tim wrote,
One question R2, did your husband's death have ANYTHING to do with beef?? As near as I can tell it was due to IATROGENIC transmission of CLASSIC CJD. Is this not correct??? ...............
holy mad cow timmyboy, those folks that passed the TSE agent via surgical tools did not develop that TSE spontaneously, they got it from a source, that
being cattle, sheep, deer, elk, 2nd passage medical/dental/surgical, etc. WAKEUP TIMMYBOY! do you actually produce a commodity for the consumer?
your starting to scare me now.
FACT ;
The current risk of acquiring vCJD from eating beef (muscle meat) and beef products produced from cattle in countries with at least a possibly increased risk of BSE cannot be determined precisely..........
http://www2.ncid.cdc.gov/travel/yb/utils/ybGet.asp?section=dis&obj=madcow.htm
tim, I don't believe i ever stated that BSE HAD been documented yet in the muscle of the bovine, and if so, maybe old tim can produce this. i have stated time and time again it most likely will be detected once testing with the most up to date sensitve testing methods are used in a large test sample, with different loads, and i am very interested to see the SRM distribution in the new BASE strain that is very similar to the sporadic CJD, not the nvCJD. i have stated that it HAS been detected in many other species, and i will document them again just for TIM, and i will also state that is my opinion that it WILL be detected in the bovine muscle eventually, just a matter of time, and it was just detected outside the CNS for the first time, PrPSc has been detected in the peripheral nerves (sciatic nerve, tibial nerve, vagus nerve) of a cow in Japan (see study below). ...
Pathological prion protein in muscles of hamsters and mice infected with rodent-adapted BSE or vCJD
Achim Thomzig1,, Franco Cardone2,, Dominique Krüger1, Maurizio Pocchiari2, Paul Brown3 and Michael Beekes1
1 Robert Koch-Institut (P24 – Transmissible Spongiform Encephalopathies), Nordufer 20, 13353 Berlin, Germany
2 Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy
3 7815 Exeter Road, Bethesda, MD 20814, USA
Correspondence
Michael Beekes
[email protected]
Recently, pathological prion protein (PrPTSE) was detected in muscle from sheep infected with scrapie, the archetype of transmissible spongiform encephalopathies (TSEs). This finding has highlighted the question of whether mammalian muscle may potentially also provide a reservoir for TSE agents related to bovine spongiform encephalopathy (BSE) and variant Creutzfeldt–Jakob Disease (vCJD). Here, results are reported from studies in hamsters and mice that provide direct experimental evidence, for the first time, of BSE- and vCJD-associated PrPTSE deposition in muscles. Our findings emphasize the need for further assessment of possible public-health risks from TSE involvement of skeletal muscle.
SNIP...
A. Thomzig and others
Table 1. Detection of PrPTSE in muscles of rodents infected intracerebrally with BSE or vCJD agents
Data represent the number of animals with PrPTSE in muscles/number of animals examined. Control, specimen from uninfected animals.
ND, Not done.
Muscle sample Hamster-adapted BSE Mouse-adapted BSE Mouse-adapted vCJD
Western blotting Immunohistochemistry Western blotting Western blotting
Control BSE Control BSE Control BSE Control vCJD
M. biceps femoris (hindlimb) 0/3 5/5 ND ND 0/2 1/4 0/2 2/4
M. tibialis cranialis (hindlimb) 0/3 5/5 0/2 2/2 0/2 0/4 0/2 1/4
M. triceps brachii (forelimb) 0/3 5/5 ND ND 0/2 2/4 0/2 2/4
M. extensor carpi radialis (forelimb) 0/3 5/5 ND ND 0/2 0/4 0/2 2/4
M. trapezius (shoulder) 0/3 5/5 ND ND 0/2 1/4 0/2 1/4
M. masseter (head) 0/3 5/5 0/2 2/2 0/2 0/4 0/2 2/4
M. psoas major (back) 0/3 5/5 0/2 2/2 0/2 2/4 0/2 1/4
M. lingualis (tongue) 0/3 5/5 0/2 2/2 0/2 1/4 0/2 0/4
Heart 0/3 5/5* ND ND 0/2 0/4 0/2 0/4
*Only weak signals for PrPTSE.
Fig. 1. (a) Western blot detection of PrP27–30, the protease-resistant core of PrPTSE, extracted from muscles and sciatic
nerve of terminally ill hamsters infected intracerebrally with hamster-passaged BSE agent. Lanes 1 and 8, proteinase
K-digested brain homogenate from BSE-infected hamsters, containing 5610”7 g brain tissue; lanes 2–7 and 9, skeletal
muscles from hindlimb (2, 3), forelimb (4, 5), shoulder (6), head (7) and back (9); lane 10, tip of tongue; lane 11, heart; lane
12, sciatic nerve; lane 13, skeletal muscles from uninfected control hamster, spiked before extraction with 5610”6 g brain
homogenate from BSE-infected hamsters; lane 14, skeletal muscle from an uninfected control hamster. All examined hamster
muscle samples corresponded to 20–50 mg tissue. (b) Western blot detection of PrP27–30 extracted from muscles of
terminally ill mice infected intracerebrally with mouse-adapted BSE (lanes 1–3) and vCJD (lanes 4–6) agent. Lane 1, muscle
from hindlimb; lanes 2–3, different muscles from forelimb; lane 4, muscle from hindlimb; lanes 5–6, different muscles from
forelimb; lane 7, skeletal muscle from uninfected control mouse, spiked before extraction with 5610”5 g brain homogenate
from vCJD-infected mice; lanes 8–9, skeletal muscles from uninfected control mouse. All examined murine muscle samples
corresponded to 15–40 mg tissue. (c, d) Location of PrPTSE in lingual muscle fibres of BSE-infected hamsters visualized by
PrP immunohistochemistry. Brownish granular immunostaining demonstrates PrPTSE deposition predominantly in the region of
the fibre surface (c, arrowheads), but also scattered within myocytes (d, arrows). Insets show higher magnification of muscle
fibres marked by an asterisk. Bars, 20 mm.
These authors contributed equally to this work.
http://vir.sgmjournals.org/cgi/content/abstract/87/1/251
From: TSS () Subject: PrPSc distribution of a natural case of bovine spongiform encephalopathy
Date: August 8, 2005 at 12:28 pm PST
PrPSc distribution of a natural case of bovine spongiform encephalopathy
Yoshifumi Iwamaru, Yuka Okubo, Tamako Ikeda, Hiroko Hayashi, Mori- kazu Imamura,
Takashi Yokoyama and Morikazu Shinagawa
Prion Disease Research Center, National Institute of Animal Health, 3-1-5 Kannondai,
Tsukuba 305-0856 Japan
[email protected]
Abstract Bovine spongiform encephalopathy (BSE) is a disease of cattle that causes progressive neurodegeneration
of the central nervous system. Infectivity of BSE agent is accompanied with an abnormal isoform of prion protein (PrPSc).
The specified risk materials (SRM) are tissues potentially carrying BSE infectivity. The following tissues are designated as SRM in Japan:
the skull including the brain and eyes but excluding the glossa and the masse- ter muscle, the vertebral column excluding the vertebrae of
the tail, spinal cord, distal illeum. For a risk management step, the use of SRM in both animal feed or human food has been prohibited.
However, detailed PrPSc distribution remains obscure in BSE cattle and it has caused controversies about definitions of SRM. Therefore we
have examined PrPSc distribution in a BSE cattle by Western blotting to reassess definitions of SRM. The 11th BSE case in Japan was
detected in fallen stock surveillance. The carcass was stocked in the refrigerator. For the detection of PrPSc, 200 mg of tissue samples
were homogenized. Following collagenase treatment, samples were digested with proteinase K. After digestion, PrPSc was precipitated
by sodium phosphotungstate (PTA). The pellets were subjected to Western blotting using the standard procedure. Anti-prion protein
monoclonal antibody (mAb) T2 conjugated horseradish peroxidase was used for the detection of PrPSc. PrPSc was detected in brain,
spinal cord, dorsal root ganglia, trigeminal ganglia, sublingual ganglion, retina. In addition, PrPSc was also detected in the peripheral
nerves (sciatic nerve, tibial nerve, vagus nerve). Our results suggest that the currently accepted definitions of SRM in 9/13/2005
179
Page 10 of 17 BSE cattle may need to be reexamined. T. Kitamoto (Ed.)
PRIONS
Food and Drug Safety
===============
Prions in Skeletal Muscles of Deer with Chronic Wasting Disease
Rachel C. Angers,1* Shawn R. Browning,1*† Tanya S. Seward,2 Christina J.
Sigurdson,4‡ Michael W. Miller,5 Edward A. Hoover,4 Glenn C. Telling1,2,3§
1Department of Microbiology, Immunology and Molecular Genetics, 2Sanders
Brown Center on Aging, 3Department of Neurology, University of Kentucky,
Lexington, KY 40536, USA. 4Department of Microbiology, Immunology and
Pathology, Colorado State University, Fort Collins, CO 80523, USA. 5Colorado
Division of Wildlife, Wildlife Research Center, Fort Collins, CO 80526, USA.
*These authors contributed equally to this work.
†Present address: Department of Infectology, Scripps Research Institute,
5353 Parkside Drive, RF-2, Jupiter, Florida, 33458, USA.
‡Present address: Institute of Neuropathology, University of Zurich,
Schmelzbergstrasse 12, 8091 Zurich, Switzerland.
§To whom correspondence should be addressed: E-mail:
[email protected]
Prions are transmissible proteinaceous agents of mammals that cause fatal
neurodegenerative diseases of the central nervous system (CNS). The presence
of infectivity in skeletal muscle of experimentally infected mice raised the
possibility that dietary exposure to prions might occur through meat
consumption (1). Chronic wasting disease (CWD), an enigmatic and contagious
prion disease of North American cervids, is of particular concern. The
emergence of CWD in an increasingly wide geographic area and the
interspecies transmission of bovine spongiform encephalopathy (BSE) to
humans as variant Creutzfeldt Jakob disease (vCJD) have raised concerns
about zoonotic transmission of CWD.
To test whether skeletal muscle of diseased cervids contained prion
infectivity, Tg(CerPrP)1536 mice (2) expressing cervid prion protein
(CerPrP), were inoculated intracerebrally with extracts prepared from the
semitendinosus/semimembranosus muscle group of CWD-affected mule deer or
from CWD-negative deer. The availability of CNS materials also afforded
direct comparisons of prion infectivity in skeletal muscle and brain. All
skeletal muscle extracts from CWD-affected deer induced progressive
neurological dysfunction in Tg(CerPrP)1536 mice with mean incubation times
ranging between 360 and ~490 d, whereas the incubation times of prions from
the CNS ranged from ~230 to 280 d (Table 1). For each inoculation group, the
diagnosis of prion disease was confirmed by the presence of PrPSc in the
brains of multiple infected Tg(CerPrP)1536 mice (see supporting online
material for examples). In contrast, skeletal muscle and brain material from
CWD-negative deer failed to induce disease in Tg(CerPrP)1536 mice (Table 1)
and PrPSc was not detected in the brains of sacrificed asymptomatic mice as
late as 523 d after inoculation (supporting online material).
Our results show that skeletal muscle as well as CNS tissue of deer with CWD
contains infectious prions. Similar analyses of skeletal muscle BSE-affected
cattle did not reveal high levels of prion infectivity (3). It will be
important to assess the cellular location of PrPSc in muscle. Notably, while
PrPSc has been detected in muscles of scrapie-affected sheep (4), previous
studies failed to detect PrPSc by immunohistochemical analysis of skeletal
muscle from deer with natural or experimental CWD (5, 6). Since the time of
disease onset is inversely proportional to prion dose (7), the longer
incubation times of prions from skeletal muscle extracts compared to matched
brain samples indicated that prion titers were lower in muscle than in CNS
where infectivity titers are known to reach high levels. Although possible
effects of CWD strains or strain mixtures on these incubation times cannot
be excluded, the variable 360 to ~490 d incubation times suggested a range
of prion titers in skeletal muscles of CWD-affected deer. Muscle prion
titers at the high end of the range produced the fastest incubation times
that were ~30% longer than the incubation times of prions from the CNS of
the same animal. Since all mice in each inoculation group developed disease,
prion titers in muscle samples producing the longest incubation times were
higher than the end point of the bioassay, defined as the infectious dose at
which half the inoculated mice develop disease. Studies are in progress to
accurately assess prion titers.
While the risk of exposure to CWD infectivity following consumption of
prions in muscle is mitigated by relatively inefficient prion transmission
via the oral route (, these
results show that semitendinosus/semimembranosus muscle, which is likely to
be consumed by humans, is a significant source of prion infectivity. Humans
consuming or handling meat from CWD-infected deer are therefore at risk to
prion exposure.
References and Notes
snip...end
=================
(American Journal of Pathology. 2006;168:927-935.)
© 2006 American Society for Investigative Pathology
Detection and Localization of PrPSc in the Skeletal Muscle of Patients with Variant, Iatrogenic, and Sporadic Forms of Creutzfeldt-Jakob Disease
Alexander H. Peden, Diane L. Ritchie, Mark W. Head and James W. Ironside
From the National Creutzfeldt-Jakob Disease Surveillance Unit and Division of Pathology, School of Molecular and Clinical Medicine, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom
Variant Creutzfeldt-Jakob disease (vCJD) differs from other human prion diseases in that the pathogenic prion protein PrPSc can be detected to a greater extent at extraneuronal sites throughout the body, principally within lymphoid tissues. However, a recent study using a high-sensitivity Western blotting technique revealed low levels of PrPSc in skeletal muscle from a quarter of Swiss patients with sporadic CJD (sCJD). This posed the question of whether PrPSc in muscle could also be detected in vCJD, sCJD, and iatrogenic (iCJD) patients from other populations. Therefore, we have used the same high-sensitivity Western blotting technique, in combination with paraffin-embedded tissue blotting, to screen for PrPSc in muscle tissue specimens taken at autopsy from 49 CJD patients in the United Kingdom. These techniques identified muscle PrPSc in 8 of 17 vCJD, 7 of 26 sCJD, and 2 of 5 iCJD patients. Paraffin-embedded tissue blotting analysis showed PrPSc in skeletal muscle in localized anatomical structures that had the morphological and immunohistochemical characteristics of nerve fibers. The detection of PrPSc in muscle tissue from all forms of CJD indicates the possible presence of infectivity in these tissues, suggesting important implications for assessing the potential risk of iatrogenic spread via contaminated surgical instruments.
=================
IN ADDITION ;
14 goats inoculated with muscle from scrapie-infected goats one developed clinical disease.
(Pattison and Millison, 1962; Pattison, 1990). A low median lethal dose was also observed in
muscle of TME-infected mink (Marsh et al, 1969). Transgenic mice inoculated
with scrapie have been reported to produce prions in muscle previously (Bosque
et al, 1997).
================
whether you accept mouse studies or not, pathological prion protein in muscles of hamsters and mice infected
with rodent-adapted BSE or vCJD cannot be ignored.
I do hope science proves no TSE infectivity in the muscle of the bovine, but TSE science has moved forward at a cows pace,
but it is moving forward, time will tell. BUT from the latest data, where the data use to say TSE did not transmit to this species
or that species, new data from more sensitive testing has in fact proven TSE has been documented in the muscle of multiple species,
and as i said, time will tell if they document it in the bovine muscle. ITs high time that extensive research is done in this area
of science. 3 decades and still debating this is not acceptable, especially with the incubation period involved. ...TSS