Publications

[new data in the study of slow virus infections].		1984	6240161
prions: novel infectious pathogens.		1984	6241423
[blood serotonin and histamine in sheep with endemic scrapie: initial results].	the whole blood histamine levels of sheep without clinical scrapie but living in infected farms, control, and scrapie infected sheep are not significantly different. by contrast whole blood serotonin is decreased both in sheep living in infected farms and in scrapie-infected sheep as compared to controls. thrombopenia may account for the hyposerotoninemia of sheep living in infected farms except those genetically linked to scrapie-infected sheep for which, as for scrapie-infected sheep, platelet ...	1984	6242033
toward development of assays for scrapie-specific antibodies.		1981	6261543
spongiform polioencephalomyelopathy caused by a murine retrovirus. ii. ultrastructural localization of virus replication and spongiform changes in the central nervous system.	the development of murine retrovirus induced spongiform polioencephalomyelopathy was studied sequentially by electron microscopy. during the initial 30 days, viral infection of the central nervous system, as evidenced by viral budding from membranes, was limited to the endothelial cells and pericytes. viral particles were observed in the lumen of blood vessels, extracellular spaces and astrocytic endfeet surrounding blood vessels, but no morphological evidence of productive infection was found i ...	1981	6272148
slow viral infections of animals: experimental models for human disease.	sigurdsson's three criterions for a slow viral infection are quoted and discussed and the background of his work briefly described. a fourth criterion for a slow viral infection, is suggested, infection of the hosts lymphoid tissues, which is a common feature of slow infections that have been observed. the general properties of the maedi-visna virus, the diseases and the immune response it causes are discussed. sheep and goats are susceptible to natural maedi-visna infection. in the goat an iden ...	1981	6273667
scrapie agent contains a hydrophobic protein.	the scrapie agent causes a degenerative nervous system disorder of sheep and goats. considerable evidence indicates that the scrapie agent contains a protein that is necessary for infectivity [prusiner, s. b., groth, d. f., cochran, s. p., masiarz, f. r., mckinley, m. p. & martinez, h. m. (1980) biochemistry 19, 4883-4891], but direct demonstration of a protein moiety has been hampered by lack of sufficiently purified preparations. employing preparations of the scrapie agent enriched 100- to 100 ...	1981	6273882
inability to transmit scrapie by transfection of mouse embryo cells in vitro.	infectivity of nucleic acid from highly infectious mouse scrapie brains was studied by transfecting the nucleic acid in vitro prior to inoculation into animals. foetal mouse brain and whole mouse embryo cultures were chosen as the cells used for the transfection. as an internal control, infectious nucleic acid was recovered from bacteriophage phi x174 and whole virus particles were obtained when cultures were transfected with herpes simplex virus dna. in contrast, none of the animals inoculated ...	1982	6278059
retrovirus antigens in brains of mice with scrapie- and murine leukemia virus-induced spongiform encephalopathy.	wild mouse ecotropic virus-induced spongiform encephalomyelopathy pathologically similar to scrapie was associated with the expression of retrovirus antigens in mouse brains. however, scrapie-infected mice with spongiform encephalopathy showed no increased expression of retrovirus antigens in brain. thus, the pathogenesis of the scrapie spongiform lesion does not appear to involve activation of endogenous retrovirus.	1982	6292099
pathogenesis of mouse scrapie: evidence for spread of infection from central to peripheral nervous system.	the onset of replication has been studied in spinal cord, dorsal root ganglia and spinal nerves of cw mice infected intraperitoneally with the 139a strain of scrapie. the patterns obtained suggest a centrifugal spread of infection from central to peripheral nervous systems. infectivity titres in the peripheral nervous system reached a plateau long before the end of the incubation period, and the maximum titres were much lower than in the central nervous system. this suggests that there is a rest ...	1983	6298352
biohazards of investigations on the transmissible spongiform encephalopathies.	there is considerable current interest in the agents that cause the spongiform encephalopathies: scrapie, transmissible mink encephalopathy, kuru, and creutzfeldt-jakob disease (cjd). the unusual properties of these agents, their elusiveness, and their pathogenicity for humans (in the cases of kuru and cjd) make these agents interesting subjects of investigation but also make imperative a consideration of their potential biohazards in the laboratory. in view of both the potential pathogenicity o ...	1980	6302811
disinfection studies with two strains of mouse-passaged scrapie agent. guidelines for creutzfeldt-jakob and related agents.	a variety of disinfection procedures were tested on two strains of scrapie agent, treated either as brain macerates (autoclaving) or as 10% homogenates (chemical treatments). it is suggested that a given treatment should produce a titre loss, of both strains of scrapie, of at least 10(4) units before it be regarded as useful for the disinfection of the agents of scrapie and creutzfeldt-jakob disease (cjd). by this criterion, treatment at room temperature with about 4% hycolin (0.6% chlorinated p ...	1983	6308174
infectivity of liposomally encapsulated nucleic acids isolated from emc virus and scrapie-infected mouse brain.	the ability of liposomes to enhance nucleic acid infectivity in vivo was studied. encephalomyocarditis (emc) virus rna was extracted and encapsulated within liposomes. the infectivity of emc rna was increased by liposomal entrapment after intraperitoneal injection of mice, but decreased after intracerebral injection. in contrast, when nucleic acids from scrapie-infected brains were entrapped in liposomes and injected into mice by one of four routes, no cases of scrapie were observed. this is the ...	1983	6313546
decreased high-affinity binding of [3h]muscimol to cerebral synaptic membranes of scrapie-infected mice.	scrapie is a transmissible disease that results in progressive degeneration of the central nervous system and death. although scrapie has been studied histopathologically, relatively little is known concerning neurotransmitter alterations. specific [3h]muscimol binding to whole brain crude synaptic membranes (csm) from mice clinically affected with scrapie was significantly (p less than 0.01) reduced, to approximately 73% of that of the controls. of the brain regions examined, binding to only ce ...	1984	6315892
intraneuronal enzymic inclusions in the histological diagnosis of scrapie.	cumulative results are presented of histopathological and enzyme histochemical findings in sheep naturally or experimentally infected with scrapie compared with healthy controls or animals with other diseases. two hundred and sixty-eight sheep were examined, including 210 cases of clinical or suspected scrapie. according to the nature and distribution of histopathological changes, especially neuropil vacuolation and neuronal vacuoles, scrapie-affected sheep were classified into groups. in partic ...	1984	6321570
slow virus diseases of the cns. 2. scrapie, kuru, and jakob-creutzfeldt disease.		1983	6336837
creutzfeld-jakob disease in the province of siena: two cases transmitted to monkeys.	two cases of histopathologically documented creutzfeldt-jakob disease were observed in the same area of the province of siena in 1974-1975. the transmission of the disease was obtained through brain homogenates and lymphnodes in one of the two cases. this confirms that the agent is present in other tissues besides the brain and underlines further the analogies between creutzfeld-jakob disease and scrapie.	1983	6345460
immunohistochemical demonstration of glial fibrillary acidic protein in scrapie.	although little is known about its metabolism, glial fibrillary acidic (gfa) protein has become widely used as a cell-specific, species-non-specific antigenic marker for normal or pathologically altered astroglia. so far there have been few investigations on gfa protein in relation to scrapie and analogous spongiform encephalopathies although there has been a need for an unequivocal method for the discrimination of different types of glia in these diseases. in the present studies, a commercially ...	1983	6345602
scrapie-associated fibrils in creutzfeldt-jakob disease.	scrapie of sheep, and creutzfeldt-jakob disease (cjd) of man belong to a group of transmissible encephalopathies which have been successfully transmitted to a variety of hosts. in susceptible hosts, these diseases are characterized by progressive degeneration of the central nervous system leading inevitably to death. the agents responsible for these diseases have not yet been identified, but they exhibit similar physicochemical characteristics. abnormal fibrils designated 'scrapie associated fib ...	1983	6358899
retinal degeneration in experimental creutzfeldt-jakob disease.	mice with experimental creutzfeldt-jakob disease (cjd) develop a progressive retinal degeneration after a prolonged incubation period. sections of the eyes stained with hematoxylin and eosin revealed pathologic changes in the optic nerve and a marked degeneration of photoreceptor cell inner and outer segment areas. both peripheral and central retina, normally 10 cells thick, were reduced to one photoreceptor cell or less in thickness. ultrastructural analysis revealed total loss of outer segment ...	1983	6361375
[slow viruses of the nervous system in man and animal. iii. creutzfeldt-jakob syndrome].		1983	6364079
amyloid plaques in the brains of mice with creutzfeldt-jakob disease.	by intracerebral inoculation with the brain homogenates from 9 patients with creutzfeldt-jakob disease, amyloid plaques were induced in mouse brains after incubation periods of 403 to 835 days. the plaques existed mainly in the cerebral white matter beneath the lateral ventricle walls and were more numerous in the hemisphere where injection was made. morphological findings of the plaques were almost identical to those seen in patients with kuru and creutzfeldt-jakob disease, and in animals with ...	1984	6372648
infection-specific particle from the unconventional slow virus diseases.	scrapie-associated fibrils, first observed in brains of scrapie-infected mice, were also observed in scrapie-infected hamsters and monkeys, in humans with creutzfeldt-jakob disease, and in kuru-infected monkeys. these fibrils were not found in a comprehensive series of control brains from humans and animals affected with central nervous system disorders resulting in histopathologies, ultrastructural features, or disease symptoms similar to those of scrapie, kuru, and creutzfeldt-jakob disease. t ...	1984	6377496
skin diseases of goats.		1984	6377655
senile dementia of the alzheimer type: possibility of infectious etiology in genetically susceptible individuals.	the concept that sdat is caused by an infectious agent acting in a genetically susceptible host was approached from a number of standpoints. the similarities between sdat and the transmissible encephalopathies are discussed. one of the areas of similarity is the influence of genetic background on the development and expression of both conditions. evidence is presented showing that genetics plays a role in many cases of sdat and that there are known genetically controlled phenomena, the incidence ...	1984	6377804
bitemporal hypometabolism in creutzfeldt-jakob disease measured by positron emission tomography with [18f]-2-fluorodeoxyglucose.	it is well established that creutzfeldt-jakob disease (cjd) is caused by a slow infectious agent similar to the scrapie prion. however, the pathogenesis of this infection is poorly understood. positron emission tomography (pet) was performed on a 54-year-old man with autopsy confirmed cjd using [18f]-2-fluorodeoxyglucose (fdg) and the donner 280-crystal tomograph. temporal lobe hypometabolism with hemispheric asymmetry was observed. these findings are similar to those previously obtained in pet- ...	1984	6381559
prions.		1984	6385236
molecular characteristics of the major scrapie prion protein.	a major protein was identified that purifies with the scrapie agent extracted from infected hamster brains. the protein, designated prp 27-30, was differentiated from other proteins in purified fractions containing the scrapie agent by its microheterogeneity (mr 27000-30000) and its unusual resistance to protease digestion. prp 27-30 was found in all fractions enriched for scrapie prions by discontinuous sucrose gradient sedimentation or sodium dodecyl sarcosinate-agarose gel electrophoresis. it ...	1984	6395885
[the role of animals in central nervous system diseases in man].		1984	6400461
the presence of complements in amyloid plaques of creutzfeldt-jakob disease and gerstmann-straussler-scheinker disease.	the presence of complements clq, c4, c3, c3b, c3c and c3d, as well as amyloid p component, in the amyloid plaques of creutzfeldt-jakob disease (cjd) and gerstmann-straussler-scheinker disease (gss) brains was demonstrated by means of immunofluorescent and immunoperoxidase techniques. positive reaction was not observed in other tissue elements, including the blood vessels. these findings may not be due to an adsorption, but to the immunological binding of complements to the amyloid. proteins such ...	1984	6400466
can scrapie titres be calculated accurately from incubation periods?	since endpoint titrations of scrapie material are costly and time-consuming, several workers have estimated titre from the correlation between the incubation period of the disease and the infectivity titre. however, we show here that the relationship between incubation period and titre cannot be assumed to be constant for all scrapie preparations. our results indicate that sodium deoxycholate treatment of scrapie preparations does not reduce the titre, but can lengthen the incubation period by a ...	1983	6403663
involvement of protein in scrapie agent infectivity.	the nature of the causative agent of scrapie is not known. previous work has demonstrated that nuclease digestion does not inactivate scrapie infectivity, but there are conflicting reports about the effects of proteases. it is shown here that the broad range protease, proteinase k, reduces scrapie infectivity under all conditions tested. control experiments demonstrated that the loss of infectivity is not artefactual and results from protein breakdown. proteolytic digestion in the presence of de ...	1983	6407080
disappearance of scrapie virus from tissues of the mouse.	examination of newborn mice, inoculated intraperitoneally with high doses of scrapie virus, revealed that the virus could not be reisolated from their tissues after about 1 week following inoculation, until almost 1 year later. the inoculum was rapidly removed and was not detectable, although the animals became latently infected. homogenization of whole inoculated newborn animals showed that only about 3% of virus could be recovered by the 2nd day postinoculation (p.i.). during the first 6 days ...	1983	6408020
genetic control of scrapie and creutzfeldt-jakob disease in mice.	genetic control of experimental scrapie and creutzfeldt-jakob disease (cjd) was studied in inbred strains of mice by measuring the times from intracerebral inoculation with the agents to the onset of neurological dysfunction. every strain of mice examined was susceptible to infection; however, a wide range of incubation times was found for both scrapie and cjd. new zealand (nz) mice, which eventually develop an autoimmune disorder, were inoculated intracerebrally with 10(6) id50 units of the scr ...	1983	6408182
resistance of the scrapie agent to inactivation by psoralens.		1983	6410423
in vitro propagation of the scrapie agent. i. transformation of mouse glia and neuroblastoma cells after infection with the mouse-adapted scrapie strain c-506.	seven cell lines including glia cells from mouse brains and mouse neuroblastoma cells were infected with the mouse-adapted scrapie strain c-506. during the early in vitro passages, a stimulation of growth was already observed but cellular morphology and differentiation did not alter. later on, after 12-16 passages, six of the seven infected lines displayed cell proliferation and morphological alterations, suggesting an in vitro morphological transformation. at this stage, differentiation was no ...	1983	6410679
towards purification of the scrapie agent.	a method for the partial purification of scrapie infectivity from hamster brain is described. about a 100-1000-fold, 20-fold, and 200-fold enrichment in scrapie infectivity with respect to protein, rna, and dna content has been achieved using differential centrifugation, enzyme and detergent treatment. the inbred clac strain of hamsters used in our experiments contained about 10 times less infectivity in brain than has been found in randomly bred animals or other inbred strains.	1983	6411468
altered scrapie infectivity estimates by titration and incubation period in the presence of detergents.	during experiments on the purification of scrapie infectivity, changes were found in the dynamics of scrapie titration. after exposure to detergent, infectivity estimates by both endpoint titration and incubation period were altered. the addition of detergent to the diluent used in titration resulted in at least a 100-fold increase in the infectivity estimate. this suggests that the amount of scrapie in a sample, as measured by serial dilution and titration, may be underestimated to different ex ...	1983	6411862
replication of the scrapie agent in hamster brain precedes neuronal vacuolation.	the scrapie agent causes a degenerative neurological disorder in sheep and goats after a prolonged incubation period. hamsters inoculated intracerebrally with 10(7) id50 units of the scrapie agent develop clinical signs of neurological dysfunction 60-65 days later. the titers of scrapie agent in selected regions of the central nervous system (cns) of hamsters were determined prior to the onset of clinical illness. at 48 days after inoculation, the cerebrum, cerebellum, brain stem, and spinal cor ...	1983	6411868
a protease-resistant protein is a structural component of the scrapie prion.	fractions purified from scrapie-infected hamster brain contain a unique protein, designated prp. it was labeled with n-succinimidyl 3-(4-hydroxy-5-[125i]-iodophenyl) propionate, which did not alter the titer of the scrapie prion. the concentration of prp was found to be directly proportional to the titer of the infectious prion. both prp and prion infectivity were resistant for 2 hr at 37 degrees c to hydrolysis by proteinase k under nondenaturing conditions. prolonging the digestion resulted in ...	1983	6414721
scrapie prions aggregate to form amyloid-like birefringent rods.	a large scale purification protocol employing zonal rotor centrifugation has been developed for scrapie prions. the extensively purified fractions derived using this protocol contained only one major protein, designated prp, and rod-shaped particles. the rods measured 10 to 20 nm in diameter and 100 to 200 nm in length by negative staining; no other particles were consistently observed. sds denaturation caused the rods to disappear, prion infectivity to diminish, and prp to become sensitive to p ...	1983	6418385
pathogenesis of mouse scrapie. evidence for direct neural spread of infection to the cns after injection of sciatic nerve.	previous studies of peripherally injected mouse scrapie suggested that invasion of the cns occurs initially in mid-thoracic cord by neural spread of infection from spleen and other visceral sites of extraneural replication. we now show that infection of the left sciatic nerve leads to direct spread of infection to brain (at a rate of approximately 1.0-2.0 mm/day), bypassing the need for extraneural replication and thus producing shorter incubation periods. however, the efficiency of intraneural ...	1983	6418861
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
neuropathology of experimental transmissible spongiform encephalopathy (263 k strain of scrapie in golden syrian hamsters). i. standard pathology and development of lesions.		1983	6420725
experimental control of cerebral amyloid in scrapie in mice.		1983	6420837
virus like sensitivity of the scrapie agent to heat inactivation.	the resistance of the infectious agent of scrapie disease to sterilization at 100 degrees or 121 degrees c is reputed to be inconsistent with the structure of conventional viruses. however, in kinetic studies the majority of hamster scrapie strain 263k infectivity was (like that of previously characterized viruses) rapidly inactivated at temperatures of 100 degrees c or greater. small resistant subpopulations remained. similar heat-resistant subpopulations were observed at 60 degrees c for phage ...	1984	6420887
preclinical changes in weight of scrapie-infected mice as a function of scrapie agent-mouse strain combination.	several inbred strains of mice were injected with different scrapie agents and their total body weight was monitored throughout the incubation period. as a control, mice were injected with normal mouse brain homogenate. for most combinations of scrapie agent and mouse strain, weights during the preclinical phase were similar to or lower than the average weight of controls. for some combinations there was a significant increase in weight (compared to controls) during the latter part of the precli ...	1984	6421769
scrapie infectious agent is virus-like in size and susceptibility to inactivation.	the virions of all known viruses are composed of small amounts of genomic nucleic acid enveloped by proteins and other macromolecules. the aetiological agents of scrapie disease and the other subacute spongiform virus encephalopathies (ssve), a group of slow, fatal degenerative diseases of the central nervous system, are, based on their resistance to sterilization and on indirect measurements suggesting subviral size, thought to have non-viral structures (see refs 1-3 for reviews). the kinetic s ...	1984	6424032
[virion or prion? reflections on the physicochemical structure of the scrapie agent].		1984	6427645
cerebral metabolic changes induced by an unconventional agent: experimental model for some human degenerative diseases of the central nervous system.		1984	6429523
[the ola major histocompatibility complex of sheep. genetic frequencies compared in prélpe sheep with and without scrapie].	the ola genic frequencies were studied in both normal "préalpe" sheep and those affected with scrapie. in the non-affected sheep of contaminated flocks, frequencies were generally decreased, compared with frequencies of the same factors in sick sheep or in non-infected controls. three ola-a genes significantly decreased; at this locus, results in "préalpe" and "ile-de-france" sheep were inversed. this observation excludes ola genes being involved in pathogeny or resistance to the disease, but su ...	1984	6430472
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
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
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
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
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
an epidemiologic critique of creutzfeldt-jakob disease.		1980	6448751
interactions between viral infection and immune mechanisms.		1980	6451349
evidence for normal cell-mediated immunity in scrapie-infected mice.	comparisons between mixed lymphocyte cultures of splenocytes from scrapie-infected and normal mouse brain-inoculated control mice did not reveal any evidence of an impaired cell-mediated immune response in scrapie-infected mice. likewise, mixed lymphocyte cultures of splenocytes from scrapie-infected and normal mice demonstrated that infected spleen cells had no scrapie-specific antigens on their surfaces. these data suggested that the absence of a detectable scrapie-specific immune response in ...	1981	6454663
histochemical and morphometric evaluation of skeletal muscle of cachectic sheep.	skeletal muscle of sheep was examined histochemically in an attempt to define muscle fiber populations capable of distinctive biological behavior. atpase at alkaline and acid ph, nadh-tr, and succinic dehydrogenase showed at least 12 fiber types, but only three often enough to be considered biologically important muscle fiber populations. the proportions of the three major types altered during early life, but not perceptibly during adult life. proportions of type i and type ii fibers were differ ...	1981	6455004
hypersensitivity to central serotonin receptor activation in scrapie-infected hamsters and the effect of serotonergic drugs on scrapie symptoms.	low doses of the serotonin agonist, quipazine, and the serotonin precursor, l-5-hydroxytryptophan methyl ester, produce small but significant reductions in scrapie-induced ataxia and action jerks in hamsters. higher doses of both drugs elicit a behavioral syndrome specific for central serotonin receptor activation. scrapie-infected hamsters show a dramatic hypersensitivity to both drugs compared to control animals. this suggests that scrapie infection in hamsters causes a disturbance in the sero ...	1981	6456788
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
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
[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
the occurrence of scrapie of sheep in japan.		1984	6513247
the sequential development of spongiform change and gliosis of scrapie in the golden syrian hamster.	the lesion profiles of spongiform change and gliosis in the hamster occurring after intracerebral (ic) inoculation of scrapie virus, are calculated and compared to the lesion profile of spongiform change of scrapie in mice and of scrapie and creutzfeldt-jakob disease (cjd) in the squirrel monkey. the profile of scrapie in hamsters differs considerably from that of a closely related strain of scrapie in mice, and both differ from scrapie and cjd in the squirrel monkey. these differences emphasize ...	1984	6539361
[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
cerebral glucose utilization: local changes after microinoculation of scrapie agent in hamster.	the effects of scrapie agent on local cerebral energy metabolism were studied by the [14c]2-deoxyglucose (2-dg) autoradiographic method of sokoloff et al. after stereomicroinoculation (0.5 microliter, 10(-2) of scrapie suspension) in hamster left striatum. from a group of 20 hamsters inoculated, 2 animals were killed every 10 days from the 30th day after inoculation to the terminal stage of the disease. experiments were carried out according to the qualitative 2-dg procedure and cerebral autorad ...	1983	6683389
neural pathogenesis of experimental scrapie after intraocular inoculation of hamsters.	hamsters were inoculated intravitreally with the scrapie agent. all animals developed scrapie and retinal degeneration typical of scrapie. the retinal degeneration was greater in the inoculated eyes than in the uninoculated eyes. replication of the scrapie agent was rapid in the inoculated eye. infectivity then spread slowly down the ipsilateral optic nerve to the brain. the replication in the brain paralleled that in the retina of the uninoculated eye. the results support a neural spread of scr ...	1983	6683661
ultrastructural morphology of amyloid fibrils from neuritic and amyloid plaques.	the structure of partially purified, cns amyloid fibrils from three different sources have been compared by negative stain em. the fibrils isolated from brains with senile dementia of alzheimer type were 4-8 nm in diameter, narrowing every 30-40 nm and apparently composed of two 2-4 nm filaments. the fibrils from a gerstmann-sträussler syndrome brain were 7-9 nm in diameter, narrowing every 70-80 nm and with a suggestion that they are composed of two 3-5 nm filaments. the fibrils isolated from 8 ...	1983	6683919
increased blood-brain barrier permeability in scrapie-infected mice.	the present investigation was designed to study the ultrastructural integrity of the blood-brain barrier (bbb) in the cerebral microvasculature of scrapie-infected mice showing clinical illness. cerebral microvessels from either im, vm, or c57bl/6j mice, terminally affected with various strains of scrapie agent showed a focal leakage of horseradish peroxidase (hrp) in all agent-strain and mouse-strain combinations. this leakage was most pronounced in and near the primary site of agent inoculatio ...	1983	6685171
scrapie infectivity, fibrils and low molecular weight protein.	the development of a short incubation model of scrapie (strain 263k), in golden hamsters has added impetus to the purification of the infectious agent. our own attempts have been based on methods pioneered by millson and developed by prusiner. we present here results indicating that a purification factor of up to 10(4) with respect to protein may now be possible. fractions from brain with high infectivity had a sedimentation range of 70-300s and contained an abundance of fibrils closely similar ...	1983	6685822
scrapie in france: some possible predisposing factors in the naturally-acquired disease of sheep.	a nationwide survey of the occurrence of scrapie in france during the 12-year period 1968-1979 has shown the disease to be more widespread than previously thought. the data suggest that certain sheep raising practices, such as transhumance (nomadic grazing), pen and pasture alternations, and use of animals for milk production, may play a possible role in disease prevalence.	1983	6685940
the antiviral compound hpa-23 can prevent scrapie when administered at the time of infection.	the effects of up to 12 daily doses of hpa-23 (ammonium 5-tungsto-2-antimoniate) on scrapie were studied using five experimental models of the disease, some with widely different incubation times. treatment of animals with hpa-23, starting just before injecting scrapie, produced survivors. in some experiments, animals were fully protected against several hundred infectious units of scrapie. treatment of animals after infection was far less effective. prolonging the treatment for several weeks wa ...	1983	6686005
[infectious activity of cell fractions isolated from the brain of mice with scrapie].	the agent of scrapie was found to induce clinically similar diseases in balb/c and nih mice but differing in the duration of the incubation period (155-180 days and 110-140 days, respectively) and pathomorphological manifestations. differentiated examinations of a brain cell pool from mice with scrapie revealed more infectious activity not neutralized with nucleases and pronasa in membrane-free cell fractions than in fractions of slowly sedimenting membranes.	1983	6686393
[epidemiology of aids].		1984	6730611
alzheimer's disease and transmissible virus dementia (creutzfeldt-jakob disease).	ample justification exists on clinical, pathologic, and biologic grounds for considering a similar pathogenesis for ad and the spongiform virus encephalopathies. however, the crux of the comparison rests squarely on results of attempts to transmit ad to experimental animals, and these results have not as yet validated a common etiology. investigations of the biologic similarities between ad and the spongiform virus encephalopathies proceed in several laboratories, and our own observation of inoc ...	1982	6758661
replication of the scrapie agent in ocular neural tissues.	optic nerves and retinas removed from hamsters experimentally inoculated with the scrapie agent contain a high titer of infectivity. ophthalmoscopic examination of these animals revealed gross lesions of retinopathy as early as 3 weeks before the onset of clinical signs of brain degeneration. these results suggest that the scrapie agent may spread centrifugally in nerve fibers after intracerebral inoculation and that the scrapie-associated retinopathy seen in hamsters is directly induced by the ...	1980	6767244
virologic and neurohistologic findings in dairy goats affected with natural scrapie.	virologic and neurohistologic findings in three dairy goats that became affected with scrapie while living with naturally infected suffolk sheep were essentially like those in affected sheep. virus, detected by mouse inoculation, was widespread in non-neural sites, particularly in lymphatic tissues and intestine. im most sites, titers of virus ranged from 3.0 to 3.5 log10 mouse intracerebral ld50/30 mg of tissue. virus was in nervous tissue in much higher titer. ranging from 5.1 to 5.8 log10, th ...	1980	6767304
sensitivity of scrapie infectivity to detergents and 2-mercaptoethanol.	exposure of fractions obtained from scrapie-infected mouse brain to triton x-100 resulted in no change in its infectivity except after sedimentation. infectivity was reduced after exposure to 2-mercaptoethanol but only in the presence of sds. these results support the view that protein is an important component of the scrapie agent and that disulfide bonds may play a part in maintaining the structural integrity of the infectious agent.	1980	6768695
electrophoretic properties of the scrapie agent in agarose gels.	the molecular properties of the scrapie agent were investigated by subjecting partially purified preparations to electrophoresis on agarose gels. when electrophoresis was performed at room temperature in the presence of sodium dodecyl sulfate (nadodso4), most of the recoverable agent was found at the top of the gel, consistent with previous studies indicating aggregation of the agent upon exposure to elevated temperatures. in addition, less than 5% of the agent applied to the gel was found after ...	1980	6771764
[cell fusion induced in vitro by spongiform encephalopathy agents. value of a diagnostic test].		1980	6771862
slow viruses: molecular properties of the agents causing scrapie in mice and hamsters.		1980	6773068
host and viral genetic determinants of the behavioral effects of scrapie encephalopathy.		1980	6773083
molecular properties, partial purification, and assay by incubation period measurements of the hamster scrapie agent.	the scrapie agent causes a progressive degeneration of the central nervous system of animals after a prolonged incubation period. measurements of incubation period length, defined as the time from inoculation to the onset of clinical signs of neurological dysfunction, were related to the titer of the agent and the dilution of the inoculated sample. equations defining the relationship provide a new assay for the agent requiring fewer animals than end point titrations. by use of this incubation pe ...	1980	6775697
gel electrophoresis and glass permeation chromatography of the hamster scrapie agent after enzymatic digestion and detergent extraction.		1980	6775698
[creutzfeld-jakob disease: recent advances; biology of unconventional viruses (author's transl)].	the authors update their earlier review (1973) of the unconventional viruses responsible for the subacute spongiform encephalopathies of man and animals. newer data about the viruses of scrapie and creutzfeldt-jakob disease are summarized. the biology and experimental pathology of the diseases are discussed.	1980	6776473
attempts to establish cell cultures infected with the viruses of subacute spongiform encephalopathies.		1980	6777783
experimental scrapie in the mouse: electrophoretic and sedimentation properties of the partially purified agent.	some biochemical and biophysical properties of the scrapie agent in a partially purified fraction p5 from murine spleen are described in this communication. the agent was stable in the nonionic detergents triton x-100 and nonidet p40 and stable in the nondenaturing, anionic detergents sodium cholate and sodium n-lauroyl sarcosinate. in contrast, sodium dodecyl sulfate (sds) inactivated the agent at high concentrations (1% or >) when the detergent-to-protein ration approached 1.5 g sds/g protein. ...	1980	6778963
progressive retinal degeneration in scrapie-infected hamsters: a light and electron microscopic analysis.	scrapie is considered a prototype of the spongiform encephalopathies. this group of diseases is characterized by a prolonged incubation period, without symptoms, followed by an insidious onset of clinical disease leading to death. attention has mainly been focused on central nervous system pathology, and reports of pathology in the retina have been limited. in this study, hamsters were inoculated intracerebrally with the scrapie agent and serially sacrificed to determine agent titers and patholo ...	1981	6779055
pathogenesis of mouse scrapie: evidence for neural spread of infection to the cns.	the replication of infectious agent has been studied in brain, thoracic cord, and lumbar cord of compton white mice (sinc87) infected with the 139a strain of scrapie. nine experiments were carried out using four different peripheral routes of injection. a highly consistent pattern of results was obtained in which replication in the cns started in the thoracic cord after about 35% of the total incubation period had elapsed (range 25 to 42%). this was followed by the simultaneous onset of replicat ...	1980	6780656