Publications

antibodies to a scrapie prion protein.	scrapie is a slow infection of the nervous system which progresses in the absence of any apparent immune response. the recent development of a large-scale purification protocol for scrapie prions made it possible to obtain substantial quantities of electrophoretically purified prion protein (prp 27-30) and we report here on the successful production of a rabbit antiserum to prp 27-30. the antiserum reacted with prp 27-30 and several lower molecular weight proteins as shown by western blots; it d ...	1984	6431296
pathogenesis of mouse scrapie: distribution of agent in the pulp and stroma of infected spleens.	fourteen spleens were collected from mice infected with the 139a strain of scrapie, at a time when the concentration of agent in spleen was at a plateau. scrapie infectivity was present in both the pulp and stromal fractions, but the concentration in stroma was about 10 times greater than that in pulp. on average, 1000 pulp cells were required to give 1 ld50 unit of scrapie infectivity. linear regression analysis of data from 64 mouse spleens showed that the total infectivity correlated with tis ...	1984	6433538
sustained viremia in experimental hamster scrapie. brief report.	after an intraperitoneal injection of scrapie agent into hamsters, a viremic phase is maintained from day 10 to at least day 40 post infection. infectivity can be detected in the brain as early as 5-10 days after inoculation.	1984	6437378
purification and structural studies of a major scrapie prion protein.	scrapie is a degenerative, neurological disorder caused by a slow infectious agent or prion. extensively purified preparations of prions were denatured by boiling in sodium dodecyl sulfate and the major protein component (prp 27-30) was isolated by preparative hplc size exclusion chromatography after proteinase k digestion. the purified prp 27-30 molecules were not infectious. ultraviolet absorption spectra of purified prp 27-30 demonstrated the absence of covalently linked polynucleotides. amin ...	1984	6432339
purification of the scrapie agent by density gradient centrifugation.	plasma membrane-enriched preparations from scrapie-infected and healthy hamster brains, as well as preparations of neural retina, were sonicated, then separated by rate-zonal sedimentation in 10 to 25% nycodenz gradients. gradient fractions were extracted with 0.5% triton x-100 and re-fractionated by equilibrium density centrifugation in linear 25 to 40% cscl gradients. infectivity was highest in a fraction having a density of 1.280 g/ml and which contained a visible band of material. digestion ...	1984	6420511
equilibrium density gradient centrifugation of the scrapie agent in nycodenz.	plasma membrane-enriched preparations from scrapie-infected and healthy hamster brains were detergent-extracted, then separated by equilibrium density centrifugation in continuous nycodenz gradients. the highest level of infectivity was always associated with the insoluble residue which sedimented through 40% nycodenz. the degree of aggregation in these insoluble complexes varied depending upon treatment. centrifugation in gradients containing 2 m- to 8 m-urea resulted in the formation of large ...	1984	6438273
in vitro replication of scrapie agent in a neuronal model: infection of pc12 cells.	a rat phaeochromocytoma cell line, termed pc12, was used to study scrapie replication. these cells, in response to the addition of nerve growth factor (ngf), exhibit a number of neuronal properties including morphological differentiation, electrophysiological responsiveness, and neurotransmitter synthesis. cultures were exposed to scrapie brain homogenate (strain 139a), harvested every week for up to 6 weeks, and assayed for scrapie infectivity. scrapie replication in vitro was monitored by inje ...	1984	6439820
attempts to establish the scrapie agent in cell lines.	attempts were made to establish a persistent infection with scrapie agent in four murine cell lines. of the four lines tested, viz. p388d1, p3-ns1-ag-1 (ns1), l cells and an ns1 spleen cell hybrid, only the ns1 cell line showed any evidence of agent replication. ten per cent dimethylsulphoxide (dmso) was included in the culture media of l cells inoculated with scrapie agent. this treatment raised the initial levels of scrapie agent associating with the l cells but did not result in a persistentl ...	1984	6440351
occurrence of ovine scrapie in japan: clinical and histological findings in mice inoculated with brain homogenates of an affected sheep.		1984	6441054
sheep lymphocyte antigens and scrapie.	the frequencies of 15 lymphocyte antigens were determined in 2 experimental flocks of herdwick sheep derived from the same foundation stock. the blue flock had been bred for resistance, and the red flock for susceptibility, to a standard dose of the ssbp/1 source of scrapie injected subcutaneously. although there were marked frequently differences between the 158 red flock and 51 blue flock sheep tested these differences could be attributed to genetic drift. within the red flock no significant f ...	1984	6470228
oncogenes--implications for human cancer.		1984	6481759
scrapie and alzheimer's disease.		1984	6494362
the occurrence of scrapie of sheep in japan.		1984	6513247
[karyological characteristics of continuous mouse cell lines infected with the scrapie agent].	a karyological study of murine cell line l, latently infected with different strains of the scrapie agent (compton and c-506) showed that the both variants number of chromosomes and the number of robertson's translocations of chromosomes decrease insignificantly with an increase in the time of subcultivation. the use of the c-method of differential chromosome staining revealed four new analogous chromosomes in both experimental cell lines. this phenomenon is probably specific for this infected c ...	1984	6539520
morphology and distribution of alzheimer neuritic (senile) and amyloid plaques in striatum and diencephalon.	mapping of striatal and diencephalic plaque distribution was conducted in 25 cases of dementia of the alzheimer type. this analysis was carried out by fluorescence microscopy of paraffin-embedded tissue sections treated with thioflavine s as fluorochrome. consistent differences in plaque morphology and density between nuclei and fiber tracts were observed. striatal and pallidal distribution was uneven, with plaque aggregation near and within certain fiber tracts: capsules, medullary laminae, and ...	1984	6542292
degenerative hippocampal pathology in mice infected with scrapie.	the lesions of scrapie are confined to the cns, and the most characteristic histopathological change in mice terminally infected with scrapie is vacuolation. with most laboratory strains of scrapie, one of the regions affected by this lesion is the cerebral cortex, including the hippocampus. under some circumstances, however, a more destructive degeneration occurs in the hippocampus, with pyramidal cell necrosis accompanied by glial reactions, which can extend to a severe hippocampal sclerosis e ...	1984	6542738
serum and cerebrospinal fluid concentrations of immunoglobulin g in suffolk sheep with scrapie.	determinations were made by laser nephelometry of serum and csf immunoglobulin (ig) g concentrations in suffolk sheep with naturally occurring scrapie. the serum igg concentrations in 3 sheep with confirmed or suspected scrapie were between 2,140 and 3,290 mg of igg/100 ml, and the csf values were between less than 10 and 75 mg of igg/100 ml. in 8 clinically healthy (control) sheep, serum igg concentrations were 2,647 to 7,380 mg/100 ml and csf igg concentrations were between 0 (undetectable) an ...	1984	6497137
experimental infection of fetal and newborn suffolk sheep with scrapie virus.	fetal (n = 21) and newborn (n = 7) suffolk sheep were inoculated with scrapie virus isolated from other suffolk sheep. twenty fetuses, 76 to 109 days of gestational age, were inoculated im in the neck through the uterine wall and were examined for virus 47 to 322 days later by mouse inoculation. scrapie virus was not detected before 254 days of age; only traces of virus were detected in 3 of 7 lambs examined thereafter (2 at 254 days of age and 1 at 322 days of age). virus was limited to the sup ...	1984	6441491
the mysterious prion.		1984	6444184
[epidemiology of aids].		1984	6730611
[spongiform encephalopathy in mice inoculated with scrapie material of sheep origin].	the authors report spongy degeneration in experimental scrapie (second passage) in mice. the scrapie agent was originally isolated from suffolk sheep imported from canada and diagnosed histopathologically to be infected with scrapie by intracerebral inoculation into jcl/icr mice. ten female sic/icr mice, 4 weeks of age, were injected intracerebrally in the right frontal lobus with 20 microliter of 10(-1) or 10(-4) dilution of jcr/icr mice brain homogenate involving scrapie agent. all animals sho ...	1984	6508958
brain glutamate decarboxylase and cholinergic enzyme activities in scrapie.	c57bl/6j mice, age 6-8 weeks were inoculated intracerebrally with brain homogenate from mice previously infected with the 139a strain of scrapie; control mice were identically treated with brain homogenate from non-infected normal mice. the activities of choline acetyltransferase (cat), acetyl cholinesterase (ache), and glutamic acid decarboxylase (gad) were determined in the forebrain and hindbrain of these animals after 67, 126 and 151 days post-inoculation. there were no significant differenc ...	1985	4039359
pathogenesis of mouse scrapie: dynamics of vacuolation in brain and spinal cord after intraperitoneal infection.	at the late clinical stage of scrapie in mice, the severity and distribution of vacuolation in the brain (the lesion profile) is largely determined by the strain of agent and the genotype of the mouse: under controlled conditions, lesion profiles can be used to distinguish between scrapie strains. this paper describes the sequential development of lesions in brain at much earlier times and includes a study of spinal cord. mice (cw) were infected intraperitoneally with 139a scrapie. grey matter v ...	1985	4041016
sheep major histocompatibility complex ola: gene frequencies in two french breeds with scrapie. evidence for a linkage between ola and resistance or susceptibility to the disease.	gene frequencies of 13 sheep lymphocyte factors (11 factors controlled by the sheep ola complex including three closely linked loci, and two factors by two minor loci) were compared in 189 sheep of two breeds: a. infected with scrapie, b. healthy in a contaminated environment, and c., normal. in a and c, ola gene frequencies were similar. in healthy sheep in a contaminated environment (b), some ola gene frequencies were higher in one breed and lower in the other. in each breed, three antigens ha ...	1985	3980051
selection of swaledale sheep of reduced susceptibility to experimental scrapie.	a flock of 294 swaledale sheep was injected with brain tissue from different sources so as to include strains of natural scrapie currently affecting the swaledale breed. discounting intercurrent deaths, 85 per cent of the flock developed clinical scrapie within an observation period of 2557 days (seven years). scrapie cases fell into distinct early and late groups, occurring at (mean +/- sem) 287 +/- 7 days and 1207 +/- 38 days after injection, respectively. breeding groups were formed from the ...	1985	3984198
[short review on the causative agent of scrapie].		1985	4014987
transmission of scrapie in hamsters.	hamsters developed scrapie 100-160 days after eating either scrapie-infected hamsters or infected brain. the clinical signs and neuropathology of scrapie transmitted by cannibalism were identical to those observed after intracerebral or intraperitoneal inoculation of the agent. oral transmission of scrapie appears to be extremely inefficient. cannibalism requires a dose of the scrapie agent of approximately 10(9) times greater than that needed to produce the disease by intracerebral injection fo ...	1985	3930630
asymmetry of retinal lesions in experimental scrapie after intracerebral inoculation of hamsters.	hamsters injected into the right cerebral hemisphere with the scrapie agent developed retinal lesions to a greater extent in the contralateral than in the ipsilateral eye. this asymmetry was evident during the incubation period as well as during the clinical encephalopathy. the results explain much of the variation in the degree of retinal disease seen earlier at specific times after inoculation. moreover, they strengthen the hypothesis that scrapie spreads via neurons.	1985	4038487
serotoninergic system in scrapie-infected hamsters.	hamsters inoculated with scrapie virus show a dramatic hypersensitivity to serotoninergic drugs, developing a behavioral syndrome not unlike that obtained with pharmacologically induced lesions of the raphe nuclei. in an attempt to explain the state of hypersensitivity and to determine whether or not serotoninergic neurons were targets of the scrapie virus, pre- and postsynaptic serotoninergic sites were studied in the cerebral cortices of scrapie-infected and sham-inoculated hamsters. [3h]imipr ...	1985	4038735
effects of in vitro infection of mouse glial and neuroblastoma cells with the scrapie agent.	mouse glial and neuroblastoma cells were infected with the mouse adapted strains c506 and 139a of scrapie agent. lysates of the in vitro infected cells (from the 3rd to the 16th passage) intracerebrally inoculated into cd-1 mice, caused the development of a neurological disease, with characteristic signs of scrapie. morphological changes in scrapie-infected neural cells were observed after about fifteen in vitro passages. in liquid medium, the cloning efficiency of these cells increased. they ac ...	1985	3925869
failure to detect scrapie virus in sheep at slaughter in a highly endemic region of france.	a study was carried out in a sheep slaughterhouse located in a region of france where scrapie has been endemic for several decades. neuropathological examination of 63 randomly selected lambs and adult sheep revealed no scrapie-related abnormalities, and inoculation of mice with brain, tonsil, lateropharyngeal ganglia, and intestine from the same animals did not transmit scrapie. the failure to detect any evidence of scrapie infection in commercially-bred sheep, the absence of an increased morta ...	1985	3939516
nature of the scrapie agent: current status of facts and hypotheses.		1985	3926950
biochemical differences among scrapie-associated fibrils support the biological diversity of scrapie agents.	scrapie-associated fibrils (saf) were isolated and purified from animals infected with three different scrapie agents: me7 and 139a in mice, and 263k in hamsters. mouse me7 and 139a saf differed from hamster 263k saf in morphology, sedimentation rate and protein composition. saf from the three scrapie agents were distinguishable from each other by their sensitivity to proteinase k digestion. saf copurified with infectivity in both the hamster and mouse systems. saf appear to be a unique class of ...	1985	3926951
agent replication dynamics in a long incubation period model of mouse scrapie.	the dynamics of scrapie agent replication in brain and spleen following intracerebral or intraperitoneal infection were investigated in a model with particularly long incubation periods [im mice (sincp7) infected with 87v scrapie]. in contrast to other mouse scrapie models previously investigated, there was no delay in onset of replication ('zero phase') in spleen using either route of infection, for both routes infectivity levels reached a plateau in spleen, which was maintained for at least 25 ...	1985	3934338
absence of autoantibodies against neurofilament proteins in the sera of scrapie infected mice.	autoantibodies against neurofilament proteins were not detected in any of the sera from the following scrapie infected mice: 19 mice infected with scrapie agent 139a in pre-clinical stage, 32 histologically confirmed scrapie mice and other 12 clinical scrapie mice infected with various strains. the test sera were assayed against acetone-fixed central neuron cultures from fetal mice by indirect immunofluorescence and immunoperoxidase techniques. the negative result suggests that autoantibodies ag ...	1985	4071543
creutzfeldt-jakob disease prion proteins in human brains.	creutzfeldt-jakob disease is caused by a slow infectious pathogen, or prion. we found that purified fractions from the brains of two patients with creutzfeldt-jakob disease contained protease-resistant proteins ranging in apparent molecular weight from 10,000 to 50,000. these proteins reacted with antibodies raised against the scrapie prion protein prp 27-30. rod-shaped particles were found in the brain tissue of the patients that were similar to those isolated from rodents with either scrapie o ...	1985	3917302
cerebellar plaques in familial alzheimer's disease (gerstmann-sträussler-scheinker variant?).	a large kindred, with two brothers coming to autopsy, of a syndrome consisting of ataxia, dementia, and some parkinsonian features is reported; inheritance appears to be autosomal dominant. neuropathologically, there were plaques and neurofibrillary tangles in the cerebral cortex as well as some in the basal ganglia, particularly reminiscent of the plaques seen in kuru; there was only minimal spinal cord disease (pyramidal tract field). the problems of classifying this condition--alzheimer's dis ...	1985	3883687
oncogenes in scrapie and creutzfeldt-jacob disease.		1985	3884811
degenerative neurologic disease in patients formerly treated with human growth hormone. report of the committee on growth hormone use of the lawson wilkins pediatric endocrine society, may 1985.	one or more lots of pituitary gh supplied by the nhpp may have been contaminated with cjd pathogen. if so, it is probable that the contaminated hormone was dispensed before 1978, and there is reason to believe that it was dispensed in the late 1960s. the contamination may have been limited to one lot of gh, but this is not known with certainty. purification methods used by the nhpp since 1978 probably exclude the cjd pathogen, but this is not yet certain. the risk to patients treated since 1978, ...	1985	3891943
[human subacute spongiform encephalopathies].		1985	3894829
[properties of the causative agent of creutzfeldt-jakob disease; current insights into the pathogenesis of dementia].		1985	3897875
prions--infectious pathogens causing the spongiform encephalopathies.	the novel properties of the scrapie and creutzfeldt-jakob disease (cjd) transmissible agents readily distinguish them from viruses and viroids; thus, they have been labeled "prions". the scrapie prion contains a protein(s) which is required for infectivity; recently a 27,000 to 30,000 mw protein which purifies with the prion has been identified. the similarities between the scrapie and cjd agents suggest that cjd is also caused by a prion. recent studies show that the time courses of both scrapi ...	1985	3915974
cloning of a gene whose expression is increased in scrapie and in senile plaques in human brain.	a complementary dna library was constructed from messenger rna's extracted from the brains of mice infected with the scrapie agent. the library was differentially screened with the objectives of finding clones that might be used as markers of infection and finding clones of genes whose increased expression might be correlated with the pathological changes common to scrapie and alzheimer's disease. a gene was identified whose expression is increased in scrapie. the complementary dna corresponding ...	1985	3840915
creutzfeldt-jakob disease.	the historical aspects of spongiform encephalopathies, creutzfeldt-jakob disease (cjd) and kuru of man, as well as scrapie and transmissible mink encephalopathy, are outlined. transmissions of these diseases to animal hosts are presented, with emphasis on cjd transmissions to guinea pigs, hamsters, and mice. the relationship of cjd to scrapie with reference to the pathological findings is discussed. in cjd the incubation period is cut in half in guinea pigs and hamsters in the second passage. th ...	1985	3880808
genetic control of amyloid plaque production and incubation period in scrapie-infected mice.	the extent of amyloid plaque production was investigated in three inbred mouse strains carrying the p7 allele of the scrapie incubation (sinc) gene (vm, im and mb). with either me7 or 87v scrapie, many more plaques were seen in the mb strain than in vm or im mice. a backcrossing experiment using 87v suggested the involvement of more than one gene. within this backcrossing experiment there was a positive correlation between mean plaque count and mean incubation period for the various strains and ...	1985	3921669
[subviral infections].		1985	3892920
[prions--the pathogens causing slow infections].		1985	3900951
scrapie prp 27-30 is a sialoglycoprotein.	the major scrapie prion protein, designated prp 27-30, exhibited both charge and size heterogeneity after purification from infected hamster brains. eight or more discrete charge isomers of prp 27-30 with isoelectric points ranging from approximately ph 4.6 to 7.9 were found by using non-equilibrium ph gradient electrophoresis in the first dimension followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the second dimension. the charge isomers were detected by silver staining a ...	1985	3918176
identification of prion amyloid filaments in scrapie-infected brain.	extracellular collections of abnormal filaments composed of prion proteins have been identified in the brains of scrapie-infected hamsters using immunoelectron microscopy. some of the filaments were 1500 nm in length; generally, they exhibited a uniform diameter of 16 nm. rarely, the filaments had a twisted appearance, raising the possibility that they are flattened cylinders or are composed of helically wound protofilaments. the prion filaments possess the same diameter and limited twisting as ...	1985	3922627
competition between strains of scrapie depends on the blocking agent being infectious.	compton white mice (sincs7) were injected twice intraperitoneally, first with the 22a strain of scrapie agent (in brain homogenates) and then, after 105 days, with the 22c strain. incubation periods were calculated from the time of the first injection. the experiment was designed so that, with no interaction between strains, the second strain (22c) should have produced cases about 300-350 days after the first injection, depending on the dose of 22c. this was well before the limit of 470 days set ...	1985	3920169
inactivation of the scrapie agent by ultraviolet irradiation in the presence of chlorpromazine.	the sensitivity of the scrapie agent to u.v. inactivation was found to be related to the purity of the tissue preparation. scrapie infectivity associated with membrane vesicles was unaffected when irradiated with 10(4) j/m2. irradiation of more highly purified preparations from detergent-extracted cscl gradient fractions reduced scrapie infectivity from 10(7.8) log10 ld50 per ml to as low as 10(4.5). sensitivity of membrane-associated scrapie infectivity to inactivation by u.v. irradiation could ...	1985	3920348
characterization of proteins in membrane vesicles from scrapie-infected hamster brain.	previous studies have shown that the scrapie agent is highly membrane-associated. we examined the protein composition of gradient fractions enriched for large membrane vesicles prepared from scrapie-infected and uninfected hamster brain using various methods to extract membrane proteins. we also examined proteins in detergent-extracted membrane vesicles fractionated on cscl gradients. no qualitative differences in protein composition were seen comparing scrapie-infected and uninfected samples by ...	1985	3920349
virogenes in scrapie and creutzfeldt-jakob disease.		1985	3906122
characterization of lipids in membrane vesicles from scrapie-infected hamster brain.	the lipid compositions of membrane vesicles from scrapie-infected and uninfected hamster brains were examined before and after detergent extraction. no differences were observed in polar lipids, glycolipids, gangliosides or neutral lipids examined by thin-layer chromatography. analysis of detergent-extracted cscl gradient fractions with high scrapie infectivity failed to reveal any glycerolphosphatides, although neutral lipids were demonstrated. the major neutral lipid associated with detergent- ...	1985	3920350
[prion antibodies and structure analysis clarify questions about atypical viruses. prion structure under the electron microscope].		1985	3920456
focusing on the nature of the scrapie agent.		1985	3921259
sheep consumption: a possible source of spongiform encephalopathy in humans.	a fatal spongiform encephalopathy of sheep and goats (scrapie) shares many characteristics with creutzfeldt-jakob disease (cjd), a similar dementing illness of humans. to investigate the possibility that cjd is acquired by ingestion of contaminated sheep products, we collected information on production, slaughtering practices, and marketing of sheep in pennsylvania. the study revealed that sheep were usually marketed before central nervous system signs of scrapie are expected to appear; breeds k ...	1985	3915057
antibodies to the scrapie protein decorate prion rods.	scrapie is a degenerative, transmissible neurologic disease of sheep and goats which occurs in the absence of any detectable host immune response. antibodies to the scrapie agent have been produced after immunization of rabbits with either scrapie prions or the prion protein, prp 27-30, purified from infected hamster brain. immunoreactivity of the antisera was assessed by dot and western immunoblots with purified prions and prp 27-30. antibodies raised against infectious prions were more immunor ...	1985	3923112
scrapie. persistently puzzling prions.		1985	3923360
retinal degeneration in experimental scrapie after intraperitoneal or subcutaneous inoculation of hamsters.	hamsters injected intraperitoneally or subcutaneously with the scrapie agent developed photoreceptor degeneration. the degree of degeneration did not correlate well with infectivity titers of retinal tissue or stage of clinical encephalopathy, and was not as great as seen in intracerebrally injected animals. we conclude that retinal degeneration is universal in hamsters experimentally inoculated with the scrapie agent regardless of the route of inoculation.	1985	3921398
identification of scrapie prion protein-specific mrna in scrapie-infected and uninfected brain.	to date no nucleic acid has been found in the purified infectious agent which causes the spongiform encephalopathy known as scrapie. in an attempt to identify a unique scrapie virus-associated messenger rna in tissues of infected animals, we have synthesized an oligonucleotide probe complementary to the mrna sequence corresponding to the amino-acid sequence of the prion protein, prp27-30 (ref. 1). we report here that, with this probe, a complementary dna clone representing prp27-30 was obtained ...	1985	3923361
the 200- and 150-kda neurofilament proteins react with igg autoantibodies from chimpanzees with kuru or creutzfeldt-jakob disease; a 62-kda neurofilament-associated protein reacts with sera from sheep with natural scrapie.	sera from 46 chimpanzees with spongiform encephalopathy (18 kuru, 28 creutzfeldt-jakob disease) and sera from 12 sheep with natural scrapie were tested for reactivity with immunoblots of neurofilament preparations obtained from mouse brain. the sera from the chimpanzees reacted mainly with the 200- and 150-kda proteins of the neurofilament triplet and less frequently with the 70-kda component of the triplet and with a 62-kda neurofilament-associated protein. in contrast, the sera of sheep with n ...	1985	3923483
targeting of scrapie lesions and spread of agent via the retino-tectal projection.	scrapie infectivity and degenerative vacuolation was initially localized within the contralateral superior colliculus following intraocular injection. the time course of these events was prolonged. with the me7 strain of scrapie in sincs7 genotype mice, infectivity began to rise in the superior colliculus from about 70 days, followed by the earliest asymmetrical lesions there from 120 days, with death occurring at about 250 days, at which time vacuolar degeneration was widespread in the brain. w ...	1985	4052769
characterization of scrapie agent isolated from sheep in japan.	a pathogenic agent isolated in mice from the brain of a sheep affected by scrapie-like disease was characterized. the incubation period of the disease in the primary transmission from the sheep to mice was longer than in the secondary and the tertiary transmission in the same strain of mice. progressive dilution of the inoculum caused prolongation of the incubation period. the infectivity of the agent in a 10% brain homogenate persisted, but decreased about 10(3) to 10(4) times after heating at ...	1985	3930925
neuronal origin of a cerebral amyloid: neurofibrillary tangles of alzheimer's disease contain the same protein as the amyloid of plaque cores and blood vessels.	the protein component of alzheimer's disease amyloid [neurofibrillary tangles (nft), amyloid plaque core and congophilic angiopathy] is an aggregated polypeptide with a subunit mass of 4 kd (the a4 monomer). based on the degree of n-terminal heterogeneity, the amyloid is first deposited in the neuron, and later in the extracellular space. using antisera raised against synthetic peptides, we show that the n terminus of a4 (residues 1-11) contains an epitope for neurofibrillary tangles, and the in ...	1985	4065091
scrapie agent unlike viruses in size and susceptibility to inactivation by ionizing or ultraviolet radiation.		1985	3932887
"slow infections"--a challenge to traditional concepts.		1985	3934107
effect of prior treatment with thioglycolate on the incubation period of intraperitoneally injected scrapie.	injection of mice with thioglycolate 5 days prior to intraperitoneal injection of scrapie brain homogenate led to a statistically significant increase in scrapie incubation periods. this was seen with two different scrapie strains (me7 and 139a), in different mouse strains (c57bl/6j and compton white), and at several dilutions of the scrapie inoculum.	1985	4066255
cona induced suppressor cells in scrapie-infected mice.	lymphocyte suspensions prepared from the spleens of mice (lacg/com) clinically affected with scrapie (me7) were cultured for 48 hrs in the presence of concanavalin (cona) in order to induce suppressor cells. these cells behaved exactly as similarly prepared cells from normal age-matched mice in suppressing the response of fresh normal splenic lymphocytes to phytohaemagglutinin (pha).	1985	3156445
amyloid plaque core protein in alzheimer disease and down syndrome.	we have purified and characterized the cerebral amyloid protein that forms the plaque core in alzheimer disease and in aged individuals with down syndrome. the protein consists of multimeric aggregates of a polypeptide of about 40 residues (4 kda). the amino acid composition, molecular mass, and nh2-terminal sequence of this amyloid protein are almost identical to those described for the amyloid deposited in the congophilic angiopathy of alzheimer disease and down syndrome, but the plaque core p ...	1985	3159021
scrapie and creutzfeldt-jakob disease prions.	scrapie and creutzfeldt-jakob disease are caused by prions which can be distinguished from both viruses and viroids. aggregates of prions are ultrastructurally and histochemically identical to amyloid. extracellular collections of prions form amyloid plaques within scrapie-infected brain. prion amyloid plaques seem analogous to viral inclusion bodies in that they are composed of causative pathogens and are not merely a consequence of the disease.	1985	3940147
specific proteins associated with creutzfeldt-jakob disease and scrapie share antigenic and carbohydrate determinants.	small amounts of brain tissue (2 g) infected with creutzfeldt-jakob disease (cjd) can be fractionated by using a simple 1-day method that includes lysis with n-lauroylsarcosine. unique fibrils have been identified previously in scrapie- and cjd-infected tissue. these fibrils were abundant in final fractions. preparations from human cjd autopsy material and from experimental hamster and guinea pig cjd all displayed readily identifiable fibrils that were not seen in control preparations. thus, the ...	1985	2408277
neurotransmitter metabolites, enzymes and receptors in experimental scrapie.	a comprehensive study has been made of metabolites, enzymes and receptors for a variety of neurotransmitter systems in different parts of the cns from mice affected with 139a scrapie. studies were made at the early clinical stage so as to minimise secondary alterations in terminally sick mice. even though histological lesions (vacuolation) are widespread in the cns in this model of scrapie, no consistent neurochemical changes were found in mid- or anterior brain. in the cerebellum, the activity ...	1985	2414405
hypothesis: interference with axonal transport of neurofilament as a common pathogenetic mechanism in certain diseases of the central nervous system.		1985	2579335
scrapie and creutzfeldt-jakob disease prion proteins share physical properties and antigenic determinants.	scrapie of sheep and goats as well as creutzfeldt-jakob disease (cjd) of humans are neurologic disorders caused by slow infectious pathogens. the novel molecular properties of the pathogen causing scrapie have prompted introduction of the term "prion" to denote a small proteinaceous infectious particle that resists inactivation by nucleic acid-modifying procedures. antiserum to the major hamster scrapie prion protein (prp 27-30) was found to cross-react with murine cjd proteins. the cjd proteins ...	1985	2579394
comparison of rna from healthy and scrapie-infected hamster brain.	density gradient fractions prepared from healthy or scrapie-infected hamster brain tissue enriched in plasma membrane vesicles were treated with nucleases prior to phenol extraction and ethanol precipitation. the recovered nucleic acids were 3' end-labelled and run on one-dimensional polyacrylamide gels. autoradiography revealed the presence of low molecular weight rnas (4s) in both healthy and scrapie samples. two-dimensional fingerprint analysis indicated that the rnas isolated from scrapie-in ...	1985	2580051
structures resembling scrapie-associated fibrils in aids encephalopathy.		1985	2863474
scrapie-associated fibrils and aids encephalopathy.		1985	2863620
scrapie-associated fibrils and aids encephalopathy.		1985	2866357
characterization of nucleic acids in membrane vesicles from scrapie-infected hamster brain.	this study reports the partial characterization of nucleic acids present in gradient fractions enriched for large membrane vesicles from scrapie-infected and uninfected hamster brains. labeling of phenol-extracted nucleic acids at the 3' or 5' ends revealed abundant amounts of low-molecular-weight rna and little or no dna. these nucleic acids survived nuclease treatment of membrane vesicles but were sensitive to rnase after phenol extraction. analysis of 5'-end-labeled nucleic acids by one- and ...	1985	2409296
isonicotinic hydrazide causes seizures in scrapie-infected hamsters with shorter latency than in control animals: a possible gabaergic defect.	isonicotinic hydrazide, a drug that decreases the level of gaba, when injected subcutaneously in control and scrapie-infected hamsters induced tonic-clonic seizures in scrapie hamsters significantly earlier (p less than 0.0001) than in control animals. this suggests depression of the gabaergic system in scrapie-infected hamsters. to determine whether this lesion is pre or postsynaptic we measured the level of gaba, glutamate, cgmp and camp and the gaba-benzodiazepine receptor complex.	1985	2857587
ultrastructural links between scrapie and alzheimer's disease.	the discovery of abnormal fibrillar structures, scrapie-associated fibrils (saf), in fractions with high infectivity from scrapie-infected brains has led to the proposal that saf are a form of the infectious agent. on the basis of this proposal and on the congophilia shared by saf and amyloid, it has been speculated elsewhere that the amyloid in alzheimer's disease is infectious. this speculation is not supported by available evidence and therefore a conventional origin for the amyloid in alzhei ...	1985	2857861
a cellular gene encodes scrapie prp 27-30 protein.	a clone encoding prp 27-30, the major protein in purified preparations of scrapie agent, was selected from a scrapie-infected hamster brain cdna library by oligonucleotide probes corresponding to the n terminus of the protein. southern blotting with prp cdna revealed a single gene with the same restriction patterns in normal and scrapie-infected brain dna. a single prp-related gene was also detected in murine and human dna. prp-related mrna was found at similar levels in normal and scrapie-infec ...	1985	2859120
[prion diseases?].		1985	2859975
antigenic changes in the cells latently infected with the scrapie agent.		1985	2869666
the protein component of scrapie-associated fibrils is a glycosylated low molecular weight protein.	scrapie-associated fibril protein (saf-protein) extracted from infectious scrapie-associated fibrils (saf) isolated from scrapie hamster brains is not infectious. saf-protein is composed of various mol. wt. species of glycoproteins differing in carbohydrate content rather than amino acid composition. the n-linked carbohydrate chains represent approximately 40-60% of the mol. wt. of saf-protein. the deglycosylated saf-protein has a surprisingly low mol. wt. of approximately 7 kd, representing app ...	1985	2863137
changes in tyrosine hydroxylase, glutamic acid decarboxylase and choline acetyltransferase after local microinoculation of scrapie agent into the nigrostriatal system of the golden hamster.	a microinjection of a homogenate of scrapie agent-infected brain (strain 263 k) into the nigrostriatal system in the golden hamster is followed by the progressive development of the disease which terminates by the death of animals around the 4th month postinoculation. these intracerebral inoculations induce more rapid changes in neuronal activity which can be revealed by the assessment of the specific synthesizing enzymes of neurotransmitter systems. the microinoculation of a homogenate of an in ...	1985	2864098
in vitro studies with the scrapie agent.	persistent infection with the scrapie agent has been established in l cells. the agent was propagated in homogenates of the cell line designated l-s. the l-s cells showed slower growth rate and morphological changes like pycnosis of nuclei and vacuolization of their cytoplasm. cytogenetic analysis revealed rearrangement of chromosomes in l-s cells. in the course of passaging the number of cells with the characteristic marker chromosome decreased. along with this cells were found with deletion of ...	1985	2864831
characterization of antisera against scrapie-associated fibrils (saf) from affected hamster and cross-reactivity with saf from scrapie-affected mice and from patients with creutzfeldt-jakob disease.	antisera raised in rabbits and also for the first time in mice against scrapie-associated fibril (saf) protein from hamster brain have been quantified by a modified elisa technique (nc-elisa) and used for a detailed analysis of saf proteins obtained from hamster, mouse, and from patients who died of creutzfeldt-jakob disease. the antisera predominantly detected five bands in a western blot analysis with apparent molecular weights of about 26000 (26k), 24k, 20k, 18k and 16k. by gel electrophoresi ...	1985	2865330
scrapie: concept of a virus-induced amyloidosis of the brain.	after an intraperitoneal infection disease-specific incorporation of [3h]leucine into protein and [3h]uridine into rna in the brain precede clinical scrapie in hamsters. onset of both incorporations are the earliest measurable events in the disease. infectivity and subsequent clinical symptoms appear only after this biochemical activity has ceased. the disease-specific [3h]protein co-purifies with scrapie-associated fibrils (saf) and infectivity during differential centrifugation and buffer extr ...	1985	2866955
genetically controlled resistance to virus infections of the central nervous system.		1985	3014607
scrapie prions, brain amyloid, and senile dementia.		1985	2934227
[morphological characteristics of the brain lesions in mice infected with a homogenate of l cells latently infected with the scrapie agent].	degeneration of neurons of the ammon horn lower branch both in the early and terminal stages of the disease of mice infected with the homogenate of l cells latently infected with the scrapie agent (the l-s system) was frequently detected alongside with brain lesions typical of slow infections (vacuolation). examinations of chromosomes in metaphase plates of l-s cells carried out by several methods including the tac system for texture analysis of the image (leutz, brd) revealed three marker chrom ...	1985	3000085
creutzfeldt-jakob infection increases adenylate cyclase activity in specific regions of guinea pig brain.	creutzfeldt-jakob disease is a slow, infectious, progressive neurological disorder which results in human dementia. synaptic membranes from various brain regions of guinea pigs infected with creutzfeldt-jakob disease show increased guanyl nucleotide- or 5-hydroxytryptamine-mediated activation of adenylate cyclase. this increased enzyme activity appears due, primarily, to facilitated 'coupling' between the gtp-binding protein which stimulates adenylate cyclase (gns) and the catalytic moiety of th ...	1986	3082670
estimation of scrapie nucleic acid mw from standard curves for virus sensitivity to ionizing radiation.		1986	3083263
distributions of amyloid plaques in four regions of the brains of mice infected with scrapie by intracerebral and intraperitoneal routes of injection.	vm mice were inoculated by intracerebral and intraperitoneal routes with brain homogenates containing the 87v strain of scrapie. the distribution and numbers of plaques were found for the parietal cortex, cingulate cortex, corpus callosum and hippocampus/dentate in coronal sections cut at the level of the thalamus and stained with masson's trichrome. for the intracerebrally injected animals, the greatest numbers were seen on the side of the brain that had been injected. in the four regions, they ...	1986	3083640
newer data on the inactivation of scrapie virus or creutzfeldt-jakob disease virus in brain tissue.		1986	3084671
separation and properties of cellular and scrapie prion proteins.	purified preparations of scrapie prions contain a sialoglycoprotein of mr 27,000-30,000, designated prp 27-30, which is derived from the scrapie prion protein [mr, 33,000-35,000 (prp 33-35sc)] by limited proteolysis. under these same conditions of proteolysis, a cellular protein of the same size (prp 33-35c) is completely degraded. subcellular fractionation of hamster brain showed that both prp 33-35sc and prp 33-35c were found only in membrane fractions. nacl, edta, and osmotic shock failed to ...	1986	3085093
purification of scrapie agent from infected animal brains and raising of antibodies to the purified fraction.	the fraction (p4) containing scrapie infectivity was obtained by treatment of scrapie-infected mouse brains with the detergent sarcosyl, differential centrifugation, and proteolytic enzyme digestion. scrapie infectivity in the p4 fraction was purified 239-2,390 times with respect to protein. similar fractions were also prepared from the brain of a sheep naturally infected with scrapie. morphological observation of the p4 fractions revealed that the main components were unique rods of 3-5 x 60-20 ...	1986	3086675
scrapie prion proteins are synthesized in neurons.	scrapie is a slow degenerative encephalopathy of animals caused by unusual infectious particles termed prions. a cdna encoding the only apparent component of the prion, a protein designated prp 27-30, has recently been cloned and sequenced. by measuring mrna levels using in situ hybridization with the prp cdna, the authors found that prion proteins are synthesized almost exclusively within neurons. the levels of prp mrna varied among different types of neurons, but did not change during scrapie ...	1986	3079955