Publications

food safety: bovine spongiform encephalopathy (mad cow disease).	bovine spongiform encephalopathy is just one of a group of diseases known as transmissible spongiform encephalopathies. only recently has it become recognized that transmissible spongiform encephalopathies are likely due to proteins known as prions. although it has been recognized that transmissible spongiform encephalopathies may readily spread within species, the recent observations that bovine spongiform encephalopathy in cattle may have originated from another transmissible spongiform enceph ...	2002	11984426
[the risk of variant creutzfeldt-jakob disease in the netherlands and the effect of preventive measures].	variant creutzfeldt-jakob disease (vcjd) is a fatal and untreatable neurological disease, in which pathogenic prions (prpsc) are involved. there is convincing epidemiological and experimental evidence that vcjd is a human expression of bovine spongiform encephalopathy (bse). the risk of transmission of pathogenic prions which cause vcjd to humans is influenced by the species barrier, genetic susceptibility of the host, dose of infection and route of exposure. transmission of pathogenic prions fr ...	2002	11998352
haemophilia 2002: emerging risks of treatment.	haemophilia care and treatment products have greatly improved over the past 2 decades. transitions in treatment produced by these changes were accompanied by the emergence of unexpected risks and new complications. in order to provide the best comprehensive care to patients with haemophilia, healthcare providers periodically need to re-evaluate and adjust their management and therapeutic products to prevent or minimize the effects produced by the emerging issues. for example, reducing the effect ...	2002	12010415
risk of variant creuzfeldt-jakob disease from factor concentrates: current perspectives.	the demonstration of iatrogenic transmission of creuzfeldt-jakob disease (cjd) through therapeutic interventions led to substantial concerns in communities requiring blood products in the 1980s and 1990s. these concerns led some regulatory authorities to adopt a very precautionary approach and require recall of plasma products, including factor concentrates, which included donors at risk of cjd. the fda's approach on recall contributed to a substantial lack of plasma products on the world market ...	2002	12010416
bse and variant creutzfeldt-jakob disease: never say never.		2002	12012095
bovine spongiform encephalopathy update.	bovine spongiform encephalopathy (bse) is a zoonosis being the origin of variant creutzfeldt-jakob disease and an important cattle disease in its own right. countries have been slow to learn the importance of protecting, not only their cattle populations, but also their human populations. since 2000, several additional european countries have reported bse in native-born stock and this has led to a concern about the bse status of countries that have imported cattle and catlle products from infect ...	2002	12014225
prnp contains both intronic and upstream regulatory regions that may influence susceptibility to creutzfeldt-jakob disease.	the prion protein (prp) plays a central role in creutzfeldt-jakob disease (cjd) and other transmissible spongiform encephalopathies (tses). mutations in the protein coding region of the human prp gene (prnp), which have been proposed to alter the stability of the prp protein, have been linked to a number of forms of tse. however, the majority of cjd cases are not associated with mutations in the prnp coding region and alternative mechanisms must therefore underlie susceptibility to these forms o ...	2002	12034503
neurological adverse events associated with vaccination.	public tolerance to adverse reactions is minimal. several reporting systems have been established to monitor adverse events following immunization. the present review summarizes data on neurologic complications following vaccination, and provides evidence that indicates whether they were directly associated with the vaccines. these complications include autism (measles vaccine), multiple sclerosis (hepatitis b vaccine), meningoencephalitis (japanese encephalitis vaccine), guillain-barré syndrome ...	2002	12045734
follicular dendritic cell of the knock-in mouse provides a new bioassay for human prions.	infectious prion diseases initiate infection within lymphoid organs where prion infectivity accumulates during the early stages of peripheral infection. in a mouse-adapted prion infection, an abnormal isoform (prp(sc)) of prion protein (prp) accumulates in follicular dendritic cells within lymphoid organs. human prions, however, did not cause an accumulation of prp(sc) in the wild type mice. here, we report that knock-in mouse expressing humanized chimeric prp demonstrated prp(sc) accumulations ...	2002	12051707
[transmission of spongiform encephalopathies (prion diseases)].	the transmissible spongiform encephalopathies (tse), or prion diseases, constitute a form of degenerative disorders of the central nervous system, which are characterized by a typical spongiform histological pattern and a fatal course. according to prusiner's theory, its agent consists of a protein without any nucleic acid, the "proteinaceous infectious agent", or prion. this is a pathologically folded form of the normal prion protein (prpc), and then called prpsc. tse are observed in different ...	2002	12063689
transmission of prion disease.	the transmission of bovine spongiform encephalopathy to humans as variant creutzfeldt-jakob disease (vcjd) has focused public attention on how prion diseases are transmitted and how prions reach the brain after exposure. prion diseases are characterised by transmissibility and neuropathological features of gliosis, neuronal loss and microscopic vacuoles, termed spongiosis. the principal component of prions is the glycoprotein prp(sc), which is a conformational modified isoform of the normal memb ...	2002	12064258
pathological diagnosis of variant creutzfeldt-jakob disease.	the neuropathological and biochemical features of the 89 histologically confirmed cases of variant creutzfeldt-jakob disease (vcjd) diagnosed up to the end of october 2001 in the uk are reviewed. histology of the central nervous system, lymphoid tissues and other organs was accompanied by immunocytochemistry and western blot analysis of the disease-associated form of the prion protein (prp(res)). all patients with vcjd were methionine homozygotes at codon 129 of the prp gene. the pathology of vc ...	2002	12064259
clinical diagnosis and differential diagnosis of cjd and vcjd. with special emphasis on laboratory tests.	the most widely distributed form of transmissible spongiform encephalopathy, sporadic creutzfeldt-jakob disease, typically affects patients in their sixties. rapidly progressive dementia is usually followed by focal neurological signs and typically myoclonus. the disease duration in sporadic cjd is shorter than in variant cjd (6 months and 14 months, respectively). the clinical diagnosis in sporadic cjd is supported by the detection of periodic sharp and slow wave complexes in the electroencepha ...	2002	12064260
current perspectives on bovine spongiform encephalopathy and variant creutzfeldt-jakob disease.	bovine spongiform encephalopathy (bse) clearly originated in the uk, where there have now been more than 180 000 cases. however, through the exportation of cattle and cattle-feed additives from the uk, bse also became established to a lesser extent in other european countries. there is current concern that bse might have been distributed more widely as a result of the exportation of cattle or bse-infected feed or foodstuff not only from the uk but also from other european countries that later be ...	2002	12084100
immunization delays the onset of prion disease in mice.	the outbreak of new variant creutzfeldt-jakob disease has raised the specter of a potentially large population being at risk to develop this prionosis. none of the prionoses currently have an effective treatment. recently, vaccination has been shown to be effective in mouse models of another neurodegenerative condition, namely alzheimer's disease. here we report that vaccination with recombinant mouse prion protein delays the onset of prion disease in mice. vaccination was performed both before ...	2002	12107084
molecular advances in understanding inherited prion diseases.	the prion diseases are neurodegenerative disorders that have attracted great interest because of the possible link between bovine spongiform encephalopathy (bse) and variant creutzfeldt-jakob disease (ctd) in humans. possible transmission of these diseases has been linked to a single protein termed the prion protein. this protein is an abnormal isoform of a normal synaptic glycoprotein. the majority of prion diseases does not appear to be caused by transmission of an infectious agent but occur s ...	2002	12109876
comparative epidemiology of scrapie outbreaks in individual sheep flocks.	data recording the course of scrapie outbreaks in 4 sheep flocks (2 in cheviot sheep and 2 in suffolks) are compared. for each outbreak the data on scrapie incidence and sheep demography and pedigrees cover periods of years or decades. a key finding is that the incidence of clinical cases peaks in sheep 2-3 years old, despite very different forces-of-infection. this is consistent with age-specific susceptibility of sheep to scrapie, as has been reported for cattle to bovine spongiform encephalop ...	2002	12113497
vcjd: the epidemic that never was. possibility of bse being cause of variant cjd is indeed biologically plausible.		2002	12125684
implications of prion diseases for neurosurgery.	prion diseases comprise a group of diseases characterised by transmissibility, spongiosis, gliosis, neuronal loss, and accumulation of an abnormally folded membrane protein, prp(sc). infectivity resists almost all chemical and physical processes that inactivate conventional viruses, whereas protein extraction abolishes infectivity. this fact is of great importance to surgery, especially neurosurgery, since conventional cleaning of surgical instruments does not abolish infectivity. as a matter of ...	2002	12172722
[human prion diseases].	prion diseases are rare neurodegenerative transmissible fatal diseases affecting humans and mammals. the causative agent is a novel pathogen termed the prion. unlike classical infectious agents such as bacteria or viruses, prions lack an independent genome and consist largely of an abnormal form of the host-encoded prion protein. creutzfeldt-jakob disease (cjd) is the main representative of human prion diseases that may be sporadic in most cases, hereditary, or acquired. clinical examination yie ...	2002	12190050
apolipoprotein e and other cerebrospinal fluid proteins differentiate ante mortem variant creutzfeldt-jakob disease from ante mortem sporadic creutzfeldt-jakob disease.	the ability to perform an ante mortem differential diagnosis of creutzfeld-jakob disease (cjd) is aided by several clinical and molecular tests. there is a need for molecular tests which can reliably distinguish ante mortem variant cjd (vcjd) from ante mortem sporadic cjd (spcjd). a proteomics approach employing two-dimensional protein electrophoresis is applied to the study of ante mortem csf samples obtained in collaboration with the cjd surveillance unit and the national hospital for neurolog ...	2002	12210228
disease transmission by blood products: past, present and future.	transfusion of blood and blood products has been associated with transmission of infectious agents. however, it is probable that blood products are currently very safe and that pooled virus-inactivated products from remunerated donors are now safer than untreated single voluntary donor components. although the transmission events of the past and the present are reasonably well understood, reliance on a linear approach to predict safety in the future is open to criticism. indeed, it was not possi ...	2002	12214137
epidemiology of variant cjd.	there are 100 confirmed cases of variant cjd (vcjd) in the u.k., with four cases in other countries (france and the republic of ireland). in the u.k., the mean age of onset is 28 years (range 12-74) with a median duration of 13 months (range 6-39). there are reported regional variations in incidence in the u.k., with a north/south difference and a 'cluster' of cases in one county, leicestershire. the incidence of cases in the u.k. is rising. there are concerns about the possibility of secondary, ...	2002	12220145
variant creutzfeldt-jakob disease--a problem for general dental practitioners?	over a hundred deaths from variant creutzfeldt-jakob disease (vcjd) have now been recorded. the incubation period for vcjd may be up to 40 years and the number of asymptomatic carriers in the population could be as many as 100,000. confirmed iatrogenic transmission of other human transmissible spongiform encephalopathies raises the possibility of cross-infection from apparently healthy persons who are incubating vcjd. decontamination techniques routinely used in general dental practice are incap ...	2002	12221758
prions, bse and food.	biochemical and biophysical properties of prions including possible inactivation methods are reviewed. possible molecular markers of transmissible spongiform encephalopathy (tse) and mechanisms behind infectivity and correlation with clinical symptoms are discussed. the risk of bovine spongiform encephalopathy (bse) for humans i.e. variant creutzfeldt-jakob disease (ccjd) is addressed in detail. the consequences of the emergence of the new ccjd and the lack of information on the infectivity of c ...	2002	12222633
analysis of the prion protein in primates reveals a new polymorphism in codon 226 (y226f).	bovine spongiform encephalopathy has been epizootic in cows for the last two decades, and most probably causes variant creutzfeldt-jakob disease in humans. a thorough understanding of prion pathogenesis relies on suitable animal models. modeling the transmission of bse to primates is a crucial public health priority, necessary for determining the tissue distribution of the agent and for devising therapies. susceptibility of humans to bse is partly determined by polymorphism within the gene encod ...	2002	12222676
[basic research on bse transmission to people].	prion diseases of animal and man belong to neurological diseases with amyloidal deposition of the respective proteins. as to prion disease, the cellular prionprotein is in its abnormal isoform(s) an essential component of prionprotein aggregates found in affected tissue. in contrast to all neurodegenerative diseases like morbus alzheimer or huntington's disease, prion diseases are transmissible. therefore, prion diseases were designated transmissible spongiform encephalopathies (tse). the diseas ...	2002	12224460
bacterial contamination of animal feed and its relationship to human foodborne illness.	animal feed is at the beginning of the food safety chain in the "farm-to-fork" model. the emergence of variant creutzfeldt-jakob disease has raised awareness of the importance of contaminated animal feed, but less attention has been paid to the role of bacterial contamination of animal feed in human foodborne illness. in the united states, animal feed is frequently contaminated with non-typhi serotypes of salmonella enterica and may lead to infection or colonization of food animals. these bacter ...	2002	12228823
prp(cwd) lymphoid cell targets in early and advanced chronic wasting disease of mule deer.	up to 15% of free-ranging mule deer in northeastern colorado and southeastern wyoming, usa, are afflicted with a prion disease, or transmissible spongiform encephalopathy (tse), known as chronic wasting disease (cwd). cwd is similar to a subset of tses including scrapie and variant creutzfeldt-jakob disease in which the abnormal prion protein isoform, prp(cwd), accumulates in lymphoid tissue. experimental scrapie studies have indicated that this early lymphoid phase is an important constituent o ...	2002	12237446
quinacrine does not prolong survival in a murine creutzfeldt-jakob disease model.	paramount among issues relating to the transmissible spongiform encephalopathies (also known as prion diseases) is the absence of any effective therapy. this need has been heightened by the substantial european and emerging global problem of bovine spongiform encephalopathy and consequent variant creutzfeldt-jakob disease. stimulated by the recent reports of a potent antiprion effect in cell culture-based clearance assays, we studied the utility of quinacrine in a well-characterized in vivo mode ...	2002	12325081
nursing patients with variant creutzfeldt-jakob disease at home.	variant creutzfeldt-jakob disease (vcjd) is a rare variant of a rare neurodegenerative disease, with a rapid and fatal course. the emergence of vcjd in humans in 1996 is believed to have resulted from the consumption of bovine spongiform encephalopathy (bse)-infected meat. by july 2002, the number of vcjd cases in the uk had increased to over 120 and it is not yet known how many more people will be affected. the majority of affected individuals are cared for within their own homes with the suppo ...	2002	12362140
variant creutzfeldt-jakob disease in an italian woman.	as of may, 2002, 128 cases of variant creutzfeldt-jakob (vcjd) disease have been identified in the uk, france, and ireland. we report the first case of vcjd in italy. the patient was a young italian woman who had never travelled to a country with bovine spongiform encephalopathy (bse). she was diagnosed by cerebral mri and western blot analysis of tonsil biopsy samples. the results of these analyses suggest that vcjd in continental europe and the uk share genetic, clinical, and neuroimaging feat ...	2002	12383671
measuring prions causing bovine spongiform encephalopathy or chronic wasting disease by immunoassays and transgenic mice.	there is increasing concern over the extent to which bovine spongiform encephalopathy (bse) prions have been transmitted to humans, as a result of the rising number of variant creutzfeldt-jakob disease (vcjd) cases. toward preventing new transmissions, diagnostic tests for prions in livestock have been developed using the conformation-dependent immunoassay (cdi), which simultaneously measures specific antibody binding to denatured and native forms of the prion protein (prp). we employed high-aff ...	2002	12389035
probable variant creutzfeldt-jakob disease in a u.s. resident--florida, 2002.	on april 18, 2002, the florida department of health and cdc announced the occurrence of a likely case of variant creutzfeldt-jakob disease (vcjd) in a florida resident aged 22 years. this report documents the investigation of this case and underscores the importance of physicians increasing their suspicion for vcjd in patients presenting with clinical features described in this report who have spent time in areas in which bovine spongiform encephalopathy (bse) is endemic.	2002	12403409
[prion diseases].	creutzfeldt-jakob disease, kuru, gerstmann sträussler scheinker syndrome and fatal familial insomnia in humans, as well as scrapie and bovine spongiform encephalopathy, in animals, are fatal disorders of the central nervous system that are part of the group of transmissible spongiform encephalopathies, (tse) or prion diseases. neuronal intracellular spongiosis and the accumulation of abnormal, protease resistant prion protein in the nervous central system characterize tse. the conformational cha ...	2002	12407310
variant creutzfeldt-jakob disease: an unfolding epidemic of misfolded proteins.	variant creutzfeldt-jakob disease (vcjd) is an emerging infectious disease believed to be the human manifestation of bovine spongiform encephalopathy (bse). variant cjd belongs to a family of human and animal diseases called transmissible spongiform encephalopathies (tse). the pathogenesis of tse is not fully understood, but a modified form of a normal cellular protein plays a central role. current measures to control vcjd aim to prevent transmission of the infectious agent from animals to human ...	2002	12410862
variant creutzfeldt-jakob disease.	variant creutzfeldt-jakob disease is caused by the transmission of bovine spongiform encephalopathy to humans. the clinical and investigative features of variant cjd are relatively distinct from sporadic cjd. the number of cases of vcjd are increasing with time in the uk, but the total future number of cases of vcjd is uncertain.	2002	12416394
neuropathology of variant creutzfeldt-jakob disease.	the clinical, neuropathological genetic and biochemical features of variant creutzfeldt-jakob disease (vcjd) are compared to the 926 other cases of suspected cjd referred to the national cjd surveillance unit laboratory from 1990-2001. histological studies of the central nervous system, lymphoid tissues and other organs were accompanied by immunocytochemistry for prion protein (prp); western blot analysis of prpres was performed on frozen brain tissue. the pathology of vcjd showed relatively uni ...	2002	12416395
bovine spongiform encephalopathy. update.	bovine spongiform encephalopathy (bse) is a zoonosis being the origin of variant creutzfeldt-jakob disease and an important cattle disease in its own right. countries have been slow to learn the importance of protecting, not only their cattle populations, but also their human populations. since 2000, several additional european countries have reported bse in native-born stock and this has led to a concern about the bse status of countries that have imported cattle and cattle products from infect ...	2002	12416396
induction of antibodies against murine full-length prion protein in wild-type mice.	the causative and infectious agent of the transmissible spongiform encephalopathies, e.g. bovine spongiform encephalopathy in cattle or variant creutzfeldt-jakob disease in humans, is a pathogenic form of the scrapie prion protein (prp(sc)) generated by a conformational rearrangement in the normal cellular prion protein (prp(c)). anti-prp antibodies have been shown to exert a protective effect against infection with prp(sc). however, the generation of anti-prp antibodies has proven quite difficu ...	2002	12417440
partitioning of human and sheep forms of the pathogenic prion protein during the purification of therapeutic proteins from human plasma.	therapeutic proteins derived from human plasma and other biologic sources have demonstrated an excellent safety record relative to the potential threat of transmissible spongiform encephalopathy (tse) transmission. previously, hamster-adapted scrapie was used as a model agent to assess tse clearance in purification steps leading to the isolation of biopharmaceutical proteins. the current study investigated the validity of hamster scrapie as a model for human tse clearance studies. the partitioni ...	2002	12421224
implications of bse infection screening data for the scale of the british bse epidemic and current european infection levels.	the incidence of confirmed clinical cases of bovine spongiform encephalopathy (bse) in great britain continues to decline, but the recent discovery of cases in previously unaffected countries (including israel, japan, poland, slovenia and spain) has heightened concerns that bse transmission was more intense and widespread than previously thought. we use back-calculation methods to undertake an integrated analysis of data on infection prevalence in apparently healthy cattle and the incidence of c ...	2002	12427310
bse prions propagate as either variant cjd-like or sporadic cjd-like prion strains in transgenic mice expressing human prion protein.	variant creutzfeldt-jakob disease (vcjd) has been recognized to date only in individuals homozygous for methionine at prnp codon 129. here we show that transgenic mice expressing human prp methionine 129, inoculated with either bovine spongiform encephalopathy (bse) or variant cjd prions, may develop the neuropathological and molecular phenotype of vcjd, consistent with these diseases being caused by the same prion strain. surprisingly, however, bse transmission to these transgenic mice, in addi ...	2002	12456643
disease-associated prion protein in vessel walls.	human prion diseases like creutzfeldt-jakob disease are infectious, inherited, or sporadic neurodegenerative disorders, characterized by the accumulation of an abnormal isoform of the host-encoded prion protein. this affects nervous tissue in sporadic creutzfeldt-jakob disease and, additionally, in lymphoid tissue in bovine spongiform encephalopathy-linked variant creutzfeldt-jakob disease. experimental studies have established the involvement of cells of the lymphoid and peripheral nervous syst ...	2002	12466112
identification of genetic loci affecting mouse-adapted bovine spongiform encephalopathy incubation time in mice.	prion diseases are fatal neurodegenerative disorders of humans and animals, which include bovine spongiform encephalopathy (bse) and its human form, variant creutzfeldt-jakob disease (vcjd). they are characterized by a prolonged incubation period, which is known to be influenced by polymorphisms in the prion protein gene. previous studies of inbred mice have demonstrated that additional genetic loci also contribute to the observed variation in incubation period. however, a substantial transmissi ...	2002	12481985
variant creutzfeldt-jakob disease and bovine spongiform encephalopathy.	strong epidemiologic and laboratory evidence indicate that a novel, variant form of creutzfeldt-jakob disease (vcjd) first reported in the united kingdom in 1996 is causally linked with bovine spongiform encephalopathy (bse). bse was first identified in the early 1980s in the united kingdom, and has since spread to other european countries and recently to japan and israel. although the united kingdom bse epizootic is on the decline, widespread exposure of humans to infected cattle products may h ...	2002	12489284
mapping the early steps in the ph-induced conformational conversion of the prion protein.	under certain conditions, the prion protein (prp) undergoes a conformational change from the normal cellular isoform, prp(c), to prp(sc), an infectious isoform capable of causing neurodegenerative diseases in many mammals. conversion can be triggered by low ph, and in vivo this appears to take place in an endocytic pathway and/or caveolae-like domains. it has thus far been impossible to characterize the conformational change at high resolution by experimental methods. therefore, to investigate t ...	2001	11248018
adaptation of the bovine spongiform encephalopathy agent to primates and comparison with creutzfeldt-- jakob disease: implications for human health.	there is substantial scientific evidence to support the notion that bovine spongiform encephalopathy (bse) has contaminated human beings, causing variant creutzfeldt-jakob disease (vcjd). this disease has raised concerns about the possibility of an iatrogenic secondary transmission to humans, because the biological properties of the primate-adapted bse agent are unknown. we show that (i) bse can be transmitted from primate to primate by intravenous route in 25 months, and (ii) an iatrogenic tran ...	2001	11259641
bovine spongiform encephalopathy and variant creutzfeldt-jakob disease: background, evolution, and current concerns.	the epidemic of bovine spongiform encephalopathy (bse) in the united kingdom, which began in 1986 and has affected nearly 200,000 cattle, is waning to a conclusion, but leaves in its wake an outbreak of human creutzfeldt-jakob disease, most probably resulting from the consumption of beef products contaminated by central nervous system tissue. although averaging only 10-15 cases a year since its first appearance in 1994, its future magnitude and geographic distribution (in countries that have imp ...	2001	11266289
[confusion surrounding bovine spongiform encephalopathy (bse) and the risk of new variant creutzfeldt-jakob disease].		2001	11268917
the emerging european epidemic of variant creutzfeldt-jakob disease and bovine spongiform encephalopathy: lessons for australia.		2001	11270752
temporary depletion of complement component c3 or genetic deficiency of c1q significantly delays onset of scrapie.	following peripheral exposure to transmissible spongiform encephalopathies (tses), infectivity usually accumulates in lymphoid tissues before neuroinvasion. the host prion protein (prpc) is critical for tse agent replication and accumulates as an abnormal, detergent insoluble, relatively proteinase-resistant isoform (prpsc) in diseased tissues. early prpsc accumulation takes place on follicular dendritic cells (fdcs) within germinal centers in lymphoid tissues of patients with variant creutzfeld ...	2001	11283677
complement facilitates early prion pathogenesis.	new-variant creutzfeldt-jakob disease and scrapie are typically initiated by extracerebral exposure to the causative agent, and exhibit early prion replication in lymphoid organs. in mouse scrapie, depletion of b-lymphocytes prevents neuropathogenesis after intraperitoneal inoculation, probably due to impaired lymphotoxin-dependent maturation of follicular dendritic cells (fdcs), which are a major extracerebral prion reservoir. fdcs trap immune complexes with fc-gamma receptors and c3d/c4b-opson ...	2001	11283678
bovine spongiform encephalopathy and variant creutzfeldt-jakob disease.		2001	11290640
geographical distribution of variant creutzfeldt-jakob disease in great britain, 1994-2000.	geographical variation in the distribution of variant creutzfeldt-jakob disease (vcjd) might indicate the transmission route of the infectious agent to man. we investigated whether regional incidences of vcjd were correlated with regional dietary data.	2001	11293592
[epidemics of bovine spongiform encephalopathy and new variant of creutzfeldt-jakob disease in humans. most recent findings on prion disease].	prion diseases have been popularized by extensive media coverage of bovine spongiform encephalopathy (bse) or "mad cow disease" epidemic, observed in great britain since 1986, and new variant creutzfeldt-jakob disease (nvcjd), reported for the first time in 1996. in contrast to the classical form of the disease, nvcjd affects younger patients, presents a relatively longer duration of illness and is caused by the same agent as bse. evidence from laboratory studies now strongly supports the hypoth ...	2001	11294108
increased expression of the normal cellular isoform of prion protein in inclusion-body myositis, inflammatory myopathies and denervation atrophy.	the cellular isoform of the prion protein (prpc) is a glycosylphosphatidylinositol-anchored glycoprotein, normally expressed in neural and non-neural tissues, including skeletal muscle. in transmissible spongiform encephalopathies, or prion diseases, prpc, which is soluble in nondenaturing detergent and sensitive to proteinase k (pk)-treatment, represents the molecular substrate for the production of a detergent-insoluble and pk-resistant isoform, termed prp(sc). in human prion diseases, prp(sc) ...	2001	11303793
prion protein and developments in its detection.	the theoretical risk of transmission of variant creutzfeldt-jakob disease (vcjd) via blood transfusions has led to replacement of uk-derived plasma for fractionation by plasma sourced outwith the uk and the introduction of leucodepletion of donated blood and its components. prion protein in an abnormal conformation (prpsc) has been identified as inextricably linked with the infectivity of transmissible spongiform encephalopathies such as vcjd and in this review some of its properties relevant to ...	2001	11328566
absence of protease-resistant prion protein in the cerebrospinal fluid of creutzfeldt-jakob disease.	creutzfeldt-jakob disease (cjd), believed to be caused by a protease-resistant isoform of prion protein (prp(sc)), usually manifests itself as a clinically distinctive age-related dementia because of its rapid progression, occasionally accompanied by cerebellar ataxia. recently, a variant cjd (vcjd) has been described, which has prominent early psychiatric symptoms and an earlier age of death. although cerebrospinal fluid (csf) is part of the extracellular fluid of the central nervous system (cn ...	2001	11329135
variant creutzfeldt-jakob disease in an elderly patient.	we report a case of variant creutzfeldt-jakob disease(vcjd) in a 74-year old man in whom diagnosis was made at necropsy. the occurrence of vcjd in an individual in this age group is unlikely to be an isolated event. doctors need to be aware that vcjd can arise in elderly patients so that appropriate investigations (including magnetic resonance imaging) can be done, and permission for neuropathological necropsy requested, in suspected cases. this case could also have important implications for pu ...	2001	11343744
identification of multiple quantitative trait loci linked to prion disease incubation period in mice.	polymorphisms in the prion protein gene are known to affect prion disease incubation times and susceptibility in humans and mice. however, studies with inbred lines of mice show that large differences in incubation times occur even with the same amino acid sequence of the prion protein, suggesting that other genes may contribute to the observed variation. to identify these loci we analyzed 1,009 animals from an f2 intercross between two strains of mice, cast/ei and nzw/olahsd, with significantly ...	2001	11353827
use of 14-3-3 and other brain-specific proteins in csf in the diagnosis of variant creutzfeldt-jakob disease.	the detection of the protein 14-3-3 in the csf has been shown to be a reliable and sensitive marker for sporadic creutzfeldt-jakob disease (cjd). other brain-specific proteins such as neuron specific enolase (nse), s-100b, and tau protein have also been reported to be increased in the csf of patients with sporadic cjd. in 1996 a variant of cjd (vcjd) was described which is likely to be causally linked to the bovine spongiform encephalopathy agent. this study reports and compares the findings of ...	2001	11385008
genetic and environmental factors modify bovine spongiform encephalopathy incubation period in mice.	the incubation period (ip) and the neuropathology of transmissible spongiform encephalopathies (tses) have been extensively used to distinguish prion isolates (or strains) inoculated into panels of inbred mouse strains. such studies have shown that the bovine spongiform encephalopathy (bse) agent is indistinguishable from the agent causing variant creutzfeldt-jakob disease (vcjd), but differs from isolates of sporadic cjd, reinforcing the idea that the vcjd epidemic in britain results from consu ...	2001	11404459
the leeuwenhoek lecture 2001. animal origins of human infectious disease.	since time immemorial animals have been a major source of human infectious disease. certain infections like rabies are recognized as zoonoses caused in each case by direct animal-to-human transmission. others like measles became independently sustained with the human population so that the causative virus has diverged from its animal progenitor. recent examples of direct zoonoses are variant creutzfeldt-jakob disease arising from bovine spongiform encephalopathy, and the h5n1 avian influenza out ...	2001	11405946
scrapie strains maintain biological phenotypes on propagation in a cell line in culture.	bovine spongiform encephalopathy (bse) and its human equivalent, variant creutzfeldt-jakob disease (vcjd), are caused by the same strain of infectious agent, which is similar to, but distinct from, >20 strains of their sheep scrapie homologue. a better understanding of the molecular strain determinants could be obtained from cells in monoculture than from whole animal studies where different cell targeting is commonly a strain-related feature. although a few cell types can be infected with diffe ...	2001	11432823
the impact of creutzfeldt-jakob disease and variant creutzfeldt-jakob disease on plasma safety.	although the true risk of transmitting (classical) creutzfeld-jakob disease (cjd) and variant cjd (vcjd) via transfusion is likely very minimal, a review of prions and the impact of these associated prion diseases is timely because of their current effect on safety policies in the blood-plasma industry. various types of human and animal prion diseases are outlined and reviewed, with emphasis on the importance of cross-species transmission as is relevant for vcjd. review of the prion theory focus ...	2001	11441420
variant creutzfeldt-jakob disease: a summary of current scientific knowledge in relation to public health.	the prion diseases pose unique scientific, medical, veterinary and regulatory challenges. here, we summarize current information bearing on the natural history, pathobiology and epidemiology of these disorders and public policy responses to the potential threats to public health posed, particularly, by bovine spongiform encephalopathy and variant creutzfeldt-jakob disease (vcjd). six years after the first case reports of vcjd, there is still no clear indication of the magnitude of the primary ep ...	2001	11468957
neuroinvasion by a creutzfeldt-jakob disease agent in the absence of b cells and follicular dendritic cells.	with the potential spread of bovine spongiform encephalopathy to people as a variant creutzfeldt-jakob disease (cjd), it becomes critical to identify cells in the periphery that carry infection. initial work with scrapie agents suggested that b cells were central vectors for neuroinvasion. subsequent studies indicated that b cells played an indirect role by promoting the development of follicular dendritic cells (fdcs) that accumulate abnormal prion protein (prp). the mechanism for the role of f ...	2001	11470899
tissue distribution of protease resistant prion protein in variant creutzfeldt-jakob disease using a highly sensitive immunoblotting assay.	variant creutzfeldt-jakob disease (vcjd) has a pathogenesis distinct from other forms of human prion disease: disease-related prion protein (prp(sc)) is readily detectable in lymphoreticular tissues. quantitation of risk of secondary transmission, and targeting of risk reduction strategies, is limited by lack of knowledge about relative prion titres in these and other peripheral tissues, the unknown prevalence of preclinical vcjd, and a transmission barrier which limits the sensitivity of bioass ...	2001	11476832
afterthoughts about bovine spongiform encephalopathy and variant creutzfeldt-jakob disease.		2001	11485682
bovine spongiform encephalopathy and variant creutzfeldt-jakob disease.		2001	11485685
sporadic creutzfeldt-jakob disease in a young dutch valine homozygote: atypical molecular phenotype.	a case of sporadic creutzfeldt-jakob disease (scjd) is described in a young dutch protein prion gene (prnp) codon 129 valine homozygote. certain clinical and molecular features of this case overlap those of variant cjd. the case highlights possible difficulties in the differential diagnosis of vcjd and the more rare scjd subtypes based on molecular features alone.	2001	11506411
variant creutzfeldt-jakob disease in australian blood donors: estimation of risk and the impact of deferral strategies.	in australia, a policy of deferring donors who have lived in the uk for longer than 6 months between 1980 and 1996 has been instituted to reduce the theoretical risk of transmitting variant creutzfeldt-jakob disease (vcjd) through the blood supply. the objective of this report was to refine estimates of the possible risks and benefits of donor-deferral strategies that are aimed at avoiding transmission of vcjd.	2001	11520409
brain in human nutrition and variant creutzfeldt-jakob disease risk (vcjd): detection of brain in retail liver sausages using cholesterol and neuron specific enolase (nse) as markers.	no information is available about the consumption of brain via meat products. with respect to the new variant of creutzfeldt-jakob disease (vcjd) and the presumed food-borne transmission of bovine spongiform encephalopathy (bse) to humans, a preliminary survey for brain and/or spinal cord (tissues of the central nervous system, cns) was conducted. we applied a previously developed integrated procedure using cholesterol and neuron specific enolase (nse) as markers. quantification of cholesterol h ...	2001	11520429
prevention of scrapie pathogenesis by transgenic expression of anti-prion protein antibodies.	variant creutzfeldt-jakob disease and bovine spongiform encephalopathy are initiated by extracerebral exposure to prions. although prion transmission from extracerebral sites to the brain represents a potential target for prophylaxis, attempts at vaccination have been limited by the poor immunogenicity of prion proteins. to circumvent this, we expressed an anti-prion protein (anti-prp) mu chain in prnp(o/o) mice. transgenic mice developed sustained anti-prp titers, which were not suppressed by i ...	2001	11546838
bovine spongiform encephalopathy and variant creutzfeldt-jakob disease: implications for australia.	the bovine spongiform encephalopathy (bse) epizootic developed in the united kingdom in the mid-1980s. feeding practices in the cattle industry amplified the causative prion, and meat contaminated with bse entered the market. human consumption of prion-contaminated meat led to the new zoonosis--variant creutzfeldt-jakob disease (vcjd). the uk bse inquiry published its report in october 2000; while praising policy decisions, it also documented failures in the execution of these policies, specific ...	2001	11548083
cna42 monoclonal antibody identifies fdc as prpsc accumulating cells in the spleen of scrapie affected sheep.	natural scrapie, new variant creutzfeldt-jakob disease and murine experimental transmissible spongiform encephalopathies (tse) are fatal neurodegenerative disorders. the agent responsible for these diseases is closely related to prpsc, an abnormal isoform of the cellular prion protein. before reaching the brain, it invades and replicates in lymphoid organs such as spleen, tonsils and lymph nodes. follicular dendritic cells (fdc) may support the prion replication in lymphoid tissues of sheep as s ...	2001	11557290
variant creutzfeldt-jakob disease is not associated with individual abilities to metabolise organophosphates.		2001	11561051
florid plaques in ovine prp transgenic mice infected with an experimental ovine bse.	the occurrence of the variant creutzfeldt-jakob disease (vcjd), related to bovine spongiform encephalopathy (bse), raises the important question of the sources of human contamination. the possibility that sheep may have been fed with bse-contaminated foodstuff raises the serious concern that bse may now be present in sheep without being distinguishable from scrapie. sensitive models are urgently needed given the dramatic consequences of such a possible contamination on animal and human health. w ...	2001	11571272
long-term subclinical carrier state precedes scrapie replication and adaptation in a resistant species: analogies to bovine spongiform encephalopathy and variant creutzfeldt-jakob disease in humans.	cattle infected with bovine spongiform encephalopathy (bse) appear to be a reservoir for transmission of variant creutzfeldt-jakob disease (vcjd) to humans. although just over 100 people have developed clinical vcjd, millions have probably been exposed to the infectivity by consumption of bse-infected beef. it is currently not known whether some of these individuals will develop disease themselves or act as asymptomatic carriers of infectivity which might infect others in the future. we have stu ...	2001	11581378
mri of creutzfeldt-jakob disease: imaging features and recommended mri protocol.	creutzfeldt-jakob disease (cjd) is a rare, progressive and invariably fatal neurodegenerative disease characterized by specific histopathological features. of the four subtypes of cjd described, the commonest is sporadic cjd (scjd). more recently, a new clinically distinct form of the disease affecting younger patients, known as variant cjd (vcjd), has been identified, and this has been causally linked to the bovine spongiform encephalopathy (bse) agent in cattle. characteristic appearances on m ...	2001	11585394
editorial: development of australia's response to bovine spongiform encephalopathy and variant creutzfeldt-jakob disease.		2001	11596725
new variant creutzfeldt-jakob disease: the epidemic that never was.		2001	11597973
variant creutzfeldt-jakob disease and blood transfusion.	variant creutzfeldt-jakob disease (vcjd) was first described in the united kingdom in 1996 and is thought to have been transmitted from cattle infected with bovine spongiform encephalopathy probably via the food chain. thus far just over 100 definite or probable clinical cases have been described, though the number of people currently infected and the eventual size and geographic distribution of any future clinical epidemic remain uncertain. there is little evidence that sporadic cjd is transmit ...	2001	11604578
[what do medical students know about cause and epidemiology of the creutzfeldt-jakob disease in germany?].	due to the increase of patients with the variant creutzfeldt-jakob disease (vcjd) in great britain and the first cases of autochthonous bse cases in germany, the study tried to investigate the knowledge of medical students about the epidemiology of cjd in germany and how they assess the influence of different factors on the etiology of cjd. altogether 63 first year medical students, 96 third year medical students and 50 nurses were included in an anonymous questionnaire survey. they were asked t ...	2001	11607873
predictability of the uk variant creutzfeldt-jakob disease epidemic.	back-calculation analysis of the variant creutzfeldt-jakob disease epidemic in the united kingdom is used to estimate the number of infected individuals and future disease incidence. the model assumes a hazard of infection proportional to the incidence of bovine spongiform encephalopathy in the united kingdom and accounts for precautionary control measures and very wide ranges of incubation periods. the model indicates that current case data are compatible with numbers of infections ranging from ...	2001	11679631
the role of mri in the diagnosis of sporadic and variant creutzfeldt-jakob disease.	creutzfeldt-jakob disease (cjd) is a rare but important fatal, dementing illness. a number of types of cjd are identified, each with distinct clinical features. characteristic mri changes have been described recently. sporadic cjd, the commonest type, is found worldwide, and causes hyperintensity of the putamen and caudate nuclei. in the recently described variant cjd, which affects younger patients and has been linked to bovine spongiform encephalopathy (bse) in cattle, a highly characteristic ...	2001	11688725
the shifting biology of prions.	transmissible spongiform encephalopathies (tses), or prion diseases, are rare fatal neurodegenerative diseases of humans and animals. although some tses, like scrapie in sheep, have been known to exist for centuries, bovine spongiform encephalopathy (bse) was recognized only 15 years ago. new variant creutzfeldt-jakob disease (nvcjd) of humans is probably caused by consumption of bse-infected materials. the nature of the infectious agent is not fully elucidated, but substantial evidence suggests ...	2001	11690621
increased susceptibility to kuru of carriers of the prnp 129 methionine/methionine genotype.	kuru reached epidemic proportions by the mid-twentieth century among the fore people of new guinea and disappeared after the abolition of cannibalistic rituals. to determine susceptibility to kuru and its role in the spread and elimination of the epidemic, we analyzed the prnp gene coding sequences in 5 kuru patients; no germline mutations were found. analysis of the prnp 129 methionine (m)/valine (v) polymorphism in 80 patients and 95 unaffected controls demonstrated that the kuru epidemic pref ...	2001	11120925
species differences in the blood content of the normal cellular isoform of prion protein, prp(c), measured by time-resolved fluoroimmunoassay.	the concern that variant creutzfeldt-jakob disease could be transmitted via blood transfusion has prompted studies of blood infectivity in animal models. as normal prion protein acts as a substrate for conversion to the abnormal form associated with infectivity, we have quantified its distribution in mice and hamsters, the most commonly used animal models.	2001	11903999
transmissible spongiform encephalopathies: vaccine issues.	the recent emergence of bovine spongiform encephalopathy (bse) and variant creutzfeldt-jakob disease (vcjd) suggests that transmissible spongiform encephalopathies (tses) pose an ongoing threat to human and animal health. to avoid iatrogenic transmission of tses in vaccines, strategies must be developed to obviate tse agent infectivity in cellular substrates, cell culture media components and enzymes, and excipients, and to validate the safety of these components and field vaccines efficiently	2001	11761262
the transmissible spongiform encephalopathies: pathogenic mechanisms and strategies for therapeutic intervention.	primary neurodegenerative diseases tend to be intractable and largely affect the elderly. there is rarely the opportunity to identify individuals at risk and the appearance of clinical symptoms usually signifies the occurrence of irreversible neurological damage. this situation describes sporadic creutzfeldt-jakob disease which occurs world-wide, affecting one person per million per annum. the epidemic of bovine spongiform encephalopathy in the uk in the 1980s and the subsequent causal appearanc ...	2001	12540284
[prions, epidemic of creutzfeldt-jakob variant disease and global emergency].	we present here the current understanding of "prion" theory and global risk for epidemics of variant creutzfeldt-jakob disease (vcjd). prion is the infectious agent of all transmissible spongiform encephalopaties (tses). it is regarded as an aggregate of a pathological conformer (prpsc) of a normal cellular glycoprotein (prpc) encoded by a gene, in humans on chromosome 20. the differences between prpsc and prpc are largely if not exclusively conformational; prpc is mostly alpha-helical while prp ...	2001	11873615
differential diagnosis of infections with the bovine spongiform encephalopathy (bse) and scrapie agents in sheep.	scrapie, bovine spongiform encephalopathy (bse), and variant creutzfeldt-jakob disease belong to the group of disorders called transmissible spongiform encephalopathies or prion diseases. the possibility that some sheep may be infected with the bse agent is of human and animal health concern. immunohistochemical methods were used to identify specific prion protein (prp) peptide sequences in specific cell types of the brain and lymphoreticular system (lrs) of sheep with natural scrapie and suffol ...	2001	11798244
pediatric adenoidectomy under vision using suction-diathermy ablation.	to compare adenoidectomy using suction-diathermy ablation with adenoidectomy by way of curettage in a pediatric tertiary care setting.	2001	11802020
transmissible spongiform encephalopathies in australia.	the australian national creutzfeldt-jakob disease registry (ancjdr) commenced surveillance in september 1993 as part of the commonwealth's response to 4 cases of pituitary hormone (gonadotrophin)-associated creutzfeldt-jakob disease (cjd). with the passage of time, the registry has become responsible for ascertaining all human transmissible spongiform encephalopathies (tse; also known as prion diseases) within australia since 1970. included in the spectrum of diseases monitored are classical (sp ...	2001	11806657
deposition patterns of disease-associated prion protein in captive mule deer brains with chronic wasting disease.	chronic wasting disease (cwd) is a transmissible spongiform encephalopathy (tse) in captive and free-ranging cervids in the usa; its origin is obscure. archival formalin-fixed and paraffin-embedded specimens of 16 captive mule deer brains with cwd were analyzed using immunocytochemistry for the disease-associated prion protein (prp). the most prominent pattern of prp deposition were plaque-like structures, a substantial proportion of which were florid plaques surrounded by a rim of spongiform va ...	2001	11699564
sporadic--but not variant--creutzfeldt-jakob disease is associated with polymorphisms upstream of prnp exon 1.	human prion diseases have inherited, sporadic, and acquired etiologies. the appearance of the novel acquired prion disease, variant creutzfeldt-jakob disease (vcjd), and the demonstration that it is caused by the same prion strain as that causing bovine spongiform encephalopathy, has led to fears of a major human epidemic. the etiology of classical (sporadic) cjd, which has a worldwide incidence, remains obscure. a common human prion-protein-gene (prnp) polymorphism (encoding either methionine o ...	2001	11704923
estimation of epidemic size and incubation time based on age characteristics of vcjd in the united kingdom.	the size of the variant creutzfeldt-jakob disease (vcjd) epidemic in the united kingdom is a major public health concern and a subject of speculation. the cases are young (mean age = 28). assuming that the risk of developing the disease in susceptible exposed subjects decreases exponentially with age after age 15, that all infections occurred between 1980 and 1989, and that the distribution of the incubation period is lognormal, we estimate that the mean duration of the incubation period is 16.7 ...	2001	11721058
the molecular pathology of cjd: old and new variants.	the study of prion disease has become an area of intense interest since experimental evidence emerged for the transmission of phenotypic variation without the involvement of a nucleic acid component. additional impetus has come from the widespread concern that exposure to bovine spongiform encephalopathy contaminated material poses a distinct and, conceivably, a severe threat to public health in the uk and other countries. the occurrence of new variant creutzfeldt-jakob disease has dramatically ...	2001	11724914