Publications

[recent advances in the transmissible spongiform encephalopathy research--with special reference to scrapie].		1990	2098959
scrapie agent in muscle.		1990	2105554
vacuolization, incubation period and survival time analyses in three mouse genotypes injected stereotactically in three brain regions with the 22l scrapie strain.	in previous studies we showed that c57bl mice injected stereotactically in the cerebellum with the 22l scrapie strain had a significantly shorter incubation period than those injected with the same agent in other brain regions. in mice injected in the cerebellum, vacuolization was limited to the cerebellum, medulla and mesencephalon, whereas injection into forebrain regions resulted in vacuolization in all brain regions. the studies suggested that the cerebellum had a selective vulnerability for ...	1990	2106573
pathogenesis and pathology of scrapie after stereotactic injection of strain 22l in intact and bisected cerebella.	the mechanisms involved in the spread of scrapie within the brain remain unclear. to examine this issue the 22l scrapie strain was injected in one side of the cerebellum of mice in which the cerebellum had been bisected prior to injection. another group of animals received the same injection into intact cerebella, i.e. without prior bisection. we found that bisection of the cerebella delayed the spread of scrapie agent from the injection site to the contralateral side of the cerebellum and that ...	1990	2106574
resistance of scrapie infectivity to steam autoclaving after formaldehyde fixation and limited survival after ashing at 360 degrees c: practical and theoretical implications.	scrapie-infected hamster brains and their extracted amyloid fibrils were subjected to formaldehyde and steam autoclaving, alone or in combination. treatment with formaldehyde before autoclaving stabilized infectivity, whereas treatment after autoclaving was either inactive or further reduced infectivity. in additional experiments on specimens (not treated with formaldehyde) that were subjected to dry heat, a small amount of infectivity still survived a 1-h exposure to temperatures as high as 360 ...	1990	2107265
bovine spongiform encephalopathy.		1990	2107889
potential retroviral rnas in creutzfeldt-jakob disease.	the molecular nature of the related infectious agents that cause creutzfeldt-jakob disease (cjd) and scrapie is poorly understood, and an agent-specific nucleic acid genome has not yet been identified. several biological manifestations of these agents resemble those seen in retrovirus-induced diseases. we therefore attempted to identify an agent-specific retrovirus-like rna transcript in cjd infectious fractions. a series of synthetic oligonucleotides complementary to known mammalian retroviral ...	1990	2108258
further characterization of scrapie replication in pc12 cells.	the rat pheochromocytoma cell line, pc12, undergoes neuron-like morphological, biochemical and electrophysiological differentiation, in the presence of low concentrations of nerve growth factor (ngf). ngf-treated pc12 cells have been shown previously to support 139a scrapie agent replication. in the present report we extended these findings and analysed the cellular conditions necessary for agent replication. following the infection of differentiated pc12 cells, scrapie replicated to relatively ...	1990	2109041
scrapie and human neurodegenerative diseases.		1990	2109648
is bse simply scrapie in cattle?		1990	2111595
methods for inactivating experimentally induced scrapie in hamster tissues.		1990	2112123
conservation of infectivity in purified fibrillary extracts of scrapie-infected hamster brain after sequential enzymatic digestion or polyacrylamide gel electrophoresis.	infectious extracts of scrapie-infected hamster brain enriched for scrapie-associated fibrils and scrapie amyloid protein (prp) were partially denatured and subjected to either polyacrylamide gel electrophoresis with subsequent isolation of the prp band or sequential enzymatic digestion with deglycosidase, phospholipase, proteinase, and several different nucleases. infectivity measurements of these various specimens revealed a convincing association between infectivity and scrapie amyloid protei ...	1990	2119503
the search for scrapie agent nucleic acid.	despite decades of research, the identity of the scrapie agent has remained elusive. recent studies have discovered much about the influence of the host genome upon scrapie infection, yet relatively little is known about the causative agent itself. the predominant hypothesis in the scrapie field (the prion hypothesis) argues that the disease is the result of an infectious protein and that nucleic acid is not required for infection. biological studies of the scrapie agent, however, suggest that a ...	1990	2120561
incubation periods and histopathological changes in mice injected stereotaxically in different brain areas with the 87v scrapie strain.	after stereotaxic injection into five different brain areas (cortex, caudate nucleus, substantia nigra, thalamus and cerebellum) of im mice with the 87v scrapie strain, the cerebellum had the shortest incubation period. the vacuolation pattern was similar regardless of the area injected with extensive vacuolation in the thalamus, mesencephalon and hypothalamus. the pattern of amyloid plaques differed markedly depending on the area injected. in particular, no plaques were seen anywhere in the bra ...	1990	2122631
what causes scrapie?		1990	2123843
[concerning the so called prions].		1990	2130248
organ-specific modification of the dose-response relationship of scrapie infectivity.	the dose-response relationships of scrapie strain 263k-infected hamster brain and spleen homogenates were compared to determine if intracerebral end-point titrations of infectivity in these homogenates were measures of the same pathogenic phenomenon. analysis of the dose-response curves indicated that the average increase in incubation period per 10-fold dilution (i.e., the dilution kinetics) of brain infectivity was significantly different from that of spleen infectivity. this difference contra ...	1990	2138656
intraperitoneal infection with scrapie is established within minutes of injection and is non-specifically enhanced by a variety of different drugs.	single intraperitoneal (i.p.) doses of 16 different drugs were given to mice 2 h before injecting scrapie i.p. scrapie was injected as serial ten-fold dilutions of standard inocula and the effective titres obtained were used as a measure of the relative efficiency of infection in treated compared to saline injected mice. despite the wide variety of drugs tested, most of them increased, non-specifically, the efficiency of infection by 0.6 to 2.1 log10 i.p. ld50 units (i.e., 4 to 126-fold), but on ...	1990	2142415
pathogenesis of hamster scrapie. adherent splenocytes are associated with relatively high levels of infectivity.		1990	2143064
appearance of tubulovesicular structures in experimental creutzfeldt-jakob disease and scrapie precedes the onset of clinical disease.	we have consistently observed tubulovesicular structures in brain tissues during the terminal stages of naturally occurring and experimentally induced spongiform encephalopathies, irrespective of the host species and virus strain. in nih swiss mice inoculated intracerebrally or intraocularly with the fujisaki strain of creutzfeldt-jakob disease (cjd) virus, tubulovesicular structures, measuring 20-50 nm in diameter, were particularly prominent in dilated, pre- and postsynaptic neuronal processes ...	1990	2160182
[current developments in the problem of prions and prion diseases].	the present paper reports data referring to the mechanism of the cns degenerating process of prion origin, the role of the biological timing in prion diseases, the interrelations between the prion diseases and alzheimer's disease, new data on the normal cell protein prpc and prion protein in the prpsc scrapie, the physico-chemical properties of the prion prp-rn am properties the presence of the nucleic acid in the structure of prion, interrelations between prion and aids/visna retroviruses. the ...	1990	2173118
bovine spongiform encephalopathy and biological products for human use. report of an informal meeting held at nibsc on 16 may 1988.		1990	2180445
mad cows and the minister.		1990	2188132
proceedings of an international roundtable on bovine spongiform encephalopathy.		1990	2189852
scrapie in france.		1990	2189853
prion diseases of the central nervous system.	prions are novel, transmissible pathogens causing degenerative diseases in humans and animals. kuru, cjd, and gss illustrate the infectious, sporadic, and genetic mechanisms for human prion diseases, respectively. scrapie of sheep and goats is the prototypic prion disorder since it was the first of these diseases to be transmitted to laboratory rodents. over the past five years, a large amount of experimental data about the particles causing scrapie has been accumulated. most of the information ...	1990	2192281
survey of encephalopathy incidence set up by health ministry.		1990	2192493
oravske kuru. a human dementia raises the stakes in mad cow disease.		1990	2198656
multidisciplinary team dismisses bse 'threat'.		1990	2198689
bovine spongiform encephalopathy/scrapie.		1990	2201127
immunoreactive a4 and gamma-trace peptide colocalization in amyloidotic arteriolar lesions in brains of patients with alzheimer's disease.	cerebral amyloid angiopathy (caa) defines a biochemically heterogeneous entity that manifests as effacement of cerebral microvessel walls by a fibrillar material with characteristic tinctorial properties. in biochemical terms, the amyloid that infiltrates blood vessels in caa is composed of the a4 or beta peptide of alzheimer's disease (ad), a molecule related to gamma trace or cystatin c (seen in patients with hereditary cerebral hemorrhage with amyloidosis in iceland, hchwa-i), or the prp char ...	1990	2201197
[british cattle plague--also a danger for man? bovine spongiform encephalopathy (bse)--scrapie disease].		1990	2210580
scrapie: minor disease, potentially major problem.		1990	2211287
bovine spongiform encephalopathy--a new disease transmissable to humans?	current concerns about the cattle disease bovine spongiform encephalopathy do not appear to take cognisance of the parallel with scrapie, the similar/identical disease of sheep/goats. this has existed for 200 years, and clearly involved a longstanding consumption of meat/offal from affected animals, but apparently without consequential human disease. a summary is given of the characteristics of the human and animal spongiform encephalopathy diseases and their causative agents. the conclusion of ...	1990	2233424
unsolved problems confronting the sheep industry.	to support a sheep production system, veterinary practitioners must integrate diagnosis, treatment, and prevention with management, nutrition, and economics. scrapie, spider syndrome, prolapses, and parasitism are a few of the less dramatic but constant problems in sheep practice. problems with drug availability and residues may be as difficult to solve as predation and economic problems.	1990	2245376
detection of single-stranded dna in scrapie-infected brain by electron microscopy.	the nucleic acid content of enriched preparations of mitochondria/tubulofilamentous particles from normal and scrapie-infected hamster brains were examined by electron microscopy. after spreading on collodion-coated grids circular molecules of approximately 15.7 kb corresponding in size to mitochondrial dna (mtdna) were observed both in normal and scrapie-infected brains. in nucleic acid preparations from scrapie-infected brains multimeric mtdna and single-stranded dna strands of about 0.49 x 10 ...	1990	2258920
a questionnaire survey of the prevalence of scrapie in sheep in britain.	an anonymous, self-administered questionnaire has been used in two independent surveys to try to determine the prevalence of scrapie in the national sheep flock. the disease was recorded in 35 counties in england and wales. about a third (26.5 and 37.3 percent) of respondents owning 100 or more sheep indicated that they had seen sheep with scrapie in their flocks. the incidences of clinical cases recorded in affected flocks in the two surveys were 0.5 and 1.1 cases/100 ewes/year. at present ther ...	1990	2260251
the use of monosodium glutamate in identifying neuronal populations in mice infected with scrapie.	the excitatory amino-acid, monosodium glutamate, which causes degeneration in the retinal ganglion cells in neonatal mice, was used to investigate the transport of scrapie within optic nerve axons. in treated mice, there was prolongation of the incubation period following intraocular infection with the me7 strain of scrapie, and a decrease in the severity of retinopathy after intracerebral infection with the 79a strain. these data confirm that scrapie infection spreads along neural pathways, and ...	1990	2263317
spongiform encephalopathy in an arabian oryx (oryx leucoryx) and a greater kudu (tragelaphus strepsiceros)	clinical, pathological and epidemiological details of scrapie-like encephalopathies are described in an arabian oryx and a greater kudu. clinical signs included ataxia and loss of condition with a short, progressive clinical course (22 and three days, respectively). histopathological examination of the brains revealed spongiform encephalopathy characteristic of that observed in scrapie and bovine spongiform encephalopathy (bse). it seems probable that these cases have a common aetiology with bse ...	1990	2264242
prevalence of scrapie in british flocks.		1990	2267716
[bovine spongiform encephalopathy: a new entity caused by a non-conventional transmissible agent].	in 1986, a new neurologic disease appeared in the great britain's cattle. according to its histological lesions, this condition belongs to the group of transmissible encephalopathies known as spongiforme encephalopathies (se). these se are associated with no-conventional transmission agent (ncta) or prion. at the time of writing, over 13,000 cases of bovine spongiforme encephalopathy (bse) have occurred in uk. the most likely origin of this dramatic outbreak would be an oral contamination of cat ...	1990	2271982
bovine spongiform encephalopathy in the united states.		1990	2278551
pancreatic lesions and hypoglycemia-hyperinsulinemia in scrapie-injected hamsters.	hamsters injected intracerebrally with scrapie strains 139h or 22ch or with normal hamster brain were assessed for body weight periodically throughout the incubation period. animals injected with the scrapie strains became obese before the appearance of the motor changes that are indicative of the start of clinical disease. during the latter part of the incubation period and during clinical disease, animals were hypoglycemic and showed marked hyperinsulinemia. at autopsy, there was marked hyperp ...	1990	2313125
bse, scrapie and laboratory models.		1990	2316164
transmission of encephalopathies.		1990	2321340
tainted feed, mad cows. could a british cattle disease infect u.s. herds?		1990	2333492
library subtraction of in vitro cdna libraries to identify differentially expressed genes in scrapie infection.	we have developed a system where double-stranded cdna can be amplified using a synthetic oligonucleotide primer and the polymerase chain reaction, generating cdna libraries in vitro. using a library subtraction strategy (1), scrapie and control brain in vitro cdna libraries were used to identify sequences whose expression is modulated in scrapie infection. one of these sequences represents beta-2 microglobulin, while the other two have not been previously described. the use of in vitro libraries ...	1990	2339063
changes in the distribution of anionic sites in brain micro-blood vessels with and without amyloid deposits in scrapie-infected mice.	cationic colloidal gold (ccg) and scrapie-infected mouse brain samples embedded in lowicryl k4m were used for ultrastructural localization of negatively charged microdomains (anionic sites) in the cerebral microvasculature. the distribution of anionic sites on both fronts (luminal and abluminal) of endothelial cells and in the basement membrane (bm) in the majority of micro-blood vessels (mbvs) located outside the plaque area and in the remaining cerebral cortex was similar to that which has bee ...	1990	2339589
new fears on transmission.		1990	2342557
an overview of scrapie in the united states.		1990	2347765
experimentally induced bovine spongiform encephalopathy in cattle in mission, tex, and the control of scrapie.		1990	2347766
the scrapie control program in the united states.		1990	2347767
recommendations for initiation of research studies on bovine spongiform encephalopathy.		1990	2347769
histopathology and image analysis of brain lesions in ovine scrapie in japan.		1990	2348610
ministerial madness avoided.		1990	2348868
the unexpected export?		1990	2348869
frankness needed.		1990	2359438
link between scrapie and bse?		1990	2366871
spongiform encephalopathy in an eland.		1990	2368268
mps to look at government handling of bse.		1990	2368285
bse risks.		1990	2368290
coexistence of creutzfeldt-jakob disease and alzheimer's disease in the same patient.	we report the case of a 73-year-old patient in whom a diagnosis of creutzfeldt-jakob disease, suggested by the clinical course, was verified by the neuropathologic finding of widespread spongiform change and astrogliosis, the presence of proteinase-resistant protein in brain extracts, and the experimental transmission of spongiform encephalopathy to primates inoculated with brain tissue. however, neuropathologic examination also revealed a profusion of senile and neuritic plaques and neurofibril ...	1990	2405293
three hamster species with different scrapie incubation times and neuropathological features encode distinct prion proteins.	given the critical role of the prion protein (prp) in the transmission and pathogenesis of experimental scrapie, we investigated the prp gene and its protein products in three hamster species, chinese (cha), armenian (aha), and syrian (sha), each of which were found to have distinctive scrapie incubation times. passaging studies demonstrated that the host species, and not the source of scrapie prions, determined the incubation time for each species, and histochemical studies of hamsters with cli ...	1990	2406562
transmissible encephalopathies in animals.	scrapie in sheep and goats is the best known of the transmissible encephalopathies of animals. the combination of maternal transmission of infection and long incubation periods effectively maintains the infection in flocks. a single sheep gene (sip) controls both experimental and natural scrapie and the discovery of allelic markers could enable the use of sire selection in the control of the natural disease. studies of experimental rodent scrapie show that neuroinvasion occurs by spread of infec ...	1990	2407328
the molecular mechanisms of scrapie encephalopathy and relevance to human neurodegenerative disease.	we have investigated alterations in the structure and function of nuclei isolated from normal and pathological brains in a number of neurodegenerative diseases including scrapie and alzheimer's disease. here we summarize both general and specific changes in chromatin structure, gene expression, and neuropathological features for each encephalopathy and compare them in terms of their molecular biological similarities and differences. while both scrapie and alzheimer's disease share a number of co ...	1990	2407330
[encephalopathy caused by prions].	the concept of prion encephalopathy has emerged from such previous notions as slow virus infections, spongiform encephalopathies or transmissible dementias. the term prion (prusiner, 1982) is now used in preference to unconventional agents. proteins and genes of prions have recently been identified by molecular biology. exactly how prion proteins are amplified in cells is still unknown. it has been demonstrated that amyloid deposits in scrapie-infected brain, creutzfeldt-jakob, gerstmann-straüss ...	1990	2408126
immunohistochemical localization of prion protein in spongiform encephalopathies and normal brain tissue.	we used polyclonal antibodies raised against hamster and mouse prp27-30 as immunologic probes to study the localization of intracellular and extracellular deposits of prion protein in normal and scrapie-infected mouse and hamster brains and in creutzfeldt-jakob disease (cjd)-infected mouse brains. in addition, we examined normal human brain and brain tissues from patients with cjd, kuru, alzheimer's disease, and idiopathic chronic encephalitis. there was positive staining in the cytoplasm of neu ...	1990	1690364
pronase does not reduce the protein content of hirt supernatant of normal mouse brain.	normal mouse brain has been used as a model in experiments to explain the reduction of infectivity obtained following incubation with pronase of brain infected with the scrapie infective agent. incubation of hirt supernatants of normal mouse brain with pronase had no effect on the protein content when compared to controls similarly incubated without pronase. this points to a resistance of the proteins in the brain extract to protease or to the presence of anti-protease activity. much of the 'rna ...	1990	1693052
a simple and effective method for inactivating virus infectivity in formalin-fixed tissue samples from patients with creutzfeldt-jakob disease.	we fixed brains from hamsters infected with scrapie virus in (1) formalin, (2) phenol-saturated formalin, (3) formalin with a 1-hour immersion in formic acid, or (4) phenol-saturated formalin with a 1-hour immersion in formic acid. in addition, we used the formalin-formic acid procedure on brains from mice infected with the virus of creutzfeldt-jakob disease. formic acid proved superior to phenol in respect to both disinfection and tissue preservation, almost completely eliminating virus infecti ...	1990	1693181
scrapie prion proteins accumulate in the cytoplasm of persistently infected cultured cells.	the cellular prion protein (prpc) is a sialoglycoprotein anchored to the external surface of cells by a glycosyl phosphatidylinositol moiety. during scrapie, an abnormal prp isoform designated prpsc accumulates, and much evidence argues that it is a major and necessary component of the infectious prion. based on the resistance of native prpsc to proteolysis and to digestion with phosphatidylinositol-specific phospholipase c as well as the enhancement of prpsc immunoreactivity after denaturation, ...	1990	1693623
ultrastructure of the cells forming amyloid fibers in alzheimer disease and scrapie.	ultrastructural, three-dimensional reconstruction of cells surrounding the amyloid star in classical plaques in alzheimer disease (ad) and histochemical studies of the cells associated with the deposits of amyloid fibers in scrapie were carried out. these studies showed that in both diseases, the fibers appear within the smooth endoplasmic reticulum (er) and infoldings of cytoplasmic membranes of microglia/macrophages. additional information about the site of formation of the amyloid fibers deri ...	1990	1963537
stem loops in hiv and prion protein mrnas.	tat-dependent trans-activation in hiv requires presentation of a cuggg pentanucleotide at the end of a stem loop within the tar site of the viral long terminal repeat. a tandem repeat within the open reading frame of the prion protein (prp) mrna is able to form similar stem loop structures with which the hiv tat protein could interact, disturbing prp translation. self-amplification of such a disturbance has been suggested as the cause of the scrapie group of diseases, including the scrapie-like ...	1990	1967310
rapid detection of creutzfeldt-jakob disease and scrapie prion proteins.	creutzfeldt-jakob disease (cjd) and gerstmann-sträussler syndrome (gss) of humans as well as scrapie of animals are caused by prions. the scrapie prion protein isoform (prpsc) is the only macromolecule identified to date which is a component of the infectious prion particle. prpsc is converted to prp 27-30 by limited proteolysis while the cellular isoform, designated prpc, is completely digested under the same conditions. elisa studies demonstrated that native prp 27-30 bound to plastic surfaces ...	1990	1967489
normal and scrapie-associated forms of prion protein differ in their sensitivities to phospholipase and proteases in intact neuroblastoma cells.	previous studies have indicated that scrapie infection results in the accumulation of a proteinase k-resistant form of an endogenous brain protein generally referred to as prion protein (prp). the molecular nature of the scrapie-associated modification of prp accounting for proteinase k resistance is not known. as an approach to understanding the cellular events associated with the prp modification in brain tissue, we sought to identify proteinase k-resistant prp (prp-res) in scrapie-infected ne ...	1990	1968104
scrapie and cellular prion proteins differ in their kinetics of synthesis and topology in cultured cells.	both the cellular and scrapie isoforms of the prion protein (prp) designated prpc and prpsc are encoded by a single-copy chromosomal gene and appear to be translated from the same 2.1-kb mrna. prpc can be distinguished from prpsc by limited proteolysis under conditions where prpc is hydrolyzed and prpsc is resistant. we report here that prpc can be released from the surface of both normal-control and scrapie-infected murine neuroblastoma (n2a) cells by phosphatidylinositol-specific phospholipase ...	1990	1968466
analysis of linkage between scrapie incubation period and the prion protein gene in mice.	a single gene is known to have a predominant influence on scrapie incubation period in mice. in crosses between strains that give a short incubation period, such as nzw mice, and those which give a long incubation period, such as i/lnj mice, long incubation period was dominant using a chandler scrapie agent isolate. recently a close linkage was found between the incubation period gene and the prion protein (prp) structural gene in i/lnj mice crossed to nzw mice. because this linkage suggested an ...	1990	1968507
subcellular distribution and physicochemical properties of scrapie-associated precursor protein and relationship with scrapie agent.	we studied the biologic properties of hamster-adapted scrapie (strain 263k) and its relationship to the precursor protein of scrapie (prp33-35sc). the highest titer of infectious material and the greatest concentration of prp33-35sc were in the fractions containing microsomal and synaptosomal membranes. we found traces of infectivity in the absence of prp33-35sc associated with matrix protein. partitioning of membranes with neutral chloroform-methanol resulted in concentration of prp33-35sc and ...	1990	1969124
scrapie infectivity and prion protein are distributed in the same ph range in agarose isoelectric focusing.	we separated lysed synaptosomal-microsomal membrane fraction from scrapie-infected hamster brain in preparative agarose isoelectric focusing. we also studied the distribution of prp27-30 and scrapie infectivity in 13 regions of the gel in the range of ph 3.5 to 9.3. most of the infectivity remained in the trough, where it had been placed at the beginning of the electrophoresis, along with prp27-30. scrapie infectious particles that encountered the gel demonstrated charge heterogeneity and were d ...	1990	1969125
scrapie-associated precursor proteins: antigenic relationship between species and immunocytochemical localization in normal, scrapie, and creutzfeldt-jakob disease brains.	we describe the antigenic properties and detection of a normal isoform of scrapie-associated precursor protein (prp33-35c) in normal, and both normal and scrapie isoforms in scrapie- or creutzfeldt-jakob disease (cjd)-infected mouse, hamster, and human brains, using a variety of specific antibodies. polyclonal antibodies raised against mouse and hamster prp27-30 and against a synthetic peptide of the n-terminal sequence of this protein were used as immunologic probes. prp27-30 purified as a prim ...	1990	1969126
cellular isoform of the scrapie agent protein participates in lymphocyte activation.	the scrapie agent protein (sp33-37 or prpsc) is the disease-associated isoform of a normal cellular membrane protein (cp33-37 or prpc) of unknown function. we report that normal human lymphocytes and lymphoid cell lines, but not erythrocytes or granulocytes, express prpc mrna and protein. prpc is detectable on the surface of lymphocytes; the surface immunoreactivity is sensitive to phosphatidylinositol-specific phospholipase c, indicating glycosyl-phosphatidylinositol membrane anchorage. lymphoc ...	1990	1969332
two alleles of a neural protein gene linked to scrapie in sheep.	sheep are the natural hosts of the pathogens that cause scrapie, an infectious degenerative disease of the central nervous system. scrapie-associated fibrils [and their major protein, prion protein (prp)] accumulate in the brains of all species affected by scrapie and related diseases. prp is encoded by a single gene that is linked to (and may be) the major gene controlling the incubation period of the various strains of scrapie pathogens. to investigate the role of prp in natural scrapie, we ha ...	1990	1969635
differential glycosylation of the protein (prp) forming scrapie-associated fibrils.	prp is a glycoprotein found in normal brain. in brain affected by scrapie it forms scrapie-associated fibrils (saf). prp from saf shows considerable heterogeneity of size and charge on two-dimensional gels. it separates into six major regions, the three more acidic regions arising as a result of partial proteolytic degradation. the two more basic higher mr forms (mr 34,000 and 29,000) of prp can be reduced in apparent mr to a lower mr form (mr 25,000) with peptide-n-glycosidase f. in addition, a ...	1990	1969925
bse in perspective.		1990	1971325
experimental transmission of scrapie to cattle.		1990	1971338
detection of bovine spongiform encephalopathy in the united kingdom.		1990	1971813
scrapie isoform of scrapie-associated protein.		1990	1971814
laboratory markers for detection of scrapie.		1990	1971815
structure of scrapie-associated protein and its relation to infectivity.		1990	1971816
attempts to detect evidence of scrapie-associated protein in bovine tissue-derived products.		1990	1971817
presence of mitochondrial d-loop dna in scrapie-infected brain preparations enriched for the prion protein.	the prion preparation has, in recent years, been the focal point of scrapie research. the inability to identify agent-specific nucleic acids in this sample has led to the formulation of the infectious protein or prion hypothesis. in this study, we analyzed three different prion protein-enriched preparations and found all to contain significant amounts of mitochondrial nucleic acid. southern blot analyses indicated that they are enriched for a specific component of the mitochondrial genome, the s ...	1990	1972202
the mrna encoding the scrapie agent protein is present in a variety of non-neuronal cells.	prp 27-30, a unique protease-resistant protein associated with scrapie infectivity, derives from the proteolytic cleavage of a larger precursor encoded by a host gene. to identify sites of prp biosynthesis, in situ hybridization was done using cloned prp cdna as a probe. in rodent brain, prp mrna was expressed in neurons, ependymal cells, choroid plexus epithelium, astrocytes, pericytes, endothelial cells and meninges of both scrapie-infected and uninfected animals. prp mrna was also detected in ...	1990	1972856
nuclease treatment results in high specific purification of creutzfeldt-jakob disease infectivity with a density characteristic of nucleic acid-protein complexes.	representative preparations of partially purified creutzfeldt-jakob disease (cjd), including disaggregated density gradient fractions, were treated with a variety of nucleases. rnases as well as exhaustive digestions with micrococcal nuclease did not significantly diminish infectivity, but resulted in an approximately 7,000-fold specific purification of infectivity with respect to nucleic acid. protected nucleic acids included species of up to 2,000 bases in length. after nuclease treatment, inf ...	1990	1974131
differential release of cellular and scrapie prion proteins from cellular membranes by phosphatidylinositol-specific phospholipase c.	the abnormal isoform of the scrapie prion protein prpsc is both a host-derived protein and a component of the infectious agent causing scrapie. prpsc and the normal cellular isoform prpc have different physical properties that apparently arise from a posttranslational event. both prp isoforms are covalently modified at the carboxy terminus by a glycoinositol phospholipid. using preparations of dissociated cells derived from normal and scrapie-infected hamster brain tissue, we find that the major ...	1990	1974460
identification of cellular proteins binding to the scrapie prion protein.	the scrapie prion protein (prpsc) is an abnormal isoform of the cellular protein prpc. prpsc is found only in animals with scrapie or other prion diseases. the invariable association of prpsc with infectivity suggests that prpsc is a component of the infectious particle. in this study, we report the identification of two proteins from hamster brain of 45 and 110 kda (denoted prp ligands pli 45 and pli 110) which were able to bind to prp 27-30, the protease-resistant core of prpsc on ligand blots ...	1990	1974464
molecular mass, biochemical composition, and physicochemical behavior of the infectious form of the scrapie precursor protein monomer.	a highly purified fraction obtained from scrapie (263-k strain)-infected hamsters' brains by an alternative procedure without proteinase k treatment contained a protease-resistant form of the scrapie precursor protein (prpsc) and infectivity of 9.9 +/- 0.7 log ld50/ml. polyclonal antibodies produced against hamster scrapie amyloid protein (prp27-30) and used in a neutralization test diminished infectivity of the prpsc preparations by 1.6 log after intracerebral inoculation and by 1 log after int ...	1990	1974720
mutation in codon 200 of scrapie amyloid protein gene in two clusters of creutzfeldt-jakob disease in slovakia.		1990	1975028
mutation in codon 200 of scrapie amyloid precursor gene linked to creutzfeldt-jakob disease in sephardic jews of libyan and non-libyan origin.		1990	1975415
bovine spongiform encephalopathy: detection and quantitation of fibrils, fibril protein (prp) and vacuolation in brain.	bovine spongiform encephalopathy (bse) is a new disease of cattle which has considerable homology with scrapie, the archetype of the transmissible spongiform encephalopathies. abnormal brain fibrils, called scrapie associated fibrils (saf), are specific ultrastructural markers for these diseases. fibril detection was compared with histopathological diagnosis in the brains of 167 cattle; 157 clinically suspect bse and 10 clinically normal. fibrils were detected in samples of pooled brain regions ...	1990	1976286
transgenetic studies implicate interactions between homologous prp isoforms in scrapie prion replication.	transgenic (tg) mice expressing both syrian hamster (ha) and mouse (mo) prion protein (prp) genes were used to probe the mechanism of scrapie prion replication. four tg lines expressing haprp exhibited distinct incubation times ranging from 48 to 277 days, which correlated inversely with haprp mrna and haprpc. bioassays of tg brain extracts showed that the prion inoculum dictates which prions are synthesized de novo. tg mice inoculated with ha prions had approximately 10(9) id50 units of ha prio ...	1990	1977523
ubiquitin conjugate immunoreactivity in the brains of scrapie infected mice.	sections of brain from normal mice or clinically-ill mice infected with either the 87v or the me7 strains of sheep scrapie were immunostained to show the localization of ubiquitin-protein conjugates or a specific marker of disease, the scrapie-associated fibril protein (prp). in both scrapie models immunoreactive ubiquitin-protein conjugates were seen in thread-like structures found throughout the neuropil, in inclusion bodies within vacuolated neurones, and in areas surrounding anti-prp positiv ...	1990	1977900