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
http://efsaopinionbseanimalprotein.blogspot.com/2014/07/efsa-scrapie-reduction-unlikely-without.html
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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