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From: TSS ()
Subject: Unexpectedly high incidence of visceral AA-amyloidosis in slaughtered cattle in Japan
Date: July 23, 2007 at 11:57 am PST

Unexpectedly high incidence of visceral AA-amyloidosis in slaughtered cattle
in Japan

Authors: Kana Tojo a; Takahiko Tokuda a; Yoshinobu Hoshii b; Xiaoying
...eiichi Higuchi c; Takane Matsui d; Fuyuki Kametani e; Dr Shu-Ichi
Ikeda a Affiliations: a Third Department of Medicine, Shinshu University
School
of Medicine. Matsumoto. Japan
b First Department of Pathology, Yamaguchi University School of Medicine.
Ube. Japan
c Department of Aging Biology, Institute on Aging and Adaptation, Shinshu
University, Graduate School of Medicine. Matsumoto. Japan
d Department of Pathobiological Science, School of Veterinary Medicine,
Obihiro University of Agriculture and Veterinary Medicine. Obihiro. Japan
e Department of Molecular Biology, Tokyo Institute of Psychiatry. Tokyo.
Japan

DOI: 10.1080/13506120500107097
Publication Frequency: 4 issues per year
Published in: Amyloid, Volume 12, Issue 2 June 2005 , pages 103 - 108
Subjects: Biochemistry; Medicine;
Number of References: 30
Formats available: HTML (English) : PDF (English)
Previously published as: Amyloid: International Journal of Experimental &
Clinical Investigation (1350-6129) until 2004
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Abstract

Experimental mouse AA amyloidosis can be transmissible by dietary ingestion
of amyloid fibrils and it is well known that AA amyloidosis occasionally
develops in aged cattle. Bovine liver and intestine have conventionally been
used in Oriental foods, and the incidence of visceral AA amyloidosis in
slaughtered cattle was evaluated. Renal tissues from 302 aged cattle older
than 4 years were obtained from a local abattoir. Amyloid deposition was
microscopically examined and amyloid protein was immunochemically
determined. Renal amyloid deposition was seen in 15 out of 302 cattle with
no previous history of diseas, an incidence of 5.0%. Amyloid protein in
these cattle was AA and they had pathological findings in their visceral
organs on gross examination. The incidence of visceral AA amyloidosis in
slaughtered cattle in this study was disturbingly high compared with those
(0.4-2.7%) previously reported from Japan and other foreign countries. AA
amyloidosis is a life-threatening complication in patients with chronic
inflammatory diseases and these patients at risk should avoid ingesting food
that may possibly contain AA amyloid fibrils. More detailed information on
cattle amyloidosis is required to guarantee the safety of our food.

Keywords: Cattle amyloidosis; transmissible amyloidosis; reactive
amyloidosis; AA amyloidosis; chronic inflammation
view references (30)


http://www.informaworld.com/smpp/content~content=a713998551~db=all~order=page


Subject: Amyloidogenic potential of foie gras
Date: June 22, 2007 at 2:23 pm PST

http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0706&L=sanet-mg&P=9621


Alzheimer's and Transmissible Spongiform Encephalopathies


Alzheimer-type neuropathology 28 year old patient with idCJD
Sun Feb 19, 2006 11:14
71.248.144.164


SHORT REPORT
Alzheimer-type neuropathology in a 28 year old patient with iatrogenic
Creutzfeldt-Jakob disease after dural grafting
M Preusser1, T Ströbel1, E Gelpi1,2, M Eiler3, G Broessner4, E Schmutzhard4
and H Budka1,2
1 Institute of Neurology, Medical University Vienna, Austria
2 Austrian Reference Centre for Human Prion Diseases (OERPE), General
Hospital Vienna, Austria
3 Department of Neurology, LKH Rankweil, Austria
4 Department of Neurology, Medical University Innsbruck, Innsbruck, Austria


Correspondence to:
Dr H Budka
Institute of Neurology, Medical University of Vienna, Waehringer Guertel
18-20, 4J, 1097 Vienna, Austria; herbert.budka@kin.at


ABSTRACT
We report the case of a 28 year old man who had received a cadaverous dura
mater graft after a traumatic open skull fracture with tearing of the dura
at the age of 5 years. A clinical suspicion of Creutzfeldt-Jakob disease
(CJD) was confirmed by a brain biopsy 5 months prior to death and by
autopsy, thus warranting the diagnosis of iatrogenic CJD (iCJD) according to
WHO criteria. Immunohistochemistry showed widespread cortical depositions of
disease associated prion protein (PrPsc) in a synaptic pattern, and western
blot analysis identified PrPsc of type 2A according to Parchi et al.
Surprisingly, we found Alzheimer-type senile plaques and cerebral amyloid
angiopathy in widespread areas of the brain. Plaque-type and vascular
amyloid was immunohistochemically identified as deposits of beta-A4 peptide.
CERAD criteria for diagnosis of definite Alzheimer’s disease (AD) were met
in the absence of neurofibrillar tangles or alpha-synuclein immunoreactive
inclusions. There was no family history of AD, CJD, or any other
neurological disease, and genetic analysis showed no disease specific
mutations of the prion protein, presenilin 1 and 2, or amyloid precursor
protein genes. This case represents (a) the iCJD case with the longest
incubation time after dural grafting reported so far, (b) the youngest
documented patient with concomitant CJD and Alzheimer-type neuropathology to
date, (c) the first description of Alzheimer-type changes in iCJD, and (d)
the second case of iCJD in Austria. Despite the young patient age, the
Alzheimer-type changes may be an incidental finding, possibly related to the
childhood trauma.


----------------------------------------------------------------------------
----

http://jnnp.bmjjournals.com/


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://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://www.bseinquiry.gov.uk/files/yb/1992/11/04001001.pdf


also, see the increase of Alzheimer's from 1981 to 1986


http://www.bseinquiry.gov.uk/files/yb/1988/07/08014001.pdf

full text ;

http://neurotalk.psychcentral.com/showthread.php?t=13175

Creutzfeldt-Jakob Disease Mortality in Japan, 1979-2004: Analysis of
National Death Certificate Data


Yuriko Doi1), Tetsuji Yokoyama2), Miyoshi Sakai2) and Yosikazu Nakamura3)

1) Department of Epidemiology, National Institute of Public Health.
2) Department of Technology Assessment and Biostatistics, National Institute
of Public Health.
3) Department of Public Health, Jichi Medical University.

(Received: September 13, 2006)
(Accepted: March 18, 2007)


Abstract
BACKGROUND: Trend of the mortality rate of Creutzfeldt-Jakob disease (CJD)
in Japan is still unclear. This study aimed to estimate annual crude
mortality rates due to CJD and examine the CJD mortality trend in Japan
during the period of 1979-2004.
METHODS: National death certificate data on CJD were used (CJD coded as
046.1 for ICD-9 and A81.0 for ICD-10). Trends in age-standardized mortality
rates for CJD were examined by using time series analyses including the
joinpoint regression analysis.
RESULTS: A total of 1,966 deaths (862 males and 1,104 females) were
identified with CJD coded as the underlying-cause-of-death. The annual
number of deaths and crude mortality rates peaked in 2004 at 163 (66 for
males and 97 for females) deaths and 1.28 (1.06 for males and 1.48 for
females) deaths per million population per year, respectively. The
age-specific mortality rates rapidly increased with age between 50 and 74
years, especially among females, and sharply declined at 80+ years.
Throughout the observed period, there were no significant change points, and
the annual percentage changes (95% confidence intervals) were +3.09 (2.18 -
4.02) % for males and +3.90 (2.98-4.83) % and females. The total number of
CJD deaths under 50 years of age was 131, and there was found no increase in
the annual number of deaths for the past few years in this age group.
CONCLUSION: CJD mortality in trend data based on death certificates has
significantly increased in Japan during the period of 1979-2004.
J Epidemiol 2007; 17: 133-139.

Key words: Creutzfeldt-Jakob Syndrome; Regression Analysis; Mortality;
Death Certificate; Japan

snip...


AS demonstrated in this study, we found a significant linear increase in
trends for age standardized mortality rates from the disease, with +3-4% of
annual percentage change, between 1979 and 2004. In interpreting the
results, we should consider some factors that might contribute to a false
increase in mortality, such as the change of ICD codes and the enhancement
of case findings (e.g., physicians9 recognition of the disease, diagnostic
tests, and quality of health care). No revolutionary new diagnostic test for
CJD became available throughout the observational period. On the other hand,
there were a few critical points of time to consider: in 1991, patients with
CJD transmitted by cadaveric dura transplants were identified in Japan9, in
1995, the ICD code for CJD was changed from 9th to 10th version in Japan;
and in 1996, a new case of vCJD causally linked to BSE was reported from the
United Kingdom.6 Without an abrupt rise of age-standardized mortality rates
from CJD after these years for both sexes, however, it is unlikely that
these events artificially affected the increase in CJD mortality.

Rather, it may be the true fact that in Japan our results reflect to a large
extent a genuine increase in CJD. The number of iCJD cases may still
increase even after the total ban on the practice of causal grafts.5,8
Regarding sporadic CJD (sCJD), a recent report from the European Unions
collective study on CJD suggests that the mortality rates from sCJD
increased with time between 1993 and 2002.20 It is quite probable that this
temporal increase of sCJD may also exist in Japan. The increase may have
been accompanied to some extent by the improvement of physicians diagnostic
skills for CJD since 1997 when a manual for clinical practice on CJD was
introduced in our country.20,21


http://www.jstage.jst.go.jp/article/jea/17/4/17_133/_article

http://www.jstage.jst.go.jp/article/jea/17/4/133/_pdf


ALZHEIMER'S ASSOCIATION JAPAN was established in Kyoto in 1980. It is a
non-profit nationwide organization concerned with people with dementia
including Alzheimer's disease and their family caregivers and has 41
chapters through the country. Our Association is consisted of family
caregivers, doctors, nurses, social workers, care workers, volunteers and so
on. The Association is a member of the Alzheimer's Disease International
(ADI),@hosted the 20th International Conference of the ADI Kyoto 2004 and
conducts some activities as shown below.


http://www2f.biglobe.ne.jp/~boke/boke2-e1.htm


Japanese here

http://210.136.156.61/jp/index.html


Original Research Article

Epidemiologic and Genetic Studies of Dementia of the Alzheimer Type in Japan
Katsuya Urakamia, Yoshiki Adachia, Yosuke Wakutania, Kenji Isoea, Yong Jia,
Kazuro Takahashib, Kenji Nakashimaa

a Division of Neurology, Institute of Neurological Sciences, Faculty of
Medicine, Tottori University, Nishimachi, Yonago,
b Tottori University, Tottori, Japan


Address of Corresponding Author

Dementia and Geriatric Cognitive Disorders 1998;9:294-298 (DOI:
10.1159/000017074)


----------------------------------------------------------------------------
----

Key Words

Prevalence
Epidemiological study
Dementia of the Alzheimer type Apolipoprotein E
Amyloid precursor protein
Presenilin

----------------------------------------------------------------------------
----

Abstract

We carried out two separate epidemiological studies on long-term changes, 10
years apart, on the prevalence rate of dementia in the elderly by the same
method for the same area in Japan. We also performed a genetic study of
patients with dementia of the Alzheimer type (DAT) based on the
epidemiological studies. The number of patients with dementia was much
larger in 1990 than in 1980. Especially, the number of mildly demented
patients was significantly larger in 1990 than in 1980. The 35 patients with
DAT did not show any mutations of amyloid- protein precursor, presenilin 1
and presenilin 2 genes. The frequency of apolipoprotein E (apo E) 4 allele
in DAT was significantly higher than that in control subjects (p < 0.005).
This study suggests that the frequency of DAT may increase by aging of the
population in the future and we confirm the close association between apoE 4
allele and DAT in a community-based study in Japan.


----------------------------------------------------------------------------
----

Author Contacts

Dr. Katsuya Urakami
Division of Neurology
Institute of Neurological Sciences, Faculty of Medicine
Tottori University, Nishimachi 36-1, Yonago 683-8504 (Japan)
Tel. +81 859 34 8032, Fax +81 859 34 8083, E-Mail
kurakami@grape.med.tottori-u.ac.jp


http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowFulltext&ArtikelNr=17074&Ausgabe=225517&ProduktNr=224226


Vol. 283 No. 13, April 5, 2000

Early-Onset Familial Alzheimer Disease With Coexisting -Amyloid and Prion
Pathology

To the Editor: Familial Alzheimer disease (AD) with early onset has been
linked to 3 different genes with an autosomal dominant mode of
inheritance: -amyloid, protein precursor, and the presenilins 1 and 2,
representing not more than 50% of all cases of early-onset AD cases.1 Thus,
the genetic defect remains unexplained in at least half of the families with
histories of early onset of AD. We have recently described such a Swiss
family whose members presented with a standard clinical and neuropathologic
profile of AD.2 In particular, severe neurofibrillary tangle degeneration
was present in the hippocampus and in several cortical areas, together with
a large amount of -amyloid deposits and senile plaques (SPs). However, known
mutations have not been found, either in the -amyloid precursor protein or
in the presenilin 1 and 2 genes.2 We now report that the brains of 5
deceased members of this family, from 2 generations, present a
coexisting -amyloid and prion protein (PrP) pathology.


snip...


Comment

Coexistence of Creutzfeldt-Jakob disease (CJD) and AD in some patients has
been described but appears mainly related to age in patients proven to have
CJD.4 However, since the individuals in the Swiss family died over a long
interval and were all similarly affected, it is unlikely that CJD is purely
coincidental. On the other hand, familial Gerstmann-Straüssler-Scheinker
disease can present a variant with concomitant neurofibrillary tangle and
prion-positive plaques, but not -amyloid–positive plaques. Within this
variant, 2 mutations in the gene for the PrP have been identified in 2
different families, and the clinical profile with cerebellar ataxia and
extrapyramidal signs5 differs from our findings.2 Base pair deletion in the
prion gene segregating as an uncommon polymorphism has been described in a
family with a history of late-onset AD, but there is no neuropathological
confirmation and the genetic association is uncertain.6

Thus, the data presented herein support the existence of a possible new
subtype of familial early-onset AD with a concomitant -amyloid and prion
brain pathology, together with a massive neurofibrillary tangle
degeneration. Although all known mutations have been excluded in the coding
regions of the AD genes, numerous candidate chromosome sites, either in the
AD genes outside the coding regions or in other genes including PrP, must be
considered.

http://jama.ama-assn.org/cgi/content/full/283/13/1689-a


A Mutation in- the Amyloid Precursor Protein
Associated with Hereditary Alzheimer's Disease
JILL MURRELL, MARTIN FARLOw, BERNARDINO GHEr,
MERRILL D. BENSON*


Alzheimer's disease is a form of localized amyloidosis characterized by cerebral cortical
amyloid plaques, neurofibrillary tangles, and amyloid deposits within the walls of
leptomeningeal vessels. Although most cases of Alzheimer's disease are sporadic, kindreds
with autosomal-dominant inheritance of the syndrome suggest that a single
mutation may be important in pathogenesis. Direct sequencing of DNA from a
family with autopsy-proven Alzheimer's disease revealed a single amino acid
substitution (Phe for Val) in the transmembrane domain of the amyloid precursor protein. This
mutation correlates with the presence of Alzheimer's disease in all patients in this
study, and may be the inherited factor causing both amyloid fibril formation and dementia.


snip...


Single amino acid substitutions are also
found in other forms of hereditary amyloidosis.
In the transthyretin amyloidoses
(FAP, types I and II), a number of single
amino acid substitutions in transthyretin are


SCIENCE, VOL. 254


associated with the amyloid syndrome (15).
Similarly, FAP type HI is associated with
amyloid deposits that contain a peptide of
apolipoprotein Al with a single amino acid
substitution (Gly to Arg) (12). In Gerstmann-
Straussler-Scheinker disease (GSS), a
hereditary adult-onset dementia with cerebral
amyloid plaques composed of a fragment
of the prion protein, every GSS family
studied to date has a mutation in the gene
coding for this protein (16-18). Hereditary
cerebral hemorrhage with amyloidosis in
Icelandic kindreds (HCHWA-I) is associated
with a single amino acid substitution in
cystatin C (19), and a similar syndrome in
Dutch kindreds (HCHWA-D) is associated
with a single amino acid substitution of Gln
for Glu in APP (20).

Although other single amino acid substitutions
in APP may be associated with amyloid
deposits and Alzheimer's disease, it is
unlikely that single amino acid substitutions
in APP can explain all sporadic forms of
Alzheimer's disease. Recently it has been
proposed that in some cases of FAP, normal
transthyretin may form amyloid deposits in
association with unknown aging factors
(21). Similarly, in Alzheimers disease, different
pathogenic processes may lead to a
common clinical presentation.


http://www.sciencemag.org/cgi/reprint/254/5028/97.pdf

News Release 4/16/2007 Worldwide Cost for Dementia Care is $315 Billion Annually

Number of people with dementia soars to more than 29 million

The total worldwide cost of dementia care is estimated to be $315.4 billion
annually, according to new data published in “An Estimate of the Total
Worldwide Societal Costs of Dementia in 2005,” in the April 2007 issue of
Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.

These costs were based on an estimated world dementia population of 29.3
million persons. Seventy-seven (77) percent of the total costs occurred in
the world’s more developed regions, which have 46 percent of the dementia
prevalence.


snip...full text ;

http://www.alz.org/media_8491.asp


RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease
in the United States

IN the reply from Dr. Maddox et al to Terry S. Singeltary Sr. ;

snip...

If BSE causes a sporadic CJD-like illness in humans, an increase in sporadic
CJD cases would be expected to first occur in the United Kingdom, where the
vast majority of vCJD cases have been reported. In the United Kingdom during
1997 through 2002, however, the overall average annual mortality rate for
sporadic CJD was not elevated; it was about 1 case per million population
per year. In addition, during this most recent 6-year period following the
first published description of vCJD in 1996, there was no increasing trend
in the reported annual number of UK sporadic CJD deaths.[3, 5] Furthermore,
surveillance in the UK has shown no increase in the proportion of sporadic
CJD cases that are homozygous for methionine (Will RG, National CJD
Surveillance Unit, United Kingdom, 2003; personal communication)...

snip...

http://www.neurology.org/cgi/eletters/60/2/176#535


THERE seems to be some difference of opinion;


The BSE Inquiry/Statement No 63
Professor John Collinge (scheduled to give oral evidence on 4/6/98)
STATEMENT TO THE BSE INQUIRY: PROFESSOR JOHN COLLINGE

18 In December 1990 I attended a seminar organised by the Medical Research Council in
London. I gave an oral presentation on work recently published in The Lancet on the
molecular diagnosis of inherited prion disease (Collinge, et al., Lancet, 2: 15-17 (1989)
[J/L/ii/15]; Collinge, et al., Lancet, 336: 7-9 (1990) [J/L/336/7]). In particular, I had
reported with colleagues a case entirely lacking the normal histological features of
spongiform encephalopathy on neuropathological examination but in which the
diagnosis could be confirmed by PRNP analysis. This drew into question the
usefulness of diagnostic terms such as Creutzfeldt-Jakob disease (CJD) and
Gerstmann-Sträussler-Scheinker disease (GSS) and I suggested that they should be
8
considered parts of a wider disease spectrum referred to as prion disease which could
now be classified at the molecular level. Such observations also raised the question as
to whether prion disease was being under-diagnosed as, clearly, it could mimic other
neurodegenerative conditions.

http://www.bseinquiry.gov.uk/files/ws/s063.pdf


Mouse model sheds new light on human prion disease

snip...

Professor John Collinge said “We are not saying that all or even most cases
of sporadic CJD are as a result of BSE exposure, but some more recent cases
may be – the incidence of sporadic CJD has shown an upward trend in the UK
over the last decade. While most of this apparent increase may be because
doctors are now more aware of CJD and better at diagnosing it, serious
consideration should be given to a proportion of this rise being
BSE-related. Switzerland, which has had a substantial BSE epidemic, has
noted a sharp recent increase in sporadic CJD.

snip...

http://www.mrc.ac.uk/txt/index/public-interest/public-news-4/public-news_archive/public-news-archive_nov_dec_02/public-bse_and_sporadic_cjd.htm

Published Online November 11, 2004
Science DOI: 10.1126/science.1103932
Science Express Index

Reports
Submitted on August 11, 2004
Accepted on October 22, 2004

Human Prion Protein with Valine 129 Prevents Expression of Variant CJD Phenotype
Jonathan D. F. Wadsworth 1, Emmanuel A. Asante 1, Melanie Desbruslais 1, Jacqueline M. Linehan 1, Susan Joiner 1, Ian Gowland 1, Julie Welch 1, Lisa Stone 1, Sarah E. Lloyd 1, Andrew F. Hill 1, Sebastian Brandner 1, John Collinge 1*
1 Medical Research Council (MRC) Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.


* To whom correspondence should be addressed.
John Collinge , E-mail: j.collinge@prion.ucl.ac.uk

Present address: Department of Biochemistry and Molecular Biology and Department of Pathology, University of Melbourne, Parkville, Victoria 3010, Australia.

Variant Creutzfeldt-Jakob disease (vCJD) is a unique and highly distinctive clinicopathological and molecular phenotype of human prion disease associated with infection with bovine spongiform encephalopathy (BSE)-like prions. Here, we found that generation of this phenotype in transgenic mice required expression of human prion protein (PrP) with methionine 129. Expression of human PrP with valine 129 resulted in a distinct phenotype and, remarkably, persistence of a barrier to transmission of BSE-derived prions on subpassage. Polymorphic residue 129 of human PrP dictated propagation of distinct prion strains after BSE prion infection. Thus, primary and secondary human infection with BSE-derived prions may result in sporadic CJD-like or novel phenotypes in addition to vCJD, depending on the genotype of the prion source and the recipient.

snip...


While caution must be exercised extrapolating from
animal models, even where, as here, faithful recapitulation of
molecular and pathological phenotypes is possible, our
findings argue that primary human BSE prion infection, and
secondary infection with vCJD prions by iatrogenic routes,
may not be restricted to a single disease phenotype. These
data, together with the recent recognition of probable
iatrogenic transmission of vCJD prions to recipients of blood
(21, 22), including a PRNP codon 129 MV heterozygote
individual (22), reiterate the need to stratify all human prion
disease patients by PrPSc type. This surveillance will facilitate
rapid recognition of novel PrPSc types and any change in
relative frequencies of particular PrPSc sub-types in relation to
either BSE exposure patterns or iatrogenic sources of vCJD
prions.
References and Notes

--------------------------------------------------------------------------------

http://www.sciencemag.org/cgi/content/abstract/1103932v1


-------- Original Message --------


Subject: re-BSE prions propagate as either variant CJD-like or sporadic CJD

Date: Thu, 28 Nov 2002 10:23:43

-0000 From: "Asante, Emmanuel A"


To: "'flounder@wt.net'"

Dear Terry,

I have been asked by Professor Collinge to respond to your request. I am

a Senior Scientist in the MRC Prion Unit and the lead author on the

paper. I have attached a pdf copy of the paper for your attention. Thank

you for your interest in the paper.

In respect of your first question, the simple answer is, yes. As you

will find in the paper, we have managed to associate the alternate

phenotype to type 2 PrPSc, the commonest sporadic CJD.

It is too early to be able to claim any further sub-classification in

respect of Heidenhain variant CJD or Vicky Rimmer's version. It will

take further studies, which are on-going, to establish if there are

sub-types to our initial finding which we are now reporting. The main

point of the paper is that, as well as leading to the expected new

variant CJD phenotype, BSE transmission to the 129-methionine genotype

can lead to an alternate phenotype which is indistinguishable from type

2 PrPSc.

I hope reading the paper will enlighten you more on the subject. If I

can be of any further assistance please to not hesitate to ask. Best wishes.

Emmanuel Asante

<>


____________________________________

Dr. Emmanuel A Asante MRC Prion Unit & Neurogenetics Dept. Imperial

College School of Medicine (St. Mary's) Norfolk Place, LONDON W2 1PG

Tel: +44 (0)20 7594 3794 Fax: +44 (0)20 7706 3272 email:

e.asante@ic.ac.uk (until 9/12/02)

New e-mail: e.asante@prion.ucl.ac.uk (active from now)

____________________________________

Asante/Collinge et al, 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;

http://www.fda.gov/ohrms/dockets/ac/03/slides/3923s1_OPH.htm


ALSO, Dr. Maddox et al states;

make routine mortality surveillance a useful surrogate for ongoing CJD surveillance...

THIS has proven not very useful in the U.K.;


THE EPIDEMIOLOGY OF CJD RG WILL 1984 (182 PAGES)

snip...

One reason for this was the _inaccuracy_ in coding of cases correctly
certified as CJD Coding is carried out by staff who are not medically
qualified and it is not surprising that coding errors occur in the
processing of large numbers of certificates. In 1982, 12,000 certificates
per week were processed at the office of population censuses and surveys bu
15 coders and 6 checkers (Alderson et al., 1983). The occurrence of both
inter- and intra-observer coding errors has been described (Curb et al.,
1983) and the _inaccuracies_ of BOTH certification and coding discovered in
this study _support_ the introduction of a more accurate system of death
certificates and a more detailed and specific coding system...

snip...

http://www.bseinquiry.gov.uk/files/mb/m26/tab01.pdf


AS implied in the Inset 25 we must not _ASSUME_ that transmission of BSE to
other species will invariably present pathology typical of a scrapie-like
disease.

snip...

http://www.bseinquiry.gov.uk/files/yb/1991/01/04004001.pdf


DR. Maddox et al states here;

In collaboration with appropriate local and state health departments and the
National Prion Disease Pathology Surveillance Center, CDC is facilitating or
conducting such surveillance and case- investigations, including related
laboratory studies to characterize CJD and CWD prions. ...


HOWEVER in a recent article in the UPI out of Washington;

CJD screening may miss thousands of cases

By Steve Mitchell UPI Medical Correspondent Published 7/21/2003 3:00 PM

snip...

In addition, the NPDPSC sees less than half of all the CJD cases each year,
so the CDC's investigational system not only is missing many of the
misdiagnosed CJD cases, it also is not conducting autopsies on most of the
detected cases.

snip...


http://www.upi.com/NewsTrack/Science/2003/12/29/mad_cow_linked_to_thousands_of_cjd_cases/4786/


ALSO in Philip Yams book 'The Pathological Protein';

''Answering critics like Terry Singeltary, who feels that the US undercounts
CJD, Schonberger _conceded_ that the current surveillance system has errors
but stated that most of the errors will be confined to the older
population''....

http://www.thepathologicalprotein.com/


THERE has been a _documented_ case of nv/v CJD in a 74 year old, so the
errors Schonberger speaks of (above) would be of significant importance, if
one believes in the nv/v CJD 'only' theory.

NOW we have _documented_ cases of very young CJD victims in the USA
continuing to appear in several different states.

HOW does Dr. Maddox explain this, and does he still believe that a National
CJD surveillance program with a CJD questionnaire to every victims family is
still not warranted?

WITH CWD and Scrapie running rampant in the USA, with BSE now _documented_
in North America, with the feeding of ruminant-to-ruminant animal protein
still happening in the USA in 2003 even though there has been a partial
voluntary ban on ruminant feeding since 8/4/97, with only 48,000 BSE/TSE
tests done on USA cattle in some 14 years of surveillance, when in any given
year there are 100 million cattle in the USA, with all this, i think
refusing to make CJD/TSEs reportable Nationally in the USA is not ONLY a
grave mistake, but in my opinion, should be looked at with great
suspicion...

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


Draft Proposal For The Monitoring of Creutzfeldt-Kakob Disease 1989 Dr. R. Will


snip...

IDENTIFICATION OF CASES

Cases of CJD may be identified from death certificates, but this alone is
unlikely to provide adequate monitoring. ERRORS are made in certification
and diagnosis; in the Oxford study death certificates were obtained on a
series of known confirmed cases and CJD was mentioned in only 66% of
certificates. In another series of 175 certified cases, 42 patients were
judged not to have suffered from CJD after examination of case notes (7)...

full text;

http://www.bseinquiry.gov.uk/files/yb/1989/05/00005001.pdf


THE EPIDEMIOLOGY OF CJD RG WILL 1984 (182 PAGES)

snip...

One reason for this was the _inaccuracy_ in coding of cases correctly
certified as CJD Coding is carried out by staff who are not medically
qualified and it is not surprising that coding errors occur in the
processing of large numbers of certificates. In 1982, 12,000 certificates
per week were processed at the office of population censuses and surveys bu
15 coders and 6 checkers (Alderson et al., 1983). The occurrence of both
inter- and intra-observer coding errors has been described (Curb et al.,
1983) and the _inaccuracies_ of BOTH certification and coding discovered in
this study _support_ the introduction of a more accurate system of death
certificates and a more detailed and specific coding system...

snip...

http://www.bseinquiry.gov.uk/files/mb/m26/tab01.pdf


IN your reply to me on 26 March 2003, Dr. Maddox, Belay, Schonberger et al
write;

[2] but only limited data seeking such evidence exist. Overall, the
previously published case-control studies that have evaluated environmental
sources of infection for sporadic CJD have not consistently identified
strong evidence for a common risk factor.

I kindly wish to submit the following to dispute this;

11 November 2004

Genetic make-up may determine what type of CJD occurs when humans are
infected with BSE

New research published by a team from the Medical Research Council (MRC)
Prion Unit offers an explanation about why only people with a particular
genetic make-up have so far developed vCJD. It also provides evidence that
other types of BSE-derived prion infection with a different pattern of
symptoms might occur in humans. The findings are published in the journal
Science.

Variant CJD (vCJD) is the human disease thought to be caused by eating food
contaminated with the infectious agent, known as a prion, responsible for
the epidemic of BSE or “mad cow disease” in cattle. So far, everyone known
to have developed vCJD has been of a particular genetic type – known as MM.
Until now it has been a mystery why everyone that has developed vCJD is of
the MM type and one possibility is that they are simply the first to develop
the disease when infected with BSE, and that people with the other genetic
types1 (known as VV and MV*) infected with BSE prions will also develop
vCJD, but some years later.

In a series of experiments spanning more than ten years, the MRC team has
been studying mice genetically modified so that they make human prion
proteins – which are used to model human susceptibility to BSE. The team has
now shown that mice with the human VV genetic type do become infected when
given BSE or vCJD prions, but manifest a different form of the disease which
looks quite different to vCJD and has a novel prion “strain” type.

Remarkably, when these novel prions were used to infect mice of the MM
genetic type, the mice either developed a disease very like vCJD, or else a
pattern of disease that looks like so-called sporadic CJD – the “classical”
form of CJD. This form has been known about for many years, is seen all over
the world and has not hitherto been associated with BSE. However, the new
strain identified in the mice, being called ‘type 5’, has not been seen yet
in people and we do not know what pattern of disease it would cause. It
could look like one of the forms of classical or sporadic CJD or perhaps be
yet another different “variant” form.

The work from the MRC team suggests that type 4 prions, the type associated
with vCJD, can only propagate themselves in people that make the M form of
the protein. It seems the V form of the protein just cannot adopt the
particular molecular shape that characterises type 4.

The studies in mice also suggest that if these prions were to pass from
person to person (for example by blood transfusion) then, depending on the
genetic type of the person becoming infected, at least three different
patterns of disease might result: type 2 (which is seen in sporadic CJD);
type 4 (which causes vCJD) or type 5 (which may cause a new pattern of
disease).

Professor John Collinge, Director of the MRC Prion Unit, which is based at
University College London, said: “These mouse studies give us vital clues
about the behaviour of prions and how they appear to modify and adapt
depending on the genetic makeup of the individual they are infecting.

“We always have to be cautious about making direct comparison to the human
condition, but our work strongly suggests that we can not assume only those
with one genetic profile are vulnerable to BSE infection.

“At this stage it is not possible to say how this should alter estimates of
those likely to become ill, but our findings do suggest we should be taking
steps to draw up a more sophisticated system of categorizing the disease so
that we don’t mistake BSE related infection for a version of sporadic CJD.”

For more information call the MRC press office on 020 7 637 6011

Notes to Editors

*The human prion protein comes in two common forms, known as M and V.
Because everyone has two copies of this gene, there are three possible
genetic types: MM, MV and VV.

Paper - Human Prion protein v129 prevent expression of vCJD phenotype –
Science On line 11.11.04

Prions are rogue forms of one of the body’s own proteins – known as the
prion protein – which are misshapen. There are several different rogue or
misshapen forms that can infect humans, and these different types of prions
are known as “strains”. This is analogous to different strains of other
germs such ‘flu virus causing influenza or strains of salmonella causing
different forms of food poisoning for example.

The strain of prion causing vCJD is known as type 4, types 1-3 cause the
different forms of sporadic or classical CJD. Each strain causes a different
pattern or type of disease. It is known that prion strains can change or
“mutate” when they pass between different animals.

The Medical Research Council (MRC) is a national organisation funded by the
UK tax-payer. Its business is medical research aimed at improving human
health; everyone stands to benefit from the outputs. The research it
supports and the scientists it trains meet the needs of the health services,
the pharmaceutical and other health-related industries and the academic
world. MRC has funded work which has led to some of the most significant
discoveries and achievements in medicine in the UK. About half of the MRC’s
expenditure of £430 million is invested in its 40 Institutes, Units and
Centres. The remaining half goes in the form of grant support and training
awards to individuals and teams in universities and medical schools.

©2004 Medical Research Council http://www.mrc.ac.uk/public-11_november_2004

THE new findings of BASE in cattle in Italy of Identification of a second
bovine amyloidotic spongiform encephalopathy: Molecular similarities with
sporadic Creutzfeldt-Jakob disease

http://www.pnas.org/cgi/content/abstract/0305777101v1


Adaptation of the bovine spongiform encephalopathy agent to primates

and comparison with Creutzfeldt- Jakob disease: Implications for

human health

THE findings from Corinne Ida Lasmézas*, [dagger] , Jean-Guy Fournier*,
Virginie Nouvel*,

Hermann Boe*, Domíníque Marcé*, François Lamoury*, Nicolas Kopp [Dagger

] , Jean-Jacques Hauw§, James Ironside¶, Moira Bruce [||] , Dominique

Dormont*, and Jean-Philippe Deslys* et al, that The agent responsible for
French iatrogenic growth hormone-linked CJD taken as a control is very
different from vCJD but is similar to that found in one case of sporadic CJD
and one sheep scrapie isolate;

http://www.pnas.org/cgi/content/full/041490898v1


Characterization of two distinct prion strains derived from bovine
spongiform encephalopathy transmissions to inbred mice

Sarah E. Lloyd, Jacqueline M. Linehan, Melanie Desbruslais, Susan Joiner,
Jennifer Buckell, Sebastian Brandner, Jonathan D. F. Wadsworth and John
Collinge

Correspondence John Collinge j.collinge@prion.ucl.ac.uk

MRC Prion Unit and Department of Neurodegenerative Disease, Institute of
Neurology, University College, London WC1N 3BG, UK Received 9 December 2003
Accepted 27 April 2004

Distinct prion strains can be distinguished by differences in incubation
period, neuropathology and biochemical properties of disease-associated
prion protein (PrPSc) in inoculated mice. Reliable comparisons of mouse
prion strain properties can only be achieved after passage in genetically
identical mice, as host prion protein sequence and genetic background are
known to modulate prion disease phenotypes. While multiple prion strains
have been identified in sheep scrapie and CreutzfeldtJakob disease, bovine
spongiform encephalopathy (BSE) is thought to be caused by a single prion
strain. Primary passage of BSE prions to different lines of inbred mice
resulted in the propagation of two distinct PrPSc types, suggesting that two
prion strains may have been isolated. To investigate this further, these
isolates were subpassaged in a single line of inbred mice (SJL) and it was
confirmed that two distinct prion strains had been identified. MRC1 was
characterized by a short incubation time (110±3 days), a
mono-glycosylated-dominant PrPSc type and a generalized diffuse pattern of
PrP-immunoreactive deposits, while MRC2 displayed a much longer incubation
time (155±1 days), a di-glycosylated-dominant PrPSc type and a distinct
pattern of PrP- immunoreactive deposits and neuronal loss. These data
indicate a crucial involvement of the host genome in modulating prion strain
selection and propagation in mice. It is possible that multiple disease
phenotypes may also be possible in BSE prion infection in humans and other
animals.

http://vir.sgmjournals.org/cgi/content/abstract/85/8/2471


THE recent discoveries of previously unidentified strains of Scrapie such as
221C44 and the Nor9845;

FULL TEXT APPRX. 91 PAGES

UK Strategy for Research and Development on Human and Animal Health Aspects
of Transmissible Spongiform Encephalopathies

2004-2007

http://www.mrc.ac.uk/pdf-uk_strategy_v5.2.pdf


IP/04/1324

Brussels, 28 October 2004

Commission submits French Research Findings on TSE in a goat to Expert

Panel

Following the findings by a research group in France that they suspect the
presence of a TSE infection in a goats brain which tests cannot distinguish
from BSE, the European Commission has submitted data received from the
French authorities to the Community Reference Laboratory (CRL) for TSEs
based in Weybridge, England, for an evaluation by an expert panel. TSEs are
transmissible spongiform encephalopathies, namely BSE affecting cattle, and
scrapie affecting goats and sheep. The expert panel will evaluate, over the
next two weeks or so, the scientific evidence to see if it indicates the
presence of BSE in the goat. This isolated incident does not present a risk
to public health as the goat and its herd did not enter the food and feed
chain.

snip...

http://europa.eu.int/rapid/pressReleasesAction.do?reference=IP/04/1324&format=HTML&aged=0&language=EN&guiLanguage=en


According to Nov. 2 Yomiuri Newspaper, researchers of the Prion Disease
Research Center, the National Institute of Animal Health of Japan reported
in the International Symposium of Prion Diseases held in Sendai from October
31 to November 2., 2004, that they detected prion in the adrenal gland and
peripheral (sciatic and peroneal) nerves of the 11th BSE case of Japan (a
94-months old cow found dead on the farm on March 4 this year).

http://www.maff.go.jp/www/press/cont2/20041101press_7.htm (only in Japanese)


Sendai and the International Symposium of Prion Diseases held here from
October 31 to November 2.,2004

Abstract

ORAL 8

Bovine spongiform encephalopathy (BSE) in Japan

Takashi Yokoyama, Kumiko M. Kimura, Morikazu Shinagawa Prion Disease
Research Center, National Institute of Animal Health, Japan

Bovine spongiform encephalopathy (BSE) has become an important problem not
only for animal industry, but also for public health. In Japan, BSE was
first recognized in September 2001 by fallen stock surveillance. Since
October 2001, BSE examination for all cattle slaughtered at abattoirs has
started. In April 2004, all dead cattle examination (over 24 months) has
been conducted at livestock hygiene service center. Samples positive in
enzyme linked immunosorbent assay (ELISA) are further subjected to western
blot (WB) and immunohistochemistry (IHC). Thirteen BSE cases have been
reported by September 2004. Twelve cases were classified as typical BSE, and
the remained one was an atypical BSE. Variant forms of BSE with atypical
histopathological and/or biochemical phenotype were reported in Italy and
France. Further study is required for BSE prion characteristics. To
characterize BSE prion properties, brain homogenates of Japanese BSE cases
were intracerebrally inoculated into wild-type mice. The first case
(BSE/Chiba) was successfully transmitted to rodents. The mean incubation
periods (409.0 days) in this experiment was preferably longer than that of
previously reported. PrPSc distribution, prion titer, mice susceptibility
and/or storage condition of sample might be influenced the result. Recently,
we introduced transgenic mice that overexpress a bovine PrP gene to overcome
the species barrier problem. These mice are expected to accelerate the
transmission experiment of BSE prion. Transmission of atypical BSE case is
undergoing by using these transgenic mice.

http://www.knt.co.jp/ec/2004/prion/E2.htm


Docket No. 2003N-0312 Animal Feed Safety System [TSS SUBMISSION]

From: Terry S. Singeltary Sr. [flounder@wt.net] Sent: Tuesday, July 29, 2003
1:03 PM To: fdadockets@oc.fda.gov Cc: ggraber@cvm.fda.gov;
Linda.Grassie@fda.gov; BSE-L Subject: Docket No. 2003N-0312 Animal Feed
Safety System [TSS SUBMISSION TO DOCKET 2003N-0312]

snip...

Greetings FDA,

PLUS, if the USA continues to flagrantly ignore the _documented_ science to
date about the known TSEs in the USA (let alone the undocumented TSEs in
cattle), it is my opinion, every other Country that is dealing with BSE/TSE
should boycott the USA and demand that the SSC reclassify the USA BSE GBR II
risk assessment to BSE/TSE GBR III 'IMMEDIATELY'. for the SSC to _flounder_
any longer on this issue, should also be regarded with great suspicion as
well. NOT to leave out the OIE and it's terribly flawed system of disease
surveillance. the OIE should make a move on CWD in the USA, and make a risk
assessment on this as a threat to human health...

snip...full text;

http://www.fda.gov/ohrms/dockets/dockets/03n0312/03N-0312_emc-000001.txt


EFSA Scientific Report on the Assessment of the Geographical BSE-Risk (GBR)
of the United States of America (USA) Publication date: 20 August 2004

Adopted July 2004 (Question N° EFSA-Q-2003-083)

* 167 kB Report

* 105 kB Summary

Summary of the Scientific Report

The European Food Safety Authority and its Scientific Expert Working Group
on the Assessment of the Geographical Bovine Spongiform Encephalopathy (BSE)
Risk (GBR) were asked by the European Commission (EC) to provide an
up-to-date scientific report on the GBR in the United States of America,
i.e. the likelihood of the presence of one or more cattle being infected
with BSE, pre-clinically as well as clinically, in USA. This scientific
report addresses the GBR of USA as assessed in 2004 based on data covering
the period 1980-2003.

The BSE agent was probably imported into USA and could have reached domestic
cattle in the middle of the eighties. These cattle imported in the mid
eighties could have been rendered in the late eighties and therefore led to
an internal challenge in the early nineties. It is possible that imported
meat and bone meal (MBM) into the USA reached domestic cattle and leads to
an internal challenge in the early nineties.

A processing risk developed in the late 80s/early 90s when cattle imports
from BSE risk countries were slaughtered or died and were processed (partly)
into feed, together with some imports of MBM. This risk continued to exist,
and grew significantly in the mid 90’s when domestic cattle, infected by
imported MBM, reached processing. Given the low stability of the system, the
risk increased over the years with continued imports of cattle and MBM from
BSE risk countries.

EFSA concludes that the current GBR level of USA is III, i.e. it is likely
but not confirmed that domestic cattle are (clinically or pre- clinically)
infected with the BSE-agent. As long as there are no significant changes in
rendering or feeding, the stability remains extremely/very unstable. Thus,
the probability of cattle to be (pre- clinically or clinically) infected
with the BSE-agent persistently increases.
http://www.efsa.eu.int/science/efsa_scientific_reports/gbr_assessments/573_en.html


IN your reply to me on 26 March 2003, Dr. Maddox, Belay, Schonberger et al
write;

If BSE causes a sporadic CJD-like illness in humans, an increase in sporadic
CJD cases would be expected to first occur in the United Kingdom, where the
vast majority of vCJD cases have been reported. In the United Kingdom during
1997 through 2002, however, the overall average annual mortality rate for
sporadic CJD was not elevated; it was about 1 case per million population
per year. In addition, during this most recent 6-year period following the
first published description of vCJD in 1996, there was no increasing trend
in the reported annual number of UK sporadic CJD deaths.[3, 5] Furthermore,
surveillance in the UK has shown no increase in the proportion of sporadic
CJD cases that are homozygous for methionine (Will RG, National CJD
Surveillance Unit, United Kingdom, 2003; personal communication).

I kindly wish to submit the following to dispute this;

Mouse model sheds new light on human prion disease

snip...

Professor John Collinge said We are not saying that all or even most cases
of sporadic CJD are as a result of BSE exposure, but some more recent cases
may be  the incidence of sporadic CJD has shown an upward trend in the UK
over the last decade. While most of this apparent increase may be because
doctors are now more aware of CJD and better at diagnosing it, serious
consideration should be given to a proportion of this rise being
BSE-related. Switzerland, which has had a substantial BSE epidemic, has
noted a sharp recent increase in sporadic CJD.

snip...

http://www.mrc.ac.uk/index/public-interest/public-bse_and_sporadic_cjd.htm


http://www.mrc.ac.uk/txt/index/public-interest/public-news-4/public-news_archive/public-news-archive_nov_dec_02/public-bse_and_sporadic_cjd.htm

A simple look at sporadic CJD statistics in EU countries with BSE will
reveal this;


CANADA 2 IN 94 COMPARED TO 30 IN 2002

FRANCE 35 IN 93 COMPARED TO 102 IN 2003

GERMANY 21 IN 93 COMPARED TO 112 IN 2003

ITALY 27 IN 93 TO COMPARED TO 75 IN 2003

UK 37 IN 93 COMPARED TO 74 IN 2003

USA (UNKNOWN...TSS)

http://www.eurocjd.ed.ac.uk/sporadic.htm


EVEN SEAC admits a rise in sporadic CJD in UK;

SPONGIFORM ENCEPHALOPATHY ADVISORY COMMITTEE Draft minutes of the open
session of the 84th meeting held on 28th September 2004

snip...

In contrast, the number of deaths in the UK from sCJD per annum had
increased but this may reflect improved case ascertainment. A similar
increase in sCJD had been observed in other countries... snip..

HOWEVER, I do not agree with this _assumption_!

I believe there are multiple routes and sources for this agent and they are
going ignored, while being called 'sporadic' and or 'spontaneous' or
'classic' CJD.

TO continue to ignore Professor Collinge/Asanta et al's advice;

“We always have to be cautious about making direct comparison to the human
condition, but our work strongly suggests that we can not assume only those
with one genetic profile are vulnerable to BSE infection.

“At this stage it is not possible to say how this should alter estimates of
those likely to become ill, but our findings do suggest we should be taking
steps to draw up a more sophisticated system of categorizing the disease so
that we don’t mistake BSE related infection for a version of sporadic CJD.”

TO continue to ingore this and the other evidence that is and has been
mounting about sporadic CJD not being as sporadic and or spontaneos as once
thought, to continue this ignorance and blantantly let this agent continue
to spread via the proven routes to date and continue to infect and kill,
should warrant a TSE Inquiry in the USA by a Congressional Investigation
followed by International Council of some kind. WE are not only infecting US
citizens by this ignorance, but also the International community that visits
our Country. With the recent findings of nv/v CJD transmitting via blood, we
must not flounder any longer;

Summary of SEACs discussion on the second presumed case of blood
transfusion-associated infection with vCJD

7. SEAC agreed that the western blot results and glycotype profile suggested
it was unlikely that the infection was preclinical sporadic CJD (sCJD). The
committee noted that a single study by Glatzel et al (2003) had reported
PrPres in the spleen of sCJD clinical cases. However, the levels of PrPres
present in sCJD cases were low and detected in patients with a lengthy
clinical illness from sporadic CJD.

http://www.seac.gov.uk/statements/state070804.htm


vCJD: Blood Transfusion Incident

http://www.publications.parliament.uk/pa/ld199697/ldhansrd/pdvn/lds03/text/31217-09.htm


CJD (all human TSEs) should be made reportable Nationally and
Internationally immediately, with a follow up investigation and
questionnaire of each victim (family) asking questions pertaining to route
and source of agent. ALL ages must be included in this. Anything less will
only allow the agent to continue to spread and kill...

Thank You,

with kindest regards, I am sincerely,

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


http://www.neurology.org/cgi/eletter-submit

http://www.neurology.org/cgi/eletters/60/2/176#535


2007

USA MAD COW STRAIN MORE VIRULENT TO HUMANS THAN UK STRAIN

18 January 2007 - Draft minutes of the SEAC 95 meeting (426 KB) held on 7
December 2006 are now available.


snip...

64. A member noted that at the recent Neuroprion meeting, a study was
presented showing that in transgenic mice BSE passaged in sheep may be more
virulent and infectious to a wider range of species than bovine derived BSE.

Other work presented suggested that BSE and bovine amyloidotic spongiform
encephalopathy (BASE) MAY BE RELATED. A mutation had been identified in the
prion protein gene in an AMERICAN BASE CASE THAT WAS SIMILAR IN NATURE TO A
MUTATION FOUND IN CASES OF SPORADIC CJD.


snip...

http://www.seac.gov.uk/minutes/95.pdf


3:30 Transmission of the Italian Atypical BSE (BASE) in Humanized Mouse

Models Qingzhong Kong, Ph.D., Assistant Professor, Pathology, Case Western Reserve
University

Bovine Amyloid Spongiform Encephalopathy (BASE) is an atypical BSE strain
discovered recently in Italy, and similar or different atypical BSE cases
were also reported in other countries. The infectivity and phenotypes of
these atypical BSE strains in humans are unknown. In collaboration with
Pierluigi Gambetti, as well as Maria Caramelli and her co-workers, we have
inoculated transgenic mice expressing human prion protein with brain
homogenates from BASE or BSE infected cattle. Our data shows that about half
of the BASE-inoculated mice became infected with an average incubation time
of about 19 months; in contrast, none of the BSE-inoculated mice appear to
be infected after more than 2 years.

***These results indicate that BASE is transmissible to humans and suggest that BASE is more virulent than
classical BSE in humans.***


6:30 Close of Day One


http://www.healthtech.com/2007/tse/day1.asp


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

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

Singeltary, Sr et al. JAMA.2001; 285: 733-734.

http://jama.ama-assn.org/http://www.neurology.org/cgi/eletters/60/2/176#535

BRITISH MEDICAL JOURNAL

BMJ

http://www.bmj.com/cgi/eletters/319/7220/1312/b#5406


BMJ

http://www.bmj.com/cgi/eletters/320/7226/8/b#6117


JOURNAL OF NEUROLOGY

MARCH 26, 2003

RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob

disease in the United States

Email Terry S. Singeltary:

flounder@wt.net

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?

http://www.neurology.org/cgi/eletters/60/2/176#535


doi:10.1016/S1473-3099(03)00715-1
Copyright © 2003 Published by Elsevier Ltd.
Newsdesk

Tracking spongiform encephalopathies in North America

Xavier Bosch

Available online 29 July 2003.


Volume 3, Issue 8, August 2003, Page 463


“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.”

............................


http://www.thelancet.com/journals/laninf/article/PIIS1473309903007151/fulltext

http://download.thelancet.com/pdfs/journals/1473-3099/PIIS1473309903007151.pdf

TSS



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