Publications

retinal damage in scrapie mice.	retinal damages in mice infected with scrapie are reported. the effects ranged from no histopathological changes, through partial loss of the outer nuclear layer (onl) to the most severe changes with complete loss of onl cells and photoreceptors. for the most part, cells of inner nuclear and ganglion layers were spared. these changes were found in 23% of c57bl/6j mice injected with the me7 strain of scrapie and in 28.5% of vm mice injected with the 87 v strain, while no changes were found in 13 ...	1982	7199805
photoreceptor degeneration preceding clinical scrapie encephalopathy in hamsters.	hamsters experimentally inoculated with scrapie had histologic and ultrastructural changes in their retinas before clinical signs of central nervous system disease became evident at 50 days postinoculation. the retinal changes were limited to the photoreceptors and began with degenerative changes in the inner segments as early as 8 days postinoculation. as the inner segment lesions became more prominent, associated degenerative changes within outer segments were seen (38 days postinoculation). a ...	1982	7200101
effects of age on cerebral amyloid plaques in murine scrapie.	the frequency of cerebral amyloid plaques in murine scrapie was not influenced by the age of the mouse at injection in a study using several combinations of agent strain and mouse strain. in addition amyloid plaques were not seen in a series of extremely old uninfected mice.	1982	7200199
retinal degeneration during clinical scrapie encephalopathy in hamsters.	weanling hamsters were inoculated intracerebrally with brain suspensions from normal or scrapie-infected hamsters. a third group of uninoculated animal was fed cuprizone. histologic and electron microscopic examination of the neural retinas and retinal pigment epithelium was done. at 50 days postinoculation, when scrapie-infected animals began to show clinical signs of encephalopathy, there was a variable degree of photoreceptor degeneration. by the time animals were moribund, at 74 days postino ...	1982	7200494
[scrapie in switzerland?].		1982	7201673
lateralized neurological signs and pathogenesis of disease experimentally induced by unconventional viruses.		1982	6956497
optic nerve degeneration in hamsters experimentally infected with scrapie.		1982	6890907
pathogenesis of neuritic (senile) and amyloid plaque formation.		1982	6891336
pathogenesis of mouse scrapie: patterns of agent replication in different parts of the cns following intraperitoneal infection.	the dynamics of agent replication were studied at 8 levels of spinal cord and in 9 areas of brain of mice infected intraperitoneally with the 139a strain of scrapie agent. replication in the cns was first detectable at 2 levels of spinal cord between thoracic vertebrae 4 and 9. the onset of replication was progressively delayed by up to 4 weeks at increasingly lower levels of spinal cord. a similar trend was seen at higher levels of spinal cord and in brain. in brain, agent replication occurred ...	1982	6809940
infectious peptides: postulated mechanisms of protovirin replication in scrapie.		1982	6811126
effect of mouse peritoneal macrophages on scrapie infectivity during extended in vitro incubation.	mouse peritoneal macrophages were exposed to scrapie (me7 strain) brain homogenate in vitro for 2 h at 37 degrees. the samples were assayed for infectivity by analysis of scrapie incubation periods and their values compared to those obtained after extended (1-28 days) in vitro incubation. the scrapie incubation periods for scrapie agent-macrophage mixtures which had undergone extended in vitro incubation were longer than for mixtures assayed after a 2-hour exposure to the scrapie agent. the diff ...	1982	6813286
natural infection of suffolk sheep with scrapie virus.	a better understanding of the infectious process in scrapie was sought by studying the temporal distribution of virus in naturally infected suffolk sheep. virus was detected (by mouse inoculation) first in lymphatic tissues and intestine of clinically normal lambs (age, 10-14 months). titers were generally low. infection of the central nervous system was first detected in a 25-month-old clinically normal sheep whose nonneural tissues had moderate amounts of virus. in sheep affected with scrapie, ...	1982	6813384
viroids and prions.	viroids are small "naked" infectious rna molecules that are pathogens of higher plants. the potato spindle tuber viroid (pstv) is composed of a covalently closed circular rna molecule containing 359 ribonucleotides. the properties of pstv were compared with those of the scrapie agent, which causes a degenerative neurological disease in animals. pstv was inactivated by ribonuclease digestion, psoralen photoadduct formation, zn2+ -catalyzed hydrolysis, and chemical modification with nh2oh. the scr ...	1982	6813855
heterogeneic autoantibody against neurofilament protein in the sera of animals with experimental kuru and creutzfeldt-jakob disease and natural scrapie infection.	heterogeneic autoantibodies against axonal neurofilament proteins of mature mouse neurons grown in vitro were detected by the indirect immunofluorescence technique in 12.7% (9 of 71) of the sera from nonhuman primates infected with kuru, in 14.5% (17 of 117) and 4% (1 of 25), respectively, of the sera from nonhuman primates and laboratory rodents infected with creutzfeldt-jakob disease, and in 35% (7 of 20) of the sera from sheep naturally infected with scrapie. autoantibody titers ranged from 1 ...	1982	6815090
identification of a protein that purifies with the scrapie prion.	purification of prions from scrapie-infected hamster brain yielded a protein that was not found in a similar fraction from uninfected brain. the protein migrated with an apparent molecular size of 27,000 to 30,000 daltons in sodium dodecyl sulfate polyacrylamide gels. the resistance of this protein to digestion by proteinase k distinguished it from proteins of similar molecular weight found in normal hamster brain. initial results suggest that the amount of this protein correlates with the titer ...	1982	6815801
[latent infection of continuous l23 cells caused by the agent of scrapie].	two models of latent infection of continuous l23 cells caused by scrapie agent were developed using the method of cell cloning as well as deae-dextran and lidase preparations. the infectious activity was found only in cell homogenate l-c and l-506 (cells of clone l23 latently infected with the compton and c-506 strains of the scrapie agent). a direct relationship between the infectious activity of the cell homogenate and the intensity of brain lesions revealed by morphological examinations of br ...	1982	6818770
further purification and characterization of scrapie prions.		1982	6818988
structure of thermal polymers of amino acids.	when glutamic acid is a predominant amino acid in a thermally polymerized mixture of amino acids, pyro glu is exclusively found at the n-terminal end of the poly-amino acid polymer. it probably initiates the polymerization process. lysine-containing polymers will probably contain epsilon n-(glutamyl)l-lysine cross links which may account for the higher molecular weights observed in these polymers (100-200 000). incorporation of some amino acids facilitates the incorporation of others. when utili ...	1982	6819870
[slow viruses of the human nervous system. ii. scrapie].		1982	6820816
neuronal spread of scrapie agent and targeting of lesions within the retino-tectal pathway.		1982	6173756
polyadenylated rna and scrapie in mice.		1982	6180544
immunological studies of scrapie infection.		1982	6183292
transmission of scrapie by oral route: effect of gingival scarification.		1982	6119548
scrapie: strategies, stalemates, and successes.		1982	6122977
research on scrapie.		1982	6125659
"an epidemiologic critique of creutzfeldt-jakob disease".		1982	7034530
viruses and chronic neurological diseases.		1982	7038246
[creutzfeldt-jakob disease in france: an epidemiological update (author's transl)].	we report here the results of a prospective epidemiological study of creutzfeldt-jakob disease in continental france during the years 1978-80, extending a retrospective study of the decade 1968-1977 previously reported. the new annual mortality figures are 0.53 cases per million people for france as a whole, and 1,01 cases per million people for the paris metropolitan area. the correlation between mortality rate and population density persists in the parisian area, and is not related to differen ...	1982	7048483
scrapie a "gene"?		1982	7110342
focal and asymmetrical vacuolar lesions in the brains of mice infected with certain strains of scrapie.		1982	7180387
study of early stages of the pathogenesis of scrapie in experimentally infected mice.	virological, histological, and electron microscopic methods were used to study the early manifestations of infection in brains and spleens of mice experimentally infected with the scrapie agent. a statistically significant increase in the spleen weight was demonstrated during the incubation period; this occurred only after intracerebral (i.c.) inoculation of the scrapie-containing brain suspensions and subcutaneous (s.c.) inoculation of the scrapie-containing spleen suspensions. no differences w ...	1983	6135333
reaction of mouse cns cells to the scrapie agent in early stages of experimental infection.	accumulation of the scrapie agent, histological lesions and cytometric parameters in layers iii and v of the cerebral cortex and caudate nucleus were investigated in balb/c mice during the incubation period of scrapie after intracerebral (i.c.) inoculation of the agent. the following cell parameters were determined: areas of the body, nucleus, and cytoplasm of neurons, concentration and amount of protein within the nucleus and cytoplasm. one month after i.c. inoculation, titre of the agent in th ...	1983	6139943
failure to modify scrapie in mice by administration of interferon or anti-interferon globulin.	administration of potent mouse interferon preparations or anti-mouse interferon globulin did not influence the evolution of scrapie in mice after intraperitoneal injection of the agent. we conclude that the interferon system is probably not involved in scrapie.	1983	6189965
familial spongiform encephalopathies.		1983	6218552
inactivation of the scrapie agent by pronase.	scrapie agent derived from infected mouse brain was partially purified by agarose-polyacrylamide gel electrophoresis. the preparation was subjected to treatment with rnase a, dnase i, pronase, sodium dodecyl sulfate and sodium dodecyl sulfate-pronase combination. almost total inactivation of scrapie infectivity resulted when the partially purified scrapie agent was treated with sodium dodecyl sulfate-pronase combination whereas the treatment with sodium dodecyl sulfate or pronase alone reduced t ...	1983	6230145
further studies on changes in immunoglobulin g in the sera and csf of herdwick sheep with natural and experimental scrapie.	previous studies showed that the concentration of igg in serum was increased in a high proportion of herdwick sheep in the clinical stage of natural scrapie. the present paper reports similar findings in herdwicks with experimental scrapie in which the clinical signs were different. further studies of the natural disease showed increased concentrations of igg in csf due to passive filtration from serum and not to local antibody production in the cns. qualitative differences in serum igg have als ...	1983	6863615
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
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
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
[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
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
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
slow virus diseases of the cns. 2. scrapie, kuru, and jakob-creutzfeldt disease.		1983	6336837
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
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
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
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
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
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
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
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
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
experimental control of cerebral amyloid in scrapie in mice.		1983	6420837
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
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
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
neuropathology of experimental transmissible spongiform encephalopathy (263 k strain of scrapie in golden syrian hamsters). i. standard pathology and development of lesions.		1983	6420725
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 scrapie agent is apparently not as small as recent claims suggest.	a potentially important claim that the minimum size of infectious scrapie agent is 50,000 mr or less has been investigated. our results suggest that the agent is larger and that the original experiment was misinterpreted.	1983	12033404
dextran sulphate 500 delays and prevents mouse scrapie by impairment of agent replication in spleen.	treatment of scrapie-infected mice with dextran sulphate (ds) 500 resulted in considerably reduced spleen titres over a long period of time. subsequently, the central nervous system disease was delayed or even prevented during the 350-day period of observation. both effects increased after multiple injections of the compound. the potency of ds 500 to protect against scrapie was greatest when treatment and infection were carried out simultaneously. under these conditions the lethality of 500 to 1 ...	1984	6205119
experimental scrapie in rats: first electrophysiological observations.	scrapie was transmitted (1st passage) to various strains of rats through intracerebral (ic) inoculation of sheep-scrapie, mouse-scrapie and hamster-scrapie brains. for the 2nd passage, wistar rats were chosen and inoculated ic with rat-scrapie brain from the 1st passage. three groups of 12 rats were considered (s for sheep, m for mouse, h for hamster). electrodes were chronically implanted for eeg recording. from 100 to 110 days after inoculation, eeg abnormalities were observed, consisting of s ...	1984	6202485
[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
monoamine abnormalities in the brain of scrapie-infected rats.	the effects of the scrapie agent on the levels of monoamines and their metabolites, and on choline acetyltransferase (cat) activity have been investigated in discrete brain areas in the rat. two strains of scrapie (8745 from sheep brain and c506 m3 from mice brain) were inoculated. scrapie-infected rats showed a reduction in the levels of serotonin (prefrontal cortex, hippocampus, striatum) and dopamine (striatum) and an elevation of 5-hiaa levels (cerebral cortex, striatum, thalamus). noradrena ...	1984	6206919
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
prions.		1984	6385236
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
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
the occurrence of scrapie of sheep in japan.		1984	6513247
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
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
choline acetyltransferase activity and [3h]quinuclidinylbenzilate binding in brains of scrapie-infected hamsters.	choline acetyltransferase (chat) activity and [3h]quinuclidinylbenzilate binding were studied in the brain of scrapie-infected hamsters and sham inoculated controls. although scrapie-infected hamsters showed no reduction of chat activity compared to the controls, they showed a decrease in the affinity and maximum number of post-synaptic muscarinic receptors. scrapie virus thus alters the cholinergic system at the post-synaptic rather than at the pre-synaptic level.	1984	6096772
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
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
[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
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
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
skin diseases of goats.		1984	6377655
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
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
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