Monday, March 25, 2013

Minnesota Firm Recalls Bone-In Ribeye That May Contain Specified Risk Materials Recall Release CLASS II RECALL FSIS-RC-024-2013

Minnesota Firm Recalls Bone-In Ribeye That May Contain Specified Risk Materials



Recall Release



CLASS II RECALL



FSIS-RC-024-2013 HEALTH RISK: LOW




Congressional and Public Affairs Atiya Khan (202) 720-9113




WASHINGTON, March 25, 2013 – Triple J Family Farms, a Buffalo Lake, Minn. establishment, is recalling approximately 15,270 pounds of bone-in ribeye products because the vertebral column may not have been completely removed, which is not compliant with regulations that require the removal of vertebral column in cattle 30 months of age or older, the U.S. Department of Agriculture's Food Safety and Inspection Service (FSIS) announced today.




The products subject to recall are: [View Labels (PDF Only)]




Approx. 40-lb boxes of "BEEF B/I RIB," bearing any of the following case codes: "91-R109H-C," "91-R109H-S," "91-R109H-C-SB," or "91-R109H-S-SB."




The products subject to recall bear the establishment number "EST.17466" inside the USDA mark of inspection. The products were produced and packaged on various dates between Feb. 8, 2013, and March 21, 2013, and were distributed to an FSIS-inspected establishment in New York for further processing and distribution.




The problem was discovered by FSIS during a routine specified risk material (SRM) verification and may have occurred as a result of a recent change in the company's carcass separation practices. Vertebral column is considered a SRM and must be removed from cattle of 30 months of age or older in accordance with FSIS regulations. SRMs are tissues that may contain the infective agent in cattle infected with Bovine Spongiform Encephalopathy (BSE), as well as materials that are closely associated with these potentially infective tissues. Therefore, FSIS prohibits SRMs from use as human food to minimize potential human exposure to the BSE agent. There is no indication that any of the cattle slaughtered displayed any signs of BSE.




FSIS routinely conducts recall effectiveness checks to verify recalling firms notify their customers of the recall and that steps are taken to make certain that the product is no longer available to consumers.




Consumers with questions about the recall should contact the company's HR and Office Manager, Kendra Williams, at (320) 833-2001. Media with questions about the recall should contact the company's QA Manager, Russell Harris, at (320) 833-0107.




Consumers with food safety questions can "Ask Karen," the FSIS virtual representative available 24 hours a day at AskKaren.gov or via smartphone at m.askkaren.gov. "Ask Karen" live chat services are available Monday through Friday from 10 a.m. to 4 p.m. ET. The toll-free USDA Meat and Poultry Hotline 1-888-MPHotline (1-888-674-6854) is available in English and Spanish and can be reached from l0 a.m. to 4 p.m. (Eastern Time) Monday through Friday. Recorded food safety messages are available 24 hours a day. The online Electronic Consumer Complaint Monitoring System can be accessed 24 hours a day at: www.fsis.usda.gov/FSIS_Recalls/ Problems_With_Food_Products/index.asp






#












see labels ;












Saturday, December 15, 2012



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











Saturday, November 10, 2012


Wisconsin Firm Recalls Beef Tongues That May Contain Specified Risk Materials Nov 9, 2012 WI Firm Recalls Beef Tongues










Saturday, July 23, 2011



CATTLE HEADS WITH TONSILS, BEEF TONGUES, SPINAL CORD, SPECIFIED RISK MATERIALS (SRM's) AND PRIONS, AKA MAD COW DISEASE










Sunday, October 18, 2009


Wisconsin Firm Recalls Beef Tongues That Contain Prohibited Materials SRM WASHINGTON, October 17, 2009










Thursday, October 15, 2009


Nebraska Firm Recalls Beef Tongues That Contain Prohibited Materials SRM WASHINGTON, Oct 15, 2009








Thursday, June 26, 2008


Texas Firm Recalls Cattle Heads That Contain Prohibited Materials









Tuesday, July 1, 2008



Missouri Firm Recalls Cattle Heads That Contain Prohibited Materials SRMs










Friday, August 8, 2008


Texas Firm Recalls Cattle Heads That Contain Prohibited Materials SRMs 941,271 pounds with tonsils not completely removed










Saturday, April 5, 2008


SRM MAD COW RECALL 406 THOUSAND POUNDS CATTLE HEADS WITH TONSILS KANSAS










Wednesday, April 30, 2008


Consumption of beef tongue: Human BSE risk associated with exposure to lymphoid tissue in bovine tongue in consideration of new research findings










Wednesday, April 30, 2008


Consumption of beef tongue: Human BSE risk associated with exposure to lymphoid tissue in bovine tongue in consideration of new research findings










Friday, October 15, 2010


BSE infectivity in the absence of detectable PrPSc accumulation in the tongue and nasal mucosa of terminally diseased cattle









SPECIFIED RISK MATERIALS SRMs












2007




10,000,000+ LBS. of PROHIBITED BANNED MAD COW FEED I.E. BLOOD LACED MBM IN COMMERCE USA 2007


Date: March 21, 2007 at 2:27 pm PST


RECALLS AND FIELD CORRECTIONS: VETERINARY MEDICINES -- CLASS II


PRODUCT


Bulk cattle feed made with recalled Darling's 85% Blood Meal, Flash Dried, Recall # V-024-2007


CODE


Cattle feed delivered between 01/12/2007 and 01/26/2007


RECALLING FIRM/MANUFACTURER


Pfeiffer, Arno, Inc, Greenbush, WI. by conversation on February 5, 2007.


Firm initiated recall is ongoing.


REASON


Blood meal used to make cattle feed was recalled because it was cross- contaminated with prohibited bovine meat and bone meal that had been manufactured on common equipment and labeling did not bear cautionary BSE statement.


VOLUME OF PRODUCT IN COMMERCE


42,090 lbs.


DISTRIBUTION


WI


___________________________________


PRODUCT


Custom dairy premix products:


MNM ALL PURPOSE Pellet, HILLSIDE/CDL Prot- Buffer Meal, LEE, M.-CLOSE UP PX Pellet, HIGH DESERT/ GHC LACT Meal, TATARKA, M CUST PROT Meal, SUNRIDGE/CDL PROTEIN Blend, LOURENZO, K PVM DAIRY Meal, DOUBLE B DAIRY/GHC LAC Mineral, WEST PIONT/GHC CLOSEUP Mineral, WEST POINT/GHC LACT Meal, JENKS, J/COMPASS PROTEIN Meal, COPPINI - 8# SPECIAL DAIRY Mix, GULICK, L-LACT Meal (Bulk), TRIPLE J - PROTEIN/LACTATION, ROCK CREEK/GHC MILK Mineral, BETTENCOURT/GHC S.SIDE MK-MN, BETTENCOURT #1/GHC MILK MINR, V&C DAIRY/GHC LACT Meal, VEENSTRA, F/GHC LACT Meal, SMUTNY, A- BYPASS ML W/SMARTA, Recall # V-025-2007


CODE


The firm does not utilize a code - only shipping documentation with commodity and weights identified.


RECALLING FIRM/MANUFACTURER


Rangen, Inc, Buhl, ID, by letters on February 13 and 14, 2007. Firm initiated recall is complete.


REASON


Products manufactured from bulk feed containing blood meal that was cross contaminated with prohibited meat and bone meal and the labeling did not bear cautionary BSE statement.


VOLUME OF PRODUCT IN COMMERCE


9,997,976 lbs.


DISTRIBUTION


ID and NV


END OF ENFORCEMENT REPORT FOR MARCH 21, 2007











Saturday, August 4, 2012


Final Feed Investigation Summary - California BSE Case - July 2012









Saturday, August 4, 2012


Update from APHIS Regarding Release of the Final Report on the BSE Epidemiological Investigation











2012-2013








Wednesday, March 20, 2013




GAO-13-244, Mar 18, 2013 Dietary Supplements FDA May Have Opportunities to Expand Its Use of Reported Health Problems to Oversee Product



From: Terry S. Singeltary Sr.



Sent: Tuesday, March 19, 2013 2:46 PM






Cc: siggerudk@gao.gov ; youngc1@gao.gov ; oighotline@gao.gov


















Wednesday, February 20, 2013



World Organization for Animal Health Recommends United States' BSE Risk Status Be Upgraded



Statement from Agriculture Secretary Tom Vilsack:















Thursday, February 14, 2013



The Many Faces of Mad Cow Disease Bovine Spongiform Encephalopathy BSE and TSE prion disease












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




Risk of oral infection with bovine spongiform encephalopathy agent in primates





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



snip...



BSE bovine brain inoculum



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



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



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



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



PrPres biochemical detection



The comparison is made on the basis of calibration of the bovine inoculum used in our study with primates against a bovine brain inoculum with a similar PrPres concentration that was inoculated into mice and cattle.8 *Data are number of animals positive/number of animals surviving at the time of clinical onset of disease in the first positive animal (%). The accuracy of bioassays is generally judged to be about plus or minus 1 log. ic ip=intracerebral and intraperitoneal.


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




Published online January 27, 2005










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




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



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



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



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



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



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



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










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









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









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













Prion 7:2, 99–108; March/April 2013; © 2013 Landes Bioscience


mini-Rev iew Mini-REVIEW


A closer look at prion strains




Characterization and important implications




Laura Solforosi,†,* Michela Milani,† Nicasio Mancini, Massimo Clementi and Roberto Burioni


Laboratory of Microbiology and Virology; University Vita-Salute San Raffaele; Milan, Italy


†These authors contributed equally to this work.


Keywords: cellular prion protein (PrPC), scrapie prion protein (PrPSc), transmissible spongiform encephalopathies (TSEs), prion strains, strain mutation, variant Creutzfeldt-Jakob disease, sporadic Creutzfeldt-Jakob disease


Abbreviations: PrPC, cellular prion protein; PrPSc, scrapie prion protein; TSEs, transmissible spongiform encephalopathies; TME, transmissible mink encephalopathy; CJD, Creutzfeldt-Jakob disease; sCJD, sporadic CJD; vCJD, variant CJD; FFI, fatal familial insomnia; BSE, bovine spongiform encephalopathy; CWD, chronic wasting disease; PK, proteinase K; SAF, scrapie-associated fibrils; CNS, central nervous system; WB, western blot; PE, phosphatidylethanolamine; sPMCA, serial protein misfolding cyclic amplification; CPA, cell panel assay




Prions are infectious proteins that are responsible for transmissible spongiform encephalopathies (TSEs) and consist primarily of scrapie prion protein (PrPSc), a pathogenic isoform of the host-encoded cellular prion protein (PrPC). The absence of nucleic acids as essential components of the infectious prions is the most striking feature associated to these diseases. Additionally, different prion strains have been isolated from animal diseases despite the lack of DNA or RNA molecules. Mounting evidence suggests that prion-strain-specific features segregate with different PrPSc conformational and aggregation states.



Strains are of practical relevance in prion diseases as they can drastically differ in many aspects, such as incubation period, PrPSc biochemical profile (e.g., electrophoretic mobility and glycoform ratio) and distribution of brain lesions. Importantly, such different features are maintained after inoculation of a prion strain into genetically identical hosts and are relatively stable across serial passages.



This review focuses on the characterization of prion strains and on the wide range of important implications that the study of prion strains involves.



Introduction



Transmissible spongiform encephalopathies (TSEs) or prion diseases, such as Creutzfeldt-Jakob disease (CJD) in human, bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease (CWD) in cervids and scrapie in sheep, are a group of fatal neurodegenerative disorders. The major neuropathological hallmarks of TSEs are extensive spongiosis, neuronal cell loss in the central nervous system, gliosis,1 and deposition of amyloid plaques.2



*Correspondence to: Laura Solforosi; Email: solforosi.laura@hsr.it Submitted: 08/13/12; Revised: 12/20/12; Accepted: 01/03/13 http://dx.doi.org/10.4161/pri.23490





Prions are infectious proteins that are responsible for transmissible spongiform encephalopathies (TSEs) and consist primarily of scrapie prion protein (PrPSc), a pathogenic isoform of the host-encoded cellular prion protein (PrPC). The absence of nucleic acids as essential components of the infectious prions is the most striking feature associated to these diseases. Additionally, different prion strains have been isolated from animal diseases despite the lack of DNA or RNA molecules. Mounting evidence suggests that prion-strain-specific features segregate with different PrPSc conformational and aggregation states.





Strains are of practical relevance in prion diseases as they can drastically differ in many aspects, such as incubation period, PrPSc biochemical profile (e.g., electrophoretic mobility and glycoform ratio) and distribution of brain lesions. Importantly, such different features are maintained after inoculation of a prion strain into genetically identical hosts and are relatively stable across serial passages.





This review focuses on the characterization of prion strains and on the wide range of important implications that the study of prion strains involves. ...





snip...





This classification arises from the hypothesis that if the polymorphism 129 can modulate the phenotype of the familial prion diseases (fCJD and FFI, as explained earlier in this review), then probably it can modulate also that of sporadic prion diseases, justifying their heterogeneity. According to this hypothesis, the cases affected by sCJD were divided into six groups according to the genotype of the polymorphism in position 129 and the type of PrPSc. Then, the phenotypes of every group were analyzed to evaluate the homogeneity within every group. The results have permitted a molecular sub-classification of the sCJD.90,91 However, this classification seems not to be sufficient to explain the complexity of the sporadic form of CJD. In fact, in some molecular subtypes, additional variants have been reported, such as MM or VV patients with amyloid plaques, which are absent in the majority of patients with these genotypes.44 Moreover, among patients belonging to the same subgroup, important phenotypic differences can be found, such as, for instance, the extent of neuronal loss or PrPSc deposition differences.92





Even at the biochemical level the complexity is higher: indeed, aside from the migratory differences of the PrPSc of types 1 and 2, there are other properties that could be important during the propagation of the strain, like the presence of other fragments derived from differential cleavage at the C- and N-terminus of the protein, which probably coincide with the presence of other forms of PrPSc with different resistance to PK digestion.44 All these molecular classifications are based upon the principle that in all CNS districts the type of PrPSc is the same, but there are pieces of evidence pointing to the fact that different types of PrPSc can be found in different brain areas.64,93 The first evidence of the presence of more than one form of PrPSc in the brain of a sCJD patient was reported by Puoti in 1999.94 These different types of PrPSc can be found to coexist in the same brain region or they can infect distinct districts. Such co-infection influences the vacuolization and the amyloid aggregates formation.95 Even the ratio between the different glycoforms is determined in a regionspecific manner according to the type of PrPSc (1 or 2) and the genotype of codon 129.





The high degree of phenotypic heterogeneity characterizing sCJD90 can lead to the conclusion that transmission studies will probably identify a broad panel of different prions with a great divergence between strains. However, quite surprisingly, many of the recent studies focusing on the characterization of sCJD subtypes have shown that there is a strong tendency to converge to a limited number of strains. This aspect can find an explanation considering the selection conditions, already described in this review, mediated by the environment in which the prion replicates and by the differences in the amino acid sequence of the PrPC. In particular, studies with bank voles96 and mice97 lead to results that support the idea that there are two principal strains responsible of the sCJD, M1 and V2, and two potential strains, M2 and V1, which need further studies to be confirmed.





Different is the case of vCJD. vCJD has been observed in 12 different countries, but in every registered case the same clinical and pathological characteristics have been found.39 In particular, the PrPSc responsible of the vCJD shows a peculiar WB profile, with the unglycosylated form of the protease-resistant PrPSc of 19 kDa (type 2) and a higher representation of the diglycosilated PrPSc (PrPSc 2B) compared with sCJD.39 Nevertheless, using specific antibodies against type 1 PrPSc, a small amount of PrPSc type 1 with a high percentage of diglycosilated form can be detected in association with PrPSc 2B.98 The 2B type is a useful marker for identifying the replication of BSE prions also in other species, including non-human primates.99 In addition, unlike sporadic and genetic CJD, in vCJD the same biological marker (2B type) has been found in all the analyzed brain areas.100 This strong biochemical and pathological homogeneity is in agreement with the hypothesis of the existence of a unique strain. However, unexpectedly, typization experiments of the strains in different transgenic models have given divergent results. In one of these studies, in a context of homotropic transmission, transgenic mice expressing high levels of human PrPC-M129 were inoculated with vCJD isolates coming from France and from the UK.101 All of the French isolates propagated as vCJD, with abundant amyloid plaques and presence of PrPSc 2B.102 Instead, the isolates from the UK led to the propagation of either vCJD or sCJD.103 In particular, the incubation time was shorter and the lesion profile was different compared with the one obtained with the propagation of the classical vCJD strain. Moreover, early replication of the typical agent of the vCJD in lymphoid tissues was detected, indicating that both strains were present in the inoculum.





This new strain with phenotypical features that were similar to sCJD was found to be of type 1 and the transmission in transgenic mice expressing the bovine PrPC failed, unlike the vCJD classical strain (Type 2B).26 The idea that the infection of vCJD contains a minor component of sCJD prions is supported by many pieces of evidence such as the presence of this prion strain at the first passage or the persistence of both types of PrPSc through serial passages in mice.98 In conclusion, although vCJD is one of the most standardized phenotypes among the prion human diseases characterized by a typical form of PrPSc, the transmission studies of vCJD have shown the great potential of divergence of prions, contrary to the results obtained from the studies of sCJD. This data challenge our ability to recognize the pathologies that can derive from the divergence of the BSE strains when they infect humans, both at the pathological and at the biochemical level.







Conclusion







The discovery of prions has led to new interpretations of the pathogenetic mechanism of protein misfolding diseases. Indeed, the common thought was that a protein misfolding disease could only be caused by a mutation in the primary sequence of an endogenous protein, but the discovery of prions changed this view. In fact, it was demonstrated that a seed of misfolded protein can arise from an exogenous infectious protein, which is able to act as a template or as a catalyst for the formation of new aberrant protein.5,6 Importantly, new evidence shows how processes similar to those described for prions could be implicated in the propagation of misfolded proteins of other neurodegenerative pathologies like Alzheimer disease, Parkinson disease, Huntington disease and amyotrophic lateral sclerosis.104,105





Certainly, one of the most puzzling aspects in the prion field is the existence of different strains of an infectious protein. Nevertheless, such diversity can be accommodated within the protein-only hypothesis, as several robust pieces of experimental evidence indicate that strain-specificity is encoded at the level of the different conformations that the pathogenic protein can adopt. The identification of factors and mechanisms influencing the generation of new prion strains or the selection, from a conformationally heterogeneous PrPSc population, of the most suitable prion conformation in a specific environment, represents an important milestone toward the understanding of the mechanisms of prion strain diversity, which can have fundamental clinical and therapeutic implications. Although considerable advances have been made in the understanding of the phenomenon of prion strains, many pieces of information are still missing, foremost among them the definitive evidence for the structural nature of the differences between prion strains.























Thursday, February 21, 2013


National Prion Disease Pathology Surveillance Center Cases Examined January 16, 2013










16 YEAR OLD SPORADIC FFI ?






Monday, January 14, 2013


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











Monday, December 31, 2012


Creutzfeldt Jakob Disease and Human TSE Prion Disease in Washington State, 2006–2011-2012











Tuesday, December 25, 2012


CREUTZFELDT JAKOB TSE PRION DISEASE HUMANS END OF YEAR REVIEW DECEMBER 25, 2012











Tuesday, June 26, 2012


Creutzfeldt Jakob Disease Human TSE report update North America, Canada, Mexico, and USDA PRION UNIT as of May 18, 2012


type determination pending Creutzfeldt Jakob Disease (tdpCJD), is on the rise in Canada and the USA











Wednesday, June 13, 2012


MEXICO IS UNDER or MIS DIAGNOSING CREUTZFELDT JAKOB DISEASE AND OTHER PRION DISEASE SOME WITH POSSIBLE nvCJD











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






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




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




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




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




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




Results. To date, 2 VPSPr cases (1 MV and 1 MM) gave positive transmission in BvM109. Overall, 3 voles were positive with survival time between 290 and 588 d post inoculation (d.p.i.). All positive voles accumulated PrPres in the form of the typical PrP27–30, which was indistinguishable to that previously observed in BvM109 inoculated with sCJDMM1 cases.




In BvI109, 3 VPSPr cases (2 VV and 1 MM) showed positive transmission until now. Overall, 5 voles were positive with survival time between 281 and 596 d.p.i.. In contrast to what observed in BvM109, all BvI109 showed a GSS-like PrPSc electrophoretic pattern, characterized by low molecular weight PrPres. These PrPres fragments were positive with mAb 9A2 and 12B2, while being negative with SAF32 and SAF84, suggesting that they are cleaved at both the C-terminus and the N-terminus. Second passages are in progress from these first successful transmissions.




Conclusions. Preliminary results from transmission studies in bank voles strongly support the notion that VPSPr is a transmissible prion disease. Interestingly, VPSPr undergoes divergent evolution in the two genetic lines of voles, with sCJD-like features in BvM109 and GSS-like properties in BvI109.




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












Wednesday, March 28, 2012


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










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






*** atypical Nor-98 Scrapie has spread from coast to coast in the USA 2012



NIAA Annual Conference April 11-14, 2011



San Antonio, Texas











TSS







No comments: