Wednesday, August 27, 2014

Highly sensitive detection of small ruminant BSE within TSE mixes by serial Protein Misfolding Cyclic Amplification

Highly sensitive detection of small ruminant BSE within TSE mixes by serial Protein Misfolding Cyclic Amplification 

 

Kevin C. Gougha, Keith Bishopb and Ben C Maddisonb# + Author Affiliations

 

School of Veterinary Medicine and Science, The University of Nottingham, Sutton Bonington, Leicestershire, UK.a ADAS UK, The University of Nottingham, Sutton Bonington, Leicestershire, UK.b

 

ABSTRACT

 

It is assumed that sheep and goats would have consumed the same BSE contaminated meat and bonemeal that was fed to cattle and which precipitated the UK BSE epidemic, which peaked more than twenty years ago. Despite intensive surveillance for cases of BSE within the small ruminant populations of the UK and EU, no instances of BSE have been detected in sheep, and in only two instances has BSE been discovered within goats. If BSE were present within the small ruminant populations it may be at subclinical levels, may manifest as scrapie or may be masked by co-infection with scrapie. To determine whether BSE is potentially circulating at low levels within the European small ruminant populations, highly sensitive assays are required that could specifically detect BSE even within the presence of scrapie prion protein. Here we present a novel assay based on the specific amplification of BSE using the serial Protein Misfolding Cyclic Amplification assay (sPMCA), which specifically amplified low amounts of ovine and caprine BSE which had been mixed into a range of scrapie positive brain homogenates. *** Detection of BSE prion protein within a large excess of classical, atypical and CH1641 scrapie isolates is demonstrated. In a blind trial this sPMCA based assay specifically amplified BSE within brain mixes with 100% specificity and 97% sensitivity when BSE is diluted into the scrapie brain homogenates at 1% v/v.

 

FOOTNOTES ↵#Address correspondence to Ben Maddison, ben.maddison@adas.co.uk Copyright © 2014, American Society for Microbiology. All Rights Reserved.

 


 

>>> *** Detection of BSE prion protein within a large excess of classical, atypical and CH1641 scrapie isolates is demonstrated.

 

now this is getting very interesting. what implications might this have on humans and other species ?

 

greetings cjd world,

 

I find this very interesting, this coexistence of different TSE prion strains from different TSE sources. this new/old study out reminds me of way back ;

 

According to Professor James Ironside of the National CJD Surveillance Unit, Miss Rimmer's case was "unique" and tests showed signs of both vCJD and new variant CJD.

 

"Our understanding of the case is not complete. It is one of the most unusual and difficult cases I have ever come across," he explained.

 

"The characteristics of the disease suffered by Miss Rimmer do not fall neatly into any category. "The investigations that we have performed so far would indicate that this case, unique as it is, has more similarities to sporadic CJD than to new variant."

 

snip...

 

Mr Hughes returned a verdict of death by natural causes and concluded that Miss Rimmer died of bronchial pneumonia caused by CJD. ...

 


 

Coexistence of multiple PrPSc types in individuals with CJD

 


 

Published online October 31, 2005

 

Coexistence of multiple PrPSc types in individuals with Creutzfeldt-Jakob disease

 

Magdalini Polymenidou, Katharina Stoeck, Markus Glatzel, Martin Vey, Anne Bellon, and Adriano Aguzzi

 

Summary Background

 

The molecular typing of sporadic Creutzfeldt-Jakob disease (CJD) is based on the size and glycoform ratio of protease-resistant prion protein (PrPSc), and on PRNP haplotype. On digestion with proteinase K, type 1 and type 2 PrPSc display unglycosylated core fragments of 21 kDa and 19 kDa, resulting from cleavage around amino acids 82 and 97, respectively.

 

Methods We generated anti-PrP monoclonal antibodies to epitopes immediately preceding the differential proteinase K cleavage sites. These antibodies, which were designated POM2 and POM12, recognise type 1, but not type 2, PrPSc.

 

Findings We studied 114 brain samples from 70 patients with sporadic CJD and three patients with variant CJD. Every patient classified as CJD type 2, and all variant CJD patients, showed POM2/POM12 reactivity in the cerebellum and other PrPSc-rich brain areas, with a typical PrPSc type 1 migration pattern.

 

Interpretation The regular coexistence of multiple PrPSc types in patients with CJD casts doubts on the validity of electrophoretic PrPSc mobilities as surrogates for prion strains, and questions the rational basis of current CJD classifications.

 

snip...

 

The above results set the existing CJD classifications into debate and introduce interesting questions about human CJD types. For example, do human prion types exist in a dynamic equilibrium in the brains of affected individuals? Do they coexist in most or even all CJD cases? Is the biochemically identified PrPSc type simply the dominant type, and not the only PrPSc species?

 


 

Published online October 31, 2005

 

what i been saying for years, that the diagnostic criteria differentiating between the nvCJD (i.e. 'the chosen ones') and the sCJD (i.e. 'the forgotten ones') has been terribly flawed from the beginning. ....

 

 Friday, October 11, 2013

 

Coexistence of Distinct Prion Types Enables Conformational Evolution of Human PrPSc by Competitive Selection

 


 

Wednesday, January 18, 2012

 

Selection of Distinct Strain Phenotypes in Mice Infected by Ovine Natural Scrapie Isolates Similar to CH1641 Experimental Scrapie

 

Journal of Neuropathology & Experimental Neurology: February 2012 - Volume 71 - Issue 2 - p 140–147

 


 

Wednesday, September 9, 2009

 

 Co-existence of scrapie prion protein types 1 and 2 in sporadic Creutzfeldt-Jakob disease: its effect on the phenotype and prion-type characteristics

 


 

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

 

Subject: Coexistence of CJD and Alzheimer's disease: An autopsy case showing typical clinical features of CJD

 

Date: Sat, 10 Apr 2004 21:01:13 –0500

 

From: "Terry S. Singeltary Sr."

 

To: Bovine Spongiform Encephalopathy

 

 Neuropathology Volume 24 Issue 1 Page 46 - March 2004 doi:10.1111/j.1440-1789.2003.00513.x

 

Coexistence of CJD and Alzheimer's disease: An autopsy case showing typical clinical features of CJD Kuniaki Tsuchiya1,2,3 , Saburo Yagishita4 , Kenji Ikeda2 , Michio Sano5 , Kazuhiro Taki6 , Keisuke Hashimoto6 , Sadakiyo Watabiki3

 

and Hidehiro Mizusawa7

 

The present report concerns an autopsy case of CJD showing typical clinical features of CJD. The patient was a Japanese woman without hereditary burden or dementing disorder anamnesis who was 70-years-old at the time of death. She developed gait disturbance at age 68, followed by memory impairment, visual disturbance, and myoclonus. A neurological examination approximately 2 months after the disease onset revealed akinetic mutism, in addition to periodic synchronous discharges on electroencephalogram. Serial neuroradiological examinations disclosed progressive atrophy of the brain. She died of bronchopneumonia 25 months after the disease onset. The brain weighed 560 g (cerebrum 490 g, brainstem with cerebellum 70 g). Macroscopically, neuropathological examination showed prominent atrophy of the cerebrum, caudate nucleus, and cerebellum, in addition to necrosis of the cerebral white matter, compatible with panencephalopathic CJD. Histologically, there was neuronal loss with or without spongiform change in the cerebral cortex, parahippocampal gyrus, amygdala, striatum, pallidum, thalamus, pontine nucleus, and cerebellar granule cells, in addition to diffuse synaptic-type prion staining in the cerebrum and cerebellum. Furthermore, senile plaques, compatible with definite Consortium to establish a registry for Alzheimer's disease rank Alzheimer's disease, and neurofibrillary changes of the limbic system, consistent with stage IV of Braak's classification, were found. Based on these clinicopathological findings and a review of the published literature, it is concluded that there were two forms of coexistence of CJD and Alzheimer's disease in the same patient.

 

Received 14 May 2003; revised and accepted 23 July 2003.

 

Affiliations

 

1Department of Laboratory Medicine and Pathology, Tokyo Metropolitan Matsuzawa Hospital, 2Department of Neuropathology, Tokyo Institute of Psychiatry, 3Department of Neurology, Musashino Red Cross Hospital, Tokyo, 4Department of Pathology, Kanagawa Rehabilitation Center, Kanagawa, 5Department of Internal Medicine, Musashisakai Hospital, 6Department of Pathology, Musashino Red Cross Hospital and 7Department of Neurology, Tokyo Medical and Dental University, Tokyo, Japan

 

Correspondence

 

Kuniaki Tsuchiya, md, PhD, Department of Laboratory Medicine and Pathology, Tokyo Metropolitan Matsuzawa Hospital, 2-1-1, Kamikitazawa, Setagaya-ku, Tokyo, 156-0057, Japan. Email: ktsuchi@jcom.home.ne.jp

 

To cite this article Tsuchiya, Kuniaki, Yagishita, Saburo, Ikeda, Kenji, Sano, Michio, Taki, Kazuhiro, Hashimoto, Keisuke, Watabiki, Sadakiyo & Mizusawa, Hidehiro (2004) Coexistence of CJD and Alzheimer's disease: An autopsy case showing typical clinical features of CJD. Neuropathology 24 (1), 46-55. doi: 10.1111/ j.1440-1789.2003.00513.x

 


 

Thursday, July 31, 2014

 

EFSA Scrapie reduction unlikely without effective breeding programme

 


 

Sunday, August 24, 2014

 

USAHA 117TH ANNUAL MEETING USDA-APHIS–VS CWD Herd Certification Program Goals TSE PRION October 17 – 23, 2013

 


 

Tuesday, August 12, 2014

 

MAD COW USDA TSE PRION COVER UP or JUST IGNORANCE, for the record AUGUST 2014

 


 

IT is of my opinion, that the OIE and the USDA et al, are the soul reason, and responsible parties, for Transmissible Spongiform Encephalopathy TSE prion diseases, including typical and atypical BSE, typical and atypical Scrapie, and all strains of CWD, and human TSE there from, spreading around the globe.

 

 

I have lost all confidence of this organization as a regulatory authority on animal disease, and consider it nothing more than a National Trading Brokerage for all strains of animal TSE, just to satisfy there commodity. AS i said before, OIE should hang up there jock strap now, since it appears they will buckle every time a country makes some political hay about trade protocol, commodities and futures. IF they are not going to be science based, they should do everyone a favor and dissolve there organization.

 

JUST because of low documented human body count with nvCJD and the long incubation periods, the lack of sound science being replaced by political and corporate science in relations with the fact that science has now linked some sporadic CJD with atypical BSE and atypical scrapie, and the very real threat of CWD being zoonosis, I believed the O.I.E. has failed terribly and again, I call for this organization to be dissolved. ...

 

 

Tuesday, July 17, 2012

 

O.I.E. BSE, CWD, SCRAPIE, TSE PRION DISEASE Final Report of the 80th General Session, 20 - 25 May 2012

 


 

 

Thursday, December 20, 2012

 

OIE GROUP RECOMMENDS THAT SCRAPE PRION DISEASE BE DELISTED AND SAME OLD BSe WITH BOVINE MAD COW DISEASE

 


 

Monday, November 30, 2009

 

*** USDA AND OIE COLLABORATE TO EXCLUDE ATYPICAL SCRAPIE NOR-98 ANIMAL HEALTH CODE, DOES NOT SURPRISE ME $

 


 

Sunday, August 24, 2014

 

USAHA 117TH ANNUAL MEETING USDA-APHIS–VS CWD Herd Certification Program Goals TSE PRION October 17 – 23, 2013

 

SNIP...

 

REPORT OF THE COMMITTEE 344 Ewes were experimentally inoculated with brain homogenate obtained from a U.S. sheep with clinical Nor98-like scrapie.

 

Recipient ewes are bred annually to examine the placenta for evidence of a transmissible agent. Placentas shed 2009-2013 were negative.

 

*** In 2013, one recipient ewe developed an unrelated disease. At postmortem examination, abundant accumulation of PrPSc was observed only in the cerebellum of this ewe with much less accumulation in the hindbrain obex. This confirms that initial inoculation of these ewes has been successful. Monitoring continues in the remaining ewes of this study.

 

Sunday, August 24, 2014

 

USAHA 117TH ANNUAL MEETING USDA-APHIS–VS CWD Herd Certification Program Goals TSE PRION October 17 – 23, 2013

 


 

Sunday, June 29, 2014

 

Transmissible Spongiform Encephalopathy TSE Prion Disease North America 2014

 


 

 

TSS

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