| rapid typing of transmissible spongiform encephalopathy strains with differential elisa. | the bovine spongiform encephalopathy (bse) agent has been transmitted to humans, leading to variant creutzfeldt-jakob disease. sheep and goats can be experimentally infected by bse and have been potentially exposed to natural bse; however, whether bse can be transmitted to small ruminants is not known. based on the particular biochemical properties of the abnormal prion protein (prpsc) associated with bse, and particularly the increased degradation induced by proteinase k in the n terminal part ... | 2008 | 18394279 |
| high titers of mucosal and systemic anti-prp antibodies abrogate oral prion infection in mucosal-vaccinated mice. | significant outbreaks of prion disease linked to oral exposure of the prion agent have occurred in animal and human populations. these disorders are associated with a conformational change of a normal protein, prp(c) (c for cellular), to a toxic and infectious form, prp(sc) (sc for scrapie). none of the prionoses currently have an effective treatment. some forms of prion disease are thought to be spread by oral ingestion of prp(sc), such as chronic wasting disease and variant creutzfeldt-jakob d ... | 2008 | 18407424 |
| cathepsin d snp associated with increased risk of variant creutzfeldt-jakob disease. | variant creutzfeldt-jakob disease (vcjd) originally resulted from the consumption of foodstuffs contaminated by bovine spongiform encephalopathy (bse) material, with 163 confirmed cases in the uk to date. many thousands are likely to have been exposed to dietary infection and so it is important (for surveillance, epidemic modelling, public health and understanding pathogenesis) to identify genetic factors that may affect individual susceptibility to infection. this study looked at a polymorphism ... | 2008 | 18426579 |
| mri and fdg pet/ct findings in a case of probable heidenhain variant creutzfeldt-jakob disease. | creutzfeldt-jakob disease (cjd) is a neurodegenerative disease caused by the accumulation of a pathogenic isoform of a prion protein in neurons that is responsible for subacute dementia. the heidenhain variant is an atypical form of cjd in which visual signs are predominant. this is a report of the case of a 65-year-old man with probable cjd of the heidenhain variant, with topographical concordance between findings on magnetic resonance imaging (mri) and 18f-fluorodeoxyglucose (fdg) photopenic a ... | 2008 | 18466976 |
| implications for creutzfeldt-jakob disease (cjd) in dentistry: a review of current knowledge. | this review explores our current understanding of the risks of (variant) creutzfeldt-jakob disease transmission via dental practice, and whether they merit the rigorous enforcement of improved standards of instrument cleaning and decontamination. the recognition of prions as novel infectious agents in humans has caused significant concern among the public and medical professionals alike. creutzfeldt-jakob disease (cjd) in humans has been shown to be transmissible via several routes, including tr ... | 2008 | 18502958 |
| alpha-hemoglobin stabilizing protein is not a suitable marker for a screening test for variant creutzfeldt-jakob disease. | a test is needed to identify blood donors who are in the preclinical phase of variant creutzfeldt-jakob disease (cjd). alpha-hemoglobin stabilizing protein (ahsp; syn. eraf, edrf) transcript levels are reduced in the blood of mice incubating transmissible spongiform encephalopathy. | 2008 | 18503615 |
| experimental transmission of bovine spongiform encephalopathy to european red deer (cervus elaphus elaphus). | bovine spongiform encephalopathy (bse), a member of the transmissible spongiform encephalopathies (tse), primarily affects cattle. transmission is via concentrate feed rations contaminated with infected meat and bone meal (mbm). in addition to cattle, other food animal species are susceptible to bse and also pose a potential threat to human health as consumption of infected meat products is the cause of variant creutzfeldt-jakob disease in humans, which is invariably fatal. in the uk, farmed and ... | 2008 | 18507844 |
| the in vitro bioassay systems for the amplification and detection of abnormal prion prp(sc) in blood and tissues. | prion diseases or transmissible spongiform encephalopathies, including creutzfeldt-jakob disease (cjd) and variant cjd (vcjd), are chronic neurodegenerative diseases characterized by accumulation of abnormal infectious prions known as prpsc. infectious prion is emerging as a blood transfusion-transmissible pathogen and is present at extremely low levels in the blood of asymptomatic patients, which is not detectable by current standard methodologies. as such, prion-related diseases impose a huge ... | 2008 | 18572098 |
| the variant creutzfeldt-jakob disease: risk, uncertainty or safety in the use of blood and blood derivatives? | abstract: it has been long since french physician jean-baptiste denys carried out the first successful blood transfusion to a human being. using bird feathers as canules, sheep blood was transfused to a young man. the patient died soon after denys' treatment and denys was accused of murder. in the xxi century, known as the biotechnology century, we face new challenges in medicine. new emerging and reemerging diseases, such as creutzfeldt-jakob disease (cjd) or "mad cow disease" and its human var ... | 2008 | 18573217 |
| kuru: its ramifications after fifty years. | kuru was the first human neurodegenerative disease in the group of transmissible spongiform encephalopathies, prion diseases or, in the past, slow unconventional virus diseases. it was reported to western medicine in 1957 by gajdusek and zigas. kuru was spread by endocannibalism and because of this the ratio of affected women and children to men was excessive. the hallmark of kuru neuropathology is the amyloid plaque. we may speculate what would happen if kuru had not been discovered or did not ... | 2009 | 18606515 |
| prion safety of transfusion plasma and plasma-derivatives typically used for prophylactic treatment. | reports about transfusion-related transmissions of variant creutzfeldt-jakob disease have urged the need for more information regarding the risk for prion contaminated units in the blood supply and the safety of transfusion plasma and biopharmaceuticals derived from this precious raw material. according to a possible epidemiological model, the risk in many european countries is the same or lower than that of human immunodeficiency virus. comprehensive investigations have shown that the prion saf ... | 2008 | 18619902 |
| inter-laboratory assessment of prpsc typing in creutzfeldt-jakob disease: a western blot study within the neuroprion consortium. | molecular typing is of considerable importance for the surveillance and epidemiology of human transmissible spongiform encephalopathies (tses). it relies on the detection of distinct protease-resistant prion protein (prp(sc)) core fragments that differ in molecular mass and/or glycoform ratio. in this collaborative study, we tested the inter-laboratory agreement in tse molecular typing. sixteen characterized brain specimens from sporadic tses and variant creutzfeldt-jakob disease (vcjd) cases we ... | 2009 | 18624793 |
| hippocampal bursts caused by changes in nmda receptor-dependent excitation in a mouse model of variant cjd. | prion diseases are heterogeneous in clinical presentation, suggesting that different prion diseases have distinct pathophysiological changes. to understand the pathophysiology specific to variant creutzfeldt-jakob disease (vcjd), in vitro electrophysiological studies were performed in a mouse model in which human-derived vcjd prions were transmitted to transgenic mice expressing human instead of murine prion protein. paired-pulse stimulation of the schaffer collaterals evoked hypersynchronous bu ... | 2008 | 18638557 |
| potential effect of excluding variant creutzfeldt-jakob disease on the eye donor pool in australia. | to quantitate the likely effect on the available eye donor pool by excluding potential donors who may have had exposure to variant creutzfeldt-jakob disease by virtue of spending time in countries where bovine spongiform encephalopathy (bse) is endemic. | 2008 | 18650661 |
| regulating factors of prp glycosylation in creutzfeldt-jakob disease--implications for the dissemination and the diagnosis of human prion strains. | the glycoprofile of pathological prion protein (prp(res)) is widely used as a diagnosis marker in creutzfeldt-jakob disease (cjd) and is thought to vary in a strain-specific manner. however, that the same glycoprofile of prp(res) always accumulates in the whole brain of one individual has been questioned. we aimed to determine whether and how prp(res) glycosylation is regulated in the brain of patients with sporadic and variant creutzfeldt-jakob disease. | 2008 | 18665216 |
| review. the changing face of kuru: a personal perspective. | the epidemic of kuru is now known to have been transmitted among the fore by ritual consumption of infected organs from deceased relatives. as cannibalism was suppressed by government patrol officers during the 1950s, most transmission had ceased by 1957, when the kuru research programme first commenced. as predicted in the 1960s, the epidemic has waned, with progressive ageing of kuru-affected cohorts over the years to 2007. the few cases seen in the twenty-first century, with the longest incub ... | 2008 | 18672465 |
| impact of donor deferrals for malaria on blood availability in the united states. | us blood availability is negatively impacted by residence or travel-related deferrals designed to prevent transmission of human immunodeficiency virus type 1 group o, variant creutzfeldt-jakob disease, leishmania, and malaria. generally, travel and residence deferrals lack sensitivity and specificity to identify infected donors, particularly for malaria. this study evaluated trends in malaria deferrals and their impact on blood availability from 2000 through 2006. | 2008 | 18673351 |
| no major change in vcjd agent strain after secondary transmission via blood transfusion. | the identification of transmission of variant creutzfeldt-jakob disease (vcjd) by blood transfusion has prompted investigation to establish whether there has been any alteration in the vcjd agent following this route of secondary transmission. any increase in virulence or host adaptation would require a reassessment of the risk analyses relating to the possibility of a significant secondary outbreak of vcjd. since there are likely to be carriers of the vcjd agent in the general population, there ... | 2008 | 18682737 |
| detection and characterization of proteinase k-sensitive disease-related prion protein with thermolysin. | disease-related prp(sc) [pathogenic prp (prion protein)] is classically distinguished from its normal cellular precursor, prp(c)(cellular prp) by its detergent insolubility and partial resistance to proteolysis. although molecular diagnosis of prion disease has historically relied upon detection of protease-resistant fragments of prp(sc) using pk (proteinase k), it is now apparent that a substantial fraction of disease-related prp is destroyed by this protease. recently, thermolysin has been ide ... | 2008 | 18684106 |
| atypical bse (base) transmitted from asymptomatic aging cattle to a primate. | human variant creutzfeldt-jakob disease (vcjd) results from foodborne transmission of prions from slaughtered cattle with classical bovine spongiform encephalopathy (cbse). atypical forms of bse, which remain mostly asymptomatic in aging cattle, were recently identified at slaughterhouses throughout europe and north america, raising a question about human susceptibility to these new prion strains. | 2008 | 18714385 |
| persistent propagation of variant creutzfeldt-jakob disease agent in murine spleen stromal cell culture with features of mesenchymal stem cells. | the transmission of variant creutzfeldt-jakob disease (vcjd) through blood transfusions has created new concerns about the iatrogenic spread of transmissible spongiform encephalopathies (tses)/prion diseases through blood and plasma-derived products and has increased the need to develop efficient methods for detection of the agent in biologics. here, we report the first successful generation of spleen-derived murine stromal cell cultures that persistently propagate two mouse-adapted isolates of ... | 2008 | 18715934 |
| age of onset and death in inherited prion disease are heritable. | the common polymorphism at codon 129 of the prion protein gene (prnp) is known to affect prion disease susceptibility, incubation period and phenotype. mouse quantitative trait locus (qtl) studies demonstrate multiple modifiers of incubation time unlinked to prnp, suggesting the existence of homologous human prion disease modifiers, but direct evidence of these has been lacking. we investigated the correlation of age at onset and death, expressed as a composite z score, between parents and offsp ... | 2009 | 18729123 |
| bse case associated with prion protein gene mutation. | bovine spongiform encephalopathy (bse) is a transmissible spongiform encephalopathy (tse) of cattle and was first detected in 1986 in the united kingdom. it is the most likely cause of variant creutzfeldt-jakob disease (cjd) in humans. the origin of bse remains an enigma. here we report an h-type bse case associated with the novel mutation e211k within the prion protein gene (prnp). sequence analysis revealed that the animal with h-type bse was heterozygous at prnp nucleotides 631 through 633. a ... | 2008 | 18787697 |
| association of a null allele of sprn with variant creutzfeldt-jakob disease. | no susceptibility genes have been identified in human prion disase, apart from the prion protein gene (prnp). the gene sprn, encodes shadoo (sho, shadow of prion protein) which has protein homology and possible functional links with the prion protein. | 2008 | 18805828 |
| wernicke's encephalopathy mimicking variant creutzfeldt-jakob disease. | a 45-year-old man from tropical australia was admitted with subacute social withdrawal, cognitive deterioration, reduced awareness and eventual mutism. variant creutzfeldt-jakob disease was considered on the basis of who case definition criteria including typical clinical features and mri showing symmetrical hyperintensity in the pulvinar (posterior) nuclei of the thalami. however, tonsillar biopsy was negative. wernicke's encephalopathy was established on the basis of low serum thiamine on admi ... | 2008 | 18829327 |
| a clinical study of kuru patients with long incubation periods at the end of the epidemic in papua new guinea. | kuru is so far the principal human epidemic prion disease. while its incidence has steadily declined since the cessation of its route of transmission, endocannibalism, in papua new guinea in the 1950s, the arrival of variant creutzfeldt-jakob disease (vcjd), also thought to be transmitted by dietary prion exposure, has given kuru a new global relevance. we investigated all suspected cases of kuru from july 1996 to june 2004 and identified 11 kuru patients. there were four females and seven males ... | 2008 | 18849289 |
| central and peripheral pathology of kuru: pathological analysis of a recent case and comparison with other forms of human prion disease. | while the neuropathology of kuru is well defined, there are few data concerning the distribution of disease-related prion protein in peripheral tissues. here we report the investigation of brain and peripheral tissues from a kuru patient who died in 2003. neuropathological findings were compared with those seen in classical (sporadic and iatrogenic) creutzfeldt-jakob disease (cjd) and variant cjd (vcjd). the neuropathological findings of the kuru patient showed all the stereotypical changes that ... | 2008 | 18849292 |
| update: creutzfeldt-jakob disease associated with cadaveric dura mater grafts--japan, 1978-2008. | creutzfeldt-jakob disease (cjd) is the most common of the human prion diseases (also known as transmissible spongiform encephalopathies), which, according to the leading hypothesis, are caused by an abnormal protein (i.e., prion) that is able to induce abnormal folding of normal cellular prion proteins. annual worldwide incidence of these always fatal neurodegenerative diseases is estimated at 0.5-2.0 cases per million population. cjd can occur sporadically, or as a genetic disease, or can be tr ... | 2008 | 18946463 |
| human platelets as a substrate source for the in vitro amplification of the abnormal prion protein (prp) associated with variant creutzfeldt-jakob disease. | four recent cases of transfusion-related transmission of variant creutzfeldt-jakob disease (vcjd) highlight the need to develop a highly sensitive and specific screening test to detect infectivity in the blood of asymptomatic infected individuals. protein misfolding cyclic amplification (pmca), a method for the amplification of minute amounts of disease-associated abnormal prion protein (prp(sc)) to readily detectable levels, could be incorporated into such a test provided that a suitable substr ... | 2009 | 18980616 |
| bacterial colitis increases susceptibility to oral prion disease. | dietary exposure to prion-contaminated materials has caused kuru and variant creutzfeldt-jakob disease in humans and transmissible spongiform encephalopathies (tses) in cattle, mink, and felines. the epidemiology of dietary prion infections suggests that host genetic modifiers and possibly exogenous cofactors may play a decisive role in determining disease susceptibility. however, few cofactors influencing susceptibility to prion infection have been identified. in the present study, we investiga ... | 2009 | 19072552 |
| human prion protein (prp) 219k is converted to prpsc but shows heterozygous inhibition in variant creutzfeldt-jakob disease infection. | prion protein gene (prnp) e219k is a human polymorphism commonly occurring in asian populations but is rarely found in patients with sporadic creutzfeldt-jakob disease (cjd). thus the polymorphism e219k has been considered protective against sporadic cjd. the corresponding mouse prion protein (prp) polymorphism variant (mouse prp 218k) is not converted to the abnormal isoform (prp(sc)) and shows a dominant negative effect on wild-type prp conversion. to define the conversion activity of this hum ... | 2009 | 19074151 |
| are further genetic factors associated with the risk of developing variant creutzfeldt-jakob disease? | | 2009 | 19081509 |
| genetic risk factors for variant creutzfeldt-jakob disease: a genome-wide association study. | human and animal prion diseases are under genetic control, but apart from prnp (the gene that encodes the prion protein), we understand little about human susceptibility to bovine spongiform encephalopathy (bse) prions, the causal agent of variant creutzfeldt-jakob disease (vcjd). | 2009 | 19081515 |
| strain-specific viral properties of variant creutzfeldt-jakob disease (vcjd) are encoded by the agent and not by host prion protein. | human cjd, endemic sheep scrapie, epidemic bovine spongiform encephalopathy (bse), and other transmissible spongiform encephalopathies (tses), are caused by a group of related but molecularly uncharacterized infectious agents. the uk-bse agent infected many species, including humans where it causes variant cjd (vcjd). as in most viral infections, different tse disease phenotypes are determined by both the agent strain and the host species. tse strains are most reliably classified by incubation t ... | 2009 | 19097123 |
| production and characterization of a panel of monoclonal antibodies against native human cellular prion protein. | the human prion diseases, such as variant creutzfeldt-jakob disease (vcjd), are characterized by the conversion of the normal cellular prion protein (prp(c)) into an abnormal disease associated form (prp(sc)). monoclonal antibodies (mabs) that recognize these different prp isoforms are valuable reagents both in the diagnosis of these diseases and in prion disease research in general but we know of no attempts to raise mabs against native human prp(c). we immunized prion protein gene ablated (prp ... | 2009 | 19132894 |
| risk of creutzfeldt-jakob disease transmission by ocular surgery and tissue transplantation. | creutzfeldt-jakob disease (cjd) is a rare, fatal neurodegenerative disease that occurs in sporadic, genetic, variant, and iatrogenic forms. the transformation of normal prion protein (prp(c)) to the abnormal form (prp(sc)) is a key step in the pathogenesis of cjd and leads to the accumulation of amyloid and spongiform changes in the brain. the presence of prp(sc) in tissue is a surrogate marker for cjd infectivity. sporadic cjd, whose cause is unknown, is by far the most frequent form with 1-2 c ... | 2009 | 19136921 |
| from mad cows to sensible blood transfusion: the risk of prion transmission by labile blood components in the united kingdom and in france. | transfusion transmission of the prion, the agent of variant creutzfeldt-jakob disease (vcjd), is now established. subjects infected through food may transmit the disease through blood donations. the two nations most affected to date by this threat are the united kingdom (uk) and france. the first transfusion cases have been observed in the uk over the past 5 years. in france, a few individuals who developed vcjd had a history of blood donation, leading to a risk of transmission to recipients, so ... | 2009 | 19170997 |
| evaluation of 99mtc(co)5i as a potential lung perfusion agent. | the use of (99m)tc-macroggregated albumin for lung perfusion imaging is well established in nuclear medicine. however, there have been safety concerns over the use of blood-derived products because of potential contamination by infective agents, for example, variant creutzfeldt jakob disease. preliminary work has indicated that tc(co)(5)i is primarily taken up in the lungs following intravenous administration. the aim of this study was to evaluate the biodistribution and pharmacokinetics of (99m ... | 2009 | 19181271 |
| the impact of social amplification and attenuation of risk and the public reaction to mad cow disease in canada. | following the detection of bovine spongiform encephalopathy (bse) in canada, and subsequently in the united states, confidence in the safety of beef products remained high. consumers actually increased their consumption of beef slightly after the news of an increased risk from mad cow disease, which has been interpreted as public support for beef farmers and confidence in government regulators. the canadian public showed a markedly different reaction to the news of domestic bse than the furious ... | 2009 | 19192234 |
| prions hijack tunnelling nanotubes for intercellular spread. | in variant creutzfeldt-jakob disease, prions (prp(sc)) enter the body with contaminated foodstuffs and can spread from the intestinal entry site to the central nervous system (cns) by intercellular transfer from the lymphoid system to the peripheral nervous system (pns). although several means and different cell types have been proposed to have a role, the mechanism of cell-to-cell spreading remains elusive. tunnelling nanotubes (tnts) have been identified between cells, both in vitro and in viv ... | 2009 | 19198598 |
| recent advances in prion chemotherapeutics. | the transmissible spongiform encephalopathies are rapidly progressive and invariably fatal neurodegenerative diseases for which there are no proven efficacious treatments. many approaches have been undertaken to find ways to prevent, halt, or reverse these prion diseases, with limited success to date. however, as both our understanding of pathogenesis and our ability to detect early disease increases, so do our potential therapeutic targets and our chances of finding effective drugs. there is in ... | 2009 | 19200018 |
| highly sensitive, quantitative cell-based assay for prions adsorbed to solid surfaces. | prions are comprised principally of aggregates of a misfolded host protein and cause fatal transmissible neurodegenerative disorders of humans and animals, such as variant creutzfeldt-jakob disease and bovine spongiform encephalopathy. prions pose significant public health concerns, including contamination of blood products and surgical instruments; require laborious and often insensitive animal bioassay to detect; and resist conventional hospital sterilization methods. a major experimental adva ... | 2009 | 19204279 |
| absence of spontaneous disease and comparative prion susceptibility of transgenic mice expressing mutant human prion proteins. | approximately 15 % of human prion disease is associated with autosomal-dominant pathogenic mutations in the prion protein (prp) gene. previous attempts to model these diseases in mice have expressed human prp mutations in murine prp, but this may have different structural consequences. here, we describe transgenic mice expressing human prp with p102l or e200k mutations and methionine (m) at the polymorphic residue 129. although no spontaneous disease developed in aged animals, these mice were re ... | 2009 | 19218199 |
| three serial passages of bovine spongiform encephalopathy in sheep do not significantly affect discriminatory test results. | during the 1980s, bovine spongiform encephalopathy (bse)-contaminated meat and bonemeal were probably fed to sheep, raising concerns that bse may have been transmitted to sheep in the uk. the human disease, variant creutzfeldt-jakob disease, arose during the bse epidemic, and oral exposure of humans to bse-infected tissues has been implicated in its aetiology. the concern is that sheep bse could provide another source of bse exposure to humans via sheep products. two immunological techniques, we ... | 2009 | 19218224 |
| what happened to the epidemic in new variant creutzfeldt-jakob disease? | the first recognised case of new variant creutzfeldt-jakob disease was in 1995 and it was only a short time thereafter that this extremely rare fatal condition was attributed to the contamination of beef products by the putative aetiological agent of bovine spongiform encephalopathy. while the united kingdom government appeared to bend over backwards in both accepting this attribution and in funding myriad research to support such an heretical conclusion many scientists while being extremely sce ... | 2009 | 19246163 |
| frequency and distribution of nerves in scrapie-affected and unaffected peyer's patches and lymph nodes. | transmission of sheep scrapie and some other prion diseases, including variant creutzfeldt-jakob disease of man, probably occurs via the oral route. a disease-associated variant of the host-coded prion protein (prp(d)) accumulates in germinal center follicles of lymphoid tissues, including peyer's patches of the gut, where it can be detected before its accumulation in the central nervous system. to investigate the potential role of lymphoid tissue nerves in neuroinvasion, we used immunohistochem ... | 2009 | 19261634 |
| variant creutzfeldt-jakob disease in france and the united kingdom: evidence for the same agent strain. | variant creutzfeldt-jakob disease (vcjd) was first reported in the united kingdom in 1996. since then, the majority of cases have been observed in the united kingdom where there was a major epidemic of bovine spongiform encephalopathy. france was the second country affected. to address the hypothesis of the involvement of a common strain of agent, we have compared clinical, neuropathological, and biochemical data on vcjd patients from both countries. | 2009 | 19334063 |
| variant creutzfeldt-jakob disease: french versus british. | | 2009 | 19334065 |
| a history of kuru. | kuru is placed in its geographic and linguistic setting in the eastern highlands of papua new guinea. the epidemic of kuru has declined over the period 1957 to 2005 from more than 200 deaths a year to 1 or none. since transmission of the kuru prion agent through the mortuary practice of transumption ceased by the early 1960s, the continuation of the epidemic into the present century demonstrates the long incubation periods that are possible in human prion diseases. several histories of kuru are ... | 2007 | 19354007 |
| bovine spongiform encephalopathy and aquaculture. | dietary consumption of fish is widely recommended because of the beneficial effects of omega-3 polyunsaturated fatty acids on the risks of cardiovascular and alzheimer's diseases. the american heart association currently recommends eating at least two servings of fish per week. we are concerned that consumption of farmed fish may provide a means of transmission of infectious prions from cows with bovine spongiform encephalopathy to humans, causing variant creutzfeldt jakob disease. | 2009 | 19363268 |
| the first japanese patient with variant creutzfeldt-jakob disease (vcjd). | eleven years after a brief visit to some european countries, a 48-year-old japanese man developed writing difficulty, irritability and general fatigue. then he complained of dysesthetic pains in his legs, for which benzodiazepines were prescribed. however, at the time pulvinar sign was retrospectively confirmed on brain mri. eighteen months after the onset, his gait became ataxic with rapid deterioration of mental status over the following several months. thirty-one months after the onset, he be ... | 2009 | 19389077 |
| pathologic prion protein infects cells by lipid-raft dependent macropinocytosis. | transmissible spongiform encephalopathies, including variant-creutzfeldt-jakob disease (vcjd) in humans and bovine spongiform encephalopathies in cattle, are fatal neurodegenerative disorders characterized by protein misfolding of the host cellular prion protein (prp(c)) to the infectious scrapie form (prp(sc)). however, the mechanism that exogenous prp(sc) infects cells and where pathologic conversion of prp(c) to the prp(sc) form occurs remains uncertain. here we report that similar to the mec ... | 2008 | 19390657 |
| prion proteins in subpopulations of white blood cells from patients with sporadic creutzfeldt-jakob disease. | recent cases of prion transmission in humans following transfusions using blood donated by patients with asymptomatic variant creutzfeldt-jakob disease (cjd) implicate the presence of prion infectivity in peripheral blood. in this study, we examined the levels of the normal, cellular prion protein (prpc), and the disease-causing isoform (prpsc) in subpopulations of circulating white blood cells (wbcs) from patients with sporadic (s) cjd, age-matched neurological controls and healthy donors. thou ... | 2009 | 19434060 |
| prevalence of disease related prion protein in anonymous tonsil specimens in britain: cross sectional opportunistic survey. | to establish with improved accuracy the prevalence of disease related prion protein (prp(cjd)) in the population of britain and thereby guide a proportionate public health response to limit the threat of healthcare associated transmission of variant creutzfeldt-jakob disease (vcjd). | 2009 | 19460798 |
| prion protein expression and processing in human mononuclear cells: the impact of the codon 129 prion gene polymorphism. | so far, all clinical cases of new variant creutzfeldt-jakob disease (vcjd), thought to result from the bovine spongiform encephalopathy (bse) prion agent, have shown methionine-methionine (m/m) homozygosity at the m129v polymorphism of the prnp gene. although established, this relationship is still not understood. in both vcjd and experimental bse models prion agents do reach the bloodstream, raising concerns regarding disease transmission through blood transfusion. | 2009 | 19495414 |
| two unusual bovine spongiform encephalopathy cases detected in great britain. | bovine spongiform encephalopathy (bse) was first identified in great britain (gb) in 1986 and was subsequently detected in many other countries, worldwide. a decade after the start of the bovine epidemic, the first cases of new variant creutzfeldt-jakob disease (vcjd) in humans were linked to probable ingestion of bse infected tissue, highlighting a new zoonotic disease. an abnormal protease-resistant protein (prp(res)) in a diseased subject, derived from a post-translational change of a normal ... | 2009 | 19497088 |
| shadoo (sprn) and prion disease incubation time in mice. | prion diseases are transmissible neurodegenerative disorders of mammalian species and include scrapie, bovine spongiform encephalopathy (bse), and variant creutzfeldt-jakob disease (vcjd). the prion protein (prp) plays a key role in the disease, with coding polymorphism in both human and mouse influencing disease susceptibility and incubation time, respectively. other genes are also thought to be important and a plausible candidate is sprn, which encodes the prp-like protein shadoo (sho). sho is ... | 2009 | 19513788 |
| antibody-based immunotherapeutic attempts in experimental animal models of prion diseases. | there has been a dramatic decrease in the risk of transmission of bovine spongiform encephalopathy to humans. in contrast, the risk of human-to-human transmission of variant creutzfeldt-jakob disease (vcjd) via medical treatments became potentially high since 4 vcjd cases were reported to be possibly transmitted through blood transfusion in the uk. however, no treatments are yet available for curing prion diseases. | 2009 | 19514955 |
| prion removal effect of a specific affinity ligand introduced into the manufacturing process of the pharmaceutical quality solvent/detergent (s/d)-treated plasma octaplaslg. | a new chromatographic step for the selective binding of abnormal prion protein (prp(sc)) was developed, and optimization for prp(sc) capture was achieved by binding to an affinity ligand attached to synthetic resin particles. this step was implemented into the manufacturing process of the solvent/detergent (s/d)-treated biopharmaceutical quality plasma octaplas to further improve the safety margin in terms of risk for variant creutzfeldt-jakob disease (vcjd) transmission. | 2009 | 19548963 |
| [risk factors for sporadic creutzfeldt-jakob disease]. | sporadic creutzfeldt-jakob disease (scjd) is the most common form of human transmissible spongiform encephalopathies (prion disease), but its cause has not been fully elucidated. according to its biochemical properties prion protein is resistant to routine sterilisation methods. thus, invasive medical procedures could be involved in the genesis of the disease. present knowledge about iatrogenic routes of transmission, oral infection and transmission via blood products in variant cjd (vcjd) under ... | 2009 | 19551608 |
| inactivation of animal and human prions by hydrogen peroxide gas plasma sterilization. | prions cause various transmissible spongiform encephalopathies. they are highly resistant to the chemical and physical decontamination and sterilization procedures routinely used in healthcare facilities. the decontamination procedures recommended for the inactivation of prions are often incompatible with the materials used in medical devices. in this study, we evaluated the use of low-temperature hydrogen peroxide gas plasma sterilization systems and other instrument-processing procedures for i ... | 2009 | 19563265 |
| elimination capacity of a tse-model agent in the manufacturing process of alphanate/fanhdi, a human factor viii/vwf complex concentrate. | the variant creutzfeldt-jakob disease (vcjd) is a transmissible spongiform encephalopathy (tse), mainly present in the uk and is associated with the ingestion of bovine products affected with bovine spongiform encephalopathy. manufacturers of biological products must investigate the ability of their production processes to remove tse agents. we studied the purification steps in the manufacturing process of two fviii/vwf concentrates (alphanate) and fanhdi in their ability to eliminate an experim ... | 2009 | 19563480 |
| genomic and post-genomic analyses of human prion diseases. | abstract : prion diseases share common features of neurodegenerative disorders, infectious diseases and pathologies linked to misfolded proteins. whether these aspects are independently and fortuitously present in prion diseases or are somewhat linked together remains unsettled, but the contribution of genomic, proteomic, metabolomic and spectroscopic techniques might give insights into this puzzle, and likely give hope for therapy to patients. although the prion protein gene (prnp) governs most ... | 2009 | 19566915 |
| human variant creutzfeldt-jakob disease and sheep scrapie prp(res) detection using seeded conversion of recombinant prion protein. | the pathological isoform of the prion protein (prp(res)) can serve as a marker for prion diseases, but more practical tests are needed for preclinical diagnosis and sensitive detection of many prion infections. previously we showed that the quaking-induced conversion (quic) assay can detect sub-femtogram levels of prp(res) in scrapie-infected hamster brain tissue and distinguish cerebral spinal fluid (csf) samples from normal and scrapie-infected hamsters. we now report the adaptation of the qui ... | 2009 | 19570812 |
| reflections on a half-century in the field of transmissible spongiform encephalopathy. | the subject of transmissible spongiform encephalopathy may properly be said to have begun with the experimental transmission of scrapie by cuillé and chelle in 1936, although creutzfeldt and jakob had described the disease that bears their names in 1920-21. thirty more years passed before the human disease was also shown to be transmissible, in 1966, and the following half century has seen the field move from classical biology to molecular biology and genetics, and from 'slow virus' to host-enco ... | 2009 | 19618333 |
| pathological phenotype of sheep scrapie after blood transfusion. | blood transfusion practices have resulted in iatrogenic cases of variant creutzfeldt-jakob disease (vcjd) and it is known that sheep blood is also infectious in the pre-clinical stages of natural scrapie and experimentally induced bovine spongiform encephalopathy (bse). further investigations have also shown that the pathological phenotype of sheep bse and human vcjd is maintained after blood transfusion. the present study describes the pathological phenotype, in terms of accumulation of the dis ... | 2010 | 19625026 |
| transmissions of variant creutzfeldt-jakob disease from brain and lymphoreticular tissue show uniform and conserved bovine spongiform encephalopathy-related phenotypic properties on primary and secondary passage in wild-type mice. | prion strains are defined by their biological properties after transmission to wild-type mice, specifically by their incubation periods and patterns of vacuolar pathology ('lesion profiles'). preliminary results from transmissions of variant creutzfeldt-jakob disease (vcjd) to wild-type mice provided the first compelling evidence for the close similarity of the vcjd agent to the agent causing bovine spongiform encephalopathy (bse). complete results from this investigation, including the transmis ... | 2009 | 19656962 |
| a traceback phenomenon can reveal the origin of prion infection. | the transmission of prions to animals with incongruent prion protein (prp) gene (referred to as cross-sequence transmission) results in a relatively long incubation period and can generate a new prion strain with unique transmissibility designated as a traceback phenomenon. for example, cross-sequence transmission of bovine spongiform encephalopathy (bse) prions to human generated variant creutzfeldt-jakob disease (vcjd) prions which retained the transmissibility to mice expressing bovine prp. t ... | 2009 | 19659941 |
| canadian media representations of mad cow disease. | a canadian case of bovine spongiform encephalopathy (bse) or "mad cow disease" was confirmed in may, 2003. an in-depth content analysis of newspaper articles was conducted to understand the portrayal of bse and variant creutzfeldt-jakob disease (vcjd) in the canadian media. articles in the "first 10 days" following the initial discovery of a cow with bse in canada on may 20, 2003, were examined based on the premise that these initial stories provide the major frames that dominate news media repo ... | 2009 | 19697246 |
| detection of prpsc in blood from sheep infected with the scrapie and bovine spongiform encephalopathy agents. | the role of blood in the iatrogenic transmission of transmissible spongiform encephalopathy (tse) or prion disease has become an increasing concern since the reports of variant creutzfeldt-jakob disease (vcjd) transmission through blood transfusion from humans with subclinical infection. the development of highly sensitive rapid assays to screen for prion infection in blood is of high priority in order to facilitate the prevention of transmission via blood and blood products. in the present stud ... | 2009 | 19740979 |
| high sensitivity detection of the glial fibrillary acidic protein as indicator for tse risk material in meat products using an immuno-pcr. | the emergence of prion diseases in cattle during the bovine spongiform encephalopathy (bse) epidemic and the transmission to humans causing variant creutzfeldt-jakob disease by consume of bse-contaminated meat has focused attention on the use of tissues from the central nervous system (cns) in food. to avoid food contamination, it is regulated by law that specified risk material has to be removed from food chains. detection of well-expressed cns indicator proteins such as the glial fibrillary ac ... | 2009 | 19753609 |
| repetitive immunization enhances the susceptibility of mice to peripherally administered prions. | the susceptibility of humans and animals to prion infections is determined by the virulence of the infectious agent, by genetic modifiers, and by hitherto unknown host and environmental risk factors. while little is known about the latter two, the activation state of the immune system was surmised to influence prion susceptibility. here we administered prions to mice that were repeatedly immunized by two initial injections of cpg oligodeoxynucleotides followed by repeated injections of bovine se ... | 2009 | 19779609 |
| the effects of host age on follicular dendritic cell status dramatically impair scrapie agent neuroinvasion in aged mice. | following peripheral exposure, many transmissible spongiform encephalopathy (tse) agents accumulate first in lymphoid tissues before spreading to the cns (termed neuroinvasion) where they cause neurodegeneration. early tse agent accumulation upon follicular dendritic cells (fdcs) in lymphoid follicles appears critical for efficient neuroinvasion. most clinical cases of variant creutzfeldt-jakob disease have occurred in young adults, although the reasons behind this apparent age-related susceptib ... | 2009 | 19786551 |
| quantitative measurement of the efficacy of protein removal by cleaning formulations; comparative evaluation of prion-directed cleaning chemistries. | the stability of the infectious agent causing variant creutzfeldt-jakob disease (vcjd) has highlighted the importance of cleaning surgical instruments for controlling potential spread of iatrogenic cjd. in this study, thermostable adenylate kinases (taks) in test soil were coated on to stainless steel and these surrogate agents used to evaluate the efficacy of a range of cleaning chemistries in a bench-top washer disinfector (btwd), or as a pre-soak either with or without subsequent treatment by ... | 2010 | 19833409 |
| increase in cd230 (cellular prion protein) fluorescence on blood lymphocytes in bovine spongiform encephalopathy-infected nonhuman primates. | the cellular prion protein (prp(c)) plays a central role in prion diseases such as variant creutzfeldt-jakob disease. this disease can be transmitted by blood transfusion. however, the exact kinetics of blood infectivity and the blood fraction carrying infectivity have not yet been identified. | 2010 | 19843289 |
| fast, broad-range disinfection of bacteria, fungi, viruses and prions. | effective disinfectants are of key importance for the safe handling and reprocessing of surgical instruments. this study tested whether new formulations containing sds, naoh and 1-propanol (n-propanol) are simultaneously active against a broad range of pathogens including bacteria, fungi, non-enveloped viruses and prions. inactivation and disinfection were examined in suspension and on carriers, using coagulated blood or brain homogenate as an organic contaminant. coomassie blue staining was use ... | 2010 | 19864502 |
| evaluation of removal of prion infectivity from red blood cells with prion reduction filters using a new rapid and highly sensitive cell culture-based infectivity assay. | the clearance of infectious prions from biologic fluids is usually quantified by bioassays based on intracerebral inoculation of hamsters or mice; these tests are slow, cumbersome, imprecise, and very expensive. in the present study we describe the use of a new and highly sensitive cell culture-based infectivity assay to evaluate the performance of several prion removal prototype filters. | 2010 | 20003057 |
| [prion disease surveillance in japan: analysis of 1,241 patients]. | the creutzfeldt-jakob disease (cjd) surveillance committee has identified 1,241 patients with prion diseases during 1999-2009, including 953 with sporadic cjd (scjd) (76.8%), 207 with genetic prion diseases (16.7%), 78 with environmentally acquired prion diseases (6.3%), and 3 with unclassified cjd. among atypical cases of scjd, most common was mm2 type including the cortical and thalamic forms. the genetic cases included 84 with a prp v180i mutation (40.6%), 37 with a p102l mutation (17.9%), 34 ... | 2009 | 20030254 |
| prnp variation in uk sporadic and variant creutzfeldt jakob disease highlights genetic risk factors and a novel non-synonymous polymorphism. | genetic analysis of the human prion protein gene (prnp) in suspect cases of creutzfeldt-jakob disease (cjd) is necessary for accurate diagnosis and case classification. previous publications on the genetic variation at the prnp locus have highlighted the presence of numerous polymorphisms, in addition to the well recognised one at codon 129, with significant variability between geographically distinct populations. it is therefore of interest to consider their influence on susceptibility or the c ... | 2009 | 20035629 |
| age-related alterations affect the susceptibility of mice to prion infection. | the sporadic and familial forms of creutzfeldt-jacob disease (scjd and fcjd) usually appear at older ages (60-70 years and approximately 50, respectively). nevertheless, infectious forms such as kuru and variant cjd (vcjd) present mostly at a much earlier age. to study the effect of age on the pathogenesis of infectious prion disease, we inoculated young and aged mice intraperitoneally with rml prions, followed them to disease end point and studied their disease characteristics. we now show that ... | 2009 | 20045218 |
| 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. | 2010 | 20049325 |
| why implement universal leukoreduction? | the improvement of transfusion medicine technology is an ongoing process primarily directed at increasing the safety of allogeneic blood component transfusions for recipients. over the years, relatively little attention had been paid to the leukocytes present in the various blood components. the availability of leukocyte removal (leukoreduction) techniques for blood components is associated with a considerable improvement in various clinical outcomes. these include a reduction in the frequency a ... | 2008 | 20063539 |
| 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 ... | 2010 | 20070383 |
| 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 ... | 2010 | 20089457 |
| 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. | 2010 | 20098730 |
| 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 ... | 2010 | 20214905 |
| [acquired human prion diseases--past and present issues]. | transmissible spongiform encephalopathies, or prion diseases, are fatal neurodegenerative disorders. in aetiological viewpoint, human prion diseases are classified into 1) sporadic creutzfeldt-jakob disease (cjd) which comprises 80-90% of the total population of human prion disaeses, 2) inherited forms, and 3) acquired types by prion-contaminated surgical instruments, biopharmaceuticals or foodstuffs. the diseases cause an accumulation of the disease-associated form(s) of prion protein (prp(sc)) ... | 2009 | 20218324 |
| 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. | 2010 | 20230536 |
| [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 ... | 2010 | 20449549 |
| [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 ... | 2010 | 20449555 |
| 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 ... | 2010 | 20487442 |
| 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 ... | 2010 | 20513567 |
| 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 ... | 2010 | 20517937 |
| 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 ... | 2011 | 20535485 |
| 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, ... | 2010 | 20546202 |
| 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 ( ... | 2010 | 20561299 |
| 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 ... | 2010 | 20581692 |
| 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 ... | 2010 | 20590878 |
| 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 ... | 2010 | 20594106 |
| 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 ... | 2010 | 20603132 |