Volume 13, Number 12–December 2007
Research
Phenotypic Similarity of Transmissible Mink Encephalopathy in Cattle and L-type Bovine Spongiform Encephalopathy in a Mouse Model
Thierry Baron,* Anna Bencsik,* Anne-Gaëlle Biacabe,* Eric Morignat,* andRichard A. Bessen†*Agence Française de Sécurité Sanitaire des Aliments–Lyon, Lyon, France; and†Montana State University, Bozeman, Montana, USA
Abstract
Transmissible mink encepholapathy (TME) is a foodborne transmissiblespongiform encephalopathy (TSE) of ranch-raised mink; infection with aruminant TSE has been proposed as the cause, but the precise origin of TMEis unknown. To compare the phenotypes of each TSE, bovine-passaged TMEisolate and 3 distinct natural bovine spongiform encephalopathy (BSE) agents(typical BSE, H-type BSE, and L-type BSE) were inoculated into an ovinetransgenic mouse line (TgOvPrP4). Transgenic mice were susceptible toinfection with bovine-passaged TME, typical BSE, and L-type BSE but not toH-type BSE. Based on survival periods, brain lesions profiles,disease-associated prion protein brain distribution, and biochemicalproperties of protease-resistant prion protein, typical BSE had a distintphenotype in ovine transgenic mice compared to L-type BSE and bovine TME.The similar phenotypic properties of L-type BSE and bovine TME in TgOvPrP4mice suggest that L-type BSE is a much more likely candidate for the originof TME than is typical BSE.
snip...
Conclusion
These studies provide experimental evidence that the Stetsonville TME agentis distinct from typical BSE but has phenotypic similarities to L-type BSEin TgOvPrP4 mice. Our conclusion is that L-type BSE is a more likelycandidate for a bovine source of TME infection than typical BSE. In thescenario that a ruminant TSE is the source for TME infection in mink, thiswould be a second example of transmission of a TSE from ruminants tonon-ruminants under natural conditions or farming practices in addition totransmission of typical BSE to humans, domestic cats, and exotic zoo animals(37). The potential importance of this finding is relevant to L-type BSE,which based on experimental transmission into humanized PrP transgenic miceand macaques, suggests that L-type BSE is more pathogenic for humans thantypical BSE (24,38).
http://www.cdc.gov/eid/content/13/12/1887.htm?s_cid=eid1887_e
J. Biol. Chem., Vol. 282, Issue 49, 35878-35886, December 7, 2007
High Titers of Transmissible Spongiform Encephalopathy InfectivityAssociated with Extremely Low Levels of PrPSc in Vivo*
Rona M. Barron12, Susan L. Campbell13, Declan King, Anne Bellon, Karen E.Chapman¶, R. Anthony Williamson, and Jean C. MansonFrom the Neuropathogenesis Unit, Roslin Institute, Ogston Building, WestMains Road, Edinburgh EH9 3JF, Scotland, United Kingdom, the Department ofImmunology, Scripps Research Institute, La Jolla, California 92037, and the¶Centre for Cardiovascular Sciences, Queen's Medical Research Institute,University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ,Scotland, United Kingdom
Diagnosis of transmissible spongiform encephalopathy (TSE) disease in humansand ruminants relies on the detection in post-mortem brain tissue of theprotease-resistant form of the host glycoprotein PrP. The presence of thisabnormal isoform (PrPSc) in tissues is taken as indicative of the presenceof TSE infectivity. Here we demonstrate conclusively that high titers of TSEinfectivity can be present in brain tissue of animals that show clinical andvacuolar signs of TSE disease but contain low or undetectable levels ofPrPSc. This work questions the correlation between PrPSc level and the titerof infectivity and shows that tissues containing little or no proteinaseK-resistant PrP can be infectious and harbor high titers of TSE infectivity.Reliance on protease-resistant PrPSc as a sole measure of infectivity maytherefore in some instances significantly underestimate biologicalproperties of diagnostic samples, thereby undermining efforts to contain anderadicate TSEs.
---------------------------------------------
Received for publication, May 25, 2007 , and in revised form, September 24,2007.
* This work was supported by United Kingdom Department for Environment,Food, and Rural Affairs Grant SE1437. The costs of publication of thisarticle were defrayed in part by the payment of page charges. This articlemust therefore be hereby marked "advertisement" in accordance with 18 U.S.C.Section 1734 solely to indicate this fact.
The on-line version of this article (available at http://www.jbc.org)contains supplemental Figs. S1–S3 and Table S1.
1 Both authors contributed equally to this work.
3 Current address: Medical Research Council Clinical Sciences Centre,Imperial College, Hammersmith Campus, Du Cane Road, London W12 0NN, UnitedKingdom.
2 To whom correspondence should be addressed. Tel.: 44-131-667-5204; Fax:44-131-668-3872; E-mail: rona.barron@bbsrc.ac.uk.
http://www.jbc.org/cgi/content/abstract/282/49/35878?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=prion&searchid=1&FIRSTINDEX=0&volume=282&issue=49&resourcetype=HWCIT
Transmissible Mink Encephalopathy TMESubject: In Confidence - Perceptions of unconventional slow virus diseasesof animals in the USA - APRIL-MAY 1989 - G A H Wells
Gerald Wells: Report of the Visit to USA, April-May 1989
snip...
The general opinion of those present was that BSE, as anovert disease phenomenon, _could exist in the USA, but if it did,it was very rare. The need for improved and specific surveillancemethods to detect it as recognised...
snip...
It is clear that USDA have little information and _no_ regulatoryresponsibility for rendering plants in the US...
snip...
3. Prof. A. Robertson gave a brief account of BSE. The US approachwas to accord it a _very low profile indeed_. Dr. A Thiermann showedthe picture in the ''Independent'' with cattle being incinerated and thoughtthis was a fanatical incident to be _avoided_ in the US _at all costs_...
snip...please read this old full text document !
http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf
To be published in the Proceedings of theFourth International Scientific Congress inFur Animal Production. Toronto, Canada,August 21-28, 1988
Evidence That Transmissible Mink EncephalopathyResults from Feeding Infected Cattle
R.F. Marsh* and G.R. Hartsough
•Department of Veterinary Science, University of Wisconsin-Madison, Madison,Wisconsin 53706; and ^Emba/Creat Lakes Ranch Service, Thiensville, Wisconsin53092
ABSTRACTEpidemiologic investigation of a new incidence oftransmissible mink encephalopathy (TME) in Stetsonville, Wisconsinsuggests that the disease may have resulted from feeding infectedcattle to mink. This observation is supported by the transmission ofa TME-like disease to experimentally inoculated cattle, and by therecent report of a new bovine spongiform encephalopathy inEngland.
INTRODUCTION
Transmissible mink encephalopathy (TME) was first reported in 1965 by Hartsoughand Burger who demonstrated that the disease was transmissible with a long incubationperiod, and that affected mink had a spongiform encephalopathy similar to that found inscrapie-affecied sheep (Hartsough and Burger, 1965; Burger and Hartsough, 1965).Because of the similarity between TME and scrapie, and the subsequent finding that thetwo transmissible agents were indistinguishable (Marsh and Hanson, 1969), it wasconcluded that TME most likely resulted from feeding mink scrapie-infecied sheep.The experimental transmission of sheep scrapie to mink (Hanson et al., 1971)confirmed the close association of TME and scrapie, but at the same time providedevidence that they may be different. Epidemiologic studies on previous incidences ofTME indicated that the incubation periods in field cases were between six months andone year in length (Harxsough and Burger, 1965). Experimentally, scrapie could not betransmitted to mink in less than one year.To investigate the possibility that TME may be caused by a (particular strain ofscrapie which might be highly pathogenic for mink, 21 different strains of the scrapieagent, including their sheep or goat sources, were inoculated into a total of 61 mink.Only one mink developed a progressive neurologic disease after an incubation period of22 mon..s (Marsh and Hanson, 1979). These results indicated that TME was either causedby a strain of sheep scrapie not yet tested, or was due to exposure to a scrapie-like agentfrom an unidentified source.
OBSERVATIONS AND RESULTS
A New Incidence of TME. In April of 1985, a mink rancher in Stetsonville, Wisconsinreported that many of his mink were "acting funny", and some had died. At this time, wevisited the farm and found that approximately 10% of all adult mink were showingtypical signs of TME: insidious onset characterized by subtle behavioral changes, loss ofnormal habits of cleanliness, deposition of droppings throughout the pen rather than in asingle area, hyperexcitability, difficulty in chewing and swallowing, and tails arched overtheir _backs like squirrels. These signs were followed by progressive deterioration ofneurologic function beginning with locomoior incoordination, long periods of somnolencein which the affected mink would stand motionless with its head in the corner of thecage, complete debilitation, and death. Over the next 8-10 weeks, approximately 40% ofall the adult mink on the farm died from TME.Since previous incidences of TME were associated with common or shared feedingpractices, we obtained a careful history of feed ingredients used over the past 12-18months. The rancher was a "dead stock" feeder using mostly (>95%) downer or dead dairycattle and a few horses. Sheep had never been fed.
Experimental Transmission. The clinical diagnosis of TME was confirmed byhistopaihologic examination and by experimental transmission to mink after incubationperiods of four months. To investigate the possible involvement of cattle in this diseasecycle, two six-week old castrated Holstein bull calves were inoculated intracerebrallywith a brain suspension from affected mink. Each developed a fatal spongiformencephalopathy after incubation periods of 18 and 19 months.
DISCUSSION
These findings suggest that TME may result from feeding mink infected cattle andwe have alerted bovine practitioners that there may exist an as yet unrecognizedscrapie-like disease of cattle in the United States (Marsh and Hartsough, 1986). A newbovine spongiform encephalopathy has recently been reported in England (Wells et al.,1987), and investigators are presently studying its transmissibility and possiblerelationship to scrapie. Because this new bovine disease in England is characterized bybehavioral changes, hyperexcitability, and agressiveness, it is very likely it would beconfused with rabies in the United Stales and not be diagnosed. Presently, brains fromcattle in the United States which are suspected of rabies infection are only tested withanti-rabies virus antibody and are not examined histopathologically for lesions ofspongiform encephalopathy.We are presently pursuing additional studies to further examine the possibleinvolvement of cattle in the epidemiology of TME. One of these is the backpassage ofour experimental bovine encephalopathy to mink. Because (here are as yet no agent-specific proteins or nucleic acids identified for these transmissible neuropathogens, onemeans of distinguishing them is by animal passage and selection of the biotype whichgrows best in a particular host. This procedure has been used to separate hamster-adapted and mink-udapted TME agents (Marsh and Hanson, 1979). The intracerebralbackpassage of the experimental bovine agent resulted in incubations of only four monthsindicating no de-adaptation of the Stetsonville agent for mink after bovine passage.Mink fed infected bovine brain remain normal after six months. It will be essential todemonstrate oral transmission fiom bovine to mink it this proposed epidemiologicassociation is to be confirmed.
ACKNOWLEDGEMENTS
These studies were supported by the College of Agricultural and Life Sciences,University of Wisconsin-Madison and by a grant (85-CRCR-1-1812) from the UnitedStates Department of Agriculture. The authors also wish to acknowledge the help andencouragement of Robert Hanson who died during the course of theseinvestigations.
REFERENCES
Burger, D. and Hartsough, G.R. 1965. Encephalopathy of mink. II.Experimental andnatural transmission. J. Infec. Dis. 115:393-399.Hanson, R.P., Eckroade, R.3., Marsh, R.F., ZuRhein, C.M., Kanitz, C.L. andGustatson,D.P. 1971. Susceptibility of mink to sheep scrapie. Science 172:859-861.Hansough, G.R. and Burger, D. 1965. Encephalopathy of mink. I.Epizoociologic andclinical observations. 3. Infec. Dis. 115:387-392.Marsh, R.F. and Hanson, R.P. 1969. Physical and chemical properties of thetransmissible mink encephalopathy agent. 3. ViroL 3:176-180.Marsh, R.F. and Hanson, R.P. 1979. On the origin of transmissible minkencephalopathy. In Hadlow, W.J. and Prusiner, S.P. (eds.) Slow transmissiblediseases of the nervous system. Vol. 1, Academic Press, New York, pp451-460.Marsh, R.F. and Hartsough, G.R. 1986. Is there a scrapie-like disease incattle?Proceedings of the Seventh Annual Western Conference for Food AnimalVeterinaryMedicine. University of Arizona, pp 20.Wells, G.A.H., Scott, A.C., Johnson, C.T., Cunning, R.F., Hancock, R.D.,Jeffrey, M.,Dawson, M. and Bradley, R. 1987. A novel progressive spongiformencephalopathyin cattle. Vet. Rec. 121:419-420.
MARSH
http://www.bseinquiry.gov.uk/files/mb/m09/tab05.pdf
In Confidence - Perceptions of unconventional slow virus diseasesof animals in the USA - APRIL-MAY 1989 - G A H Wells
http://www.bseinquiry.gov.uk/files/mb/m11b/tab01.pdf
SEE FULL TEXT TME
http://transmissible-mink-encephalopathy.blogspot.com/
TME hyper/drowsy, INTER-SPECIES TRANSMISSION CWD and strain properties
https://www.blogger.com/comment.g?blogID=37955408&postID=116577315153980667
NOR-98 ATYPICAL SCRAPIE USA UPDATE AS AT OCT 2007
ABSTRACTS SPORADIC CJD AND H BASE MAD COW ALABAMA AND TEXAS SEPTEMBER 2007Date: Mon, 24 Sep 2007 21:31:55 -0500
I suggest that you all read the data out about h-BASE and sporadic CJD,GSS,blood, and some of the other abstracts from the PRION2007. ...
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0709&L=sanet-mg&T=0&F=&S=&P=19744
*** PLEASE READ AND UNDERSTAND THE RAMIFICATIONS OF THIS !!!THE PRICE OF POKER INDEED GOES UP. ...TSS
USA BASE CASE, (ATYPICAL BSE), AND OR TSE (whatever they are calling ittoday), please note that both the ALABAMA COW, AND THE TEXAS COW, bothwere''H-TYPE'', personal communication Detwiler et al Wednesday, August 22,200711:52 PM. ...TSS
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=19779
see full text 143 pages ;
http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf
full text ;
http://nor-98.blogspot.com/
******[2] USA: National Prion Disease Pathology Surveillance CenterDate: June 2007Source: National Prion Disease Pathology Surveillance Center (USA) [edited]<http://www.cjdsurveillance.com/pdf/case-table.pdf>
CJD Cases examined----------------------Year / Referrals / Prion disease / Sporadic / Familial / Iatrogenic / vCJD
1996 / 42 / 32 / 26 / 4 / 0 / 01997 / 115 / 68 / 57 / 9 / 0 / 01998 / 93 / 53 / 45 / 7 / 1 / 01999 / 114 / 69 / 61 / 8 / 0 / 02000 / 151 / 103 / 89 / 14 / 0 / 02001 / 208 / 116 / 106 / 9 / 0 / 02002 / 255 / 143 / 118 / 23 / 2 / 02003 / 272 / 174 / 132 / 41 / 0 / 02004 / 334 / 183 / 157 / 21 / 0 / 1*2005 / 352 / 195 / 152 / 37 / 1 / 02006 / 372 / 186 / 143 / 30 / 0 / 1**2007 / 120 / 68 / 35 / 7 / 0 / 0TOTAL / 2428*** / 1390**** / 1121 / 210 / 4 / 2
*Acquired in UK** Acquired in Saudi Arabia*** Includes 17 inconclusive and 9 pending (1 from 2006, 8 from 2007.**** Includes 17 non-vCJD type unknown (2 from 1996, 2 from 1997, 1from 2001, 1 from 2003, 4 from 2004, 3 from 2005, 4 from 2006) and 36type pending (2 from 2005, 8 from 2006, 26 from 2007).
Notes:
-- Cases are listed based on the year of death when available. If theyear of death is not available, the year of sample receipt is used.
-- Referrals: Cases with possible or probable prion disease fromwhich brain tissue or blood in the case of familial disease were submitted.
-- Inconclusive: Cases in which the samples were not sufficient tomake a diagnosis.
-- Non-vCJD type unknown are cases in which the tissue submitted wasadequate to establish the presence but not the type; in all cases,vCJD could be excluded.
--Communicated by:Terry S. Singeltary Sr. <flounder9@verizon.net>
[In submitting these data, Terry S. Singeltary Sr. draws attention tothe steady increase in the "type unknown" category, which, accordingto their definition, comprises cases in which vCJD could be excluded.The total of 26 cases for the current year (2007) is disturbing,possibly symptomatic of the circulation of novel agents.Characterization of these agents should be given a high priority. - Mod.CP]
[see also:
snip...
************************************************************Become a ProMED-mail Premium Subscriber at<http://www.isid.org/ProMEDMail_Premium.shtml>************************************************************Visit ProMED-mail's web site at <http://www.promedmail.org>.
http://pro-med.blogspot.com/2007/11/proahedr-prion-disease-update-2007-07.html
SEE STEADY INCREASE IN SPORADIC CJD IN THE USA FROM1997 TO 2006. SPORADIC CJD CASES TRIPLED, with phenotypeof 'UNKNOWN' strain growing. ...
http://www.cjdsurveillance.com/resources-casereport.html
There is a growing number of human CJD cases, and they were presented lastweek in San Francisco by Luigi Gambatti(?) from his CJD surveillancecollection.
He estimates that it may be up to 14 or 15 persons which display selectivelySPRPSC and practically no detected RPRPSC proteins.
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf
PLEASE NOTE IN USA CJD UPDATE AS AT JUNE 2007, please note steady increasein ''TYPE UNKNOWN''. ...TSS
1 Acquired in the United Kingdom; 2 Acquired in Saudi Arabia; 3 Includes 17inconclusive and 9 pending (1 from 2006, 8from 2007); 4 Includes 17 non-vCJD type unknown (2 from 1996, 2 from 1997, 1from 2001, 1 from 2003, 4 from 2004, 3from 2005, 4 from 2006) and 36 type pending (2 from 2005, 8 from 2006,
*** 26 from 2007)
http://www.cjdsurveillance.com/pdf/case-table.pdf
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734.
http://jama.ama-assn.org/http://www.neurology.org/cgi/eletters/60/2/176#535
JOURNAL OF NEUROLOGY
MARCH 26, 2003
RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob
disease in the United States
Email Terry S. Singeltary:
flounder@wt.net
I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to
comment on the CDC's attempts to monitor the occurrence of emerging
forms of CJD. Asante, Collinge et al [1] have reported that BSE
transmission to the 129-methionine genotype can lead to an alternate
phenotype that is indistinguishable from type 2 PrPSc, the commonest
sporadic CJD. However, CJD and all human TSEs are not reportable
nationally. CJD and all human TSEs must be made reportable in every
state and internationally. I hope that the CDC does not continue to
expect us to still believe that the 85%+ of all CJD cases which are
sporadic are all spontaneous, without route/source. We have many TSEs in
the USA in both animal and man. CWD in deer/elk is spreading rapidly and
CWD does transmit to mink, ferret, cattle, and squirrel monkey by
intracerebral inoculation. With the known incubation periods in other
TSEs, oral transmission studies of CWD may take much longer. Every
victim/family of CJD/TSEs should be asked about route and source of this
agent. To prolong this will only spread the agent and needlessly expose
others. In light of the findings of Asante and Collinge et al, there
should be drastic measures to safeguard the medical and surgical arena
from sporadic CJDs and all human TSEs. I only ponder how many sporadic
CJDs in the USA are type 2 PrPSc?
http://www.neurology.org/cgi/eletters/60/2/176#535
doi:10.1016/S1473-3099(03)00715-1Copyright © 2003 Published by Elsevier Ltd.Newsdesk
Tracking spongiform encephalopathies in North America
Xavier Bosch
Available online 29 July 2003.
Volume 3, Issue 8, August 2003, Page 463
“My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost mymom to hvCJD (Heidenhain variant CJD)and have been searching for answers ever since. What I have found is that wehave not been told the truth. CWDin deer and elk is a small portion of a much bigger problem.”............................
http://www.thelancet.com/journals/laninf/article/PIIS1473309903007151/fulltext
http://download.thelancet.com/pdfs/journals/1473-3099/PIIS1473309903007151.pdf
see history of cjd questionnaire
http://brain.hastypastry.net/forums/showthread.php?t=2408
Sent: Monday May 28, 2007
Subject: THE BIG LIE SPORADIC CJD AND MAD COW DISEASEs i.e. TSE
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0705&L=sanet-mg&T=0&P=25276
Subject: HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and theUKBSEnvCJD only theoryDate: January 29, 2006 at 9:03 am PST
Comments sent via JAMA Feedback Page------------------------------------------------------------NAME: Terry S. Singeltary Sr.E-MAIL: flounder9@verizon.netIP ADDRESS: xxxxxxxxHOSTNAME: xxxxxxxxPREVIOUS PAGE: http://jama.ama-assn.org/misc/authors.dtlBROWSER: Mozilla/5.0 (Windows; U; Win98; en-US; rv:1.0.2) Gecko/20030208Netscape/7.02PROMOTIONAL USE: (not answered)
HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJDonly theory
TSEs have been rampant in the USA for decades in many species, and they allhave been rendered and fed back to animals for human/animal consumption.propose that the current diagnostic criteria for human TSEs only enhancesand helps the spreading of human TSE from the continued belief of theUKBSEnvCJD only theory in 2007. With all the science to date refuting it, tocontinue to validate this myth, will only spread this TSE agent through amultitude of potential routes and sources i.e. consumption, surgical, blood,medical, cosmetics etc. I propose as with Aguzzi, Asante, Collinge, Caughey,Deslys, Dormont, Gibbs, Ironside, Manuelidis, Marsh, et al and many more,that the world of TSE Transmissible Spongiform Encephalopathy is far from anexact science, but there is enough provenscience to date that this myth should be put to rest once and for all, andthat we move forward with a new classification for human and animal TSE thatwould properly identify the infected species, the source species, and thenthe route.
This would further have to be broken down to strain of species and then theroute of transmission would further have to be broken down. Accumulation andTransmission are key to the threshold from sub-clinical to clinical disease,and key to all this, is to stop the amplification and transmission of thisagent, the spreading of, no matter what strain. In my opinion, to continuewith this myth that the U.K. strain of BSE (one strain TSE in cows), and thenv/v CJD (one strain TSE humans) and that all the rest of human TSE are justone single strain i.e. sporadic CJD (when to date there are 6 differentphenotypes of sCJD, and growing per Gambetti et al), and that no otheranimal TSE transmits to humans, to continue with this masquerade will onlycontinue to spread, expose, and kill, who knows how many more in the yearsand decades to come. ONE was enough for me, My Mom, hvCJD i.e. HeidenhainVariant CJD, DOD 12/14/97 confirmed, which is nothing more than another mansname added to CJD, like CJD itself, Jakob and Creutzfeldt, orGerstmann-Straussler-Scheinker syndrome, just another CJD or human TSE,named after another human.
WE are only kidding ourselves with the current diagnostic criteria for humanand animal TSE, especially differentiating between the nvCJD vs the sporadicCJDstrains and then the GSS strains and also the FFI fatal familial insomniastrains or the ones that mimics one or the other of those TSE? Tissueinfectivity and strain typing of the many variants of the human and animalTSEs are paramount in all variants of all TSE. There must be a properclassification that will differentiate between all these human TSE in orderto do this. With the CDI and other more sensitive testing coming about, Ionly hope that my proposal will some day be taken seriously. ...
Terry S. Singeltary Sr.P.O. Box 42Bacliff, Texas USA 77518flounder9@verizon.net
Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease inthe United States
http://cjdusa.blogspot.com/
i am reminded of a few things deep throat (high ranking official at usda)told me years ago;
==========================================
The most frightening thing I have read all day is thereport of Gambetti's finding of a new strain ofsporadic cjd in young people.........Dear God,
https://www.blogger.com/comment.g?blogID=7842737484277562285&postID=5759550357128128100
TSS
Friday, November 30, 2007
Saturday, November 24, 2007
CJD UPDATE USA NOV. 2007
FC5.5.1
BASE Transmitted to Primates and MV2 sCJD Subtype Share PrP27-30 and PrPSc
C-terminal Truncated Fragments Zanusso, G1; Commoy, E2; Fasoli, E3; Fiorini, M3; Lescoutra, N4; Ruchoux,MM4; Casalone, C5; Caramelli, M5; Ferrari, S3; Lasmezas, C6; Deslys, J-P4; Monaco, S31University of Verona, of Neurological and Visual Sciences, Italy; 2CEA, IMETI/SEPIA,France; 3University of Verona, Neurological and Visual Sciences, Italy; 4IMETI/SEPIA,France; 5IZSPLVA, Italy; 6The Scripps Research Insitute, USA
The etiology of sporadic Creutzfeldt-Jakob disease (sCJD), the most frequent humanprion disease, remains still unknown. The marked disease phenotype heterogeneityobserved in sCJD is thought to be influenced by the type of proteinase K-resistantprion protein, or PrPSc (type 1 or type 2 according to the electrophoretic mobility ofthe unglycosylated backbone), and by the host polymorphic Methionine/Valine (M/V)codon 129 of the PRNP. By using a two-dimensional gel electrophoresis (2D-PAGE)and imunoblotting we previously showed that in sCJD, in addition to the PrPSc type,distinct PrPSc C-terminal truncated fragments (CTFs) correlated with different sCJDsubtypes. Based on the combination of CTFs and PrPSc type, we distinguished threePrPSc patterns: (i) the first was observed in sCJD with PrPSc type 1 of all genotypes,;(ii) the second was found in M/M-2 (cortical form); (iii) the third in amyloidogenic M/V-2 and V/V-2 subtypes (Zanusso et al., JBC 2004) . Recently, we showed that sCJDsubtype M/V-2 shared molecular and pathological features with an atypical form ofBSE, named BASE, thus suggesting a potential link between the two conditions. Thisconnection was further confirmed after 2D-PAGE analysis, which showed an identicalPrPSc signature, including the biochemical pattern of CTFs. To pursue this issue, weobtained brain homogenates from Cynomolgus macaques intracerebrally inoculatedwith brain homogenates from BASE. Samples were separated by using a twodimensional electrophoresis (2D-PAGE) followed by immunoblotting. We here showthat the PrPSc pattern obtained in infected primates is identical to BASE and sCJDMV-2 subtype. These data strongly support the link, or at least a common ancestry,between a sCJD subtype and BASE.
This work was supported by Neuroprion (FOOD-CT-2004-506579)
FC5.5.2
Transmission of Italian BSE and BASE Isolates in Cattle Results into a TypicalBSE Phenotype and a Muscle Wasting Disease
Zanusso, G1; Lombardi, G2; Casalone, C3; D’Angelo, A4; Gelmetti, D2; Torcoli, G2;Barbieri, I2; Corona, C3; Fasoli, E1; Farinazzo, A1; Fiorini, M1; Gelati, M1; Iulini, B3;Tagliavini, F5; Ferrari, S1; Monaco, S1; Caramelli, M3; Capucci, L21University of Verona, Neurological and Visual Sciences, Italy; 2IZSLER, Italy; 3IZSPLVA,Italy; 4University of Turin, Animal Pathology, Italy; 5Isituto Carlo Besta, Italy
The clinical phenotype of bovine spongiform encephalopathy has been extensivelyreported in early accounts of the disorder. Following the introduction of statutory activesurveillance, almost all BSE cases have been diagnosed on a pathological/molecularbasis, in a pre-symptomatic clinical stage. In recent years, the active surveillancesystem has uncovered atypical BSE cases, which are characterized by distinctconformers of the PrPSc, named high-type (BSE-H) and low-type (BSE-L), whoseclinicopathological phenotypes remain unknown. We recently reported two Italianatypical cases with a PrPSc type similar to BSE-L, pathologically characterized by PrPamyloid plaques. Experimental transmission to TgBov mice has recently disclosed thatBASE is caused by a distinct prion strain which is extremely virulent. A major limitationof transmission studies to mice is the lack of reliable information on clinical phenotypeof BASE in its natural host. In the present study, we experimentally infectedFresian/Holstein and Alpine/Brown cattle with Italian BSE and BASE isolates by i.c.route. BASE infected cattle showed survival times significantly shorter than BSE, afinding more readily evident in Fresian/Holstein, and in keeping with previousobservations in TgBov mice. Clinically, BSE-infected cattle developed a diseasephenotype highly comparable with that described in field BSE cases and inexperimentally challenged cattle. On the contrary, BASE-inoculated cattle developedan amyotrophic disorder accompanied by mental dullness.The molecular and neuropathological profiles, including PrP deposition pattern, closelymatched those observed in the original cases. This study further confirms that BASEis caused by a distinct prion isolate and discloses a novel disease phenotype in cattle,closely resembling the phenotype previous reported in scrapie-inoculated cattle and insome subtypes of inherited and sporadic Creutzfeldt-Jakob disease.
http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf
The MM2-cortical form of sporadic Creutzfeldt–Jakob disease presenting withvisual disturbance
Abstract—A subclass of sporadic Creutzfeldt–Jakob disease (sCJD) characterizedby onset with visual symptoms (Heidenhain variant) has been reported tobelong to the MM1 or MV1 type according to Parchi’s classification. The authorsreport a 65-year-old woman with MM2-cortical sCJD with slowly progressivevisual disturbance as the initial symptom. Diffusion-weighted MRIsrevealed hyperintensity in both occipital cortices at an early stage.
NEUROLOGY 2006;67:531–533
I. Nozaki, MD; T. Hamaguchi, MD, PhD; M. Noguchi-Shinohara, MD; K. Ono, MD, PhD; H. Shirasaki, MD;K. Komai, MD, PhD; T. Kitamoto, MD, PhD; and M. Yamada, MD, PhD
snip...
Discussion. This case was classified as MM2-cortical sCJD for the following reasons: no history ofdural grafting; spongiform changes and PrP depositswith a perivacuolar pattern in the cerebral cortices,but no thalamic or inferior olivary degeneration asfound in the thalamic form; no mutation and MM atpolymorphic codon 129 in the PrP gene; and a Type2A pattern (Parchi) of PrPres. Although it has beenreported that Type 1 and Type 2 PrPres coexist in a
third of patients with sCJD,7 Type 1 PrPres was notfound in our case as far as we examined.sCJD was not diagnosed on the basis of clinicaldiagnostic criteria8 before death because of few neurologicmanifestations and the absence of PSDs onEEG and of CSF 14-3-3 protein; however, we suspectedsCJD because of areas of hyperintensity onDW images of the brain. We have previously reportedthat cortical hyperintensity on DW images isuseful for the diagnosis of MM2-cortical sCJD.9
In a recent report, 22 (3.7%) of 594 patients in theUnited Kingdom with pathologically proven sCJDhad isolated visual symptoms at onset (Heidenhainvariant).4 The Heidenhain variant of sCJD is commonlyassociated with rapid progression of variousneuropsychiatric manifestations and presents withthe MM1 or MV1 PrP in all examined cases.1,3,4 Althougha case of the Heidenhain variant with a longclinical course (23 months) has been reported, molecularanalysis of PrP was not performed.10On the other hand, in the MM2-cortical sCJD,dementia is the most common manifestation at onset,and the clinical course is relatively slow, whileataxia and PSDs on EEG are typically absent.1 Visualdisturbance has never been reported throughoutthe clinical course of MM2 sCJD.1 In our patient, it isconsistent with the visual disturbance at onset thatthe early and most severe involvement of the occipitalcortex was proven with MR and pathologic examination.We emphasize that visual disturbance atonset (Heidenhain variant) in sCJD can be found notonly in the MM1 and MV1 types, but also in MM2-cortical type associated with relatively slow progressionof visual symptoms. In such cases, occipitalcortical hyperintensity on DW images helps to establishthe clinical diagnosis of sCJD, even if neurologicmanifestations, EEG, and CSF 14-3-3 protein do notsatisfy the diagnostic criteria for sCJD.8
Acknowledgment
The authors thank Dr. Minoru Tobiume (Department of Pathology,National Institute of Infectious Disease) for the measurementsof 14-3-3 protein, and Drs. Eisuke Furui, Ayumi Shibata,Akiyoshi Morinaga, Tomohiko Machiya, Takahiro Maruta, andKazuo Iwasa for technical support at autopsy.
References...snip...end
http://www.neurology.org/cgi/content/abstract/67/3/531
PRION DISEASE UPDATE 2007 (07)
******************************
A ProMED-mail post<http://www.promedmail.org>ProMED-mail is a program of theInternational Society for Infectious Diseases<http://www.isid.org>
[Note: With continuing decline of the number of cases of variant Creutzfeldt-Jacob disease (abbreviated previously as vCJD or CJD (new var.) in ProMED-mail) in the human population, it has been decided to broaden the scope of the occasional ProMED-mail reports to include other prion-related diseases. These updates supersede the previous update thread.
snip ...
******
[2] USA: National Prion Disease Pathology Surveillance CenterDate: June 2007Source: National Prion Disease Pathology Surveillance Center (USA) [edited]<http://www.cjdsurveillance.com/pdf/case-table.pdf>
CJD Cases examined----------------------Year / Referrals / Prion disease / Sporadic / Familial / Iatrogenic / vCJD
1996 / 42 / 32 / 26 / 4 / 0 / 01997 / 115 / 68 / 57 / 9 / 0 / 01998 / 93 / 53 / 45 / 7 / 1 / 01999 / 114 / 69 / 61 / 8 / 0 / 02000 / 151 / 103 / 89 / 14 / 0 / 02001 / 208 / 116 / 106 / 9 / 0 / 02002 / 255 / 143 / 118 / 23 / 2 / 02003 / 272 / 174 / 132 / 41 / 0 / 02004 / 334 / 183 / 157 / 21 / 0 / 1*2005 / 352 / 195 / 152 / 37 / 1 / 02006 / 372 / 186 / 143 / 30 / 0 / 1**2007 / 120 / 68 / 35 / 7 / 0 / 0TOTAL / 2428*** / 1390**** / 1121 / 210 / 4 / 2
*Acquired in UK** Acquired in Saudi Arabia*** Includes 17 inconclusive and 9 pending (1 from 2006, 8 from 2007.**** Includes 17 non-vCJD type unknown (2 from 1996, 2 from 1997, 1 from 2001, 1 from 2003, 4 from 2004, 3 from 2005, 4 from 2006) and 36 type pending (2 from 2005, 8 from 2006, 26 from 2007).
Notes:
-- Cases are listed based on the year of death when available. If the year of death is not available, the year of sample receipt is used.
-- Referrals: Cases with possible or probable prion disease from which brain tissue or blood in the case of familial disease were submitted.
-- Inconclusive: Cases in which the samples were not sufficient to make a diagnosis.
-- Non-vCJD type unknown are cases in which the tissue submitted was adequate to establish the presence but not the type; in all cases, vCJD could be excluded.
--Communicated by:Terry S. Singeltary Sr. <flounder9@verizon.net>
[In submitting these data, Terry S. Singeltary Sr. draws attention to the steady increase in the "type unknown" category, which, according to their definition, comprises cases in which vCJD could be excluded. The total of 26 cases for the current year (2007) is disturbing, possibly symptomatic of the circulation of novel agents. Characterization of these agents should be given a high priority. - Mod.CP]
Visit ProMED-mail's web site at <http://www.promedmail.org>.
snip...end...TSS
*** PLEASE READ AND UNDERSTAND THE RAMIFICATIONS OF THIS !!! THE PRICE OFPOKER INDEED GOES UP. ...TSS
USA BASE CASE, (ATYPICAL BSE), AND OR TSE (whatever they are calling ittoday), please note that both the ALABAMA COW, AND THE TEXAS COW, both were''H-TYPE'', personal communication Detwiler et al Wednesday, August 22, 200711:52 PM. ...TSS
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=19779
MADCOW USDA the untold story
http://madcowusda.blogspot.com/
USA NOR-98 SCRAPIE UPDATE AUGUST 31, 2007 RISES TO 5 DOCUMENTED CASES
http://nor-98.blogspot.com/
Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease inthe United States
http://cjdusa.blogspot.com/
i am reminded of a few things deep throat (high ranking official at usda)told me years ago;
The most frightening thing I have read all day is thereport of Gambetti's finding of a new strain ofsporadic cjd in young people.........Dear God,
https://www.blogger.com/comment.g?blogID=7842737484277562285&postID=5759550357128128100
TSS
BASE Transmitted to Primates and MV2 sCJD Subtype Share PrP27-30 and PrPSc
C-terminal Truncated Fragments Zanusso, G1; Commoy, E2; Fasoli, E3; Fiorini, M3; Lescoutra, N4; Ruchoux,MM4; Casalone, C5; Caramelli, M5; Ferrari, S3; Lasmezas, C6; Deslys, J-P4; Monaco, S31University of Verona, of Neurological and Visual Sciences, Italy; 2CEA, IMETI/SEPIA,France; 3University of Verona, Neurological and Visual Sciences, Italy; 4IMETI/SEPIA,France; 5IZSPLVA, Italy; 6The Scripps Research Insitute, USA
The etiology of sporadic Creutzfeldt-Jakob disease (sCJD), the most frequent humanprion disease, remains still unknown. The marked disease phenotype heterogeneityobserved in sCJD is thought to be influenced by the type of proteinase K-resistantprion protein, or PrPSc (type 1 or type 2 according to the electrophoretic mobility ofthe unglycosylated backbone), and by the host polymorphic Methionine/Valine (M/V)codon 129 of the PRNP. By using a two-dimensional gel electrophoresis (2D-PAGE)and imunoblotting we previously showed that in sCJD, in addition to the PrPSc type,distinct PrPSc C-terminal truncated fragments (CTFs) correlated with different sCJDsubtypes. Based on the combination of CTFs and PrPSc type, we distinguished threePrPSc patterns: (i) the first was observed in sCJD with PrPSc type 1 of all genotypes,;(ii) the second was found in M/M-2 (cortical form); (iii) the third in amyloidogenic M/V-2 and V/V-2 subtypes (Zanusso et al., JBC 2004) . Recently, we showed that sCJDsubtype M/V-2 shared molecular and pathological features with an atypical form ofBSE, named BASE, thus suggesting a potential link between the two conditions. Thisconnection was further confirmed after 2D-PAGE analysis, which showed an identicalPrPSc signature, including the biochemical pattern of CTFs. To pursue this issue, weobtained brain homogenates from Cynomolgus macaques intracerebrally inoculatedwith brain homogenates from BASE. Samples were separated by using a twodimensional electrophoresis (2D-PAGE) followed by immunoblotting. We here showthat the PrPSc pattern obtained in infected primates is identical to BASE and sCJDMV-2 subtype. These data strongly support the link, or at least a common ancestry,between a sCJD subtype and BASE.
This work was supported by Neuroprion (FOOD-CT-2004-506579)
FC5.5.2
Transmission of Italian BSE and BASE Isolates in Cattle Results into a TypicalBSE Phenotype and a Muscle Wasting Disease
Zanusso, G1; Lombardi, G2; Casalone, C3; D’Angelo, A4; Gelmetti, D2; Torcoli, G2;Barbieri, I2; Corona, C3; Fasoli, E1; Farinazzo, A1; Fiorini, M1; Gelati, M1; Iulini, B3;Tagliavini, F5; Ferrari, S1; Monaco, S1; Caramelli, M3; Capucci, L21University of Verona, Neurological and Visual Sciences, Italy; 2IZSLER, Italy; 3IZSPLVA,Italy; 4University of Turin, Animal Pathology, Italy; 5Isituto Carlo Besta, Italy
The clinical phenotype of bovine spongiform encephalopathy has been extensivelyreported in early accounts of the disorder. Following the introduction of statutory activesurveillance, almost all BSE cases have been diagnosed on a pathological/molecularbasis, in a pre-symptomatic clinical stage. In recent years, the active surveillancesystem has uncovered atypical BSE cases, which are characterized by distinctconformers of the PrPSc, named high-type (BSE-H) and low-type (BSE-L), whoseclinicopathological phenotypes remain unknown. We recently reported two Italianatypical cases with a PrPSc type similar to BSE-L, pathologically characterized by PrPamyloid plaques. Experimental transmission to TgBov mice has recently disclosed thatBASE is caused by a distinct prion strain which is extremely virulent. A major limitationof transmission studies to mice is the lack of reliable information on clinical phenotypeof BASE in its natural host. In the present study, we experimentally infectedFresian/Holstein and Alpine/Brown cattle with Italian BSE and BASE isolates by i.c.route. BASE infected cattle showed survival times significantly shorter than BSE, afinding more readily evident in Fresian/Holstein, and in keeping with previousobservations in TgBov mice. Clinically, BSE-infected cattle developed a diseasephenotype highly comparable with that described in field BSE cases and inexperimentally challenged cattle. On the contrary, BASE-inoculated cattle developedan amyotrophic disorder accompanied by mental dullness.The molecular and neuropathological profiles, including PrP deposition pattern, closelymatched those observed in the original cases. This study further confirms that BASEis caused by a distinct prion isolate and discloses a novel disease phenotype in cattle,closely resembling the phenotype previous reported in scrapie-inoculated cattle and insome subtypes of inherited and sporadic Creutzfeldt-Jakob disease.
http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf
The MM2-cortical form of sporadic Creutzfeldt–Jakob disease presenting withvisual disturbance
Abstract—A subclass of sporadic Creutzfeldt–Jakob disease (sCJD) characterizedby onset with visual symptoms (Heidenhain variant) has been reported tobelong to the MM1 or MV1 type according to Parchi’s classification. The authorsreport a 65-year-old woman with MM2-cortical sCJD with slowly progressivevisual disturbance as the initial symptom. Diffusion-weighted MRIsrevealed hyperintensity in both occipital cortices at an early stage.
NEUROLOGY 2006;67:531–533
I. Nozaki, MD; T. Hamaguchi, MD, PhD; M. Noguchi-Shinohara, MD; K. Ono, MD, PhD; H. Shirasaki, MD;K. Komai, MD, PhD; T. Kitamoto, MD, PhD; and M. Yamada, MD, PhD
snip...
Discussion. This case was classified as MM2-cortical sCJD for the following reasons: no history ofdural grafting; spongiform changes and PrP depositswith a perivacuolar pattern in the cerebral cortices,but no thalamic or inferior olivary degeneration asfound in the thalamic form; no mutation and MM atpolymorphic codon 129 in the PrP gene; and a Type2A pattern (Parchi) of PrPres. Although it has beenreported that Type 1 and Type 2 PrPres coexist in a
third of patients with sCJD,7 Type 1 PrPres was notfound in our case as far as we examined.sCJD was not diagnosed on the basis of clinicaldiagnostic criteria8 before death because of few neurologicmanifestations and the absence of PSDs onEEG and of CSF 14-3-3 protein; however, we suspectedsCJD because of areas of hyperintensity onDW images of the brain. We have previously reportedthat cortical hyperintensity on DW images isuseful for the diagnosis of MM2-cortical sCJD.9
In a recent report, 22 (3.7%) of 594 patients in theUnited Kingdom with pathologically proven sCJDhad isolated visual symptoms at onset (Heidenhainvariant).4 The Heidenhain variant of sCJD is commonlyassociated with rapid progression of variousneuropsychiatric manifestations and presents withthe MM1 or MV1 PrP in all examined cases.1,3,4 Althougha case of the Heidenhain variant with a longclinical course (23 months) has been reported, molecularanalysis of PrP was not performed.10On the other hand, in the MM2-cortical sCJD,dementia is the most common manifestation at onset,and the clinical course is relatively slow, whileataxia and PSDs on EEG are typically absent.1 Visualdisturbance has never been reported throughoutthe clinical course of MM2 sCJD.1 In our patient, it isconsistent with the visual disturbance at onset thatthe early and most severe involvement of the occipitalcortex was proven with MR and pathologic examination.We emphasize that visual disturbance atonset (Heidenhain variant) in sCJD can be found notonly in the MM1 and MV1 types, but also in MM2-cortical type associated with relatively slow progressionof visual symptoms. In such cases, occipitalcortical hyperintensity on DW images helps to establishthe clinical diagnosis of sCJD, even if neurologicmanifestations, EEG, and CSF 14-3-3 protein do notsatisfy the diagnostic criteria for sCJD.8
Acknowledgment
The authors thank Dr. Minoru Tobiume (Department of Pathology,National Institute of Infectious Disease) for the measurementsof 14-3-3 protein, and Drs. Eisuke Furui, Ayumi Shibata,Akiyoshi Morinaga, Tomohiko Machiya, Takahiro Maruta, andKazuo Iwasa for technical support at autopsy.
References...snip...end
http://www.neurology.org/cgi/content/abstract/67/3/531
PRION DISEASE UPDATE 2007 (07)
******************************
A ProMED-mail post<http://www.promedmail.org>ProMED-mail is a program of theInternational Society for Infectious Diseases<http://www.isid.org>
[Note: With continuing decline of the number of cases of variant Creutzfeldt-Jacob disease (abbreviated previously as vCJD or CJD (new var.) in ProMED-mail) in the human population, it has been decided to broaden the scope of the occasional ProMED-mail reports to include other prion-related diseases. These updates supersede the previous update thread.
snip ...
******
[2] USA: National Prion Disease Pathology Surveillance CenterDate: June 2007Source: National Prion Disease Pathology Surveillance Center (USA) [edited]<http://www.cjdsurveillance.com/pdf/case-table.pdf>
CJD Cases examined----------------------Year / Referrals / Prion disease / Sporadic / Familial / Iatrogenic / vCJD
1996 / 42 / 32 / 26 / 4 / 0 / 01997 / 115 / 68 / 57 / 9 / 0 / 01998 / 93 / 53 / 45 / 7 / 1 / 01999 / 114 / 69 / 61 / 8 / 0 / 02000 / 151 / 103 / 89 / 14 / 0 / 02001 / 208 / 116 / 106 / 9 / 0 / 02002 / 255 / 143 / 118 / 23 / 2 / 02003 / 272 / 174 / 132 / 41 / 0 / 02004 / 334 / 183 / 157 / 21 / 0 / 1*2005 / 352 / 195 / 152 / 37 / 1 / 02006 / 372 / 186 / 143 / 30 / 0 / 1**2007 / 120 / 68 / 35 / 7 / 0 / 0TOTAL / 2428*** / 1390**** / 1121 / 210 / 4 / 2
*Acquired in UK** Acquired in Saudi Arabia*** Includes 17 inconclusive and 9 pending (1 from 2006, 8 from 2007.**** Includes 17 non-vCJD type unknown (2 from 1996, 2 from 1997, 1 from 2001, 1 from 2003, 4 from 2004, 3 from 2005, 4 from 2006) and 36 type pending (2 from 2005, 8 from 2006, 26 from 2007).
Notes:
-- Cases are listed based on the year of death when available. If the year of death is not available, the year of sample receipt is used.
-- Referrals: Cases with possible or probable prion disease from which brain tissue or blood in the case of familial disease were submitted.
-- Inconclusive: Cases in which the samples were not sufficient to make a diagnosis.
-- Non-vCJD type unknown are cases in which the tissue submitted was adequate to establish the presence but not the type; in all cases, vCJD could be excluded.
--Communicated by:Terry S. Singeltary Sr. <flounder9@verizon.net>
[In submitting these data, Terry S. Singeltary Sr. draws attention to the steady increase in the "type unknown" category, which, according to their definition, comprises cases in which vCJD could be excluded. The total of 26 cases for the current year (2007) is disturbing, possibly symptomatic of the circulation of novel agents. Characterization of these agents should be given a high priority. - Mod.CP]
Visit ProMED-mail's web site at <http://www.promedmail.org>.
snip...end...TSS
*** PLEASE READ AND UNDERSTAND THE RAMIFICATIONS OF THIS !!! THE PRICE OFPOKER INDEED GOES UP. ...TSS
USA BASE CASE, (ATYPICAL BSE), AND OR TSE (whatever they are calling ittoday), please note that both the ALABAMA COW, AND THE TEXAS COW, both were''H-TYPE'', personal communication Detwiler et al Wednesday, August 22, 200711:52 PM. ...TSS
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=19779
MADCOW USDA the untold story
http://madcowusda.blogspot.com/
USA NOR-98 SCRAPIE UPDATE AUGUST 31, 2007 RISES TO 5 DOCUMENTED CASES
http://nor-98.blogspot.com/
Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease inthe United States
http://cjdusa.blogspot.com/
i am reminded of a few things deep throat (high ranking official at usda)told me years ago;
The most frightening thing I have read all day is thereport of Gambetti's finding of a new strain ofsporadic cjd in young people.........Dear God,
https://www.blogger.com/comment.g?blogID=7842737484277562285&postID=5759550357128128100
TSS
Monday, October 8, 2007
UPDATE CJD USA 'UNKNOWN TYPE' 26 CASES FROM 2007
PLEASE NOTE IN USA CJD UPDATE AS AT JUNE 2007, please note steady increase in ''TYPE UNKNOWN''. ...TSS
1 Acquired in the United Kingdom; 2 Acquired in Saudi Arabia; 3 Includes 17 inconclusive and 9 pending (1 from 2006, 8 from 2007); 4 Includes 17 non-vCJD type unknown (2 from 1996, 2 from 1997, 1 from 2001, 1 from 2003, 4 from 2004, 3 from 2005, 4 from 2006)
and 36 type pending (2 from 2005, 8 from 2006, *** 26 from 2007)
http://www.cjdsurveillance.com/pdf/case-table.pdf
TSS
1 Acquired in the United Kingdom; 2 Acquired in Saudi Arabia; 3 Includes 17 inconclusive and 9 pending (1 from 2006, 8 from 2007); 4 Includes 17 non-vCJD type unknown (2 from 1996, 2 from 1997, 1 from 2001, 1 from 2003, 4 from 2004, 3 from 2005, 4 from 2006)
and 36 type pending (2 from 2005, 8 from 2006, *** 26 from 2007)
http://www.cjdsurveillance.com/pdf/case-table.pdf
TSS
Tuesday, October 2, 2007
CREUTZFELDT JAKOB DISEASE MAD COW BASE, CWD, SCRAPIE UPDATE OCT 2007
----- Original Message -----
From: "Terry S. Singeltary Sr." <flounder9@VERIZON.NET>
To: <BSE-L@LISTS.AEGEE.ORG>
Sent: Tuesday, October 02, 2007 10:43 AM
Subject: [BSE-L] Monthly Creutzfeldt Jakob Disease statistics 2 October 2007
Subject: Monthly Creutzfeldt Jakob Disease statistics 2 October 2007Date: October 2, 2007 at 8:10 am PST
Monthly Creutzfeldt Jakob Disease statistics
DEPARTMENT OF HEALTH News Release issued by The Government News Network on 2October 2007The Department of Health is today issuing the latest information about thenumbers of known cases of Creutzfeldt Jakob disease. This includes cases ofvariant Creutzfeldt Jakob disease (vCJD) - the form of the disease thoughtto be linked to BSE. The position is as follows:Definite and probable CJD cases in the UK:
As at 28 September 2007Summary of vCJD cases
Deaths
Deaths from definite vCJD (confirmed): 114
Deaths from probable vCJD (without neuropathological confirmation): 47
Deaths from probable vCJD (neuropathological confirmation pending): 0
Number of deaths from definite or probable vCJD (as above): 161Alive
Number of definite/probable vCJD cases still alive: 5
Total number of definite or probable vCJD (dead and alive): 166Following this press notice the Department of Health will stop issuingmonthly CJD press notices because the same data is also published by theNational CJD Surveillance Unit in Edinburgh. Up to date figures for thenumber of vCJD cases in the UK can be found on the website of the NationalCJD Surveillance Unit at: http://www.cjd.ed.ac.uk/figures.htm.
CREUTZFELDT-JAKOB DISEASE IN THE UKBy Calendar Year
see chart of steady increase of sporadic CJD cases ...tss
snip...
* As at 28th September 2007Referrals: a simple count of all the cases which have been referred to theNational CJD Surveillance Unit for further investigation in the year inquestion. CJD may be no more than suspected; about half the cases referredin the past have turned out not to be CJD. Cases are notified to the Unitfrom a variety of sources including neurologists, neuropathologists,neurophysiologists, general physicians, psychiatrists, electroencephalogram(EEG) departments etc. As a safety net, death certificates coded under thespecific rubrics 046.1 and 331.9 in the 9th ICD Revisions are obtained fromthe Office for National Statistics in England and Wales, the GeneralRegister Office for Scotland and the General Register Office for NorthernIreland.
Deaths: All columns show the number of deaths that have occurred in definiteand probable cases of all types of CJD and GSS in the year shown. Thefigures include both cases referred to the Unit for investigation while thepatient was still alive and those where CJD was only discovered post mortem(including a few cases picked up by the Unit from death certificates). Thereis therefore no read across from these columns to the referrals column. Thefigures will be subject to retrospective adjustment as diagnoses areconfirmed.
Definite cases: this refers to the diagnostic status of cases. In definitecases the diagnosis will have been pathologically confirmed, in most casesby post mortem examination of brain tissue (rarely it may be possible toestablish a definite diagnosis by brain biopsy while the patient is stillalive).
Probable vCJD cases: are those who fulfil the 'probable' criteria set out inthe Annex and are either still alive, or have died and await post mortempathological confirmation. Those still alive will always be shown within thecurrent year's figures.
Sporadic: Classic CJD cases with typical EEG and brain pathology. Sporadiccases appear to occur spontaneously with no identifiable cause and accountfor 85% of all cases.
Probable sporadic: Cases with a history of rapidly progressive dementia,typical EEG and at least two of the following clinical features; myoclonus,visual or cerebellar signs, pyramidal/extrapyramidalsigns or akineticmutism.
Iatrogenic: where infection with classic CJD has occurred accidentally asthe result of a medical procedure. All UK cases have resulted from treatmentwith human derived pituitary growth hormones or from grafts using dura mater(a membrane lining the skull).
Familial: cases occurring in families associated with mutations in the PrPgene (10 - 15% of cases).
GSS: Gerstmann-Straussler-Scheinker syndrome - an exceedingly rare inheritedautosomal dominant disease, typified by chronic progressive ataxia andterminal dementia. The clinical duration is from 2 to 10 years, much longerthan for CJD.
vCJD: Variant CJD, the hitherto unrecognised variant of CJD discovered bythe National CJD Surveillance Unit and reported in The Lancet on 6 April1996. This is characterised clinically by a progressive neuropsychiatricdisorder leading to ataxia, dementia and myoclonus (or chorea) without thetypical EEG appearance of CJD. Neuropathology shows marked spongiform changeand extensive florid plaques throughout the brain.
Definite vCJD cases still alive: These will be cases where the diagnosis hasbeen pathologically confirmed (by brain biopsy).
[ENDS]
http://www.wired-gov.net/wg/wg-news-1.nsf/lfi/152230
P02.15
Beyond the PrPres Type1/ Type2 dichotomy in Creutzfeldt-Jakob Disease
Cassard, H1; Uro-Coste, E2; Simon, S3; Bilheude, JM4; Perret-Liaudet, A5;Ironside, J6; Haik, S7; Basset-Leobon, C2; Lacroux, C1; Peoch’, K8;Stressenberger, N9;Langeveld, J10; Head, M11; Hauw, JJ12; Schecher, F1; Delisle, MB13;Andreoletti, O11Ecole Natinale Vétérinaire de Toulouse, France; 22Service d’AnatomiePathologiqueand INSERM U466 R, France; 3DRM, CEA/Saclay, France; 4 Bio-Rad, R&D, France;5 Hôpital Neurologique Service de Neurochimie, France; 6School of Molecular& Clinical Medicine (Pathology),, National Creutzfeldt-Jakob DiseaseSurveillance Un,UK; 7Pitié Salpetriere Universitary Hospital, France; 8Hôpital Lariboisière,Service deBiochimie et Biologie Moléculaire,, France; 9Hôpital Neurologique -ServicedeNeurochimie, France; 10CIDC-Lelystad, Netherlands; 11University ofEdinburgh, Western GeneralHospital, UK; 12Pitié Salpetriere Universitary Hospital,, Laboratoire deNeuropathologie, France;13Rangueil Universitary Hospital, Service d’Anatomie Pathologique, France
Creutzfeldt-Jakob disease (CJD) cases are currently classified according toestablished diagnostic criteria and by the genotype at codon 129 of the PRNPgene and the Western blotting of the proteinase K digested abnormal prionprotein that distinguishes a type 1 and a type 2 profile. Thesebiochemicallydistinct PrPres types have been proposed to represent distinct prionstrains.However, since the cooccurence of type 1 and type 2 PrPres in the samepatientis common, the rationale of this classification and strain concept asapplied toCJD are currently under discussion.
Five different brain areas from of 40 sporadic CJD and 11 iatrogenic CJD(both dura matter-, and growth hormone-associated) cases, originating fromUK and France, were systematically investigated, using Western blottingtyping,and by two others biochemical assays that depend on the behaviour of PrPScinvariable PK digestion conditions.
As described previously, co-occurrence of type 1 and type 2 PrPres wasfound in 30% of the CJD patients examined. However, our novel PKconcentrationdependent assays identified a single uniform PrP type in cases where bothtype 1 andtype 2 were present. Moreover, in sCJD four distinct biochemical PrPScsignatures were identified by the PK concentration dependent assays andthesecorrelated to the current genotype/clinico-pathological sCJD groups. In iCJDthe foursimilar biochemical signatures were observed, but were not correlated toparticularPRNP 129 polymorphism or Western Blot PrPres patterns. Moreover notabledifferenceswere observed between PrPSc biochemical properties of French and UK GH-CJDcases,which could reflect, as already suspected, differences in the causativeagents.
Identification, in sCJD and iCJD, of four different PrPSc phenotypesirrespective of patients PRNP polymorphism at codon 129 and Western blotprofile provides new insights into human prion disease aetiology and couldreflects anunsuspected diversity of TSE agents in human disease. Further investigationsarecurrently underway using animal transmission to correlate agent strain withour newdiscriminant biochemical assays.
P04.33
Diagnostic Utility of CSF Biomarkers and General CSF Findings in a U.SSporadic CJD Cohort
Geschwind, MD; Haman, A; Torres-Chae, C; Raudabaugh, BJ; Devereux, G;Miller, BL University of California, San Francisco, USA
Background:
The diagnostic utility of CSF biomarkers, including 14-3-3 protein,neuron-specific enolase (NSE), AB42, total Tau (T-Tau), and phosphorylatedTau (PTau)/ T-Tau ratio are often are used for sporadic CJD (sCJD) diagnosisis controversial. We have previously reported the CSF 14-3-3 protein to havepoor sensitivity for CJD diagnosis. In this study, now report thesensitivity and specificityof several CSF biomarkers and general characteristics in a U.S. cohort ofsCJDand non-prion rapidly progressive dementia (RPD) controls (Non-CJD cohort)subjects.
Design/Methods:
Clinical diagnoses are made through review of medical records, clinicalevaluation, andin many cases pathology. Data is stored in a secure clinical relationaldatabase, which wasqueried for various CSF findings, including cell count, protein, IgG index,oligoclonal bands(OCBs), 14-3-3, NSE, T-Tau in patients with probable or definite sporadicCJD andnon-prion rapidly progressive dementias (RPD), most of whom were referred toour centerwith a potential diagnosis of CJD. For probable sCJD diagnosis, we used UCSFcriteria thatare modified from WHO to substitute MRI for 14-3-3. T-Tau and NSE wereconsideredpositive if > 1300 pg/ml and > 35 ng/ml, respectively. For this analysis,ambiguous 14-3-3results were considered as negative.
Results:
14-3-3 protein (n=149) sensitivity was only 48% (47% for definite; 50% forprobable sCJD). NSE (n=49) sensitivity was 63% (66% for definite; 59% forprobablesCJD). T-Tau (n=28) was the most sensitive at 68% (69% for definite; 67% forprobable sCJD). The specificity of these biomarkers among our CJD and RPDcontrols(n=72) was 66% for 14-3-3 (n=47), 81% for NSE (n=21), and 100% for T-Tau(n=7). The14-3-3 had the lowest sensitivity and specificity. Mildly elevated CSFprotein(<100>20, is uncommon in sCJD.
Conclusions/Relevance:
In a cohort from a major U.S. CJD referral center, the 14-3-3is neither sensitive nor specific for sCJD. NSE and T-Tau also show poorsensitivity forsCJD. T-Tau may be more specific than 14-3-3 and NSE, but our “n” is small.WHO sCJD criteria should be revised; by eliminating 14-3-3 and includingbrainMRI into the criteria. We are currently analyzing the effects of diseaseduration andcodon 129 polymorphism on these CSF biomarker results.
http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf
see full text 143 pages ;
http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf
Subject: PRION2007 ABSTRACTS SPORADIC CJD AND H BASE MAD COW ALABAMA ANDTEXAS SEPTEMBER 2007Date: September 24, 2007 at 6:52 pm PST
P02.35Molecular Features of the Protease-resistant Prion Protein (PrPres) inH-type BSE
Biacabe, A-G1; Jacobs, JG2; Gavier-Widén, D3; Vulin, J1; Langeveld, JPM2;Baron, TGM1 1AFSSA, France; 2CIDC-Lelystad, Netherlands; 3SVA, Sweden
Western blot analyses of PrPres accumulating in the brain of BSE-infectedcattle havedemonstrated 3 different molecular phenotypes regarding to the apparentmolecularmasses and glycoform ratios of PrPres bands. We initially described isolates(H-typeBSE) essentially characterized by higher PrPres molecular mass and decreasedlevels of the diglycosylated PrPres band, in contrast to the classical typeof BSE.This type is also distinct from another BSE phenotype named L-type BSE, oralso BASE (for Bovine Amyloid Spongiform Encephalopathy), mainlycharacterized by alow representation of the diglycosylated PrPres band as well as a lowerPrPresmolecular mass. Retrospective molecular studies in France of all availableBSE casesolder than 8 years old and of part of the other cases identified since thebeginning of theexhaustive surveillance of the disease in 20001 allowed to identify 7 H-typeBSE cases, among 594 BSE cases that could be classified as classical, L- orH-type BSE.By Western blot analysis of H-type PrPres, we described a remarkablespecific feature with antibodies raised against the C-terminal region of PrPthatdemonstrated the existence of a more C-terminal cleaved form of PrPres(named PrPres#2 ),in addition to the usual PrPres form (PrPres #1). In the unglycosylatedform,PrPres #2 migrates at about 14 kDa, compared to 20 kDa for PrPres #1. Theproportionof the PrPres#2 in cattle seems to by higher compared to the PrPres#1.Furthermoreanother PK–resistant fragment at about 7 kDa was detected by some moreN-terminalantibodies and presumed to be the result of cleavages of both N- andC-terminal partsof PrP. These singular features were maintained after transmission of thedisease toC57Bl/6 mice. The identification of these two additional PrPres fragments(PrPres #2 and7kDa band) reminds features reported respectively in sporadicCreutzfeldt-Jakob diseaseand in Gerstmann-Sträussler-Scheinker (GSS) syndrome in humans.
FC5.5.1BASE Transmitted to Primates and MV2 sCJD Subtype Share PrP27-30 and PrPScC-terminal Truncated Fragments
Zanusso, G1; Commoy, E2; Fasoli, E3; Fiorini, M3; Lescoutra, N4; Ruchoux,MM4; Casalone, C5; Caramelli, M5; Ferrari, S3; Lasmezas, C6; Deslys, J-P4;Monaco, S3 1University of Verona, of Neurological and Visual Sciences,Italy; 2CEA, IMETI/SEPIA, France; 3University of Verona, Neurological andVisual Sciences, Italy; 4IMETI/SEPIA, France; 5IZSPLVA, Italy; 6The ScrippsResearch Insitute, USA
The etiology of sporadic Creutzfeldt-Jakob disease (sCJD), the most frequenthumanprion disease, remains still unknown. The marked disease phenotypeheterogeneityobserved in sCJD is thought to be influenced by the type of proteinaseK-resistantprion protein, or PrPSc (type 1 or type 2 according to the electrophoreticmobility ofthe unglycosylated backbone), and by the host polymorphic Methionine/Valine(M/V) codon 129 of the PRNP. By using a two-dimensional gel electrophoresis(2D-PAGE) and imunoblotting we previously showed that in sCJD, in additionto thePrPSc type, distinct PrPSc C-terminal truncated fragments (CTFs) correlatedwithdifferent sCJD subtypes. Based on the combination of CTFs and PrPSc type, wedistinguishedthree PrPSc patterns: (i) the first was observed in sCJD with PrPSc type 1of allgenotypes,;
(ii) the second was found in M/M-2 (cortical form); (iii) the third inamyloidogenic M/V-2 and V/V-2 subtypes (Zanusso et al., JBC 2004) . Recently, we showed thatsCJDsubtype M/V-2 shared molecular and pathological features with an atypicalform ofBSE, named BASE, thus suggesting a potential link between the twoconditions. Thisconnection was further confirmed after 2D-PAGE analysis, which showed anidentical PrPSc signature, including the biochemical pattern of CTFs. Topursue thisissue, we obtained brain homogenates from Cynomolgus macaquesintracerebrallyinoculated with brain homogenates from BASE. Samples were separated by usinga twodimensional electrophoresis (2D-PAGE) followed by immunoblotting. Wehere show that the PrPSc pattern obtained in infected primates is identicaltoBASE and sCJD MV-2 subtype. These data strongly support the link, or atleast acommon ancestry, between a sCJD subtype and BASE. This work was supported byNeuroprion(FOOD-CT-2004-506579)
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USA MAD COW CASES IN ALABAMA AND TEXAS
***PLEASE NOTE***
USA BASE CASE, (ATYPICAL BSE), AND OR TSE (whatever they are calling ittoday), please note that both the ALABAMA COW, AND THE TEXAS COW, both were''H-TYPE'', personal communication Detwiler et al Wednesday, August 22, 200711:52 PM. ...TSS
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=19779
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FC5.5.2 Transmission of Italian BSE and BASE Isolates in Cattle Results intoa Typical BSE Phenotype and a Muscle Wasting Disease
Zanusso, G1; Lombardi, G2; Casalone, C3; D’Angelo, A4; Gelmetti, D2;Torcoli, G2;Barbieri, I2; Corona, C3; Fasoli, E1; Farinazzo, A1; Fiorini, M1; Gelati,M1; Iulini, B3;Tagliavini, F5; Ferrari, S1; Monaco, S1; Caramelli, M3; Capucci, L21University of Verona, Neurological and Visual Sciences, Italy; 2IZSLER,Italy; 3IZSPLVA,Italy; 4University of Turin, Animal Pathology, Italy; 5Isituto Carlo Besta,Italy
The clinical phenotype of bovine spongiform encephalopathy has beenextensivelyreported in early accounts of the disorder. Following the introduction ofstatutory activesurveillance, almost all BSE cases have been diagnosed on apathological/molecularbasis, in a pre-symptomatic clinical stage. In recent years, the activesurveillancesystem has uncovered atypical BSE cases, which are characterized by distinctconformers of the PrPSc, named high-type (BSE-H) and low-type (BSE-L), whoseclinicopathological phenotypes remain unknown. We recently reported twoItalian atypical cases with a PrPSc type similar to BSE-L, pathologicallycharacterized by PrP amyloid plaques. Experimental transmission to TgBovmice hasrecently disclosed that BASE is caused by a distinct prion strain which isextremelyvirulent. A major limitation of transmission studies to mice is the lack ofreliableinformation on clinical phenotype of BASE in its natural host. In thepresent study, weexperimentally infected Fresian/Holstein and Alpine/Brown cattle withItalian BSE andBASE isolates by i.c. route. BASE infected cattle showed survival timessignificantlyshorter than BSE, a finding more readily evident in Fresian/Holstein, and inkeeping withprevious observations in TgBov mice. Clinically, BSE-infected cattledeveloped adisease phenotype highly comparable with that described in field BSE casesand in experimentally challenged cattle. On the contrary, BASE-inoculatedcattledeveloped an amyotrophic disorder accompanied by mental dullness.The molecular and neuropathological profiles, including PrP depositionpattern, closely matched those observed in the original cases. This studyfurther confirmsthat BASE is caused by a distinct prion isolate and discloses a noveldiseasephenotype in cattle, closely resembling the phenotype previous reported inscrapie-inoculatedcattle and in some subtypes of inherited and sporadic Creutzfeldt-Jakobdisease.Oral Abstracts14
FC5.1.1Transmission Results in Squirrel Monkeys Inoculated with Human sCJD, vCJD,and GSS Blood Specimens: the Baxter Study
Brown, P1; Gibson, S2; Williams, L3; Ironside, J4; Will, R4; Kreil, T5;Abee, C3 1Fondation Alliance BioSecure, France; 2University of SouthAlabama, USA;3University of Texas MD Anderson Cancer Center, USA; 4Western GeneralHospital, UK; 5Baxter BioSience, Austria
Background: Rodent and sheep models of Transmissible SpongiformEncephalopathy(TSE) have documented blood infectivity in both the pre-clinical andclinical phases ofdisease. Results in a (presumably more appropriate) non-human primate modelhave not been reported.
Objective: To determine if blood components (red cells, white cells,platelets, andplasma) from various forms of human TSE are infectious.
Methods: Blood components were inoculated intra-cerebrally (0.1 ml) andintravenously (0.5 ml) into squirrel monkeys from 2 patients with sporadicCreutzfeldt- Jakob disease (sCJD) and 3 patients with variantCreutzfeldt-Jakob disease(vCJD). Additional monkeys were inoculated with buffy coat or plasma samplesfromchimpanzees infected with either sCJD or Gerstmann-Sträussler-Scheinkerdisease (GSS). Animals were monitored for a period of 5 years, and all dyingor sacrificed animals had post-mortem neuropathological examinations andWestern blots to determine the presence or absence of the misfolded ‘prion’protein (PrPTSE).
Results: No transmissions occurred in any of the animals inoculated withblood components from patients with sporadic or variant CJD. All donorchimpanzees(sCJD and GSS) became symptomatic within 6 weeks of their pre-clinical phaseplasmapheresis, several months earlier than the expected onset of illness.One monkey inoculated with purified leukocytes from a pre-clinical GSSchimpanzee developed disease after 36 months.
Conclusion: No infectivity was found in small volumes of blood componentsfrom 4 patients with sporadic CJD and 3 patients with variant CJD.
***However, a single transmission from a chimpanzee-passaged strain of GSSshows that infectivity may be present in leukocytes, and the ‘shock’ ofgeneral anaesthesia and plasmspheresis appears to have triggered the onsetof illness in pre-clinical donor chimpanzees.
FC5.1.2Interim Transmission Results in Cynomolgus Macaques Inoculated with BSE and
vCJD Blood Specimens
Lasmezas, C1; Lescoutra, N2; Comoy, E2; Holznagel, E3; Loewer, J3; Motzkus,D4; Hunsmann, G4; Ingrosso, L5; Bierke, P6; Pocchiari, M5; Ironside, J7;Will,R7; Deslys, JP2 1Scripps Florida, Infectology, USA; 2CEA, France; 3PEI,Germany; 4DPZ, Germany; 5Istituto Superiore di Sanita, Italy; 6SMI, Sweden;7CJD Surveillance Unit, UK
BSE and vCJD transmitted to cynomolgus macaques reproduce many features ofhuman vCJD, including clinical symptoms, neuropathological hallmarks ofvCJD,PrPres electrophoretical pattern and, most importantly, the widedistribution ofinfectivity in peripheral organs. The latter characteristic distinguishesvCJD from sCJDin both humans and cynomolgus macaques, and prompted us to use thisnon-humanprimate model for further investigations of vCJD and its risk for humanhealth. Theoccurrence of four vCJD infections in humans transfused with blood frompatients wholater developed vCJD has raised concern about blood transfusion safety incountries with vCJD.In this collaborative European study, we investigated the infectivity ofblood components and whole blood administered by intracerebral (ic) andintravenous (iv) routes. Buffy-coat and whole blood was inoculated by ic andiv route, respectively, from two vCJD patients and from two clinicalvCJD-inoculatedmacaques. Transfusions were also performed from whole blood and bloodleucodepletedaccording to hospital practice standards from two clinical BSE inoculatedmacaques. Blood infectivity during the preclinical phase is being examinedin orallyinfected macaques. Whole blood was collected and transfused from one suchanimaltwo years after oral challenge, whereas buffy-coat and plasma from twoanimalsat 2 and 4.5 years post-challenge, respectively, have been inoculated by theic route.This is an ongoing study in which recipient animals continue to be observedat various times post-inoculation. So far, we have had one positivetransmission in oneanimal transfused 65 months earlier with 40 ml of whole blood from a vCJDmacaque(the characteristics of the disease in this animal will be shown in aseparate poster by E.Comoy). This positive transmission reproduces transfusion transmission ofvCJD inhumans, with an incubation of 5.5 years compatible with incubation periodsobserved in humans.
FC5.3Assessing the Risk of vCJD Transmission by Dentistry; Distribution ofInfectivity in Oral Tissues of VM Mice after Simulated Oral Feeding ofBSE-301V
Sutton, JM1; Kirby, E1; Dickinson, J1; Dennis, M1; Cornwall, M1; Vassey,MJ1; Smith, A2; Marsh, PD3; Walker, JT1; Raven, NDH11Health Protection Agency, Centre for Emergency Preparedness and Response,,TSE Research group, UK; 2University of Glasgow, Dental School, UK; 3HealthProtection Agency, Centre for Emergency Preparedness and Response,, UK
Background: Ongoing concerns about the prevalence of variant CreutzfeldtJakobDisease (vCJD) in the UK population has heightened concerns about the risksof iatrogenic transmission of the disease. Although there have been no casesto date of transmission by surgery there have been 4 cases involving bloodtransfusion. This study aims to assess the potential of transmission of thedisease bydental procedures. Whilst the risks are undoubtably low the very largenumbers ofprocedures carried out annually have the potential to amplify the risksconsiderablyand there is very little data in this area to form the basis for accurateriskassessments. Aim(s)/Objective(s): To assess the relative levels ofinfectivity in oraltissues from a murine model following exposure to BSE-301V through the smallintestine.
Methods. The study uses a BSE-301V, VM mouse model as a clinically relevantmodel for assessing iatrogenic vCJD transmission between humans. Infectiousmousebrain homogenate was prepared and inoculated into a loop of the duodenum, toprevent direct contamination of the oral tissues. Mice were sacrificed at3-weeklyintervals and at appearance of clinical symptoms. A range of oral tissues,including dental pulp, gingival margin, salivary gland, saliva, lingualtonsil andtrigeminal ganglia, together with brain and spleen tissues were removed,processed ashomogenates and reinoculated intracranially (ic.) into indicator mice.
Results: The primary challenge proved to be a very efficient route ofinfection with a 100% attack rate and a mean incubation to clinical diseaseof 157 ± 17 days (compared to 120 days for the same titre inoculum ic.).Infectivity was observed in all oral and control tissues with varyingtime-coursesand titres estimated from incubation period.
Discussion: The results throw new light on the potential routes ofdissemination and spread of infectivity from the small intestine to the oralcavity and its implications for possible iatrogenic transmission of vCJD viadental,endoscopic or other forms of surgery.
Conclusion: The data generated from the study provides support for ongoingrisk assessments to look at the potential for vCJD transmission via dentalprocedures alongside other elements of studies looking at effectiveness ofdecontamination and re-use of dental instruments.
From: "Terry S. Singeltary Sr."Subject: CWD UPDATE 88 AUGUST 31, 2007
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0709&L=sanet-mg&T=0&P=450
Date: Wed, 29 Aug 2007 21:13:08 -0500From: "Terry S. Singeltary Sr."Subject: CWD NEW MEXICO RECORDS IT'S 19 CASE (near Texas border again)
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=26079
Monitoring the Potential Transmission of Chronic Wasting Disease to HumansUsing a Hunter Registry Database in Wyoming (405 lines)From: Terry S. Singeltary Sr. <[log in to unmask]>Date: Thu, 30 Aug 2007 21:23:42 -0500
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&F=&S=&P=27654
P01.47
Quantifying the Species Barrier in Chronic Wasting Disease by a Novel invitro Conversion Assay
Li, L1; Coulthart, MB2; Balachandran, A3; Chakrabartty, A4; Cashman, NR11University of British Columbia, Brain Research Centre, Canada; 2PublicHealth Agencyof Canada, National Microbiology Laboratory, Canada; 3Animal DiseasesResearchInstitute, Canada Food Inspection Agency, National Reference Laboratory forScrapieand CWD, Canada; 4Ontario Cancer Institute and Department of MedicalBiophysics, University of Toronto, Canada
Background: Chronic wasting disease (CWD) is a transmissible spongiformencephalopathy that can affect North American cervids (deer, elk, andmoose).Although the risk of CWD crossing the species barrier and causing humandisease isstill unknown, however, definite bovine spongiform encephalopathy (BSE)transmissionto humans as variant CJD (vCJD), it would seem prudent to limit the exposureofhumans to CWD.
Aim: In view of the fact that BSE can be readily transmitted to non-bovidspecies, it isimportant to establish the species susceptibility range of CWD.
Methods: In vitro conversion system was performed by incubation of prionswithnormal brain homogenates as described before, and protease K (PK) resistantPrP was determined by immunoblotting with 6H4 monoclonal prion antibody.
Results: Our results demonstrate that PrPC from cervids (including moose)can beefficiently converted to a protease-resistant form by incubation with elkCWD prions,presumably due to sequence and structural similarities between thesespecies.Interestingly, hamster shows a high conversion ratio by PrPCWD. Moreover,partialdenaturation of substrate PrPC can apparently overcome the structuralbarriersbetween more distant species.
Conclusions: Our work correctly predicted the transmission of CWD to a wildmoose. We find a species barrier for prion protein conversion betweencervids andother species, however, this barrier might be overcome if the PrPC substratehasbeen partially denatured in a cellular environment. Such an environmentmightalso promote CWD transmission to non-cervid species, *** including humans.Acid/GdnHCl-treated brain PrPC was a superior substrate for the in vitroconversionthan PrPC treated at physiological pH. This has implications for the processby whichthe prion protein is converted in disease.
http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf
Subject: Cross-sequence transmission of sporadic Creutzfeldt-Jakob diseasecreates a new prion strain
Date: August 25, 2007 at 12:42 pm PST
Subject: Cross-sequence transmission of sporadic Creutzfeldt-Jakob diseasecreates a new prion strainDate: August 25, 2007 at 12:42 pm PST
J Biol Chem. 2007 Aug 20; : 17709374
Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease creates anew prion strain.
[My paper] Atsushi Kobayashi , Masahiro Asano , Shirou Mohri , TetsuyukiKitamoto
The genotype (methionine or valine) at polymorphic codon 129 of the humanprion protein (PrP) gene and the type (type 1 or type 2) of abnormal isoformof PrP (PrP(Sc)) are major determinants of the clinicopathologicalphenotypes of sporadic Creutzfeldt-Jakob disease (sCJD). Here we found thattransmission of sCJD prions from a patient with valine homozygosity (129V/V)and type 2 PrP(Sc) (sCJD-VV2 prions) to mice expressing human PrP withmethionine homozygosity (129M/M) generated unusual PrP(Sc) intermediate insize between type 1 and type 2. The intermediate type PrP(Sc) was seen inall examined dura mater graft-associated CJD cases with 129M/M andplaque-type PrP deposits (p-dCJD). p-dCJD prions and sCJD-VV2 prionsexhibited similar transmissibility and neuropathology, and the identicaltype of PrP(Sc) when inoculated into PrP-humanized mice with 129M/M or129V/V. These findings suggest that p-dCJD could be caused by cross-sequencetransmission of sCJD-VV2 prions.
snip...
In this study, the strain-dependent traits of sCJDMM1prions were inherited through cross-sequencetransmission without any modification. Thehumanized mice with 129V/V produced type 1 PrPresafter inoculation with sCJD-MM1 prions. BecausesCJD-VV1 cases are extremely rare (at most 1-2%of the total number of sCJD cases) and characterizedby early onset (mean age at onset: 39.3 years) (5),
####################################
our results raise the possibility that CJD casesclassified as VV1 may include cases caused byiatrogenic transmission of sCJD-MM1 prions orfood-borne infection by type 1 prions from animals,e.g., chronic wasting disease prions in cervid. In fact,two CJD-VV1 patients who hunted deer orconsumed venison have been reported (40, 41). Theresults of the present study emphasize the need fortraceback studies and careful re-examination of thebiochemical properties of sCJD-VV1 prions.
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In conclusion, cross-sequence transmission ofsCJD-VV2 prions generates a new prion strain withaltered conformational properties and diseasephenotypes as p-dCJD prions. Furthermore, thenewly generated prions have unique transmissibilityincluding the traceback phenomenon. In the future, ifatypical prion strains emerge through cross-sequencetransmission, especially from animals, tracebackstudies will enable us to identify the origin of theprions.
REFERENCES...snip...end
FULL TEXT ;
http://www.jbc.org/cgi/content/abstract/M704597200v1?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=Cross-sequence+transmission+of+sporadic+Creutzfeldt-Jakob+disease+creates+a+new+&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=21267
Re: Colorado Surveillance Program for Chronic Wasting DiseaseTransmission to Humans (TWO SUSPECT CASES)
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0704&L=sanet-mg&T=0&P=1165
Subject: Aspects of the Cerebellar Neuropathology in Nor98Date: September 26, 2007 at 4:06 pm PST
P03.141
Aspects of the Cerebellar Neuropathology in Nor98
Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E11National Veterinary Insitute, Sweden; 2National Veterinary Institute,Norway
Nor98 is a prion disease of old sheep and goats. This atypical form ofscrapie was first described in Norway in 1998. Several features of Nor98were shown to be different from classical scrapie including the distributionof disease associated prion protein (PrPd) accumulation in the brain. Thecerebellum is generally the most affected brain area in Nor98. The studyherepresented aimed at adding information on the neuropathology in thecerebellumof Nor98 naturally affected sheep of various genotypes in Sweden and Norway.A panel of histochemical and immunohistochemical (IHC) stainings such as IHCfor PrPd, synaptophysin, glial fibrillary acidic protein, amyloid, and cellmarkersfor phagocytic cells were conducted. The type of histological lesions andtissuereactions were evaluated. The types of PrPd deposition were characterized.Thecerebellar cortex was regularly affected, even though there was a variationin the severity of the lesions from case to case.Neuropil vacuolation was more marked in the molecular layer, but affectedalso the granular cell layer. There was a loss of granule cells. Punctatedeposition of PrPd was characteristic. It was morphologically and indistributionidentical with that of synaptophysin, suggesting that PrPd accumulates inthe synaptic structures. PrPd was also observed in the granule cell layerand in thewhite matter.*** The pathology features of Nor98 in the cerebellum of the affected sheepshowed similarities with those of sporadic Creutzfeldt-Jakob disease inhumans.
http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf
From: "Terry S. Singeltary Sr."Sent: Tuesday, August 21, 2007 9:50 AMSubject: TWO MORE Nor98 atypical Scrapie cases detected in USA bringingtotal to 3 cases to date
Infected and Source Flocks
As of June 30, 2007, there were .....
snip...
One field case and one validation case were consistent with Nor-98 scrapie.
http://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/monthly_scrapie_rpt.pps
IN the February 2007 Scrapie report it only mentions ;
''One case was consistent with Nor98 scrapie.''
http://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/
(please note flocks of origin were in WY, CO, AND CA. PERSONAL COMMUNCATIONSUSDA, APHIS, VS ET AL. ...TSS)
NOR98 SHOWS MOLECULAR FEATURES REMINISCENT OF GSS
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=14553
An evaluation of scrapie surveillance in the United States
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=3427
FOIA REQUEST FOR ATYPICAL TSE INFORMATION ON VERMONT SHEEP
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=10451
Subject: FSIS NOTICE SAMPLE COLLECTION FROM CATTLE UNDER THE BOVINESPONGIFORM ENCEPHALOPATHY (BSE)ONGOING SURVEILLANCE PROGRAMFrom: "Terry S. Singeltary Sr."Reply-To: Sustainable Agriculture Network Discussion GroupDate: Fri, 2 Feb 2007 17:32:58 -0600
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0702&L=sanet-mg&P=720
SEE STEADY INCREASE IN SPORADIC CJD IN THE USA FROM1997 TO 2006. SPORADIC CJD CASES TRIPLED, with phenotypeof 'UNKNOWN' strain growing. ...
http://www.cjdsurveillance.com/resources-casereport.html
There is a growing number of human CJD cases, and they were presented lastweek in San Francisco by Luigi Gambatti(?) from his CJD surveillancecollection.
He estimates that it may be up to 14 or 15 persons which display selectivelySPRPSC and practically no detected RPRPSC proteins.
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734.
http://jama.ama-assn.org/http://www.neurology.org/cgi/eletters/60/2/176#535
JOURNAL OF NEUROLOGY
MARCH 26, 2003
RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob
disease in the United States
Email Terry S. Singeltary:
flounder@wt.net
I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to
comment on the CDC's attempts to monitor the occurrence of emerging
forms of CJD. Asante, Collinge et al [1] have reported that BSE
transmission to the 129-methionine genotype can lead to an alternate
phenotype that is indistinguishable from type 2 PrPSc, the commonest
sporadic CJD. However, CJD and all human TSEs are not reportable
nationally. CJD and all human TSEs must be made reportable in every
state and internationally. I hope that the CDC does not continue to
expect us to still believe that the 85%+ of all CJD cases which are
sporadic are all spontaneous, without route/source. We have many TSEs in
the USA in both animal and man. CWD in deer/elk is spreading rapidly and
CWD does transmit to mink, ferret, cattle, and squirrel monkey by
intracerebral inoculation. With the known incubation periods in other
TSEs, oral transmission studies of CWD may take much longer. Every
victim/family of CJD/TSEs should be asked about route and source of this
agent. To prolong this will only spread the agent and needlessly expose
others. In light of the findings of Asante and Collinge et al, there
should be drastic measures to safeguard the medical and surgical arena
from sporadic CJDs and all human TSEs. I only ponder how many sporadic
CJDs in the USA are type 2 PrPSc?
http://www.neurology.org/cgi/eletters/60/2/176#535
doi:10.1016/S1473-3099(03)00715-1Copyright © 2003 Published by Elsevier Ltd.Newsdesk
Tracking spongiform encephalopathies in North America
Xavier Bosch
Available online 29 July 2003.
Volume 3, Issue 8, August 2003, Page 463
“My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost mymom to hvCJD (Heidenhain variant CJD)and have been searching for answers ever since. What I have found is that wehave not been told the truth. CWDin deer and elk is a small portion of a much bigger problem.”............................
http://www.thelancet.com/journals/laninf/article/PIIS1473309903007151/fulltext
http://download.thelancet.com/pdfs/journals/1473-3099/PIIS1473309903007151.pdf
see history of cjd questionnaire
http://brain.hastypastry.net/forums/showthread.php?t=2408
Sent: Monday May 28, 2007
Subject: THE BIG LIE SPORADIC CJD AND MAD COW DISEASEs i.e. TSE
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0705&L=sanet-mg&T=0&P=25276
Subject: HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and theUKBSEnvCJD only theoryDate: January 29, 2006 at 9:03 am PST
Comments sent via JAMA Feedback Page------------------------------------------------------------NAME: Terry S. Singeltary Sr.E-MAIL: flounder9@verizon.netIP ADDRESS: xxxxxxxxHOSTNAME: xxxxxxxxPREVIOUS PAGE: http://jama.ama-assn.org/misc/authors.dtlBROWSER: Mozilla/5.0 (Windows; U; Win98; en-US; rv:1.0.2) Gecko/20030208Netscape/7.02PROMOTIONAL USE: (not answered)
HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJDonly theory
TSEs have been rampant in the USA for decades in many species, and they allhave been rendered and fed back to animals for human/animal consumption.propose that the current diagnostic criteria for human TSEs only enhancesand helps the spreading of human TSE from the continued belief of theUKBSEnvCJD only theory in 2007. With all the science to date refuting it, tocontinue to validate this myth, will only spread this TSE agent through amultitude of potential routes and sources i.e. consumption, surgical, blood,medical, cosmetics etc. I propose as with Aguzzi, Asante, Collinge, Caughey,Deslys, Dormont, Gibbs, Ironside, Manuelidis, Marsh, et al and many more,that the world of TSE Transmissible Spongiform Encephalopathy is far from anexact science, but there is enough provenscience to date that this myth should be put to rest once and for all, andthat we move forward with a new classification for human and animal TSE thatwould properly identify the infected species, the source species, and thenthe route.
This would further have to be broken down to strain of species and then theroute of transmission would further have to be broken down. Accumulation andTransmission are key to the threshold from sub-clinical to clinical disease,and key to all this, is to stop the amplification and transmission of thisagent, the spreading of, no matter what strain. In my opinion, to continuewith this myth that the U.K. strain of BSE (one strain TSE in cows), and thenv/v CJD (one strain TSE humans) and that all the rest of human TSE are justone single strain i.e. sporadic CJD (when to date there are 6 differentphenotypes of sCJD, and growing per Gambetti et al), and that no otheranimal TSE transmits to humans, to continue with this masquerade will onlycontinue to spread, expose, and kill, who knows how many more in the yearsand decades to come. ONE was enough for me, My Mom, hvCJD i.e. HeidenhainVariant CJD, DOD 12/14/97 confirmed, which is nothing more than another mansname added to CJD, like CJD itself, Jakob and Creutzfeldt, orGerstmann-Straussler-Scheinker syndrome, just another CJD or human TSE,named after another human.
WE are only kidding ourselves with the current diagnostic criteria for humanand animal TSE, especially differentiating between the nvCJD vs the sporadicCJDstrains and then the GSS strains and also the FFI fatal familial insomniastrains or the ones that mimics one or the other of those TSE? Tissueinfectivity and strain typing of the many variants of the human and animalTSEs are paramount in all variants of all TSE. There must be a properclassification that will differentiate between all these human TSE in orderto do this. With the CDI and other more sensitive testing coming about, Ionly hope that my proposal will some day be taken seriously. ...
Terry S. Singeltary Sr.P.O. Box 42Bacliff, Texas USA 77518flounder9@verizon.net
CJD NEWS
http://disc.server.com/Indices/236650.html
CJD VOICE (voice for _all_ victims of human TSE)
http://members.aol.com/larmstr853/cjdvoice/cjdvoice.htm
TSS
From: "Terry S. Singeltary Sr." <flounder9@VERIZON.NET>
To: <BSE-L@LISTS.AEGEE.ORG>
Sent: Tuesday, October 02, 2007 10:43 AM
Subject: [BSE-L] Monthly Creutzfeldt Jakob Disease statistics 2 October 2007
Subject: Monthly Creutzfeldt Jakob Disease statistics 2 October 2007Date: October 2, 2007 at 8:10 am PST
Monthly Creutzfeldt Jakob Disease statistics
DEPARTMENT OF HEALTH News Release issued by The Government News Network on 2October 2007The Department of Health is today issuing the latest information about thenumbers of known cases of Creutzfeldt Jakob disease. This includes cases ofvariant Creutzfeldt Jakob disease (vCJD) - the form of the disease thoughtto be linked to BSE. The position is as follows:Definite and probable CJD cases in the UK:
As at 28 September 2007Summary of vCJD cases
Deaths
Deaths from definite vCJD (confirmed): 114
Deaths from probable vCJD (without neuropathological confirmation): 47
Deaths from probable vCJD (neuropathological confirmation pending): 0
Number of deaths from definite or probable vCJD (as above): 161Alive
Number of definite/probable vCJD cases still alive: 5
Total number of definite or probable vCJD (dead and alive): 166Following this press notice the Department of Health will stop issuingmonthly CJD press notices because the same data is also published by theNational CJD Surveillance Unit in Edinburgh. Up to date figures for thenumber of vCJD cases in the UK can be found on the website of the NationalCJD Surveillance Unit at: http://www.cjd.ed.ac.uk/figures.htm.
CREUTZFELDT-JAKOB DISEASE IN THE UKBy Calendar Year
see chart of steady increase of sporadic CJD cases ...tss
snip...
* As at 28th September 2007Referrals: a simple count of all the cases which have been referred to theNational CJD Surveillance Unit for further investigation in the year inquestion. CJD may be no more than suspected; about half the cases referredin the past have turned out not to be CJD. Cases are notified to the Unitfrom a variety of sources including neurologists, neuropathologists,neurophysiologists, general physicians, psychiatrists, electroencephalogram(EEG) departments etc. As a safety net, death certificates coded under thespecific rubrics 046.1 and 331.9 in the 9th ICD Revisions are obtained fromthe Office for National Statistics in England and Wales, the GeneralRegister Office for Scotland and the General Register Office for NorthernIreland.
Deaths: All columns show the number of deaths that have occurred in definiteand probable cases of all types of CJD and GSS in the year shown. Thefigures include both cases referred to the Unit for investigation while thepatient was still alive and those where CJD was only discovered post mortem(including a few cases picked up by the Unit from death certificates). Thereis therefore no read across from these columns to the referrals column. Thefigures will be subject to retrospective adjustment as diagnoses areconfirmed.
Definite cases: this refers to the diagnostic status of cases. In definitecases the diagnosis will have been pathologically confirmed, in most casesby post mortem examination of brain tissue (rarely it may be possible toestablish a definite diagnosis by brain biopsy while the patient is stillalive).
Probable vCJD cases: are those who fulfil the 'probable' criteria set out inthe Annex and are either still alive, or have died and await post mortempathological confirmation. Those still alive will always be shown within thecurrent year's figures.
Sporadic: Classic CJD cases with typical EEG and brain pathology. Sporadiccases appear to occur spontaneously with no identifiable cause and accountfor 85% of all cases.
Probable sporadic: Cases with a history of rapidly progressive dementia,typical EEG and at least two of the following clinical features; myoclonus,visual or cerebellar signs, pyramidal/extrapyramidalsigns or akineticmutism.
Iatrogenic: where infection with classic CJD has occurred accidentally asthe result of a medical procedure. All UK cases have resulted from treatmentwith human derived pituitary growth hormones or from grafts using dura mater(a membrane lining the skull).
Familial: cases occurring in families associated with mutations in the PrPgene (10 - 15% of cases).
GSS: Gerstmann-Straussler-Scheinker syndrome - an exceedingly rare inheritedautosomal dominant disease, typified by chronic progressive ataxia andterminal dementia. The clinical duration is from 2 to 10 years, much longerthan for CJD.
vCJD: Variant CJD, the hitherto unrecognised variant of CJD discovered bythe National CJD Surveillance Unit and reported in The Lancet on 6 April1996. This is characterised clinically by a progressive neuropsychiatricdisorder leading to ataxia, dementia and myoclonus (or chorea) without thetypical EEG appearance of CJD. Neuropathology shows marked spongiform changeand extensive florid plaques throughout the brain.
Definite vCJD cases still alive: These will be cases where the diagnosis hasbeen pathologically confirmed (by brain biopsy).
[ENDS]
http://www.wired-gov.net/wg/wg-news-1.nsf/lfi/152230
P02.15
Beyond the PrPres Type1/ Type2 dichotomy in Creutzfeldt-Jakob Disease
Cassard, H1; Uro-Coste, E2; Simon, S3; Bilheude, JM4; Perret-Liaudet, A5;Ironside, J6; Haik, S7; Basset-Leobon, C2; Lacroux, C1; Peoch’, K8;Stressenberger, N9;Langeveld, J10; Head, M11; Hauw, JJ12; Schecher, F1; Delisle, MB13;Andreoletti, O11Ecole Natinale Vétérinaire de Toulouse, France; 22Service d’AnatomiePathologiqueand INSERM U466 R, France; 3DRM, CEA/Saclay, France; 4 Bio-Rad, R&D, France;5 Hôpital Neurologique Service de Neurochimie, France; 6School of Molecular& Clinical Medicine (Pathology),, National Creutzfeldt-Jakob DiseaseSurveillance Un,UK; 7Pitié Salpetriere Universitary Hospital, France; 8Hôpital Lariboisière,Service deBiochimie et Biologie Moléculaire,, France; 9Hôpital Neurologique -ServicedeNeurochimie, France; 10CIDC-Lelystad, Netherlands; 11University ofEdinburgh, Western GeneralHospital, UK; 12Pitié Salpetriere Universitary Hospital,, Laboratoire deNeuropathologie, France;13Rangueil Universitary Hospital, Service d’Anatomie Pathologique, France
Creutzfeldt-Jakob disease (CJD) cases are currently classified according toestablished diagnostic criteria and by the genotype at codon 129 of the PRNPgene and the Western blotting of the proteinase K digested abnormal prionprotein that distinguishes a type 1 and a type 2 profile. Thesebiochemicallydistinct PrPres types have been proposed to represent distinct prionstrains.However, since the cooccurence of type 1 and type 2 PrPres in the samepatientis common, the rationale of this classification and strain concept asapplied toCJD are currently under discussion.
Five different brain areas from of 40 sporadic CJD and 11 iatrogenic CJD(both dura matter-, and growth hormone-associated) cases, originating fromUK and France, were systematically investigated, using Western blottingtyping,and by two others biochemical assays that depend on the behaviour of PrPScinvariable PK digestion conditions.
As described previously, co-occurrence of type 1 and type 2 PrPres wasfound in 30% of the CJD patients examined. However, our novel PKconcentrationdependent assays identified a single uniform PrP type in cases where bothtype 1 andtype 2 were present. Moreover, in sCJD four distinct biochemical PrPScsignatures were identified by the PK concentration dependent assays andthesecorrelated to the current genotype/clinico-pathological sCJD groups. In iCJDthe foursimilar biochemical signatures were observed, but were not correlated toparticularPRNP 129 polymorphism or Western Blot PrPres patterns. Moreover notabledifferenceswere observed between PrPSc biochemical properties of French and UK GH-CJDcases,which could reflect, as already suspected, differences in the causativeagents.
Identification, in sCJD and iCJD, of four different PrPSc phenotypesirrespective of patients PRNP polymorphism at codon 129 and Western blotprofile provides new insights into human prion disease aetiology and couldreflects anunsuspected diversity of TSE agents in human disease. Further investigationsarecurrently underway using animal transmission to correlate agent strain withour newdiscriminant biochemical assays.
P04.33
Diagnostic Utility of CSF Biomarkers and General CSF Findings in a U.SSporadic CJD Cohort
Geschwind, MD; Haman, A; Torres-Chae, C; Raudabaugh, BJ; Devereux, G;Miller, BL University of California, San Francisco, USA
Background:
The diagnostic utility of CSF biomarkers, including 14-3-3 protein,neuron-specific enolase (NSE), AB42, total Tau (T-Tau), and phosphorylatedTau (PTau)/ T-Tau ratio are often are used for sporadic CJD (sCJD) diagnosisis controversial. We have previously reported the CSF 14-3-3 protein to havepoor sensitivity for CJD diagnosis. In this study, now report thesensitivity and specificityof several CSF biomarkers and general characteristics in a U.S. cohort ofsCJDand non-prion rapidly progressive dementia (RPD) controls (Non-CJD cohort)subjects.
Design/Methods:
Clinical diagnoses are made through review of medical records, clinicalevaluation, andin many cases pathology. Data is stored in a secure clinical relationaldatabase, which wasqueried for various CSF findings, including cell count, protein, IgG index,oligoclonal bands(OCBs), 14-3-3, NSE, T-Tau in patients with probable or definite sporadicCJD andnon-prion rapidly progressive dementias (RPD), most of whom were referred toour centerwith a potential diagnosis of CJD. For probable sCJD diagnosis, we used UCSFcriteria thatare modified from WHO to substitute MRI for 14-3-3. T-Tau and NSE wereconsideredpositive if > 1300 pg/ml and > 35 ng/ml, respectively. For this analysis,ambiguous 14-3-3results were considered as negative.
Results:
14-3-3 protein (n=149) sensitivity was only 48% (47% for definite; 50% forprobable sCJD). NSE (n=49) sensitivity was 63% (66% for definite; 59% forprobablesCJD). T-Tau (n=28) was the most sensitive at 68% (69% for definite; 67% forprobable sCJD). The specificity of these biomarkers among our CJD and RPDcontrols(n=72) was 66% for 14-3-3 (n=47), 81% for NSE (n=21), and 100% for T-Tau(n=7). The14-3-3 had the lowest sensitivity and specificity. Mildly elevated CSFprotein(<100>20, is uncommon in sCJD.
Conclusions/Relevance:
In a cohort from a major U.S. CJD referral center, the 14-3-3is neither sensitive nor specific for sCJD. NSE and T-Tau also show poorsensitivity forsCJD. T-Tau may be more specific than 14-3-3 and NSE, but our “n” is small.WHO sCJD criteria should be revised; by eliminating 14-3-3 and includingbrainMRI into the criteria. We are currently analyzing the effects of diseaseduration andcodon 129 polymorphism on these CSF biomarker results.
http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf
see full text 143 pages ;
http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf
Subject: PRION2007 ABSTRACTS SPORADIC CJD AND H BASE MAD COW ALABAMA ANDTEXAS SEPTEMBER 2007Date: September 24, 2007 at 6:52 pm PST
P02.35Molecular Features of the Protease-resistant Prion Protein (PrPres) inH-type BSE
Biacabe, A-G1; Jacobs, JG2; Gavier-Widén, D3; Vulin, J1; Langeveld, JPM2;Baron, TGM1 1AFSSA, France; 2CIDC-Lelystad, Netherlands; 3SVA, Sweden
Western blot analyses of PrPres accumulating in the brain of BSE-infectedcattle havedemonstrated 3 different molecular phenotypes regarding to the apparentmolecularmasses and glycoform ratios of PrPres bands. We initially described isolates(H-typeBSE) essentially characterized by higher PrPres molecular mass and decreasedlevels of the diglycosylated PrPres band, in contrast to the classical typeof BSE.This type is also distinct from another BSE phenotype named L-type BSE, oralso BASE (for Bovine Amyloid Spongiform Encephalopathy), mainlycharacterized by alow representation of the diglycosylated PrPres band as well as a lowerPrPresmolecular mass. Retrospective molecular studies in France of all availableBSE casesolder than 8 years old and of part of the other cases identified since thebeginning of theexhaustive surveillance of the disease in 20001 allowed to identify 7 H-typeBSE cases, among 594 BSE cases that could be classified as classical, L- orH-type BSE.By Western blot analysis of H-type PrPres, we described a remarkablespecific feature with antibodies raised against the C-terminal region of PrPthatdemonstrated the existence of a more C-terminal cleaved form of PrPres(named PrPres#2 ),in addition to the usual PrPres form (PrPres #1). In the unglycosylatedform,PrPres #2 migrates at about 14 kDa, compared to 20 kDa for PrPres #1. Theproportionof the PrPres#2 in cattle seems to by higher compared to the PrPres#1.Furthermoreanother PK–resistant fragment at about 7 kDa was detected by some moreN-terminalantibodies and presumed to be the result of cleavages of both N- andC-terminal partsof PrP. These singular features were maintained after transmission of thedisease toC57Bl/6 mice. The identification of these two additional PrPres fragments(PrPres #2 and7kDa band) reminds features reported respectively in sporadicCreutzfeldt-Jakob diseaseand in Gerstmann-Sträussler-Scheinker (GSS) syndrome in humans.
FC5.5.1BASE Transmitted to Primates and MV2 sCJD Subtype Share PrP27-30 and PrPScC-terminal Truncated Fragments
Zanusso, G1; Commoy, E2; Fasoli, E3; Fiorini, M3; Lescoutra, N4; Ruchoux,MM4; Casalone, C5; Caramelli, M5; Ferrari, S3; Lasmezas, C6; Deslys, J-P4;Monaco, S3 1University of Verona, of Neurological and Visual Sciences,Italy; 2CEA, IMETI/SEPIA, France; 3University of Verona, Neurological andVisual Sciences, Italy; 4IMETI/SEPIA, France; 5IZSPLVA, Italy; 6The ScrippsResearch Insitute, USA
The etiology of sporadic Creutzfeldt-Jakob disease (sCJD), the most frequenthumanprion disease, remains still unknown. The marked disease phenotypeheterogeneityobserved in sCJD is thought to be influenced by the type of proteinaseK-resistantprion protein, or PrPSc (type 1 or type 2 according to the electrophoreticmobility ofthe unglycosylated backbone), and by the host polymorphic Methionine/Valine(M/V) codon 129 of the PRNP. By using a two-dimensional gel electrophoresis(2D-PAGE) and imunoblotting we previously showed that in sCJD, in additionto thePrPSc type, distinct PrPSc C-terminal truncated fragments (CTFs) correlatedwithdifferent sCJD subtypes. Based on the combination of CTFs and PrPSc type, wedistinguishedthree PrPSc patterns: (i) the first was observed in sCJD with PrPSc type 1of allgenotypes,;
(ii) the second was found in M/M-2 (cortical form); (iii) the third inamyloidogenic M/V-2 and V/V-2 subtypes (Zanusso et al., JBC 2004) . Recently, we showed thatsCJDsubtype M/V-2 shared molecular and pathological features with an atypicalform ofBSE, named BASE, thus suggesting a potential link between the twoconditions. Thisconnection was further confirmed after 2D-PAGE analysis, which showed anidentical PrPSc signature, including the biochemical pattern of CTFs. Topursue thisissue, we obtained brain homogenates from Cynomolgus macaquesintracerebrallyinoculated with brain homogenates from BASE. Samples were separated by usinga twodimensional electrophoresis (2D-PAGE) followed by immunoblotting. Wehere show that the PrPSc pattern obtained in infected primates is identicaltoBASE and sCJD MV-2 subtype. These data strongly support the link, or atleast acommon ancestry, between a sCJD subtype and BASE. This work was supported byNeuroprion(FOOD-CT-2004-506579)
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USA MAD COW CASES IN ALABAMA AND TEXAS
***PLEASE NOTE***
USA BASE CASE, (ATYPICAL BSE), AND OR TSE (whatever they are calling ittoday), please note that both the ALABAMA COW, AND THE TEXAS COW, both were''H-TYPE'', personal communication Detwiler et al Wednesday, August 22, 200711:52 PM. ...TSS
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=19779
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FC5.5.2 Transmission of Italian BSE and BASE Isolates in Cattle Results intoa Typical BSE Phenotype and a Muscle Wasting Disease
Zanusso, G1; Lombardi, G2; Casalone, C3; D’Angelo, A4; Gelmetti, D2;Torcoli, G2;Barbieri, I2; Corona, C3; Fasoli, E1; Farinazzo, A1; Fiorini, M1; Gelati,M1; Iulini, B3;Tagliavini, F5; Ferrari, S1; Monaco, S1; Caramelli, M3; Capucci, L21University of Verona, Neurological and Visual Sciences, Italy; 2IZSLER,Italy; 3IZSPLVA,Italy; 4University of Turin, Animal Pathology, Italy; 5Isituto Carlo Besta,Italy
The clinical phenotype of bovine spongiform encephalopathy has beenextensivelyreported in early accounts of the disorder. Following the introduction ofstatutory activesurveillance, almost all BSE cases have been diagnosed on apathological/molecularbasis, in a pre-symptomatic clinical stage. In recent years, the activesurveillancesystem has uncovered atypical BSE cases, which are characterized by distinctconformers of the PrPSc, named high-type (BSE-H) and low-type (BSE-L), whoseclinicopathological phenotypes remain unknown. We recently reported twoItalian atypical cases with a PrPSc type similar to BSE-L, pathologicallycharacterized by PrP amyloid plaques. Experimental transmission to TgBovmice hasrecently disclosed that BASE is caused by a distinct prion strain which isextremelyvirulent. A major limitation of transmission studies to mice is the lack ofreliableinformation on clinical phenotype of BASE in its natural host. In thepresent study, weexperimentally infected Fresian/Holstein and Alpine/Brown cattle withItalian BSE andBASE isolates by i.c. route. BASE infected cattle showed survival timessignificantlyshorter than BSE, a finding more readily evident in Fresian/Holstein, and inkeeping withprevious observations in TgBov mice. Clinically, BSE-infected cattledeveloped adisease phenotype highly comparable with that described in field BSE casesand in experimentally challenged cattle. On the contrary, BASE-inoculatedcattledeveloped an amyotrophic disorder accompanied by mental dullness.The molecular and neuropathological profiles, including PrP depositionpattern, closely matched those observed in the original cases. This studyfurther confirmsthat BASE is caused by a distinct prion isolate and discloses a noveldiseasephenotype in cattle, closely resembling the phenotype previous reported inscrapie-inoculatedcattle and in some subtypes of inherited and sporadic Creutzfeldt-Jakobdisease.Oral Abstracts14
FC5.1.1Transmission Results in Squirrel Monkeys Inoculated with Human sCJD, vCJD,and GSS Blood Specimens: the Baxter Study
Brown, P1; Gibson, S2; Williams, L3; Ironside, J4; Will, R4; Kreil, T5;Abee, C3 1Fondation Alliance BioSecure, France; 2University of SouthAlabama, USA;3University of Texas MD Anderson Cancer Center, USA; 4Western GeneralHospital, UK; 5Baxter BioSience, Austria
Background: Rodent and sheep models of Transmissible SpongiformEncephalopathy(TSE) have documented blood infectivity in both the pre-clinical andclinical phases ofdisease. Results in a (presumably more appropriate) non-human primate modelhave not been reported.
Objective: To determine if blood components (red cells, white cells,platelets, andplasma) from various forms of human TSE are infectious.
Methods: Blood components were inoculated intra-cerebrally (0.1 ml) andintravenously (0.5 ml) into squirrel monkeys from 2 patients with sporadicCreutzfeldt- Jakob disease (sCJD) and 3 patients with variantCreutzfeldt-Jakob disease(vCJD). Additional monkeys were inoculated with buffy coat or plasma samplesfromchimpanzees infected with either sCJD or Gerstmann-Sträussler-Scheinkerdisease (GSS). Animals were monitored for a period of 5 years, and all dyingor sacrificed animals had post-mortem neuropathological examinations andWestern blots to determine the presence or absence of the misfolded ‘prion’protein (PrPTSE).
Results: No transmissions occurred in any of the animals inoculated withblood components from patients with sporadic or variant CJD. All donorchimpanzees(sCJD and GSS) became symptomatic within 6 weeks of their pre-clinical phaseplasmapheresis, several months earlier than the expected onset of illness.One monkey inoculated with purified leukocytes from a pre-clinical GSSchimpanzee developed disease after 36 months.
Conclusion: No infectivity was found in small volumes of blood componentsfrom 4 patients with sporadic CJD and 3 patients with variant CJD.
***However, a single transmission from a chimpanzee-passaged strain of GSSshows that infectivity may be present in leukocytes, and the ‘shock’ ofgeneral anaesthesia and plasmspheresis appears to have triggered the onsetof illness in pre-clinical donor chimpanzees.
FC5.1.2Interim Transmission Results in Cynomolgus Macaques Inoculated with BSE and
vCJD Blood Specimens
Lasmezas, C1; Lescoutra, N2; Comoy, E2; Holznagel, E3; Loewer, J3; Motzkus,D4; Hunsmann, G4; Ingrosso, L5; Bierke, P6; Pocchiari, M5; Ironside, J7;Will,R7; Deslys, JP2 1Scripps Florida, Infectology, USA; 2CEA, France; 3PEI,Germany; 4DPZ, Germany; 5Istituto Superiore di Sanita, Italy; 6SMI, Sweden;7CJD Surveillance Unit, UK
BSE and vCJD transmitted to cynomolgus macaques reproduce many features ofhuman vCJD, including clinical symptoms, neuropathological hallmarks ofvCJD,PrPres electrophoretical pattern and, most importantly, the widedistribution ofinfectivity in peripheral organs. The latter characteristic distinguishesvCJD from sCJDin both humans and cynomolgus macaques, and prompted us to use thisnon-humanprimate model for further investigations of vCJD and its risk for humanhealth. Theoccurrence of four vCJD infections in humans transfused with blood frompatients wholater developed vCJD has raised concern about blood transfusion safety incountries with vCJD.In this collaborative European study, we investigated the infectivity ofblood components and whole blood administered by intracerebral (ic) andintravenous (iv) routes. Buffy-coat and whole blood was inoculated by ic andiv route, respectively, from two vCJD patients and from two clinicalvCJD-inoculatedmacaques. Transfusions were also performed from whole blood and bloodleucodepletedaccording to hospital practice standards from two clinical BSE inoculatedmacaques. Blood infectivity during the preclinical phase is being examinedin orallyinfected macaques. Whole blood was collected and transfused from one suchanimaltwo years after oral challenge, whereas buffy-coat and plasma from twoanimalsat 2 and 4.5 years post-challenge, respectively, have been inoculated by theic route.This is an ongoing study in which recipient animals continue to be observedat various times post-inoculation. So far, we have had one positivetransmission in oneanimal transfused 65 months earlier with 40 ml of whole blood from a vCJDmacaque(the characteristics of the disease in this animal will be shown in aseparate poster by E.Comoy). This positive transmission reproduces transfusion transmission ofvCJD inhumans, with an incubation of 5.5 years compatible with incubation periodsobserved in humans.
FC5.3Assessing the Risk of vCJD Transmission by Dentistry; Distribution ofInfectivity in Oral Tissues of VM Mice after Simulated Oral Feeding ofBSE-301V
Sutton, JM1; Kirby, E1; Dickinson, J1; Dennis, M1; Cornwall, M1; Vassey,MJ1; Smith, A2; Marsh, PD3; Walker, JT1; Raven, NDH11Health Protection Agency, Centre for Emergency Preparedness and Response,,TSE Research group, UK; 2University of Glasgow, Dental School, UK; 3HealthProtection Agency, Centre for Emergency Preparedness and Response,, UK
Background: Ongoing concerns about the prevalence of variant CreutzfeldtJakobDisease (vCJD) in the UK population has heightened concerns about the risksof iatrogenic transmission of the disease. Although there have been no casesto date of transmission by surgery there have been 4 cases involving bloodtransfusion. This study aims to assess the potential of transmission of thedisease bydental procedures. Whilst the risks are undoubtably low the very largenumbers ofprocedures carried out annually have the potential to amplify the risksconsiderablyand there is very little data in this area to form the basis for accurateriskassessments. Aim(s)/Objective(s): To assess the relative levels ofinfectivity in oraltissues from a murine model following exposure to BSE-301V through the smallintestine.
Methods. The study uses a BSE-301V, VM mouse model as a clinically relevantmodel for assessing iatrogenic vCJD transmission between humans. Infectiousmousebrain homogenate was prepared and inoculated into a loop of the duodenum, toprevent direct contamination of the oral tissues. Mice were sacrificed at3-weeklyintervals and at appearance of clinical symptoms. A range of oral tissues,including dental pulp, gingival margin, salivary gland, saliva, lingualtonsil andtrigeminal ganglia, together with brain and spleen tissues were removed,processed ashomogenates and reinoculated intracranially (ic.) into indicator mice.
Results: The primary challenge proved to be a very efficient route ofinfection with a 100% attack rate and a mean incubation to clinical diseaseof 157 ± 17 days (compared to 120 days for the same titre inoculum ic.).Infectivity was observed in all oral and control tissues with varyingtime-coursesand titres estimated from incubation period.
Discussion: The results throw new light on the potential routes ofdissemination and spread of infectivity from the small intestine to the oralcavity and its implications for possible iatrogenic transmission of vCJD viadental,endoscopic or other forms of surgery.
Conclusion: The data generated from the study provides support for ongoingrisk assessments to look at the potential for vCJD transmission via dentalprocedures alongside other elements of studies looking at effectiveness ofdecontamination and re-use of dental instruments.
From: "Terry S. Singeltary Sr."Subject: CWD UPDATE 88 AUGUST 31, 2007
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0709&L=sanet-mg&T=0&P=450
Date: Wed, 29 Aug 2007 21:13:08 -0500From: "Terry S. Singeltary Sr."Subject: CWD NEW MEXICO RECORDS IT'S 19 CASE (near Texas border again)
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=26079
Monitoring the Potential Transmission of Chronic Wasting Disease to HumansUsing a Hunter Registry Database in Wyoming (405 lines)From: Terry S. Singeltary Sr. <[log in to unmask]>Date: Thu, 30 Aug 2007 21:23:42 -0500
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&F=&S=&P=27654
P01.47
Quantifying the Species Barrier in Chronic Wasting Disease by a Novel invitro Conversion Assay
Li, L1; Coulthart, MB2; Balachandran, A3; Chakrabartty, A4; Cashman, NR11University of British Columbia, Brain Research Centre, Canada; 2PublicHealth Agencyof Canada, National Microbiology Laboratory, Canada; 3Animal DiseasesResearchInstitute, Canada Food Inspection Agency, National Reference Laboratory forScrapieand CWD, Canada; 4Ontario Cancer Institute and Department of MedicalBiophysics, University of Toronto, Canada
Background: Chronic wasting disease (CWD) is a transmissible spongiformencephalopathy that can affect North American cervids (deer, elk, andmoose).Although the risk of CWD crossing the species barrier and causing humandisease isstill unknown, however, definite bovine spongiform encephalopathy (BSE)transmissionto humans as variant CJD (vCJD), it would seem prudent to limit the exposureofhumans to CWD.
Aim: In view of the fact that BSE can be readily transmitted to non-bovidspecies, it isimportant to establish the species susceptibility range of CWD.
Methods: In vitro conversion system was performed by incubation of prionswithnormal brain homogenates as described before, and protease K (PK) resistantPrP was determined by immunoblotting with 6H4 monoclonal prion antibody.
Results: Our results demonstrate that PrPC from cervids (including moose)can beefficiently converted to a protease-resistant form by incubation with elkCWD prions,presumably due to sequence and structural similarities between thesespecies.Interestingly, hamster shows a high conversion ratio by PrPCWD. Moreover,partialdenaturation of substrate PrPC can apparently overcome the structuralbarriersbetween more distant species.
Conclusions: Our work correctly predicted the transmission of CWD to a wildmoose. We find a species barrier for prion protein conversion betweencervids andother species, however, this barrier might be overcome if the PrPC substratehasbeen partially denatured in a cellular environment. Such an environmentmightalso promote CWD transmission to non-cervid species, *** including humans.Acid/GdnHCl-treated brain PrPC was a superior substrate for the in vitroconversionthan PrPC treated at physiological pH. This has implications for the processby whichthe prion protein is converted in disease.
http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf
Subject: Cross-sequence transmission of sporadic Creutzfeldt-Jakob diseasecreates a new prion strain
Date: August 25, 2007 at 12:42 pm PST
Subject: Cross-sequence transmission of sporadic Creutzfeldt-Jakob diseasecreates a new prion strainDate: August 25, 2007 at 12:42 pm PST
J Biol Chem. 2007 Aug 20; : 17709374
Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease creates anew prion strain.
[My paper] Atsushi Kobayashi , Masahiro Asano , Shirou Mohri , TetsuyukiKitamoto
The genotype (methionine or valine) at polymorphic codon 129 of the humanprion protein (PrP) gene and the type (type 1 or type 2) of abnormal isoformof PrP (PrP(Sc)) are major determinants of the clinicopathologicalphenotypes of sporadic Creutzfeldt-Jakob disease (sCJD). Here we found thattransmission of sCJD prions from a patient with valine homozygosity (129V/V)and type 2 PrP(Sc) (sCJD-VV2 prions) to mice expressing human PrP withmethionine homozygosity (129M/M) generated unusual PrP(Sc) intermediate insize between type 1 and type 2. The intermediate type PrP(Sc) was seen inall examined dura mater graft-associated CJD cases with 129M/M andplaque-type PrP deposits (p-dCJD). p-dCJD prions and sCJD-VV2 prionsexhibited similar transmissibility and neuropathology, and the identicaltype of PrP(Sc) when inoculated into PrP-humanized mice with 129M/M or129V/V. These findings suggest that p-dCJD could be caused by cross-sequencetransmission of sCJD-VV2 prions.
snip...
In this study, the strain-dependent traits of sCJDMM1prions were inherited through cross-sequencetransmission without any modification. Thehumanized mice with 129V/V produced type 1 PrPresafter inoculation with sCJD-MM1 prions. BecausesCJD-VV1 cases are extremely rare (at most 1-2%of the total number of sCJD cases) and characterizedby early onset (mean age at onset: 39.3 years) (5),
####################################
our results raise the possibility that CJD casesclassified as VV1 may include cases caused byiatrogenic transmission of sCJD-MM1 prions orfood-borne infection by type 1 prions from animals,e.g., chronic wasting disease prions in cervid. In fact,two CJD-VV1 patients who hunted deer orconsumed venison have been reported (40, 41). Theresults of the present study emphasize the need fortraceback studies and careful re-examination of thebiochemical properties of sCJD-VV1 prions.
###################################
In conclusion, cross-sequence transmission ofsCJD-VV2 prions generates a new prion strain withaltered conformational properties and diseasephenotypes as p-dCJD prions. Furthermore, thenewly generated prions have unique transmissibilityincluding the traceback phenomenon. In the future, ifatypical prion strains emerge through cross-sequencetransmission, especially from animals, tracebackstudies will enable us to identify the origin of theprions.
REFERENCES...snip...end
FULL TEXT ;
http://www.jbc.org/cgi/content/abstract/M704597200v1?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=Cross-sequence+transmission+of+sporadic+Creutzfeldt-Jakob+disease+creates+a+new+&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=21267
Re: Colorado Surveillance Program for Chronic Wasting DiseaseTransmission to Humans (TWO SUSPECT CASES)
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0704&L=sanet-mg&T=0&P=1165
Subject: Aspects of the Cerebellar Neuropathology in Nor98Date: September 26, 2007 at 4:06 pm PST
P03.141
Aspects of the Cerebellar Neuropathology in Nor98
Gavier-Widén, D1; Benestad, SL2; Ottander, L1; Westergren, E11National Veterinary Insitute, Sweden; 2National Veterinary Institute,Norway
Nor98 is a prion disease of old sheep and goats. This atypical form ofscrapie was first described in Norway in 1998. Several features of Nor98were shown to be different from classical scrapie including the distributionof disease associated prion protein (PrPd) accumulation in the brain. Thecerebellum is generally the most affected brain area in Nor98. The studyherepresented aimed at adding information on the neuropathology in thecerebellumof Nor98 naturally affected sheep of various genotypes in Sweden and Norway.A panel of histochemical and immunohistochemical (IHC) stainings such as IHCfor PrPd, synaptophysin, glial fibrillary acidic protein, amyloid, and cellmarkersfor phagocytic cells were conducted. The type of histological lesions andtissuereactions were evaluated. The types of PrPd deposition were characterized.Thecerebellar cortex was regularly affected, even though there was a variationin the severity of the lesions from case to case.Neuropil vacuolation was more marked in the molecular layer, but affectedalso the granular cell layer. There was a loss of granule cells. Punctatedeposition of PrPd was characteristic. It was morphologically and indistributionidentical with that of synaptophysin, suggesting that PrPd accumulates inthe synaptic structures. PrPd was also observed in the granule cell layerand in thewhite matter.*** The pathology features of Nor98 in the cerebellum of the affected sheepshowed similarities with those of sporadic Creutzfeldt-Jakob disease inhumans.
http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf
From: "Terry S. Singeltary Sr."Sent: Tuesday, August 21, 2007 9:50 AMSubject: TWO MORE Nor98 atypical Scrapie cases detected in USA bringingtotal to 3 cases to date
Infected and Source Flocks
As of June 30, 2007, there were .....
snip...
One field case and one validation case were consistent with Nor-98 scrapie.
http://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/monthly_scrapie_rpt.pps
IN the February 2007 Scrapie report it only mentions ;
''One case was consistent with Nor98 scrapie.''
http://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/
(please note flocks of origin were in WY, CO, AND CA. PERSONAL COMMUNCATIONSUSDA, APHIS, VS ET AL. ...TSS)
NOR98 SHOWS MOLECULAR FEATURES REMINISCENT OF GSS
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=14553
An evaluation of scrapie surveillance in the United States
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=3427
FOIA REQUEST FOR ATYPICAL TSE INFORMATION ON VERMONT SHEEP
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=10451
Subject: FSIS NOTICE SAMPLE COLLECTION FROM CATTLE UNDER THE BOVINESPONGIFORM ENCEPHALOPATHY (BSE)ONGOING SURVEILLANCE PROGRAMFrom: "Terry S. Singeltary Sr."Reply-To: Sustainable Agriculture Network Discussion GroupDate: Fri, 2 Feb 2007 17:32:58 -0600
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0702&L=sanet-mg&P=720
SEE STEADY INCREASE IN SPORADIC CJD IN THE USA FROM1997 TO 2006. SPORADIC CJD CASES TRIPLED, with phenotypeof 'UNKNOWN' strain growing. ...
http://www.cjdsurveillance.com/resources-casereport.html
There is a growing number of human CJD cases, and they were presented lastweek in San Francisco by Luigi Gambatti(?) from his CJD surveillancecollection.
He estimates that it may be up to 14 or 15 persons which display selectivelySPRPSC and practically no detected RPRPSC proteins.
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm
http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf
Diagnosis and Reporting of Creutzfeldt-Jakob Disease
Singeltary, Sr et al. JAMA.2001; 285: 733-734.
http://jama.ama-assn.org/http://www.neurology.org/cgi/eletters/60/2/176#535
JOURNAL OF NEUROLOGY
MARCH 26, 2003
RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob
disease in the United States
Email Terry S. Singeltary:
flounder@wt.net
I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to
comment on the CDC's attempts to monitor the occurrence of emerging
forms of CJD. Asante, Collinge et al [1] have reported that BSE
transmission to the 129-methionine genotype can lead to an alternate
phenotype that is indistinguishable from type 2 PrPSc, the commonest
sporadic CJD. However, CJD and all human TSEs are not reportable
nationally. CJD and all human TSEs must be made reportable in every
state and internationally. I hope that the CDC does not continue to
expect us to still believe that the 85%+ of all CJD cases which are
sporadic are all spontaneous, without route/source. We have many TSEs in
the USA in both animal and man. CWD in deer/elk is spreading rapidly and
CWD does transmit to mink, ferret, cattle, and squirrel monkey by
intracerebral inoculation. With the known incubation periods in other
TSEs, oral transmission studies of CWD may take much longer. Every
victim/family of CJD/TSEs should be asked about route and source of this
agent. To prolong this will only spread the agent and needlessly expose
others. In light of the findings of Asante and Collinge et al, there
should be drastic measures to safeguard the medical and surgical arena
from sporadic CJDs and all human TSEs. I only ponder how many sporadic
CJDs in the USA are type 2 PrPSc?
http://www.neurology.org/cgi/eletters/60/2/176#535
doi:10.1016/S1473-3099(03)00715-1Copyright © 2003 Published by Elsevier Ltd.Newsdesk
Tracking spongiform encephalopathies in North America
Xavier Bosch
Available online 29 July 2003.
Volume 3, Issue 8, August 2003, Page 463
“My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost mymom to hvCJD (Heidenhain variant CJD)and have been searching for answers ever since. What I have found is that wehave not been told the truth. CWDin deer and elk is a small portion of a much bigger problem.”............................
http://www.thelancet.com/journals/laninf/article/PIIS1473309903007151/fulltext
http://download.thelancet.com/pdfs/journals/1473-3099/PIIS1473309903007151.pdf
see history of cjd questionnaire
http://brain.hastypastry.net/forums/showthread.php?t=2408
Sent: Monday May 28, 2007
Subject: THE BIG LIE SPORADIC CJD AND MAD COW DISEASEs i.e. TSE
http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0705&L=sanet-mg&T=0&P=25276
Subject: HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and theUKBSEnvCJD only theoryDate: January 29, 2006 at 9:03 am PST
Comments sent via JAMA Feedback Page------------------------------------------------------------NAME: Terry S. Singeltary Sr.E-MAIL: flounder9@verizon.netIP ADDRESS: xxxxxxxxHOSTNAME: xxxxxxxxPREVIOUS PAGE: http://jama.ama-assn.org/misc/authors.dtlBROWSER: Mozilla/5.0 (Windows; U; Win98; en-US; rv:1.0.2) Gecko/20030208Netscape/7.02PROMOTIONAL USE: (not answered)
HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJDonly theory
TSEs have been rampant in the USA for decades in many species, and they allhave been rendered and fed back to animals for human/animal consumption.propose that the current diagnostic criteria for human TSEs only enhancesand helps the spreading of human TSE from the continued belief of theUKBSEnvCJD only theory in 2007. With all the science to date refuting it, tocontinue to validate this myth, will only spread this TSE agent through amultitude of potential routes and sources i.e. consumption, surgical, blood,medical, cosmetics etc. I propose as with Aguzzi, Asante, Collinge, Caughey,Deslys, Dormont, Gibbs, Ironside, Manuelidis, Marsh, et al and many more,that the world of TSE Transmissible Spongiform Encephalopathy is far from anexact science, but there is enough provenscience to date that this myth should be put to rest once and for all, andthat we move forward with a new classification for human and animal TSE thatwould properly identify the infected species, the source species, and thenthe route.
This would further have to be broken down to strain of species and then theroute of transmission would further have to be broken down. Accumulation andTransmission are key to the threshold from sub-clinical to clinical disease,and key to all this, is to stop the amplification and transmission of thisagent, the spreading of, no matter what strain. In my opinion, to continuewith this myth that the U.K. strain of BSE (one strain TSE in cows), and thenv/v CJD (one strain TSE humans) and that all the rest of human TSE are justone single strain i.e. sporadic CJD (when to date there are 6 differentphenotypes of sCJD, and growing per Gambetti et al), and that no otheranimal TSE transmits to humans, to continue with this masquerade will onlycontinue to spread, expose, and kill, who knows how many more in the yearsand decades to come. ONE was enough for me, My Mom, hvCJD i.e. HeidenhainVariant CJD, DOD 12/14/97 confirmed, which is nothing more than another mansname added to CJD, like CJD itself, Jakob and Creutzfeldt, orGerstmann-Straussler-Scheinker syndrome, just another CJD or human TSE,named after another human.
WE are only kidding ourselves with the current diagnostic criteria for humanand animal TSE, especially differentiating between the nvCJD vs the sporadicCJDstrains and then the GSS strains and also the FFI fatal familial insomniastrains or the ones that mimics one or the other of those TSE? Tissueinfectivity and strain typing of the many variants of the human and animalTSEs are paramount in all variants of all TSE. There must be a properclassification that will differentiate between all these human TSE in orderto do this. With the CDI and other more sensitive testing coming about, Ionly hope that my proposal will some day be taken seriously. ...
Terry S. Singeltary Sr.P.O. Box 42Bacliff, Texas USA 77518flounder9@verizon.net
CJD NEWS
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