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NCBA, R-CALF, COOL, USDA (No Politics!)
PRION2007 ABSTRACTS SPORADIC CJD AND H BASE MAD COW
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<blockquote data-quote="flounder" data-source="post: 442053" data-attributes="member: 3519"><p>Subject: PRION2007 ABSTRACTS SPORADIC CJD AND H BASE MAD COW ALABAMA AND TEXAS SEPTEMBER 2007</p><p>Date: September 24, 2007 at 6:52 pm PST</p><p></p><p>P02.35</p><p>Molecular Features of the Protease-resistant Prion Protein (PrPres) in H-type BSE</p><p>Biacabe, A-G1; Jacobs, JG2; Gavier-Widén, D3; Vulin, J1; Langeveld, JPM2; Baron,</p><p>TGM1</p><p>1AFSSA, France; 2CIDC-Lelystad, Netherlands; 3SVA, Sweden</p><p>Western blot analyses of PrPres accumulating in the brain of BSE-infected cattle have</p><p>demonstrated 3 different molecular phenotypes regarding to the apparent molecular</p><p>masses and glycoform ratios of PrPres bands. We initially described isolates (H-type</p><p>BSE) essentially characterized by higher PrPres molecular mass and decreased levels</p><p>of the diglycosylated PrPres band, in contrast to the classical type of BSE. This type</p><p>is also distinct from another BSE phenotype named L-type BSE, or also BASE (for</p><p>Bovine Amyloid Spongiform Encephalopathy), mainly characterized by a low</p><p>representation of the diglycosylated PrPres band as well as a lower PrPres molecular</p><p>mass. Retrospective molecular studies in France of all available BSE cases older than 8 years</p><p>old and of part of the other cases identified since the beginning of the exhaustive</p><p>surveillance of the disease in 20001 allowed to identify 7 H-type BSE cases, among</p><p>594 BSE cases that could be classified as classical, L- or H-type BSE.</p><p>By Western blot analysis of H-type PrPres, we described a remarkable specific feature</p><p>with antibodies raised against the C-terminal region of PrP that demonstrated the</p><p>existence of a more C-terminal cleaved form of PrPres (named PrPres#2 ), in addition</p><p>to the usual PrPres form (PrPres #1). In the unglycosylated form, PrPres #2 migrates at</p><p>about 14 kDa, compared to 20 kDa for PrPres #1. The proportion of the PrPres#2 in</p><p>cattle seems to by higher compared to the PrPres#1. Furthermore another</p><p>PKâ€"resistant fragment at about 7 kDa was detected by some more N-terminal</p><p>antibodies and presumed to be the result of cleavages of both N- and C-terminal parts</p><p>of PrP. These singular features were maintained after transmission of the disease to</p><p>C57Bl/6 mice.</p><p>The identification of these two additional PrPres fragments (PrPres #2 and 7kDa band)</p><p>reminds features reported respectively in sporadic Creutzfeldt-Jakob disease and in</p><p>Gerstmann-Sträussler-Scheinker (GSS) syndrome in humans.</p><p></p><p></p><p>FC5.5.1</p><p>BASE Transmitted to Primates and MV2 sCJD Subtype Share PrP27-30 and PrPSc</p><p>C-terminal Truncated Fragments</p><p></p><p>Zanusso, G1; Commoy, E2; Fasoli, E3; Fiorini, M3; Lescoutra, N4; Ruchoux,</p><p>MM4; Casalone, C5; Caramelli, M5; Ferrari, S3; Lasmezas, C6; Deslys, J-P4;</p><p>Monaco, S3 1University of Verona, of Neurological and Visual Sciences, Italy; 2CEA,</p><p>IMETI/SEPIA, France; 3University of Verona, Neurological and Visual Sciences, Italy;</p><p>4IMETI/SEPIA, France; 5IZSPLVA, Italy; 6The Scripps Research Insitute, USA</p><p></p><p></p><p>The etiology of sporadic Creutzfeldt-Jakob disease (sCJD), the most frequent human</p><p>prion disease, remains still unknown. The marked disease phenotype heterogeneity</p><p>observed in sCJD is thought to be influenced by the type of proteinase K-resistant</p><p>prion protein, or PrPSc (type 1 or type 2 according to the electrophoretic mobility of</p><p>the unglycosylated backbone), and by the host polymorphic Methionine/Valine (M/V)</p><p>codon 129 of the PRNP. By using a two-dimensional gel electrophoresis (2D-PAGE)</p><p>and imunoblotting we previously showed that in sCJD, in addition to the PrPSc type,</p><p>distinct PrPSc C-terminal truncated fragments (CTFs) correlated with different sCJD</p><p>subtypes. Based on the combination of CTFs and PrPSc type, we distinguished three</p><p>PrPSc patterns: (i) the first was observed in sCJD with PrPSc type 1 of all</p><p>genotypes,;</p><p></p><p>(ii) the second was found in M/M-2 (cortical form); (iii) the third in amyloidogenic M/V-</p><p>2 and V/V-2 subtypes (Zanusso et al., JBC 2004) . Recently, we showed that sCJD</p><p>subtype M/V-2 shared molecular and pathological features with an atypical form of</p><p>BSE, named BASE, thus suggesting a potential link between the two conditions. This</p><p>connection was further confirmed after 2D-PAGE analysis, which showed an</p><p>identical PrPSc signature, including the biochemical pattern of CTFs. To pursue this</p><p>issue, we obtained brain homogenates from Cynomolgus macaques intracerebrally</p><p>inoculated with brain homogenates from BASE. Samples were separated by using a</p><p>twodimensional electrophoresis (2D-PAGE) followed by immunoblotting. We here show</p><p>that the PrPSc pattern obtained in infected primates is identical to BASE and sCJD MV-2 </p><p>subtype. These data strongly support the link, or at least a common ancestry, between a </p><p>sCJD subtype and BASE. This work was supported by Neuroprion (FOOD-CT-2004-506579)</p><p></p><p></p><p>*******************************************************</p><p></p><p></p><p>USA MAD COW CASES IN ALABAMA AND TEXAS</p><p></p><p></p><p>***PLEASE NOTE***</p><p></p><p></p><p>USA BASE CASE, (ATYPICAL BSE), AND OR TSE (whatever they are calling it</p><p>today), please note that both the ALABAMA COW, AND THE TEXAS COW, both were</p><p>''H-TYPE'', personal communication Detwiler et al Wednesday, August 22, 2007</p><p>11:52 PM. ...TSS</p><p></p><p></p><p><a href="http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=19779" target="_blank">http://lists.ifas.ufl.edu/cgi-bin/wa.ex ... =0&P=19779</a></p><p></p><p></p><p>*******************************************************</p><p></p><p></p><p>FC5.5.2 Transmission of Italian BSE and BASE Isolates in Cattle Results into a</p><p>Typical BSE Phenotype and a Muscle Wasting Disease</p><p></p><p></p><p>Zanusso, G1; Lombardi, G2; Casalone, C3; D’Angelo, A4; Gelmetti, D2; Torcoli, G2;</p><p>Barbieri, I2; Corona, C3; Fasoli, E1; Farinazzo, A1; Fiorini, M1; Gelati, M1; Iulini, B3;</p><p>Tagliavini, F5; Ferrari, S1; Monaco, S1; Caramelli, M3; Capucci, L2</p><p>1University of Verona, Neurological and Visual Sciences, Italy; 2IZSLER, Italy; 3IZSPLVA,</p><p>Italy; 4University of Turin, Animal Pathology, Italy; 5Isituto Carlo Besta, Italy</p><p></p><p></p><p>The clinical phenotype of bovine spongiform encephalopathy has been extensively</p><p>reported in early accounts of the disorder. Following the introduction of statutory active</p><p>surveillance, almost all BSE cases have been diagnosed on a pathological/molecular</p><p>basis, in a pre-symptomatic clinical stage. In recent years, the active surveillance</p><p>system has uncovered atypical BSE cases, which are characterized by distinct</p><p>conformers of the PrPSc, named high-type (BSE-H) and low-type (BSE-L), whose</p><p>clinicopathological phenotypes remain unknown. We recently reported two</p><p>Italian atypical cases with a PrPSc type similar to BSE-L, pathologically</p><p>characterized by PrP amyloid plaques. Experimental transmission to TgBov mice has recently</p><p>disclosed that BASE is caused by a distinct prion strain which is extremely virulent. A</p><p>major limitation of transmission studies to mice is the lack of reliable information on</p><p>clinical phenotype of BASE in its natural host. In the present study, we experimentally</p><p>infected Fresian/Holstein and Alpine/Brown cattle with Italian BSE and BASE isolates</p><p>by i.c. route. BASE infected cattle showed survival times significantly shorter than</p><p>BSE, a finding more readily evident in Fresian/Holstein, and in keeping with</p><p>previous observations in TgBov mice. Clinically, BSE-infected cattle developed a</p><p>disease phenotype highly comparable with that described in field BSE cases and in</p><p>experimentally challenged cattle. On the contrary, BASE-inoculated cattle</p><p>developed an amyotrophic disorder accompanied by mental dullness.</p><p>The molecular and neuropathological profiles, including PrP deposition</p><p>pattern, closely matched those observed in the original cases. This study further confirms</p><p>that BASE is caused by a distinct prion isolate and discloses a novel disease</p><p>phenotype in cattle, closely resembling the phenotype previous reported in scrapie-inoculated</p><p>cattle and in some subtypes of inherited and sporadic Creutzfeldt-Jakob disease.</p><p>Oral Abstracts</p><p>14</p><p></p><p></p><p>FC5.1.1</p><p>Transmission Results in Squirrel Monkeys Inoculated with Human sCJD, vCJD,</p><p>and GSS Blood Specimens: the Baxter Study</p><p></p><p>Brown, P1; Gibson, S2; Williams, L3; Ironside, J4; Will, R4; Kreil, T5; Abee, C3</p><p>1Fondation Alliance BioSecure, France; 2University of South Alabama, USA;</p><p>3University of Texas MD Anderson Cancer Center, USA; 4Western General Hospital, UK;</p><p>5Baxter BioSience, Austria</p><p></p><p></p><p>Background: Rodent and sheep models of Transmissible Spongiform Encephalopathy</p><p>(TSE) have documented blood infectivity in both the pre-clinical and clinical phases of</p><p>disease. Results in a (presumably more appropriate) non-human primate model</p><p>have not been reported.</p><p>Objective: To determine if blood components (red cells, white cells, platelets, and</p><p>plasma) from various forms of human TSE are infectious.</p><p>Methods: Blood components were inoculated intra-cerebrally (0.1 ml) and</p><p>intravenously (0.5 ml) into squirrel monkeys from 2 patients with sporadic</p><p>Creutzfeldt- Jakob disease (sCJD) and 3 patients with variant Creutzfeldt-Jakob disease</p><p>(vCJD). Additional monkeys were inoculated with buffy coat or plasma samples from</p><p>chimpanzees infected with either sCJD or Gerstmann-Sträussler-Scheinker</p><p>disease (GSS). Animals were monitored for a period of 5 years, and all dying or</p><p>sacrificed animals had post-mortem neuropathological examinations and Western blots to</p><p>determine the presence or absence of the misfolded ‘prion’ protein (PrPTSE).</p><p>Results: No transmissions occurred in any of the animals inoculated with</p><p>blood components from patients with sporadic or variant CJD. All donor chimpanzees</p><p>(sCJD and GSS) became symptomatic within 6 weeks of their pre-clinical phase</p><p>plasmapheresis, several months earlier than the expected onset of illness.</p><p>One monkey inoculated with purified leukocytes from a pre-clinical GSS</p><p>chimpanzee developed disease after 36 months.</p><p>Conclusion: No infectivity was found in small volumes of blood components</p><p>from 4 patients with sporadic CJD and 3 patients with variant CJD. </p><p></p><p></p><p>***However, a single transmission from a chimpanzee-passaged strain of GSS </p><p>shows that infectivity may be present in leukocytes, and the ‘shock’ of general anaesthesia and</p><p>plasmspheresis appears to have triggered the onset of illness in pre-clinical donor chimpanzees.</p><p></p><p></p><p></p><p>FC5.1.2</p><p>Interim Transmission Results in Cynomolgus Macaques Inoculated with BSE and</p><p>vCJD Blood Specimens</p><p></p><p></p><p>Lasmezas, C1; Lescoutra, N2; Comoy, E2; Holznagel, E3; Loewer, J3; Motzkus, D4;</p><p>Hunsmann, G4; Ingrosso, L5; Bierke, P6; Pocchiari, M5; Ironside, J7; Will,</p><p>R7; Deslys, JP2 1Scripps Florida, Infectology, USA; 2CEA, France; 3PEI, Germany; 4DPZ,</p><p>Germany; 5Istituto Superiore di Sanita, Italy; 6SMI, Sweden; 7CJD Surveillance Unit, UK</p><p></p><p></p><p>BSE and vCJD transmitted to cynomolgus macaques reproduce many features of</p><p>human vCJD, including clinical symptoms, neuropathological hallmarks of vCJD,</p><p>PrPres electrophoretical pattern and, most importantly, the wide distribution of</p><p>infectivity in peripheral organs. The latter characteristic distinguishes vCJD from sCJD</p><p>in both humans and cynomolgus macaques, and prompted us to use this non-human</p><p>primate model for further investigations of vCJD and its risk for human health. The</p><p>occurrence of four vCJD infections in humans transfused with blood from patients who</p><p>later developed vCJD has raised concern about blood transfusion safety in countries</p><p>with vCJD.</p><p>In this collaborative European study, we investigated the infectivity of</p><p>blood components and whole blood administered by intracerebral (ic) and</p><p>intravenous (iv) routes. Buffy-coat and whole blood was inoculated by ic and iv route,</p><p>respectively, from two vCJD patients and from two clinical vCJD-inoculated macaques.</p><p>Transfusions were also performed from whole blood and blood leucodepleted</p><p>according to hospital practice standards from two clinical BSE inoculated</p><p>macaques.</p><p>Blood infectivity during the preclinical phase is being examined in orally infected</p><p>macaques. Whole blood was collected and transfused from one such animal two</p><p>years after oral challenge, whereas buffy-coat and plasma from two animals at 2</p><p>and 4.5 years post-challenge, respectively, have been inoculated by the ic route.</p><p>This is an ongoing study in which recipient animals continue to be observed</p><p>at various times post-inoculation. So far, we have had one positive transmission in one</p><p>animal transfused 65 months earlier with 40 ml of whole blood from a vCJD macaque</p><p>(the characteristics of the disease in this animal will be shown in a separate poster by E.</p><p>Comoy). This positive transmission reproduces transfusion transmission of vCJD in</p><p>humans, with an incubation of 5.5 years compatible with incubation periods</p><p>observed in humans.</p><p></p><p></p><p>FC5.3</p><p>Assessing the Risk of vCJD Transmission by Dentistry; Distribution of</p><p>Infectivity in Oral Tissues of VM Mice after Simulated Oral Feeding of BSE-301V</p><p></p><p>Sutton, JM1; Kirby, E1; Dickinson, J1; Dennis, M1; Cornwall, M1; Vassey,</p><p>MJ1; Smith, A2; Marsh, PD3; Walker, JT1; Raven, NDH1</p><p>1Health Protection Agency, Centre for Emergency Preparedness and Response,,</p><p>TSE Research group, UK; 2University of Glasgow, Dental School, UK; 3Health</p><p>Protection Agency, Centre for Emergency Preparedness and Response,, UK</p><p></p><p></p><p>Background: Ongoing concerns about the prevalence of variant Creutzfeldt Jakob</p><p>Disease (vCJD) in the UK population has heightened concerns about the risks</p><p>of iatrogenic transmission of the disease. Although there have been no cases to</p><p>date of transmission by surgery there have been 4 cases involving blood transfusion.</p><p>This study aims to assess the potential of transmission of the disease by dental</p><p>procedures. Whilst the risks are undoubtably low the very large numbers of procedures</p><p>carried out annually have the potential to amplify the risks considerably and there is</p><p>very little data in this area to form the basis for accurate risk assessments.</p><p>Aim(s)/Objective(s): To assess the relative levels of infectivity in oral tissues from a</p><p>murine model following exposure to BSE-301V through the small intestine.</p><p>Methods.</p><p>The study uses a BSE-301V, VM mouse model as a clinically relevant model for</p><p>assessing iatrogenic vCJD transmission between humans. Infectious mouse brain</p><p>homogenate was prepared and inoculated into a loop of the duodenum, to prevent</p><p>direct contamination of the oral tissues. Mice were sacrificed at 3-weekly</p><p>intervals and at appearance of clinical symptoms. A range of oral tissues, including</p><p>dental pulp, gingival margin, salivary gland, saliva, lingual tonsil and trigeminal ganglia, </p><p>together with brain and spleen tissues were removed, processed as homogenates and</p><p>reinoculated intracranially (ic.) into indicator mice.</p><p>Results: The primary challenge proved to be a very efficient route of</p><p>infection with a 100% attack rate and a mean incubation to clinical disease of 157 ± 17 days</p><p>(compared to 120 days for the same titre inoculum ic.). Infectivity was observed in all</p><p>oral and control tissues with varying time-courses and titres estimated from incubation</p><p>period.</p><p>Discussion: The results throw new light on the potential routes of dissemination and</p><p>spread of infectivity from the small intestine to the oral cavity and its implications for</p><p>possible iatrogenic transmission of vCJD via dental, endoscopic or other forms of</p><p>surgery.</p><p>Conclusion: The data generated from the study provides support for ongoing risk</p><p>assessments to look at the potential for vCJD transmission via dental procedures</p><p>alongside other elements of studies looking at effectiveness of decontamination and</p><p>re-use of dental instruments.</p><p></p><p></p><p>P02.15</p><p>Beyond the PrPres Type1/ Type2 dichotomy in Creutzfeldt-Jakob Disease</p><p></p><p>Cassard, H1; Uro-Coste, E2; Simon, S3; Bilheude, JM4; Perret-Liaudet, A5; Ironside, J6;</p><p>Haik, S7; Basset-Leobon, C2; Lacroux, C1; Peoch’, K8; Stressenberger, N9; Langeveld,</p><p>J10; Head, M11; Hauw, JJ12; Schecher, F1; Delisle, MB13; Andreoletti, O1</p><p>1Ecole Natinale Vétérinaire de Toulouse, France; 22Service d’Anatomie Pathologique</p><p>and INSERM U466 R, France; 3DRM, CEA/Saclay, France; 4 Bio-Rad, R&D, France; 5</p><p>Hôpital Neurologique Service de Neurochimie, France; 6School of Molecular & Clinical</p><p>Medicine (Pathology),, National Creutzfeldt-Jakob Disease Surveillance Un, UK; 7Pitié</p><p>Salpetriere Universitary Hospital, France; 8Hôpital Lariboisière, Service de Biochimie et</p><p>Biologie Moléculaire,, France; 9Hôpital Neurologique -Service de Neurochimie, France;</p><p>10CIDC-Lelystad, Netherlands; 11University of Edinburgh, Western General Hospital,</p><p>UK; 12Pitié Salpetriere Universitary Hospital,, Laboratoire de Neuropathologie, France;</p><p>13Rangueil Universitary Hospital, Service d’Anatomie Pathologique, France</p><p></p><p></p><p>Creutzfeldt-Jakob disease (CJD) cases are currently classified according to</p><p>established diagnostic criteria and by the genotype at codon 129 of the PRNP gene</p><p>and the Western blotting of the proteinase K digested abnormal prion protein that</p><p>distinguishes a type 1 and a type 2 profile. These biochemically distinct PrPres types</p><p>have been proposed to represent distinct prion strains. However, since the cooccurence</p><p>of type 1 and type 2 PrPres in the same patient is common, the rationale of</p><p>this classification and strain concept as applied to CJD are currently under discussion.</p><p>Five different brain areas from of 40 sporadic CJD and 11 iatrogenic CJD (both dura</p><p>matter-, and growth hormone-associated) cases, originating from UK and France, were</p><p>systematically investigated, using Western blotting typing, and by two others</p><p>biochemical assays that depend on the behaviour of PrPSc in variable PK digestion</p><p>conditions. As described previously, co-occurrence of type 1 and type 2 PrPres was</p><p>found in 30% of the CJD patients examined. However, our novel PK concentration</p><p>dependent assays identified a single uniform PrP type in cases where both type 1 and</p><p>type 2 were present. Moreover, in sCJD four distinct biochemical PrPSc signatures</p><p>were identified by the PK concentration dependent assays and these correlated to the</p><p>current genotype/clinico-pathological sCJD groups. In iCJD the four similar</p><p>biochemical signatures were observed, but were not correlated to particular PRNP 129</p><p>polymorphism or Western Blot PrPres patterns. Moreover notable differences were</p><p>observed between PrPSc biochemical properties of French and UK GH-CJD cases,</p><p>which could reflect, as already suspected, differences in the causative agents.</p><p>Identification, in sCJD and iCJD, of four different PrPSc phenotypes irrespective of</p><p>patients PRNP polymorphism at codon 129 and Western blot profile provides new</p><p>insights into human prion disease aetiology and could reflects an unsuspected</p><p>diversity of TSE agents in human disease. Further investigations are currently</p><p>underway using animal transmission to correlate agent strain with our new discriminant</p><p>biochemical assays.</p><p></p><p></p><p>see full text 143 pages ;</p><p></p><p></p><p><a href="http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf" target="_blank">http://www.prion2007.com/pdf/Prion%20Bo ... tracts.pdf</a></p><p></p><p></p><p>From: "Terry S. Singeltary Sr."</p><p>Subject: CWD UPDATE 88 AUGUST 31, 2007</p><p></p><p></p><p><a href="http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0709&L=sanet-mg&T=0&P=450" target="_blank">http://lists.ifas.ufl.edu/cgi-bin/wa.ex ... &T=0&P=450</a></p><p></p><p></p><p>Date: Wed, 29 Aug 2007 21:13:08 -0500</p><p>From: "Terry S. Singeltary Sr."</p><p>Subject: CWD NEW MEXICO RECORDS IT'S 19 CASE (near Texas border again)</p><p></p><p></p><p><a href="http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=26079" target="_blank">http://lists.ifas.ufl.edu/cgi-bin/wa.ex ... =0&P=26079</a></p><p></p><p></p><p>Monitoring the Potential Transmission of Chronic Wasting Disease to Humans</p><p>Using a Hunter Registry Database in Wyoming (405 lines)</p><p>From: Terry S. Singeltary Sr. <[log in to unmask]></p><p>Date: Thu, 30 Aug 2007 21:23:42 -0500</p><p></p><p></p><p><a href="http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&F=&S=&P=27654" target="_blank">http://lists.ifas.ufl.edu/cgi-bin/wa.ex ... S=&P=27654</a></p><p></p><p></p><p>Subject: Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease</p><p>creates a new prion strain</p><p></p><p>Date: August 25, 2007 at 12:42 pm PST</p><p></p><p></p><p>Subject: Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease</p><p>creates a new prion strain</p><p>Date: August 25, 2007 at 12:42 pm PST</p><p></p><p>J Biol Chem. 2007 Aug 20; : 17709374</p><p></p><p>Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease creates a</p><p>new prion strain.</p><p></p><p>[My paper] Atsushi Kobayashi , Masahiro Asano , Shirou Mohri , Tetsuyuki</p><p>Kitamoto</p><p></p><p>The genotype (methionine or valine) at polymorphic codon 129 of the human</p><p>prion protein (PrP) gene and the type (type 1 or type 2) of abnormal isoform</p><p>of PrP (PrP(Sc)) are major determinants of the clinicopathological</p><p>phenotypes of sporadic Creutzfeldt-Jakob disease (sCJD). Here we found that</p><p>transmission of sCJD prions from a patient with valine homozygosity (129V/V)</p><p>and type 2 PrP(Sc) (sCJD-VV2 prions) to mice expressing human PrP with</p><p>methionine homozygosity (129M/M) generated unusual PrP(Sc) intermediate in</p><p>size between type 1 and type 2. The intermediate type PrP(Sc) was seen in</p><p>all examined dura mater graft-associated CJD cases with 129M/M and</p><p>plaque-type PrP deposits (p-dCJD). p-dCJD prions and sCJD-VV2 prions</p><p>exhibited similar transmissibility and neuropathology, and the identical</p><p>type of PrP(Sc) when inoculated into PrP-humanized mice with 129M/M or</p><p>129V/V. These findings suggest that p-dCJD could be caused by cross-sequence</p><p>transmission of sCJD-VV2 prions.</p><p></p><p></p><p>snip...</p><p></p><p></p><p>In this study, the strain-dependent traits of sCJDMM1</p><p>prions were inherited through cross-sequence</p><p>transmission without any modification. The</p><p>humanized mice with 129V/V produced type 1 PrPres</p><p>after inoculation with sCJD-MM1 prions. Because</p><p>sCJD-VV1 cases are extremely rare (at most 1-2%</p><p>of the total number of sCJD cases) and characterized</p><p>by early onset (mean age at onset: 39.3 years) (5),</p><p></p><p>####################################</p><p></p><p>our results raise the possibility that CJD cases</p><p>classified as VV1 may include cases caused by</p><p>iatrogenic transmission of sCJD-MM1 prions or</p><p>food-borne infection by type 1 prions from animals,</p><p>e.g., chronic wasting disease prions in cervid. In fact,</p><p>two CJD-VV1 patients who hunted deer or</p><p>consumed venison have been reported (40, 41). The</p><p>results of the present study emphasize the need for</p><p>traceback studies and careful re-examination of the</p><p>biochemical properties of sCJD-VV1 prions.</p><p></p><p>###################################</p><p></p><p>In conclusion, cross-sequence transmission of</p><p>sCJD-VV2 prions generates a new prion strain with</p><p>altered conformational properties and disease</p><p>phenotypes as p-dCJD prions. Furthermore, the</p><p>newly generated prions have unique transmissibility</p><p>including the traceback phenomenon. In the future, if</p><p>atypical prion strains emerge through cross-sequence</p><p>transmission, especially from animals, traceback</p><p>studies will enable us to identify the origin of the</p><p>prions.</p><p></p><p>REFERENCES...snip...end</p><p></p><p>FULL TEXT ;</p><p></p><p></p><p><a href="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" target="_blank">http://www.jbc.org/cgi/content/abstract ... type=HWCIT</a></p><p></p><p></p><p><a href="http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=21267" target="_blank">http://lists.ifas.ufl.edu/cgi-bin/wa.ex ... =0&P=21267</a></p><p></p><p></p><p>Re: Colorado Surveillance Program for Chronic Wasting Disease</p><p>Transmission to Humans (TWO SUSPECT CASES)</p><p></p><p></p><p><a href="http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0704&L=sanet-mg&T=0&P=1165" target="_blank">http://lists.ifas.ufl.edu/cgi-bin/wa.ex ... T=0&P=1165</a></p><p></p><p></p><p>From: "Terry S. Singeltary Sr." </p><p>Sent: Tuesday, August 21, 2007 9:50 AM</p><p>Subject: TWO MORE Nor98 atypical Scrapie cases detected in USA bringing</p><p>total to 3 cases to date</p><p></p><p></p><p>Infected and Source Flocks</p><p></p><p>As of June 30, 2007, there were .....</p><p></p><p>snip...</p><p></p><p>One field case and one validation case were consistent with Nor-98 scrapie.</p><p></p><p><a href="http://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/monthly_scrapie_rpt.pps" target="_blank">http://www.aphis.usda.gov/animal_health ... ie_rpt.pps</a></p><p></p><p></p><p>IN the February 2007 Scrapie report it only mentions ;</p><p></p><p>''One case was consistent with Nor98 scrapie.''</p><p></p><p><a href="http://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/" target="_blank">http://www.aphis.usda.gov/animal_health ... s/scrapie/</a></p><p></p><p></p><p>(please note flocks of origin were in WY, CO, AND CA. PERSONAL COMMUNCATIONS</p><p>USDA, APHIS, VS ET AL. ...TSS)</p><p></p><p></p><p>NOR98 SHOWS MOLECULAR FEATURES REMINISCENT OF GSS</p><p></p><p></p><p><a href="http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=14553" target="_blank">http://lists.ifas.ufl.edu/cgi-bin/wa.ex ... =0&P=14553</a></p><p></p><p></p><p>An evaluation of scrapie surveillance in the United States</p><p></p><p></p><p><a href="http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=3427" target="_blank">http://lists.ifas.ufl.edu/cgi-bin/wa.ex ... T=0&P=3427</a></p><p></p><p></p><p>FOIA REQUEST FOR ATYPICAL TSE INFORMATION ON VERMONT SHEEP</p><p></p><p></p><p><a href="http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=10451" target="_blank">http://lists.ifas.ufl.edu/cgi-bin/wa.ex ... =0&P=10451</a></p><p></p><p></p><p>Subject: FSIS NOTICE SAMPLE COLLECTION FROM CATTLE UNDER THE BOVINE</p><p>SPONGIFORM ENCEPHALOPATHY (BSE)</p><p>ONGOING SURVEILLANCE PROGRAM</p><p>From: "Terry S. Singeltary Sr."</p><p>Reply-To: Sustainable Agriculture Network Discussion Group</p><p>Date: Fri, 2 Feb 2007 17:32:58 -0600</p><p></p><p><a href="http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0702&L=sanet-mg&P=720" target="_blank">http://lists.ifas.ufl.edu/cgi-bin/wa.ex ... t-mg&P=720</a></p><p></p><p></p><p>SEE STEADY INCREASE IN SPORADIC CJD IN THE USA FROM</p><p>1997 TO 2006. SPORADIC CJD CASES TRIPLED, with phenotype</p><p>of 'UNKNOWN' strain growing. ...</p><p></p><p></p><p><a href="http://www.cjdsurveillance.com/resources-casereport.html" target="_blank">http://www.cjdsurveillance.com/resource ... eport.html</a></p><p></p><p></p><p>There is a growing number of human CJD cases, and they were presented last</p><p>week in San Francisco by Luigi Gambatti(?) from his CJD surveillance</p><p>collection.</p><p></p><p>He estimates that it may be up to 14 or 15 persons which display selectively</p><p>SPRPSC and practically no detected RPRPSC proteins.</p><p></p><p></p><p><a href="http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm" target="_blank">http://www.fda.gov/ohrms/dockets/ac/06/ ... 4240t1.htm</a></p><p></p><p></p><p><a href="http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf" target="_blank">http://www.fda.gov/ohrms/dockets/ac/06/ ... 4240t1.pdf</a></p><p></p><p></p><p>Diagnosis and Reporting of Creutzfeldt-Jakob Disease</p><p></p><p>Singeltary, Sr et al. JAMA.2001; 285: 733-734.</p><p></p><p><a href="http://jama.ama-assn.org/http://www.neurology.org/cgi/eletters/60/2/176#535" target="_blank">http://jama.ama-assn.org/http://www.neu ... /2/176#535</a></p><p></p><p></p><p>JOURNAL OF NEUROLOGY</p><p></p><p>MARCH 26, 2003</p><p></p><p>RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob</p><p></p><p>disease in the United States</p><p></p><p>Email Terry S. Singeltary:</p><p></p><p><a href="mailto:flounder@wt.net">flounder@wt.net</a></p><p></p><p>I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to</p><p></p><p>comment on the CDC's attempts to monitor the occurrence of emerging</p><p></p><p>forms of CJD. Asante, Collinge et al [1] have reported that BSE</p><p></p><p>transmission to the 129-methionine genotype can lead to an alternate</p><p></p><p>phenotype that is indistinguishable from type 2 PrPSc, the commonest</p><p></p><p>sporadic CJD. However, CJD and all human TSEs are not reportable</p><p></p><p>nationally. CJD and all human TSEs must be made reportable in every</p><p></p><p>state and internationally. I hope that the CDC does not continue to</p><p></p><p>expect us to still believe that the 85%+ of all CJD cases which are</p><p></p><p>sporadic are all spontaneous, without route/source. We have many TSEs in</p><p></p><p>the USA in both animal and man. CWD in deer/elk is spreading rapidly and</p><p></p><p>CWD does transmit to mink, ferret, cattle, and squirrel monkey by</p><p></p><p>intracerebral inoculation. With the known incubation periods in other</p><p></p><p>TSEs, oral transmission studies of CWD may take much longer. Every</p><p></p><p>victim/family of CJD/TSEs should be asked about route and source of this</p><p></p><p>agent. To prolong this will only spread the agent and needlessly expose</p><p></p><p>others. In light of the findings of Asante and Collinge et al, there</p><p></p><p>should be drastic measures to safeguard the medical and surgical arena</p><p></p><p>from sporadic CJDs and all human TSEs. I only ponder how many sporadic</p><p></p><p>CJDs in the USA are type 2 PrPSc?</p><p></p><p><a href="http://www.neurology.org/cgi/eletters/60/2/176#535" target="_blank">http://www.neurology.org/cgi/eletters/60/2/176#535</a></p><p></p><p></p><p>doi:10.1016/S1473-3099(03)00715-1</p><p>Copyright © 2003 Published by Elsevier Ltd.</p><p>Newsdesk</p><p></p><p>Tracking spongiform encephalopathies in North America</p><p></p><p>Xavier Bosch</p><p></p><p>Available online 29 July 2003.</p><p></p><p></p><p>Volume 3, Issue 8, August 2003, Page 463</p><p></p><p></p><p>“My name is Terry S Singeltary Sr, and I live in Bacliff, Texas. I lost my</p><p>mom to hvCJD (Heidenhain variant CJD)</p><p>and have been searching for answers ever since. What I have found is that we</p><p>have not been told the truth. CWD</p><p>in deer and elk is a small portion of a much bigger problem.â€</p><p>............................</p><p></p><p></p><p><a href="http://www.thelancet.com/journals/laninf/article/PIIS1473309903007151/fulltext" target="_blank">http://www.thelancet.com/journals/lanin ... 1/fulltext</a></p><p></p><p><a href="http://download.thelancet.com/pdfs/journals/1473-3099/PIIS1473309903007151.pdf" target="_blank">http://download.thelancet.com/pdfs/jour ... 007151.pdf</a></p><p></p><p></p><p>see history of cjd questionnaire</p><p></p><p><a href="http://brain.hastypastry.net/forums/showthread.php?t=2408" target="_blank">http://brain.hastypastry.net/forums/sho ... php?t=2408</a></p><p></p><p></p><p>Sent: Monday May 28, 2007</p><p></p><p>Subject: THE BIG LIE SPORADIC CJD AND MAD COW DISEASEs i.e. TSE</p><p></p><p></p><p><a href="http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0705&L=sanet-mg&T=0&P=25276" target="_blank">http://lists.ifas.ufl.edu/cgi-bin/wa.ex ... =0&P=25276</a></p><p></p><p></p><p>HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD</p><p>only theory</p><p></p><p></p><p>TSEs have been rampant in the USA for decades in many species, and they all</p><p>have been rendered and fed back to animals for human/animal consumption.</p><p>propose that the current diagnostic criteria for human TSEs only enhances</p><p>and helps the spreading of human TSE from the continued belief of the</p><p>UKBSEnvCJD only theory in 2007. With all the science to date refuting it, to</p><p>continue to validate this myth, will only spread this TSE agent through a</p><p>multitude of potential routes and sources i.e. consumption, surgical, blood,</p><p>medical, cosmetics etc. I propose as with Aguzzi, Asante, Collinge, Caughey,</p><p>Deslys, Dormont, Gibbs, Ironside, Manuelidis, Marsh, et al and many more,</p><p>that the world of TSE Transmissible Spongiform Encephalopathy is far from an</p><p>exact science, but there is enough proven</p><p>science to date that this myth should be put to rest once and for all, and</p><p>that we move forward with a new classification for human and animal TSE that</p><p>would properly identify the infected species, the source species, and then</p><p>the route.</p><p></p><p></p><p>This would further have to be broken down to strain of species and then the</p><p>route of transmission would further have to be broken down. Accumulation and</p><p>Transmission are key to the threshold from sub-clinical to clinical disease,</p><p>and key to all this, is to stop the amplification and transmission of this</p><p>agent, the spreading of, no matter what strain. In my opinion, to continue</p><p>with this myth that the U.K. strain of BSE (one strain TSE in cows), and the</p><p>nv/v CJD (one strain TSE humans) and that all the rest of human TSE are just</p><p>one single strain i.e. sporadic CJD (when to date there are 6 different</p><p>phenotypes of sCJD, and growing per Gambetti et al), and that no other</p><p>animal TSE transmits to humans, to continue with this masquerade will only</p><p>continue to spread, expose, and kill, who knows how many more in the years</p><p>and decades to come. ONE was enough for me, My Mom, hvCJD i.e. Heidenhain</p><p>Variant CJD, DOD 12/14/97 confirmed, which is nothing more than another mans</p><p>name added to CJD, like CJD itself, Jakob and Creutzfeldt, or</p><p>Gerstmann-Straussler-Scheinker syndrome, just another CJD or human TSE,</p><p>named after another human.</p><p></p><p></p><p>WE are only kidding ourselves with the current diagnostic criteria for human</p><p>and animal TSE, especially differentiating between the nvCJD vs the sporadic</p><p>CJD</p><p>strains and then the GSS strains and also the FFI fatal familial insomnia</p><p>strains or the ones that mimics one or the other of those TSE? Tissue</p><p>infectivity and strain typing of the many variants of the human and animal</p><p>TSEs are paramount in all variants of all TSE. There must be a proper</p><p>classification that will differentiate between all these human TSE in order</p><p>to do this. With the CDI and other more sensitive testing coming about, I</p><p>only hope that my proposal will some day be taken seriously. ...</p><p></p><p></p><p>Terry S. Singeltary Sr.</p><p>P.O. Box 42</p><p>Bacliff, Texas USA 77518</p><p><a href="mailto:flounder9@verizon.net">flounder9@verizon.net</a></p><p></p><p></p><p>CJD NEWS</p><p></p><p><a href="http://disc.server.com/Indices/236650.html" target="_blank">http://disc.server.com/Indices/236650.html</a></p><p></p><p></p><p>CJD VOICE (voice for _all_ victims of human TSE)</p><p></p><p><a href="http://members.aol.com/larmstr853/cjdvoice/cjdvoice.htm" target="_blank">http://members.aol.com/larmstr853/cjdvoice/cjdvoice.htm</a></p></blockquote><p></p>
[QUOTE="flounder, post: 442053, member: 3519"] Subject: PRION2007 ABSTRACTS SPORADIC CJD AND H BASE MAD COW ALABAMA AND TEXAS SEPTEMBER 2007 Date: September 24, 2007 at 6:52 pm PST P02.35 Molecular Features of the Protease-resistant Prion Protein (PrPres) in H-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-infected cattle have demonstrated 3 different molecular phenotypes regarding to the apparent molecular masses and glycoform ratios of PrPres bands. We initially described isolates (H-type BSE) essentially characterized by higher PrPres molecular mass and decreased levels of the diglycosylated PrPres band, in contrast to the classical type of BSE. This type is also distinct from another BSE phenotype named L-type BSE, or also BASE (for Bovine Amyloid Spongiform Encephalopathy), mainly characterized by a low representation of the diglycosylated PrPres band as well as a lower PrPres molecular mass. Retrospective molecular studies in France of all available BSE cases older than 8 years old and of part of the other cases identified since the beginning of the exhaustive surveillance of the disease in 20001 allowed to identify 7 H-type BSE cases, among 594 BSE cases that could be classified as classical, L- or H-type BSE. By Western blot analysis of H-type PrPres, we described a remarkable specific feature with antibodies raised against the C-terminal region of PrP that demonstrated 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 unglycosylated form, PrPres #2 migrates at about 14 kDa, compared to 20 kDa for PrPres #1. The proportion of the PrPres#2 in cattle seems to by higher compared to the PrPres#1. Furthermore another PK–resistant fragment at about 7 kDa was detected by some more N-terminal antibodies and presumed to be the result of cleavages of both N- and C-terminal parts of PrP. These singular features were maintained after transmission of the disease to C57Bl/6 mice. The identification of these two additional PrPres fragments (PrPres #2 and 7kDa band) reminds features reported respectively in sporadic Creutzfeldt-Jakob disease and in Gerstmann-Sträussler-Scheinker (GSS) syndrome in humans. 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, S3 1University 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 human prion disease, remains still unknown. The marked disease phenotype heterogeneity observed in sCJD is thought to be influenced by the type of proteinase K-resistant prion protein, or PrPSc (type 1 or type 2 according to the electrophoretic mobility of the 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 sCJD subtypes. Based on the combination of CTFs and PrPSc type, we distinguished three PrPSc 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 sCJD subtype M/V-2 shared molecular and pathological features with an atypical form of BSE, named BASE, thus suggesting a potential link between the two conditions. This connection was further confirmed after 2D-PAGE analysis, which showed an identical PrPSc signature, including the biochemical pattern of CTFs. To pursue this issue, we obtained brain homogenates from Cynomolgus macaques intracerebrally inoculated with brain homogenates from BASE. Samples were separated by using a twodimensional electrophoresis (2D-PAGE) followed by immunoblotting. We here show that the PrPSc pattern obtained in infected primates is identical to BASE and sCJD MV-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) ******************************************************* USA MAD COW CASES IN ALABAMA AND TEXAS ***PLEASE NOTE*** USA BASE CASE, (ATYPICAL BSE), AND OR TSE (whatever they are calling it today), please note that both the ALABAMA COW, AND THE TEXAS COW, both were ''H-TYPE'', personal communication Detwiler et al Wednesday, August 22, 2007 11:52 PM. ...TSS [url=http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=19779]http://lists.ifas.ufl.edu/cgi-bin/wa.ex ... =0&P=19779[/url] ******************************************************* FC5.5.2 Transmission of Italian BSE and BASE Isolates in Cattle Results into a 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, L2 1University 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 extensively reported in early accounts of the disorder. Following the introduction of statutory active surveillance, almost all BSE cases have been diagnosed on a pathological/molecular basis, in a pre-symptomatic clinical stage. In recent years, the active surveillance system has uncovered atypical BSE cases, which are characterized by distinct conformers of the PrPSc, named high-type (BSE-H) and low-type (BSE-L), whose clinicopathological phenotypes remain unknown. We recently reported two Italian atypical cases with a PrPSc type similar to BSE-L, pathologically characterized by PrP amyloid plaques. Experimental transmission to TgBov mice has recently disclosed that BASE is caused by a distinct prion strain which is extremely virulent. A major limitation of transmission studies to mice is the lack of reliable information on clinical phenotype of BASE in its natural host. In the present study, we experimentally infected Fresian/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, a finding more readily evident in Fresian/Holstein, and in keeping with previous observations in TgBov mice. Clinically, BSE-infected cattle developed a disease phenotype highly comparable with that described in field BSE cases and in experimentally challenged cattle. On the contrary, BASE-inoculated cattle developed an amyotrophic disorder accompanied by mental dullness. The molecular and neuropathological profiles, including PrP deposition pattern, closely matched those observed in the original cases. This study further confirms that BASE is 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 in some subtypes of inherited and sporadic Creutzfeldt-Jakob disease. Oral Abstracts 14 FC5.1.1 Transmission 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 South Alabama, USA; 3University of Texas MD Anderson Cancer Center, USA; 4Western General Hospital, UK; 5Baxter BioSience, Austria Background: Rodent and sheep models of Transmissible Spongiform Encephalopathy (TSE) have documented blood infectivity in both the pre-clinical and clinical phases of disease. Results in a (presumably more appropriate) non-human primate model have not been reported. Objective: To determine if blood components (red cells, white cells, platelets, and plasma) from various forms of human TSE are infectious. Methods: Blood components were inoculated intra-cerebrally (0.1 ml) and intravenously (0.5 ml) into squirrel monkeys from 2 patients with sporadic Creutzfeldt- Jakob disease (sCJD) and 3 patients with variant Creutzfeldt-Jakob disease (vCJD). Additional monkeys were inoculated with buffy coat or plasma samples from chimpanzees infected with either sCJD or Gerstmann-Sträussler-Scheinker disease (GSS). Animals were monitored for a period of 5 years, and all dying or sacrificed animals had post-mortem neuropathological examinations and Western blots to determine the presence or absence of the misfolded ‘prion’ protein (PrPTSE). Results: No transmissions occurred in any of the animals inoculated with blood components from patients with sporadic or variant CJD. All donor chimpanzees (sCJD and GSS) became symptomatic within 6 weeks of their pre-clinical phase plasmapheresis, several months earlier than the expected onset of illness. One monkey inoculated with purified leukocytes from a pre-clinical GSS chimpanzee developed disease after 36 months. Conclusion: No infectivity was found in small volumes of blood components from 4 patients with sporadic CJD and 3 patients with variant CJD. ***However, a single transmission from a chimpanzee-passaged strain of GSS shows that infectivity may be present in leukocytes, and the ‘shock’ of general anaesthesia and plasmspheresis appears to have triggered the onset of illness in pre-clinical donor chimpanzees. FC5.1.2 Interim 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 of human vCJD, including clinical symptoms, neuropathological hallmarks of vCJD, PrPres electrophoretical pattern and, most importantly, the wide distribution of infectivity in peripheral organs. The latter characteristic distinguishes vCJD from sCJD in both humans and cynomolgus macaques, and prompted us to use this non-human primate model for further investigations of vCJD and its risk for human health. The occurrence of four vCJD infections in humans transfused with blood from patients who later developed vCJD has raised concern about blood transfusion safety in countries with vCJD. In this collaborative European study, we investigated the infectivity of blood components and whole blood administered by intracerebral (ic) and intravenous (iv) routes. Buffy-coat and whole blood was inoculated by ic and iv route, respectively, from two vCJD patients and from two clinical vCJD-inoculated macaques. Transfusions were also performed from whole blood and blood leucodepleted according to hospital practice standards from two clinical BSE inoculated macaques. Blood infectivity during the preclinical phase is being examined in orally infected macaques. Whole blood was collected and transfused from one such animal two years after oral challenge, whereas buffy-coat and plasma from two animals at 2 and 4.5 years post-challenge, respectively, have been inoculated by the ic route. This is an ongoing study in which recipient animals continue to be observed at various times post-inoculation. So far, we have had one positive transmission in one animal transfused 65 months earlier with 40 ml of whole blood from a vCJD macaque (the characteristics of the disease in this animal will be shown in a separate poster by E. Comoy). This positive transmission reproduces transfusion transmission of vCJD in humans, with an incubation of 5.5 years compatible with incubation periods observed in humans. FC5.3 Assessing the Risk of vCJD Transmission by Dentistry; Distribution of Infectivity in Oral Tissues of VM Mice after Simulated Oral Feeding of BSE-301V Sutton, JM1; Kirby, E1; Dickinson, J1; Dennis, M1; Cornwall, M1; Vassey, MJ1; Smith, A2; Marsh, PD3; Walker, JT1; Raven, NDH1 1Health Protection Agency, Centre for Emergency Preparedness and Response,, TSE Research group, UK; 2University of Glasgow, Dental School, UK; 3Health Protection Agency, Centre for Emergency Preparedness and Response,, UK Background: Ongoing concerns about the prevalence of variant Creutzfeldt Jakob Disease (vCJD) in the UK population has heightened concerns about the risks of iatrogenic transmission of the disease. Although there have been no cases to date of transmission by surgery there have been 4 cases involving blood transfusion. This study aims to assess the potential of transmission of the disease by dental procedures. Whilst the risks are undoubtably low the very large numbers of procedures carried out annually have the potential to amplify the risks considerably and there is very little data in this area to form the basis for accurate risk assessments. Aim(s)/Objective(s): To assess the relative levels of infectivity in oral tissues from a murine model following exposure to BSE-301V through the small intestine. Methods. The study uses a BSE-301V, VM mouse model as a clinically relevant model for assessing iatrogenic vCJD transmission between humans. Infectious mouse brain homogenate was prepared and inoculated into a loop of the duodenum, to prevent direct contamination of the oral tissues. Mice were sacrificed at 3-weekly intervals and at appearance of clinical symptoms. A range of oral tissues, including dental pulp, gingival margin, salivary gland, saliva, lingual tonsil and trigeminal ganglia, together with brain and spleen tissues were removed, processed as homogenates and reinoculated intracranially (ic.) into indicator mice. Results: The primary challenge proved to be a very efficient route of infection with a 100% attack rate and a mean incubation to clinical disease of 157 ± 17 days (compared to 120 days for the same titre inoculum ic.). Infectivity was observed in all oral and control tissues with varying time-courses and titres estimated from incubation period. Discussion: The results throw new light on the potential routes of dissemination and spread of infectivity from the small intestine to the oral cavity and its implications for possible iatrogenic transmission of vCJD via dental, endoscopic or other forms of surgery. Conclusion: The data generated from the study provides support for ongoing risk assessments to look at the potential for vCJD transmission via dental procedures alongside other elements of studies looking at effectiveness of decontamination and re-use of dental instruments. 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, O1 1Ecole Natinale Vétérinaire de Toulouse, France; 22Service d’Anatomie Pathologique and 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 Disease Surveillance Un, UK; 7Pitié Salpetriere Universitary Hospital, France; 8Hôpital Lariboisière, Service de Biochimie et Biologie Moléculaire,, France; 9Hôpital Neurologique -Service de Neurochimie, France; 10CIDC-Lelystad, Netherlands; 11University of Edinburgh, Western General Hospital, UK; 12Pitié Salpetriere Universitary Hospital,, Laboratoire de Neuropathologie, France; 13Rangueil Universitary Hospital, Service d’Anatomie Pathologique, France Creutzfeldt-Jakob disease (CJD) cases are currently classified according to established diagnostic criteria and by the genotype at codon 129 of the PRNP gene and the Western blotting of the proteinase K digested abnormal prion protein that distinguishes a type 1 and a type 2 profile. These biochemically distinct PrPres types have been proposed to represent distinct prion strains. However, since the cooccurence of type 1 and type 2 PrPres in the same patient is common, the rationale of this classification and strain concept as applied to CJD 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 from UK and France, were systematically investigated, using Western blotting typing, and by two others biochemical assays that depend on the behaviour of PrPSc in variable PK digestion conditions. As described previously, co-occurrence of type 1 and type 2 PrPres was found in 30% of the CJD patients examined. However, our novel PK concentration dependent assays identified a single uniform PrP type in cases where both type 1 and type 2 were present. Moreover, in sCJD four distinct biochemical PrPSc signatures were identified by the PK concentration dependent assays and these correlated to the current genotype/clinico-pathological sCJD groups. In iCJD the four similar biochemical signatures were observed, but were not correlated to particular PRNP 129 polymorphism or Western Blot PrPres patterns. Moreover notable differences were observed between PrPSc biochemical properties of French and UK GH-CJD cases, which could reflect, as already suspected, differences in the causative agents. Identification, in sCJD and iCJD, of four different PrPSc phenotypes irrespective of patients PRNP polymorphism at codon 129 and Western blot profile provides new insights into human prion disease aetiology and could reflects an unsuspected diversity of TSE agents in human disease. Further investigations are currently underway using animal transmission to correlate agent strain with our new discriminant biochemical assays. see full text 143 pages ; [url=http://www.prion2007.com/pdf/Prion%20Book%20of%20Abstracts.pdf]http://www.prion2007.com/pdf/Prion%20Bo ... tracts.pdf[/url] From: "Terry S. Singeltary Sr." Subject: CWD UPDATE 88 AUGUST 31, 2007 [url=http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0709&L=sanet-mg&T=0&P=450]http://lists.ifas.ufl.edu/cgi-bin/wa.ex ... &T=0&P=450[/url] Date: Wed, 29 Aug 2007 21:13:08 -0500 From: "Terry S. Singeltary Sr." Subject: CWD NEW MEXICO RECORDS IT'S 19 CASE (near Texas border again) [url=http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=26079]http://lists.ifas.ufl.edu/cgi-bin/wa.ex ... =0&P=26079[/url] Monitoring the Potential Transmission of Chronic Wasting Disease to Humans Using 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 [url=http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&F=&S=&P=27654]http://lists.ifas.ufl.edu/cgi-bin/wa.ex ... S=&P=27654[/url] Subject: Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease creates a new prion strain Date: August 25, 2007 at 12:42 pm PST Subject: Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease creates a new prion strain Date: August 25, 2007 at 12:42 pm PST J Biol Chem. 2007 Aug 20; : 17709374 Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease creates a new prion strain. [My paper] Atsushi Kobayashi , Masahiro Asano , Shirou Mohri , Tetsuyuki Kitamoto The genotype (methionine or valine) at polymorphic codon 129 of the human prion protein (PrP) gene and the type (type 1 or type 2) of abnormal isoform of PrP (PrP(Sc)) are major determinants of the clinicopathological phenotypes of sporadic Creutzfeldt-Jakob disease (sCJD). Here we found that transmission of sCJD prions from a patient with valine homozygosity (129V/V) and type 2 PrP(Sc) (sCJD-VV2 prions) to mice expressing human PrP with methionine homozygosity (129M/M) generated unusual PrP(Sc) intermediate in size between type 1 and type 2. The intermediate type PrP(Sc) was seen in all examined dura mater graft-associated CJD cases with 129M/M and plaque-type PrP deposits (p-dCJD). p-dCJD prions and sCJD-VV2 prions exhibited similar transmissibility and neuropathology, and the identical type of PrP(Sc) when inoculated into PrP-humanized mice with 129M/M or 129V/V. These findings suggest that p-dCJD could be caused by cross-sequence transmission of sCJD-VV2 prions. snip... In this study, the strain-dependent traits of sCJDMM1 prions were inherited through cross-sequence transmission without any modification. The humanized mice with 129V/V produced type 1 PrPres after inoculation with sCJD-MM1 prions. Because sCJD-VV1 cases are extremely rare (at most 1-2% of the total number of sCJD cases) and characterized by early onset (mean age at onset: 39.3 years) (5), #################################### our results raise the possibility that CJD cases classified as VV1 may include cases caused by iatrogenic transmission of sCJD-MM1 prions or food-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 or consumed venison have been reported (40, 41). The results of the present study emphasize the need for traceback studies and careful re-examination of the biochemical properties of sCJD-VV1 prions. ################################### In conclusion, cross-sequence transmission of sCJD-VV2 prions generates a new prion strain with altered conformational properties and disease phenotypes as p-dCJD prions. Furthermore, the newly generated prions have unique transmissibility including the traceback phenomenon. In the future, if atypical prion strains emerge through cross-sequence transmission, especially from animals, traceback studies will enable us to identify the origin of the prions. REFERENCES...snip...end FULL TEXT ; [url=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://www.jbc.org/cgi/content/abstract ... type=HWCIT[/url] [url=http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=21267]http://lists.ifas.ufl.edu/cgi-bin/wa.ex ... =0&P=21267[/url] Re: Colorado Surveillance Program for Chronic Wasting Disease Transmission to Humans (TWO SUSPECT CASES) [url=http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0704&L=sanet-mg&T=0&P=1165]http://lists.ifas.ufl.edu/cgi-bin/wa.ex ... T=0&P=1165[/url] From: "Terry S. Singeltary Sr." Sent: Tuesday, August 21, 2007 9:50 AM Subject: TWO MORE Nor98 atypical Scrapie cases detected in USA bringing total 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. [url=http://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/downloads/monthly_scrapie_rpt.pps]http://www.aphis.usda.gov/animal_health ... ie_rpt.pps[/url] IN the February 2007 Scrapie report it only mentions ; ''One case was consistent with Nor98 scrapie.'' [url=http://www.aphis.usda.gov/animal_health/animal_diseases/scrapie/]http://www.aphis.usda.gov/animal_health ... s/scrapie/[/url] (please note flocks of origin were in WY, CO, AND CA. PERSONAL COMMUNCATIONS USDA, APHIS, VS ET AL. ...TSS) NOR98 SHOWS MOLECULAR FEATURES REMINISCENT OF GSS [url=http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=14553]http://lists.ifas.ufl.edu/cgi-bin/wa.ex ... =0&P=14553[/url] An evaluation of scrapie surveillance in the United States [url=http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=3427]http://lists.ifas.ufl.edu/cgi-bin/wa.ex ... T=0&P=3427[/url] FOIA REQUEST FOR ATYPICAL TSE INFORMATION ON VERMONT SHEEP [url=http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0708&L=sanet-mg&T=0&P=10451]http://lists.ifas.ufl.edu/cgi-bin/wa.ex ... =0&P=10451[/url] Subject: FSIS NOTICE SAMPLE COLLECTION FROM CATTLE UNDER THE BOVINE SPONGIFORM ENCEPHALOPATHY (BSE) ONGOING SURVEILLANCE PROGRAM From: "Terry S. Singeltary Sr." Reply-To: Sustainable Agriculture Network Discussion Group Date: Fri, 2 Feb 2007 17:32:58 -0600 [url=http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0702&L=sanet-mg&P=720]http://lists.ifas.ufl.edu/cgi-bin/wa.ex ... t-mg&P=720[/url] SEE STEADY INCREASE IN SPORADIC CJD IN THE USA FROM 1997 TO 2006. SPORADIC CJD CASES TRIPLED, with phenotype of 'UNKNOWN' strain growing. ... [url=http://www.cjdsurveillance.com/resources-casereport.html]http://www.cjdsurveillance.com/resource ... eport.html[/url] There is a growing number of human CJD cases, and they were presented last week in San Francisco by Luigi Gambatti(?) from his CJD surveillance collection. He estimates that it may be up to 14 or 15 persons which display selectively SPRPSC and practically no detected RPRPSC proteins. [url=http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm]http://www.fda.gov/ohrms/dockets/ac/06/ ... 4240t1.htm[/url] [url=http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf]http://www.fda.gov/ohrms/dockets/ac/06/ ... 4240t1.pdf[/url] Diagnosis and Reporting of Creutzfeldt-Jakob Disease Singeltary, Sr et al. JAMA.2001; 285: 733-734. [url=http://jama.ama-assn.org/http://www.neurology.org/cgi/eletters/60/2/176#535]http://jama.ama-assn.org/http://www.neu ... /2/176#535[/url] 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: [email=flounder@wt.net]flounder@wt.net[/email] 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? [url=http://www.neurology.org/cgi/eletters/60/2/176#535]http://www.neurology.org/cgi/eletters/60/2/176#535[/url] doi:10.1016/S1473-3099(03)00715-1 Copyright © 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 my mom to hvCJD (Heidenhain variant CJD) and have been searching for answers ever since. What I have found is that we have not been told the truth. CWD in deer and elk is a small portion of a much bigger problem.†............................ [url=http://www.thelancet.com/journals/laninf/article/PIIS1473309903007151/fulltext]http://www.thelancet.com/journals/lanin ... 1/fulltext[/url] [url=http://download.thelancet.com/pdfs/journals/1473-3099/PIIS1473309903007151.pdf]http://download.thelancet.com/pdfs/jour ... 007151.pdf[/url] see history of cjd questionnaire [url=http://brain.hastypastry.net/forums/showthread.php?t=2408]http://brain.hastypastry.net/forums/sho ... php?t=2408[/url] Sent: Monday May 28, 2007 Subject: THE BIG LIE SPORADIC CJD AND MAD COW DISEASEs i.e. TSE [url=http://lists.ifas.ufl.edu/cgi-bin/wa.exe?A2=ind0705&L=sanet-mg&T=0&P=25276]http://lists.ifas.ufl.edu/cgi-bin/wa.ex ... =0&P=25276[/url] HUMAN and ANIMAL TSE Classifications i.e. mad cow disease and the UKBSEnvCJD only theory TSEs have been rampant in the USA for decades in many species, and they all have been rendered and fed back to animals for human/animal consumption. propose that the current diagnostic criteria for human TSEs only enhances and helps the spreading of human TSE from the continued belief of the UKBSEnvCJD only theory in 2007. With all the science to date refuting it, to continue to validate this myth, will only spread this TSE agent through a multitude 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 an exact science, but there is enough proven science to date that this myth should be put to rest once and for all, and that we move forward with a new classification for human and animal TSE that would properly identify the infected species, the source species, and then the route. This would further have to be broken down to strain of species and then the route of transmission would further have to be broken down. Accumulation and Transmission are key to the threshold from sub-clinical to clinical disease, and key to all this, is to stop the amplification and transmission of this agent, the spreading of, no matter what strain. In my opinion, to continue with this myth that the U.K. strain of BSE (one strain TSE in cows), and the nv/v CJD (one strain TSE humans) and that all the rest of human TSE are just one single strain i.e. sporadic CJD (when to date there are 6 different phenotypes of sCJD, and growing per Gambetti et al), and that no other animal TSE transmits to humans, to continue with this masquerade will only continue to spread, expose, and kill, who knows how many more in the years and decades to come. ONE was enough for me, My Mom, hvCJD i.e. Heidenhain Variant CJD, DOD 12/14/97 confirmed, which is nothing more than another mans name added to CJD, like CJD itself, Jakob and Creutzfeldt, or Gerstmann-Straussler-Scheinker syndrome, just another CJD or human TSE, named after another human. WE are only kidding ourselves with the current diagnostic criteria for human and animal TSE, especially differentiating between the nvCJD vs the sporadic CJD strains and then the GSS strains and also the FFI fatal familial insomnia strains or the ones that mimics one or the other of those TSE? Tissue infectivity and strain typing of the many variants of the human and animal TSEs are paramount in all variants of all TSE. There must be a proper classification that will differentiate between all these human TSE in order to do this. With the CDI and other more sensitive testing coming about, I only hope that my proposal will some day be taken seriously. ... Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518 [email=flounder9@verizon.net]flounder9@verizon.net[/email] CJD NEWS [url=http://disc.server.com/Indices/236650.html]http://disc.server.com/Indices/236650.html[/url] CJD VOICE (voice for _all_ victims of human TSE) [url=http://members.aol.com/larmstr853/cjdvoice/cjdvoice.htm]http://members.aol.com/larmstr853/cjdvoice/cjdvoice.htm[/url] [/QUOTE]
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