shows indeed the atypical BSE, both the l-type and the h-type BSE more virulent, what about the SRM factor ???
should the specified risk material regulations be upgraded as ARS said above, since now science shows that they atypical BSEs are more virulent?
or will the USDA et al just roll the dice again $$$ remember those dead stock downer cows, and the USDA NSLP, where for 4 years, dead stock downers, the most high risk cattle for mad cow disease and other deadly pathogens, were fed you our children all across the Nation.
WHO WILL WATCH THE CHILDREN FOR CJD OVER THE NEXT 5 + DECADES ???
Do you actually believe that the USDA et al jumped in on the law suit against Westland/Hallmark, at the time the largest beef recall in USA history, just because a few animals were abused on a video, or to cover their ass, for letting our children, from school district to school district, from state to state, be fed dead stock downer cows.
In the papers, the government alleges the meatpacking plant slaughtered and processed downer cows for nearly four years — from January 2004 to September 2007 — at the average rate of one every six weeks...
http://downercattle.blogspot.com/2009/09/suit-meatpacker-used-downer-cows-for-4.html
Do you actually believe all these schools recalled this meat because of a few cattle being abused, see list ; FNS All Regions Affected School Food Authorities By State United States Department of Agriculture Food and Nutrition Service National School Lunch Program March 24, 2008 School Food Authorities Affected by Hallmark/Westland Meat Packing Co. Beef Recall February 2006 - February 2008
http://www.fns.usda.gov/fns/safety/pdf/Hallmark-Westland_byState.pdf
PLEASE SEE ALSO ;
Members of The HSUS are also concerned about the meat products provided to their children through the National School Lunch Program. More than 31 million school children receive lunches through the program each school day. To assist states in providing healthful, low-cost or free meals, USDA provides states with various commodities including ground beef. As evidenced by the HallmarkNVestland investigation and recall, the potential for downed animals to make their way into the National School Lunch Program is neither speculative nor hypothetical.
http://biotech.law.lsu.edu/cases/FDA/hsus-v-schafer-usda-complaint.pdf
PLEASE NOTE *
Over the next 8-10 weeks, approximately 40% of all the adult mink on the farm died from TME.
snip...
The rancher was a ''dead stock'' feeder using mostly (>95%) downer or dead dairy cattle...
http://web.archive.org/web/20030516051623/http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf
PLEASE be aware, for 4 years, the USDA fed our children all across the Nation dead stock downer cows, the most high risk cattle for BSE aka mad cow disease and other dangerous pathogens. who will watch our children for CJD for the next 5+ decades ???
SCHOOL LUNCH PROGRAM FROM DOWNER CATTLE UPDATE
http://downercattle.blogspot.com/2009/05/who-will-watch-children.html
http://downercattle.blogspot.com/
Differences in tissue distribution could require new regulations regarding specific risk material (SRM) removal.
Saturday, November 6, 2010
TAFS1 Position Paper on Position Paper on Relaxation of the Feed Ban in the EU Berne, 2010 TAFS
INTERNATIONAL FORUM FOR TRANSMISSIBLE ANIMAL DISEASES AND FOOD SAFETY a non-profit Swiss Foundation
http://madcowfeed.blogspot.com/2010/11/tafs1-position-paper-on-position-paper.html
Archive Number 20101206.4364
Published Date 06-DEC-2010
Subject PRO/AH/EDR; Prion disease update 2010 (11)
PRION DISEASE UPDATE 2010 (11)
http://www.promedmail.org/pls/apex/f?p=2400:1001:5492868805159684::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,86129
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.
http://www.neuroprion.com/pdf_docs/conferences/prion2007/abstract_book.pdf
Thursday, October 07, 2010
Experimental Transmission of H-type Bovine Spongiform Encephalopathy to Bovinized Transgenic Mice
Thursday, October 07, 2010 Experimental Transmission of H-type Bovine Spongiform Encephalopathy to Bovinized Transgenic Mice
Vet Pathol 0300985810382672, first published on October 4, 2010
Experimental Transmission of H-type Bovine Spongiform Encephalopathy to Bovinized Transgenic Mice
H. Okada okadahi@affrc.go.jp Prion Disease Research Center, National Institute of Animal Health, Tsukuba, K. Masujin Prion Disease Research Center, National Institute of Animal Health, Tsukuba, Y. Imamaru Prion Disease Research Center, National Institute of Animal Health, Tsukuba, M. Imamura Prion Disease Research Center, National Institute of Animal Health, Tsukuba, Y. Matsuura Prion Disease Research Center, National Institute of Animal Health, Tsukuba, S. Mohri Prion Disease Research Center, National Institute of Animal Health, Tsukuba, S. Czub Animal Disease Research Institute, Canadian Food Inspection Agency, T. Yokoyama Prion Disease Research Center, National Institute of Animal Health, Tsukuba,
Abstract
To characterize the biological and biochemical properties of H-type bovine spongiform encephalopathy (BSE), a transmission study with a Canadian H-type isolate was performed with bovinized transgenic mice (TgBoPrP), which were inoculated intracerebrally with brain homogenate from cattle with H-type BSE. All mice exhibited characteristic neurologic signs, and the subsequent passage showed a shortened incubation period. The distribution of disease-associated prion protein (PrPSc) was determined by immunohistochemistry, Western blot, and paraffin-embedded tissue (PET) blot. Biochemical properties and higher molecular weight of the glycoform pattern were well conserved within mice. Immunolabeled granular PrPSc, aggregates, and/or plaque-like deposits were mainly detected in the following brain locations: septal nuclei, subcallosal regions, hypothalamus, paraventricular nucleus of the thalamus, interstitial nucleus of the stria terminalis, and the reticular formation of the midbrain. Weak reactivity was detected by immunohistochemistry and PET blot in the cerebral cortex, most thalamic nuclei, the hippocampus, medulla oblongata, and cerebellum. These findings indicate that the H-type BSE prion has biological and biochemical properties distinct from those of C-type and L-type BSE in TgBoPrP mice, which suggests that TgBoPrP mice constitute a useful animal model to distinguish isolates from BSE-infected cattle.
© 2010 Sage Publications, Inc.
http://vet.sagepub.com/content/early/2010/10/02/0300985810382672.abstract
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.
http://www.prion2009.com/sites/default/files/Prion2009_Book_of_Abstracts.pdf
P.4.23
Transmission of atypical BSE in humanized mouse models
Liuting Qing1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5, Qingzhong Kong1 1Case Western Reserve University, USA; 2Instituto Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research Institute, Poland; 5Kansas State University (Previously at USDA National Animal Disease Center), USA
Background: Classical BSE is a world-wide prion disease in cattle, and the classical BSE strain (BSE-C) has led to over 200 cases of clinical human infection (variant CJD). Atypical BSE cases have been discovered in three continents since 2004; they include the L-type (also named BASE), the H-type, and the first reported case of naturally occurring BSE with mutated bovine PRNP (termed BSE-M). The public health risks posed by atypical BSE were largely undefined.
Objectives: To investigate these atypical BSE types in terms of their transmissibility and phenotypes in humanized mice. Methods: Transgenic mice expressing human PrP were inoculated with several classical (C-type) and atypical (L-, H-, or Mtype) BSE isolates, and the transmission rate, incubation time, characteristics and distribution of PrPSc, symptoms, and histopathology were or will be examined and compared.
Results: Sixty percent of BASE-inoculated humanized mice became infected with minimal spongiosis and an average incubation time of 20-22 months, whereas only one of the C-type BSE-inoculated mice developed prion disease after more than 2 years. Protease-resistant PrPSc in BASE-infected humanized Tg mouse brains was biochemically different from bovine BASE or sCJD. PrPSc was also detected in the spleen of 22% of BASE-infected humanized mice, but not in those infected with sCJD. Secondary transmission of BASE in the humanized mice led to a small reduction in incubation time.*** The atypical BSE-H strain is also transmissible with distinct phenotypes in the humanized mice, but no BSE-M transmission has been observed so far.
Discussion: Our results demonstrate that BASE is more virulent than classical BSE, has a lymphotropic phenotype, and displays a modest transmission barrier in our humanized mice. BSE-H is also transmissible in our humanized Tg mice. The possibility of more than two atypical BSE strains will be discussed.
Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.
P02.16
Analysis of Bovine Prion Protein Gene Sequence Variation in Animals with Classical and Atypical BSE
Polak, MP; Larska, M; Rola, J; Zmudzinski, JF National Veterinary Research Institute, Department of Virology, Poland B.
Variation within prion protein gene sequence have major impact on the susceptibility to prion diseases in humans and sheep. However no major differences between healthy cattle and bovine spongiform encephalopathy (BSE) affected individuals were identified. Recent studies indicate that susceptibility to bovine spongiform encephalopathy is associated with 23-base pair (bp) and 12-bp indel sequences. Identification of atypical BSE in older cattle in several countries pointed at the possibility of spontaneous origin of this new form of prion disease due to possible mutations within prion gene (PRNP) sequence. A./O. Therefore the aim of the study was to analyze and to compare prion protein gene sequences in animals showing classical and atypical BSE for any genetic traits differentating both forms of the disease. M. Analysis included: octapeptide-repeat polymorphism; sequence analysis of exon 3 region; deletion/insertion polymorphism within the promoter sequence (23-bp), intron 1 (12-bp) and 3'untranslated region - UTR (14-bp) of PRNP gene. R. No major differences were found as for the octapeptide-repeats. Most dominant genotype in both classical and atypical BSE involved 6/6 homozygous animals. Sequence comparison within exon 3 region also showed no differences. Results from indel sequence analysis within three regions of PRNP gene were also quite uniform between both forms of BSE. D. Therefore no genetic traits explaining the appearance of atypical BSE could be found. However, it is too early to reject the hypothesis that genetic makeup is not involved in atypical BSE. Further and more detailed studies including more cases of atypical BSE would be more reliable to draw such a conclusion.
O.10.6
Biological typing of sporadic Creutzfeldt- Jakob disease isolates and comparison with animal prion isolates
Romolo Nonno1, Michele Di Bari1, Laura Pirisinu1, Stefano Marcon1, Claudia D'Agostino1, Elena Esposito1, Paola Fazzi1, Shimon Simson1, Paolo Frassanito1, Cristina Casalone3, Franco Cardone2, Maurizio Pocchiari2, Gabriele Vaccari1, Umberto Agrimi1 1Dept. SPVSA, Istituto Superiore di Sanità, Italy; 2Dept. BCN, Istituto Superiore di Sanità, Italy; 3Istituto Zooprofilattico del Piemonte, Liguria e Valle D'Aosta, Italy
Background: Our incomplete understanding of the nature of TSE agents, along with the current technical limitations in the analysis of PrPSc structure, prevent the direct typing of prion isolates. The characterization of prion strains still relies upon bioassay in rodents. Bank vole (Myodes glareolus), being susceptible to a wide range of prion sources, offers the opportunity to investigate the biological properties of prion isolates from different species in a single model.
Objectives: To study the biological properties of sCJD subtypes and compare them with animal TSEs. Methods: We analysed the phenotype of transmission of MM1, MV1, MM2, MV2, and VV2 sCJD subtypes to voles, in comparison with BSE, BASE and classical scrapie isolates from different EU countries. Molecular analysis of PrPSc from the original isolates preceded voles inoculation. Survival time and attack rate were calculated upon primary transmissions and subsequent passages. The brain of voles were analysed by WB for PrPSc type, by Gnd- HCl denaturation for PrPSc conformational stability, by immunohistochemistry and PET-blot for PrPSc deposition pattern and by E&E for lesion profile.
Results: This study demonstrated that prion diseases induce in voles a variety of molecular and pathological phenotypes. CJD isolates were grouped into 4 categories: i) MM1/MV1 (n=3), ii) MM2 (n=1), iii) MV2 (n=2) and iv) VV2 (n=1). Scrapie isolates were categorised in at least 4 groups, with no overlapping with sCJD isolates. BSE was distinct from scrapie and sCJD phenotypes. Finally, BASE gave a phenotype distinct from BSE and scrapie but indistinguishable from VV2 sCJD.
Discussion: Overall, the biological classification of sCJD subtypes concurs with their clinico-pathological classification.*** Similarities in the transmission pattern of prion isolates from different host species were very rare, with the notable exception of BASE and VV2 sCJD. Herein, the meaning of such similarities is discussed in the context of current knowledge on strains and of available tools for their typing.
http://www.prion2009.com/sites/default/files/Prion2009_Book_of_Abstracts.pdf
P26 TRANSMISSION OF ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY (BSE) IN HUMANIZED MOUSE MODELS
Liuting Qing1, Fusong Chen1, Michael Payne1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5*, and Qingzhong Kong1 1Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA; 2CEA, Istituto Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research Institute, Poland; 5Kansas State University, Diagnostic Medicine/Pathobiology Department, Manhattan, KS 66506, USA. *Previous address: USDA National Animal Disease Center, Ames, IA 50010, USA
Classical BSE is a world-wide prion disease in cattle, and the classical BSE strain (BSE-C) has led to over 200 cases of clinical human infection (variant CJD). Two atypical BSE strains, BSE-L (also named BASE) and BSE-H, have been discovered in three continents since 2004. The first case of naturally occurring BSE with mutated bovine PrP gene (termed BSE-M) was also found in 2006 in the USA. The transmissibility and phenotypes of these atypical BSE strains/isolates in humans were unknown. We have inoculated humanized transgenic mice with classical and atypical BSE strains (BSE-C, BSE-L, BSE-H) and the BSE-M isolate. We have found that the atypical BSE-L strain is much more virulent than the classical BSE-C.*** The atypical BSE-H strain is also transmissible in the humanized transgenic mice with distinct phenotype, but no transmission has been observed for the BSE-M isolate so far.
III International Symposium on THE NEW PRION BIOLOGY: BASIC SCIENCE, DIAGNOSIS AND THERAPY 2 - 4 APRIL 2009, VENEZIA (ITALY)
http://www.istitutoveneto.it/prion_09/Abstracts_09.pdf
I ask Professor Kong ;
Thursday, December 04, 2008 3:37 PM Subject: RE: re--Chronic Wating Disease (CWD) and Bovine Spongiform Encephalopathies (BSE): Public Health Risk Assessment
''IS the h-BSE more virulent than typical BSE as well, or the same as cBSE, or less virulent than cBSE? just curious.....''
Professor Kong reply ;
.....snip
''As to the H-BSE, we do not have sufficient data to say one way or another, but we have found that H-BSE can infect humans. I hope we could publish these data once the study is complete. Thanks for your interest.''
Best regards, Qingzhong Kong, PhD Associate Professor Department of Pathology Case Western Reserve University Cleveland, OH 44106 USA
END...TSS
Tuesday, November 02, 2010
BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only) diagnostic criteria CVL 1992
http://bse-atypical.blogspot.com/2010/11/bse-atypical-lesion-distribution-rbse.html
BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein
Emmanuel A. Asante, Jacqueline M. Linehan, Melanie Desbruslais, Susan Joiner, Ian Gowland, Andrew L. Wood, Julie Welch, Andrew F. Hill, Sarah E. Lloyd, Jonathan D.F. Wadsworth, and John Collinge1 MRC Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College, Queen Square, London WC1N 3BG, UK 1Corresponding author e-mail: j.collinge@prion.ucl.ac.ukReceived August 1, 2002; Revised September 24, 2002; Accepted October 17, 2002.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC136957/?tool=pubmed
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: j.collinge@prion.ucl.ac.uk
Received 1 August 2002; Accepted 17 October 2002; Revised 24 September 2002
----------------------------------------------------------
Abstract
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
http://www.nature.com/emboj/journal/v21/n23/abs/7594869a.html
let's take a closer look at this new prionpathy or prionopathy, and then let's look at the g-h-BSEalabama mad cow.
This new prionopathy in humans? the genetic makeup is IDENTICAL to the g-h-BSEalabama mad cow, the only _documented_ mad cow in the world to date like this, ......wait, it get's better. this new prionpathy is killing young and old humans, with LONG DURATION from onset of symptoms to death, and the symptoms are very similar to nvCJD victims, OH, and the plaques are very similar in some cases too, bbbut, it's not related to the g-h-BSEalabama cow, WAIT NOW, it gets even better, the new human prionpathy that they claim is a genetic TSE, has no relation to any gene mutation in that family. daaa, ya think it could be related to that mad cow with the same genetic make-up ??? there were literally tons and tons of banned mad cow protein in Alabama in commerce, and none of it transmitted to cows, and the cows to humans there from ??? r i g h t $$$
ALABAMA MAD COW g-h-BSEalabama
In this study, we identified a novel mutation in the bovine prion protein gene (Prnp), called E211K, of a confirmed BSE positive cow from Alabama, United States of America. This mutation is identical to the E200K pathogenic mutation found in humans with a genetic form of CJD. This finding represents the first report of a confirmed case of BSE with a potential pathogenic mutation within the bovine Prnp gene. We hypothesize that the bovine Prnp E211K mutation most likely has caused BSE in "the approximately 10-year-old cow" carrying the E221K mutation.
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000156
http://www.plospathogens.org/article/fetchObjectAttachment.action?uri=info%3Adoi%2F10.1371%2Fjournal.ppat.1000156&representation=PDF
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)
http://prionpathy.blogspot.com/2010/08/bse-case-associated-with-prion-protein.html
Sunday, May 01, 2011
STUDY OF ATYPICAL BSE 2010 Annual Report May 2011
http://bse-atypical.blogspot.com/2011/05/study-of-atypical-bse-2010-annual.html
What is the potential cost of pre- and post-slaughter testing? The estimated cost of post-mortem testing is $40 per head. This amount is comprised almost entirely of the cost of the test kit and sample analysis. It is expected that ante-mortem tests (live animal), if a test is developed, will reduce BSE testing costs to approximately $15 per head.
http://www.prionetcanada.ca/detail.aspx?menu=12&dt=293720&app=70&cat1=211&tp=12&lk=no
Wednesday, March 31, 2010
Atypical BSE in Cattle
To date the OIE/WAHO assumes that the human and animal health standards set out in the BSE chapter for classical BSE (C-Type) applies to all forms of BSE which include the H-type and L-type atypical forms. This assumption is scientifically not completely justified and accumulating evidence suggests that this may in fact not be the case. Molecular characterization and the spatial distribution pattern of histopathologic lesions and immunohistochemistry (IHC) signals are used to identify and characterize atypical BSE. Both the L-type and H-type atypical cases display significant differences in the conformation and spatial accumulation of the disease associated prion protein (PrPSc) in brains of afflicted cattle. Transmission studies in bovine transgenic and wild type mouse models support that the atypical BSE types might be unique strains because they have different incubation times and lesion profiles when compared to C-type BSE. When L-type BSE was inoculated into ovine transgenic mice and Syrian hamster the resulting molecular fingerprint had changed, either in the first or a subsequent passage, from L-type into C-type BSE.
In addition, non-human primates are specifically susceptible for atypical BSE as demonstrated by an approximately 50% shortened incubation time for L-type BSE as compared to C-type. Considering the current scientific information available, it cannot be assumed that these different BSE types pose the same human health risks as C-type BSE or that these risks are mitigated by the same protective measures.
This study will contribute to a correct definition of specified risk material (SRM) in atypical BSE. The incumbent of this position will develop new and transfer existing, ultra-sensitive methods for the detection of atypical BSE in tissue of experimentally infected cattle.
http://www.prionetcanada.ca/detail.aspx?menu=5&dt=293380&app=93&cat1=387&tp=20&lk=no&cat2
Wednesday, June 15, 2011
Galveston, Texas - Isle port moves through thousands of heifers headed to Russia, none from Texas, Alabama, or Washington, due to BSE risk factor
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/galveston-texas-isle-port-moves-through.html
What is the potential cost of pre- and post-slaughter testing? The estimated cost of post-mortem testing is $40 per head. This amount is comprised almost entirely of the cost of the test kit and sample analysis. It is expected that ante-mortem tests (live animal), if a test is developed, will reduce BSE testing costs to approximately $15 per head.
http://www.prionetcanada.ca/detail.aspx?menu=12&dt=293720&app=70&cat1=211&tp=12&lk=no
O.I.E. AND THE USDA, have knowingly exposed the globe with atypical TSE prion, knowing that there was a risk factor to humans and animals. they did just what the U.K. did whey they infected the globe with BSE aka mad cow disease. $$$
England worried briefly about infecting other countries
27 Aug 00
confidential correspondence obtained by Terry S. Singeltary Sr.
BSE11/2 020;
SC1337p
DEPARTMENT OF HEALTH AND SOCIAL SECURITY Richmond House, 79 Whitehall, London SWIA 2NS Telephone 01-210 3000 From the Chief Medical Officer Sir Donald Achson KBE DM DSc FRCP FFCM FFOM
Mr K C Meldrum Chief Veterinary Officer Ministry of Agriculture, Fisheries and Food Government Buildings Hook Rise South Tolworth Surbiton Surrey KT6 7NG 3 January 1990
Dear Mr Meldrum
BOVINE SPONGIFORM ENCEPHALOPATHY
You will recall that we have previously discussed the potential risks of BSE occurring in other countries as a result of the continuing export from the UK of meat and bone that may be contaminated by scrapie or possibly BSE.
I remain concerned that we are not being consistent in our attempts to contain the risks of BSE. Having banned the feeding of meat and bone meal to ruminamts in 1988, we should take steps to prevent these UK products being fed to ruminants in other countries. This could be achieved either through a ban on the export of meat and bone meal, or at least by the proper labelling of these products to make it absolutely clear they should not be fed to ruminants [or zoo animals, including rare and endangered primates -- webmaster]. Unless some such action is taken the difficult problems we have faced with BSE may well occur in other countries who import UK meat and bone meal. Surely it is short sighted for us to risk being seen in future as having been responsible for the introduction of BSE to the food chain in other countries.
http://www.mad-cow.org/00/aug00_last_news.html#fff
Subject: MBM/U.K. imports of MBM to the U.S./BSE Inquiry http://www.bse.org.uk/dfa/dfa25.htm
Date:Mon, 10 Apr 2000 15:14:21 -0700
From: "Terry S. Singeltary Sr." To: flounder@wt.net
69. On 14 February 1990, Mr Meldrum wrote a letter to the Chief Veterinary Officers of a number of countries. [76] On 15 February 1990, Mrs Attridge and other officials were sent a copy of the letter of 14 February 1990 and a list of the countries to which it had been sent. They were stated to be the countries which had imported ruminant based meat and bone meal from the United Kingdom. The countries listed were Norway; Sweden, Switzerland, Czechoslovakia, Hungary, Nigeria, Thailand, South Africa, Malaysia, Taiwan, Hong Kong, South Korea, Japan, Canada, USA, Turkey, Kenya, Malta, Libera, Lebanon, Saudi Arabia, Sri Lanka, Puerto Rico, Curacao, Finland.[77] The letter from Mr Meldrum included the following: Although we have kept the Office Internationale des Epizooties (OIE) fully informed about this new disease, and they will shortly be disseminating information and recommendations to member countries, I am writing to you on a personal basis to ensure that you are aware of all the developments in relation to BSE, including its likely cause. The majority of our findings have now been published in the Veterinary Record.?[78]
70. On 20 February 1990, Dr Pickles wrote to Ms Verity (APS/CMO). Dr Pickles? minute included the following:
1. Mr Meldrum is arguing that MAFF have already taken all the necessary and responsible steps to warn importing countries of the BSE dangers in UK meat and bone meal. Yet the action taken so far overseas suggest the message has not got through, or where it has this has been late. The first nation that woke up to the danger did so a year after our own feed ban. It seems even now several EC countries neither ban our imports or the general feeding of ruminant protein. It also seems the OIE and CVO have yet to inform the rest of the world.
2. I do not see how this can be claimed to be responsible?. We do not need an expert group of the Scientific Veterinary Committee to tell us British meat and bone meal is unsafe for ruminants. I fail to understand why this cannot be tackled from the British end which seems to be the only sure way of doing it, preferably by banning exports. As CMO says in his letter of 3 January surely it is short sighted for us to risk being seen in future as having been responsible for the introduction of BSE to the food chain in other countries.??[79]
http://www.mad-cow.org/00/jul00_dont_eat_sheep.html#hhh
http://www.mad-cow.org/00/may00_news.html#aaa
WHAT ABOUT those old studies at Mission, Texas, where USA scrapie was transmitted to USA cattle, but the results was not c-BSE. IT was a different TSE.
WHAT ABOUT atypical Nor-98 Scrapie in the USA, and TSE there from to other species ???
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 ;
http://www.promedmail.org/pls/apex/f?p=2400:1001:568933508083034::NO::F2400_P1001_BACK_PAGE,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
http://web.archive.org/web/20040823105233/www.bseinquiry.gov.uk/files/yb/1988/10/00001001.pdf
Monday, June 20, 2011 2011
Annual Conference of the National Institute for Animal Agriculture ATYPICAL NOR-98 LIKE SCRAPIE UPDATE USA
http://nor-98.blogspot.com/2011/06/2011-annual-conference-of-national.html
Suspect symptoms
What if you can catch old-fashioned CJD by eating meat from a sheep infected with scrapie?
28 Mar 01
Like lambs to the slaughter 31 March 2001 by Debora MacKenzie Magazine issue 2284. Subscribe and get 4 free issues. 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 mice as sCJD.
"This means we cannot rule out that at least some sCJD may be caused by some strains of scrapie," says team member Jean-Philippe Deslys of the French Atomic Energy Commission's medical research laboratory in Fontenay-aux-Roses, south-west of Paris. Hans Kretschmar of the University of Göttingen, who coordinates CJD surveillance in Germany, is so concerned by the findings that he now wants to trawl back through past sCJD cases to see if any might have been caused by eating infected mutton or lamb.
Scrapie has been around for centuries and until now there has been no evidence that it poses a risk to human health. But if the French finding means that scrapie can cause sCJD in people, countries around the world may have overlooked a CJD crisis to rival that caused by BSE.
Deslys and colleagues were originally studying vCJD, not sCJD. They injected the brains of macaque monkeys with brain from BSE cattle, and from French and British vCJD patients. The brain damage and clinical symptoms in the monkeys were the same for all three. Mice injected with the original sets of brain tissue or with infected monkey brain also developed the same symptoms.
As a control experiment, the team also injected mice with brain tissue from people and animals with other prion diseases: a French case of sCJD; a French patient who caught sCJD from human-derived growth hormone; sheep with a French strain of scrapie; and mice carrying a prion derived from an American scrapie strain. As expected, they all affected the brain in a different way from BSE and vCJD. But while the American strain of scrapie caused different damage from sCJD, the French strain produced exactly the same pathology.
"The main evidence that scrapie does not affect humans has been epidemiology," says Moira Bruce of the neuropathogenesis unit of the Institute for Animal Health in Edinburgh, who was a member of the same team as Deslys. "You see about the same incidence of the disease everywhere, whether or not there are many sheep, and in countries such as New Zealand with no scrapie." In the only previous comparisons of sCJD and scrapie in mice, Bruce found they were dissimilar.
But there are more than 20 strains of scrapie, and six of sCJD. "You would not necessarily see a relationship between the two with epidemiology if only some strains affect only some people," says Deslys. Bruce is cautious about the mouse results, but agrees they require further investigation. Other trials of scrapie and sCJD in mice, she says, are in progress.
People can have three different genetic variations of the human prion protein, and each type of protein can fold up two different ways. Kretschmar has found that these six combinations correspond to six clinical types of sCJD: each type of normal prion produces a particular pathology when it spontaneously deforms to produce sCJD.
But if these proteins deform because of infection with a disease-causing prion, the relationship between pathology and prion type should be different, as it is in vCJD. "If we look at brain samples from sporadic CJD cases and find some that do not fit the pattern," says Kretschmar, "that could mean they were caused by infection."
There are 250 deaths per year from sCJD in the US, and a similar incidence elsewhere. Singeltary and other US activists think that some of these people died after eating contaminated meat or "nutritional" pills containing dried animal brain. Governments will have a hard time facing activists like Singeltary if it turns out that some sCJD isn't as spontaneous as doctors have insisted.
Deslys's work on macaques also provides further proof that the human disease vCJD is caused by BSE. And the experiments showed that vCJD is much more virulent to primates than BSE, even when injected into the bloodstream rather than the brain. This, says Deslys, means that there is an even bigger risk than we thought that vCJD can be passed from one patient to another through contaminated blood transfusions and surgical instruments.
http://www.newscientist.com/article/mg16922840.300-like-lambs-to-the-slaughter.html
Monday, December 14, 2009
Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types
(hmmm, this is getting interesting now...TSS)
Sporadic CJD type 1 and atypical/ Nor98 scrapie are characterized by fine (reticular) deposits,
see also ;
All of the Heidenhain variants were of the methionine/ methionine type 1 molecular subtype.
http://cjdusa.blogspot.com/2009/09/co-existence-of-scrapie-prion-protein.html
see full text ;
Monday, December 14, 2009
Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types
http://nor-98.blogspot.com/2009/12/similarities-between-forms-of-sheep.html
Thursday, June 2, 2011
USDA scrapie report for April 2011 NEW ATYPICAL NOR-98 SCRAPIE CASES Pennsylvania AND California
http://nor-98.blogspot.com/2011/06/usda-scrapie-report-for-april-2011-new.html
http://nor-98.blogspot.com/2011/06/2011-annual-conference-of-national.html
Please see the following warning from CDC about prion TSE consumption in North America ;
Thursday, May 26, 2011
Travel History, Hunting, and Venison Consumption Related to Prion Disease Exposure, 2006-2007 FoodNet Population Survey
Journal of the American Dietetic Association Volume 111, Issue 6 , Pages 858-863, June 2011.
http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/travel-history-hunting-and-venison.html
Thursday, August 12, 2010
Seven main threats for the future linked to prions
First threat
The TSE road map defining the evolution of European policy for protection against prion diseases is based on a certain numbers of hypotheses some of which may turn out to be erroneous. In particular, a form of BSE (called atypical Bovine Spongiform Encephalopathy), recently identified by systematic testing in aged cattle without clinical signs, may be the origin of classical BSE and thus potentially constitute a reservoir, which may be impossible to eradicate if a sporadic origin is confirmed.
***Also, a link is suspected between atypical BSE and some apparently sporadic cases of Creutzfeldt-Jakob disease in humans. These atypical BSE cases constitute an unforeseen first threat that could sharply modify the European approach to prion diseases.
Second threat
snip...
http://www.neuroprion.org/en/np-neuroprion.html
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
2.66 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
http://www.aph.gov.au/senate/committee/rrat_ctte/mad_cows/report/report.pdf
Tuesday, June 14, 2011
Clinical research in CJD at a U.S. clinical prion research center: CJD Quinacrine Study results and improved diagnosis of prion disease
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/clinical-research-in-cjd-at-us-clinical.html
Sunday, August 10, 2008
A New Prionopathy OR more of the same old BSe and sporadic CJD
http://creutzfeldt-jakob-disease.blogspot.com/2008/08/new-prionopathy-or-more-of-same-old-bse.html
Sunday, July 11, 2010
CJD 2 CASES McLennan County Texas population 230,213 both cases in their 40s
http://creutzfeldt-jakob-disease.blogspot.com/2010/07/cjd-2-cases-mclennan-county-texas.html
CJD TEXAS 38 YEAR OLD FEMALE WORKED SLAUGHTERING CATTLE EXPOSED TO BRAIN AND SPINAL CORD MATTER
"Up until about 6 years ago, the pt worked at Tyson foods where she worked on the assembly line, slaughtering cattle and preparing them for packaging. She was exposed to brain and spinal cord matter when she would euthanize the cattle."
Irma Linda Andablo CJD Victim, she died at 38 years old on February 6, 2010 in Mesquite Texas
Irma Linda Andablo CJD Victim, she died at 38 years old on February 6, 2010 in Mesquite Texas.She left 6 Kids and a Husband.The Purpose of this web is to give information in Spanish to the Hispanic community, and to all the community who want's information about this terrible disease.-
Physician Discharge Summary, Parkland Hospital, Dallas Texas
Admit Date: 12/29/2009 Discharge Date: 1/20/2010 Attending Provider: Greenberg, Benjamin Morris; General Neurology Team: General Neurology Team
Linda was a Hispanic female with no past medical history presents with 14 months of incresing/progressive altered mental status, generalized weakness, inability to walk, loss of appetite, inability to speak, tremor and bowel/blader incontinence.She was, in her usual state of health up until February, 2009, when her husbans notes that she began forgetting things like names and short term memories. He also noticed mild/vague personality changes such as increased aggression. In March, she was involved in a hit and run MVA,although she was not injured. The police tracked her down and ticketed her. At that time, her son deployed to Iraq with the Army and her husband assumed her mentation changes were due to stress over these two events. Also in March, she began to have weakness in her legs, making it difficult to walk. Over the next few months, her mentation and personality changes worsened, getting to a point where she could no longer recognized her children. She was eating less and less. She was losing more weight. In the last 2-3 months, she reached the point where she could not walk without an assist, then 1 month ago, she stopped talking, only making grunting/aggressive sounds when anyone came near her. She also became both bowel and bladder incontinent, having to wear diapers. Her '"tremor'" and body jerks worsened and her hands assumed a sort of permanent grip position, leading her family to put tennis balls in her hands to protect her fingers.
The husband says that they have lived in Nebraska for the past 21 years. They had seen a doctor there during the summer time who prescribed her Seroquel and Lexapro, Thinking these were sx of a mood disorder. However, the medications did not help and she continued to deteriorate clinically. Up until about 6 years ago, the pt worked at Tyson foods where she worked on the assembly line, slaughtering cattle and preparing them for packaging. She was exposed to brain and spinal cord matter when she would euthanize the cattle. The husband says that he does not know any fellow workers with a similar illness. He also says that she did not have any preceeding illness or travel.
http://www.recordandoalinda.com/index.php?option=com_content&view=article&id=19:cjd-english-info&catid=9:cjd-ingles&Itemid=8
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
http://whqlibdoc.who.int/publications/2003/9241545887.pdf
http://www.promedmail.org/pls/apex/f?p=2400:1001:568933508083034::NO::F2400_P1001_BACK_PAGE,F2400_P1001_PUB_MAIL_ID:1000,82101
Wednesday, May 18, 2011
Variably Protease-Sensitive Prionopathy: a Novel Disease of the Prion Protein 17 May 2011
Journal of Molecular Neuroscience DOI: 10.1007/s12031-011-9543-1
http://transmissiblespongiformencephalopathy.blogspot.com/2011/05/variably-protease-sensitive-prionopathy.html
Saturday, March 5, 2011
MAD COW ATYPICAL CJD PRION TSE CASES WITH CLASSIFICATIONS PENDING ON THE RISE IN NORTH AMERICA
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/mad-cow-atypical-cjd-prion-tse-cases.html
Tuesday, April 26, 2011
sporadic CJD RISING Text and figures of the latest annual report of the NCJDRSU covering the period 1990-2009 (published 11th March 2011)
http://creutzfeldt-jakob-disease.blogspot.com/2011/04/sporadic-cjd-rising-text-and-figures-of.html
DID EVERYONE FILL OUT THEIR CJD QUESIONNAIRE FROM THE CDC AND OR THE CJD FOUNDATION ???
Friday, November 30, 2007
CJD QUESTIONNAIRE USA CWRU AND CJD FOUNDATION
http://cjdquestionnaire.blogspot.com/2007/11/cjd-questionnaire.html
http://cjdquestionnaire.blogspot.com/
Transmissible Spongiform encephalopathy (TSE) animal and human TSE in North America
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
Background:
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.
Methods:
12 years independent research of available data
Results:
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.
Conclusion:
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 ;
http://ww2.isid.org/Downloads/14th_ICID_ISE_Abstracts.pdf
International Society for Infectious Diseases Web: http://www.isid.org/
please see full text ;
http://transmissiblespongiformencephalopathy.blogspot.com/
TSS
Thursday, June 23, 2011
Saturday, June 18, 2011
Self-propagation and transmission of misfolded mutant SOD1 Prion or Prion-like phenomenon?
Self-propagation and transmission of misfolded mutant SOD1 Prion or Prion-like phenomenon?
Christian Münch and Anne Bertolotti* MRC Laboratory of Molecular Biology; Cambridge, England UK
*Correspondence to: Anne Bertolotti; Email: aberto@mrc-lmb.cam.ac.uk Submitted: 03/21/11; Accepted: 03/22/11 DOI: 10.4161/cc.10.11.15560 Comment on: Münch C, et al. Proc Natl Acad Sci USA 2011; 108:3548–53.
The hallmark of both sporadic and familial forms of amyotrophic lateral sclerosis (ALS), a common and inevitably fatal motor neuron disease, is the presence of proteinaceous deposits in motor neurons. Mutations in the gene encoding the abundantly expressed cytosolic superoxide dismutase- 1 (SOD1) cause aggregation of the protein in some familial forms of the disease.1 While it is clear that misfolding of mutant SOD1 is central to the disease and somehow leads to the degeneration of motor neurons, what elicits aggregation of mutant SOD1 in ALS is unknown. ALS has an adult onset and is rapidly progressive. Likewise, both the deposition of SOD1 aggregates and the appearance of symptoms are progressive in mouse models of ALS.2 Curiously, just like in motor neurons prior to the onset of the disease, SOD1 mutants do not spontaneously form the disease-characteristic deposits in cell culture.2
In a study recently published in PNAS,3 we report that exogenous aggregates prepared from highly purified recombinant SOD1 protein, penetrate inside cells with a surprising efficiency. Like some viruses, SOD1 aggregates use macropinocytosis to enter cells and then rapidly escape this compartment to reach the cytosol. Just like the disease deposits, the internalized SOD1 aggregates are ubiquitinated. Once they have penetrated inside the cytosol, mutant SOD1 aggregates convert the otherwise soluble, intracellular protein to their aberrant conformation.
This is a point of no return. The newly synthetized mutant SOD1 proteins are inevitably corrupted by the internalized aggregates. Furthermore, aggregates are continuously released by cells and taken up by neighbouring cells, hence endlessly continuing this vicious cycle: penetration of aggregates into cells, seeding aggregation of the cellular, normally soluble, homologous protein and transmission of the misfolding pathology to neighbouring cells. Once induced by very small amounts of exogenous seeds, mutant SOD1 aggregation is a self-propagating* phenotype that stably persists in dividing cells, long after the disappearance of the seeds. Thus, mutant SOD1 is the second mammalian protein to fully recapitulate, in cells, the cycle of events characteristic of prions.
Prion disorders such as, Bovine Spongiform Encephalopathy (BSE), scrapie in sheep and Creutzfeld-Jakob disease in human are infectious diseases caused by the aggregated form of the prion protein, PrPSc, which endlessly self-propagate by imposing its altered conformation to the cellular protein PrPC.4 Like the prion, mutant SOD1 aggregates can infect cells: penetrate inside cells, seed aggregation of the homologous protein and replicate.3 Similar to the scrapie agent, mutant SOD1 aggregates display hydrophobic surfaces,5,6 a feature that may underlie their ability to cross cellular membranes. However, unlike prions, there is no evidence that SOD1 aggregates could be transmitted between individuals. The prion realm is not restricted to metazoans and is not necessarily associated with fears of epidemics. A few unrelated yeast prion proteins can adopt self-propagating conformations, responsible for a non-mendelian, cytoplasmic, “proteinonly” mode of inheritance.7 Mutant SOD1 displays the defining properties of a prion, according to the definition proposed by Reed Wickner: “any protein that indefinitely propagates an altered form of itself and is transmissible”.8
Can there be more human prions? Recent studies have revealed that the misfolding pathology characteristic of Alzheimer, Parkinson and Huntington disease can be transmitted experimentally in animal or cellular models (reviewed in ref. 9). These observations are reminiscent of the seeding property of prions and have led to the proposal that misfolding diseases could all be prion-like disorders. However, it remains to be established whether the misfolded proteins associated with Alzheimer, Parkinson and Huntington disease have the ability to self-propagate a change in their conformation in the absence of exogenous seeds, like prions. Further investigations will help defining a clearer distinction between prion and prion-like phenomena.
Note *Self-propagation indicates that the protein indefinitely replicates its altered conformation.
http://www.landesbioscience.com/journals/cc/MunchCC10-11.pdf
Einstein once said, 'The definition of insanity is doing the same thing over and over again and expecting different results.' re-transmission studies on TSE's...TSS
CJD1/9 0185
Ref: 1M51A
IN STRICT CONFIDENCE
Dr McGovern From: Dr A Wight
Date: 5 January 1993
Copies: Dr Metters
Dr Skinner
Dr Pickles
Dr Morris
Mr Murray
TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
1. CMO will wish to be aware that a meeting was held at DH yesterday, 4 January, to discuss the above findings. It was chaired by Professor Murray (Chairman of the MRC Co-ordinating Committee on Research in the Spongiform Encephalopathies in Man), and attended by relevant experts in the fields of Neurology, Neuropathology, molecular biology, amyloid biochemistry, and the spongiform encephalopathies, and by representatives of the MRC and AFRC.
2. Briefly, the meeting agreed that:
i) Dr Ridley et als findings of experimental induction of p amyloid in primates were valid, interesting and a significant advance in the understanding of neurodegenerative disorders;
ii) there were no immediate implications for the public health, and no further safeguards were thought to be necessary at present; and
iii) additional research was desirable, both epidemiological and at the molecular level. Possible avenues are being followed up by DH and the MRC, but the details will require further discussion.
93/01.05/4.1tss
http://collections.europarchive.org/tna/20080102191246/http://www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf
BSE101/1 0136
IN CONFIDENCE
5 NOV 1992
CMO From: Dr J S Metters DCMO 4 November 1992
TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
1. Thank you for showing me Diana Dunstan's letter. I am glad that MRC have recognized the public sensitivity of these findings and intend to report them in their proper context. This hopefully will avoid misunderstanding and possible distortion by the media to portray the results as having more greater significance than the findings so far justify.
2. Using a highly unusual route of transmission (intra-cerebral injection) the researchers have demonstrated the transmission of a pathological process from two cases one of severe Alzheimer's disease the other of Gerstmann-Straussler disease to marmosets. However they have not demonstrated the transmission of either clinical condition as the "animals were behaving normally when killed'. As the report emphasizes the unanswered question is whether the disease condition would have revealed itself if the marmosets had lived longer. They are planning further research to see if the conditions, as opposed to the partial pathological process, is transmissible.
What are the implications for public health?
3. . The route of transmission is very specific and in the natural state of things highly unusual. However it could be argued that the results reveal a potential risk, in that brain tissue from these two patients has been shown to transmit a pathological process. Should therefore brain tissue from such cases be regarded as potentially infective? Pathologists, morticians, neuro surgeons and those assisting at neuro surgical procedures and others coming into contact with "raw" human brain tissue could in theory be at risk. However, on a priori grounds given the highly specific route of transmission in these experiments that risk must be negligible if the usual precautions for handling brain tissue are observed.
92/11.4/1-1
BSE101/1 0137
4. The other dimension to consider is the public reaction. To some extent the GSS case demonstrates little more than the transmission of BSE to a pig by intra-cerebral injection. If other prion diseases can be transmitted in this way it is little surprise that some pathological findings observed in GSS were also transmissible to a marmoset. But the transmission of features of Alzheimer's pathology is a different matter, given the much greater frequency of this disease and raises the unanswered question whether some cases are the result of a transmissible prion. The only tenable public line will be that "more research is required" before that hypothesis could be evaluated. The possibility on a transmissible prion remains open. In the meantime MRC needs carefully to consider the range and sequence of studies needed to follow through from the preliminary observations in these two cases. Not a particularly comfortable message, but until we know more about the causation of Alzheimer's disease the total reassurance is not practical.
JS METTERS Room 509 Richmond House Pager No: 081-884 3344 Callsign: DOH 832
121/YdeStss
92/11.4/1.2
http://collections.europarchive.org/tna/20080102232842/http://www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf
iatrogenic ???
Wednesday, April 27, 2011
GENERATION ALZHEIMER'S: THE DEFINING DISEASE OF THE BABY BOOMERS
http://betaamyloidcjd.blogspot.com/2011/04/generation-alzheimers-defining-disease.html
what are they going to do with all us baby boomers by 2050 where an estimated 13.5 million Americans will be stricken with Alzheimer's, up from 5 million plus ? what about the non paid caregivers of these Alzheimer's figures, where by 2050, these figures for caregivers will rise as well, to some 20 million, if we are all still here ? sadly, to add to all this misery, the price of poker is going up too. i apologize for my mood, but i am mad about all these cuts. they have cut funding for prion disease to ZERO DOLLARS!
All Other Emerging and Zoonotic Infectious Diseases CDC's FY 2012 request of $52,658,000 for all other emerging and zoonotic infectious disease activities is a decrease of $13,607,000 below the FY 2010 level, which includes the elimination of Prion activities ($5,473,000), a reduction for other cross-cutting infectious disease activities, and administrative savings. These funds support a range of critical emerging and zoonotic infectious disease programs such Lyme Disease, Chronic Fatigue Syndrome, and Special Pathogens, as well as other activities described below.
http://www.cdc.gov/fmo/topic/Budget%20Information/appropriations_budget_form_pdf/FY2012_CDC_CJ_Final.pdf
what is Alzheimer's anyway ?
strictly NOT private and confidential $$$
Saturday, January 22, 2011
Alzheimer's, Prion, and Neurological disease, and the misdiagnosis there of, a review 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/alzheimers-prion-and-neurological.html
Friday, September 3, 2010
Alzheimer's, Autism, Amyotrophic Lateral Sclerosis, Parkinson's, Prionoids, Prionpathy, Prionopathy, TSE
http://betaamyloidcjd.blogspot.com/2010/09/alzheimers-autism-amyotrophic-lateral.html
Thursday, December 23, 2010
Alimentary prion infections: Touch-down in the intestine, Alzheimer, Parkinson disease and TSE mad cow diseases $ The Center for Consumer Freedom
http://betaamyloidcjd.blogspot.com/2010/12/alimentary-prion-infections-touch-down.html
Saturday, March 22, 2008
10 Million Baby Boomers to have Alzheimer's in the coming decades
snip...
Alzheimer’s disease is the seventh leading cause of all deaths in the United States and the fifth leading cause of death in Americans older than the age of 65 years. More than 5 million Americans are estimated to have Alzheimer’s disease. Every 71 seconds someone in America develops Alzheimer’s disease; by 2050 it is expected to occur every 33 seconds. During the coming decades, baby boomers are projected to add 10 million people to these numbers. By 2050, the incidence of Alzheimer’s disease is expected to approach nearly a million people per year, with a total estimated prevalence of 11 to 16 million persons. Significant cost implications related to Alzheimer’s disease and other dementias include an estimated $148 billion annually in direct (Medicare/Medicaid) and indirect (eg, caregiver lost wages and out-of-pocket expenses, decreased business productivity) costs. Not included in these figures are the estimated 10 million caregivers who annually provide $89 billion in unpaid services to individuals with Alzheimer’s disease.
snip...
http://www.alzheimersanddementia.org/webfiles/images/journals/jalz/JALZ_739.pdf
see full text and more ;
http://betaamyloidcjd.blogspot.com/2008/03/10-million-baby-boomers-to-have.html
http://betaamyloidcjd.blogspot.com/
Wednesday, January 5, 2011
ENLARGING SPECTRUM OF PRION-LIKE DISEASES Prusiner Colby et al 2011
Prions
David W. Colby1,* and Stanley B. Prusiner1,2
----- Original Message -----
From: David Colby
To: flounder9@verizon.net
Cc: stanley@XXXXXXXX
Sent: Tuesday, March 01, 2011 8:25 AM
Subject: Re: FW: re-Prions David W. Colby1,* and Stanley B. Prusiner1,2 + Author Affiliations
Dear Terry Singeltary,
Thank you for your correspondence regarding the review article Stanley Prusiner and I recently wrote for Cold Spring Harbor Perspectives. Dr. Prusiner asked that I reply to your message due to his busy schedule. We agree that the transmission of CWD prions to beef livestock would be a troubling development and assessing that risk is important. In our article, we cite a peer-reviewed publication reporting confirmed cases of laboratory transmission based on stringent criteria. The less stringent criteria for transmission described in the abstract you refer to lead to the discrepancy between your numbers and ours and thus the interpretation of the transmission rate. We stand by our assessment of the literature--namely that the transmission rate of CWD to bovines appears relatively low, but we recognize that even a low transmission rate could have important implications for public health and we thank you for bringing attention to this matter.
Warm Regards, David Colby
--
David Colby, PhDAssistant ProfessorDepartment of Chemical EngineeringUniversity of Delaware
====================END...TSS==============
re-ENLARGING SPECTRUM OF PRION-LIKE DISEASES Prusiner Colby et al 2011 Prions
CWD to cattle figures CORRECTION
Greetings,
I believe the statement and quote below is incorrect ;
"CWD has been transmitted to cattle after intracerebral inoculation, although the infection rate was low (4 of 13 animals [Hamir et al. 2001]). This finding raised concerns that CWD prions might be transmitted to cattle grazing in contaminated pastures."
Please see ;
Within 26 months post inoculation, 12 inoculated animals had lost weight, revealed abnormal clinical signs, and were euthanatized. Laboratory tests revealed the presence of a unique pattern of the disease agent in tissues of these animals. These findings demonstrate that when CWD is directly inoculated into the brain of cattle, 86% of inoculated cattle develop clinical signs of the disease.
http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=194089
"although the infection rate was low (4 of 13 animals [Hamir et al. 2001])."
shouldn't this be corrected, 86% is NOT a low rate. ...
kindest regards,
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518
Thank you!
Thanks so much for your updates/comments. We intend to publish as rapidly as possible all updates/comments that contribute substantially to the topic under discussion.
http://cshperspectives.cshlp.org/letters/submit
re-Prions David W. Colby1,* and Stanley B. Prusiner1,2 + Author Affiliations
1Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, California 94143 2Department of Neurology, University of California, San Francisco, San Francisco, California 94143 Correspondence: stanley@ind.ucsf.edu
http://cshperspectives.cshlp.org/content/3/1/a006833.full.pdf+html
snip...full text ;
Wednesday, January 5, 2011
ENLARGING SPECTRUM OF PRION-LIKE DISEASES Prusiner Colby et al 2011 Prions
David W. Colby1,* and Stanley B. Prusiner1,2
http://cshperspectives.cshlp.org/content/3/1/a006833.full.pdf+html
http://betaamyloidcjd.blogspot.com/2011/01/enlarging-spectrum-of-prion-like.html
http://betaamyloidcjd.blogspot.com/
Saturday, March 19, 2011
Familial prion disease with alzheimer disease-like tau pathology and clinical phenotype
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/familial-prion-disease-with-alzheimer.html
Tuesday, June 14, 2011
Clinical research in CJD at a U.S. clinical prion research center: CJD Quinacrine Study results and improved diagnosis of prion disease
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/clinical-research-in-cjd-at-us-clinical.html
http://transmissiblespongiformencephalopathy.blogspot.com/
TSS
Christian Münch and Anne Bertolotti* MRC Laboratory of Molecular Biology; Cambridge, England UK
*Correspondence to: Anne Bertolotti; Email: aberto@mrc-lmb.cam.ac.uk Submitted: 03/21/11; Accepted: 03/22/11 DOI: 10.4161/cc.10.11.15560 Comment on: Münch C, et al. Proc Natl Acad Sci USA 2011; 108:3548–53.
The hallmark of both sporadic and familial forms of amyotrophic lateral sclerosis (ALS), a common and inevitably fatal motor neuron disease, is the presence of proteinaceous deposits in motor neurons. Mutations in the gene encoding the abundantly expressed cytosolic superoxide dismutase- 1 (SOD1) cause aggregation of the protein in some familial forms of the disease.1 While it is clear that misfolding of mutant SOD1 is central to the disease and somehow leads to the degeneration of motor neurons, what elicits aggregation of mutant SOD1 in ALS is unknown. ALS has an adult onset and is rapidly progressive. Likewise, both the deposition of SOD1 aggregates and the appearance of symptoms are progressive in mouse models of ALS.2 Curiously, just like in motor neurons prior to the onset of the disease, SOD1 mutants do not spontaneously form the disease-characteristic deposits in cell culture.2
In a study recently published in PNAS,3 we report that exogenous aggregates prepared from highly purified recombinant SOD1 protein, penetrate inside cells with a surprising efficiency. Like some viruses, SOD1 aggregates use macropinocytosis to enter cells and then rapidly escape this compartment to reach the cytosol. Just like the disease deposits, the internalized SOD1 aggregates are ubiquitinated. Once they have penetrated inside the cytosol, mutant SOD1 aggregates convert the otherwise soluble, intracellular protein to their aberrant conformation.
This is a point of no return. The newly synthetized mutant SOD1 proteins are inevitably corrupted by the internalized aggregates. Furthermore, aggregates are continuously released by cells and taken up by neighbouring cells, hence endlessly continuing this vicious cycle: penetration of aggregates into cells, seeding aggregation of the cellular, normally soluble, homologous protein and transmission of the misfolding pathology to neighbouring cells. Once induced by very small amounts of exogenous seeds, mutant SOD1 aggregation is a self-propagating* phenotype that stably persists in dividing cells, long after the disappearance of the seeds. Thus, mutant SOD1 is the second mammalian protein to fully recapitulate, in cells, the cycle of events characteristic of prions.
Prion disorders such as, Bovine Spongiform Encephalopathy (BSE), scrapie in sheep and Creutzfeld-Jakob disease in human are infectious diseases caused by the aggregated form of the prion protein, PrPSc, which endlessly self-propagate by imposing its altered conformation to the cellular protein PrPC.4 Like the prion, mutant SOD1 aggregates can infect cells: penetrate inside cells, seed aggregation of the homologous protein and replicate.3 Similar to the scrapie agent, mutant SOD1 aggregates display hydrophobic surfaces,5,6 a feature that may underlie their ability to cross cellular membranes. However, unlike prions, there is no evidence that SOD1 aggregates could be transmitted between individuals. The prion realm is not restricted to metazoans and is not necessarily associated with fears of epidemics. A few unrelated yeast prion proteins can adopt self-propagating conformations, responsible for a non-mendelian, cytoplasmic, “proteinonly” mode of inheritance.7 Mutant SOD1 displays the defining properties of a prion, according to the definition proposed by Reed Wickner: “any protein that indefinitely propagates an altered form of itself and is transmissible”.8
Can there be more human prions? Recent studies have revealed that the misfolding pathology characteristic of Alzheimer, Parkinson and Huntington disease can be transmitted experimentally in animal or cellular models (reviewed in ref. 9). These observations are reminiscent of the seeding property of prions and have led to the proposal that misfolding diseases could all be prion-like disorders. However, it remains to be established whether the misfolded proteins associated with Alzheimer, Parkinson and Huntington disease have the ability to self-propagate a change in their conformation in the absence of exogenous seeds, like prions. Further investigations will help defining a clearer distinction between prion and prion-like phenomena.
Note *Self-propagation indicates that the protein indefinitely replicates its altered conformation.
http://www.landesbioscience.com/journals/cc/MunchCC10-11.pdf
Einstein once said, 'The definition of insanity is doing the same thing over and over again and expecting different results.' re-transmission studies on TSE's...TSS
CJD1/9 0185
Ref: 1M51A
IN STRICT CONFIDENCE
Dr McGovern From: Dr A Wight
Date: 5 January 1993
Copies: Dr Metters
Dr Skinner
Dr Pickles
Dr Morris
Mr Murray
TRANSMISSION OF ALZHEIMER-TYPE PLAQUES TO PRIMATES
1. CMO will wish to be aware that a meeting was held at DH yesterday, 4 January, to discuss the above findings. It was chaired by Professor Murray (Chairman of the MRC Co-ordinating Committee on Research in the Spongiform Encephalopathies in Man), and attended by relevant experts in the fields of Neurology, Neuropathology, molecular biology, amyloid biochemistry, and the spongiform encephalopathies, and by representatives of the MRC and AFRC.
2. Briefly, the meeting agreed that:
i) Dr Ridley et als findings of experimental induction of p amyloid in primates were valid, interesting and a significant advance in the understanding of neurodegenerative disorders;
ii) there were no immediate implications for the public health, and no further safeguards were thought to be necessary at present; and
iii) additional research was desirable, both epidemiological and at the molecular level. Possible avenues are being followed up by DH and the MRC, but the details will require further discussion.
93/01.05/4.1tss
http://collections.europarchive.org/tna/20080102191246/http://www.bseinquiry.gov.uk/files/yb/1993/01/05004001.pdf
BSE101/1 0136
IN CONFIDENCE
5 NOV 1992
CMO From: Dr J S Metters DCMO 4 November 1992
TRANSMISSION OF ALZHEIMER TYPE PLAQUES TO PRIMATES
1. Thank you for showing me Diana Dunstan's letter. I am glad that MRC have recognized the public sensitivity of these findings and intend to report them in their proper context. This hopefully will avoid misunderstanding and possible distortion by the media to portray the results as having more greater significance than the findings so far justify.
2. Using a highly unusual route of transmission (intra-cerebral injection) the researchers have demonstrated the transmission of a pathological process from two cases one of severe Alzheimer's disease the other of Gerstmann-Straussler disease to marmosets. However they have not demonstrated the transmission of either clinical condition as the "animals were behaving normally when killed'. As the report emphasizes the unanswered question is whether the disease condition would have revealed itself if the marmosets had lived longer. They are planning further research to see if the conditions, as opposed to the partial pathological process, is transmissible.
What are the implications for public health?
3. . The route of transmission is very specific and in the natural state of things highly unusual. However it could be argued that the results reveal a potential risk, in that brain tissue from these two patients has been shown to transmit a pathological process. Should therefore brain tissue from such cases be regarded as potentially infective? Pathologists, morticians, neuro surgeons and those assisting at neuro surgical procedures and others coming into contact with "raw" human brain tissue could in theory be at risk. However, on a priori grounds given the highly specific route of transmission in these experiments that risk must be negligible if the usual precautions for handling brain tissue are observed.
92/11.4/1-1
BSE101/1 0137
4. The other dimension to consider is the public reaction. To some extent the GSS case demonstrates little more than the transmission of BSE to a pig by intra-cerebral injection. If other prion diseases can be transmitted in this way it is little surprise that some pathological findings observed in GSS were also transmissible to a marmoset. But the transmission of features of Alzheimer's pathology is a different matter, given the much greater frequency of this disease and raises the unanswered question whether some cases are the result of a transmissible prion. The only tenable public line will be that "more research is required" before that hypothesis could be evaluated. The possibility on a transmissible prion remains open. In the meantime MRC needs carefully to consider the range and sequence of studies needed to follow through from the preliminary observations in these two cases. Not a particularly comfortable message, but until we know more about the causation of Alzheimer's disease the total reassurance is not practical.
JS METTERS Room 509 Richmond House Pager No: 081-884 3344 Callsign: DOH 832
121/YdeStss
92/11.4/1.2
http://collections.europarchive.org/tna/20080102232842/http://www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf
iatrogenic ???
Wednesday, April 27, 2011
GENERATION ALZHEIMER'S: THE DEFINING DISEASE OF THE BABY BOOMERS
http://betaamyloidcjd.blogspot.com/2011/04/generation-alzheimers-defining-disease.html
what are they going to do with all us baby boomers by 2050 where an estimated 13.5 million Americans will be stricken with Alzheimer's, up from 5 million plus ? what about the non paid caregivers of these Alzheimer's figures, where by 2050, these figures for caregivers will rise as well, to some 20 million, if we are all still here ? sadly, to add to all this misery, the price of poker is going up too. i apologize for my mood, but i am mad about all these cuts. they have cut funding for prion disease to ZERO DOLLARS!
All Other Emerging and Zoonotic Infectious Diseases CDC's FY 2012 request of $52,658,000 for all other emerging and zoonotic infectious disease activities is a decrease of $13,607,000 below the FY 2010 level, which includes the elimination of Prion activities ($5,473,000), a reduction for other cross-cutting infectious disease activities, and administrative savings. These funds support a range of critical emerging and zoonotic infectious disease programs such Lyme Disease, Chronic Fatigue Syndrome, and Special Pathogens, as well as other activities described below.
http://www.cdc.gov/fmo/topic/Budget%20Information/appropriations_budget_form_pdf/FY2012_CDC_CJ_Final.pdf
what is Alzheimer's anyway ?
strictly NOT private and confidential $$$
Saturday, January 22, 2011
Alzheimer's, Prion, and Neurological disease, and the misdiagnosis there of, a review 2011
http://transmissiblespongiformencephalopathy.blogspot.com/2011/01/alzheimers-prion-and-neurological.html
Friday, September 3, 2010
Alzheimer's, Autism, Amyotrophic Lateral Sclerosis, Parkinson's, Prionoids, Prionpathy, Prionopathy, TSE
http://betaamyloidcjd.blogspot.com/2010/09/alzheimers-autism-amyotrophic-lateral.html
Thursday, December 23, 2010
Alimentary prion infections: Touch-down in the intestine, Alzheimer, Parkinson disease and TSE mad cow diseases $ The Center for Consumer Freedom
http://betaamyloidcjd.blogspot.com/2010/12/alimentary-prion-infections-touch-down.html
Saturday, March 22, 2008
10 Million Baby Boomers to have Alzheimer's in the coming decades
snip...
Alzheimer’s disease is the seventh leading cause of all deaths in the United States and the fifth leading cause of death in Americans older than the age of 65 years. More than 5 million Americans are estimated to have Alzheimer’s disease. Every 71 seconds someone in America develops Alzheimer’s disease; by 2050 it is expected to occur every 33 seconds. During the coming decades, baby boomers are projected to add 10 million people to these numbers. By 2050, the incidence of Alzheimer’s disease is expected to approach nearly a million people per year, with a total estimated prevalence of 11 to 16 million persons. Significant cost implications related to Alzheimer’s disease and other dementias include an estimated $148 billion annually in direct (Medicare/Medicaid) and indirect (eg, caregiver lost wages and out-of-pocket expenses, decreased business productivity) costs. Not included in these figures are the estimated 10 million caregivers who annually provide $89 billion in unpaid services to individuals with Alzheimer’s disease.
snip...
http://www.alzheimersanddementia.org/webfiles/images/journals/jalz/JALZ_739.pdf
see full text and more ;
http://betaamyloidcjd.blogspot.com/2008/03/10-million-baby-boomers-to-have.html
http://betaamyloidcjd.blogspot.com/
Wednesday, January 5, 2011
ENLARGING SPECTRUM OF PRION-LIKE DISEASES Prusiner Colby et al 2011
Prions
David W. Colby1,* and Stanley B. Prusiner1,2
----- Original Message -----
From: David Colby
To: flounder9@verizon.net
Cc: stanley@XXXXXXXX
Sent: Tuesday, March 01, 2011 8:25 AM
Subject: Re: FW: re-Prions David W. Colby1,* and Stanley B. Prusiner1,2 + Author Affiliations
Dear Terry Singeltary,
Thank you for your correspondence regarding the review article Stanley Prusiner and I recently wrote for Cold Spring Harbor Perspectives. Dr. Prusiner asked that I reply to your message due to his busy schedule. We agree that the transmission of CWD prions to beef livestock would be a troubling development and assessing that risk is important. In our article, we cite a peer-reviewed publication reporting confirmed cases of laboratory transmission based on stringent criteria. The less stringent criteria for transmission described in the abstract you refer to lead to the discrepancy between your numbers and ours and thus the interpretation of the transmission rate. We stand by our assessment of the literature--namely that the transmission rate of CWD to bovines appears relatively low, but we recognize that even a low transmission rate could have important implications for public health and we thank you for bringing attention to this matter.
Warm Regards, David Colby
--
David Colby, PhDAssistant ProfessorDepartment of Chemical EngineeringUniversity of Delaware
====================END...TSS==============
re-ENLARGING SPECTRUM OF PRION-LIKE DISEASES Prusiner Colby et al 2011 Prions
CWD to cattle figures CORRECTION
Greetings,
I believe the statement and quote below is incorrect ;
"CWD has been transmitted to cattle after intracerebral inoculation, although the infection rate was low (4 of 13 animals [Hamir et al. 2001]). This finding raised concerns that CWD prions might be transmitted to cattle grazing in contaminated pastures."
Please see ;
Within 26 months post inoculation, 12 inoculated animals had lost weight, revealed abnormal clinical signs, and were euthanatized. Laboratory tests revealed the presence of a unique pattern of the disease agent in tissues of these animals. These findings demonstrate that when CWD is directly inoculated into the brain of cattle, 86% of inoculated cattle develop clinical signs of the disease.
http://www.ars.usda.gov/research/publications/publications.htm?seq_no_115=194089
"although the infection rate was low (4 of 13 animals [Hamir et al. 2001])."
shouldn't this be corrected, 86% is NOT a low rate. ...
kindest regards,
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518
Thank you!
Thanks so much for your updates/comments. We intend to publish as rapidly as possible all updates/comments that contribute substantially to the topic under discussion.
http://cshperspectives.cshlp.org/letters/submit
re-Prions David W. Colby1,* and Stanley B. Prusiner1,2 + Author Affiliations
1Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, California 94143 2Department of Neurology, University of California, San Francisco, San Francisco, California 94143 Correspondence: stanley@ind.ucsf.edu
http://cshperspectives.cshlp.org/content/3/1/a006833.full.pdf+html
snip...full text ;
Wednesday, January 5, 2011
ENLARGING SPECTRUM OF PRION-LIKE DISEASES Prusiner Colby et al 2011 Prions
David W. Colby1,* and Stanley B. Prusiner1,2
http://cshperspectives.cshlp.org/content/3/1/a006833.full.pdf+html
http://betaamyloidcjd.blogspot.com/2011/01/enlarging-spectrum-of-prion-like.html
http://betaamyloidcjd.blogspot.com/
Saturday, March 19, 2011
Familial prion disease with alzheimer disease-like tau pathology and clinical phenotype
http://transmissiblespongiformencephalopathy.blogspot.com/2011/03/familial-prion-disease-with-alzheimer.html
Tuesday, June 14, 2011
Clinical research in CJD at a U.S. clinical prion research center: CJD Quinacrine Study results and improved diagnosis of prion disease
http://transmissiblespongiformencephalopathy.blogspot.com/2011/06/clinical-research-in-cjd-at-us-clinical.html
http://transmissiblespongiformencephalopathy.blogspot.com/
TSS
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