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
To: gomezj@gao.gov
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
