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Location: BACLIFF, Texas, United States

My mother was murdered by what I call corporate and political homicide i.e. FOR PROFIT! she died from a rare phenotype of CJD i.e. the Heidenhain Variant of Creutzfeldt Jakob Disease i.e. sporadic, simply meaning from unknown route and source. I have simply been trying to validate her death DOD 12/14/97 with the truth. There is a route, and there is a source. There are many here in the USA. WE must make CJD and all human TSE, of all age groups 'reportable' Nationally and Internationally, with a written CJD questionnaire asking real questions pertaining to route and source of this agent. Friendly fire has the potential to play a huge role in the continued transmission of this agent via the medical, dental, and surgical arena. We must not flounder any longer. ...TSS

Monday, May 19, 2014

Variant CJD: 18 years of research and surveillance

Variant CJD: 18 years of research and surveillance

 

Abigail B Diack, 1, † Mark W Head, 2, † Sandra McCutcheon, 1 Aileen Boyle, 1 Richard Knight, 2 James W Ironside, 2 Jean C Manson, 1, †, * Robert G Will 2, † Abstract It is now 18 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 177 cases reports in the UK and a further 51 cases worldwide in 11 different countries. Since establishing that BSE and vCJD are of the same strain of agent, we have also shown that there is broad similarity between UK and non-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 potential asymptomatic vCJD infection in a PRNP 129MV patient. 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 recently established that a PRNP 129MV patient 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.

 

snip...

 

Emergence of novel strains

 

Identification of novel strains involves veterinary and medical vigilance, but it also requires a proper and full characterization of known prion agents. While the deployment of wild-type mouse panels, transgenic mice, and non-human primates all rapidly concluded that vCJD was a novel human prion strain related to BSE (see above), determining how many distinct human prion strains there are has proved surprisingly difficult, especially for sCJD. Transmission studies in humanised transgenic mice and non-human primates point to 4 major groups within sporadic, iatrogenic CJD, Kuru, and some genetic CJD cases, termed M1, V1, M2, and V2.21,106 Sporadic fatal insomnia and fatal familial insomnia (FFI) together may represent a sixth strain107 and 2 further transmissible phenotypes can be derived from GSS disease: one involving a transmissible amyloid phenotype, the other a fully transmissible spongiform encephalopathy.108,109 The transmission properties of PrP cerebral amyloid angiopathy and Variable Protease Sensitive Prionopathy (VPSPr) remain to be reported. The relationship between human disease phenotypes, agent strain, and prion biochemistry is further complicated by the now widely recognized phenomenon of distinct PrPres type co-occurrence in the sCJD, vCJD and VPSPr brain.14,23,110

 

8

 

Surveillance for BSE in cattle, sheep, and goats has identified new (or newly discovered) animal prion diseases including atypical scrapie in sheep and so called H- and L-type BSE in cattle. These along with chronic wasting disease (CWD) in deer and elk represent a potential zoonotic risk to human health that is hard to quantify. While Wilson et al.111 have shown no transmission of CWD, BASE, H-type BSE, and atypical scrapie to mice expressing wild-type levels of human PrP, Kong et al.112 demonstrated transmission of BASE to an alternative line of mice expressing wild-type levels of human PrP. In contrast, Beringue et al.113 showed transmission of BASE to mice overexpressing human PrP but no evidence of H-type BSE transmission, furthermore no evidence of CWD transmission to overexpressing mice has been identified.114,115 This difference in transmission results may be due to different genetic backgrounds or differences in PrP expression levels between the different mouse lines. An alternative to modeling the species barrier is the cell-free conversion assay which points to CWD as the animal prion disease with the greatest zoonotic potential, after (and very much less than) BSE.116

 

6

 

Surveillance

 

Continued surveillance for long-term effects of BSE exposure in the UK human population appears necessary for the foreseeable future in order to discount possible second wave epidemics that might depend on genetic susceptibility, subclinical infection, and secondary transmission or disease in defined at risk patient groups such as hemophiliacs or patient groups in which full ascertainment is difficult, such as the elderly.

 

However, an additional concern is associated with idiopathic human prion disease. Sporadic CJD is not a uniform condition and the phenotype is clearly influenced by the codon 129 genotype of the patient and the prion protein type that accumulates in their brain. The etiological basis of the condition might be presumed to be spontaneously occurring, but this is not known with certainty in general, or in individual specific cases. Neither are the molecular mechanisms of spontaneous conversion of the prion protein to its pathogenic form well understood or easily investigated. Additionally, surveillance identifies apparently sporadic cases of human prion disease that do not fit well into currently accepted classification systems. This is exemplified by the recent identification of a new human prion disease (VPSPr by Gambetti et al.,117) and its prospective and retrospective identification in other countries subsequently.16,110 The true prevalence, the relationship to sCJD and the risk to public health of VPSPr are yet to be determined. 3

 

Conclusions

 

Since the identification of vCJD we have made progress in identifying routes of infection, controlling further infection, producing models of disease, developing decontamination procedures, and understanding susceptibility to disease. The vCJD epidemic in the UK now appears to be in decline and it appears that the control measures in food production and blood supplies have prevented further vCJD cases arising through dietary/infected blood exposure. Despite this, there are still ongoing concerns over cases of vCJD arising in countries where little or no exposure to UK meat products have occurred, the presence of subclinical vCJD in the UK population with the possibility of further human-to-human transmission and the identification of new strains of human prion disease. These scenarios necessitate ongoing studies in understanding transmission properties, disease diagnosis, and therapeutics. The identification of novel human prion diseases and the current estimates of subclinical vCJD infections show the importance of continued CJD surveillance and maintaining control measures already in place to protect human health.

 


 

*** The discovery of previously unrecognized prion diseases in both humans and animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion diseases might be wider than expected and raises crucial questions about the epidemiology and strain properties of these new forms. We are investigating this latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.

 


 

Wednesday, March 28, 2012

 

VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE, price of prion poker goes up again $

 


 

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)

 


 

Monday, January 14, 2013

 

Gambetti et al USA Prion Unit change another highly suspect USA mad cow victim to another fake name i.e. sporadic FFI at age 16 CJD Foundation goes along with this BSe

 


 

VARIABLY PROTEASE-SENSITVE PRIONOPATHY IS TRANSMISSIBLE ...price of prion poker goes up again $

 

OR-10 15:25 - 15:40 VARIABLY PROTEASE-SENSITIVE PRIONOPATHY IS TRANSMISSIBLE IN BANK VOLES Nonno

 


 

OR-10: Variably protease-sensitive prionopathy is transmissible in bank voles

 

Romolo Nonno,1 Michele Di Bari,1 Laura Pirisinu,1 Claudia D’Agostino,1 Stefano Marcon,1 Geraldina Riccardi,1 Gabriele Vaccari,1 Piero Parchi,2 Wenquan Zou,3 Pierluigi Gambetti,3 Umberto Agrimi1 1Istituto Superiore di Sanità; Rome, Italy; 2Dipartimento di Scienze Neurologiche, Università di Bologna; Bologna, Italy; 3Case Western Reserve University; Cleveland, OH USA

 

Background. Variably protease-sensitive prionopathy (VPSPr) is a recently described “sporadic”neurodegenerative disease involving prion protein aggregation, which has clinical similarities with non-Alzheimer dementias, such as fronto-temporal dementia. Currently, 30 cases of VPSPr have been reported in Europe and USA, of which 19 cases were homozygous for valine at codon 129 of the prion protein (VV), 8 were MV and 3 were MM. A distinctive feature of VPSPr is the electrophoretic pattern of PrPSc after digestion with proteinase K (PK). After PK-treatment, PrP from VPSPr forms a ladder-like electrophoretic pattern similar to that described in GSS cases. The clinical and pathological features of VPSPr raised the question of the correct classification of VPSPr among prion diseases or other forms of neurodegenerative disorders. Here we report preliminary data on the transmissibility and pathological features of VPSPr cases in bank voles.

 

Materials and Methods. Seven VPSPr cases were inoculated in two genetic lines of bank voles, carrying either methionine or isoleucine at codon 109 of the prion protein (named BvM109 and BvI109, respectively). Among the VPSPr cases selected, 2 were VV at PrP codon 129, 3 were MV and 2 were MM. Clinical diagnosis in voles was confirmed by brain pathological assessment and western blot for PK-resistant PrPSc (PrPres) with mAbs SAF32, SAF84, 12B2 and 9A2.

 

Results. To date, 2 VPSPr cases (1 MV and 1 MM) gave positive transmission in BvM109. Overall, 3 voles were positive with survival time between 290 and 588 d post inoculation (d.p.i.). All positive voles accumulated PrPres in the form of the typical PrP27–30, which was indistinguishable to that previously observed in BvM109 inoculated with sCJDMM1 cases. In BvI109, 3 VPSPr cases (2 VV and 1 MM) showed positive transmission until now. Overall, 5 voles were positive with survival time between 281 and 596 d.p.i.. In contrast to what observed in BvM109, all BvI109 showed a GSS-like PrPSc electrophoretic pattern, characterized by low molecular weight PrPres. These PrPres fragments were positive with mAb 9A2 and 12B2, while being negative with SAF32 and SAF84, suggesting that they are cleaved at both the C-terminus and the N-terminus. Second passages are in progress from these first successful transmissions.

 

Conclusions. Preliminary results from transmission studies in bank voles strongly support the notion that VPSPr is a transmissible prion disease. Interestingly, VPSPr undergoes divergent evolution in the two genetic lines of voles, with sCJD-like features in BvM109 and GSS-like properties in BvI109. The discovery of previously unrecognized prion diseases in both humans and animals (i.e., Nor98 in small ruminants) demonstrates that the range of prion diseases might be wider than expected and raises crucial questions about the epidemiology and strain properties of these new forms. We are investigating this latter issue by molecular and biological comparison of VPSPr, GSS and Nor98.

 

SOURCE PRION2012

 


 

I believe it was Gambetti et al that coined this term sporadic FFI, from some conspicuous sub-type of sporadic CJD possibly?

 

seems they could not tie it to a true FFI by diagnostic standards to date, so it was then termed a sFFI, confusing matters even worse. ...

 

A subtype of sporadic prion disease mimicking fatal familial insomnia

 


 

THIS seems to raise more questions than answers, confusing the TSEs even worse.

 

WHAT is sporadic CJD, and how many sub-types and atypical strains, phenotypes etc. will there be, arising from nothing. a spontaneous happening of sorts???

 

i think not. ...tss

 


 

Wednesday, October 27, 2010

 

A novel variant of human disease with a protease-sensitive prion protein and heterozygosity methionine/valine at codon 129: Case report

 

snip...

 

Genetic findings

 

No mutations were found in the open reading frame after sequencing the prion protein gene (PRNP). A heterozygosis methionine valine (MV) was observed in codon 129.

 

snip...

 


 

Thursday, July 10, 2008

 

A Novel Human Disease with Abnormal Prion Protein Sensitive to Protease update July 10, 2008

 

Although several subjects had family histories of dementia, no mutations were found in the PrP gene open reading frame.

 


 

Thursday, July 10, 2008

 

A New Prionopathy update July 10, 2008

 


 

***+++***

 

Thursday, July 10, 2008

 

A Novel Human Disease with Abnormal Prion Protein Sensitive to Protease update July 10, 2008 Friday, June 20, 2008

 


 

Here we go folks. AS predicted. THIS JUST OUT !

 

Tuesday, August 03, 2010

 

Variably protease-sensitive prionopathy: A new sporadic disease of the prion protein

 


 

Monday, August 9, 2010

 

Variably protease-sensitive prionopathy: A new sporadic disease of the prion protein or just more PRIONBALONEY ?

 

snip...see full text ;

 


 


 

O.K. let's compare some recent cases of this prionpathy in other countries besides Gambetti's first 10 recently, that he claims is a spontaneous event, from a genetic disorder, that is not genetic, but sporadic, that is related to no animal TSE in North America, or the world. ...

 


 

Wednesday, October 27, 2010

 

A novel variant of human disease with a protease-sensitive prion protein and heterozygosity methionine/valine at codon 129: Case report

 


 

Sunday, August 09, 2009

 

CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009

 


 

Tuesday, August 18, 2009

 

BSE-The Untold Story - joe gibbs and singeltary 1999 – 2009

 


 

====================================

 

The familial mutations, Gajdusek proposed, lowered the barrier to such accidental conversion. "Thus," he wrote in 1996, "with these mutations, this ordinarily rare event becomes a ... dominant inherited trait." But Weissmann's qualification still remained to be refuted: the mutations might simply allow easier entry to a lurking virus. ...page 202 Deadly Feast

 

===================================

 

something to think about for sure.

 

but i interpret this as (1st not the gold standard, just my opinion;-), as because of certain gene mutations, one or a family, would be more susceptible to the many different strains of TSE, and the many different proven routes and sources, (which will cause different symptoms, different incubation periods from onset of clinical symptoms to death, different parts of the brain infected, etc.). in other words, it's NOT the gene mutation that CAUSES the disease, but the fact that it makes you more SUSCEPTIBLE, to the TSEs from the surrounding environment, and PLUS accumulation, i think this plays a critical role. maybe there is a one dose scenario, but i think there is more of the 'accumulators' that go clinical, than the 'one dose'. and what is the threshold to sub-clinical to clinical ?

 

anyway, just pondering out loud here.

 

also, for anyone interested, there are some studies with links to follow here ;

 


 

Thursday, June 21, 2012

 

Clinical and Pathologic Features of H-Type Bovine Spongiform Encephalopathy Associated with E211K Prion Protein Polymorphism

 


 

Friday, May 9, 2014

 

Distinct Transmissibility Features of TSE Sources Derived from Ruminant Prion Diseases by the Oral Route in a Transgenic Mouse Model (TgOvPrP4) Overexpressing the Ovine Prion Protein

 


 

*** 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.”

 


 

The present study demonstrated successful intraspecies transmission of H-type BSE to cattle and the distribution and immunolabeling patterns of PrPSc in the brain of the H-type BSE-challenged cattle. TSE agent virulence can be minimally defined by oral transmission of different TSE agents (C-type, L-type, and H-type BSE agents) [59]. Oral transmission studies with H-type BSE infected cattle have been initiated and are underway to provide information regarding the extent of similarity in the immunohistochemical and molecular features before and after transmission.

 

In addition, the present data will support risk assessments in some peripheral tissues derived from cattle affected with H-type BSE.

 


 

*** 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. ***

 

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. ***

 

see page 176 of 201 pages...tss

 


 

*** Singeltary reply ; Molecular, Biochemical and Genetic Characteristics of BSE in Canada Singeltary reply ;

 


 

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)

 


 

UPDATE

 

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

 


 

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)

 


 

 her healthy calf also carried the mutation

 

(J. A. Richt and S. M. Hall PLoS Pathog. 4, e1000156; 2008).

 

This raises the possibility that the disease could occasionally be genetic in origin. Indeed, the report of the UK BSE Inquiry in 2000 suggested that the UK epidemic had most likely originated from such a mutation and argued against the scrapierelated assumption. Such rare potential pathogenic PRNP mutations could occur in countries at present considered to be free of BSE, such as Australia and New Zealand. So it is important to maintain strict surveillance for BSE in cattle, with rigorous enforcement of the ruminant feed ban (many countries still feed ruminant proteins to pigs). Removal of specified risk material, such as brain and spinal cord, from cattle at slaughter prevents infected material from entering the human food chain. Routine genetic screening of cattle for PRNP mutations, which is now available, could provide additional data on the risk to the public. Because the point mutation identified in the Alabama animals is identical to that responsible for the commonest type of familial (genetic) CJD in humans, it is possible that the resulting infective prion protein might cross the bovine-human species barrier more easily. Patients with vCJD continue to be identified. The fact that this is happening less often should not lead to relaxation of the controls necessary to prevent future outbreaks. Malcolm A. Ferguson-Smith Cambridge University Department of Veterinary Medicine, Madingley Road, Cambridge CB3 0ES, UK e-mail: maf12@cam.ac.uk Jürgen A. Richt College of Veterinary Medicine, Kansas State University, K224B Mosier Hall, Manhattan, Kansas 66506-5601, USA NATURE|Vol 457|26 February 2009

 


 

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 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)

 


 

Sunday, December 15, 2013

 

FDA PART 589 -- SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED VIOLATIONS OFFICIAL ACTION INDICATED OIA UPDATE DECEMBER 2013 UPDATE

 


 

P04.27

 

Experimental BSE Infection of Non-human Primates: Efficacy of the Oral Route

 

Holznagel, E1; Yutzy, B1; Deslys, J-P2; Lasmézas, C2; Pocchiari, M3; Ingrosso, L3; Bierke, P4; Schulz-Schaeffer, W5; Motzkus, D6; Hunsmann, G6; Löwer, J1 1Paul-Ehrlich-Institut, Germany; 2Commissariat à l´Energie Atomique, France; 3Instituto Superiore di Sanità, Italy; 4Swedish Institute for Infectious Disease control, Sweden; 5Georg August University, Germany; 6German Primate Center, Germany

 

Background:

 

In 2001, a study was initiated in primates to assess the risk for humans to contract BSE through contaminated food. For this purpose, BSE brain was titrated in cynomolgus monkeys.

 

Aims:

 

The primary objective is the determination of the minimal infectious dose (MID50) for oral exposure to BSE in a simian model, and, by in doing this, to assess the risk for humans. Secondly, we aimed at examining the course of the disease to identify possible biomarkers.

 

Methods:

 

Groups with six monkeys each were orally dosed with lowering amounts of BSE brain: 16g, 5g, 0.5g, 0.05g, and 0.005g. In a second titration study, animals were intracerebrally (i.c.) dosed (50, 5, 0.5, 0.05, and 0.005 mg).

 

Results:

 

In an ongoing study, a considerable number of high-dosed macaques already developed simian vCJD upon oral or intracerebral exposure or are at the onset of the clinical phase. However, there are differences in the clinical course between orally and intracerebrally infected animals that may influence the detection of biomarkers.

 

Conclusions:

 

Simian vCJD can be easily triggered in cynomolgus monkeys on the oral route using less than 5 g BSE brain homogenate. The difference in the incubation period between 5 g oral and 5 mg i.c. is only 1 year (5 years versus 4 years). However, there are rapid progressors among orally dosed monkeys that develop simian v CJD as fast as intracerebrally inoculated animals.

 

The work referenced was performed in partial fulfillment of the study “BSE in primates“ supported by the EU (QLK1-2002-01096).

 


 

Simian vCJD can be easily triggered in cynomolgus monkeys on the oral route using less than 5 g BSE brain homogenate.

 


 

look at the table and you'll see that as little as 1 mg (or 0.001 gm) caused 7% (1 of 14) of the cows to come down with BSE;

 

 Risk of oral infection with bovine spongiform encephalopathy agent in primates

 

Corinne Ida Lasmézas, Emmanuel Comoy, Stephen Hawkins, Christian Herzog, Franck Mouthon, Timm Konold, Frédéric Auvré, Evelyne Correia, Nathalie Lescoutra-Etchegaray, Nicole Salès, Gerald Wells, Paul Brown, Jean-Philippe Deslys Summary The uncertain extent of human exposure to bovine spongiform encephalopathy (BSE)--which can lead to variant Creutzfeldt-Jakob disease (vCJD)--is compounded by incomplete knowledge about the efficiency of oral infection and the magnitude of any bovine-to-human biological barrier to transmission. We therefore investigated oral transmission of BSE to non-human primates. We gave two macaques a 5 g oral dose of brain homogenate from a BSE-infected cow. One macaque developed vCJD-like neurological disease 60 months after exposure, whereas the other remained free of disease at 76 months. On the basis of these findings and data from other studies, we made a preliminary estimate of the food exposure risk for man, which provides additional assurance that existing public health measures can prevent transmission of BSE to man.

 

snip...

 

BSE bovine brain inoculum

 

100 g 10 g 5 g 1 g 100 mg 10 mg 1 mg 0·1 mg 0·01 mg

 

Primate (oral route)* 1/2 (50%)

 

Cattle (oral route)* 10/10 (100%) 7/9 (78%) 7/10 (70%) 3/15 (20%) 1/15 (7%) 1/15 (7%)

 

RIII mice (ic ip route)* 17/18 (94%) 15/17 (88%) 1/14 (7%)

 

PrPres biochemical detection

 

The comparison is made on the basis of calibration of the bovine inoculum used in our study with primates against a bovine brain inoculum with a similar PrPres concentration that was

 

inoculated into mice and cattle.8 *Data are number of animals positive/number of animals surviving at the time of clinical onset of disease in the first positive animal (%). The accuracy of

 

bioassays is generally judged to be about plus or minus 1 log. ic ip=intracerebral and intraperitoneal.

 

Table 1: Comparison of transmission rates in primates and cattle infected orally with similar BSE brain inocula

 

Published online January 27, 2005

 


 

Calves were challenged by mouth with homogenised brain from confirmed cases of BSE. Some received 300g (3 doses of 100g), some 100g, 10g or 1g. They were then left to develop BSE, but were not subjected to the normal stresses that they might have encountered in a dairy herd. Animals in all four groups developed BSE. There has been a considerable spread of incubation period in some of the groups, but it appears as if those in the 1 and 10g challenge groups most closely fit the picture of incubation periods seen in the epidemic. Experiments in progress indicate that oral infection can occur in some animals with doses as low as 0.01g and 0.001g. ......... http://www.defra.gov.uk/animalh/bse/science-research/pathog.html#dose

 

It is clear that the designing scientists must also have shared Mr Bradley's surprise at the results because all the dose levels right down to 1 gram triggered infection.

 


 

6. It also appears to me that Mr Bradley's answer (that it would take less than say 100 grams) was probably given with the benefit of hindsight; particularly if one considers that later in the same answer Mr Bradley expresses his surprise that it could take as little of 1 gram of brain to cause BSE by the oral route within the same species. This information did not become available until the "attack rate" experiment had been completed in 1995/96. This was a titration experiment designed to ascertain the infective dose. A range of dosages was used to ensure that the actual result was within both a lower and an upper limit within the study and the designing scientists would not have expected all the dose levels to trigger infection. The dose ranges chosen by the most informed scientists at that time ranged from 1 gram to three times one hundred grams. It is clear that the designing scientists must have also shared Mr Bradley's surprise at the results because all the dose levels right down to 1 gram triggered infection.

 


 

2012

 

 ***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...

 


 

MAD COW USDA ATYPICAL L-TYPE BASE BSE, the rest of the story...

 

***Oral Transmission of L-type Bovine Spongiform Encephalopathy in Primate Model

 


 

***Infectivity in skeletal muscle of BASE-infected cattle

 


 

Saturday, December 15, 2012

 

Bovine spongiform encephalopathy: the effect of oral exposure dose on attack rate and incubation period in cattle -- an update 5 December 2012

 


 

 Friday, May 9, 2014

 

Distinct Transmissibility Features of TSE Sources Derived from Ruminant Prion Diseases by the Oral Route in a Transgenic Mouse Model (TgOvPrP4) Overexpressing the Ovine Prion Protein

 


 

Distribution of Peripheral PrPSc in Sheep with Naturally Acquired Scrapie

 

Research Article

 


 

Sunday, May 18, 2014

 

*** Chronic Wasting Disease CWD TSE PRION DISEASE and the transmission to other species

 


 

Thursday, April 17, 2014

 

Novant: Three more may have been exposed to disease CJD

 


 

Sunday, August 09, 2009

 

CJD...Straight talk with...James Ironside...and...Terry Singeltary... 2009

 


 


 


 

Subject: Re: Hello Dr. Gibbs...........

 

Date: Wed, 29 Nov 2000 14:14:18 –0500

 

From: "Clarence J. Gibbs, Jr., Ph.D."

 

To: "Terry S. Singeltary Sr." References: <3a254430 .9fb97284="" wt.net="">

 

Hi Terry:

 

326 E Stret N.E., Washington, D. C. 20002.

 

Better shrimp and oysters than cards!!!!

 

Have a happy holiday and thanks for all the information you bring to the screen.

 

Joe Gibbs ==========

 

Tuesday, August 18, 2009

 

* BSE-The Untold Story - joe gibbs and singeltary 1999 - 2009

 


 

CJD QUESTIONNAIRE USA

 


 


 

CJD and Baby foods (the great debate 1999)

 

Subject: Re: Girl, 13, shows CJD symptoms.

 

From: "Terry S. Singeltary Sr."

 

Reply-To: Bovine Spongiform Encephalopathy

 

Date: Wed, 24 Nov 1999 11:35:44 -0600 Content-Type: text/plain Parts/Attachments: text/plain (67 lines)

 


 

Sunday, May 18, 2008

 

MAD COW DISEASE BSE CJD CHILDREN VACCINES

 


 

Sunday, May 18, 2008

 

BSE Inquiry DRAFT FACTUAL ACCOUNTS DFAs

 


 

Monday, May 19, 2008

 

*** SPORADIC CJD IN FARMERS, FARMERS WIVES, FROM FARMS WITH BSE HERD AND ABATTOIRS ***

 


 

Saturday, April 19, 2014

 

*** Exploring the zoonotic potential of animal prion diseases: In vivo and in vitro approaches ***

 

*** These results would seem to suggest that CWD does indeed have zoonotic potential, at least as judged by the compatibility of CWD prions and their human PrPC target. Furthermore, extrapolation from this simple in vitro assay suggests that if zoonotic CWD occurred, it would most likely effect those of the PRNP codon 129-MM genotype and that the PrPres type would be similar to that found in the most common subtype of sCJD (MM1).

 


 

Friday, April 25, 2014

 

Accuracy of administrative diagnostic data for pathologically confirmed cases of Creutzfeldt-Jakob disease in Massachusetts, 2000-2008

 

Article in Press

 


 

CANADA SEE STEADY INCREASE OF THE SPORADIC CJD’S AND THE VPSPR’S (sporadic CJD’s). ...tss

 

PLEASE NOTE, type determination pending Creutzfeldt Jakob Disease (tdpCJD) in Canada is also on a steady increase.

 

please see ;

 

> 3. Final classification of 50 cases from 2009, 2010, 2011 and 2012 is pending.

 

CJD Deaths Reported by CJDSS1, 1994-20122

 

CJD Deaths Reported by CJDSS1, 1994-20122

 

As of May 31, 2012

 


 


 

SEE DECEMBER 2012 CANADA

 


 

USA SEE STEADY INCREASE OF THE SPORADIC CJD’S AND THE VPSPR’S (sporadic CJD’s). ...tss

 

National Prion Disease Pathology Surveillance Center

 

Cases Examined1

 

(May 18, 2012)

 

5 Includes 14 cases in which the diagnosis is pending, and 18 inconclusive cases;

 

6 Includes 17 (16 from 2012) cases with type determination pending in which the diagnosis of vCJD has been excluded. The Sporadic cases include 16 cases of sporadic Fatal Insomnia (sFI) and 42 cases of Variably Protease-Sensitive Prionopathy (VPSPr) and 2118 cases of sporadic Creutzfeldt-Jakob disease (sCJD).

 

Rev 5/18/2012

 


 

> 6 Includes

 

> 17 (16 from 2012) cases with type determination pending in which the diagnosis of vCJD has been excluded.

 

> The Sporadic cases include 16 cases of sporadic Fatal Insomnia (sFI) and 42 cases of Variably Protease-Sensitive Prionopathy (VPSPr) and 2118 cases of sporadic Creutzfeldt-Jakob disease (sCJD).

 

WELL, it seems the USA mad cow strains in humans classified as type determination pending tdpCJD, VPSPr, sFFI, and sCJD) have steadily increased over the years, and the same old song and dance continues with sporadic CJD cases $$$

 


 

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, October 13, 2013

 

*** CJD TSE Prion Disease Cases in Texas by Year, 2003-2012

 


 

Tuesday, April 01, 2014

 

Questions linger in U.S. CJD cases 2005, and still do in 2014

 


 

Sunday, March 09, 2014

 

A Creutzfeldt-Jakob Disease (CJD) Lookback Study: Assessing the Risk of Blood Borne Transmission of Classic Forms of Creutzfeldt-Jakob Disease

 

FDA TSEAC CIRCUS AND TRAVELING ROAD SHOW FOR THE TSE PRION DISEASES

 


 

Sunday, April 06, 2014

 

SPORADIC CJD and the potential for zoonotic transmission there from, either directly or indirectly via friendly fire iatrogenic mode, evidence to date

 


 

Wednesday, December 11, 2013

 

*** Detection of Infectivity in Blood of Persons with Variant and Sporadic Creutzfeldt-Jakob Disease ***

 


 

Sunday, April 06, 2014

 

SPORADIC CJD and the potential for zoonotic transmission there from, either directly or indirectly via friendly fire iatrogenic mode, evidence to date

 


 

Friday, January 10, 2014

 

vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ???

 


 
 
layperson

 

Terry S. Singeltary Sr.

 

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