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immunolocalization of heparan sulfate proteoglycans to the prion protein amyloid plaques of gerstmann-straussler syndrome, creutzfeldt-jakob disease and scrapie.previous histochemical studies have demonstrated highly sulfated glycosaminoglycans (gags) localized to the amyloid plaques in the brains of humans and animals with prion diseases (snow et al., acta neuropathol 77:337, 1989). however, the identity of the specific class of proteoglycan/gag present was not known. the current investigation used immunocytochemical techniques to identify and localize heparan sulfate proteoglycans (hspgs) in human cases of gerstmann-straussler syndrome and creutzfeldt ...19901977959
bovine spongiform encephalopathy. 19901978125
acquisition of protease resistance by prion proteins in scrapie-infected cells does not require asparagine-linked glycosylation.the scrapie and cellular isoforms of the prion protein (prpsc and prpc) differ strikingly in a number of their biochemical and metabolic properties. the structural features underlying these differences are unknown, but they are thought to result from a posttranslational process. both prp isoforms contain complex type oligosaccharides, raising the possibility that differences in the asparagine-linked glycosylation account for the properties that distinguish prpc and prpsc. scn2a and schab cells i ...19901978322
identification of glycoinositol phospholipid linked and truncated forms of the scrapie prion protein.analysis of carboxy-terminal peptides derived from endoproteinase lys-c digests of the scrapie isoform of the hamster prion protein revealed that the majority of the molecules are glycoinositol phospholipid linked through ethanolamine attached at serin-231. however, approximately 15% of prpsc had a carboxy-terminal peptide that ends at glycine-228. it is intriguing that this glycine is part of the prp sequence gly-arg-arg, which is an established target sequence for the proteolysis and release o ...19901980209
spontaneous neurodegeneration in transgenic mice with mutant prion protein.transgenic mice were created to assess genetic linkage between gerstmann-sträussler-scheinker syndrome and a leucine substitution at codon 102 of the human prion protein gene. spontaneous neurologic disease with spongiform degeneration and gliosis similar to that in mouse scrapie developed at a mean age of 166 days in 35 mice expressing mouse prion protein with the leucine substitution. thus, many of the clinical and pathological features of gerstmann-sträussler-scheinker syndrome are reproduced ...19901980379
permethylation and tandem mass spectrometry of oligosaccharides having free hexosamine: analysis of the glycoinositol phospholipid anchor glycan from the scrapie prion protein.permethylation of the glycan isolated from the glycoinositol phospholipid (gpi) anchor of the scrapie prion protein (prpsc) trimethylates a free hexosamine to form a quarternary ammonium salt, substantially increasing the sensitivity for analysis by mass spectrometry. this derivatization induces specific fragmentation reactions in collision-induced dissociation spectra obtained on a four-sector tandem mass spectrometer, identifying the branching pattern of the prpsc gpi glycan.19901981823
genetics of response to slow virus (prion) infection. 19901982401
inhibition of neutrophil functions by scrapie prion protein: description of some inhibitory properties.the effect of scrapie prion protein (prp) either in the native or in the denatured form was studied on in vitro responses of human neutrophils. incubation of neutrophils with native prp caused an inhibition of their aggregation induced by cytochalasin b. moreover, the denatured form was in itself a strong aggregation inducer. when evaluating the effect on generation of neutrophil superoxide anion (o2) we found that neutrophils released o2 in response to the denatured from only but the native for ...19901983177
alterations of arginase activity in scrapie-infected mice and in amyotrophic lateral sclerosis.we followed the dynamics of arginase activity, the ultrastructural changes, and accumulation of the scrapie agent in the cns of scrapie-infected mice. the arginase activity has been shown to increase 5-fold within the first 3-4 months of the incubation period followed by subsequent fall at its end. the peak of increased arginase activity coincided with appearance of multilayer membranes, whereas the decrease of this activity was associated with the greatest development of status spongiosus, syna ...19901983181
intracellular accumulation of the cellular prion protein after mutagenesis of its asn-linked glycosylation sites.the cellular isoform of the prion protein (prpc) is a sialoglycoprotein bound almost exclusively on the external surface of the plasma membrane by a glycosyl phosphatidylinositol anchor. the deduced amino acid sequence of syrian hamster prpc identifies two potential sites for the addition of asn-linked carbohydrates at amino acids 181-183 (asn-ile-thr) and 197-199 (asn-phe-thr). we have altered these sites by replacing the threonine residues with alanine and expressed the mutant proteins transie ...19901983782
acceleration of scrapie in trisomy 16----diploid aggregation chimeras.we studied the susceptibility to prion infection of the trisomy 16----diploid chimeric mouse, a putative model of down syndrome. when weanling chimeras were inoculated intracerebrally with scrapie prions, the time until appearance of the first symptoms of scrapie was reduced by 17 days (from a mean control time of 153 days) and the time to death was reduced by 30 days (from control time of 170 days). our results with trisomy 16 chimeras argue that the susceptibility to central nervous system deg ...19911996884
antemortem diagnosis of scrapie and bovine spongiform encephalopathy. 19912010324
molecular biology and genetics of prions--implications for sheep scrapie, "mad cows" and the bse epidemic. historical background. 19912029844
amyloidosis.amyloidosis is a disease involving the fibrillar deposition of proteins in a manner that uniformly leads to the presence of green birefringence on polarization microscopy after staining the involved tissues with congo red. in the year summarized, a wide range of new information has accumulated about this disease. in this article, attention has been paid to several newly described proteins now known to precipitate into amyloid deposits, including the proteins transthyretin, apolipoprotein a-1, cy ...19912043438
workshop on scrapie-related disease control. 19912065368
are prions misfolded molecular chaperones?a theory has been developed that could explain prion infection. prions could be molecular chaperones that are required for their own assembly. the theory has been deduced from an analysis of protein folding and consequences explored by computer simulations. thermo-kinetic analysis of protein folding shows that a misfolded chaperone gives rise to new misfolded chaperones. consequently such a protein could behave as a new kind of informative molecule and replicate misfolding according to a process ...19911756852
creutzfeldt-jakob disease among libyan jews.the focus of cjd among jews of libyan origin has been recognized for two decades, but the reasons underlying it were unknown. prevailing views suggested transmission from sheep infected with scrapie. however, recent data show that in fact cjd in this ethnic group is a genetically determined disease due to a point mutation on the codon 200 of the prion protein gene. the clinical characteristics of cjd in this group, and particularly the less common periodic activity in the eeg, are reviewed. new ...19911761106
"clusters" of cjd in slovakia: the first laboratory evidence of scrapie.epidemic-like occurrence of creutzfeldt-jakob disease was observed in 1987 in slovakia (orava). search for the cause of cjd focus indicated a coincidence of genetic and environmental risks in clustering patients. since spongiform encephalopathies might be transmitted orally, (bovine spongiform encephalopathy), the possibility of zoonotic source of cjd cases in orava was also considered. a deficient knowledge about the occurrence of scrapie in slovakia stimulated an examination of sheep with sign ...19911761109
slow neurological diseases (scrapie and visna) of the sheep in the ussr. 19911761110
some problems of diagnosis of the spongiform encephalopathies in ruminants.the difficulties of a positive diagnosis in the spongiform encephalopathies based only on epidemiological and clinical data are briefly reviewed. however, in b.s.e. as in scrapie, the epidemiology and the clinical data may frequently suggest these diseases. the main diseases which must be taken into account in the differential diagnosis of both spongiform encephalopathies are discussed and the criteria of the differential diagnosis are tabulated.19911761111
bovine spongiform encephalopathy (bse): the current situation and research.bovine spongiform encephalopathy (bse), discovered in great britain in 1986, was to pose one of the most serious threats to the well-being of the british cattle industry this century. the disease is now established as a member of the group of diseases known as the sub-acute spongiform encephalopathies caused by unconventional, transmissible agents and which includes scrapie of sheep. it is from scrapie of sheep that it appears bse has resulted though it is possible bse may have existed in a sub- ...19911761112
tubulovesicular structures in human and experimental creutzfeldt-jakob disease.tubulovesicular structures (tvs) have been consistently observed in brain tissue of animals with transmissible spongiform encephalopathies such as natural and experimental scrapie, bovine spongiform encephalopathy, and experimental creutzfeldt-jakob disease (cjd). in this communication we demonstrate for the first time the presence of tvs in natural cjd. tvs were detected in all 3 cjd specimens. however, they were rare and were found only in one or two locations per grid. they were seen in diste ...19911761114
experimental drug treatment of scrapie: a pathogenetic basis for rationale therapeutics.pharmacological treatment with polyanions or amphotericin b in hamsters with experimental scrapie reveals that it is possible to delay the appearance of the disease only when the drug is given before the invasion of the agent into the clinical target areas of the brain. we suggest such early treatment may be possible for individuals at high risk of acquiring the disease, such as healthy mutation-positive relatives of patients with familial creutzfeldt-jakob disease or gerstmann-sträussler syndro ...19911761115
the ultrastructural diversity of scrapie-associated fibrils isolated from experimental scrapie and creutzfeldt-jakob disease.several different samples of scrapie-associated fibrils (saf) were extracted in identical fashion from the brains of golden syrian hamsters infected with the 263k strain of scrapie agent and nih swiss mice infected with the fujisaki strain of creutzfeldt-jakob disease (cjd) agent. based on a total of over 500 measurements in individual fibrils in different extracts, hamster fibrils were more abundant, thicker and had better defined substructure than mouse fibrils. hamster protofibrils were usual ...19911770176
detection of scrapie-associated fibrils in scrapie in goats. 19911776227
scrapie investigation. 19911776229
comparison of bovine spongiform encephalopathy risk factors in the united states and great britain. 19911778735
evidence for intrinsic control of scrapie pathogenesis in the murine visual system.using the optic nerve to route scrapie infection into the brain reduces the initial spread of the disease to well-defined neuronal relays, and simplifies the observation of cause and effect of agent transport, replication and degeneration of the nervous system. one drawback of intraocular targeting of infection is the relatively long incubation periods required to produce clinical disease. by using highly-enriched fractions of infectivity and two models of murine scrapie, we have found that this ...19911791991
inactivation of bse agent.although there are no data reported yet for inactivation of bse agent it is reasonable in the interim, to draw upon existing data for other transmissible degenerative encephalopathies (tde), much of which derives from experiments with the scrapie agent. such studies suggest that no standard chemical or physical decontamination procedure will reliably inactivate the amount of scrapie/bse infectivity present in worst-case situations but high concentrations of sodium hypochlorite or sodium hydroxid ...19911794635
genetic and environmental factors determining the development of creutzfeldt-jakob disease in libyan jews.the cluster of creutzfeldt-jakob disease (cjd) among jews of libyan origin is one of the largest in the world. a number of hypotheses have been proposed to account for this cluster, the most prevalent but unsubstantiated hypothesis being that a transmissible agent was ingested in the form of scrapie-infected sheep brains. it has, however, been shown that a modified host protein encoded by the gene specifying the scrapie amyloid precursor is critically involved in the pathogenesis of transmissibl ...19911798423
combination ultrafiltration and 6 m urea treatment of human growth hormone effectively minimizes risk from potential creutzfeldt-jakob disease virus contamination.although genetically engineered human growth hormone (hgh) is now commercially available, native pituitary-derived hgh is still used by physicians in many countries for the treatment of hormone deficiency states. we describe a method using ultrafiltration and 6 m urea that reduced infectivity in human pituitary tissue that had been deliberately contaminated with scrapie virus (an animal analogue of human creutzfeldt-jakob disease virus) from an initial level of 10(9.7) infectious units to just 5 ...19911806470
transmissible spongiform encephalopathies: scrapie, bse and related human disorders. 19911810706
scrapie strain variation and its implications. 19911810707
natural transmission and genetic control of susceptibility of sheep to scrapie. 19911810708
the scrapie agent in vitro. 19911810709
bovine spongiform encephalopathy. 19911810710
[creutzfeldt-jakob syndrome--a disease of viral etiology and genetic pathogenesis: transmitted cerebral amyloidosis induced by viral infection].i summarized the newest data concerning the etiopathogenesis of slow virus disorders, mainly scrapie and creutzfeldt-jakob disease. while there is no doubt that prp plays a pivotal role in scrapie pathogenesis, the direct proof that it is also a part of, or the entire scrapie virus is still lacking. point mutations discovered in the human prp gene, prnp, may actually cause the disease or they may contribute only to the process of amyloid deposition similar to other cerebral amyloidoses.19911811184
bovine spongiform encephalopathy: epidemiological studies on the origin.the results of further epidemiological studies of bovine spongiform encephalopathy (bse) support the previous findings that the onset of exposure of the cattle population to a scrapie-like agent, sufficient to result in clinical disease, occurred in 1981/82. the onset of this exposure was related to the cessation, in all but two rendering plants, of the hydrocarbon solvent extraction of fat from meat and bone meal. a further possible explanation, related to the geographical variation in the repr ...19911823120
epidemiological and experimental studies on a new incident of transmissible mink encephalopathy.epidemiological investigation of a new incident of transmissible mink encephalopathy (tme) in stetsonville, wisconsin, u.s.a. in 1985 revealed that the mink rancher had never fed sheep products to his mink but did feed them large amounts of products from fallen or sick dairy cattle. to investigate the possibility that this occurrence of tme may have resulted from exposure to infected cattle, two holstein bull calves were injected intracerebrally with mink brain from the stetsonville ranch. each ...19911826023
localization of amyloidogenic proteins and sulfated glycosaminoglycans in nontransmissible and transmissible cerebral amyloidoses.we report the localization of amyloid beta-protein and sulfated glycosaminoglycans in senile plaques and vascular amyloid deposits in brain tissues from patients with down's syndrome and alzheimer's disease, and in neurofibrillary tangles of these diseases and those of guamanian parkinsonism-dementia and amyotrophic lateral sclerosis. we also report the immunolocalization of scrapie amyloid in amyloid plaques containing glycosaminoglycans in kuru, creutzfeldt-jakob disease, and gerstmann-sträuss ...19911833944
an overview of bovine spongiform encephalopathy.none of the diseases caused by the "unconventional slow viruses" is highly infectious in its natural host. transmission of infection to other species only occurs if the effective dose is high enough to overcome the species barrier. the current epidemic of bovine spongiform encephalopathy (bse) in the u.k. is believed to have been initiated by scrapie infection of cattle via contaminated meat and bone meal in concentrated feedstuffs. but the effective exposure was extremely low. subsequently the ...19911838995
genetic aspects of amyloidosis. 19911839349
protease sensitivity and nuclease resistance of the scrapie agent propagated in vitro in neuroblastoma cells.the scrapie agent has been propagated in vitro in mouse neuroblastoma cells. to further characterize the tissue culture-derived scrapie agent, we studied the effects of protease and nuclease digestion on the agent derived from these cells. the scrapie agent in these cells was found to be resistant to protease digestions for short times but was inactivated by prolonged digestion at high protease concentrations. in contrast, digestion with a variety of nucleases did not alter the agent titer. thes ...19911846182
nucleoside diphosphatase (ndpase) activity associated with human beta-protein amyloid fibers.nucleoside diphosphatase (ndpase) activity was studied by electron microscope cytochemistry in surgical specimens obtained from aged human cerebral cortices. the presence of ndpase activity on the surface of the microglial cells (mcs) and especially within the endoplasmic reticulum (er) cisternae that are filled with amyloid fibers and that are in continuity with the extracellular amyloid deposits in plaques suggests a possible role of this enzyme in final elaboration of amyloid protein. the clo ...19911851361
scrapie inoculation of mice: light and electron microscopy of the superior colliculi.ultrastructural examination of the superior colliculi of mice intraocularly inoculated with the me7 strain of scrapie showed vacuolation early in the course of infection. brains were examined between 85-260 days after monocular inoculation with scrapie. the mean incubation period for the development of clinical disease was 302 days. vacuolation was seen initially in the contralateral superior colliculus and subsequently in the ipsilateral colliculus. in coded trials light microscopical vacuolati ...19911858484
diagnosis of scrapie. 19911859542
scrapie in cyprus.scrapie was first recorded in cyprus in 1985 in two flocks of sheep and subsequently the disease was diagnosed in dairy goats kept in mixed flocks with affected sheep. by 1989 scrapie had been diagnosed in 23 flocks. epidemiological data presented in the present study are essentially from clinicopathological investigations between 1985 and 1989. a total of 356 out of 957 sheep and 10 out of 30 goats examined from flocks in nicosia, larnaca and limassol districts showed histopathological lesions ...19911868319
neuropathological changes in scrapie and alzheimer's disease are associated with increased expression of apolipoprotein e and cathepsin d in astrocytes.with the rationale that the neuropathological similarities between scrapie and alzheimer's disease reflect convergent pathological mechanisms involving altered gene expression, we set out to identify molecular events involved in both processes, using scrapie as a model to study the time course of these changes. we differentially screened a cdna library constructed from scrapie-infected mice to identify mrnas that increase or decrease during disease and discovered in this way two mrnas that are i ...19911870200
concerned about scrapie. 19911874660
a 'unified theory' of prion propagation.there is now very persuasive evidence that the transmissible agent for spongiform encephalopathies such as scrapie, consists of a modified form of the normal host protein prpc, devoid of any nucleic acid. on the other hand, because there are many different strains of scrapie agent with distinct phenotypes which can be propagated in animals homozygous for the prpc gene, it has been suggested that a nucleic acid must be a component of the agent. can the two views be reconciled?19911876183
[spongiform encephalopathy in a red-necked ostrich (struthio camelus)].the paper describes anamnestic, macroscopic and microscopic findings in a female ostrich (struthio camelus), euthanatized because of central nervous and locomotion disorders. systemic arteriosclerotic lesions were combined with adiposis and signs of spongiform encephalopathy, localized in the brain stem and the medulla oblongata. aetiopathogenesis of the disease remains unknown. differential diagnosis is discussed and the disease compared to similar findings in mammals which suffered from bse/sc ...19911887441
search for a putative scrapie genome in purified prion fractions reveals a paucity of nucleic acids.scrapie can be transmitted by novel infectious pathogens termed prions. no evidence for a scrapie-specific nucleic acid has been detected to date. to investigate amounts, types and sizes of nucleic acid molecules associated with prions in purified preparations, aliquots were deproteinized, and the nucleic acids analysed by page and silver staining. digestion with nucleases and exposure to zn2+ prior to analysis substantially diminished the content of nucleic acids, but did not alter the prion ti ...19911899270
variation in the characteristics of 10 mouse-passaged scrapie lines derived from five scrapie-positive sheep.ten mouse-passaged scrapie lines were initiated from five sheep with clinical scrapie. of the lines, five were initiated and passaged exclusively in mice with the s7s7 genotype and the remaining five lines were initiated in mice with the p7p7 genotype, with two of these lines subsequently being passaged exclusively in p7p7 mice and two being passaged mainly in p7p7 mice. lines were passaged three or four times and two parameters were compared: incubation period and the induction of a weight incr ...19911899690
genetics of prion infections.although the infectious prions causing scrapie and several human transmissible neurodegenerative diseases resemble viruses in many respects, molecular and genetic analyses indicate that prions are fundamentally different from viruses in their structure and the mechanisms by which they cause disease. the only macromolecule that has been identified in infectious prion preparations is a disease-specific isoform of the prion protein, which is encoded by a host gene. a growing body of data supports t ...19911903568
[scrapie, still always a puzzling infection].scrapie belongs to the spongiform encephalopathies in man and animals. the nature of the infectious agent, an "unconventional virus", has not been elucidated so far. the agent starts to replicate in lymphoid tissue, reaches high titers in the brain and induces the formation of amyloid in this organ. after trials to purify the agent, the infectivity proved to be associated with a protein, which has therefore been called "prion", and with rod-like structures from brain tissue (scrapie-associated f ...19911904658
resistance of the me7 scrapie agent to peracetic acid.mouse brain infected with the me7 strain of scrapie agent was exposed for 24 h to a range of concentrations of paa, either as fragments of intact brain or as supernates of homogenised brain. two % paa inactivated the infectivity in intact tissue but not in a supernate. none of the concentrations tested (up to 19%) was effective with supernates, and this was considered to result from the protection afforded by aggregation of infectivity-containing particles.19911904666
[the formation of infectious scrapie-like structures in the persistence of the agent of amyotrophic leukospongiosis in a brain cell culture].electron microscopic analysis of specimens from guinea-pig brain cell cultures infected with amyotrophic leucospongiosis agent (belonging to "unconventional" viruses) revealed accumulation in the culture fluid of abnormal filamentous structures similar to scrapie-associated fibrils (saf) differing in morphology. most of these saf-like structures 10-15 nm in diameter contained helically wound protofilaments with a repeat at certain intervals (50-150 nm). when these structures were inoculated into ...19911907054
impaired thermal inactivation of me7 scrapie agent in the presence of carbon. 19911909069
natural scrapie: detection of fibrils in extracts from the central nervous system of sheep.extracts from the cervical spinal cord and from the medulla, thalamus, cerebellum and cerebral cortex of the brains of 10 sheep, histopathologically confirmed as cases of scrapie, were examined by electron microscopy for the presence of scrapie-associated fibrils. characteristic fibrils were observed in all the extracts except for that from the thalamus of one sheep. no fibrils were found in any extracts from three control sheep. a comparison of these results with a similar study of 22 cases of ...19911909476
[creutzfeldt-jakob disease and gerstmann-sträussler syndrome with reference to their differential diagnosis].differential diagnosis has quite often proved to be difficult between creutzfeldt-jakob disease (cjd) and gerstmann-straussler syndrome. clinical and morphological aspects as well as the pathological course and differential diagnosis of cjd and gerstmann-strüssler syndrome are discussed in some detail. slow influence can be morphologically diagnosed with reference to the overall pattern of individual alterations with inclusion of scrapie-associated fibrils. this morphological diagnosis can be ve ...19911911728
creutzfeldt-jakob disease and blood transfusion. 19911912871
prions and prion proteins.neurodegenerative diseases of animals and humans including scrapie, bovine spongiform encephalopathy, and creutzfeldt-jakob disease are caused by unusual infectious pathogens called prions. there is no evidence for a nucleic acid in the prion, but diverse experimental results indicate that a host-derived protein called prpsc is a component of the infectious particle. experiments with scrapie-infected cultured cells show that prpsc is derived from a normal cellular protein called prpc through an ...19911916104
human gliomas and epileptic foci express high levels of a mrna related to rat testicular sulfated glycoprotein 2, a purported marker of cell death.clone ptb16 has been isolated by differential screening of a human glioma cdna library. northern blot analysis has shown that ptb16 expression is several times (greater than 11-fold) higher in gliomas than in a primitive neuroectodermal tumor. this observation was supported by in situ hybridization and extended to nine other gliomas. expression was virtually absent in adenocarcinoma cells metastasized to brain. malignant gliomas showed stronger hybridization than benign gliomas, while blood capi ...19911924317
sheep and goat health scheme. 19911926688
neuronal autophagy in experimental scrapie.in this study we report the formation of giant autophagic vacuoles (av) in neurons in experimental scrapie in hamsters. autophagy is an important step in the cellular turnover of proteins and organelles. it is known to occur in neurons under physiological as under pathological conditions. giant av, however, are seen very rarely only in pathological states. in our model av are much more numerous after intracerebral (i.c.) transmission of the scrapie agent than after the transmission via the intra ...19911927279
measurement of the concentration of amphotericin b in brain tissue of scrapie-infected hamsters with a simple and sensitive method.a simple, sensitive, and reproducible assay for the measurement of the amphotericin b concentration in tissue extracts was developed by using the fourth derivative of the absorption spectrum of amphotericin b between wavelengths of 330 and 430 nm. the amphotericin b concentration in spleen and brain was proportional to the total amount administered. the amphotericin b concentration in the brain was highly correlated with the increase in the mean incubation period of intracerebrally scrapie-infec ...19911929313
virus-induced amyloidoses.after a short introduction into the general concept of amyloidoses and the genetic disposition involved in these diseases, the genetic disposition for unconventional virus diseases (or transmissible spongiform encephalopathies) and the disease specific amyloid are described. experimental studies on the pathogenesis and the infectious agent suggest that scrapie and related diseases are virus-induced amyloidoses of the brain.19911930093
[spongiform encephalopathies caused by slow viruses from the inorganic world?]. 19911937256
increased multimeric mitochondrial dna in the brain of scrapie-infected hamsters.we observed a marked increase in multimeric mitochondrial dna (mtdna) in brains of scrapie-infected hamsters compared with those of uninfected hamsters. homogenized brain tissue was subjected to subcellular fractionation to isolate scrapie-associated fibrils and tubulofilamentous structures. nucleic acids were extracted from the scrapie-associated fibril/tubulofilament fraction which also contained mitochondria. agarose gel electrophoresis revealed a band corresponding to the size of circular ha ...19911938303
does the infective agent of scrapie replicate without nucleic acid? an assessment.the dogma of a unique status for the scrapie agent falling outside the virological spectrum is critically examined in the light of the circumstances which gave rise to it, and it is concluded that such an extreme view cannot be justified. the dogma arose in the first place by a combination of inadequate methodology and the lack of comparable data from other systems. it has been sustained partly by the same factors, and partly by a general failure to understand the impact on all relevant investig ...19911943871
more on scrapie. 19911955355
naturally occurring scrapie-like spongiform encephalopathy in five domestic cats.naturally occurring transmissible spongiform encephalopathies have been recognised in sheep, man, mink, captive deer and cattle. recently a similar disease was reported in a domestic cat. this paper describes the clinical and pathological findings in five cats with similar signs, including further observations on the original case. all the cats had a progressive, neurological disease involving locomotor disturbances, abnormal behaviour and, in most cases, altered sensory responses. histopatholog ...19911957458
[bovine spongiform encephalopathy: a review].transmissible spongiform encephalopathies are a group of chronic, always fatal diseases affecting the central nervous system of humans and animals. they occur in all species and are probably caused by agents called prions. in this minireview, a first part provides an overview of the various disease forms, a second part is devoted to the molecular biology of transmissible spongiform encephalopathies, and a last part deals with the specific problems of the bovine spongiform encephalopathy.19911962178
in vivo detection of metabolic changes in a mouse model of scrapie using nuclear magnetic resonance spectroscopy.in vivo proton nuclear magnetic resonance (nmr) spectroscopy studies of scrapie in a mouse model have shown the appearance of an abnormal peak in the brain early in the incubation period. this abnormal peak was detected weeks before the detection of a protease-resistant form of a membrane protein and vacuolar histopathology in vitro, and several months before clinical signs, and the signal increased in intensity as the disease progressed. in the chronic stage of the disease, a reduction in n-ace ...19911655955
clostridium difficile infection in adult hamsters.diarrhea was encountered in a group of adult female golden syrian hamsters (mesocricetus auratus) used for titrating the scrapie agent. ninety percent of the cases occurred in animals over 210 days old even though animals of all age groups lived in the colony concurrently. the cause of diarrhea was investigated in both uninoculated animals and those receiving greater than a limiting dilution of scrapie infectivity, i.e., animals that were not expected to contract the experimental scrapie disease ...19911667195
the role of protein ubiquitination in neurodegenerative disease.ubiquitin immunocytochemistry with an antiserum which reacts with ubiquitin-protein conjugates demonstrates the presence of ubiquitinated proteins in filamentous inclusions found in neurones in the major human neurodegenerative diseases, i.e. alzheimer's disease, diffuse lewy body disease, motor neurone disease. ubiquitin immunohistochemistry has revolutionized the neuropathological diagnosis of dementia showing that diffuse lewy body disease is not, as previously supposed, a rare cause of demen ...19911668896
molecular biology and pathology of scrapie and the prion diseases of humans.scrapie and bovine spongiform encephalopathy of animals and creutzfeldt-jakob and gerstmann-sträussler-scheinker diseases of humans are transmissible and genetic neurodegenerative diseases caused by prions. infectious prion particles are composed largely, if not entirely, of an abnormal isoform of the prion protein which is encoded by a chromosomal gene. an as yet unidentified post-translational process converts the cellular prion protein into an abnormal isoform. scrapie neuropathology, incubat ...19911669719
prion biology and diseases. 19911670551
bovine spongiform encephalopathy and man. 19911670807
survival of scrapie virus after 3 years' interment.supernatant fluid from a scrapie-infected hamster brain homogenate was mixed with soil, packed into perforated petri dishes that were then embedded within soil-containing pots, and buried in a garden for 3 years. between 2 and 3 log units of the input infectivity of nearly 5 log units survived this exposure, with little leaching of virus into deeper soil layers. these results have implications for environmental contamination by scrapie and by similar agents, including those of bovine spongiform ...19911671114
scrapie-associated prion protein accumulates in astrocytes during scrapie infection.in the course of scrapie, a transmissible spongiform encephalopathy caused by an unconventional agent, a normal cellular protein is converted to an abnormal form that copurifies with infectivity and aggregates to form deposits of amyloid. we have used immunocytochemistry and methods that enhance detection of amyloidogenic proteins to investigate the types of cells in the central nervous system which are involved in the formation of the abnormal scrapie-associated protein. we show that this prote ...19911671170
different forms of the bovine prp gene have five or six copies of a short, g-c-rich element within the protein-coding exon.current models of the virus-like agents of scrapie and bovine spongiform encephalopathy (bse) have to take into account that structural changes in a host-encoded protein (prp protein) exhibit an effect on the time course of these diseases and the survival time of any man or animal exposed to these pathogens. we report here the sequence of different forms of the bovine prp gene which contain either five or six copies of a short, g-c-rich element which encodes the octapeptide pro-his-gly-gly-gly-t ...19911671225
new mutation in scrapie amyloid precursor gene (at codon 178) in finnish creutzfeldt-jakob kindred. 19911671440
differences in the membrane interaction of scrapie amyloid precursor proteins in normal and scrapie- or creutzfeldt-jakob disease-infected brains.the membrane interaction and hydrophobicity of the normal (prpc) and infectious isoform (prpsc/cjd) of scrapie and creutzfeldt-jakob disease amyloid precursor proteins was studied. the normal isoform of hamster and human scrapie amyloid precursor protein was found on the microsomal/synaptosomal membranes anchored solely by the c-terminal glycolipid. glycolipid cleavage resulted in dissociation from the membranes and change of behavior from a highly hydrophobic to a hydrophilic protein, susceptib ...19911671680
amyloid protein of gerstmann-sträussler-scheinker disease (indiana kindred) is an 11 kd fragment of prion protein with an n-terminal glycine at codon 58.gerstmann-sträussler-scheinker (gss) disease is a familial neurological disorder pathologically characterized by amyloid deposition in the cerebrum and cerebellum. the gss amyloid is immunoreactive to antisera raised against the hamster prion protein (prp) 27-30. this is a proteinase k-resistant glycoprotein of 27-30 kd that is derived from an abnormal isoform of a neuronal glycoprotein of 33-35 kd designated prpsc and is a molecular marker of amyloid fibrils isolated from animals with scrapie a ...19911672107
the disease characteristics of different strains of scrapie in sinc congenic mouse lines: implications for the nature of the agent and host control of pathogenesis.mouse lines which are congenic for sinc, the major gene controlling scrapie incubation period, have been produced by selective breeding from the inbred c57bl(sincs7) and vm(sincp7) strains; the s7 allele of sinc has been introduced into a vm background by 18 serial backcrosses, at each generation selecting on the basis of the incubation period with the me7 scrapie strain. the characteristics of the disease produced by seven scrapie strains have been compared in sincs7 and sincp7 congenic mice an ...19911672371
clinical and molecular genetic study of a large german kindred with gerstmann-sträussler-scheinker syndrome.we have verified, by full open reading frame sequencing, the presence of an amino-acid-altering mutation in codon 102 of the scrapie amyloid protein gene in three affected members of a large and well-documented german family with experimentally transmitted gerstmann-sträussler-scheinker syndrome. in addition, we identified the mutation by partial sequencing or dna restriction enzyme analysis in three of 12 presently healthy family members with an affected parent, and none of 12 members without a ...19911672447
pre-clinical and clinical diagnosis of scrapie by detection of prp protein in tissues of sheep.the usefulness of detecting the scrapie-associated fibrillar protein (prp) in the lymphoreticular organs of sheep as a diagnostic tool was investigated. the prp was detected by means of a rabbit-anti-sheep prp polyclonal antibody by western blot analysis. prp was detected in samples from the central nervous system (cns) of five of six sheep showing clinical signs of natural scrapie infection, in spleen samples from four of the six sheep and in lymph node samples taken from three of the sheep. pr ...19911674826
evidence of ssdna in tubulofilamentous particles: their relationship to scrapie-associated fibrils.abnormal tubulofilamentous particles were identified by electron microscopy using a simple touch negative staining technique from brains of mice infected with four strains of the scrapie agent. treatment by three proteolytic enzymes and subsequent treatment with dnase and mung bean nuclease of grids prepared from the infected animals confirmed previous observations that the tubulofilamentous particles observed in scrapie-effected brains are complex structures. the core of the tubulofilamentous p ...19911674941
morphological and biochemical evidence that scrapie-associated fibrils are derived from aggregated amyloid-like filaments.the membrane fraction from scrapie infected mouse brains was dissolved in saturated urea, centrifuged on a 10 to 50% glycerol gradient at 35,000 rpm for 24 h, and fractionated from the bottom of the tube into 11 fractions. prp was detected throughout the gradient. however, the relative prp concentrations of fractions 4 and 8 were the highest. the relative prp concentration versus protein concentration of fractions 1 to 4 was higher than that of the other fractions. scrapie infectivity also was d ...19911675031
alterations in neurotransmitter-related enzyme activity in scrapie-infected pc12 cells.enzyme activities associated with the neurotransmitter pathways in nerve growth factor-treated, 139a scrapie strain-infected pc12 cells were examined. since these cells show no morphological alterations during the time of agent replication, any scrapie-induced effects would have to be associated with non-vital cellular functions. when compared to controls, infection with the 139a scrapie strain resulted in decreased activity of the cholinergic pathway-related enzymes, choline acetyltransferase a ...19911675247
restriction fragment length polymorphisms of the scrapie-associated fibril protein (prp) gene and their association with susceptibility to natural scrapie in british sheep.we have investigated the correlation between restriction fragment length polymorphisms of the scrapie-associated fibril protein (prp) gene and the incidence of natural scrapie in british sheep during the period from july 1988 to november 1990. sixty percent of the scrapie-positive animals studied were homozygous for a 6.8 kb ecori fragment (e1) and a further 26% carried e1 as heterozygotes. this fragment is linked to susceptibility to experimental scrapie in a closed flock of cheviot sheep. twel ...19911675248
molecular biology of prion diseases.prions cause transmissible and genetic neurodegenerative diseases, including scrapie and bovine spongiform encephalopathy of animals and creutzfeldt-jakob and gerstmann-sträussler-scheinker diseases of humans. infectious prion particles are composed largely, if not entirely, of an abnormal isoform of the prion protein, which is encoded by a chromosomal gene. a posttranslational process, as yet unidentified, converts the cellular prion protein into an abnormal isoform. scrapie incubation times, n ...19911675487
virus-induced amyloidosis in scrapie involves a change in covalent linkages in the preamyloid.preparations of the preamyloid and the amyloid protein from normal and scrapie hamster brains show different solubilization behaviours towards triton x-114 extraction. the normal isoform is completely extractable from microsomal membranes by the detergent, whereas the pathological one is not. both forms can be isolated using preparative sds electrophoresis as the final step in order to remove all non-covalently associated materials. after removal of the sds these purified proteins retain their s ...19911675561
scrapie-infected spleens: analysis of infectivity, scrapie-associated fibrils, and protease-resistant proteins.scrapie-associated fibrils (saf) and protease-resistant proteins (prp) were isolated from spleens and brains of clinical animals (mice and hamsters) from three scrapie agent-host strain combinations, and their concentrations were compared with infectivity levels. the spleens of infected animals contained lower levels of infectivity, prp, and saf than did brains. regardless of the route of infection, both saf and infectivity were detected in spleen before brain. infectivity increased in brains an ...19911676044
paradoxical shortening of scrapie incubation times by expression of prion protein transgenes derived from long incubation period mice.prolonged incubation times for experimental scrapie in i/lnj mice are dictated by a dominant gene linked to the prion protein gene (prn-p). transgenic mice were analyzed to discriminate between an effect of the i/lnj prn-pb allele and a distinct incubation time locus designated prn-i. paradoxically, 4 independent prn-pb transgenic mouse lines had scrapie incubation times shorter than nontransgenic controls, instead of the anticipated prolonged incubation periods. aberrant or overexpression of th ...19911676894
human and experimental spongiform encephalopathies: recent progress in pathogenesis.the spongiform encephalopathies belong to the group of "slow virus infections" of the nervous system, characterized by a long incubation period, a protracted course and involvement of the nervous system with a lethal outcome. in contrast to the conventional virus infections, such as visna in sheep and progressive multifocal leukoencephalopathy (pml) in humans, the etiological agent for the spongiform encephalopathies has not been clearly defined. the known forms in animals are scrapie in sheep a ...19911676992
homozygous prion protein genotype predisposes to sporadic creutzfeldt-jakob disease.the human prion diseases, creutzfeldt-jakob disease (cjd) and gerstmann-sträussler syndrome (gss), are neurodegenerative diseases that are unique in being both infectious and genetic. transmission of both diseases and the animal spongiform encephalopathies (for example, scrapie and bovine spongiform encephalopathy) to experimental animals by intracerebral inoculation with brain homogenates is well documented. despite their experimental transmissibility, missense and insertional mutations in the ...19911677164
secondary structure analysis of the scrapie-associated protein prp 27-30 in water by infrared spectroscopy.a protease-resistant form of the protein prp (prp-res) accumulates in tissues of mammals infected with scrapie, creutzfeldt-jakob disease, and related transmissible neurodegenerative diseases. this abnormal form of prp can aggregate into insoluble amyloid-like fibrils and plaques and has been identified as the major component of brain fractions enriched for scrapie infectivity. using a recently developed technique in fourier transform infrared spectroscopy which allows protein conformational ana ...19911678278
partial dominance of the sa allele of the sip gene for controlling experimental scrapie. 19911679574
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