Publications

scrapie incubation time can exceed natural lifespan.		1975	807857
[slow virus infections].		1975	809761
isolation of 14-nm virus-like particles from mouse brain infected with scrapie agent.		1975	810725
the effect of homogenisation on the level of scrapie activity detected in cells from spleens of scrapie affected mice.	suspensions of cells from the spleens of mice inoculated with scrapie agent were titrated for scrapie activity at two stages, before and after disruption to release activity. similarity between the titres obtained from the two types of suspension provided evidence to support the suggestion that there is one unit of activity per affected cell and that multiplication of scrapie agent is associated with cell replication.	1976	815976
partial purification of the scrapie agent from mouse brain by pressure disruption and zonal centrifugation in sucrose-sodium chloride gradients.		1976	816078
introduction to the scrapie diseases: self-replicating agents surviving standard autoclaving for an hour and 10% formalin for a year.		1976	817091
infection of a cell line of mouse l fibroblasts with scrapie agent.		1976	818568
a small virus-like agent found in association with multiple sclerosis material.		1976	818577
[a study of the agent of scrapie adapted to hamsters].	the scraepie agent (compton strain) proved to be transmitted frrom mice to hamsters; incubation period of the disease was 5 to 6 months. the scraepie agent was passaged ten times with brain tissue suspension. the scraepie agent was revealed in the spinal cord and spleen, but none was found in the liver, kidneys, suprarenal glands and the lungs of infected animals during the last stage of the disease.	1976	819061
the membrane location of scrapie infectivity.	using 5'-nucleotidase and nadph: cytochrome c reductase as respective enzyme markers for the plasma membrane and endoplasmic reticulum, a satisfactory separation of these two membrane fractions from a cell line (smb) derived from a scrapie mouse brain has been achieved. the coincident distribution of scrapie infectivity and 5'-nucleotidase in various fractions isolated from these cells indicates that most of the scrapie infectivity present in this cell line is associated with the plasma membrane ...	1976	819627
scrapie in vitro: agent replication and reduced cell yield.	exposure of pam cells, a spontaneously transformed mouse cell line, to brain homogenates from mice infected with scrapie caused a relative decrease in total cell yield, which persisted from passage 2 or 3 to passage 18 after treatment. the effect was elicited by each of the eight independent scrapie isolates tested. lysates prepared from cultures 16 passages after treatment with scrapie caused the decrease when applied to fresh pam cultures. mice inoculated with passage 14 and 18 lysates develop ...	1976	820640
the effects of cuprizone toxicity on the incubation period of scrapie in mice.		1976	820729
the fate of me7 scrapie infection in rats, guinea-pigs and rabbits.	the fate of an intracerebral injection of me7 scrapie has been followed in groups of rats, guinea-pigs and rabbits. six days after injection scrapie activity in the brain was similar in all three species and low levels of activity were also present in rat and guinea-pig spleen. thereafter in the rat the pattern of accumulation of scrapie agent in brain and spleen resembled that frequently described in mice, the disease becoming clinically manifest 20 months after injection. in guinea-pig and rab ...	1976	821118
scrapie in sheep and goats.		1976	821790
the pathogenesis of scrapie in mice.		1976	821791
is the scrapie agent a virus?		1976	822341
experimental scrapie in the mouse: a review of an important model disease.		1976	823641
search for scrapie-specific rna and attempts to detect an infectious dna or rna.	preparations of in vivo labelled rna from normal and scrapie infected mouse brains were fractionated by polyacrylamide gel electrophoresis. no appreciable differences were detected between the two preparations. the biological activity of preparations of rna and dna from scrapie brain was also examined. in each case the nucleic acid was obtained by one method envolving the use of phenol and one without phenol. attempts were made to bind the nucleic acid to normal membrane by three different metho ...	1976	828199
scrapie: a review of its relation to human disease and ageing.		1976	828205
nucleic acids associated with detergent-treated synaptosomal plasma membranes from normal and scrapie-infected mouse brain.		1976	828592
changes in a protein-nucleic acid complex from synaptic plasma membrane of scrapie-infected mouse brain.		1976	828593
an investigation of the macrophage electrophoretic mobility test in the diagnosis of scrapie in sheep.		1977	858810
profiles of brain glycosidase activity in cuprizone-fed syrian hamsters and in scrapie-affected mice, rats, chinese hamsters and syrian hamsters.		1976	943426
[some forms of disease associated with impaired locomotion in sheep (author's transl)].	a number of flock diseases in sheep associated with impaired locomotion, which are of importance or may assume importance in the netherlands, are reviewed. attention is paid to the following metabolic disorders and deficiencies: acetonaemia, hypocalcaemia, hypomagnesaemia, some forms of osteopathy, enzootic ataxia and cerebrocortical necrosis. the following forms of infectious diseases are described: listeric encephalitis, purulent meningitis following injury to the throat, scrapie, visna, aujes ...	1976	960067
motor activity changes in scrapie-affected mice.	measurements of spontaneous motor activity using animex equipment have been made throughout the incubation period in mice developing scrapie. a progressive fall in activity has been noted from an early stage in the disease process well before clinical signs of scrapie were evident. the initial fall was followed by an upsurge in activity at about the time when clinical signs of disease develop.	1976	1034481
polyadenylated ribonucleic acid in normal and scrapie-infected mouse brain.		1976	1035555
progress in the scrapie eradication program.		1976	1078087
pathology of dendrites in subacute spongiform virus encephalopathies.	the spongiform changes in the cerebral cortex of scrapie mice and of chimpanzees afflicted with experimental kuru and creutzfeldt-jakob disease were examined by electron microscopy. the pathognomonic findings consisted of swelling and vacuolation of neurons, particularly of dendrites. fusion of swollen cells and processes occurred. the changes were associated with alterations of plasma membranes. curled fragments of membranes accumulated at points of cell fusion and at the margin of vacuoles wit ...	1975	1098420
cucumber shaped and 35 nm particles in creutzfeldt-jakob disease.	a 63 year old female with the ataxic form of creutzfeldt-jakob disease (cjd) is presented. in addition to amyloid plaques which were not associated with alzheimer's neurofibrillary tangles, rare profiles similar to those reported in scrapie were also seen. to our knowledge, these profiles have never been observed in cjd and their presence in this condition adds a further morphologic similarity between the human and animal forms of subacute spongiform "viral" encephalopathies.	1975	1100214
[slow virus infections of the central nervous system: a concept of a slow cell death (author's transl)].		1975	1107212
comparison of scrapie and transmissible mink encephalopathy in hamsters. ii. clinical signs, pathology, and pathogenesis.	scrapie and transmissible mink encephalopathy were studied in hamsters; clinical signs, pathology, and the replication of the agents of each disease in brain and spleen were compared. the most noticeable clinical sign in scrapie-affected hamsters was a distinct cerebellar ataxia beginning 16 weeks after inoculation. ataxia was not prominent in animals affected with transmissible mink encephalopathy; these animals gradually became more and more lethargic. the pathology in the central nervous syst ...	1975	1167884
comparison of scrapie and transmissible mink encephalopathy in hamsters. i. biochemical studies of brain during development of disease.	a series of 15 different biochemical measurements were made on brains taken at stages throughout the development of scrapie and of transmissible mink encephalopathy in hamsters. with both diseases biochemical abnormalities were found only after the development of early histologic lesions, when animals showed clinical signs of disease. changes were recorded in body weight, in the activities of six glycosidases, and the rates of incorporation of dna and of glycoprotein precursors. the profiles of ...	1975	1167887
[case of scrapie in a goat].		1975	1168094
multiple sclerosis: relation to scrapie and slow infection; ageing and measles.	multiple sclerosis (ms) is shown to have no relation to scrapie and the evidence for a "slow infective" aetiology is very meagre. it is not related to an ageing process during which scrapie-like antigens make their appearance as they do in young animal with the disease. the emergence of scrapie-like antigens in ageing tissues is discussed. the increased sensitization of ms lymphocytes to scrapie, as opposed to normal brain (or spleen), is not characteristic of the disease, but occurs in other co ...	1975	1217459
transferrin polymorphism in herdwick sheep.	the transferrin system in herdwick sheep, bred at compton, was investigated with special reference to the susceptibility of the flock to experimentally produced scrapie. no significant correlations were observed between susceptibility and transferrin phenotypes.	1975	1217754
infectious etiology of neuritic (senile) plaques in mice.	brains of inbred female vm mice infected with scrapie agent were studied with the use of the bodian silver impregnation method and by electron microscopy. in brains affected with scrapie, after an incubation period of between 587 and 655 days, numerous primitive, classical, and amyloid plaques were found. no plaques of any type were seen in the control mice.	1975	1237933
feline spongiform encephalopathy: fibril and prp studies.	the brains from 18 cats were examined for the presence of the fibrils and modified prp protein which are molecular diagnostic markers for scrapie-like diseases. thirteen cats were referred with clinical neurological signs potentially indicative of feline spongiform encephalopathy (fse). of these, five had histopathological changes of fse, five had other lesions of the central nervous system, and in three the brain was normal. the remaining five cats had no clinical neurological signs and were se ...	1992	1279883
[prion encephalopathies].	spongiform encephalopathies, also called prion encephalopathies, are characterized, in human as well as in animals, by (1) their clinical picture which indicates strict localisation in central nervous system, (2) their histological aspect: spongiform degeneration and neuronal loss, and (3) their transmissibility in the same animal species but also from man to animal. the nature of the pathogenic agent is still debated. this agent could be one isoform of the prion protein which, probably because ...	1992	1288542
new insight into the nature of scrapie from old radiation results.		1992	1290682
[human transmissible dementia: prion diseases?].	subacute transmissible spongiform encephalopathies (stse) represent a cause of presenile dementias, found in man (creutzfeldt-jakob disease, gerstmann-straussler syndrome, kuru), in sheep and goats (scrapie), in cattle (bovine spongiform encephalopathy) and in various mammals. it seems that the frequency of the human spongiform encephalopathy (hse) is more frequent than thought up to now and an alimentary origin is not to be discarded. many discussions are held concerning the nature of the trans ...	1992	1300226
immunoreactivity to ubiquitin-protein conjugates is present early in the disease process in the brains of scrapie-infected mice.	brains from mice infected with either the 87v or the me7 strains of mouse-passaged sheep scrapie were taken at stages during the disease process and immunostained to show the localization of ubiquitin-protein conjugates. in both models, conjugates were seen as fine, dot-like structures; as coarser, granular lesions within or adjacent to neurones; and in areas surrounding plaques. the dot-like structures were visible at 28 days post-me7 infection and at 55 days in 87v-infected mice. in both model ...	1992	1334140
scrapie-associated tubulofilamentous particles in scrapie hamsters.	examination of thin sections from the cerebral cortex of scrapie-infected hamster brains revealed characteristic circular 26-30 nm diameter tubulofilamentous particles, identical to those previously described in both experimentally induced scrapie in mice, hamsters and natural scrapie of sheep, bovine spongiform encephalopathy and human creutzfeldt-jakob disease and mice and chimpanzees infected with creutzfeldt-jakob disease. longitudinal forms of tubulofilamentous particles were also observed ...	1992	1338060
chimeric prion protein expression in cultured cells and transgenic mice.	the efficient expression of exogenous prion protein (prp) molecules in mouse neuroblastoma cells that are chronically infected with murine scrapie prions (scn2a cells; butler, d.a., et al., 1988, j. virol. 62, 1558-1564) and in transgenic mice is described. this technology allows investigation of the prp molecule for structural regions involved in determining species specificity, as well as ablation experiments designed to address the functionality of particular regions of the prp molecule. prev ...	1992	1338978
creutzfeldt-jakob disease with tubulovesicular structures: an ultrastructural study.	tubulovesicular structures (tvs) have been consistently observed in brain tissue of the transmissible spongiform virus encephalopathies such as natural and experimental scrapie, bovine spongiform encephalopathy and experimentally induced creutzfeldt-jakob disease (cjd). tvs were recently demonstrated in 3 cases of naturally occurring cjd. we report here the presence of tvs in another human brain with cjd, as detected in all 3 specimens by thin section electron microscopy. their occurrence in all ...	1992	1340922
nearly ubiquitous tissue distribution of the scrapie agent precursor protein.	the "modified host protein" model of scrapie proposes that the transmissible agent is composed of the degradation-resistant protein, sp33-37, and that clinical and pathologic signs result from neurotoxic accumulations of this protein. sp33-37 is an abnormal, amyloidogenic isoform of the normally occurring cellular protein cp33-37. this study investigated the tissue distribution of cp33-37 in hamster. in brain, cp33-37 was most concentrated in the hippocampal formation. immunohistochemical studie ...	1992	1346470
biochemical and physical properties of the prion protein from two strains of the transmissible mink encephalopathy agent.	transmissible mink encephalopathy (tme) has been transmitted to syrian golden hamsters, and two strains of the causative agent, hyper (hy) and drowsy (dy), have been identified that have different biological properties. during scrapie, a tme-like disease, an endogenous cellular protein, the prion protein (prpc), is modified (to prpsc) and accumulates in the brain. prpsc is partially resistant to proteases and is claimed to be an essential component of the infectious agent. purification and analy ...	1992	1347795
recommendations of the international roundtable workshop on bovine spongiform encephalopathy.	recommendations of the working party were summarized as follows: determine the status in all countries of their national cattle herds with respect to bse. attempt to develop a test to recognize bse-infected animals before they become clinically ill. establish procedures to prevent spread of bse agent into the cattle populations, especially by eliminating feeds containing rendered ruminant proteins. review the rendering processes, identify the sources and destinations of rendered products, and su ...	1992	1348501
spongiform encephalopathies. prp and the scrapie agent.		1992	1348569
amphotericin b treatment dissociates in vivo replication of the scrapie agent from prp accumulation.	scrapie and related animal and human disorders are neurodegenerative diseases characterized by the formation of a modified, partly proteinase-resistant protein (prp) of the host, which tends to aggregate as amyloid fibrils and accumulate in the brain of infected individuals. there is a general consensus that the pathological form of prp (prpsc) is essential for the clinical appearance of the disease, but whether it is part of the scrapie agent or a by-product of viral infection is still controve ...	1992	1348570
studies on maternal transmission of scrapie in sheep by embryo transfer.	the technique of embryo transfer was used to investigate the maternal transmission of scrapie in sheep. embryo donor ewes were experimentally infected with scrapie (all eventually developing the disease) and artificially inseminated six months later with semen from an uninfected scrapie-susceptible ram. embryos were harvested five and six days after insemination and transferred by laparoscopy, unwashed, into recipient ewes which had been genetically selected for very low susceptibility to scrapi ...	1992	1350694
glycosylinositol phospholipid anchors of the scrapie and cellular prion proteins contain sialic acid.	the only identified component of the scrapie prion is prpsc, a glycosylinositol phospholipid (gpi)-linked protein that is derived from the cellular isoform (prpc) by an as yet unknown posttranslational event. analysis of the prpsc gpi has revealed six different glycoforms, three of which are unprecedented. two of the glycoforms contain n-acetylneuraminic acid, which has not been previously reported as a component of any gpi. the largest form of the gpi is proposed to have a glycan core consistin ...	1992	1350920
natural scrapie in british sheep: breeds, ages and prp gene polymorphisms.	one hundred and sixty-seven sheep of 32 breeds and crossbreeds affected by natural scrapie throughout britain were tested for the presence of restriction fragment length polymorphisms of the prp gene observed when their dna was digested with ecori or hindiii. these polymorphisms have already been associated with different susceptibilities to experimental scrapie (controlled by alleles of the sip gene) in a flock of cheviot sheep. in two studies 86 to 92 per cent of the sheep were found to carry ...	1992	1351694
accumulation of transcripts coding for prion protein in human astrocytes during infection with human immunodeficiency virus.	the abnormal isoforms of the normal cellular prion protein (prp), also termed scrapie-associated fibril protein, are assumed to be one causative factor of spongiform encephalopathies. the mrna of prp contains stem-loop structures which are very similar to the human immunodeficiency virus-1 (hiv-1) cis-acting sequence tar within the ltr; both structures contain the pentanucleotide cuggg in the loop, and the uridine- and adenine-bulge in the stem. in this study, using purified hiv-encoded trans-ac ...	1992	1351748
molecular biology of scrapie-like agents.	a detailed account is given of the nature of the causal agent of scrapie and other transmissible spongiform encephalopathies, with reference to proteinase-resistant protein and its gene, subviral particles and the prion hypothesis.	1992	1352155
biological activity of subfractions from scrapie-associated fibrils.	subfractions, a nucleic acid fraction and a prp fraction consisting of prp17-25, a core fragment of prpsc, were prepared from the scrapie-associated fibril-enriched fraction from scapie-affected mouse brains. the nucleic acid fraction consisted mainly of variously fragmented dna and no scrapie-specific nucleic acid was detected in the fraction by sds polyacrylamide gel electrophoresis. to examine the biological activity, the nucleic acid fraction was either first introduced into mouse l-929 cell ...	1992	1352653
diagnostic implications of detection of proteinase k-resistant protein in spleen, lymph nodes, and brain of sheep.	brain, spleen, and selected lymph nodes from sheep with clinical signs of scrapie were analyzed for presence of proteinase k-resistant protein (prp-res). diagnosis of scrapie on the basis of detection of prp-res was compared with diagnosis on the basis of histologic evaluation of the brain from clinically affected or exposed sheep. proteinase k-resistant protein was found in every brain that was histologically positive for scrapie, and in addition, was found in the brain of several clinically po ...	1992	1352664
variations in prion protein and glial fibrillary acidic protein mrnas in the brain of scrapie-infected newborn mouse.	to begin to understand the molecular basis of cases of creutzfeldt-jakob disease recently described in young children, the expression of prion protein and glial fibrillary acidic protein (gfap) mrnas was investigated during the development of the brain of scrapie-infected newborn mice. changes in the time course of expression were identified by northern blot quantification between days 1 and 172. although scrapie-infected and control animals showed no detectable changes in brain development (fir ...	1992	1352797
potent inhibition of scrapie-associated prp accumulation by congo red.	transmissible spongiform encephalopathies (prion diseases), alzheimer's disease, and other amyloidoses result in the accumulation of certain abnormally stable proteins that are thought by many to play central roles in disease pathogenesis. using scrapie-infected neuroblastoma cells as a model system, we found that congo red, an amyloid-binding dye, potently inhibits the accumulation of the scrapie-associated, protease-resistant isoform of protein prp without affecting the metabolism of the norma ...	1992	1352803
further analysis of nucleic acids in purified scrapie prion preparations by improved return refocusing gel electrophoresis.	although increasingly unlikely, the possibility of a scrapie-specific nucleic acid carried by infectious prion particles is still unresolved. return refocusing gel electrophoresis was developed to detect homogeneous and heterogeneous nucleic acids extracted from highly purified scrapie prion preparations. this method was improved with respect to the size range from 13 to 1100 nucleotides (nt) over which analyses could be performed. the yield of nucleic acid, particularly of small dna oligonucleo ...	1992	1353106
immunohistochemical study of kuru plaques using antibodies against synthetic prion protein peptides.	prion protein (prp) is a protein closely associated with the transmission of scrapie and creutzfeldt-jakob disease (cjd). kuru plaques are composed of this protein. prp33-35 is converted to protease-resistant prp27-30 by proteinase k digestion. it has not yet been determined which of these prps is present in kuru plaques in vivo. accordingly we synthesized two peptides (peptide-n and peptide-m) that, respectively, corresponded to the protease-sensitive and protease-resistant portions of prp33-35 ...	1992	1353279
the prion protein gene: a role in mouse embryogenesis?	the neural membrane glycoprotein prp (prion protein) has a key role in the development of scrapie and related neurodegenerative diseases. during pathogenesis, prp accumulates in and around cells of the brain from which it can be isolated in a disease-specific, protease-resistant form. although the involvement of prp in the pathology of these diseases has long been known, the normal function of prp remains unknown. previous studies have shown that the prp gene is expressed tissue specifically in ...	1992	1353438
spontaneous conversion of prpc to prpsc.	octa-repeats of prion proteins (prp) contain histidine and tryptophan residues which are known to function as ligands for transition metals. it is proposed that the spontaneous conversion of the prpc (cellular) isoform into prpsc (scrapie) isoform may be triggered by the coordination of these metals.	1992	1353727
evidence for synthesis of scrapie prion proteins in the endocytic pathway.	infectious scrapie prions are composed largely, if not entirely, of an abnormal isoform of the prion protein (prp) which is designated prpsc. a chromosomal gene encodes both the cellular prion protein (prpc) as well as prpsc. pulse-chase experiments with scrapie-infected cultured cells indicate that prpsc is formed by a post-translational process. prp is translated in the endoplasmic reticulum, modified as it passes through the golgi, and is transported to the cell surface. release of nascent pr ...	1992	1353761
regional mapping of prion proteins in brain.	scrapie is characterized by the accumulation of a protease-resistant isoform of the prion protein prpsc. limited proteolysis and chaotropes were used to map the distribution of prpsc in cryostat sections of scrapie-infected brain blotted onto nitrocellulose membranes, designated histoblots. proteolysis was omitted in order to map the cellular isoform of the prion protein (prpc) in uninfected brains. compared with immunohistochemistry, histoblots increased the sensitivity for prpsc detection and ...	1992	1354357
possible cell-free prion replication.	spongiform encephalopathies, such as scrapie or bovine spongiform encephalopathy in animals, or kuru, creutzfeld-jakob disease (cjd) and gerstmann-sträussler-scheinker disease (gss) in man, seem to be caused by a transmissible agent whose nature is still a matter of debate. the properties of this agent which has been designated as prion, differ from those of any other known infectious agents, including viruses and viroids. several lines of evidence suggest that the prion is devoid of nucleic aci ...	1992	1355257
the infectivity of spongiform encephalopathies: does a modified membrane hypothesis account for lack of immune response?	scrapie, the prototype of a group of diseases which have the unique property of being both hereditary and infectious, is also exceptional in that it fails to evoke an immune response. purification of crude scrapie preparations revealed a strong association of infectivity with a membrane protein ('prpsc'); but a protein with the same amino acid sequence ('prpc') was subsequently also found in normal mammalian nervous tissue. it is postulated by some investigators that 'prpsc' is itself the infect ...	1992	1355344
lysosomes as key organelles in the pathogenesis of prion encephalopathies.	the causation, structural origin, and mechanism of formation of spongiform lesions in transmissible encephalopathies are unknown. we have used immunogold electron microscopy to locate ubiquitin conjugates, hsp 70, and beta-glucuronidase (markers of the lysosomal compartment) and prion protein (prp) in both control and scrapie-infected mouse brain. in scrapie-infected brain, lysosomes and lysosome-related structures (multivesicular and tubulovesicular dense bodies) are present in abnormally high ...	1992	1355530
attempts to convert the cellular prion protein into the scrapie isoform in cell-free systems.	the scrapie prion protein (prpsc) is derived from a cellular isoform (prpc) that acquires protease resistance posttranslationally. we have used several different experimental approaches in attempts to reconstitute in vitro the processes leading to protease-resistant prpsc molecules. in the first study, we performed mixing experiments by adding mouse prp 27-30 (moprp27-30), the protease-resistant core of prpsc, to prpc and then incubating the mixture to investigate the possibility of heterodimer ...	1992	1356161
synthesis and trafficking of prion proteins in cultured cells.	scrapie prions are composed largely, if not entirely, of the scrapie prion protein (prpsc) that is encoded by a chromosomal gene. scrapie-infected mouse neuroblastoma (scn2a) and hamster brain (schab) cells synthesize prpsc from the normal prp isoform (prpc) or a precursor through a posttranslational process. in pulse-chase radiolabeling experiments, we found that presence of brefeldin a (bfa) during both the pulse and the chase periods prevented the synthesis of prpsc. removal of bfa after the ...	1992	1356522
are sinc and the prp gene congruent? evidence from prp gene analysis in sinc congenic mice.	congenic mouse strains vm/dk and vm-sincs7/dk differ at the sinc gene, which controls the incubation period of scrapie in mice; vm/dk mice are sincp7p7 and vm-sincs7/dk mice are sincs7s7. restriction fragment length polymorphism and dna sequencing analysis demonstrated that the prp genes also differ in these strains, confirming the close genetic linkage of sinc and prp. using the restriction enzyme hhai, we have shown that at least 100 kb of dna flanking the prp gene differs between the two stra ...	1992	1357080
a role for lysosomes in scrapie pathogenesis.		1992	1358723
demonstration of scrapie strain diversity in infected pc12 cells.	scrapie strain replication in the nerve growth factor-induced, differentiated pc12 cell culture system was examined. differences in replication between mouse-derived agents were demonstrated, with the 139a scrapie strain yielding 100- to 1000-fold higher levels of infectivity than the me7 scrapie strain. replication was not detected in pc12 cells infected with either the hamster-derived 263k or rat-derived 139r scrapie strains. studies on the neurotransmitters in infected pc12 cells demonstrated ...	1992	1359002
polymorphisms of a scrapie-associated fibril protein (prp) gene and their association with susceptibility to experimentally induced scrapie in cheviot sheep in the united states.	the duration of the incubation period for scrapie, a fatal transmissible neurodegenerative disorder of sheep and goats, is mainly determined by the sip gene, which has 2 alleles (sa--susceptible and pa--resistant). a diagnostic test is not available to detect scrapie in live animals. we analyzed genomic dna extracted from frozen sheep brains collected from cheviot sheep of the united states that had been inoculated with the ssbp/1 scrapie inoculum. digestion of the dna with ecori or hindiii foll ...	1992	1360777
a specific rflp type associated with the occurrence of sheep scrapie in japan.	we have investigated restriction fragment length polymorphism (rflp) on the prp gene and the frequencies of rflp patterns in 35 healthy suffolk sheep randomly collected. according to the combinations of prp encoding dna fragments generated by restriction enzymes eco ri and hind iii, the rflp patterns were classified into six types and designated as types i to vi. the frequencies of these types were as follows: i, 8.6%; ii, 11.4%; iii, 17.6%; iv, 11.4%; v, 28.6%; and vi, 22.9%. in 10 sheep diagno ...	1992	1360795
detection of proteinase k-resistant prion protein and infectivity in mouse spleen by 2 weeks after scrapie agent inoculation.	the sequential accumulation of the protease-resistant form of the endogenous prion protein (prp-res) was compared to levels of scrapie infectivity in the spleen and brain of scrapie-infected mice at various times after inoculation. in mouse spleen prp-res was detected 1 week after inoculation, and increased 65-fold between 1 and 3 weeks post-inoculation and an additional 15-fold during the next 17 weeks. infectivity in spleen reached a maximum plateau level by 3 weeks. in contrast, in mouse brai ...	1992	1361522
immunodetection of a disease specific prp fraction in scrapie-affected sheep and bse-affected cattle.		1992	1362015
comparative sequence analysis and expression of bovine prp gene in mouse l-929 cells.	a cdna clone encoding bovine scrapie-associated fibril protein, prp, from a bovine brain cdna library and six amplified genomic dna clones of bovine prp were characterized. these clones possessed specific characteristics observed in other animal prp genes. however, the bovine prp was divided into two types by the number of repeats. one possessed four octapeptide repetitive sequences, like other animal prp genes, and consisted of 256 amino acids; the other had five such repetitive sequences and 2 ...	1992	1362024
prp protein is associated with follicular dendritic cells of spleens and lymph nodes in uninfected and scrapie-infected mice.	abnormal forms of a host protein, prp, accumulate in the central nervous system in scrapie-affected animals. here, prp protein was detected immunocytochemically in tissue sections of spleen, lymph node, peyer's patches, thymus, and pancreas from uninfected mice and from mice infected with a range of mouse-passaged scrapie strains and bovine spongiform encephalopathy (bse). in the spleen, lymph node and peyer's patches, prp-positive cells were identified as follicular dendritic cells (fdc) by the ...	1992	1362440
prpsc causes nerve cell death and stimulates astrocyte proliferation: a paradox.		1992	1363148
relationship of protease-resistant protein, scrapie-associated fibrils and tubulofilamentous particles to the agent of spongiform encephalopathies.	tubulofilamentous particles and scrapie-associated fibrils (saf) are ultrastructural markers, while protease-resistant protein (prp) is a molecular biological marker for all spongiform encephalopathies. review of all published work has suggested that prp molecules aggregate to form a three-dimensional saf. further reports have suggested that a single-stranded dna wraps round saf and acquires an outer protein coat to form tubulofilamentous particles. as incubation period increases in the infected ...	1992	1363618
scrapie-associated tubulofilamentous particles in human creutzfeldt-jakob disease.	scrapie-associated fibrils (saf) were demonstrated by a simple negative staining method for electron microscopy from fresh and frozen brains with naturally occurring human creutzfeldt-jakob disease (cjd). the findings confirm that saf occur as an internal part of a larger three-layer particle. the two outer coats of saf can be disrupted by detergent alone or can be digested in two stages by a combination of proteolytic enzymes and subsequent treatment with dnase and mung bean nuclease. examinati ...	1992	1363619
purification and properties of the cellular prion protein from syrian hamster brain.	the cellular prion protein (prpc) is encoded by a chromosomal gene, and its scrapie isoform (prpsc) features in all aspects of the prion diseases. prior to the studies reported here, purification of prpc has only been accomplished using immunoaffinity chromatography yielding small amounts of protein. brain homogenates contain two prpc forms designated prpc-i and -ii. these proteins were purified from a microsomal fraction by detergent extraction and separated by immobilized cu2+ ion affinity chr ...	1992	1363897
hidden amyloidoses.	the pathogenesis as well as the genetic disposition to develop clinical symptoms in transmissible spongiform encephalopathies (e.g. creutzfeldt-jakob disease, scrapie, bovine spongiform encephalopathy) relate these diseases to classical noninfectious amyloidoses (familial amyloidotic polyneuropathy as an example) and to alzheimer's disease. this is not obvious to the nonexpert at first glance. this communication tries to elucidate this association, to reveal which immunochemical techniques have ...	1992	1364008
bovine spongiform encephalopathy (bse): a stimulus to wider research.	the severity of the epidemic of bovine spongiform encephalopathy which is currently afflicting cattle in the british isles has stimulated a considerable research effort, much of which is directed toward understanding the aetiology and pathogenesis of the bovine disease. however, a significant thrust has also been orchestrated to address more fundamental issues such as the nature of the uncharacterized causal agents of the wider range of unusual animal and human diseases which share similar chara ...	1992	1364085
sulphate polyanions prolong the incubation period of scrapie-infected hamsters.	the effect of the organic sulphated polyanions, pentosan sulphate (sp54), dextran sulphate 500 (ds500) and suramin, have been tested on golden syrian hamsters infected with the 263k strain of scrapie by the intraperitoneal (i.p.) or the intracerebral route. sp54 had the greatest effect in prolonging the incubation period of the disease when administered within 2 h of the i.p. inoculum. the same amount of sp54 given 24 h after scrapie inoculation had a potent effect in some animals and no effect ...	1992	1372039
normal development and behaviour of mice lacking the neuronal cell-surface prp protein.	prpc is a host protein anchored to the outer surface of neurons and to a lesser extent of lymphocytes and other cells. the transmissible agent (prion) responsible for scrapie is believed to be a modified form of prpc. mice homozygous for disrupted prp genes have been generated. surprisingly, they develop and behave normally for at least seven months, and no immunological defects are apparent. it is now feasible to determine whether mice devoid of prpc can propagate prions and are susceptible to ...	1992	1373228
molecular cloning of a mink prion protein gene.	transmissible mink encephalopathy (tme) is a rare disease which is presumably transmitted to ranch-raised mink from scrapie-infected sheep offal or bovine spongiform encephalopathy-infected cattle products. although the infectious agent of tme has not been isolated, there is circumstantial evidence that tme is caused by prions. the experimental host range of tme includes sheep, cattle, monkeys and hamsters. however, tme has never been transmitted to mice. since experiments in transgenic animals ...	1992	1383401
recently described scrapie-like encephalopathies of animals: case definitions.	since 1986, naturally occurring scrapie-like encephalopathies have been described in the united kingdom in domestic cattle, in five species of captive exotic bovids and in domestic cats. the disease in domestic cattle, bovine spongiform encephalopathy, has been characterised by all currently available diagnostic criteria as a transmissible spongiform encephalopathy or 'prion' disease, and has been shown to have a dietary origin. the pathology in the other species is also entirely consistent with ...	1992	1410804
tubulovesicular structures in creutzfeldt-jakob disease.	by electron microscopy tubulovesicular structures (tvs) have been consistently observed in brain tissue of transmissible spongiform encephalopathies such as natural and experimental scrapie, bovine spongiform encephalopathy and experimentally induced, but not naturally occurring, creutzfeldt-jakob disease (cjd). for the first time we report here the presence of tvs in human brains with cjd as detected by transmission electron microscopy. tvs were observed in all three cjd specimens (two biopsies ...	1992	1414277
natural and experimental prion diseases of humans and animals.	prions cause transmissible and genetic neurodegenerative diseases. infectious prion particles are composed largely, if not entirely, of an abnormal isoform of the prion protein (prpsc), which is encoded by a chromosomal gene. although the prp gene is single copy, transgenic mice with both alleles of the prp gene ablated develop normally. a post-translational process, as yet unidentified, converts the cellular prion protein (prpc) into prpsc. scrapie incubation times, neuropathology and prion syn ...	1992	1422120
predicted alpha-helical regions of the prion protein when synthesized as peptides form amyloid.	by comparing the amino acid sequences of 11 mammalian and 1 avian prion proteins (prp), structural analyses predicted four alpha-helical regions. peptides corresponding to these regions of syrian hamster prp were synthesized, and, contrary to predictions, three of the four spontaneously formed amyloids as shown by electron microscopy and congo red staining. by ir spectroscopy, these amyloid peptides exhibited secondary structures composed largely of beta-sheets. the first of the predicted helice ...	1992	1438300
[suspicion of visna in a sheep from graubünden canton].	a lentivirus belonging to the group of retroviridae causes a chronic progressive interstitial pneumopathy (maedi) or a demyelinating encephalo-myelitis (visna) in sheep and goats. pulmonary lesions of maedi as well as sero-positive, clinically healthy animals can be observed in switzerland; visna, which even in countries with endemic infection does not occur frequently, is extremely rare. the head and cervical spine of an ewe with severe nervous troubles suspected of scrapie were submitted for p ...	1992	1439707
[the interrelationship of the causative agents of subacute transmissible spongiform encephalopathies].	virological, histological, and electron microscopy methods were used to study the features of the infectious process in minks infected with scrapie agent as compared with that in minks infected with the agent of mink transmissive encephalopathy and in mice infected with scrapie. the results of the study showed the similarity in the clinical picture and the pattern of histological and ultramicroscopic lesions in minks infected with either of the agents. on the basis of the authors' own data and t ...	1992	1441441
the role of perivascular and microglial cells in fibrillogenesis of beta-amyloid and prp protein in alzheimer's disease and scrapie.		1992	1455056
biological hazards in the workplace.		1992	1455591
spongiform encephalopathy in a captive puma (felis concolor).	a captive adult puma developed ataxia, a hypermetric gait and whole body tremor. the signs progressed over a period of six weeks. histopathological examination following euthanasia demonstrated spongiform encephalopathy, gliosis and mild non-suppurative meningoencephalitis. immunostaining with a polyclonal antiserum revealed prion protein (prp) associated with these changes in sections of cervical spinal cord and medulla. this is the first confirmed case of a scrapie-like spongiform encephalopat ...	1992	1455592
assessment of western immunoblotting for the confirmatory diagnosis of ovine scrapie and bovine spongiform encephalopathy (bse).		1992	1457549
ultrastructural features of spongiform encephalopathy transmitted to mice from three species of bovidae.	the ultrastructural neuropathology of mice experimentally inoculated with brain tissue of nyala (tragelaphus angasi; subfamily bovinae), or kudu (tragelaphus strepsiceros; subfamily bovinae) affected with spongiform encephalopathy was compared with that of mice inoculated with brain tissue from cows (bos taurus; subfamily bovinae) with bovine spongiform encephalopathy (bse). as fresh brain tissue was not available for nyala or kudu, formalin-fixed tissues were used for transmission from these sp ...	1992	1462768
infection specific prion protein (prp) accumulates on neuronal plasmalemma in scrapie infected mice.	prion protein (prp) is an abundant membrane-associated host protein which accumulates in abnormal, relatively protease-resistant forms in the brains of animals with scrapie and related diseases. using correlative light and electron microscopy we determined the sites of subcellular localisation of prp in mice infected with the 87v strain of scrapie. disease specific accumulation of prp was observed at light microscopy as amyloid plaques or as diffuse or granular staining within the neuropil, ofte ...	1992	1480316
[an outbreak of scrapie].		1992	1481211