Wednesday, September 25, 2013

Presence of subclinical infection in gene-targeted human prion protein transgenic mice exposed to atypical BSE

 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.

 


 

www.landesbioscience.com

 

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

posted by Terry S. Singeltary Sr. at 1:13 PM

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