.
http://pro-med.blogspot.com/2007/11/proahedr-prion-disease-update-2007-07.html
SEE STEADY INCREASE IN SPORADIC CJD IN THE USA FROM
1997 TO 2006. SPORADIC CJD CASES TRIPLED, with phenotype
of 'UNKNOWN' strain growing. ...
http://www.cjdsurveillance.com/resources-casereport.html
There is a growing number of human CJD cases, and they were presented last
week in San Francisco by Luigi Gambatti(?) from his CJD surveillance
collection.
He estimates that it may be up to 14 or 15 persons which display selectively
SPRPSC and practically no detected RPRPSC proteins.
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf
PLEASE SEE !
P02.35 Molecular Features of the Protease-resistant Prion Protein (PrPres)
in H- type BSE
Biacabe, A-G1; Jacobs, JG2; Gavier-Widén, D3; Vulin, J1; Langeveld, JPM2;
Baron, TGM1 1AFSSA, France; 2CIDC-Lelystad, Netherlands; 3SVA, Sweden
Western blot analyses of PrPres accumulating in the brain of BSE- infected
cattle have demonstrated 3 different molecular phenotypes regarding to the
apparent molecular masses and glycoform ratios of PrPres bands. We initially
described isolates (H-type BSE) essentially characterized by higher PrPres
molecular mass and decreased levels of the diglycosylated PrPres band, in
contrast to the classical type of BSE. This type is also distinct from
another BSE phenotype named L-type BSE, or also BASE (for Bovine Amyloid
Spongiform Encephalopathy), mainly characterized by a low representation of
the diglycosylated PrPres band as well as a lower PrPres molecular mass.
Retrospective molecular studies in France of all available BSE cases older
than 8 years old and of part of the other cases identified since the
beginning of the exhaustive surveillance of the disease in 20001 allowed to
identify 7 H- type BSE cases, among 594 BSE cases that could be classified
as classical, L- or H-type BSE. By Western blot analysis of H-type PrPres,
we described a remarkable specific feature with antibodies raised against
the C-terminal region of PrP that demonstrated the existence of a more
C-terminal cleaved form of PrPres (named PrPres#2 ), in addition to the
usual PrPres form (PrPres #1). In the unglycosylated form, PrPres #2
migrates at about 14 kDa, compared to 20 kDa for PrPres #1. The proportion
of the PrPres#2 in cattle seems to by higher compared to the PrPres#1.
Furthermore another PK–resistant fragment at about 7 kDa was detected by
some more N-terminal antibodies and presumed to be the result of cleavages
of both N- and C- terminal parts of PrP. These singular features were
maintained after transmission of the disease to C57Bl/6 mice. The
identification of these two additional PrPres fragments (PrPres #2 and 7kDa
band)
*** reminds features reported respectively in sporadic Creutzfeldt-Jakob
disease and in Gerstmann-Sträussler-Scheinker (GSS) syndrome in humans.
FC5.5.1 BASE Transmitted to Primates and MV2 sCJD Subtype Share PrP27-30 and
PrPSc C-terminal Truncated Fragments
Zanusso, G1; Commoy, E2; Fasoli, E3; Fiorini, M3; Lescoutra, N4; Ruchoux,
MM4; Casalone, C5; Caramelli, M5; Ferrari, S3; Lasmezas, C6; Deslys, J-P4;
Monaco, S3 1University of Verona, of Neurological and Visual Sciences,
Italy; 2CEA, IMETI/SEPIA, France; 3University of Verona, Neurological and
Visual Sciences, Italy; 4IMETI/SEPIA, France; 5IZSPLVA, Italy; 6The Scripps
Research Insitute, USA
The etiology of sporadic Creutzfeldt-Jakob disease (sCJD), the most frequent
human prion disease, remains still unknown. The marked disease phenotype
heterogeneity observed in sCJD is thought to be influenced by the type of
proteinase K- resistant prion protein, or PrPSc (type 1 or type 2 according
to the electrophoretic mobility of the unglycosylated backbone), and by the
host polymorphic Methionine/Valine (M/V) codon 129 of the PRNP. By using a
two-dimensional gel electrophoresis (2D-PAGE) and imunoblotting we
previously showed that in sCJD, in addition to the PrPSc type, distinct
PrPSc C-terminal truncated fragments (CTFs) correlated with different sCJD
subtypes. Based on the combination of CTFs and PrPSc type, we distinguished
three PrPSc patterns: (i) the first was observed in sCJD with PrPSc type 1
of all genotypes,;
(ii) the second was found in M/M-2 (cortical form); (iii) the third in
amyloidogenic M/V- 2 and V/V-2 subtypes (Zanusso et al., JBC 2004) .
Recently, we showed that sCJD subtype M/V-2 shared molecular and
pathological features with an atypical form of BSE, named BASE, thus
suggesting a potential link between the two conditions. This connection was
further confirmed after 2D-PAGE analysis, which showed an identical PrPSc
signature, including the biochemical pattern of CTFs. To pursue this issue,
we obtained brain homogenates from Cynomolgus macaques intracerebrally
inoculated with brain homogenates from BASE. Samples were separated by using
a twodimensional electrophoresis (2D-PAGE) followed by immunoblotting. We
here show that the PrPSc pattern obtained in infected primates is identical
to BASE and sCJD MV-2 subtype.
*** These data strongly support the link, or at least a common ancestry,
between a sCJD subtype and BASE.
This work was supported by Neuroprion (FOOD-CT-2004-506579)
************************************************** *****
USA MAD COW CASES IN ALABAMA AND TEXAS
***PLEASE NOTE***
USA BASE CASE, (ATYPICAL BSE), AND OR TSE (whatever they are calling it
today), please note that both the ALABAMA COW, AND THE TEXAS COW,both were
''H-TYPE'', personal communication Detwiler et al Wednesday, August 22, 2007
11:52 PM. ...TSS
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=19779
************************************************** *****
FC5.5.2 Transmission of Italian BSE and BASE Isolates in Cattle Results into
a Typical BSE Phenotype and a Muscle Wasting Disease
Zanusso, G1; Lombardi, G2; Casalone, C3; D’Angelo, A4; Gelmetti, D2;
Torcoli, G2; Barbieri, I2; Corona, C3; Fasoli, E1; Farinazzo, A1; Fiorini,
M1; Gelati, M1; Iulini, B3; Tagliavini, F5; Ferrari, S1; Monaco, S1;
Caramelli, M3; Capucci, L2 1University of Verona, Neurological and Visual
Sciences, Italy; 2IZSLER, Italy; 3IZSPLVA, Italy; 4University of Turin,
Animal Pathology, Italy; 5Isituto Carlo Besta, Italy
The clinical phenotype of bovine spongiform encephalopathy has been
extensively reported in early accounts of the disorder. Following the
introduction of statutory active surveillance, almost all BSE cases have
been diagnosed on a pathological/molecular basis, in a pre-symptomatic
clinical stage. In recent years, the active surveillance system has
uncovered atypical BSE cases, which are characterized by distinct conformers
of the PrPSc, named high-type (BSE-H) and low-type (BSE-L), whose
clinicopathological phenotypes remain unknown. We recently reported two
Italian atypical cases with a PrPSc type similar to BSE-L, pathologically
characterized by PrP amyloid plaques. Experimental transmission to TgBov
mice has recently disclosed that BASE is caused by a distinct prion strain
which is extremely virulent. A major limitation of transmission studies to
mice is the lack of reliable information on clinical phenotype of BASE in
its natural host. In the present study, we experimentally infected
Fresian/Holstein and Alpine/Brown cattle with Italian BSE and BASE isolates
by i.c. route. BASE infected cattle showed survival times significantly
shorter than BSE, a finding more readily evident in Fresian/Holstein, and in
keeping with previous observations in TgBov mice. Clinically, BSE-infected
cattle developed a disease phenotype highly comparable with that described
in field BSE cases and in experimentally challenged cattle. On the contrary,
BASE-inoculated cattle developed an amyotrophic disorder accompanied by
mental dullness. The molecular and neuropathological profiles, including PrP
deposition pattern, closely matched those observed in the original cases.
This study further confirms that BASE is caused by a distinct prion isolate
and discloses a novel disease phenotype in cattle, closely resembling the
phenotype previous reported in scrapie-inoculated cattle
*** and in some subtypes of inherited and sporadic Creutzfeldt-Jakob
disease.
Oral Abstracts 14
snip...
P04.27
Experimental BSE Infection of Non-human Primates: Efficacy of the Oral Route
Holznagel, E1; Yutzy, B1; Deslys, J-P2; Lasmézas, C2; Pocchiari, M3;
Ingrosso, L3; Bierke, P4; Schulz-Schaeffer, W5; Motzkus, D6; Hunsmann, G6;
Löwer, J1 1Paul-Ehrlich-Institut, Germany; 2Commissariat à l´Energie
Atomique, France; 3Instituto Superiore di Sanità, Italy; 4Swedish Institute
for Infectious Disease control, Sweden; 5Georg August University, Germany;
6German Primate Center, Germany
Background:
In 2001, a study was initiated in primates to assess the risk for humans to
contract BSE through contaminated food. For this purpose, BSE brain was
titrated in cynomolgus monkeys.
Aims:
The primary objective is the determination of the minimal infectious dose
(MID50) for oral exposure to BSE in a simian model, and, by in doing this,
to assess the risk for humans. Secondly, we aimed at examining the course of
the disease to identify possible biomarkers.
Methods:
Groups with six monkeys each were orally dosed with lowering amounts of BSE
brain: 16g, 5g, 0.5g, 0.05g, and 0.005g. In a second titration study,
animals were intracerebrally (i.c.) dosed (50, 5, 0.5, 0.05, and 0.005 mg).
Results:
In an ongoing study, a considerable number of high-dosed macaques already
developed simian vCJD upon oral or intracerebral exposure or are at the
onset of the clinical phase. However, there are differences in the clinical
course between orally and intracerebrally infected animals that may
influence the detection of biomarkers.
Conclusions:
Simian vCJD can be easily triggered in cynomolgus monkeys on the oral route
using less than 5 g BSE brain homogenate. The difference in the incubation
period between 5 g oral and 5 mg i.c. is only 1 year (5 years versus 4
years). However, there are rapid progressors among orally dosed monkeys that
develop simian v CJD as fast as intracerebrally inoculated animals.
The work referenced was performed in partial fulfilment of the study “BSE in
primates“ supported by the EU (QLK1-2002-01096).
http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf
Subject: Aspects of the Cerebellar Neuropathology in Nor98
Date: September 26, 2007 at 4:06 pm PST
P03.141
Aspects of the Cerebellar Neuropathology in Nor98
Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E1 1National
Veterinary Insitute, Sweden; 2National Veterinary Institute, Norway
Nor98 is a prion disease of old sheep and goats. This atypical form of
scrapie was first described in Norway in 1998. Several features of Nor98
were shown to be different from classical scrapie including the distribution
of disease associated prion protein (PrPd) accumulation in the brain. The
cerebellum is generally the most affected brain area in Nor98. The study
here presented aimed at adding information on the neuropathology in the
cerebellum of Nor98 naturally affected sheep of various genotypes in Sweden
and Norway. A panel of histochemical and immunohistochemical (IHC) stainings
such as IHC for PrPd, synaptophysin, glial fibrillary acidic protein,
amyloid, and cell markers for phagocytic cells were conducted. The type of
histological lesions and tissue reactions were evaluated. The types of PrPd
deposition were characterized. The cerebellar cortex was regularly affected,
even though there was a variation in the severity of the lesions from case
to case. Neuropil vacuolation was more marked in the molecular layer, but
affected also the granular cell layer. There was a loss of granule cells.
Punctate deposition of PrPd was characteristic. It was morphologically and
in distribution identical with that of synaptophysin, suggesting that PrPd
accumulates in the synaptic structures. PrPd was also observed in the
granule cell layer and in the white matter.
*** The pathology features of Nor98 in the cerebellum of the affected sheep
showed similarities with those of sporadic Creutzfeldt-Jakob disease in
humans.
http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf
full text ;
ATYPICAL NOR-98 SCRAPIE LOCATION UPDATE ON 5 DOCUMENTED CASES THIS YEAR ;
The flocks of origin are WY, CO, CA, IN, and MN.
personal communication USDA et al. ...TSS
http://nor-98.blogspot.com/
ANIMAL HEALTH REPORT 2006 (BSE h-BASE EVENT IN ALABAMA, Scrapie, and CWD)
http://animalhealthreport2006.blogspot.com/
CREUTZFELDT JAKOB DISEASE MAD COW BASE UPDATE USA
http://cjdmadcowbaseoct2007.blogspot.com/
CREUTZFELDT JAKOB DISEASE MAD COW BASE UPDATE USA
http://cjdmadcowbaseoct2007.blogspot.com/2008/02/evaluation-of-human-transmission-risk.html
Friday, February 8, 2008
Creutzfeldt Jakob Disease Delaware UPDATE
http://cjdmadcowbaseoct2007.blogspot.com/2008/02/creutzfeldt-jakob-disease-delaware.html
CJD TEXAS
http://cjdtexas.blogspot.com/
Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in
the United States
http://cjdusa.blogspot.com/
Creutzfeldt Jakob Disease
http://creutzfeldt-jakob-disease.blogspot.com/
Creutzfeldt-Jakob Disease, Prion Protein Gene Codon 129VV, and a Novel PrPSc
Type in a Young British Woman
http://creutzfeldt-jakob-disease.blogspot.com/2008/01/creutzfeldt-jakob-disease-prion-protein.html
Friday, January 11, 2008
CJD HUMAN TSE REPORT UK, USA, CANADA, and Mexico JANUARY 2008
http://cjdmadcowbaseoct2007.blogspot.com/2008/01/cjd-human-tse-report-uk-usa-canada-and.html
Sunday, December 16, 2007
Risk factors for sporadic Creutzfeldt-Jakob disease
Published Online: 11 Dec 2007
http://creutzfeldt-jakob-disease.blogspot.com/2007/12/risk-factors-for-sporadic-creutzfeldt.html
http://creutzfeldt-jakob-disease.blogspot.com/2008/01/risk-factors-for-sporadic-creutzfeldt.html
Monday, December 31, 2007
Risk Assessment of Transmission of Sporadic Creutzfeldt-Jakob Disease in
Endodontic Practice in Absence of Adequate Prion Inactivation
http://creutzfeldt-jakob-disease.blogspot.com/2007/12/risk-assessment-of-transmission-of.html
Friday, January 25, 2008
January 2008 Update on Feed Enforcement Activities to Limit the Spread of
BSE
http://madcowspontaneousnot.blogspot.com/2008/01/january-2008-update-on-feed-enforcement.html
http://madcowspontaneousnot.blogspot.com/
BSE BASE MAD COW TESTING TEXAS, USA, AND CANADA
http://madcowtesting.blogspot.com/
Sunday, February 17, 2008
Release No. 0046.08
Statement by Secretary of Agriculture Ed Schafer Regarding Hallmark/Westland
Meat Packing Company Two Year Product Recall
USDA Press Office (202) 720-4623
http://cjdmadcowbaseoct2007.blogspot.com/2008/02/release-no-004608-statement-by.html
NON-AMBULATORY (DOWNER) COW
http://downercattle.blogspot.com/
Wednesday, February 27, 2008
BEEF RECALL NATIONWIDE - SCHOOL LUNCH PROGRAM UPDATE
http://downercattle.blogspot.com/2008/02/beef-recall-nationwide-school-lunch.html
CJD QUESTIONNAIRE
http://cjdquestionnaire.blogspot.com/
Specified Risk Material SRM
http://madcowspontaneousnot.blogspot.com/2008/02/specified-risk-materials-srm.html
Subject: [Docket No. 03-025IFA] FSIS Prohibition of the Use of Specified
Risk Materials for Human Food and Requirements for the Disposition of
Non-Ambulatory Disabled Cattle
Greetings FSIS,
I would kindly like to submit the following to [Docket No. 03-025IFA] FSIS
Prohibition of the Use of Specified Risk Materials for Human Food and
Requirements for the Disposition of Non-Ambulatory Disabled Cattle
THE BSE/TSE SUB CLINICAL
Non-Ambulatory Disabled Cattle Broken bones and such may be the first signs
of a sub clinical BSE/TSE Non-Ambulatory Disabled Cattle ;
SUB CLINICAL PRION INFECTION MRC-43-00 Issued: Monday, 28 August 2000
NEW EVIDENCE OF SUB-CLINICAL PRION INFECTION: IMPORTANT RESEARCH FINDINGS
RELEVANT TO CJD AND BSE
A team of researchers led by Professor John Collinge at the Medical Research
Council Prion Unit1 report today in the Proceedings of the National Academy
of Sciences, on new evidence for the existence of a ?sub-clinical? form of
BSE in mice which was unknown until now. The scientists took a closer look
at what is known as the ?species barrier? - the main protective factor which
limits the ability of prions2 to jump from one species to infect another.
They found the mice had a ?sub-clinical? form of disease where they carried
high levels of infectivity but did not develop the clinical disease during
their normal lifespan. The idea that individuals can carry a disease and
show no clinical symptoms is not new. It is commonly seen in conventional
infectious diseases. Researchers tried to infect laboratory mice with
hamster prions3 called Sc237 and found that the mice showed no apparent
signs of disease. However, on closer inspection they found that the mice had
high levels of mouse prions in their brains. This was surprising because it
has always been assumed that hamster prions could not cause the disease in
mice, even when injected directly into the brain. In addition the
researchers showed that this new sub-clinical infection could be easily
passed on when injected into healthy mice and hamsters. The height of the
species barrier varies widely between different combinations of animals and
also varies with the type or strain of prions. While some barriers are quite
small (for instance BSE easily infects mice), other combinations of strain
and species show a seemingly impenetrable barrier. Traditionally, the
particular barrier studied here was assumed to be robust. Professor John
Collinge said: "These results have a number of important implications. They
suggest that we should re-think how we measure species barriers in the
laboratory, and that we should not assume that just because one species
appears resistant to a strain of prions they have been exposed to, that they
do not silently carry the infection.
This research raises the possibility, which has been mentioned before, that
apparently healthy cattle could harbour, but never show signs of, BSE. "This
is a timely and unexpected result, increasing what we know about prion
disease. These new findings have important implications for those
researching prion disease, those responsible for preventing infected
material getting into the food chain and for those considering how best to
safeguard health and reduce the risk that theoretically, prion disease could
be contracted through medical and surgical procedures."
ISSUED FRIDAY 25 AUGUST UNDER EMBARGO. PLEASE NOTE THAT THE EMBARGO IS SET
BY THE JOURNAL.
http://www.mrc.ac.uk/index/public_interest/public-press_office/public-press_releases_2000/public-mrc-43-00.htm
SNIP...
https://web01.aphis.usda.gov/regpublic.nsf/0/eff9eff1f7c5cf2b87256ecf000df08d?OpenDocument
PNAS | August 29, 2000 | vol. 97 | no. 18 | 10248-10253 Neurobiology
Species-barrier-independent prion replication in apparentlyresistant species
Andrew F. Hill*, Susan Joiner*, Jackie Linehan*, Melanie Desbruslais*, Peter
L. Lantos , and John Collinge*,
SEE FULL TEXT 17 pages ;
http://www.fsis.usda.gov/OPPDE/Comments/03-025IFA/03-025IFA-2.pdf
Terry S. Singeltary Sr.
P.O. Box 42
Bacliff, Texas USA 77518
