Presence of subclinical infection in gene-targeted human prion protein
transgenic mice exposed to atypical BSE
Rona Wilson1, Karen Dobie1, Nora Hunter1, Cristina Casalone2, Thierry
Baron3 and Rona Barron1,4 + Author Affiliations
1 The Roslin Institute and Royal (Dick) School of Veterinary Studies,
University of Edinburgh; 2 Istituto Zooprofilattico Sperimentale del Piemonte,
Liguria e Valle d’Aosta, Turin, Italy; 3 Agence Nationale de Sécurité Sanitaire,
Lyon, France ↵4 E-mail: rona.barron@roslin.ed.ac.uk Received 26 February 2013.
Accepted 17 September 2013.
Abstract
The transmission of bovine spongiform encephalopathy (BSE) to humans,
leading to variant Creutzfeldt-Jakob disease (vCJD) has demonstrated that cattle
transmissible spongiform encephalopathies (TSEs) can pose a risk to human
health. Until recently, TSE disease in cattle was thought to be caused by a
single agent strain, BSE, also known as classical BSE, or BSE-C. However, due to
the initiation of a large scale surveillance programme throughout Europe, two
atypical BSE strains, bovine amyloidotic spongiform encephalopathy (BASE, also
named BSE-L) and BSE-H have since been discovered. To model the risk to human
health, we previously inoculated these two forms of atypical BSE (BASE and
BSE-H) into gene-targeted transgenic (Tg) mice expressing the human prion
protein (PrP) (HuTg) but were unable to detect any signs of TSE pathology in
these mice. However, despite the absence of TSE pathology, upon subpassage of
some BASE challenged HuTg mice, a TSE was observed in recipient gene-targeted
bovine PrP Tg (Bov6) mice, but not in HuTg mice. Disease transmission from
apparently healthy individuals indicates the presence of subclinical BASE
infection in mice expressing human PrP that cannot be identified by current
diagnostic methods. However, due to the lack of transmission to HuTg mice on
subpassage, the efficiency of mouse to mouse transmission of BASE appears to be
low when mice express human rather than bovine PrP.
Atypical BSE Human transgenic Prion Subclinical infection
sub-clinical CWD !
LET'S take a closer look at this new prionpathy or prionopathy, and then
let's look at the g-h-BSEalabama mad cow. This new prionopathy in humans? the
genetic makeup is IDENTICAL to the g-h-BSEalabama mad cow, the only _documented_
mad cow in the world to date like this, ......wait, it get's better. this new
prionpathy is killing young and old humans, with LONG DURATION from onset of
symptoms to death, and the symptoms are very similar to nvCJD victims, OH, and
the plaques are very similar in some cases too, bbbut, it's not related to the
g-h-BSEalabama cow, WAIT NOW, it gets even better, the new human prionpathy that
they claim is a genetic TSE, has no relation to any gene mutation in that
family. daaa, ya think it could be related to that mad cow with the same genetic
make-up ??? there were literally tons and tons of banned mad cow protein in
Alabama in commerce, and none of it transmitted to cows, and the cows to humans
there from ??? r i g h t $$$ ALABAMA MAD COW g-h-BSEalabama In this study, we
identified a novel mutation in the bovine prion protein gene (Prnp), called
E211K, of a confirmed BSE positive cow from Alabama, United States of America.
This mutation is identical to the E200K pathogenic mutation found in humans with
a genetic form of CJD. This finding represents the first report of a confirmed
case of BSE with a potential pathogenic mutation within the bovine Prnp gene. We
hypothesize that the bovine Prnp E211K mutation most likely has caused BSE in
"the approximately 10-year-old cow" carrying the E221K mutation.
Saturday, August 14, 2010
BSE Case Associated with Prion Protein Gene Mutation (g-h-BSEalabama) and
VPSPr PRIONPATHY
(see mad cow feed in COMMERCE IN ALABAMA...TSS)
***It also suggests a similar cause or source for atypical BSE in these
countries.
P.9.21
Molecular characterization of BSE in Canada
Jianmin Yang1, Sandor Dudas2, Catherine Graham2, Markus Czub3, Tim
McAllister1, Stefanie Czub1 1Agriculture and Agri-Food Canada Research Centre,
Canada; 2National and OIE BSE Reference Laboratory, Canada; 3University of
Calgary, Canada
Background: Three BSE types (classical and two atypical) have been
identified on the basis of molecular characteristics of the misfolded protein
associated with the disease. To date, each of these three types have been
detected in Canadian cattle.
Objectives: This study was conducted to further characterize the 16
Canadian BSE cases based on the biochemical properties of there associated
PrPres. Methods: Immuno-reactivity, molecular weight, glycoform profiles and
relative proteinase K sensitivity of the PrPres from each of the 16 confirmed
Canadian BSE cases was determined using modified Western blot analysis.
Results: Fourteen of the 16 Canadian BSE cases were C type, 1 was H type
and 1 was L type. The Canadian H and L-type BSE cases exhibited size shifts and
changes in glycosylation similar to other atypical BSE cases. PK digestion under
mild and stringent conditions revealed a reduced protease resistance of the
atypical cases compared to the C-type cases. N terminal- specific antibodies
bound to PrPres from H type but not from C or L type. The C-terminal-specific
antibodies resulted in a shift in the glycoform profile and detected a fourth
band in the Canadian H-type BSE.
Discussion: The C, L and H type BSE cases in Canada exhibit molecular
characteristics similar to those described for classical and atypical BSE cases
from Europe and Japan. This supports the theory that the importation of BSE
contaminated feedstuff is the source of C-type BSE in Canada. ***It also
suggests a similar cause or source for atypical BSE in these countries.
Saturday, August 4, 2012
*** Final Feed Investigation Summary - California BSE Case - July 2012
What irks many scientists is the USDA’s April 25 statement that the rare
disease is “not generally associated with an animal consuming infected feed.”
The USDA’s conclusion is a “gross oversimplification,” said Dr. Paul Brown,
one of the world’s experts on this type of disease who retired recently from the
National Institutes of Health.
"(The agency) has no foundation on which to base that statement.”
“We can’t say it’s not feed related,” agreed Dr. Linda Detwiler, an
official with the USDA during the Clinton Administration now at Mississippi
State.
In the May 1 email to me, USDA’s Cole backed off a bit. “No one knows the
origins of atypical cases of BSE,” she said
Saturday, May 26, 2012
Are USDA assurances on mad cow case 'gross oversimplification'?
snip...see full text ;
Monday, September 02, 2013
Atypical BSE: role of the E211K prion polymorphism
Research Project: TRANSMISSION, DIFFERENTIATION, AND PATHOBIOLOGY OF
TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES
Location: Virus and Prion Research Unit
Sunday, September 1, 2013
Evaluation of the Zoonotic Potential of Transmissible Mink Encephalopathy
We previously described the biochemical similarities between PrPres derived
from L-BSE infected macaque and cortical MM2 sporadic CJD: those observations
suggest a link between these two uncommon prion phenotypes in a primate model
(it is to note that such a link has not been observed in other models less
relevant from the human situation as hamsters or transgenic mice overexpressing
ovine PrP [28]). We speculate that a group of related animal prion strains
(L-BSE, c-BSE and TME) would have a zoonotic potential and lead to prion
diseases in humans with a type 2 PrPres molecular signature (and more
specifically type 2B for vCJD)
snip...
Together with previous experiments performed in ovinized and bovinized
transgenic mice and hamsters [8,9] indicating similarities between TME and
L-BSE, the data support the hypothesis that L-BSE could be the origin of the TME
outbreaks in North America and Europe during the mid-1900s.
Sunday, July 21, 2013
Welsh Government and Food Standards Agency Wales Joint Public Consultation
on the Proposed Transmissible Spongiform Encephalopathies (Wales) Regulations
2013 Singeltary Submission WG18417
Saturday, September 21, 2013
Westland/Hallmark: 2008 Beef Recall A Case Study by The Food Industry
Center January 2010 THE FLIM-FLAM REPORT
Tuesday, September 17, 2013
USAHA 116TH ANNUAL MEETING October 18 – 24, 2012 CWD, Scrapie, BSE, TSE
prion (September 17, 2013)
Wednesday, September 25, 2013
Inspections, Compliance, Enforcement, and Criminal Investigations BSE TSE
PRION 2013
P.4.23
Transmission of atypical BSE in humanized mouse models
Liuting Qing1, Wenquan Zou1, Cristina Casalone2, Martin Groschup3, Miroslaw
Polak4, Maria Caramelli2, Pierluigi Gambetti1, Juergen Richt5, Qingzhong Kong1
1Case Western Reserve University, USA; 2Instituto Zooprofilattico Sperimentale,
Italy; 3Friedrich-Loeffler-Institut, Germany; 4National Veterinary Research
Institute, Poland; 5Kansas State University (Previously at USDA National Animal
Disease Center), USA
Background: Classical BSE is a world-wide prion disease in cattle, and the
classical BSE strain (BSE-C) has led to over 200 cases of clinical human
infection (variant CJD). Atypical BSE cases have been discovered in three
continents since 2004; they include the L-type (also named BASE), the H-type,
and the first reported case of naturally occurring BSE with mutated bovine PRNP
(termed BSE-M). The public health risks posed by atypical BSE were largely
undefined.
Objectives: To investigate these atypical BSE types in terms of their
transmissibility and phenotypes in humanized mice. Methods: Transgenic mice
expressing human PrP were inoculated with several classical (C-type) and
atypical (L-, H-, or Mtype) BSE isolates, and the transmission rate, incubation
time, characteristics and distribution of PrPSc, symptoms, and histopathology
were or will be examined and compared.
Results: Sixty percent of BASE-inoculated humanized mice became infected
with minimal spongiosis and an average incubation time of 20-22 months, whereas
only one of the C-type BSE-inoculated mice developed prion disease after more
than 2 years. Protease-resistant PrPSc in BASE-infected humanized Tg mouse
brains was biochemically different from bovine BASE or sCJD. PrPSc was also
detected in the spleen of 22% of BASE-infected humanized mice, but not in those
infected with sCJD. Secondary transmission of BASE in the humanized mice led to
a small reduction in incubation time.*** The atypical BSE-H strain is also
transmissible with distinct phenotypes in the humanized mice, but no BSE-M
transmission has been observed so far.
Discussion: Our results demonstrate that BASE is more virulent than
classical BSE, has a lymphotropic phenotype, and displays a modest transmission
barrier in our humanized mice. BSE-H is also transmissible in our humanized Tg
mice. The possibility of more than two atypical BSE strains will be discussed.
Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.
P26 TRANSMISSION OF ATYPICAL BOVINE SPONGIFORM ENCEPHALOPATHY (BSE) IN
HUMANIZED MOUSE MODELS
Liuting Qing1, Fusong Chen1, Michael Payne1, Wenquan Zou1, Cristina
Casalone2, Martin Groschup3, Miroslaw Polak4, Maria Caramelli2, Pierluigi
Gambetti1, Juergen Richt5*, and Qingzhong Kong1 1Department of Pathology, Case
Western Reserve University, Cleveland, OH 44106, USA; 2CEA, Istituto
Zooprofilattico Sperimentale, Italy; 3Friedrich-Loeffler-Institut, Germany;
4National Veterinary Research Institute, Poland; 5Kansas State University,
Diagnostic Medicine/Pathobiology Department, Manhattan, KS 66506, USA. *Previous
address: USDA National Animal Disease Center, Ames, IA 50010, USA
Classical BSE is a world-wide prion disease in cattle, and the classical
BSE strain (BSE-C) has led to over 200 cases of clinical human infection
(variant CJD). Two atypical BSE strains, BSE-L (also named BASE) and BSE-H, have
been discovered in three continents since 2004. The first case of naturally
occurring BSE with mutated bovine PrP gene (termed BSE-M) was also found in 2006
in the USA. The transmissibility and phenotypes of these atypical BSE
strains/isolates in humans were unknown. We have inoculated humanized transgenic
mice with classical and atypical BSE strains (BSE-C, BSE-L, BSE-H) and the BSE-M
isolate. We have found that the atypical BSE-L strain is much more virulent than
the classical BSE-C.*** The atypical BSE-H strain is also transmissible in the
humanized transgenic mice with distinct phenotype, but no transmission has been
observed for the BSE-M isolate so far.
III International Symposium on THE NEW PRION BIOLOGY: BASIC SCIENCE,
DIAGNOSIS AND THERAPY 2 - 4 APRIL 2009, VENEZIA (ITALY)
I ask Professor Kong ;
Thursday, December 04, 2008 3:37 PM Subject: RE: re--Chronic Wating Disease
(CWD) and Bovine Spongiform Encephalopathies (BSE): Public Health Risk
Assessment
''IS the h-BSE more virulent than typical BSE as well, or the same as cBSE,
or less virulent than cBSE? just curious.....''
Professor Kong reply ;
.....snip
''As to the H-BSE, we do not have sufficient data to say one way or
another, but we have found that H-BSE can infect humans. I hope we could publish
these data once the study is complete. Thanks for your interest.''
Best regards, Qingzhong Kong, PhD Associate Professor Department of
Pathology Case Western Reserve University Cleveland, OH 44106 USA
END...TSS
Thursday, December 04, 2008 2:37 PM
"we have found that H-BSE can infect humans."
personal communication with Professor Kong. ...TSS
BSE-H is also transmissible in our humanized Tg mice.
The possibility of more than two atypical BSE strains will be discussed.
Supported by NINDS NS052319, NIA AG14359, and NIH AI 77774.
please see below from PRION2013 ;
*** This study imply the possibility that the novel BSE prions with high
virulence in cattle will be emerged during intraspecies transmission.
AD.56: The emergence of novel BSE prions by serial passages of H-type BSE
in bovinized mice
Kentaro Masujin, Naoko Tabeta, Ritsuko Miwa, Kohtaro Miyazawa, Hiroyuki
Okada, Shirou Mohri and Takashi Yokoyama
National Institute of Animal Health; Tsukuba, Japan
H-type bovine spongiform encephalopathy (BSE) is an atypical form of BSE,
and has been detected in several European countries, and North America.
Transmission studies of H-type BSE led to the emergence of the classical BSE
(C-BSE) phenotypes during passages in inbred wild type and bovinized
PrP-overexpressing transgenic mice. In this study, we conducted serial passages
of Canadian H-type BSE isolate in bovinized PrP-overexpressing transgenic mice
(TgBoPrP). H-type BSE isolate was transmitted to TgBoPrP with incubation periods
of 320 ± 12.2 d at primary passage. The incubation period of 2nd and 3rd passage
were constant (~= 220 d), no clear differences were observed in their biological
and biochemical properties. However, at the forth passage, 2 different BSE
phenotypes were confirmed; one is shorter survival times (109 ± 4 d) and the
other is longer survival times. TgBoPrP mice with longer incubation period
showed the H-type phenotype of PrPsc profile and pathology. However, those of
shorter incubation period were different phenotypes from previously existed BSE
prions (C-BSE, L-type BSE, and H-type BSE). *** This study imply the possibility
that the novel BSE prions with high virulence in cattle will be emerged during
intraspecies transmission.
www.landesbioscience.com
please see ;
Thursday, August 15, 2013
The emergence of novel BSE prions by serial passages of H-type BSE in
bovinized mice
Thursday, August 15, 2013
Stability properties of PrPSc from cattle with experimental transmissible
spongiform encephalopathies: use of a rapid whole homogenate, protease-free
assay
Monday, March 19, 2012
Infectivity in Skeletal Muscle of Cattle with Atypical Bovine Spongiform
Encephalopathy
PLoS One. 2012; 7(2): e31449.
Monday, August 26, 2013
The Presence of Disease-Associated Prion Protein in Skeletal Muscle of
Cattle Infected with Classical Bovine Spongiform Encephalopathy
Tuesday, June 11, 2013
Weld County Bi-Products dba Fort Morgan Pet Foods 6/1/12 significant
deviations from requirements in FDA regulations that are intended to reduce the
risk of bovine spongiform encephalopathy (BSE) within the United States
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
Tuesday, July 2, 2013
APHIS USDA Administrator Message to Stakeholders: Agency Vision and Goals
Eliminating ALL remaining BSE barriers to export market
Wednesday, July 28, 2010
Atypical prion proteins and IBNC in cattle DEFRA project code SE1796 FOIA
Final report
IN CONFIDENCE
BSE ATYPICAL LESION DISTRIBUTION
Tuesday, November 02, 2010
BSE - ATYPICAL LESION DISTRIBUTION (RBSE 92-21367) statutory (obex only)
diagnostic criteria CVL 1992
Tuesday, September 17, 2013
USAHA 116TH ANNUAL MEETING October 18 – 24, 2012 CWD, Scrapie, BSE, TSE
prion (September 17, 2013)
From: Terry S. Singeltary Sr. Sent: Sunday, July 21, 2013 1:44 PM To:
endemics@wales.gsi.gov.uk Cc: wag-en@mailuk.custhelp.com ;
Carwyn.jones@wales.gsi.gov.uk ; Correspondence.Alun.Davies@Wales.gsi.gov.uk ;
Correspondence.Carl.Sargeant@Wales.gsi.gov.uk ;
Correspondence.Edwina.Hart@Wales.gsi.gov.uk ;
Correspondence.Huw.Lewis@Wales.gsi.gov.uk ;
Correspondence.Jane.Hutt@Wales.gsi.gov.uk ;
Correspondence.John.Griffiths@Wales.gsi.gov.uk ;
Correspondence.Lesley.Griffiths@Wales.gsi.gov.uk ;
Correspondence.Mark.Drakeford@Wales.gsi.gov.uk ;
Correspondence.Jeff.Cuthbert@Wales.gsi.gov.uk ;
Correspondence.Vaughan.Gething@wales.gsi.gov.uk ;
Correspondence.Ken.Skates@wales.gsi.gov.uk ;
Correspondence.Gwenda.Thomas@Wales.gsi.gov.uk Subject: Welsh Government and Food
Standards Agency Wales Joint Public Consultation on the Proposed Transmissible
Spongiform Encephalopathies (Wales) Regulations 2013
July 21, 2013
Subject: Welsh Government and Food Standards Agency Wales Joint Public
Consultation on the Proposed Transmissible Spongiform Encephalopathies (Wales)
Regulations 2013
endemics@wales.gsi.gov.uk; fenris@caramail.com;
Greetings Welsh Government and Food Standards Agency Wales,
With great urgency, I would kindly like to comment on ;
Number: WG18417
Joint Public Consultation on the Proposed Transmissible Spongiform
Encephalopathies (Wales) Regulations 2013
The European Food Safety Authority (EFSA) and the European Centre for
Disease Prevention and Control jointly advised in 2011 that BSE is the only
animal TSE that has been shown to be a risk to human health and that there is no
epidemiological evidence to suggest that classical scrapie is a risk to human
health.
and
What are the main issues under consideration?
2.1 The main issues under consideration relate to changes in BSE testing
requirements; more proportionate measures for controlling classical scrapie in
sheep flocks and goat herds in which classical scrapie is confirmed; and more
proportionate controls on animal feed. The Welsh Government also wishes to
consult on proposed amendments to the BSE cattle compensation system in light of
identified anomalies in the current system, in addition to a variety of other
proposed technical and procedural amendments to the 2008 Regulations.
2.2 The key specific amendments are summarised and then considered in more
detail below. Other proposed technical amendments, which are considered to have
a negligible impact or have already been implemented administratively, are
listed at Annex A. What are the main issues under consideration?
2.1
* The main issues under consideration relate to changes in BSE testing
requirements;
* more proportionate measures for controlling classical scrapie in sheep
flocks
* and goat herds in which classical scrapie is confirmed; and
* more proportionate controls on animal feed.
Greetings again Welsh Government and Food Standards Agency Wales, with
another TSE prion medical blunder happening just this past week ;
Friday, July 19, 2013
Beaumont Hospital in Dublin assessing patients for CJD
I STRENUOUSLY urge you take my submission with the greatest urgency. My
submission and concerns as follows, and in part mixed in and throughout the
WG18417 Proposed Transmissible Spongiform Encephalopathies (Wales) Regulations
2013. First and foremost, I think it is very important for the Welsh Government
and Food Standards Agency Wales, to take a full inventory of your imports from
North America, and other Countries, especially your pet and fish foods, for
reasons and scientific facts I have supplied below. I think the attempt by
Governments around the globe to do away with the Transmissible Spongiform
Encephalopathy TSE prion disease, via weakening of the BSE TSE prion
surveillance, lowering of age limits in testing, weakening the feed bans, caving
in to industry, ignoring all the science of the past 3 decades, ignoring these
different atypical TSE prion disease breaking out, making up new names for these
TSE prion disease, and by the way, what ever happened to the IBNC BSE, and the
pathology there, and what about testing there from?
The USDA, CFIA, with the help of the OIE, have made it there goal to
extinguish all BSE TSE prion trade barriers, before all the science on the TSE
prion disease is in, and are working hard to exempt all TSE prion in all species
from any trade barrier, and the OIE is working right along with them. This
happened December 2003, when the USA lost it’s OIE BSE Gold Card, when BSE was
first documented in the USA, after a long hard fought battle trying to cover mad
cow disease up. This proven time and time again by the OIG and the GAO of the
USA. I will supply url links of submissions I have made to the USDA et al over
the years, since the death of my Mother to the Heidenhain Variant of Creutzfeldt
Jakob Disease i.e. hvCJD ‘confirmed’ 12/14/97. just another happenstance of bad
luck they tell me, that it only happens in the UK, and that it’s a UK disease,
this mad cow disease, that no other animal species TSE prion disease in the
world, at no other location, can transmit a TSE prion disease to a human, and
then basing all trading protocol from country to country, based on this junk
science, destroys the past 3 decades of trying to eradicate the damn disease,
and the OIE, USDA, CFIA, and all the other countries that know better, that just
goes along with this due to trade purposes, just because it’s a long incubating
disease, just because the science is still in it’s infancy, does not mean we
should start ignoring what early science has taught us, and start weakening any
safety protocols there from.
North America has the most documented TSE prion disease in the wild and in
farmed livestock than any other country in the world, excluding the TSE prion
disease documented in zoo animals. Chronic Wasting Disease CWD in cervids is
running rampant, the USA and Canada can’t stop it, while Mexico has not a clue
of any TSE prion disease. The shooting pens, and CWD there from in the USA, is a
real risk factor, one the game farms refuse to admit they are a big problem with
the spreading of the CWD TSE prion disease, fighting tooth and nail completely
ignoring the evolving science on the CWD TSE prion disease, and how it’s spread,
and these antler mills are multiplying from state to state in big numbers. There
is ample evidence of CWD transmission to humans, to warrant a warning to the
world, of the IATROGENIC potential for this TSE prion disease in cervids, via
the multitude of potential routes of infection, via the medical, dental,
surgical, blood, tissue. CWD has now mutated to multiple strains. The science is
there to warrant this very real concern, it’s just the same as with what
happened in the U.K., the industry and USDA inc., are stopping these concerns to
be made public, with the same watered down junk science used in the beginning of
the BSE blunder. you should all be very aware of this, if you come abroad to
North America. DEFRA has put out a warning on CWD TSE prion disease in the USA
and have put out a document I supplied with additional risk factors from North
America, this is supplied below as well.
Another concern is with your assumptions that typical classical scrapie is
not a risk factor for humans, when there _is_ evidence to show otherwise, that
indeed typical scrapie is a risk factor for humans, as with atypical Scrapie.
The OIE, USDA inc, and the CFIA, have come to the conclusion that neither
typical scrapie nor the atypical Nor-98 scrapie are neither a risk factor for
humans, they have urged the OIE to conclude that atypical Nor-98 to be exempt
from any trading protocols, and indeed have made the Nor-98 atypical scrapie
EXEMPT, and made it legal to trade, and they are also in the works to make
typical scrapie exempt.
typical scrapie consist of many different strains of scrapie, not just one.
and the atypical Nor-98 has very similar features with human
Gerstmann-Sträussler-Scheinker Disease GSS and Variably Protease-Sensitive
Prionopathy VPSPr. I have not seen anywhere in the Bible, or the scrolls of the
Dead Sea, where it was stipulated that indeed typical c-BSE is the only zoonosis
Transmissible Spongiform Encephalopathy TSE prion disease. This is ludicrous in
2013 to still believe this junk science.
With the science to date of the 1st 10 nvCJD victims of Dr. Ironside et al,
and the diagnostic criteria then to diagnose the nvCJD, compared to what Dr.
Gambetti et al diagnosed in their 1st 10, of which young victims are being
diagnosed, but yet changed the name to VPSPr type CJD human TSE, is not
scientific in my opinion. I believe that the UKBSEnvCJD only theory is bogus, it
is not scientific, and should be put to bed once and for all. you cannot have
your cake and eat it too. either Ironside was wrong, or Gambetti is wrong. to
continue this UKBSEnvCJD only myth, will only help continue spread the TSE prion
agent long and far.
typical Scrapie has been studied for decades and decades, and has proven to
be transmitted to non-human primates by their NON-FORCED oral consumption (Gibbs
et al). when you write in absolute terms as this is fact that ‘’BSE is the only
animal TSE that has been shown to be a risk to human health and that there is no
epidemiological evidence to suggest that classical scrapie is a risk to human
health’’ may be true in terms of documentation, but in terms of science to date,
I think you are wishing. I kindly wish to submit the following in good faith ;
snip... Singeltary Complete submission located in PDF attachment in this email,
or in the link below...
Sunday, July 21, 2013
Welsh Government and Food Standards Agency Wales Joint Public Consultation
on the Proposed Transmissible Spongiform Encephalopathies (Wales) Regulations
2013 Singeltary Submission WG18417
Friday, August 16, 2013
*** Creutzfeldt-Jakob disease (CJD) biannual update August 2013 U.K. and
Contaminated blood products induce a highly atypical prion disease devoid of
PrPres in primates
Sunday, August 11, 2013
Creutzfeldt-Jakob Disease CJD cases rising North America updated report
August 2013
*** Creutzfeldt-Jakob Disease CJD cases rising North America with Canada
seeing an extreme increase of 48% between 2008 and 2010
Sunday, September 08, 2013
Iatrogenic Creutzfeldt-Jakob disease via surgical instruments and
decontamination possibilities for the TSE prion
Wednesday, September 25, 2013
Cleaning, disinfection and sterilization of surface prion contamination
Tuesday, September 24, 2013
NORDION (US), INC., AND BIOAXONE BIOSCIENCES, INC., Settles $90M Mad Cow
TSE prion Contamination Suit Cethrin(R)
Case 0:12-cv-60739-RNS Document 1 Entered on FLSD Docket 04/26/2012 Page 1
of 15
Prion2013
Oral.05: Contaminated blood products induce a highly atypical prion disease
devoid of PrPres in primates
Emmanuel Corney,1 Nina Jaffre,1 Jacqueline Mikol,1 Valerie Durand,1
Christelle Jas-Duval,1,2 Sophie Luccantoni-Freire,1 Evelyne Correia,1 Nathalie
Lescoutra-Etcheqaray,3 Nathalie Streichenberqer,4 Stephane Haik,5 Chryslain
Sumian,3 Paul Brown1 and Jean-Philippe Deslys1
1Commissariat a l'Energie Atomique; Institute of Emerging Diseases and
Innovative Therapies (iMETI); Division of Prions and Related Diseases (SEPIA);
Fontenay-aux- Roses, France; 2EFS·Nord de France; Lille, France; 3MacoPharm;
Tourcoing, France; 4Hospices Civils de Lyon; Prion Unit; Neurobiology
Department; Bron, France; 5Inserm; U 975·CNRS; UMR 7225 - Universite Pierre et
Marie Curie; Paris, France
Background, Concerns about the blood-borne risk of prion infection have
been confirmed by the occurrence in the UK of four transfusion-related
infections of vCJD and an apparently silent infection in an hemophiliac patient.
Asymptomatic incubation periods in prion diseases can extend over decades in
humans. We present here unexpected results of experiments evaluating blood
transmission risk in a non-human primate model.
Material and Methods, Cynomolgus macaques were inoculated with brain or
blood specimens from vCJD infected humans or monkeys. Neuropathological and
biochemical findings were obtained using current methods used for human
patients.
Results, Thirteen out of 23 primates exposed to various human or macaque
blood products exhibited a previously undescribed myelopathic syndrome, devoid
of the classical features of prion disease, notably abnormal prion protein
(PrPres) deposition, whereas the 14 corresponding brain-inoculated donor animals
and 1 transfused animal exhibited the classical vCJD pattern. In passage
experiments, plasma transfusion induced the same atypical phenotype after two
years (again, with no detectable PrPres), whereas the intracerebral inoculation
of spinal cord led to a typical prion disease with cerebral spongiosis and
PrPres accumulation in the brain of the primate recipient. Interestingly,
passage experiments in transgenic mice were largely unsuccessful.
In another experiment designed to test the efficacy of antiprion filters,
three recipients of filtered red blood cells suspended in plasma are still
healthy 4.5 y after transfusion whereas the recipients of unfiltered inocula
died after 2.5 y with the atypical neurological profile.
Conclusion. We describe a new fatal neurological myelopathic syndrome in
monkeys exposed to various vCJD/BSE-infected blood components.
Secondary transmission in primates confirms
(I) the transmissibility of this myelopathy, and
(2) its prion origin which could not be diagnosed as such in the first
recipients.
This myelopathy might be compared in some respects to certain forms of
human lower motor neuron disease, including neuromyelitis optica, the flail arm
syndrome of amyotrophic lateral sclerosis (ALS), and the recently described
FOSMN (facial onset sensory and motor neuronopathy) syndrome.
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AD.56: The emergence of novel BSE prions by serial passages of H-type BSE
in bovinized mice
Kentaro Masujin, Naoko Tabeta, Ritsuko Miwa, Kohtaro Miyazawa, Hiroyuki
Okada, Shirou Mohri and Takashi Yokoyama
National Institute of Animal Health; Tsukuba, Japan
H-type bovine spongiform encephalopathy (BSE) is an atypical form of BSE,
and has been detected in several European countries, and North America.
Transmission studies of H-type BSE led to the emergence of the classical BSE
(C-BSE) phenotypes during passages in inbred wild type and bovinized
PrP-overexpressing transgenic mice. In this study, we conducted serial passages
of Canadian H-type BSE isolate in bovinized PrP-overexpressing transgenic mice
(TgBoPrP). H-type BSE isolate was transmitted to TgBoPrP with incubation periods
of 320 ± 12.2 d at primary passage. The incubation period of 2nd and 3rd passage
were constant (~= 220 d), no clear differences were observed in their biological
and biochemical properties. However, at the forth passage, 2 different BSE
phenotypes were confirmed; one is shorter survival times (109 ± 4 d) and the
other is longer survival times. TgBoPrP mice with longer incubation period
showed the H-type phenotype of PrPsc profile and pathology. However, those of
shorter incubation period were different phenotypes from previously existed BSE
prions (C-BSE, L-type BSE, and H-type BSE).
*** This study imply the possibility that the novel BSE prions with high
virulence in cattle will be emerged during intraspecies transmission.
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see also ;
Thursday, August 15, 2013
The emergence of novel BSE prions by serial passages of H-type BSE in
bovinized mice
PRION2013
Oral.11: Variant CJD 17 years on
Jean C. Manson,1 Matthew Bishop,2 Abigail B. Diack,1 Diane Ritchie,2 Sandra
McCutcheon, Richard Alejo Blanco,1 Pedro Piccardo,1,3 James ironside2 and Robert
Will2 1The Roslin Institute & R(D)SVS; Easter Bush, UK; 2National CJD
Research and Surveillance Unit; University of Edinburgh; Edinburgh, UK; 3Center
for Biologics Evaluation and Research; Food and Drug Administration; Rockville,
MD USA
It is now 17 years since the first identification of a case of vCJD in the
UK. Since that time there has been much speculation over how vCJD might impact
on human health. To date there have been 176 cases reports in the UK and a
further 51 cases worldwide in 11 different countries. It has been important to
establish
(1) if all worldwide cases represent the same strain of agent;
(2) the potential for human to human transmission;
(3) if the strain of agent will adapt to the human host and become more
virulent; and
(4) the extent to which asymptomatic infection may impact on human health.
We have now established by examining a number of worldwide vCJD cases that
there is broad similarity to UK vCJD cases on first passage to mice. Transgenic
mouse studies have indicated that all codon 129 genotypes are susceptible to
vCJD and that genotype may influence whether disease appears in a clinical or
asymptomatic form, supported by the appearance of the first case of asymptomatic
vCJD infection in a PRNP 129MV patient. We have established, by transmission to
RIII mice, that there is little evidence for strain modification following human
to human transmission of vCJD by blood transfusion of an MM case to an MM or MV
recipient. Some differences in incubation times in VM mice observed in these
transmissions are now being assessed on second passage to establish if
alterations represent differences in strain characteristics or are due to
species barrier effects in primary passage.
Following evidence of blood transfusion as a route of transmission, we have
ascertained that all blood components and leucoreduced blood, in a sheep model
of vCJD have the ability to transmit disease.
Importantly, we have recently established that a blood recipient with an
asymptomatic infection with limited PrPsc deposition in the spleen could readily
transmit disease into mice, demonstrating the potential for peripheral infection
in the absence of clinical disease. This, along with the recent appendix survey
which identified 16 positive appendices in a study of 32,441 cases, underlines
the importance of continued CJD surveillance and maintaining control measures
already in place to protect human health.
References
1. Bishop MT, Hart P, Airchison L, Baybutt HN, Plinston C. Thomson V, er
al. Predicting susceptibility and incubation time of human-to-human transmission
of vCJD. Lance. Neurol 2006; 5:393·8; PMID: 16632309;
http://dx.doi.org/10.1016/S1474-4422(06)70413-6
2. McCutcheon S, AJejo Blanco AR, Houston EF, de Wolf C. Tan BC, Smith A, et al.
All clinically-relevant blood components transmit prion disease following a
single blood transfusion: a sheep model of vCJD. PLoS One 2011; 6:e23169;
PMID:21858015;
http://dx.doi.org/10.1371/journal.pone.0023169
3. Diack AB, Ritchie D, Bishop M, Pinion V, Brandel JP, Haik S, e. al.
Constant trans- mission properties of variant Creutzfeldt-jakob disease in 5
countries. Emerg Infect Dis 2012; 18: 1574-9; PMID:23017202;
http://dx.doi.org/10.3201/eid1810.120792.
4. HPA. Health Protection Report 2012; 6(32).
5. Bishop MT, Diack AB, Ritchie DL, Ironside JW, Will RG, Manson JC. Prion
infectivity in the spleen of a PRNP heterozygous individual with subclinical
variant Creutzfeldt- Jakob disease. Brain 2013; 136:1139-45; PMID:23449776;
http://dx.doi.org/10.1093/brain/awt032
Oral.12: Preclinical detection of variant CJD and BSE prions in blood
Caroline Lacroux,1 Jean Yves Douet,1 Emmanuel Corney,2 Hugh Simmons,3
Vincent Beringue,4 Jean Philippe Deslys,2 Didier Vilette1 and Olivier
Andreoletti1 1INRA; Toulouse, France; 2CEA; Fontenay aux roses, France; 3AHVLA;
Weybridge, UK; 4INRA VIM; Jouy en Josas, France
The emergence of variant Creutzfeldt Jakob Disease (vCJD) is considered a
likely consequence of human dietary exposure to Bovine Spongiform Encephalopathy
(BSE) agent. More recently, secondary vCJD cases were identified in patients
transfused with blood products prepared from apparently healthy donors who later
went on to develop the disease. As there is no validated assay for detection of
vCJD/BSE infected individuals the prevalence of the disease in the population
remains uncertain. In that context the risk of vCJD blood borne transmission is
considered as a serious concern by health authorities.
In this study, appropriate conditions and substrates for highly efficient
and specific in vitro amplification of vCJD/BSE agent using Protein Misfolding
Cyclic Assay (PMCA) were first identified. This showed that whatever the origin
(species) of vCJD/BSE agent, the ovine Q171 PrP substrates provided the best
amplification performances. These results indicate that the homology of PrP
amino-acid sequence between the seed and the substrate is not the crucial
determinant of the vCJD agent in vitro propagation.
The ability of this method to detect endogenous vCJD/BSE agent in the blood
was then defined. In both sheep and primate models of the disease, the assay
enabled the identification of infected individuals in the early preclinical
stage of the incubation period. Finally, blood from two vCJD affected patients
and 135 healthy controls were tested. The assay detected the presence of the
vCJD case within a pool of several dozens of human blood samples. The equivalent
0.05 uL of whole blood from the vCJD affected patient was sufficient for
amplifying PrPres. These results open new possibilities for vCJD screening and
prevention of its iatrogenic transmission.
Oral.13: Prion detection in urine of patients with variant
Creutzfeldt-Jakob disease
Fabio Moda,1 Silvio Notari,2 Pierluigi Gambetti,2 Valeria Fuqnanesi,3
Kyung-Won Park,1 Michela Morbin,3 Silvia Suardi,3 Fabrizio Tagliavini3 and
Claudio Soto1 1Mitchell Center for Alzheimer's Disease and Related Brain
Disorders; University of Texas Medical School; Houston, TX USA; 2Case Western
Reserve University; Cleveland, OH USA; 3Carlo Besta Neurological Institute;
Milan, Italy
Definitive diagnosis of prion disease can only be made by tissue
examination and relies on the detection of misfolded prion protein (PrPSc) and
associated histopathological changes in the brain. PrPSc is the main component
of the infectious agent and is the only validated surrogate marker for the
disease. The unique mechanism of prion transmission and the appearance of a new
variant form of CJD (vCJD), which has been linked to the consumption of meat
from BSE-affected cattle, have raised concerns for public health. Recently, four
cases of vCJD have been associated with blood transfusion from asymptomatic
donors who subsequently died from vC]D. This suggests that prions exist in the
blood of individuals silently incubating the disease. It is likely that minute
amount of prions can be present in urine of vCJD patients, as product of blood
filtration, but no evidences of prion detection in urine of humans with CJD have
been provided so far. With the advent of PMCA (protein mysfolding cyclic
amplification) several groups have been able to detect infectious prion in urine
of cervids infected by chronic wasting disease (CWD), sheep infected by Scrapie
and rodents (mouse and hamsters) infected with different prion agents. Taking
advantage of the extreme sensitivity of PMCA, we have analyzed urine from
several patients suffering from different forms of CJD (variant, sporadic and
genetic). Of all the cases analyzed, only those affected by vCJD were found to
contain PrPSc that can be amplified to obtain a signal that has the typical
electrophoretic profile of PrPSc associated to vCJD. Many controls including
urine from patients affected by other neurological diseases (Alzheimer disease,
Frontotemporal dementia, Parkinson disease, progressive supranuclear palsy), as
well as healthy control subjects were all found to be negative for PrPSc in
urine. To the best of our knowledge, this is the first report showing the
presence of prions in human urine. Due to the limited number of vCJD urine
samples examined, we cannot definitively establish whether PrPSc presence is
common in all vCJD patients or depends on the existence of other pathologies
(e.g., renal malfunction). The detection of prions in human urine may be
utilized as a non-invasive diagnostic test of vCJD, and also uncovers a possible
risk related with the use of urinary-derived products (hormones, enzymes and
other proteins) as well as the collection and disposal of urine from vCJD
patients.
Acknowledgments. This research was partially fund by NIH grants
R42NS079060, P01AI077774 and P01AG14359 to CS and P01AG14359 and Charles S.
Britton Fund to PG.
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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.
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...
kind regards, terry
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