Publications

severe autolysis does not prevent scrapie diagnosis in sheep.		1994	7858030
endosome-lysosomes and neurodegeneration.	a number of the major human and animal neurodegenerative diseases, such as alzheimer's disease and sheep scrapie, are characterised by deposits of amyloid, arising through incomplete breakdown of membrane proteins. although our knowledge concerning these diseases is increasing, they remain largely untreatable. recently, attention has focussed on the mechanisms of production of different types of amyloid and the likely involvement within cells of acid compartments called endosome-lysosomes. these ...	1994	7858158
animal spongiform encephalopathies--an update. part 1. scrapie and lesser known animal spongiform encephalopathies.	the present article (part i) reviews recent developments in animal spongiform encephalopathies (ses), with the exception of bovine spongiform encephalopathy (bse), which is dealt with in part ii. the article focuses on scrapie and describes epidemiological aspects and the prospects for a preclinical diagnosis. up to now, confirmatory diagnosis of scrapie depended on histological examination of the brain, collected during post-mortem examination from sheep with clinical signs of the disease. an a ...	1994	7871704
diagnosis of scrapie.		1994	7886893
effect of sinc genotype, agent isolate and route of infection on the accumulation of protease-resistant prp in non-central nervous system tissues during the development of murine scrapie.	mice congenic for the sinc gene were infected intracerebrally with two scrapie strains, me7 and 22a. at various times during the incubation period tissues were monitored for the infection-specific form of prp (prpsc). prpsc was found in brain, spleen, lymph nodes, pancreas, submaxillary gland and thymus. after intraperitoneal inoculation prpsc was found in spleen, lymph nodes, pancreas and submaxillary glands prior to its detection in brain. the kinetics of accumulation of prpsc in these tissues ...	1994	7907357
detection of prpsc in sheep at the preclinical stage of scrapie and its significance for diagnosis of insidious infection.	a field sheep insidiously infected with natural scrapie was diagnosed at the preclinical stage through detection of the core fragment of prpsc (prpcore) in peripheral lymph nodes by the biopsy method. three out of 32 euthanized healthy sheep were found positive for prpcore in the spleen and lymph nodes. mice that were inoculated with spleen homogenate of one of these sheep showed clinical signs of scrapie and were positive for prpcore in their brain samples. these results suggest that the detect ...	1994	7907466
small virus-like structure in fractions from scrapie hamster brain.	the scrapie model in hamsters has been used to search for the agents that cause creutzfeldt-jakob disease in man and similar transmissible encephalopathies in animals. we found structures that are extraordinarily small for a virus, but exhibit viral structural properties in negatively stained samples, by electron microscopy in fractions containing scrapie-associated fibrils.	1994	7908360
prp genotype and agent effects in scrapie: change in allelic interaction with different isolates of agent in sheep, a natural host of scrapie.	man and sheep are the two species in which spongiform encephalopathies occur naturally, and in which there are recognized genetic components that predispose an individual person or sheep to clinical disease. in both species mutations/polymorphisms in the prp gene have been linked to the incidence of natural disease, but only in sheep is it possible to investigate by deliberate exposure to infection whether these polymorphisms are directly correlated with survival time. cheviot sheep of different ...	1994	7909834
properties of the scrapie prion protein: quantitative analysis of protease resistance.	the disease-specific isoform of the prion protein (prpsc) is an essential part of the infectious particle which causes spongiform degeneration in various mammalian species. prpsc differs from prp of normal animals (prpc) by its relative protease resistance. the physical nature of this difference is still unknown. we analyzed the protease resistance of prpsc quantitatively using an enzyme-linked immunofiltration assay. prpsc was rendered completely protease-sensitive at alkaline ph or in > 1.5 m ...	1994	7910036
prion isolate specified allotypic interactions between the cellular and scrapie prion proteins in congenic and transgenic mice.	different prion isolates, often referred to as "strains," present an enigma because considerable evidence argues that prions are devoid of nucleic acid. to investigate prion diversity, we inoculated three "strains" of prions into congenic and transgenic mice harboring variable numbers of two different alleles, designated a and b, of the prion protein (prp) structural gene, prn-p. the length of the incubation time was inversely related to the number of prn-p(a) genes in mice inoculated with the r ...	1994	7911243
scrapie, creutzfeldt-jakob disease and bovine spongiform encephalopathy: the key role of a nerve membrane protein (prp).		1994	7911437
protease-resistant prp accumulation and scrapie agent replication: a role for sulphated glycosaminoglycans?		1994	7911438
a glycolipid-anchored prion protein is endocytosed via clathrin-coated pits.	the cellular prion protein (prpc) is a glycolipid-anchored, cell surface protein of unknown function, a posttranslationally modified isoform of which prpsc is involved in the pathogenesis of creutzfeldt-jakob disease, scrapie, and other spongiform encephalopathies. we have shown previously that chprp, a chicken homologue of mammalian prpc, constitutively cycles between the cell surface and an endocytic compartment, with a transit time of approximately 60 min in cultured neuroblastoma cells. we n ...	1994	7911471
characterisation of antisera raised against species-specific peptide sequences from scrapie-associated fibril protein and their application for post-mortem immunodiagnosis of spongiform encephalopathies.	transmissible spongiform encephalopathies (tse), such as scrapie or creutzfeldt-jakob disease (cjd), are fatal neurodegenerative diseases of the central nervous system caused by a yet unidentified virus. they are accompanied by a brain specific amyloidosis, during which a host coded protein irreversibly aggregates to form the scrapie-associated fibrils. the diagnosis of tse relies on histopathological detection of spongiform lesions, on electron microscopical detection of fibrils, or on the immu ...	1994	7911655
no propagation of prions in mice devoid of prp.		1994	7912659
structure and polymorphism of the mouse prion protein gene.	missense mutations in the prion protein (prp) gene, overexpression of the cellular isoform of prp (prpc), and infection with prions containing the scrapie isoform of prp (prpsc) all cause neurodegenerative disease. to understand better the physiology and expression of prpc, we retrieved mouse prp gene (prn-p) yeast artificial chromosome (yac), cosmid, phage, and cdna clones. physical mapping positions prn-p approximately 300 kb from ecotropic virus integration site number 4 (evi-4), compatible w ...	1994	7912827
prpsc in icelandic sheep naturally infected with scrapie.		1994	7913301
the significance of prpsc detection for the diagnosis of insidious scrapie.		1994	7913303
heterologous prp molecules interfere with accumulation of protease-resistant prp in scrapie-infected murine neuroblastoma cells.	mutations within a host cellular protein, prp, have been associated with disease in the transmissible spongiform encephalopathies. murine neuroblastoma cells persistently infected with mouse scrapie accumulate protease-resistant prp (prp-res), the abnormal form of prp associated with disease in the transmissible spongiform encephalopathies. these cells provide a controlled system in which to study the molecular interactions which are important in the formation of prp-res. we have expressed recom ...	1994	7913509
histopathological changes in the islets of langerhans in scrapie 139h-affected hamsters.	previous studies showed that the 139h strain of scrapie injected into hamsters caused obesity, a marked hypertrophy of the islets of langerhans, generalized endocrinopathy and marked hypoglycaemia-hyperinsulinaemia. in the current study, female weanling syrian hamsters (lvg/lak strain) were inoculated intracerebrally with scrapie strain 139h or 263k, or with normal hamster brain. sections of the pancreas stained with haematoxylin and eosin or gomori's one-step trichrome were examined by light mi ...	1994	7913716
genetics of prion diseases and prion diversity in mice.	linkage of the prion protein (prp) and scrapie incubation time genes in mice provided strong evidence for the central role of prp in determining susceptibility to prion disorders. considerable evidence now argues that the prion protein and incubation time genes are identical. the mouse prion protein gene (prn-p) may act both quantitatively and qualitatively in modulating prion incubation time. differences at positions 108 and 189 between prp-a and prp-b allotypes can place constraints on interac ...	1994	7913753
scrapie-associated prp accumulation and agent replication: effects of sulphated glycosaminoglycan analogues.	an abnormally protease-resistant and apparently neuropathogenic form of prp accumulates in the brains of hosts with scrapie and related transmissible spongiform encephalopathies. studies with scrapie-infected neuroblastoma cells have highlighted dramatic differences in the metabolism of the normal (protease-sensitive) and scrapie-associated (protease-resistant) isoforms of prp. furthermore, this model has been useful in identifying inhibitors of protease-resistant prp accumulation and scrapie ag ...	1994	7913757
transmission of bovine spongiform encephalopathy and scrapie to mice: strain variation and the species barrier.	transmissions of bovine spongiform encephalopathy (bse) from seven unrelated cattle sources have given remarkably uniform disease characteristics in mice, differing from over twenty previous and contemporary transmissions of sheep and goat scrapie. transmissions to mice of spongiform encephalopathy from six species (including sheep and goats) which have been experimentally or naturally infected with bse have given similar results to direct bse transmissions from cattle. therefore the bse agent h ...	1994	7913758
physicochemical and biological characterizations of distinct strains of the transmissible mink encephalopathy agent.	inoculation of the stetsonville, wisconsin source of transmissible mink encephalopathy (tme) into syrian hamsters has identified two strains of the tme agent having distinct biological properties and producing disease-specific prion proteins (prptme) having different physicochemical properties. although several strains of the sheep scrapie agent have been identified in great britain, this is the first indication that agents producing transmissible spongiform encephalopathies in the united states ...	1994	7913759
the neuropathological phenotype in transgenic mice expressing different prion protein constructs.	neuropathologic examination of transgenic (tg) mice which express different prion protein (prp) constructs is essential because spongiform (vacuolar) degeneration of neurons, the distribution of prpsc and whether prp amyloid plaques form are the phenotypes of prion diseases. in tg models of experimental scrapie, it was found that all of the parameters that define prion isolates ('strains') can be manipulated by changing the structure of prp. in those studies, further evidence that prpsc causes s ...	1994	7913760
nucleic acids in prion preparations: unspecific background or essential component?	as recently published (kellings et al. j. gen vir. 73, 1025-1029 (1992)), the analysis of purified scrapie prions by return refocusing gel electrophoresis revealed remaining nucleic acids in the size range up to 1100 nucleotides. the results defined the possible characteristics of a hypothetical scrapie-specific nucleic acid. if homogeneous in size, such a molecule would be less than 80 nucleotides in length at a particle-to-infectivity ratio (p:i) near unity; if heterogeneous, scrapie-specific ...	1994	7913761
susceptibility to scrapie in mice is dependent on prpc.	mice devoid of functional prp genes (prn-p(o/o) mice) showed normal development and behaviour. when inoculated with mouse scrapie prions they remained free of scrapie symptoms for at least 18 months whereas wild-type controls all died within 6 months. no propagation of infectivity could be detected in the prp null mice. surprisingly, heterozygous prn-p(o/+) mice also showed enhanced resistance to scrapie. after introduction of syrian hamster prp transgenes, prn-p(o/o) mice became highly suscepti ...	1994	7913762
spectroscopic characterization of conformational differences between prpc and prpsc: an alpha-helix to beta-sheet transition.	although no chemical modifications have been found to distinguish the cellular prion protein prpc from its infectious analogue prpsc, spectroscopic methods such as fourier transform infrared (ftir) spectroscopy reveal a major conformational difference. prpc is rich in alpha-helix but is devoid of beta-sheet, whereas prpsc is high in beta-sheet. n-terminal truncation of prpsc by limited proteolysis does not destroy infectivity but it increases the beta-sheet content and shifts the ftir absorption ...	1994	7913763
characterization of prp binding proteins.	prions cause spongiform degeneration in various mammalian species. the scrapie prion protein (prpsc) is part of the infectious particle and may mediate infection and spreading of the disease in the brain. it was therefore of interest to purify and analyse prp ligands (plis). plis were identified on ligand blots using either intact prp or peptides corresponding to the central portion of prp. here, characterization of a 110 and a 125 kda pli is reported. both plis were found in total membrane frac ...	1994	7913764
molecular biology and genetics of prion diseases.	scrapie was thought for many years to be caused by a virus. enriching fractions from syrian hamster (sha) brain for scrapie infectivity led to the discovery of the prion protein (prp). to date, no scrapie-specific nucleic acid has been found. as well as scrapie, prion diseases include bovine spongiform encephalopathy (bse) of cattle, as well as creutzfeldt-jakob disease (cjd) and gerstmann-sträussler-scheinker syndrome (gss) of humans. transgenic (tg) mice expressing both sha and mouse (mo) prp ...	1994	7913765
cell-free formation of protease-resistant prion protein.	the infectious agent (or 'prion') of the transmissible spongiform encephalopathies (tses) such as scrapie resembles a virus in that it replicates in vivo and has distinct strains, but it was postulated long ago to contain only protein. more recently, prpsc, a pathogenic, scrapie-associated form of the host-encoded prion protein (prp), was identified as a possible primary tse agent protein. prpsc is defined biochemically by its insolubility and resistance to proteases and is derived post-translat ...	1994	7913989
pharmacological studies of a new derivative of amphotericin b, ms-8209, in mouse and hamster scrapie.	transmissible subacute spongiform encephalopathies (tsse) are neurodegenerative diseases characterized by the presence of a modified, partially proteinase-resistant host protein, prpsc, which accumulates in the brains of infected individuals. recently it has been reported that amphotericin b (amb) treatment of hamsters infected with scrapie strain 263k prolongs the incubation period of the disease, and dissociates in vivo replication of the scrapie agent from prpsc accumulation. we report here o ...	1994	7915757
serial transmission in rodents of neurodegeneration from transgenic mice expressing mutant prion protein.	two lines of transgenic (tg) mice expressing high (h) levels of the mutant p101l prion protein (prp) developed a neurologic illness and central nervous system pathology indistinguishable from experimental murine scrapie; these mice were designated tg(moprp-p101l)h. brain homogenates from tg(moprp-p101l)h mice were inoculated intracerebrally into cd-1 swiss mice, syrian hamsters, and tg196 mice, tg mice expressing the moprp-p101l transgene at low levels. none of the cd-1 mice developed central ne ...	1994	7916462
expression of glial fibrillary acidic protein and glutamine synthetase genes in the natural scrapie of sheep.	gene expression of two astroglial markers, glial fibrillary acidic protein (gfap) and glutamine synthetase (gs), was investigated in cerebellum and brainstem from scrapie-affected sheep. the gfap and gfap-mrna concentrations were increased in the two cerebral regions studied in the scrapie-affected animals as compared to the controls. the good correlation between the increase in gfap and gfap-mrna concentrations found in scrapie-affected sheep indicates a significant de novo synthesis of gfap in ...	1994	7916768
transmissible spongiform encephalopathies or prion disorders--current views.	basic hypotheses concerning nature of an infectious agent of the transmissible spongiform encephalopathies are reported here. the agent may consist of a protein only (prpsc), and for such a molecular structure the term "prion" has been coined. it may consist of a yet-to-be-discovered small oligonucleotide and a shell protein and this is the "virino" concept. or, the agent may be a virus which has still eluded detection. the experiments with transgenic and knock-out mice proved that prpsc is cruc ...	1994	7922109
[risk assessment for importing bovine spongiform encephalopathy (bse)].	since the occurrence of bovine spongiform encephalopathy (bse) in switzerland in 1990, extensive epidemiological investigations and risk factor analyses were carried out. in this study, statistical data on meat and bone meal traded from 1985 to 1989 were analysed addressing the following questions: i) what amount of meat and bone meal was exported from great britain (gb) and where to and ii) what amount of meat and bone meal was imported into switzerland and where from? the findings led to the h ...	1994	7924970
homozygosity for prion protein alleles encoding glutamine-171 renders sheep susceptible to natural scrapie.	natural scrapie has been viewed both as a recessive trait and as a contagious disease modulated by a host locus. to address this conundrum, we determined the structure of the sheep prion protein (prp) gene, which contains three exons and extends over 20 kb of dna. in the united states 86.4% of scrapie cases occur in suffolk sheep, and within this breed 49 +/- 6% (+/- s.d., n = 69) of healthy animals carry one or more prp alleles encoding arg (r)-171. four scrapie-affected sheep were homozygous f ...	1994	7926780
amphotericin b delays both scrapie agent replication and prp-res accumulation early in infection.	amphotericin b delays the onset of clinical symptoms in hamsters infected with scrapie agent strain 263k. here we show that accumulation of a scrapie-specific isoform of the prion protein (prp-res) and agent replication were delayed early in amphotericin b-treated animals. by 8 weeks postinfection, only untreated animals exhibited clinical symptoms of scrapie infection whereas prp-res levels and titers were similar in treated and untreated animals. this suggests that although prp-res accumulatio ...	1994	7933137
small virus-like structure in brains from cases of sporadic and familial creutzfeldt-jakob disease.	we have previously observed small virus-like particles in the brain of hamsters with experimental scrapie. here we report that small virus-like structures can be isolated from brains of patients with creutzfeldt-jakob disease and identified by electronmicroscopy.	1994	7934349
transmission of creutzfeldt-jakob disease from humans to transgenic mice expressing chimeric human-mouse prion protein.	transgenic (tg) mice were constructed that express a chimeric prion protein (prp) in which a segment of mouse (mo) prp was replaced with the corresponding human (hu) prp sequence. the chimeric prp, designated mhu2mprp, differs from moprp by 9 amino acids between residues 96 and 167. all of the tg(mhu2m) mice developed neurologic disease approximately 200 days after inoculation with brain homogenates from three patients dying of creutzfeldt-jakob disease (cjd). inoculation of tg(mhu2m) mice with ...	1994	7937921
effect of infection with the 139h scrapie strain on the number, area and/or location of hypothalamic crf- and vp-immunostained neurons.	scrapie is a transmissible neurodegenerative disease which shares some characteristics with alzheimer disease (ad). recent studies show abnormal enlargement of the adrenal glands and kidneys in 139h-affected hamsters. using immunocytochemical techniques with antibodies to corticotropin-releasing factor (crf) and vasopressin (vp), we observed the following: (1) a significantly higher number of crf-immunostained neurons in the preoptic nucleus of hypothalamus of 139h-affected hamsters than control ...	1994	7941971
detection of prion protein in formalin-fixed brain by hydrated autoclaving immunohistochemistry for the diagnosis of scrapie in sheep.		1994	7948209
bovine spongiform encephalopathy surveillance in argentina.	bovine spongiform encephalopathy (bse) is a new disease of cattle first described in the united kingdom in november 1986. bse belongs to the scrapie-related group of diseases. the epidemiological studies performed in the united kingdom demonstrate that the bse epidemic was caused by feeding cattle with ruminant-derived protein contaminated by a scrapie-like agent. until june 1994, the disease had been detected in indigenous cattle in ireland, switzerland and france. three cases reported in germa ...	1994	7949355
[natural history of transmissible subacute spongiform encephalopathy (tsse)].	sheep scrapie is the archetype of esst it has been described for more than 200 years but the first scientific papers were published less than 60 years ago. the link between doctors and veterinary surgeons enabled our knowledge to develop. first, a slow virus was evoked, then hadlow dvm (usa) suggested using brain filtrates from deceased patients of kuru in order to inoculate primates or small rodents; this was carried out by the team of d.c. gajdusek. the complete absence of immune reaction has ...	1994	7953894
[transmissible animal spongiform encephalopathies].	scrapie in sheep and goats was the first animal spongiform encephalopathy diagnosed. it has since been described in a large number of species (cattle, wild and exotic ruminants, mink, cat). they form an original group of diseases because they are transmissible by a specific pathogen and they depend on the genetic predisposition of the recipient animal. transmission between species and the possibility of oral transmission underline the need to assess the risk to man.	1994	7953895
astrocyte gene expression in experimental mouse scrapie.	the biological hallmark of transmissible spongiform encephalopathies is a significant accumulation, in brain, of the scrapie prion protein (prpsc), often associated with an increased glial fibrillary acidic protein (gfap) expression. this study was focused on astrocyte gene expression during scrapie development over a period of 172 days in intracerebrally inoculated newborn mice. the levels of expression of prp and two specific astrocyte proteins, -gfap and glutamine synthetase (gs)-, were inves ...	1994	7962730
'prion' diseases.		1994	7965986
distinct prp properties suggest the molecular basis of strain variation in transmissible mink encephalopathy.	the molecular basis of strain variation in scrapie diseases is unknown. the only identified component of the agent is the posttranslationally modified host prion protein (prpsc). the biochemical and physical properties of prp from two strains of transmissible mink encephalopathy (tme), called hyper (hy) and drowsy (dy), were compared to investigate if prp heterogeneity could account for strain diversity. the degradation rate of prptme digested with proteinase k was found to be strain specific an ...	1994	7966576
murine scrapie-infected neurons in vivo release excess prion protein into the extracellular space.	an originally heretical proposition that the transmissible spongiform encephalopathies are caused by a host-coded protein (the prion hypothesis) is now current dogma. indeed these disorders are commonly called prion diseases but the prion hypothesis provides no readily acceptable explanation for the source of the informational component of the agent necessary to code for the diversity of strains of scrapie. ultrastructural immunolocalisation of prion protein (prp) in murine scrapie shows that pr ...	1994	7970151
scrapie associated fibrils in found dead sheep.		1994	7975058
neurodegeneration in humans caused by prions.	prion diseases include kuru, creutzfeldt-jakob disease, gerstmann-sträussler-scheinker disease, and fatal familial insomnia of humans as well as scrapie and bovine spongiform encephalopathy of animals. for many years, the prion diseases were thought to be caused by viruses despite evidence to the contrary. the unique characteristic common to all of these disorders, whether sporadic, dominantly inherited, or acquired by infection, is that they involve aberrant metabolism of the prion protein. in ...	1994	7975565
the association of a codon 136 prp gene variant with the occurrence of natural scrapie.	incidence of both experimental and natural scrapie in sheep has been associated with polymorphisms of the prp gene. in case/control studies the prp allele which encodes valine at codon 136 (val136) is found in 96-100% of naturally infected scrapie sheep of shetland, scottish halfbred and blue du maine breeds. in contrast, in healthy animals from the same flocks, the most frequent allele encodes ala136 (91-100% of sheep). however val136 does not correlate with incidence of scrapie in two other fl ...	1994	7979991
capillary electrophoresis of the scrapie prion protein from sheep brain.	scrapie in sheep and goats causes a progressive, degenerative disease of the central nervous system and is the prototype of other transmissible spongiform encephalopathies (tse) found in humans and in animals. in samples of tse-affected brains, unique rod-shaped structures are found and are infectious. these rods are composed of a protease-resistant, post-translationally modified cellular protein (prpsc) that has a molecular mass of ca. 27,000 on sodium dodecyl sulfate-polyacrylamide gel electro ...	1994	7981826
electron microscopic findings in brain of rocky mountain elk with chronic wasting disease.	we report here the electron microscopic findings in brain of rocky mountain elk with chronic wasting disease (cdw), a progressive and fatal neurological disorder of wild ruminants characterized neuropathologically by intraneuronal vacuolation, spongiform change of the neuropil and astrocytic hypertrophy and hyperplasia. ultrastructural findings included membrane-bound vacuoles in neuronal elements, increased number of glial filaments, dystrophic neurites, numerous neuritic plaques, hirano bodies ...	1994	7982031
comment on the paper of h.k. narang. 'evidence that scrapie-associated tubulofilamentous particles contain a single-stranded dna'.		1994	7698886
astroglial reactivity in natural scrapie of sheep.	astrogliosis is known to be a common histological feature in experimental scrapie, but astroglial reactivity in natural scrapie of sheep has not yet been precisely studied. we investigated the expression of two markers of glial plasticity, glial fibrillary acidic protein (gfap) and glutamine synthetase (gs), by western and northern blotting, in different areas of the sheep brain. we report that both gfap-mrna and gfap are overexpressed in the cerebellum and the pons. in the thalamus, overexpress ...	1994	7723656
tubulovesicular structures (tvs): virus-like particles specific for all subacute spongiform virus encephalopathies--what are they really?	tubulovesicular structures (tvs) are virus-like particles specific for all the subacute spongiform virus encephalopathies (ssve). i report here the presence of tvs in the highest range of naturally occurring and experimentally induced ssve studied so far: natural and experimental creutzfeld-jakob disease (cjd), gerstmann-sträussler-scheinker syndrome, natural bovine spongiform encephalopathy (bse) and bse transmitted to pigs and four models of experimental scrapie in hamsters. tvs are spherical ...	1994	7503652
binding of the protease-sensitive form of prp (prion protein) to sulfated glycosaminoglycan and congo red [corrected].	congo red and certain sulfated glycans are potent inhibitors of protease-resistant prp accumulation in scrapie-infected cells. one hypothesis is that these inhibitors act by blocking the association between protease-resistant prp and sulfated glycosaminoglycans or proteoglycans (e.g., heparan sulfate proteoglycan) that is observed in amyloid plaques of scrapie-infected brain tissue. accordingly, we have investigated whether the apparent precursor of protease-resistant prp, protease-sensitive prp ...	1994	7511169
expression of polyubiquitin and heat-shock protein 70 genes increases in the later stages of disease progression in scrapie-infected mouse brain.	we have shown by northern analyses that the expression of the mouse polyubiquitin c gene is increased severalfold in the brains of mice infected with both the me7 and 87v strains of scrapie. expression of the polyubiquitin gene does not change significantly, compared with controls, until the later stages of disease progression when there is a 2.5-fold increase in me7-infected brains and a 1.8-fold increase in 87v-infected brains. the patterns of changes of expression of the polyubiquitin genes i ...	1994	7512619
rapid anterograde axonal transport of the cellular prion glycoprotein in the peripheral and central nervous systems.	in prion diseases, the cellular prion protein (prpc), abundant in neurons, is converted posttranslationally into an amyloid-forming scrapie prion protein (prpsc), which accumulates in white matter tracts and nerve terminals. the trafficking of prpc in neurons was investigated in vivo by injecting [35s]methionine into the l4 and l5 dorsal root ganglia and the entorhinal cortices of adult rats and by tracing the movement of radiolabeled prpc. in both paradigms, labeled 33-35-kda prpc was transport ...	1994	7514179
the puzzle of prpsc and infectivity--do the pieces fit?		1994	7517592
the major species specific epitope in prion proteins of ruminants.	the species specific nature of an antigenic determinant previously discovered in the scrapie form of prion protein (prpd) from cattle, sheep and mice, was further investigated in normal prion protein (prpc) from these and other species. this was carried out with eight different anti-peptide sera raised in rabbits against various synthetic peptides representing segments of the amino acid (aa) sequence 101-122 of ovine, bovine, murine and hamster prp. antipeptide serum against a peptide representi ...	1994	7518226
neurophysiological follow-up in two children with creutzfeldt-jakob disease after human growth hormone treatment.	a serial neurophysiological study has been performed of 2 children during the clinical course of creutzfeldt-jakob disease after human growth hormone (hgh) treatment. evolution of the eeg pattern was typical: slow waves, periodic sharp wave complexes, then extinction. vep components were moderately altered. baers performed in only 1 child were normal. the blink reflex (br) showed an early alteration of the r1 component. the erg exhibited early and profound anomalies. pathological changes were ob ...	1994	7519139
transmissible cerebral amyloidoses as a model for alzheimer's disease. an ultrastructural perspective.	alzheimer's disease, a prototypic nontransmissible cerebral amyloidosis, has no adequate experimental model. several pathogenetic events, however, may be modeled and accurately studied in the transmissible cerebral amyloidoses of kuru, creutzfeldt-jakob disease, gerstmann-sträussler-scheinker disease, and scrapie. the common neuropathological denominator in both types of cerebral amyloidoses is the presence of stellate kuru plaques, senile plaques, and pure neuritic plaques. these amyloid plaque ...	1994	7522013
insights into the role of the immune system in prion diseases.		1994	7904753
[scrapie from the clinical aspect].	the first cases of scrapie in the federal republic of germany since 1945 occurred in 1990 and 1991. the disease was found in three flocks of suffolk sheep and it was probably brought to germany by breeding sheep from france. scrapie is a transmissible degenerative disease of the central nervous system with a slowly progressing but always fatal course. the scrapie agent is highly resistant against environmental influences as well as against disinfectants. incubation period and clinical signs of s ...	1994	8209358
morphogenesis of amyloid plaques in 87v murine scrapie.	amyloid plaques of scrapie-infected mouse brains are composed of fibrillar forms of a host coded, cell surface sialoglycoprotein called prp (prion protein). serial ultrastructural immunogold staining was performed on plaques identified by light microscopic immunocytochemistry of brains of vm mice infected with the 87v strain of scrapie. classical plaques, of a kuru-type morphology, were composed of a central core of bundles of amyloid fibrils. amyloid fibrils of classical plaques were immunoreac ...	1994	7898615
high prion and prpsc levels but delayed onset of disease in scrapie-inoculated mice heterozygous for a disrupted prp gene.	it has been proposed that the prion, the infectious agent of transmissible spongiform encephalopathies, is prpsc, a post-translationally modified form of the normal host protein prpc. we showed previously that mice devoid of prpc (prn-p0/0) are completely resistant to scrapie. we now report on the unexpected response of heterozygous (prn-p0/+) mice to scrapie infection.	1994	8790598
scrapie infection of transgenic mice leads to network and intrinsic dysfunction of cortical and hippocampal neurones.	the human prion encephalopathy creutzfeldt-jakob disease often is manifest as rapidly progressing dementia with myoclonus and synchronous, periodic discharges. to investigate the electrophysiology of prion disease we used intra- and extra-cellular recordings from brain slices from tg(shaprp+/+) 81 mice, which express syrian hamster prion protein and which are susceptible to hamster-passaged scrapie isolates. forty days after intracerebral inoculation with scrapie isolate sc237, we recorded prolo ...	1994	9216983
scrapie prions: a three-dimensional model of an infectious fragment.	backgound. a conformational change seems to represent the major difference between the scrapie prion protein (prpsc) and its normal cellular isoform (prpc). we recently proposed a set of four helix bundle models for the three-dimensional structure of prpc that are consistent with a variety of spectroscopic and genetic data. results. we report a plausible model for the three-dimensional structure of a biologically important fragment of prpsc. the model of residues 108-218 was constructed by an ap ...	1995	9162135
the chemistry of scrapie infection: implications of the 'ice 9' metaphor.	the transmissible spongiform encephalopathies pose an increasing problem for animal, and perhaps human, health. the infectious agent seems to lack a nucleic acid component, posing the question of how it can reproduce. a model of reproduction by nucleated polymerization suggests a number of novel approaches to the problem.	1995	9383397
the core alzheimer's peptide nac forms amyloid fibrils which seed and are seeded by beta-amyloid: is nac a common trigger or target in neurodegenerative disease?	nac is a 35-amino-acid peptide which has been isolated from the insoluble core of alzheimer's disease (ad) amyloid plaque. it is a fragment of alpha-synuclein (or nacp), a neuronal protein of unknown function. we noted a striking sequence similarity between nac, the carboxyl terminus of the beta-amyloid protein, and a region of the scrapie prion protein (prp) which has been implicated in amyloid formation.	1995	9383418
theoretical studies of sequence effects on the conformational properties of a fragment of the prion protein: implications for scrapie formation.	prion diseases are neurodegenerative disorders that appear to be due to a conformational change, involving the conversion of alpha-helices in the normal, cellular isoform of the prion protein (prpc) to beta-structure in the infectious scrapie form (prpsc). one form of gerstmann-sträussler-scheinker syndrome (gss), an inherited prion disease, is caused by mutation of ala117 of prpc to val. we therefore set out to evaluate the effects of this mutation on the stability of the prpc form.	1995	9383432
analysis of prpc mrna by in situ hybridization in brain, placenta, uterus and testis of rats.	an amyloid-like isoform of a 33- to 34-kd glycoprotein, termed as the scrapie prion protein (prpsc), plays a critical role in transmissible spongiform encephalopathies of animals and humans. it has even been suggested to present the responsible infectious agent. this protein is a posttranslationally modified form of the cellular isoform of prion protein (prpc). hitherto, little has been known about the functions of prpc. in order to examine the localization of prpc mrna in rat tissues, the in si ...	1995	8880380
[psi] and [ure3] as yeast prions.	[ure3] is a non-mendelian genetic element that mimics recessive mutations in the chromosomal ure2 gene making cells derepressed for nitrogen catabolic enzymes. [psi] is a non-mendelian enhancer of readthrough of translational termination similar in its effects to some mutations in the chromosomal sup35 gene. three lines of evidence led to the proposal that both [ure3] and [psi] are prions, infectious proteins analogous to the scrapie agent mediating transmissible spongiform encephalopathies of m ...	1995	8720070
aggregates of scrapie-associated prion protein induce the cell-free conversion of protease-sensitive prion protein to the protease-resistant state.	scrapie infection instigates the in vivo conversion of normal, protease-sensitive prion protein (prpc) into a protease-resistant form (prpsc) by an unknown mechanism. in vitro studies have indicated that prpsc can induce this conversion, consistent with proposals that prpsc itself might be the infectious scrapie agent. using this cell-free model of the prpc to prpsc conversion, we have studied the dependence of conversion on reactant concentration, and the properties of the prpsc-derived species ...	1995	8807814
patch-clamp analysis of synaptic transmission to cerebellar purkinje cells of prion protein knockout mice.	the prion protein (prp) plays a pivotal role in transmissible spongiform encephalopathies such as creutzfeldt-jakob disease in humans and scrapie and bovine spongiform encephalopathy in animals. previous experiments have suggested that the normal cellular prion protein (prpc) is involved in synaptic function in the hippocampus. here, we utilized the controlled recording conditions of the patch-clamp technique to investigate the synaptic function of prion protein in cerebellar purkinje cells. by ...	1995	8845956
neuropathological diagnostic criteria for creutzfeldt-jakob disease (cjd) and other human spongiform encephalopathies (prion diseases).	neuropathological diagnostic criteria for creutzfeldt-jakob disease (cjd) and other human transmissible spongiform encephalopathies (prion diseases) are proposed for the following disease entities: cjd--sporadic, iatrogenic (recognised risk) or familial (same disease in 1st degree relative): spongiform encephalopathy in cerebral and/or cerebellar cortex and/or subcortical grey matter; or encephalopathy with prion protein (prp) immunoreactivity (plaque and/or diffuse synaptic and/or patchy/periva ...	1995	8974629
the pathological changes in peripheral organs of scrapie-infected animals.	scrapie is an unconventional neurodegenerative disease in sheep and goats that has been known in europe for over 260 years. the scrapie agents affect the brain and are transmissible from animal to animal. key features of scrapie infections are abnormal behavior and deficits in motor function. these clinical findings can be related to the damage found in the central nervous system. in some scrapie strain-host model systems there are other manifestations of disease that appear to be related to pat ...	1995	8574018
inactivation of the bovine spongiform encephalopathy agent by rendering procedures.	bovine brain infected with the bovine spongiform encephalopathy (bse) agent was used to spike material processed in pilot scale facsimiles of 12 rendering processes which are used within the european union, and three which are not. the raw materials for experimental rendering represented those used in practice, and consisted of appropriate proportions of bse-infected brain tissue, bovine or porcine intestine, and bovine bone. meat and bone meal, and tallow were produced from the rendered tissues ...	1995	8746849
[importance of genetic factors in pathogenesis of subacute spongiform viral encephalitis].	recently there has been achieved a substantial progress in research concerning pathogenesis of subacute spongiform viral encephalopathies. for this group of disorders, there has been found a common unconventional virus - proteinaceous infectious particle (prp). there has been recognised a molecular mass, biochemical composition and physicochemical properties of this infectious form. mutations of scrapie amyloid precursor gene discovered in gerstmann-sträussler-scheinker syndrome (gss) and famili ...	1995	8657630
unaltered susceptibility to bse in transgenic mice expressing human prion protein.	prion diseases are transmissible neurodegenerative conditions of humans and animals. prions consist principally of a post-translationally modified form of prion protein (prp), prp(sc), which is partly protease resistant. transmission of prion diseases between species is limited by a 'species barrier' determined in part by the degree of sequence homology between host prp and inoculated prp(sc) (ref.3) and by prion strain type. the epidemic of bovine spongiform encephalopathy (bse) in the united k ...	1995	8524411
sulfated glycans stimulate endocytosis of the cellular isoform of the prion protein, prpc, in cultured cells.	there is currently no effective therapy for human prion diseases. however, several polyanionic glycans, including pentosan sulfate and dextran sulfate, prolong the incubation time of scrapie in rodents, and inhibit the production of the scrapie isoform of the prion protein (prpsc), the major component of infectious prions, in cultured neuroblastoma cells. we report here that pentosan sulfate and related compounds rapidly and dramatically reduce the amount of prpc, the non-infectious precursor of ...	1995	8530433
the 'infective' process in scrapie and human spongiform encephalopathy disease.	it is suggested that spongiform encephalopathy (se) disease transmission does not occur by any classically defined 'infective' process. rather, it is the case that conformationally altered prions in diseased animals are able, by targeting what may be an inherited, widely distributed, endogenous retroviral fragment, comprising the prion 'gene' system, to initiate the escalating synthesis of similar, but host-specified protein. both initiation and the resulting progression are controlled and regul ...	1995	8531845
detection of apoptosis in murine scrapie.	in order to determine whether apoptosis contributes to the neuronal loss in scrapie, in situ end labeling was applied on brains of mice showing clinical signs of the disease. positively labeled, apoptotic neurons were observed in the cerebellum, cerebral cortex and hippocampus, areas known to show characteristic scrapie-related vacuolation, and were absent in the brains of control mice. we conclude that apoptosis plays a role in the neuronal loss that occurs in scrapie. the importance of apoptos ...	1995	8552317
"tubulofilamentous particles" are not scrapie-specific and are unrelated to tubulovesicular structures.	"tubulofilamentous particles" has been defined as "thick" tubules, apparently distinguishable from other cytoskeletal elements, in touch-preparations from scrapie- and creutzfeldt-jakob disease (cjd)-infected brains. i report here that "tubulofilamentous particles" are nonspecific findings unrelated to "tubulovesicular structures" (tvs) which are the only particles consistently observed in brains of naturally occurring and experimentally induced ssve.	1995	8553908
comparative study of electron microscopical techniques for the detection of scrapie-associated fibrils.	samples of cervical spinal cord and four anatomical regions of the brains of 12 sheep with natural scrapie and six control sheep were examined by electron microscopy, after the tissues had been stored at 4 degrees c and -20 degrees c. the tissues were tested for the presence of scrapie-associated fibrils by a centrifugal extraction technique and by a touch-grid technique. the touch-grid technique was no better than the centrifugal extraction technique for the detection of fibrils. structures whi ...	1995	8588101
experimental infection of cattle with the agents of transmissible mink encephalopathy and scrapie.	cattle are susceptible to experimental infection with the stetsonville isolate of the transmissible mink encephalopathy (tme) agent. to determine if they are susceptible to other tme isolates, two groups of calves were inoculated intracerebrally with homogenate of mink brain containing the hayward isolate or the blackfoot isolate. for comparison, a third group was inoculated with a brain homogenate from a steer infected with the stetsonville isolate in its primary cattle passage and a fourth gro ...	1995	8592050
ms-8209, a new amphotericin b derivative, provides enhanced efficacy in delaying hamster scrapie.	to test the efficacy of a new amphotericin b derivative, ms-8209, in delaying scrapie, hamsters were infected intracerebrally with the 263k scrapie agent and treated with ms-8209 either early in the course of the disease or continuously. the results show that (i) all treatments lengthened the incubation period of hamster scrapie, (ii) continuous treatment with ms-8209 doubled the length of the incubation period compared with that observed in infected, untreated animals, and (iii) all treatments ...	1995	8593027
in situ hybridization and immunohistochemistry for prion protein (prp) in bovine spongiform encephalopathy (bse).	in about 5% of the cows showing clinical signs of bovine spongiform encephalopathy (bse) the histopathological examination is not conclusive. in order to rule out bse in these cases, additional methods are necessary. for that reason, non-radioactive in situ hybridization (ish) was performed using a riboprobe against the messenger rna coding for the prion protein (prp). in addition, a polyclonal antibody for immunohistochemistry (ihc) was generated against a synthetic peptide derived from bovine ...	1995	8594839
neuronal cell death in scrapie-infected mice is due to apoptosis.	neuronal loss is a salient yet poorly understood feature in the pathology of transmissible spongiform encephalopathies (prion diseases). cell culture experiments with neurotoxic prion protein fragments suggest that neuronal cell death in these diseases may be due to apoptosis. to test this hypothesis in vivo we used the in situ end-labeling (isel) technique and electron microscopy to study cell death in an experimental scrapie system in the mouse. isel, which relies on the incorporation of label ...	1995	8520720
preparation and characterization of antibodies against mouse prion protein (prp) peptides.	antisera were raised in rabbits against three peptides, representing amino acid sequences 150 to 159, 165 to 174, and 213 to 226 of mouse prion (prp), which were synthesized by using a multiple antigenic peptide (map) system. the reactivities of these sera to prp were examined by an enzyme-linked immunosorbent assay (elisa), western immunoblotting (wb), and immunohistochemical procedures. the results of both elisa and wb showed that antisera to peptide sequence 150 to 159 (ab150-159) did not rea ...	1995	7535178
conformational transitions in peptides containing two putative alpha-helices of the prion protein.	prions are composed largely, if not entirely, of the scrapie isoform of the prion protein (prpsc). conversion of the cellular isoform (prpc) to prpsc is accompanied by a diminution in the alpha-helical content and an increase in the beta-sheet structure. to investigate the structural basis of this transition, peptide fragments corresponding to syrian hamster prp residues 90 to 145 and 109 to 141, which contain the most conserved residues of the prion protein and the first two putative alpha-heli ...	1995	7542350
altered gaba distribution in hamster brain is an early molecular consequence of infection by scrapie prions.	antibodies specific for gaba, glutamate and taurine were used to study the distribution of these amino acid neurotransmitters during the progression of scrapie in hamsters. immunohistochemical distribution of glutamate and taurine were unaffected in scrapie hamsters compared with controls, but the distribution of gaba was altered by 21 days after inoculation. we found both a greater number of neurons showing gaba-like immunoreactivity and more intense staining in those neurons in scrapie-inocula ...	1995	7552289
neuroaxonal dystrophy in experimental creutzfeldt-jakob disease: electron microscopical and immunohistochemical demonstration of neurofilament accumulations within affected neurites.	neuroaxonal dystrophy is a feature of neuronal degeneration encountered in all subacute spongiform "virus" encephalopathies, including scrapie and creutzfeldt-jakob disease (cjd). by immunohistochemical techniques, the accumulation of 200 kda neurofilament protein was demonstrated in affected neurites in murine cjd. these neurites exhibited the ultrastructural features of dystrophic neurites encountered in other neurodegenerative disorders, particularly alzheimer's disease. these findings suppor ...	1995	7560300
the abnormal isoform of the prion protein accumulates in late-endosome-like organelles in scrapie-infected mouse brain.	the prion encephalopathies are characterized by accumulation in the brain of the abnormal form prpsc of a normal host gene product prpc. the mechanism and site of formation of prpsc from prpc are currently unknown. in this study, me7 scrapie-infected mouse brain was used to show, both biochemically and by double-labelled immunogold electron microscopy, that proteinase k-resistant prpsc is enriched in subcellular structures which contain the cation-independent mannose 6-phosphate receptor, ubiqui ...	1995	7562256
x-ray diffraction of scrapie prion rods and prp peptides.	certain neurodegenerative diseases in humans and animals are caused by small proteinaceous infectious particles called prions. limited proteolysis and detergent extraction of the prions containing prpsc generate prion rods that are composed of a polypeptide having an apparent molecular mass of 27 to 30 kda. this polypeptide, termed prion protein prp 27-30, has a ragged n terminus that begins at about residue 90, but retains scrapie infectivity. moreover, the findings in a patient having an inher ...	1995	7563061
reflections on scrapie and related disorders, with consideration of the possibility of a viral aetiology.	the transmissible spongiform encephalopathies of domesticated animals, scrapie in sheep and bovine spongiform encephalopathy (bse), and transmissible mink encephalopathy are more than a scientific curiosity; under certain circumstances their impact on commercial activities can be calamitous. knowledge of their causation and pathogenesis is still rudimentary, but many consider than an unconventional agent, the prion (a brain protein, prp), that is not associated with nucleic acid is involved in b ...	1995	7571397
neuron-specific expression of a hamster prion protein minigene in transgenic mice induces susceptibility to hamster scrapie agent.	to study the effect of cell type-restricted hamster prp expression on susceptibility to the hamster scrapie agent, we generated transgenic mice using a 1 kb hamster cdna clone containing the 0.76 kb hprp open reading frame under control of the neuron-specific enolase promoter. in these mice, expression of hprp was detected only in brain tissue, with highest levels found in neurons of the cerebellum, hippocampus, thalamus, and cerebral cortex. these transgenic mice were susceptible to infection b ...	1995	7576660
the myth of maternal transmission of spongiform encephalopathy.	it has long been accepted that the pattern of occurrence of scrapie--the form of spongiform encephalopathy associated with sheep--is determined mainly by maternal transmission, and this view has had a profound influence on policy decisions in the control of bovine spongiform encephalopathy and on public concern over the risk to human health form this disease. the occurrence of maternal transmission is, however, not predicted by modern knowledge of the aetiology of spongiform encephalopathy, and ...	1995	7580668