Characterization of variant Creutzfeldt-Jakob disease prions in prion protein-humanized mice carrying distinct codon 129 genotypes
Characterization of variant Creutzfeldt-Jakob disease prions in prion
protein-humanized mice carrying distinct codon 129 genotypes
Atsuko Takeuchi1, Atsushi Kobayashi1, James W. Ironside2, Shirou Mohri3 and
Tetsuyuki Kitamoto1* + Author Affiliations
1 Tohoku University Graduate School of Medicine, Japan;
2 University of Edinburgh Western General Hospital, United Kingdom;
3 National Institute of Animal Health, Japan ↵*
Corresponding author; email: kitamoto@med.tohoku.ac.jp
Capsule
Background: Secondary variant Creutzfeldt-Jakob disease (vCJD) infection
may occur in all human PRNP genotypes, but its clinicopathological and
biochemical phenotype is uncertain.
Results: The biochemical characteristics and transmission properties of the
newly generated vCJD prions are not affected by the host PRNP genotypes.
Conclusion: Secondary vCJD infection can be adequately diagnosed by
biochemical analysis and experimental transmission.
Significance: Effective means to identify secondary vCJD infection are
presented.
Abstract
To date, all clinical variant Creutzfeldt-Jakob disease (vCJD) patients are
homozygous for methionine at polymorphic codon 129 (129M/M) of the prion protein
(PrP) gene. However, the appearance of asymptomatic secondary vCJD infection in
individuals with a PRNP codon 129 genotype other than M/M, and transmission
studies using animal models have raised the concern that all humans might be
susceptible to vCJD prions, especially via secondary infection. To reevaluate
this possibility and to analyze in detail the transmission properties of vCJD
prions to transgenic animals carrying distinct codon 129 genotype, we performed
intracerebral inoculation of vCJD prions to humanized knock-in mice carrying all
possible codon 129 genotypes (129M/M, 129M/V, or 129V/V). All humanized knock-in
mouse lines were susceptible to vCJD infection, although the attack rate
gradually decreased from 129M/M to 129M/V and to 129V/V. The amount of PrP
deposition including florid/amyloid plaques in the brain also gradually
decreased from 129M/M to 129M/V and to 129V/V. The biochemical properties of
protease-resistant abnormal PrP in the brain and transmissibility of these
humanized mouse-passaged vCJD prions upon subpassage into knock-in mice
expressing bovine PrP were not affected by the codon 129 genotype. These results
indicate that individuals with the 129V/V genotype may be more susceptible to
secondary vCJD infection than expected, and may lack the neuropathological
characteristics observed in vCJD patients with the 129M/M genotype. Besides the
molecular typing of protease resistant PrP in the brain, transmission studies
using knock-in mice carrying bovine PrP may aid the differential diagnosis of
secondary vCJD infection, especially in individuals with the 129V/V genotype.
snip...
DISCUSSION
Here we report a detailed comparison of the transmission properties of vCJD
prions among humanized knock-in mice carrying distinct PRNP codon 129 genotypes.
All three humanized knock-in mouse lines were susceptible to vCJD infection,
although the attack rate gradually decreased from 129M/M to 129M/V to 129V/V.
The amount of PrP deposition including florid/amyloid plaques in the brain also
gradually decreased from 129M/M to 129M/V to 129V/V. The biochemical properties
of PrPres in the brain and the transmissibility of these humanized
mouse-passaged vCJD prions upon subpassage into Ki-Bov/Bov were not affected by
the codon 129 genotype. These results indicate that individuals with the 129V/V
genotype may be more susceptible to secondary vCJD infection than expected and
may lack some neuropathological characteristics observed in vCJD patients with
the 129M/M genotype.
These results have potential public health implications concerning the
future occurrence of secondary vCJD transmission to individuals carrying the
129M/V or 129V/V genotype. We had expected that Ki-Hu129V/V were highly
resistant to vCJD infection because these mice showed negative results when
intraperitoneally challenged with vCJD prions (17, 29). In addition, Bishop et
al. reported a very low attack rate (1/16 (6.25%)) in humanized knock-in mice
with the 129V/V genotype intracerebrally inoculated with vCJD prions (15).
However, Ki-Hu129V/V showed moderate susceptibility to intracerebral
transmission of vCJD in the present study (the sum total attack rate from two
independent experiments using different inocula: 5/12 (41.7%)). This
susceptibility is comparable to the reported attack rate in transgenic mice
expressing human PrP with 129V (the sum total attack rate from six independent
experiments using different inocula: 25/56 (44.6%)) (11, 13). Since the
expression level of PrP directly affects the susceptibility to prion infection
regardless of the codon 129 genotype, the susceptibility reported in the
transgenic mice carrying human PrP with 129V to vCJD prions had been considered
to be due to their high PrP expression level (15). However, the present study
clearly shows that this is not solely due to the overexpression of PrP. The
route of infection in the present study is not that expected for the
human-to-human transmission of vCJD, e.g., blood transfusion contaminated with a
lower dose of vCJD prions, suggesting that the possible secondary infection
might be restricted. Meanwhile, intravenous transmission of BSE is as efficient
as the intracerebral inoculation (29). We reported previously that knock-in mice
expressing human PrP with heterozygosity for glutamine/lysine at another
polymorphic codon 219 (219E/K) are susceptible to vCJD prions (28). Indeed, two
vCJD patients with the 219E/K genotype were reported subsequently (30).
Therefore, our transmission study using humanized knock-in mice could properly
predict that individuals with the 219E/K genotype, which is rarely observed in
the European population (31, 32), have a potential risk for vCJD infection.
Taken together, the present intracerebral transmission data raises the concern
that individuals with the 129V/V genotype are more susceptible to secondary vCJD
infection than had been expected.
The reason for the fluctuating transmissibility of vCJD prions between the
two inocula (vCJD96/02 and 05/02; attack rates in Ki-Hu129V/V were 0/4 (0%) and
5/8 (62.5%), respectively) is unclear. Similar fluctuation in transmissibility
among vCJD inocula has been observed in transmission study using transgenic mice
(from 0% to 80%) (13). These fluctuations might be due to differences in the
prion titers in the inoculum. Western blot analysis of PrPres in the brain of
the patients showed that vCJD05/02 had greater amounts of PrPres (about 5 times)
than vCJD96/02, perhaps reflecting the clinical course of vCJD05/02 (43 months),
which was much longer than that of vCJD96/02 (18 months). The low vCJD attack
rate in humanized knock-in mice with the 129V/V genotype reported by another
group (15) might be also explained by the prion titer in the inoculum, as their
inoculum was diluted to 10-2, whereas our inoculum was a 10-1 dilution. Although
typical vCJD cases were selected for this study, further extensive analysis with
additional cases having various PrPres concentrations should be carried out in
the future.
We confirmed that the characteristic neuropathological features of vCJD can
be modified through transmission to the 129M/V or 129V/V genotype as reported
previously (11, 13-15). Particularly, the amount of PrP deposition and the
number of florid/amyloid plaques in the brain, one of the most important
clinicopathological hallmarks of vCJD, markedly reduced in Ki-Hu129V/V in the
present study. Four out of five (80%) diseased Ki-Hu129V/V lacked florid/amyloid
plaques, despite extensive examination of the brain. Similarly, florid/amyloid
plaques have never been observed in other mouse models of vCJD carrying the
129V/V (or 129M/V) genotype (11, 14, 15). Although the neuropathological
features of humanized knock-in mice with vCJD may not be fully recapitulated in
human brain tissue with vCJD, the present study, together with data from other
groups, raises the concern that vCJD with the 129V/V genotype cannot be
neuropathologically distinguished from sCJD patients with the 129V/V genotype
(e.g., sCJD-VV2). In contrast to the neuropathological phenotype, the
biochemical properties of PrPres were not altered through transmission to the
129M/V or 129V/V genotype as reported in another knock-in mouse model (15).
These results support the view that the molecular typing of PrPres will remain a
useful diagnostic feature of secondary vCJD infection irrespective of the codon
129 genotype (15).
The present study shows that transmission studies using Ki-Bov/Bov are also
a useful means to detect vCJD prions, even in secondary infection. Not only
Ki-Hu129M/M[vCJD05/02] but also Ki-Hu129M/V[vCJD05/02] and
Ki-Hu129V/V[vCJD05/02] showed positive transmissibility to Ki-Bov/Bov, i.e., the
traceback phenomenon, whereas all sCJD or dCJD prions examined failed to be
transmitted. These results suggest that BSE prions retain their host preference
after repeated passages through human PrP regardless of the codon 129 genotype.
Intracerebral transmission generally shows higher sensitivity compared with
intraperitoneal transmission, but requires a very long incubation period of over
2 years to obtain results. In contrast, the FDC assay after intraperitoneal
inoculation requires only 75 days to assess the transmissibility. In addition,
the positive rate of the FDC assay was as high as that of intracerebral
transmission in the present study. Therefore, the FDC assay after
intraperitoneal inoculation of patient materials to Ki-Bov/Bov may help in the
differential diagnosis of vCJD when atypical cases emerge in CJD surveillance
(33, 34).
In conclusion, the present study underpins the importance of systematic
assessment of all human prion disease patients based on the clinicopathological
phenotype and molecular typing of PrPres to monitor secondary vCJD infection
(13-15). Traceback studies using Ki-Bov/Bov may facilitate the differential
diagnosis of secondary vCJD infection, especially in individuals with the PRNP
129V/V genotype.
Amyloid Microbiology Neurobiology Prions Protein misfolding Knock-in mouse
codon 129 genotype folicular dendritic cell vCJD Received March 19, 2013.
Accepted June 21, 2013. Copyright © 2013, The American Society for Biochemistry
and Molecular Biology
***Although the neuropathological features of humanized knock-in mice with
vCJD may not be fully recapitulated in human brain tissue with vCJD, the present
study, together with data from other groups, raises the concern that vCJD with
the 129V/V genotype cannot be neuropathologically distinguished from sCJD
patients with the 129V/V genotype (e.g., sCJD-VV2)....disturbing...how many have
been misdiagnosed as sporadic CJD, AND what about iatrogenic potential therefrom
??? ...tss
Saturday, September 5, 2009
TSEAC MEETING FEBRUARY 12, 2004 THE BAXTER STUDY GSS
snip...
Saturday, September 5, 2009
TSEAC MEETING FEBRUARY 12, 2004 THE BAXTER STUDY GSS
snip...see full text ;
Monday, May 6, 2013
Warning of mad cow disease threat to blood transfusions
Tuesday, April 30, 2013
Mad cow infected blood 'to kill 1,000’
Sunday, February 10, 2013
Creutzfeldt-Jakob disease (CJD) biannual update (February 2013) Infection
report/CJD
Tuesday, May 28, 2013
Late-in-life surgery associated with Creutzfeldt-Jakob disease: a
methodological outline for evidence-based guidance
Thursday, June 6, 2013
BSE TSE PRION USDA FDA MAD COW FEED COMPLIANCE REPORT and NAI, OAI, and VAI
ratings as at June 5, 2013
Thursday, February 14, 2013
The Many Faces of Mad Cow Disease Bovine Spongiform Encephalopathy BSE and
TSE prion disease
Sunday, June 9, 2013
TSEAC March 14, 2013: Transmissible Spongiform Encephalopathies Advisory
Committee Meeting Webcast
Thursday, June 13, 2013
*** Experimental interspecies transmission studies of the transmissible
spongiform encephalopathies to cattle: comparison to bovine spongiform
encephalopathy in cattle
Monday, June 17, 2013
Evaluation of a test for its suitability in the diagnosis of variant
Creutzfeldt–Jakob disease
Saturday, January 22, 2011
Alzheimer's, Prion, and Neurological disease, and the misdiagnosis there
of, a review 2011
Wednesday, June 19, 2013
Spreading of tau pathology in Alzheimer's disease by cell-to-cell
transmission
Monday, October 10, 2011
EFSA Journal 2011 The European Response to BSE: A Success Story
snip...
EFSA and the European Centre for Disease Prevention and Control (ECDC)
recently delivered a scientific opinion on any possible epidemiological or
molecular association between TSEs in animals and humans (EFSA Panel on
Biological Hazards (BIOHAZ) and ECDC, 2011).
*** This opinion confirmed Classical BSE prions as the only TSE agents
demonstrated to be zoonotic so far but the possibility that a small proportion
of human cases so far classified as "sporadic" CJD are of zoonotic origin could
not be excluded.
Moreover, transmission experiments to non-human primates suggest that some
TSE agents in addition to Classical BSE prions in cattle (namely L-type Atypical
BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic
wasting disease (CWD) agents) might have zoonotic potential.
snip...
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...
Rural and Regional Affairs and Transport References Committee
The possible impacts and consequences for public health, trade and
agriculture of the Government's decision to relax import restrictions on beef
Final report June 2010
2.65 At its hearing on 14 May 2010, the committee heard evidence from Dr
Alan Fahey who has recently submitted a thesis on the clinical neuropsychiatric,
epidemiological and diagnostic features of Creutzfeldt-Jakob disease.48 Dr Fahey
told the committee of his concerns regarding the lengthy incubation period for
transmissible spongiform encephalopathies, the inadequacy of current tests and
the limited nature of our current understanding of this group of
diseases.49
2.66 Dr Fahey also told the committee that in the last two years a link has
been established between forms of atypical CJD and atypical BSE. *** Dr Fahey
said that: They now believe that those atypical BSEs overseas are in fact
causing sporadic Creutzfeldt-Jakob disease. They were not sure if it was due to
mad sheep disease or a different form. If you look in the textbooks it looks
like this is just arising by itself. But in my research I have a summary of a
document which states that there has never been any proof that sporadic
Creutzfeldt-Jakob disease has arisen de novo-has arisen of itself. There is no
proof of that. The recent research is that in fact it is due to atypical forms
of mad cow disease which have been found across Europe, have been found in
America and have been found in Asia. These atypical forms of mad cow disease
typically have even longer incubation periods than the classical mad cow
disease.50
Wednesday, 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.
*** The potential impact of prion diseases on human health was greatly
magnified by the recognition that interspecies transfer of BSE to humans by beef
ingestion resulted in vCJD. While changes in animal feed constituents and
slaughter practices appear to have curtailed vCJD, there is concern that CWD of
free-ranging deer and elk in the U.S. might also cross the species barrier.
Thus, consuming venison could be a source of human prion disease. Whether BSE
and CWD represent interspecies scrapie transfer or are newly arisen prion
diseases is unknown. Therefore, the possibility of transmission of prion disease
through other food animals cannot be ruled out. There is evidence that vCJD can
be transmitted through blood transfusion. There is likely a pool of unknown size
of asymptomatic individuals infected with vCJD, and there may be asymptomatic
individuals infected with the CWD equivalent. These circumstances represent a
potential threat to blood, blood products, and plasma supplies.
Saturday, June 15, 2013
Canada Fraser Health Statement on Creutzfeldt-Jakob Disease outbreak
Tuesday, March 5, 2013
Use of Materials Derived From Cattle in Human Food and Cosmetics; Reopening
of the Comment Period FDA-2004-N-0188-0051 (TSS SUBMISSION)
FDA believes current regulation protects the public from BSE but reopens
comment period due to new studies
Saturday, December 15, 2012
Bovine spongiform encephalopathy: the effect of oral exposure dose on
attack rate and incubation period in cattle -- an update 5 December 2012
Wednesday, March 20, 2013
GAO-13-244, Mar 18, 2013 Dietary Supplements FDA May Have Opportunities to
Expand Its Use of Reported Health Problems to Oversee Product
From: Terry S. Singeltary Sr.
Sent: Tuesday, March 19, 2013 2:46 PM
To: gomezj@gao.gov
Cc: siggerudk@gao.gov ; youngc1@gao.gov ; oighotline@gao.gov
Thursday, February 14, 2013
The Many Faces of Mad Cow Disease Bovine Spongiform Encephalopathy BSE and
TSE prion disease
Thursday, May 30, 2013
World Organization for Animal Health (OIE) has upgraded the United States'
risk classification for mad cow disease to "negligible" from "controlled", and
risk further exposing the globe to the TSE prion mad cow type disease
U.S. gets top mad-cow rating from international group and risk further
exposing the globe to the TSE prion mad cow type disease
Thursday, June 20, 2013
atypical, BSE, CWD, Scrapie, Captive Farmed shooting pens (livestock), Wild
Cervids, Rectal Mucosa Biopsy 2012 USAHA Proceedings, and CJD TSE prion Update
Heidenhain Variant Creutzfeldt Jakob Disease autopsy case report 'MOM'
DIVISION OF NEUROPATHOLOGY University of Texas Medical Branch 114
McCullough Bldg. Galveston, Texas 77555-0785
FAX COVER SHEET
DATE: 4-23-98
TO: Mr. Terry Singeltary @ -------
FROM: Gerald Campbell
FAX: (409) 772-5315 PHONE: (409) 772-2881
Number of Pages (including cover sheet):
Message:
*CONFIDENTIALITY NOTICE*
This document accompanying this transmission contains confidential
information belonging to the sender that is legally privileged. This information
is intended only for the use of the individual or entry names above. If you are
not the intended recipient, you are hereby notified that any disclosure, copying
distribution, or the taking of any action in reliances on the contents of this
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error, please notify us by telephone immediately to arrange for return of the
original documents. -------------------------- Patient Account: 90000014-518
Med. Rec. No.: (0160)118511Q Patient Name: POULTER, BARBARA Age: 63 YRS DOB:
10/17/34 Sex: F Admitting Race: C
Attending Dr.: Date / Time Admitted : 12/14/97 1228 Copies to:
UTMB University of Texas Medical Branch Galveston, Texas 77555-0543 (409)
772-1238 Fax (409) 772-5683 Pathology Report
FINAL AUTOPSY DIAGNOSIS Autopsy' Office (409)772-2858
Autopsy NO.: AU-97-00435
AUTOPSY INFORMATION: Occupation: Unknown Birthplace: Unknown Residence:
Crystal Beach Date/Time of Death: 12/14/97 13:30 Date/Time of Autopsy: 12/15/97
15:00 Pathologist/Resident: Pencil/Fernandez Service: Private Restriction: Brain
only
FINAL AUTOPSY DIAGNOSIS
I. Brain: Creutzfeldt-Jakob disease, Heidenhain variant.
***TYPE: Anatomic(A) or Clinical(C) Diagnosis. IMPORTANCE: 1-immediate
cause of death (COD); 2.ureterlying COD; 3-contributory COD: 4.concomitant,
significant; 5-incidental ***
Patient Name: POULTER, BARBARA Patient Location: AUTOPSY Room/Bed: Printed
Date; Time: 01/30/98 - 0832
Page: 1 Continued .... --------------
UTMB University of Texas Medical Branch Galveston, Texas 77555-
Published March 26, 2003
RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease
in the United States
Terry S. Singeltary, retired (medically)
I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to comment
on the CDC's attempts to monitor the occurrence of emerging forms of CJD.
Asante, Collinge et al [1] have reported that BSE transmission to the
129-methionine genotype can lead to an alternate phenotype that is
indistinguishable from type 2 PrPSc, the commonest sporadic CJD. However, CJD
and all human TSEs are not reportable nationally. CJD and all human TSEs must be
made reportable in every state and internationally. I hope that the CDC does not
continue to expect us to still believe that the 85%+ of all CJD cases which are
sporadic are all spontaneous, without route/source. We have many TSEs in the USA
in both animal and man. CWD in deer/elk is spreading rapidly and CWD does
transmit to mink, ferret, cattle, and squirrel monkey by intracerebral
inoculation. With the known incubation periods in other TSEs, oral transmission
studies of CWD may take much longer. Every victim/family of CJD/TSEs should be
asked about route and source of this agent. To prolong this will only spread the
agent and needlessly expose others. In light of the findings of Asante and
Collinge et al, there should be drastic measures to safeguard the medical and
surgical arena from sporadic CJDs and all human TSEs. I only ponder how many
sporadic CJDs in the USA are type 2 PrPSc?
Published March 26, 2003
Letters
JAMA. 2001;285(6):733-734. doi: 10.1001/jama.285.6.733
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Terry S. Singeltary, Sr Bacliff, Tex
Since this article does not have an abstract, we have provided the first
150 words of the full text.
KEYWORDS: creutzfeldt-jakob disease, diagnosis. To the Editor: In their
Research Letter, Dr Gibbons and colleagues1 reported that the annual US death
rate due to Creutzfeldt-Jakob disease (CJD) has been stable since 1985. These
estimates, however, are based only on reported cases, and do not include
misdiagnosed or preclinical cases. It seems to me that misdiagnosis alone would
drastically change these figures. An unknown number of persons with a diagnosis
of Alzheimer disease in fact may have CJD, although only a small number of these
patients receive the postmortem examination necessary to make this diagnosis.
Furthermore, only a few states have made CJD reportable. Human and animal
transmissible spongiform encephalopathies should be reportable nationwide and
internationally.
References 1. Gibbons RV, Holman RC, Belay ED, Schonberger LB.
Creutzfeldt-Jakob disease in the United States: 1979-1998. JAMA.
2000;284:2322-2323.
THE PATHOLOGICAL PROTEIN
BY Philip Yam
Yam Philip Yam News Editor Scientific American www.sciam.com
Answering critics like Terry Singeltary, who feels that the U.S. under-
counts CJD, Schonberger conceded that the current surveillance system has errors
but stated that most of the errors will be confined to the older population.
CHAPTER 14
Laying Odds
Are prion diseases more prevalent than we thought?
Researchers and government officials badly underestimated the threat that
mad cow disease posed when it first appeared in Britain. They didn't think
bovine spongiform encephalopathy was a zoonosis-an animal disease that can
sicken people. The 1996 news that BSE could infect humans with a new form of
Creutzfeldt-Jakob disease stunned the world. It also got some biomedical
researchers wondering whether sporadic CJD may really be a manifestation of a
zoonotic sickness. Might it be caused by the ingestion of prions, as variant CJD
is?
Revisiting Sporadic CJD
It's not hard to get Terry Singeltary going. "I have my conspiracy
theories," admitted the 49-year-old Texan.1 Singeltary is probably the nation's
most relentless consumer advocate when it comes to issues in prion diseases. He
has helped families learn about the sickness and coordinated efforts with
support groups such as CJD Voice and the CJD Foundation. He has also connected
with others who are critical of the American way of handling the threat of prion
diseases. Such critics include Consumers Union's Michael Hansen, journalist John
Stauber, and Thomas Pringle, who used to run the voluminous www.madcow. org Web
site. These three lend their expertise to newspaper and magazine stories about
prion diseases, and they usually argue that prions represent more of a threat
than people realize, and that the government has responded poorly to the dangers
because it is more concerned about protecting the beef industry than people's
health.
Singeltary has similar inclinations. ...
snip...
THE PATHOLOGICAL PROTEIN
Hardcover, 304 pages plus photos and illustrations. ISBN 0-387-95508-9
June 2003
BY Philip Yam
CHAPTER 14 LAYING ODDS
Answering critics like Terry Singeltary, who feels that the U.S. under-
counts CJD, Schonberger conceded that the current surveillance system has errors
but stated that most of the errors will be confined to the older population.
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.
CJD Singeltary submission to PLOS ;
No competing interests declared.
see full text ;
The Lancet Infectious Diseases, Volume 3, Issue 8, Page 463, August 2003
doi:10.1016/S1473-3099(03)00715-1Cite or Link Using DOI
Tracking spongiform encephalopathies in North America
Original
Xavier Bosch
“My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my
mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever
since. What I have found is that we have not been told the truth. CWD in deer
and elk is a small portion of a much bigger problem.” 49-year—old Singeltary is
one of a number of people who have remained largely unsatisfied after being told
that a close relative died from a rapidly progressive dementia compatible with
spontaneous Creutzfeldt—Jakob ...
SEE FULL TEXT ;
-------- Original Message --------
Subject: Tracking spongiform encephalopathies in North America LANCET
INFECTIOUS DISEASE Volume 3, Number 8 01 August 2003
Date: Tue, 29 Jul 2003 17:35:30 –0500
From: "Terry S. Singeltary Sr." Reply-To: Bovine Spongiform Encephalopathy
To: BSE-L@uni-karlsruhe.de
Volume 3, Number 8 01 August 2003
Newsdesk
Tracking spongiform encephalopathies in North America
Xavier Bosch
My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my
mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever
since. What I have found is that we have not been told the truth. CWD in deer
and elk is a small portion of a much bigger problem.
49-year-old Singeltary is one of a number of people who have remained
largely unsatisfied after being told that a close relative died from a rapidly
progressive dementia compatible with spontaneous Creutzfeldt-Jakob disease
(CJD). So he decided to gather hundreds of documents on transmissible spongiform
encephalopathies (TSE) and realised that if Britons could get variant CJD from
bovine spongiform encephalopathy (BSE), Americans might get a similar disorder
from chronic wasting disease (CWD)the relative of mad cow disease seen among
deer and elk in the USA. Although his feverish search did not lead him to the
smoking gun linking CWD to a similar disease in North American people, it did
uncover a largely disappointing situation.
Singeltary was greatly demoralised at the few attempts to monitor the
occurrence of CJD and CWD in the USA. Only a few states have made CJD
reportable. Human and animal TSEs should be reportable nationwide and
internationally, he complained in a letter to the Journal of the American
Medical Association (JAMA 2003; 285: 733). I hope that the CDC does not continue
to expect us to still believe that the 85% plus of all CJD cases which are
sporadic are all spontaneous, without route or source.
Until recently, CWD was thought to be confined to the wild in a small
region in Colorado. But since early 2002, it has been reported in other areas,
including Wisconsin, South Dakota, and the Canadian province of Saskatchewan.
Indeed, the occurrence of CWD in states that were not endemic previously
increased concern about a widespread outbreak and possible transmission to
people and cattle.
To date, experimental studies have proven that the CWD agent can be
transmitted to cattle by intracerebral inoculation and that it can cross the
mucous membranes of the digestive tract to initiate infection in lymphoid tissue
before invasion of the central nervous system. Yet the plausibility of CWD
spreading to people has remained elusive.
Part of the problem seems to stem from the US surveillance system. CJD is
only reported in those areas known to be endemic foci of CWD. Moreover, US
authorities have been criticised for not having performed enough prionic tests
in farm deer and elk.
Although in November last year the US Food and Drug Administration issued a
directive to state public-health and agriculture officials prohibiting material
from CWD-positive animals from being used as an ingredient in feed for any
animal species, epidemiological control and research in the USA has been quite
different from the situation in the UK and Europe regarding BSE.
Getting data on TSEs in the USA from the government is like pulling teeth,
Singeltary argues. You get it when they want you to have it, and only what they
want you to have.
Norman Foster, director of the Cognitive Disorders Clinic at the University
of Michigan (Ann Arbor, MI, USA), says that current surveillance of prion
disease in people in the USA is inadequate to detect whether CWD is occurring in
human beings; adding that, the cases that we know about are reassuring, because
they do not suggest the appearance of a new variant of CJD in the USA or
atypical features in patients that might be exposed to CWD. However, until we
establish a system that identifies and analyses a high proportion of suspected
prion disease cases we will not know for sure. The USA should develop a system
modelled on that established in the UK, he points out.
Ali Samii, a neurologist at Seattle VA Medical Center who recently reported
the cases of three hunterstwo of whom were friendswho died from pathologically
confirmed CJD, says that at present there are insufficient data to claim
transmission of CWD into humans; adding that [only] by asking [the questions of
venison consumption and deer/elk hunting] in every case can we collect suspect
cases and look into the plausibility of transmission further. Samii argues that
by making both doctors and hunters more aware of the possibility of prions
spreading through eating venison, doctors treating hunters with dementia can
consider a possible prion disease, and doctors treating CJD patients will know
to ask whether they ate venison.
CDC spokesman Ermias Belay says that the CDC will not be investigating the
[Samii] cases because there is no evidence that the men ate CWD-infected meat.
He notes that although the likelihood of CWD jumping the species barrier to
infect humans cannot be ruled out 100% and that [we] cannot be 100% sure that
CWD does not exist in humans& the data seeking evidence of CWD transmission
to humans have been very limited.
Greetings,
> > > he complained in a letter to the Journal of the American
Medical Association (JAMA 2003; 285: 733). I hope that the CDC does not continue
to expect us to still believe that the 85% plus of all CJD cases which are
sporadic are all spontaneous, without route or source. < < <
actually, that quote was from a more recent article in the Journal of
Neurology (see below), not the JAMA article.
Full Text
Diagnosis and Reporting of Creutzfeldt-Jakob Disease Singeltary, Sr et al.
JAMA.2001; 285: 733-734.
snip...end...tss
Re: vCJD in the USA * BSE in U.S.
15 November 1999 Terry S Singeltary, NA
In reading the recent article in the BMJ about the potential BSE tests
being developed in the U.S. and Bart Van Everbroeck reply. It does not surprize
me, that the U.S. has been concealing vCJD. There have been people dying from
CJD, with all the symptoms and pathological findings that resemble U.K. vCJD for
some time. It just seems that when there is one found, they seem to change the
clarical classification of the disease, to fit their agenda. I have several
autopsies, stating kuru type amyloid plaques, one of the victims was 41 years of
age. Also, my Mom died a most hideous death, Heidenhain Variant Creutzfeldt
Jakob disease.
Her symptoms resemble that of all the U.K. vCJD victims. She would jerk so
bad at times, it would take 3 of us to hold her down, while she screamed "God,
what's wrong with me, why can't I stop this." 1st of symptoms to death, 10
weeks, she went blind in the first few weeks. But, then they told me that this
was just another strain of sporadic CJD. They can call it what ever they want,
but I know what I saw, and what she went through. Sporadic, simply means, they
do not know.
My neighbors Mom also died from CJD. She had been taking a nutritional
supplement which contained the following;
vacuum dried bovine BRAIN, bone meal, bovine EYE, veal bone, bovine liver
powder, bovine adrenal, vacuum dried bovine kidney, and vacuum dried porcine
stomach. As I said, this woman taking these nutritional supplements, died from
CJD.
The particular batch of pills that was located, in which she was taking,
was tested. From what I have heard, they came up negative, for the prion
protein. But, in the same breath, they said their testing, may not have been
strong enough to pick up the infectivity. Plus, she had been taking these type
pills for years, so, could it have come from another batch?
CWD is just a small piece of a very big puzzle. I have seen while deer
hunting, deer, squirrels and birds, eating from cattle feed troughs where they
feed cattle, the high protein cattle by products, at least up until Aug. 4,
1997.
So why would it be so hard to believe that this is how they might become
infected with a TSE. Or, even by potentially infected land. It's been well
documented that it could be possible, from scrapie. Cats becoming infected with
a TSE. Have you ever read the ingredients on the labels of cat and dog food?
But, they do not put these tissues from these animals in pharmaceuticals,
cosmetics, nutritional supplements, hGH, hPG, blood products, heart valves, and
the many more products that come from bovine, ovine, or porcine tissues and
organs. So, as I said, this CWD would be a small piece of a very big puzzle.
But, it is here, and it most likely has killed. You see, greed is what caused
this catastrophe, rendering and feeding practices. But, once Pandora's box was
opened, the potential routes of infection became endless.
No BSE in the U.S.A.? I would not be so sure of that considering that since
1990;
Since 1990 the U.S. has raised 1,250,880,700 cattle;
Since 1990 the U.S. has ONLY checked 8,881 cattle brains for BSE, as of
Oct. 4, 1999;
There are apprx. 100,000 DOWNER cattle annually in the U.S., that up until
Aug. 4, 1997 went to the renders for feed;
Scrapie running rampant for years in the U.S., 950 infected FLOCKS, as of
Aug. 1999;
Our feeding and rendering practices have mirrored that of the U.K. for
years, some say it was worse. Everything from the downer cattle, to those
scrapie infected sheep, to any roadkill, including the city police horse and the
circus elephant went to the renders for feed and other products for consumption.
Then they only implemented a partial feed ban on Aug. 4, 1997, but pigs,
chickens, dogs, and cats, and humans were exempt from that ban. So they can
still feed pigs and chickens those potentially TSE tainted by-products, and then
they can still feed those by-products back to the cows. I believe it was Dr. Joe
Gibbs, that said, the prion protein, can survive the digestinal track. So you
have stopped nothing. It was proven in Oprah Winfrey's trial, that Cactus Cattle
feeders, sent neurologically ill cattle, some with encephalopathy stamped on the
dead slips, were picked up and sent to the renders, along with sheep carcasses.
Speaking of autopsies, I have a stack of them, from CJD victims. You would be
surprised of the number of them, who ate cow brains, elk brains, deer brains, or
hog brains.
I believe all these TSE's are going to be related, and originally caused by
the same greedy Industries, and they will be many. Not just the Renders, but you
now see, that they are re-using medical devices that were meant for disposal.
Some medical institutions do not follow proper auto- claving procedures (even
Olympus has put out a medical warning on their endescopes about CJD, and the
fact you cannot properly clean these instruments from TSE's), and this is just
one product. Another route of infection.
Regardless what the Federal Government in the U.S. says. It's here, I have
seen it, and the longer they keep sweeping it under the rug and denying the fact
that we have a serious problem, one that could surpass aids (not now, but in the
years to come, due to the incubation period), they will be responsible for the
continued spreading of this deadly disease.
It's their move, it's CHECK, but once CHECKMATE has been called, how many
thousands or millions, will be at risk or infected or even dead. You can't play
around with these TSE's. I cannot stress that enough. They are only looking at
body bags, and the fact the count is so low. But, then you have to look at the
fact it is not a reportable disease in most states, mis-diagnosis, no autopsies
performed. The fact that their one-in-a- million theory is a crude survey done
about 5 years ago, that's a joke, under the above circumstances. A bad joke
indeed........
The truth will come, but how many more have to die such a hideous death.
It's the Government's call, and they need to make a serious move, soon. This
problem, potential epidemic, is not going away, by itself.
Terry S. Singeltary Sr.
P.O. Box 42, Bacliff, Texas 77518 USA
flounder@wt.net
Competing interests:None declared
U.S. Scientist should be concerned with a CJD epidemic in the U.S., as
well...
2 January 2000
Terry S Singeltary
In reading your short article about 'Scientist warn of CJD epidemic' news
in brief Jan. 1, 2000. I find the findings in the PNAS old news, made famous
again. Why is the U.S. still sitting on their butts, ignoring the facts? We have
the beginning of a CJD epidemic in the U.S., and the U.S. Gov. is doing
everything in it's power to conceal it.
The exact same recipe for B.S.E. existed in the U.S. for years and years.
In reading over the Qualitative Analysis of BSE Risk Factors-1, this is a 25
page report by the USDA:APHIS:VS. It could have been done in one page. The first
page, fourth paragraph says it all;
"Similarities exist in the two countries usage of continuous rendering
technology and the lack of usage of solvents, however, large differences still
remain with other risk factors which greatly reduce the potential risk at the
national level."
Then, the next 24 pages tries to down-play the high risks of B.S.E. in the
U.S., with nothing more than the cattle to sheep ratio count, and the
geographical locations of herds and flocks. That's all the evidence they can
come up with, in the next 24 pages.
Something else I find odd, page 16;
"In the United Kingdom there is much concern for a specific continuous
rendering technology which uses lower temperatures and accounts for 25 percent
of total output. This technology was _originally_ designed and imported from the
United States. However, the specific application in the production process is
_believed_ to be different in the two countries."
A few more factors to consider, page 15;
"Figure 26 compares animal protein production for the two countries. The
calculations are based on slaughter numbers, fallen stock estimates, and product
yield coefficients. This approach is used due to variation of up to 80 percent
from different reported sources. At 3.6 million tons, the United States produces
8 times more animal rendered product than the United Kingdom."
"The risk of introducing the BSE agent through sheep meat and bone meal is
more acute in both relative and absolute terms in the United Kingdom (Figures 27
and 28). Note that sheep meat and bone meal accounts for 14 percent, or 61
thousand tons, in the United Kingdom versus 0.6 percent or 22 thousand tons in
the United States. For sheep greater than 1 year, this is less than one-tenth of
one percent of the United States supply."
"The potential risk of amplification of the BSE agent through cattle meat
and bone meal is much greater in the United States where it accounts for 59
percent of total product or almost 5 times more than the total amount of
rendered product in the United Kingdom."
Considering, it would only take _one_ scrapie infected sheep to contaminate
the feed. Considering Scrapie has run rampant in the U.S. for years, as of Aug.
1999, 950 scrapie infected flocks. Also, Considering only one quarter spoonful
of scrapie infected material is lethal to a cow.
Considering all this, the sheep to cow ration is meaningless. As I said,
it's 24 pages of B.S.e.
To be continued...
Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA
Competing interests:None declared
Sunday, August 21, 2011
The British disease, or a disease gone global, The TSE Prion Disease
(see video here)
U.S.A. HIDING MAD COW DISEASE VICTIMS AS SPORADIC CJD ?
(see video at bottom)
Sunday, September 6, 2009
MAD COW USA 1997
(SEE SECRET VIDEO)
Creutzfeldt-Jakob Disease Public Health Crisis
just made a promise to mom...back then, there was very little information
to the public on the human and animal TSE prion disease. ... layperson...tss
posted by Terry S. Singeltary Sr. | 10:08 AM
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