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review: contribution of transgenic models to understanding human prion disease.transgenic mice expressing human prion protein in the absence of endogenous mouse prion protein faithfully replicate human prions. these models reproduce all of the key features of human disease, including long clinically silent incubation periods prior to fatal neurodegeneration with neuropathological phenotypes that mirror human prion strain diversity. critical contributions to our understanding of human prion disease pathogenesis and aetiology have only been possible through the use of transg ...201020880036
magnetization transfer ratio may be a surrogate of spongiform change in human prion diseases.human prion diseases are fatal neurodegenerative disorders caused by misfolding of the prion protein. there are no useful biomarkers of disease progression. cerebral cortex spongiform change, one of the classical pathological features of prion disease, resolves in prion-infected transgenic mice following prion protein gene knockout. we investigated the cross-sectional, longitudinal and post-mortem cerebral magnetization transfer ratios as a surrogate for prion disease pathology. twenty-three pri ...201020881162
large-scale immunohistochemical examination for lymphoreticular prion protein in tonsil specimens collected in britain.there have been 173 cases of variant creutzfeldt-jakob disease (vcjd) in the uk, as of 5 july 2010, as a result of the bovine spongiform encephalopathy epidemic. the number of individuals subclinically infected with vcjd, and thus the eventual number of cases, remains, however, uncertain. in an attempt to address this problem, 63,007 tonsil tissue specimens were previously tested by enzyme immunoassay (eia) for the presence of disease-related prion protein (prp(res)) and found to be negative. to ...201020922767
dispersion of prion protein deposits around blood vessels in variant creutzfeldt-jakob disease.in variant creutzfeldt-jakob disease (vcjd), a disease linked to bovine spongiform encephalopathy (bse), florid-type prion protein (prp(sc)) deposits are aggregated around the larger diameter (> 10 µm) cerebral microvessels. clustering of prp(sc) deposits around blood vessels may result from blood-borne prions or be a consequence of the cerebral vasculature influencing the development of the florid deposits. to clarify the factors involved, the dispersion of the florid prp(sc) deposits was studi ...201020924999
[anaesthetic management for caesarean delivery and creutzfeldt-jakob disease].variant creutzfeldt-jakob disease (vcjd) is the only form of prion diseases linked to bovine spongiform encephalopathy (bse). the surgical and anaesthetic management in patients having creutzfeldt-jakob disease is rare. maternofoetal and human transmission of creutzfeldt-jakob disease is still unknown. the principles for managing these new risks are not described in obstetric recommendations. we report the case of an 18-year-old woman, who developed the variant creutzfeldt-jakob disease during h ...201020934303
the prion diseases.the prion diseases are a family of rare neurodegenerative disorders that result from the accumulation of a misfolded isoform of the prion protein (prp), a normal constituent of the neuronal membrane. five subtypes constitute the known human prion diseases; kuru, creutzfeldt-jakob disease (cjd), gerstmann-sträussler-scheinker syndrome (gss), fatal insomnia (fi), and variant cjd (vcjd). these subtypes are distinguished, in part, by their clinical phenotype, but primarily by their associated brain ...201020938044
differentiation of ruminant transmissible spongiform encephalopathy isolate types, including bovine spongiform encephalopathy and ch1641 scrapie.with increased awareness of the diversity of transmissible spongiform encephalopathy (tse) strains in the ruminant population, comes an appreciation of the need for improved methods of differential diagnosis. exposure to bovine spongiform encephalopathy (bse) has been associated with the human tse, variant creutzfeldt-jakob disease, emphasizing the necessity in distinguishing low-risk tse types from bse. tse type discrimination in ruminants such as cattle, sheep, goats and deer, requires the app ...201020943889
correlation of polydispersed prion protein and characteristic pathology in the thalamus in variant creutzfeldt-jakob disease: implication of small oligomeric species.the vacuolation, neuronal loss and gliosis that characterize human prion disease pathology are accompanied by the accumulation of an aggregated, insoluble and protease-resistant form (termed prp(sc)) of the host-encoded normal cellular prion protein (prp(c)). in variant creutzfeldt-jakob disease the frontal cortex and cerebellum exhibit intense vacuolation and the accumulation of prp(sc) in the form of amyloid plaques and plaque-like structures. in contrast the posterior thalamus is characterize ...201021029243
underestimation of the expression of cellular prion protein on human red blood cells.recent transmissions of variant creutzfeldt-jakob disease by blood transfusion emphasize the need for the development of prion screening tests. the detection of prions in blood is complicated by the presence of poorly characterized cellular prion protein (prp(c) ) in both plasma and blood cells. according to published studies, most of prp(c) in blood cells resides in platelets (plts) and white blood cells.201021058954
the risk of transmitting prion disease by blood or plasma products.various experimental studies have shown infectivity in blood in relation to bovine spongiform encephalitis (bse) and variant creutzfeldt-jakob disease (vcjd). human to human transmission vcjd infection has been reported via transfusion of non-leukocyte-reduced red cells and, probably, via factor viii concentrates. a number of precautionary measures are in place but uncertainties remain, especially concerning the number of bse-infected people in the population. additional measures such as prion f ...201021071277
a standardized comparison of commercially available prion decontamination reagents using the standard steel-binding assay.prions are comprised principally of aggregates of a misfolded host protein and cause fatal transmissible neurodegenerative disorders of mammals, such as variant creutzfeldt-jakob disease in humans and bovine spongiform encephalopathy in cattle. prions pose significant public health concerns through contamination of blood products and surgical instruments, and can resist conventional hospital sterilization methods. prion infectivity binds avidly to surgical steel and can efficiently transfer infe ...201021084494
preclinical deposition of pathological prion protein in muscle of experimentally infected primates.prion diseases are transmissible fatal neurodegenerative disorders affecting humans and animals. a central step in disease progression is the accumulation of a misfolded form (prp(sc)) of the host encoded prion protein (prp(c)) in neuronal and non-neuronal tissues. the involvement of peripheral tissues in preclinical states increases the risk of accidental transmission. on the other hand, detection of prp(sc) in non-neuronal easy-accessible compartments such as muscle may offer a novel diagnosti ...201021085647
atypical transmissible spongiform encephalopathies in ruminants: a challenge for disease surveillance and control.since 1987, when bovine spongiform encephalopathy (bse) emerged as a novel disease in cattle, enormous efforts were undertaken to monitor and control the disease in ruminants worldwide. the driving force was its high economic impact, which resulted from trade restrictions and the loss of consumer confidence in beef products, the latter because bse turned out to be a fatal zoonosis, causing variant creutzfeldt-jakob disease in human beings. the ban on meat and bone meal in livestock feed and the ...201021088166
immunomodulation for prion and prion-related diseases.prion diseases are a unique category of illness, affecting both animals and humans, where the underlying pathogenesis is related to a conformational change of a normal self protein called cellular prion protein to a pathological and infectious conformer known as scrapie prion protein (prp(sc)). currently, all prion diseases lack effective treatment and are universally fatal. past experiences with bovine spongiform encephalopathy and variant creutzfeldt-jakob disease mainly in europe, as well as ...201021105779
the retinoic acid receptor beta (rarb) region of mmu14 is associated with prion disease incubation time in mouse.in neurodegenerative conditions such as alzheimer's and prion disease it has been shown that host genetic background can have a significant effect on susceptibility. indeed, human genome-wide association studies (gwas) have implicated several candidate genes. understanding such genetic susceptibility is relevant to risks of developing variant cjd (vcjd) in populations exposed to bovine spongiform encephalopathy (bse) and understanding mechanisms of neurodegeneration. in mice, aspects of prion di ...201021151910
probable variant creutzfeldt–jakob disease in asia: a case report from taiwan and review of two prior cases.new variant creutzfeldt–jakob disease (vcjd) was first identified in the uk in 1996, and was causally linked to bovine spongiform encephalopathy. herein we report the first case of vcjd in taiwan: a 34-year-old man who had lived in the uk between 1989 and 1997. the patient presented with depression, irritability, personality change, painful feet and allodynia, followed by gait ataxia and cognitive impairment. electroencephalograms did not show the typical appearance of sporadic cjd. the cerebros ...201021155168
uncertainty in the tail of the variant creutzfeldt-jakob disease epidemic in the uk.despite low case numbers the variant creutzfeldt-jakob disease epidemic poses many challenges for public health planning due to remaining uncertainties in disease biology and transmission routes. we develop a stochastic model for variant cjd transmission, taking into account the known transmission routes (food and red-cell transfusion) to assess the remaining uncertainty in the epidemic. we use bayesian methods to obtain scenarios consistent with current data. our results show a potentially long ...201021203419
laminar distribution of the pathological changes in sporadic and variant creutzfeldt-jakob disease.the laminar distributions of the pathological changes in the cerebral cortex were compared in the prion diseases sporadic creutzfeldt-jakob disease (scjd) and variant cjd (vcjd). first, in some cortical regions, the vacuolation ("spongiform change") was more generally distributed across the cortex in scjd. second, there was greater neuronal loss in the upper cortex in vcjd and in the lower cortex in scjd. third, the "diffuse" and "florid" prion protein (prp(sc)) deposits were more frequently dis ...201021209711
variant creutzfeldt-jakob disease in a transfusion recipient: coincidence or cause?to date there have been four instances of infection transmitted through blood transfusions derived from individuals who later developed variant creutzfeldt-jakob disease (vcjd). the identification of further transmission of vcjd through this route would have important implications for risk assessment and public health.201020230536
[variant creutzfeld-jakob disease (vcjd) : epidemiology and prevention from human to human secondary transmission].in the wake of the bovine spongiform encephalopathy (bse) epidemic, variant creutzfeldt-jakob disease (vcjd) has emerged as a previously unknown prion disease of humans. the initial occurrence of vcjd was observed in 1995/1996, and, so far, a total of 219 vcjd cases have been reported worldwide from seven european and four non-european countries. of these, 172 cases were observed in the united kingdom. the exact prevalence of sub- or pre-clinical vcjd infections is unclear. despite effective mea ...201020449549
[protection from bse : efforts, measures, success, and costs].by the mid 1980s, bovine spongiform encephalopathy (bse) emerged in the united kingdom (uk) and reached its peak in the early 1990s with up to 37,000 cases. in the year 2000, bse was diagnosed for the first time for a cow born in germany. since then, 413 cases of bse have been detected. about 10 years after the first bse cases were detected, variant creutzfeldt-jakob disease (vcjd), a new variant of creutzfeldt-jakob disease (cjd), was described in the uk. legal measures for protection from bse ...201020449555
risk reduction strategies for variant creutzfeldt-jakob disease transmission by uk plasma products and their impact on patients with inherited bleeding disorders.summary: the appearance and rapid evolution of bse in uk cattle in the mid 1980s, with compelling data supporting variant creutzfeldt-jakob disease (vcjd) as its human manifestation, pose a potentially severe threat to public health. three clinical cases and one asymptomatic case of vcjd infection have been reported in uk recipients of non-leucodepleted red cell transfusions from donors subsequently diagnosed with vcjd. plasma from both these and other donors who later developed vcjd has contrib ...201020487442
emerging pathogens in transfusion medicine.although the risk of infection with hepatitis and human immunodeficiency viruses from blood transfusions has been reduced to negligible levels, emerging infections continue to offer threats. such threats occur with any infection that has an asymptomatic, blood-borne phase. in the past, it was thought that any emerging transfusion-transmitted disease would have epidemiologic properties similar to those of aids or viral hepatitis. over the past 20 years, however, greatest concern has arisen from v ...201020513567
validation of diagnostic criteria for variant creutzfeldt-jakob disease.variant creutzfeldt-jakob disease (vcjd), a novel form of human prion disease, was recognized in 1996. the disease affected a younger cohort than sporadic cjd, and the early clinical course was dominated by psychiatric and sensory symptoms. in an attempt to aid diagnosis and establish standardization between surveillance networks, diagnostic criteria were established. these were devised from the features of a small number of cases and modified in 2000 as the clinical phenotype was established. s ...201020517937
human prion diseases in the united states.prion diseases are a family of rare, progressive, neurodegenerative disorders that affect humans and animals. the most common form of human prion disease, creutzfeldt-jakob disease (cjd), occurs worldwide. variant cjd (vcjd), a recently emerged human prion disease, is a zoonotic foodborne disorder that occurs almost exclusively in countries with outbreaks of bovine spongiform encephalopathy. this study describes the occurrence and epidemiology of cjd and vcjd in the united states.201020049325
variant cjd infection in the spleen of a neurologically asymptomatic uk adult patient with haemophilia.summary: all uk patients with bleeding disorders treated with any uk-sourced pooled factor concentrates between 1980 and 2001 have been informed that they may be at an increased risk of infection with variant creutzfeldt-jakob disease (vcjd). we describe a study to detect disease-associated, protease-resistant prion protein (prp(res)) in 17 neurologically aymptomatic patients with haemophilia considered to be at increased risk of vcjd. materials from 11 autopsy and seven biopsy cases were analys ...201020070383
scotblood 2009: the quest for understanding vcjd; claudia's trachea implantation; transfusion triggers; scottish histocompatibility and immunogenetics network; and islet cell transplantation.scotblood 2009 consisted of a varied combination of leading edge presentations incorporating the past, present and future. variant cjd was a major feature of the meeting comprising the quest for its understanding and the impact the disease was having on blood donation. the meeting also included the fascinating and groundbreaking story of claudia's trachea transplantation, along with progress in the establishment of the scottish histocompatibility and immunogenetics network and islet transplantat ...201020089457
multiorgan detection and characterization of protease-resistant prion protein in a case of variant cjd examined in the united states.variant creutzfeldt-jakob disease (vcjd) is a prion disease thought to be acquired by the consumption of prion-contaminated beef products. to date, over 200 cases have been identified around the world, but mainly in the united kingdom. three cases have been identified in the united states; however, these subjects were likely exposed to prion infection elsewhere. here we report on the first of these subjects.201020098730
a single step multiplex immunofluorometric assay for differential diagnosis of bse and scrapie.although there is no evidence that the european sheep population has been infected with bovine spongiform encephalopathy (bse), distinguishing this from scrapie is paramount, given the association between bse exposure and the human transmissible spongiform encephalopathy (tse), variant creutzfeldt-jakob disease. the capability to differentially diagnose tses in sheep is thus essential in order to safeguard the food chain and human health. biochemical methods for differentiating bse and scrapie a ...201020214905
detection of blood-transmissible agents: can screening be miniaturized?transfusion safety relating to blood-transmissible agents is a major public health concern, particularly when faced with the continuing emergence of new infectious agents. these include new viruses appearing alongside other known reemerging viruses (west nile virus, chikungunya) as well as new strains of bacteria and parasites (plasmodium falciparum, trypanosoma cruzi) and finally pathologic prion protein (variant creutzfeldt-jakob disease). genomic mutations of known viruses (hepatitis b virus, ...201020546202
a highly sensitive immunoassay for the detection of prion-infected material in whole human blood without the use of proteinase k.the causal association of variant creutzfeldt-jakob disease (vcjd) with bovine spongiform encephalopathy has raised significant concerns for public health. assays for vcjd infection are vital for the application of therapeutics, for the screening of organ donations, and to maintain a safe blood supply. currently the best diagnostic tools for vcjd depend upon the detection of disease-associated prion protein (prp(sc) ), which is distinguished from normal background prp (prp(c) ) by proteinase k ( ...201020561299
photo essay. mri and positron emission tomography findings in heidenhain variant creutzfeldt-jakob disease.the typical presentation of heidenhain variant creutzfeldt-jakob disease (cjd) is a rapidly progressive visual loss in the setting of a relatively normal ophthalmologic examination. at presentation, patients with this uniformly fatal illness frequently demonstrate only minor cortical abnormalities on mri. here, we document the clinical presentation and imaging results of a patient with heidenhain variant cjd in whom abnormalities on positron emission tomographic imaging were more evident than ch ...201020581692
variant creutzfeldt-jakob disease.summary: variant creutzfeldt-jakob disease (cjd) is an emerging form of human prion disease caused by oral exposure to the bovine spongiform encephalopathy agent. most cases have occurred in the uk, but smaller numbers of cases have been identified in 10 other countries worldwide. all confirmed cases belong to a single genetic subgroup defined by methionine homozygosity at codon 129 in the prion protein gene. variant cjd has a widespread distribution of infectivity in the body, involving lymphoi ...201020590878
sex effect in mouse and human prion disease.sex effect on the incubation period of variant creutzfeldt-jakob disease (vcjd) disease in human and me-7 murine models was investigated. in the 167 vcjd cases reported in the united kingdom as of january 2009, age at onset was significantly lower in female patients (by 2 years) than in male patients after stratification on birth cohort. in c57/bl6n mice infected with me-7 scrapie strain, incubation was shorter in female than in male mice. the incubation period increased in castrated male mice a ...201020594106
prion interaction with the 37-kda/67-kda laminin receptor on enterocytes as a cellular model for intestinal uptake of prions.enterocytes, a major cell population of the intestinal epithelium, represent one possible barrier to the entry of prions after oral exposure. we established a cell culture system employing enterocytes from different species to study alimentary prion interaction with the 37-kda/67-kda laminin receptor lrp/lr. human, bovine, porcine, ovine, and cervid enterocytes were cocultured with brain homogenates from cervid, sheep, and cattle suffering from chronic wasting disease (cwd), scrapie, and bovine ...201020603132
heterozygosity at polymorphic codon 219 in variant creutzfeldt-jakob disease.genetic variants of the prion protein gene (prnp) strongly determine susceptibility to prion diseases. all tested patients with definite variant creutzfeldt-jakob disease (vcjd) are homozygous for methionine at a common polymorphism at codon 129. a further genetic polymorphism at codon 219, a common variant in several asian populations, is considered protective against sporadic cjd.201020697057
differences in the density and spatial distribution of florid and diffuse plaques in variant creutzfeldt-jakob disease (vcjd).to determine whether in cases of variant creutzfeldt-jakob disease (vcjd), the florid-type plaques are derived from the diffuse plaques or whether the 2 plaque types develop independently.201014531544
phase i/ii safety study of transfusion of prion-filtered red cell concentrates in transfusion-dependent patients.variant creutzfeldt-jakob (vcjd) is a fatal transfusion transmissible prion infection. no test for vcjd in the donor population is currently available. therefore, prion removal by filtration of red cell concentrate (rcc) is an attractive option for prevention.201020345513
feasibility study of a screening assay that identifies the abnormal prion protein prptse in plasma: initial results with 20,000 samples.it is likely that transmission of variant creutzfeldt-jakob disease (vcjd) occurs by transfusion and that the candidate infectious agent (prp(tse)) is present in small concentrations in the blood of infected donors in the asymptomatic phase of the disease. a new blood screening assay has been developed to detect prp(tse) in citrated plasma samples.201020088835
variant creutzfeldt-jakob disease: the first confirmed case from portugal shows early onset, long duration and unusual pathology.we present clinical and autopsy findings in the first case of variant creutzfeldt-jakob disease diagnosed and confirmed in portugal. onset was at 11 years, the earliest onset reported, and the course (32 months) relatively long. western blot showed protease resistant prion protein, mainly of type 4 (2b) isoform. the cerebral cortex revealed severe spongiform change with numerous amyloid plaques, which did not fit the definition of florid plaques. in the striatum, spongiform change was limited bu ...201020019229
the epidemiology of progressive intellectual and neurological deterioration in childhood.to study the epidemiology of diseases that cause progressive intellectual and neurological deterioration (pind) in uk children.201019948513
a quantitative study of the pathological changes in the cortical white matter in variant creutzfeldt-jakob disease (vcjd).to quantify cortical white matter pathology in variant creutzfeldt-jakob disease (vcjd) and to correlate white and grey matter pathologies.201021073844
variant creutzfeldt-jakob disease in the united kingdom: a countrywide or local risk?the aim of this study was to identify factors that may have augmented local risks for variant creutzfeldt-jakob disease (vcjd).201019692715
strategies to reduce transfusion acquired vcjd.variant creutzfeldt-jakob disease (vcjd) can be transmitted by transfusion. the risk depends on the number of infected donors in the community. an estimate of these numbers in a less genetically susceptible population, based on the epidemic seen so far, suggests a maximum of 300 more cases. from this, it is possible to predict a maximum of one transfusion acquired case in 3 years from plasma transfusion. importation of plasma from outside the uk has been advocated to prevent these cases and woul ...201121070399
transmission of sporadic creutzfeldt-jakob disease by blood transfusion: risk factor or possible biases.the occurrence of transfusion transmissions of variant creutzfeldt-jakob disease (cjd) cases has reawakened attention to the possible similar risk posed by other forms of cjd.201121214582
diagnosing variant creutzfeldt-jakob disease: a retrospective analysis of the first 150 cases in the uk.establishing an early clinical diagnosis in variant creutzfeldt-jakob disease (vcjd) can be difficult, resulting in extended periods of uncertainty for many families and sometimes a view that patients have been subjected to unnecessary investigations. this issue is accentuated by the progressive nature of vcjd and by the difficulty in achieving a confident clinical diagnosis before an advanced stage of illness. although diagnostic delay may be a result of the non-specific early clinical features ...201121172857
unusual dopaminergic depletion in variant creutzfeldt-jakob disease with early and rapid cognitive decline. 201121625143
risk reduction strategies for variant creutzfeldt-jakob disease transmission by uk plasma products. 201121362112
comment on validation of diagnostic criteria for variant creutzfeldt-jakob disease. 201121280094
is there evidence of vertical transmission of variant creutzfeldt-jakob disease?the possibility of vertical transmission of variant creutzfeldt-jakob disease (vcjd) has been raised because of the widespread distribution of infectivity in vcjd and the demonstration that this condition can be transmitted through blood transfusion. the aim of this study is to search for evidence of this type of transmission of vcjd.201119401289
[variant creutzfeldt-jakob disease (vcjd)]. 201122755226
the first report of a patient with probable variant creutzfeldt-jakob disease in turkey.variant creutzfeldt-jakob disease (vcjd) was first reported in the uk in 1996. here, we report the first turkish case of vcjd. a 47-year-old man, who has never lived outside of turkey and had had no transfusion, was admitted to the university hospital with speech disorder, cognitive decline and ataxia following depression, irritability, and personality change. the immunoassay of the 14-3-3 protein in the cerebrospinal fluid was negative. brain magnetic resonance imaging revealed high-signal lesi ...201122279448
Candidate cell substrates, vaccine production, and transmissible spongiform encephalopathies.Transmissible spongiform encephalopathy (TSE) agents have contaminated human tissue-derived medical products, human blood components, and animal vaccines. The objective of this study was to determine the potential susceptibility to infection of 5 cell lines used or proposed for manufacture of biological products, as well as other lines. Cell lines were exposed to the infectious agents of sporadic and variant Creutzfeldt-Jakob disease and bovine spongiform encephalopathy (BSE). Exposed cultures w ...201122172513
experimental interspecies transmission studies of the transmissible spongiform encephalopathies to cattle: comparison to bovine spongiform encephalopathy in cattle.prion diseases or transmissible spongiform encephalopathies (tses) of animals include scrapie of sheep and goats; transmissible mink encephalopathy (tme); chronic wasting disease (cwd) of deer, elk and moose; and bovine spongiform encephalopathy (bse) of cattle. the emergence of bse and its spread to human beings in the form of variant creutzfeldt-jakob disease (vcjd) resulted in interest in susceptibility of cattle to cwd, tme and scrapie. experimental cross-species transmission of tse agents p ...201121908269
leu138 in bovine prion peptide fibrils is involved in seeding discrimination related to codon 129 m/v polymorphism in the prion peptide seeding experiment.the risk of acquiring variant creutzfeldt-jakob disease is closely related to polymorphism at codon 129 of the human prion gene, because almost all variant creutzfeldt-jakob disease patients are met/met homozygotes. although animal transmission experiments corroborated this seeding discrimination, the origin of the differential seeding efficiency of the bovine prion seed for human codon 129 polymorphism remained elusive. here, we used a short prion protein (prp) peptide as a model system to test ...201121920025
inhibitors of gastric acid secretion increase the risk of prion infection in mice.gastric juice is a unique combination of hydrochloric acid and the proteolytic enzyme pepsin. its main function is to inactivate ingested microorganisms. prions cause fatal transmissible degenerative encephalopathies in animals and man. these diseases have attracted attention due to the proposed link between bovine spongiform encephalopathy in cattle and the occurrence of a new variant creutzfeldt-jakob disease in humans where the most probable route of transmission is via contaminated food. the ...201121936725
squirrel monkeys (saimiri sciureus) infected with the agent of bovine spongiform encephalopathy develop tau pathology.squirrel monkeys (saimiri sciureus) were infected experimentally with the agent of classical bovine spongiform encephalopathy (bse). two to four years later, six of the monkeys developed alterations in interactive behaviour and cognition and other neurological signs typical of transmissible spongiform encephalopathy (tse). at necropsy examination, the brains from all of the monkeys showed pathological changes similar to those described in variant creutzfeldt-jakob disease (vcjd) of man, except t ...201122018806
comparison of nanofiltration efficacy in reducing infectivity of centrifuged versus ultracentrifuged 263k scrapie-infected brain homogenates in "spiked" albumin solutions.background: the safety of plasma-derived products is of concern for possible transmission of variant creutzfeldt-jakob disease. the absence of validated screening tests requires the use of procedures to remove or inactivate prions during the manufacture of plasma-derived products to minimize the risk of transmission. these procedures need proper validation studies based on spiking human plasma or intermediate fractions of plasma fractionation with prions in a form as close as possible to that pr ...201122082124
consumers' understanding and concerns about bovine spongiform encephalopathy (bse): comparison among canadian, american, and japanese consumers.in spite of much analysis of the impact of bovine spongiform encephalopathy (bse) on consumer perceptions and meat purchases, there has been little explicit analysis of the level of bse knowledge. in this study the role of knowledge about bse was examined in canada, the united states, and japan. in addition, the level of knowledge was linked to human health concerns regarding bse and whether there is agreement with paying a premium for beef with bse animal tests. from a public policy perspective ...201122043916
Comparison of candidate vCJD in vitro diagnostic assays using identical sample sets.Background and Objectives With four transfusion related transmissions of variant Creutzfeldt-Jakob Disease (vCJD), three of which developed clinical disease and the other died of other causes but was positive for markers of infection, there is an increased urgency to identify and implement a test for blood donor screening. With limited amounts of blood samples from vCJD cases available test evaluation is challenging. Alternative approaches are therefore needed. Control and vCJD tissues homogena ...201122126309
risk of prion disease transmission through bovine-derived bone substitutes: a systematic review.background: despite the causal association between variant creutzfeldt - jakob disease and bovine spongiform encephalopathy (bse), bovine origin graft materials are widely used during dental surgical procedures. the aim of this study was to assess the risk of bse transmission through anorganic bovine bone substitutes. methods: electronic database of medline was searched to identify relevant studies regarding our focused questions, presence of bse prion infectivity in raw bovine bone, bse prion i ...201122171533
The Management of Blood Safety in the Presence of Uncertain Risk: A United Kingdom Perspective.Millions of patients in the UK benefit from the use of both plasma derivatives and blood components that are seen as critical interventions in current medicine. Measures are in place to significantly reduce the risks associated with blood transfusion and plasma derivatives; however, these measures themselves are not risk free. Over the past 20 years, advances in technology and regulation have seen major reductions in the risks associated with transfusion. International blood services, industry, ...201122126710
The structural stability of wild-type horse prion protein.Prion diseases (e.g. Creutzfeldt-Jakob disease (CJD), variant CJD (vCJD), Gerstmann-Straussler-Scheinker syndrome (GSS), Fatal Familial Insomnia (FFI) and Kuru in humans, scrapie in sheep, bovine spongiform encephalopathy (BSE or 'mad-cow' disease) and chronic wasting disease (CWD) in cattles) are invariably fatal and highly infectious neurodegenerative diseases affecting humans and animals. However, by now there have not been some effective therapeutic approaches or medications to treat all the ...201121875155
transcriptional modulation in a leukocyte-depleted splenic cell population during prion disease.prion replication in the periphery precedes neuroinvasion in many experimental rodent scrapie models, and in natural sheep scrapie and chronic wasting disease (cwd) in cervids. prions propagate in the germinal centers of secondary lymphoid organs and are strongly associated with follicular dendritic cells (fdc) and possibly circulating dendritic cells and macrophages. given the importance of lymphoid organs in prion disease transmission and pathogenesis, gene expression studies may reveal host f ...201122043911
detection of prion protein in urine-derived injectable fertility products by a targeted proteomic approach.iatrogenic transmission of human prion disease can occur through medical or surgical procedures, including injection of hormones such as gonadotropins extracted from cadaver pituitaries. annually, more than 300,000 women in the united states and canada are prescribed urine-derived gonadotropins for infertility. although menopausal urine donors are screened for symptomatic neurological disease, incubation of creutzfeldt-jakob disease (cjd) is impossible to exclude by non-invasive testing. risk of ...201121448279
molecular dynamics studies on the structural stability of wild-type dog prion protein.prion diseases such as creutzfeldt-jakob disease, variant creutzfeldt-jakob diseases, gerstmann-sträussler-scheinker syndrome, fatal familial insomnia, kuru in humans, scrapie in sheep, bovine spongiform encephalopathy (or 'mad-cow' disease) and chronic wasting disease in cattle are invariably fatal and highly infectious neurodegenerative diseases affecting humans and animals. however, by now there have not been some effective therapeutic approaches to treat all these prion diseases. in 2008, ca ...201121469747
prion disease blood test using immunoprecipitation and improved quaking-induced conversion.abstract a key challenge in managing transmissible spongiform encephalopathies (tses) or prion diseases in medicine, agriculture, and wildlife biology is the development of practical tests for prions that are at or below infectious levels. of particular interest are tests capable of detecting prions in blood components such as plasma, but blood typically has extremely low prion concentrations and contains inhibitors of the most sensitive prion tests. one of the latter tests is quaking-induced co ...201121558432
heparin enhances the cell-protein misfolding cyclic amplification efficiency of variant creutzfeldt-jakob disease.highly sensitive in vitro screening tests are required to prevent the iatrogenic spread of variant creutzfeldt-jakob disease (vcjd). protein misfolding cyclic amplification (pmca) is a candidate for such a test, but the sensitivity of this method is insufficient. polyanions were reported to enhance pmca efficiency, but their effects on vcjd are unclear. we developed a cell-pmca of vcjd, wherein cell lysate containing exogenously expressed human prp was used as substrates, to investigate the effe ...201121565253
atypical prion diseases in humans and animals.although prion diseases, such as creutzfeldt-jakob disease (cjd) in humans and scrapie in sheep, have long been recognized, our understanding of their epidemiology and pathogenesis is still in its early stages. progress is hampered by the lengthy incubation periods and the lack of effective ways of monitoring and characterizing these agents. protease-resistant conformers of the prion protein (prp), known as the "scrapie form" (prp(sc)), are used as disease markers, and for taxonomic purposes, in ...201121598097
chronic wasting disease.chronic wasting disease (cwd) is a prion disease of free-ranging and farmed ungulates (deer, elk, and moose) in north america and south korea. first described by the late e.s. williams and colleagues in northern colorado and southern wyoming in the 1970s, cwd has increased tremendously both in numerical and geographical distribution, reaching prevalence rates as high as 50% in free-ranging and >90% in captive deer herds in certain areas of usa and canada. cwd is certainly the most contagious pri ...201121598099
rapid screening and confirmatory methods for biochemical diagnosis of human prion disease.transmissible spongiform encephalopathies (tses) are characterised by accumulation of an abnormal isoform of prion protein (prp(sc)), mainly in the brain but also in various peripheral tissues. home-made assays consisting of non-standardised protocols are used currently for laboratory diagnosis of human tse. the purpose of the present study was to test the ability of two commercial assays, tesee™ cjd elisa and tesee™ western blot, to detect prpsc in cerebral and lymphoid tissues of tse patients. ...201121619894
structural and functional neuroimaging in human prion diseases.introduction: prion diseases are neurodegenerative disorders resulting from the accumulation of a misfolded isoform of the cellular prion protein (prpc). they can occur as acquired, sporadic or hereditary forms. although prion diseases show a wide range of phenotypic variations, pathological features and clinical evolution, they are all characterised by a common unfavourable course and a fatal outcome. review summary: some variants, such as kuru, have practically disappeared, while others, for e ...201121621879
estimation of variant creutzfeldt-jakob disease infectivity titers in human blood.background: blood of individuals with variant creutzfeldt-jakob disease (vcjd) is infectious but the titer is unknown. current estimates of possible vcjd infectivity titers in blood have largely relied on an assumption that the titers of vcjd agent in human blood are likely to be similar to those in blood of rodents infected with model transmissible spongiform encephalopathy agents, assayed by intracerebral inoculations of rodents of the same species. study design and methods: we analyzed publis ...201121645006
biochemical and strain properties of cjd prions: complexity versus simplicity.prions, the agents responsible for transmissible spongiform encephalopathies, are infectious proteins consisting primarily of scrapie prion protein (prp(sc) ), a misfolded, beta-sheet enriched and aggregated form of the host-encoded cellular prion protein (prp(c) ). their propagation is based on an autocatalytic prp conversion process. despite the lack of a nucleic acid genome, different prion strains have been isolated from animal diseases. increasing evidence supports the view that strain-spec ...201121790605
conserved properties of human and bovine prion strains on transmission to guinea pigs.the first transmissions of human prion diseases to rodents used guinea pigs (gps, cavia porcellus). later, transgenic mice expressing human or chimeric human/mouse prp replaced gps, but the small size of the mouse limits some investigations. to investigate the fidelity of strain-specific prion transmission to gps, we inoculated 'type 1' and 'type 2' prion strains into gps, and we measured the incubation times and determined the strain-specified size of the unglycosylated, protease-resistant (r) ...201121727894
the risk to human islet cell transplant recipients of acquiring variant creutzfeldt-jakob disease: a provisional quantitative risk assessment. 201121691192
genome wide association studies and prion disease.over the last decade remarkable advances in genotyping and sequencing technology have resulted in hundreds of novel gene associations with disease. these have typically involved high frequency alleles in common diseases and with the advent of next generation sequencing, disease causing recessive mutations in rare inherited syndromes. here we discuss the impact of these advances and other gene discovery methods in the prion diseases. several quantitative trait loci in mouse have been mapped and t ...201121844666
isolation of prion with bse properties from farmed goat.transmissible spongiform encephalopathies are fatal neurodegenerative diseases that include variant creutzfeldt-jakob disease in humans, scrapie in small ruminants, and bovine spongiform encephalopathy (bse) in cattle. scrapie is not considered a public health risk, but bse has been linked to variant creutzfeldt-jakob disease. small ruminants are susceptible to bse, and in 2005 bse was identified in a farmed goat in france. we confirm another bse case in a goat in which scrapie was originally di ...201122172149
Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNP.Prion diseases are fatal neurodegenerative diseases of humans and animals caused by the misfolding and aggregation of prion protein (PrP). Mammalian prion diseases are under strong genetic control but few risk factors are known aside from the PrP gene locus (PRNP). No genome-wide association study (GWAS) has been done aside from a small sample of variant Creutzfeldt-Jakob disease. We conducted GWAS of sporadic CJD, variant CJD, iatrogenic CJD, inherited prion disease, kuru and resistance to kuru ...201122210626
demographics of successful, unsuccessful and deferral visits at six blood centers over a 4-year period.background: descriptions of donor demographics are of value in formulating recruitment and retention strategies. the demographics of successful (sv), unsuccessful (uv; meaning a nonuseable unit), and deferred (dv) donor visits over a 4-year period were investigated using retrovirus epidemiology donor study (reds)-ii databases. study design and methods: fourteen deferral categories were created that included low hematocrit (hct) or hemoglobin (hb), feeling unwell, malaria travel, malaria other, c ...201121950621
translocation of cellular prion protein to non-lipid rafts protects human prion-mediated neuronal damage.prions are the causative agents of transmissible spongiform encephalopathies, such as variant creutzfeldt-jakob disease in humans. cellular prion proteins (prpc) connect with cholesterol- and glycosphingolipid-rich lipid rafts through association of their glycosyl-phosphatidylinositol (gpi) anchor with saturated raft lipids and interaction of their n-terminal regions. our previous study showed that cellular cholesterol enrichment preven ...201122179431
all clinically-relevant blood components transmit prion disease following a single blood transfusion: a sheep model of vcjd.variant cjd (vcjd) is an incurable, infectious human disease, likely arising from the consumption of bse-contaminated meat products. whilst the epidemic appears to be waning, there is much concern that vcjd infection may be perpetuated in humans by the transfusion of contaminated blood products. since 2004, several cases of transfusion-associated vcjd transmission have been reported and linked to blood collected from pre-clinically affected donors. using an animal model in which the disease mani ...201121858015
notification and support for people exposed to the risk of creutzfeldt-jakob disease (cjd) (or other prion diseases) through medical treatment (iatrogenically).creutzfeldt-jakob disease (cjd) and variant cjd (vcjd) are rare and always-fatal diseases transmissible via certain medical procedures. if a person is exposed to the disease risk through medical treatment, they may need to be notified of this to prevent them passing the risk to others in healthcare settings and to enable additional infection control measures to be put in place for certain procedures. as cjd is incurable, and unable to be screened for or effectively treated, communicating this ri ...201121412905
The molecular epidemiology of variant CJD.The emergence of the novel prion diseases bovine spongiform encephalopathy (BSE) and, subsequently, variant Creutzfeldt-Jakob disease (vCJD) in epidemic forms has attracted much scientific attention. The oral transmission of these disorders, the causative relationship of vCJD to BSE and the resistance of the transmissible agents in both disorders to conventional forms of decontamination has caused great public health concern. The size of the still emerging vCJD epidemic is thankfully much lower ...201121915360
the application of in vitro cell-free conversion systems to human prion diseases.a key event in the pathogenesis of prion diseases is the conversion of the normal cellular isoform of the prion protein into the disease-associated isoform, but the mechanisms operating in this critical event are not yet fully understood. a number of novel approaches have recently been developed to study factors influencing this process. one of these, the protein misfolding cyclical amplification (pmca) technique, has been used to explore defined factors influencing the conversion of cellular pr ...201120535485
expert elicitation for the judgment of prion disease risk uncertainties.there is a high level of uncertainty surrounding the potential for iatrogenic prion transmission through transplantation, medical instrument reuse, blood transfusion, and blood product use due to a lack of evidence-based research on this important risk issue. a group of specialists was enlisted to evaluate some of the knowledge gaps in this area using the "classical model," a structured elicitation procedure for weighting and pooling expert judgment. the elicitation exercise was undertaken in ma ...201121218351
rna integrity in post mortem human variant creutzfeldt-jakob disease (vcjd) and control brain tissue.k. r. sherwood, m. w. head, r. walker, c. smith, j. w. ironside and j. k. fazakerley (2011) neuropathology and applied neurobiology37, 633-642 rna integrity in post mortem human variant creutzfeldt-jakob disease (vcjd) and control brain tissue aims: to determine premortem and post mortem factors affecting quality and yield of rna isolated from the unique archived brain material in the uk national creutzfeldt-jakob disease surveillance unit brain and tissue bank and to compare this to control bra ...201121251044
experimental transmission of bovine spongiform encephalopathy (bse) to cynomolgus macaques, a non-human primate.bovine spongiform encephalopathy (bse) was transmitted to three macaques by intracerebral inoculation of a brain homogenate from affected cattle detected in japan. all monkeys developed abnormal behavioral signs, such as intermittent anorexia and hyperekplexia, around 24 months after inoculation. neuronal symptoms, such as tremor, myoclonic jerking, and paralysis, appeared 27-44 months after inoculation. these symptoms worsened and total paralysis ensued within a year after onset. the disease du ...201121266755
atypical l-type bovine spongiform encephalopathy (l-bse) transmission to cynomolgus macaques, a non-human primate.a low molecular weight type of atypical bovine spongiform encephalopathy (l-bse) was transmitted to two cynomolgus macaques by intracerebral inoculation of a brain homogenate of cattle with atypical bse detected in japan. they developed neurological signs and symptoms at 19 or 20 months post-inoculation and were euthanized 6 months after the onset of total paralysis. both the incubation period and duration of the disease were shorter than those for experimental transmission of classical bse (c-b ...201121266763
detection of prion infection in variant creutzfeldt-jakob disease: a blood-based assay.variant creutzfeldt-jakob disease (vcjd) is a fatal neurodegenerative disorder originating from exposure to bovine-spongiform-encephalopathy-like prions. prion infections are associated with long and clinically silent incubations. the number of asymptomatic individuals with vcjd prion infection is unknown, posing risk to others via blood transfusion, blood products, organ or tissue grafts, and contaminated medical instruments. we aimed to establish the sensitivity and specificity of a blood-base ...201121295339
approaches to minimize infection risk in blood banking and transfusion practice.the use of blood donor history and state-of-the-art fda-licensed serological and nucleic acid testing (nat) assays have greatly reduced the "infectious window" for several transfusion-transmitted pathogens. currently transmission of human immunodeficiency virus (hiv), human t-cell lymphotropic virus (htlv), hepatitis viruses and west nile virus are rare events. the seroprevalence of cytomegalovirus in the donor population is high and cytomegalovirus infection can cause significant complications ...201121303341
the risk of variant creutzfeldt-jakob disease among uk patients with bleeding disorders, known to have received potentially contaminated plasma products.summary. the risk of variant creutzfeldt-jakob disease (vcjd) from potentially infected plasma products remains unquantified. this risk has been assessed for 787 uk patients with an inherited bleeding disorder prospectively followed-up for 10-20 years through the uk haemophilia centre doctors' organisation (ukhcdo) surveillance study. these patients had been treated with any of 25 'implicated' clotting factor batches from 1987 to 1999, which included in their manufacture, plasma from eight dono ...201121342369
universal white blood cell reduction in europe: has transmission of variant creutzfeldt-jakob disease been prevented?universal white blood cell (wbc) reduction was introduced in europe to prevent transmission of variant creutzfeldt-jakob disease (vcjd) by transfusion. findings from rodent models indicate that wbc reduction should not prevent vcjd transmission because the residual plasma infectivity suffices to infect transfusion recipients even under optimistic infectivity assumptions. although infectivity in human blood may not partition in the manner in which it is distributed in rodents, prion-reduction fil ...201121345641
biological effects and use of prpsc- and prp-specific antibodies generated by immunization with purified full-length native mouse prions.the prion agent is the infectious particle causing spongiform encephalopathies in animals and humans and is thought to consist of an altered conformation (prp(sc)) of the normal and ubiquitous prion protein prp(c). the interaction of the prion agent with the immune system, particularly the humoral immune response, has remained unresolved. here we investigated the immunogenicity of full-length native and infectious prions, as well as the specific biological effects of the resulting monoclonal ant ...201121345946
variant creutzfeldt-jakob disease: an update.variant creutzfeldt-jakob disease (vcjd) is a novel human prion disease caused by the bovine spongiform encephalopathy agent. most cases have occurred in the uk, with smaller numbers in 11 other countries. all definite vcjd cases have occurred in methionine homozygotes at codon 129 in the prion protein gene. following oral infection, the vcjd agent appears to replicate in lymphoid tissues during the asymptomatic phase of the incubation period. at present, four probable cases of vcjd infection ha ...201222505363
chronic wasting disease and atypical forms of bovine spongiform encephalopathy and scrapie are not transmissible to mice expressing wild-type levels of human prion protein.the association between bovine spongiform encephalopathy (bse) and variant creutzfeldt-jakob disease (vcjd) has demonstrated that cattle transmissible spongiform encephalopathies (tses) can pose a risk to human health and raises the possibility that other ruminant tses may be transmissible to humans. in recent years, several novel tses in sheep, cattle and deer have been described and the risk posed to humans by these agents is currently unknown. in this study, we inoculated two forms of atypica ...201222495232
prion disease: chemotherapeutic strategies.prion diseases, also known as transmissible spongiform encephalopathies, are invariably fatal neurodegenerative diseases for which there are no efficacious treatments. thousands of compounds have been screened for anti-prion effect, and yet of those that have effect in vitro, very few show effect in vivo, especially if administered in the later stages of disease. however, with new techniques for early diagnosis being developed, and with further insight into the pathogenesis of early disease, inc ...201222420513
could immunomodulation be used to prevent prion diseases?all prion diseases are currently without effective treatment and are universally fatal. the underlying pathogenesis of prion diseases (prionoses) is related to an autocatalytic conformational conversion of prp(c) (c for cellular) to a pathological and infectious conformer known as prp(sc) (sc for scrapie) or prp(res) (res for proteinase k resistant). the past experience with variant creutzfeldt-jakob disease, which originated from bovine spongiform encephalopathy, as well as the ongoing epidemic ...201222397565
the effects of host age on the transport of complement-bound complexes to the spleen and the pathogenesis of intravenous scrapie infection.infections with variant creutzfeldt-jakob disease (vcjd) have almost exclusively occurred in young patients, but the reasons for this age distribution are uncertain. our data suggest that the pathogenesis of many peripherally acquired transmissible spongiform encephalopathy (tse) agents is less efficient in aged individuals. four vcjd cases linked to transfusion of vcjd-contaminated blood or blood products have been described. three cases occurred in elderly patients, implying that intravenous e ...201222031932
Epidemiological indication for a role of sheep in the emergence of variant Creutzfeldt-Jakob disease. 201221945301
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