Publications

in vitro expression in eukaryotic cells of a prion protein gene cloned from scrapie-infected mouse brain.	it has been proposed that the causative agent of scrapie represents a class of infectious particle that is devoid of nucleic acid and that an altered form of the endogenous prion protein (prp) is the agent. however, it has been difficult to exclude the possibility that prp purified from scrapie tissues might be contaminated with a more conventional viral agent. to obtain prp uncontaminated by scrapie-infected tissues, prp cdna cloned from a scrapie-infected mouse brain was expressed in mouse c12 ...	1988	2898780
replication of the scrapie agent in hamsters infected intracerebrally confirms the pathogenesis of an amyloid-inducing virosis.	following intracerebral infection of hamsters with scrapie agent replication started with or without a very short lag phase. infectivity titres increased exponentially within 35 to 40 days post-infection to a maximum level of 3 x 10(9) ld50 per brain and then remained constant until death. minimal detectable amounts of scrapie-associated fibrils (saf) appeared at 42 days and reached high levels 56 days after inoculation. the first clinical symptoms were diagnosed at about 65 days and animals die ...	1988	2899129
analyses of frequency of infection, specific infectivity, and prion protein biosynthesis in scrapie-infected neuroblastoma cell clones.	scrapie, a spongiform encephalopathy of sheep and goats, is caused by a poorly understood transmissible agent in which no nucleic acid has been conclusively identified. biochemical characterization of agent derived from animal tissues has not been precise because of the tenacious association of the agent with tissue components. as an approach toward obtaining homogeneous preparations of agent generated in vitro, we cloned scrapie-infected neuroblastoma cells. by frequency analysis, nearly every ...	1988	2899175
immunological analysis of host and agent effects on creutzfeldt-jakob disease and scrapie prion proteins.	creutzfeldt-jakob disease (cjd) and scrapie are degenerative neurological diseases caused by unusual infectious pathogens. the term prion has been introduced to underscore the apparent distinctness of these agents from viruses and viroids. the only macromolecule shown to be associated with the infectious agent, the cjd or scrapie prion protein (prpcjd or prpsc, respectively), is encoded by the same gene as a normal cellular protein. in several studies biochemical differences have been reported i ...	1988	2900341
developmental regulation of prion protein mrna in brain.	during development of the hamster brain, synthesis of the cellular isoform of the scrapie prion protein (prpc) was found to be regulated. low levels of prp poly(a)+ mrna were detectable one day after birth. prp poly(a)+ mrna reached maximal levels between 10 and 20 days post-partum; thereafter, no change in its level could be detected at ages up to 13 months. in contrast, myelin basic protein poly(a)+ mrna was shown to reach maximal levels by 30 days of age and thereafter steadily declined in ad ...	1988	2900716
scrapie: a virus-induced amyloidosis of the brain.	we have studied the pathogenesis of scrapie in hamsters, in particular the increase of infectivity and the formation of scrapie-associated fibrils in relation to clinical disease. the results of such studies after intraperitoneal or intracerebral infection are consistent with the idea that transmissible spongiform encephalopathies are a type of virus-induced, brain-specific amyloidosis. therefore, an appropriate name for the class of viruses that cause these diseases might be amyloid-inducing vi ...	1988	2900717
scrapie-associated fibrils, prp protein and the sinc gene.	scrapie-associated fibrils (saf) are disease-specific structures found in extracts of the brains of animals affected with scrapie. these structures are pathological aggregates of a normal host protein called prp. in collaboration with konrad beyreuther (heidelberg), we have characterized the multiple forms of prp found in saf fractions from mouse brain affected by the me7 strain of scrapie. there is no in vivo n-terminal cleavage of the most abundant forms of prp. however, n-terminal cleavage of ...	1988	2900718
properties of scrapie prion proteins in liposomes and amyloid rods.	the scrapie prion protein (prp 27-30) has been demonstrated to be required for infectivity. aggregates of prp 27-30 form insoluble amyloid rods which resist dissociation by non-denaturing detergents. mixtures of the detergent cholate and phospholipids were found to solubilize prp 27-30 with full retention of scrapie prion infectivity. no evidence for a prion-associated nucleic acid could be found when the phospholipid vesicles with prp 27-30 were digested with nucleases and zn2+. under digestion ...	1988	2900719
novel mechanisms of degeneration of the central nervous system--prion structure and biology.	prion is a term for the novel infectious agents which cause scrapie and creutzfeldt-jakob disease; these infectious pathogens are composed largely, if not entirely, of prion protein (prp) molecules. no prion-specific polynucleotide has been identified. considerable evidence indicates that prp 27-30 is required for and inseparable from scrapie infectivity. prp 27-30 is derived from a larger protein, denoted prpsc. a cellular isoform, designated prpc, and prpsc are both encoded by a single copy ch ...	1988	2900720
genetic control of prion incubation period in mice.	the prion gene complex (prn) is located on mouse chromosome 2 between the beta-2-microglobulin (b2m) and agouti (a) genes. within this complex are the prion protein gene (prn-p), which encodes the only identified macromolecule (prp) that purifies with infectious scrapie agent, and a scrapie incubation time gene (prn-i). using a variety of restriction endonucleases, six allelic forms of the prn-p gene have been distinguished by their patterns of restriction fragment length polymorphisms. we had p ...	1988	2900721
bse and scrapie: agents for change.		1988	2900982
cns amyloid proteins in neurodegenerative diseases.	the amyloid plaques found in neurodegenerative diseases show considerable morphologic diversity. two amyloidogenic proteins have been isolated from the brains of humans and animals with neurodegenerative diseases--beta-protein from alzheimer's disease (ad) and down's syndrome, and prion protein (prp) from scrapie and creutzfeldt-jakob disease (cjd). using monoclonal antibodies to a synthetic peptide corresponding to a portion of beta-protein and rabbit antiserum to hamster scrapie prp 27-30, we ...	1988	2901696
messenger rnas of beta-amyloid precursor protein and prion protein are regulated by nerve growth factor in pc12 cells.	the effect of the neurotrophic factor ngf on the expression of two genes involved in the accumulation of amyloid deposits in neurodegenerative disorders was studied in a clonal cell line, pc12. use of hybridization methods showed that ngf increased the cellular pool of the mrna of the prion protein, a macromolecule known to generate fibrillary aggregates in the brain of scrapie-infected animals. maximal levels of prion mrna were obtained after 7 days of treatment, but a significant increase was ...	1988	2903615
fibrils from brains of cows with new cattle disease contain scrapie-associated protein.	during the past two years, more than 1,000 cases of a neurological disorder of cattle, bovine spongiform encephalopathy (bse), have been confirmed from farms throughout great britain. the neurological signs and brain pathology of bse resemble those produced in other species by the pathogens of scrapie and related disorders. the discovery of fibrils similar to scrapie-associated fibrils in detergent extracts o bse-affected brain supported the clinical and pathological diagnosis of the disease, bu ...	1988	2904126
purification and partial characterization of the normal cellular homologue of the scrapie agent protein.	the scrapie agent protein (sp33-37) is a degradation-resistant protein that aggregates into fibrils and amyloid plaques. this protein is derived from a normal cellular protein (cp33-37). understanding the mechanism responsible for the conversion of cp33-37 to sp33-37 may explain scrapie agent replication. cp33-37 was extracted from normal hamster brain and purified 2700-fold by an immunoaffinity method. both cp33-37 purified from normal hamster brain and sp33-37 purified from scrapie-affected ha ...	1988	2904472
nerve growth factor increases mrna levels for the prion protein and the beta-amyloid protein precursor in developing hamster brain.	deposition of amyloid filaments serves as a pathologic hallmark for some neurodegenerative disorders. the prion protein (prp) is found in amyloid of animals with scrapie and humans with creutzfeldt-jakob disease; the beta protein is present in amyloid deposits in alzheimer disease and down syndrome patients. these two proteins are derived from precursors that in the brain are expressed primarily in neurons and are membrane bound. we found that gene expression for prp and the beta-protein precurs ...	1988	2904679
molecular structure, biology, and genetics of prions.		1988	2906782
predicted secondary structure and membrane topology of the scrapie prion protein.	the integral membrane sialoglycoprotein prpsc is the only identifiable component of the scrapie prion. scrapie in animals and creutzfeldt-jakob disease in humans are transmissible, degenerative neurological diseases caused by prions. standard predictive strategies have been used to analyze the secondary structure of the prion protein in conjunction with fourier analysis of the primary sequence hydrophobicities to detect potential amphipathic regions. several hydrophobic segments, a proline- and ...	1987	2907134
prion protein gene expression in cultured cells.	a single copy gene encodes both the scrapie (prpsc) and cellular (prpc) isoforms of the prion protein (prp). cultured cell lines were found to express the endogenous prp mrna at levels comparable to those observed in the brains of adult rodents; however, these cells were invariably found to express greatly reduced levels of prp. in all the cell lines examined, prp was undetectable by western immunoblot analysis. these cells were also poor recipients for expression constructs linking the hamster ...	1988	2908139
the scrapie agent and the prion hypothesis.		1988	2908696
quicker progress on slow diseases.		1986	2908806
cattle disease set for cure.		1989	2918927
scrapie prions, brain amyloid, and senile dementia.		1985	2934227
[creutzfeldt-jakob disease in france. value of familial forms. is there a gene controlling the length of the incubation period?].	an extensive search for patients who died of creutzfeld-jakob disease in france between 1968 and 1982 resulted in the discovery of 327 cases, 233 of which were histologically proven and 29 transmitted to animals; 17 patients belonged to 6 families. further investigations among members of these 6 families yielded 21 additional cases, i.e. a total of 38 familial cases. studies among sibships suggested an autosomal dominant pattern of transmission but did not exclude lateral contamination infancy. ...	1986	2938156
transmissible mink encephalopathy (tme) in chinese hamsters: identification of two strains of tme and comparisons with scrapie.	tme from a single source was transmitted by intracerebral injection to chinese hamsters, producing clinical disease in all seven animals after incubation periods of over 600 days. the brain from each of the primary cases was used to establish separate intracerebral passage-lines of tme and this led to the isolation of two different strains of agent, designated 333k and 333w. these strains were easily distinguished by the incubation periods they produced (about 130 and 230 days, respectively) und ...	1986	2940469
evidence that transmissible mink encephalopathy agent is biologically inactive in mice.	transmissible mink encephalopathy (tme) is probably a form of the sheep disease, scrapie, introduced by accidentally feeding mink with scrapie-infected sheep tissues. although no successful transmissions of tme to mice have been achieved previous work has involved various limitations. to maximize the possibility of transmission, 176 mice, representing 14 different genotypes mostly not previously tested with tme, were injected with tme-infected mink brain from three sources with different histori ...	1986	2940470
cerebrocortical degeneration in goats inoculated with mink-passaged scrapie virus.	widespread spongiform degeneration of the cerebral cortex occurred in four african pygmy goats that became affected with scrapie after intracerebral inoculation with scrapie virus (suffolk sheep brain origin) that had been passed three times in ranch mink. the occurrence of such cerebrocortical degeneration was a distinct departure from the topographic pattern of neuropathologic changes that characterizes scrapie in sheep and goats. but the cortical lesion was identical to the one found in goats ...	1986	2946103
experimental infection of sheep and goats with transmissible mink encephalopathy virus.	in a study to learn more about the pathogenicity of transmissible mink encephalopathy virus for the natural hosts of scrapie, 20 cheviot sheep and 19 dairy goats were inoculated intracerebrally with the idaho strain of the virus. five sheep and nine goats became affected with a progressive neurological disease. the incubation period in the sheep varied from 45 to 80 months (mean, 65 months) and in the goats from 31 to 40 months (mean, 35 months). except for degeneration of the cerebral cortex (n ...	1987	2952237
photoreceptor degeneration in experimental transmissible mink encephalopathy of hamsters.	hamsters were inoculated intracerebrally with the agent of transmissible mink encephalopathy and developed clerical signs of encephalopathy. photoreceptor degeneration occurred in all animals examined histologically. the changes were similar to those in scrapie, although less extensive. the findings suggest that either transmissible mink encephalopathy is a mink-adapted form of scrapie or, in rodents, photoreceptor degeneration is a characteristic of infection with agents of the spongiform encep ...	1987	2953620
temporal distribution of transmissible mink encephalopathy virus in mink inoculated subcutaneously.	information was sought on the temporal distribution of transmissible mink encephalopathy virus in royal pastel mink inoculated subcutaneously with 10(3.0) 50% intracerebral lethal doses of the idaho strain. as determined by intracerebral assay in mink, extremely little replication of the virus occurred during the preclinical stage of infection. it seemed largely limited to lymph nodes draining the site of inoculation. virus first appeared in the central nervous system (cns) at 20 weeks, when all ...	1987	2957510
pathogenesis of amyloid formation in alzheimer's disease, down's syndrome and scrapie.	paired helical filaments (phf) are abnormal fibrous structures found in human nerve cells and their processes. ultrastructural studies of the proto-filaments that make up the phf revealed that the individual proto-filaments have a different substructure from normal neurofilaments or any other known fibrous profiles. studies using immunological and biochemical methods suggested that abnormally phosphorylated tau, ubiquitin and neurofilament peptides are part of the phf. deposits of amyloid fibres ...	1988	2970373
[prions].		1988	2972052
[morphological characteristics of the brain lesions in mice infected with a homogenate of l cells latently infected with the scrapie agent].	degeneration of neurons of the ammon horn lower branch both in the early and terminal stages of the disease of mice infected with the homogenate of l cells latently infected with the scrapie agent (the l-s system) was frequently detected alongside with brain lesions typical of slow infections (vacuolation). examinations of chromosomes in metaphase plates of l-s cells carried out by several methods including the tac system for texture analysis of the image (leutz, brd) revealed three marker chrom ...	1985	3000085
acceleration of scrapie disease in mice by an adenovirus.	coinfected mice were examined for a possible interaction between the scrapie agent and an adenovirus. a low titer (10(2) tcd50) of mouse adenovirus (madv) caused a significant acceleration of clinical signs of scrapie in mice infected 128 days previously with scrapie. in this experiment, the coinfected mice died 19 days earlier than mice infected with scrapie alone. when a higher titer of madv (10(4)-10(5) pfu) was used, a more drastic acceleration of scrapie disease was seen in mice infected 85 ...	1986	3013796
genetically controlled resistance to virus infections of the central nervous system.		1985	3014607
human prion protein cdna: molecular cloning, chromosomal mapping, and biological implications.	a human complementary dna whose protein product is considered to be the major component of scrapie-associated fibrils in creutzfeldt-jakob disease, kuru, and gerstmann-straussler syndrome has been identified and characterized. the extensive homology of this gene sequence to the hamster prp 27- to 30-kilodalton prion protein complementary dna clone, and its existence as a single copy in the human genome, leads to the conclusion that this is the human prion gene. this human prion gene has been map ...	1986	3014653
linkage of prion protein and scrapie incubation time genes.	a single gene (prn-i) that affects scrapie incubation period in mice has been identified. i/lnj mice have a very long incubation period after inoculation of scrapie prions (200-385 days) and nzw/lacj mice have a short one (113 +/- 2.8 days). (nzw x i/ln)f1 hybrid mice had incubation times of 223 +/- 2.8 days indicating longer incubation times were dominant. incubation periods in the backcross progeny of (nzw/lacj x i/lnj)f1 x nzw/lacj segregated into two groups (64 mice, 130 +/- 1.1 d; 66 mice, ...	1986	3015416
alterations of the functional properties of the parallel fibers in the cerebellum of the "scrapie mouse".	alterations of the functional properties of the cerebellar parallel fibers have been investigated in scrapie mice by recording the compound action potential elicited by the superficial stimulation of the cerebellum. as soon as the 12th week following intracerebral inoculation, i.e. during the silent incubation period, there is a clear decrease of the response amplitude and of the recruiting properties. depth profiles of the response indicate the progressive disappearance of the most superficial ...	1986	3017249
aids virus and scrapie agent share protein.		1986	3018589
isolation and characterization of macrophages from scrapie-infected mouse brain.	we have isolated and characterized a population of brain macrophages from normal and scrapie-infected mice. the cells are phagocytic, possess fc-igg receptors, mac-1 surface antigen and proliferate in the presence of macrophage colony stimulating factor. they resemble microglia in that they have a plasmalemmal distribution of the enzyme nucleoside diphosphatase, a property tht is characteristic of microglia in situ. in two of the three combinations of scrapie agent and mouse strain examined, the ...	1987	3031922
growth factor production by creutzfeldt-jakob disease cell lines.	creutzfeldt-jakob disease (cjd), a progressive dementia of humans, is caused by an infectious agent that is closely related to the scrapie agent of sheep. although the molecular nature of these "unconventional" agents is still a matter of speculation and controversy, even less is known concerning the mechanism(s) of their effects on the central nervous system. to gain insight into the cellular effects of these agents, we have examined a series of cell lines derived directly from cjd-infected ham ...	1988	3043023
neuropathology of unconventional virus infections: molecular pathology of spongiform change and amyloid plaque deposition.	to the triad of neuronal loss, gliosis and spongiform change as characteristic morphological changes associated with infection of the central nervous system, one can now add the presence of scrapie-associated filaments (saf)/prp rods. while the host's immune response is conspicuous by its absence, the vigorous astrocytic response is presumptive evidence of the host's ability to recognize and respond to the primary neuronal insult. we assume that the spongiform change and vacuolation of neurons a ...	1988	3044707
genetic aspects of unconventional virus infections: the basis of the virino hypothesis.	the properties of genes involved directly or indirectly in the pathogenesis of scrapie and other unconventional (ucv) virus infections are reviewed. reasons are presented for assigning paramount importance to the sinc gene in mice and the sip gene in sheep (the likely homologue of sinc). the rationale is given for concluding that the agents of ucv infections have their own genomic molecules coding for strain differences. the virino hypothesis, which proposes that the infective form of the agent ...	1988	3044709
hypotheses concerning the aetiology of alzheimer's disease.	theories on the aetiology and pathogenesis of alzheimer's disease (ad) are revised. after discussing senile involution, the principal characteristic alterations of ad are presented. these pathological changes include involutive morphological phenomena (neurofibrillar tangles, senile neuritic plaques with varying = amyloid content) and functional phenomena (alterations in energy metabolism, in protein synthesis, and in the neurotransmitter metabolism). currently it is assumed that the neurons mos ...	1988	3064109
fifty years with scrapie: a personal reminiscence.		1988	3066007
[has scrapie of sheep and goats a role in the transmission of creutzfeldt-jakob disease?].		1988	3068726
scrapie prion proteins are synthesized in neurons.	scrapie is a slow degenerative encephalopathy of animals caused by unusual infectious particles termed prions. a cdna encoding the only apparent component of the prion, a protein designated prp 27-30, has recently been cloned and sequenced. by measuring mrna levels using in situ hybridization with the prp cdna, the authors found that prion proteins are synthesized almost exclusively within neurons. the levels of prp mrna varied among different types of neurons, but did not change during scrapie ...	1986	3079955
pathogenesis of scrapie (strain 263k) in hamsters infected intracerebrally, intraperitoneally or intraocularly.	after intracerebral (i.c.) infection of hamsters, the 263k strain of scrapie replicated at a nearly constant exponential rate until clinical disease developed when titres in brain averaged 9.8 log10 ld50 i.c. units/g. after intraperitoneal infection, scrapie replication was first detected in spleen, then in thoracic spinal cord and finally in lumbar cord and brain. this pattern suggests that invasion of the central nervous system occurs by spread of infection along certain visceral autonomic ner ...	1986	3080549
molecular hybridization studies with scrapie brain nucleic acids. i. search for specific dna sequences.	chromatography and hybridization techniques employing scrapie enriched fractions of hamster brains were employed to detect a scrapie-specific dna molecule. 125i-labeled dna from eight different scrapie-enriched hamster brain fractions was hybridized to total dna and rna from normal and scrapie hamster and mouse and to dna from normal human brain and brain tissue from patients dying with creutzfeldt-jakob disease. enrichment for infectivity was obtained by cellular partition, gel filtration and g ...	1986	3082311
creutzfeldt-jakob infection increases adenylate cyclase activity in specific regions of guinea pig brain.	creutzfeldt-jakob disease is a slow, infectious, progressive neurological disorder which results in human dementia. synaptic membranes from various brain regions of guinea pigs infected with creutzfeldt-jakob disease show increased guanyl nucleotide- or 5-hydroxytryptamine-mediated activation of adenylate cyclase. this increased enzyme activity appears due, primarily, to facilitated 'coupling' between the gtp-binding protein which stimulates adenylate cyclase (gns) and the catalytic moiety of th ...	1986	3082670
estimation of scrapie nucleic acid mw from standard curves for virus sensitivity to ionizing radiation.		1986	3083263
distributions of amyloid plaques in four regions of the brains of mice infected with scrapie by intracerebral and intraperitoneal routes of injection.	vm mice were inoculated by intracerebral and intraperitoneal routes with brain homogenates containing the 87v strain of scrapie. the distribution and numbers of plaques were found for the parietal cortex, cingulate cortex, corpus callosum and hippocampus/dentate in coronal sections cut at the level of the thalamus and stained with masson's trichrome. for the intracerebrally injected animals, the greatest numbers were seen on the side of the brain that had been injected. in the four regions, they ...	1986	3083640
newer data on the inactivation of scrapie virus or creutzfeldt-jakob disease virus in brain tissue.		1986	3084671
separation and properties of cellular and scrapie prion proteins.	purified preparations of scrapie prions contain a sialoglycoprotein of mr 27,000-30,000, designated prp 27-30, which is derived from the scrapie prion protein [mr, 33,000-35,000 (prp 33-35sc)] by limited proteolysis. under these same conditions of proteolysis, a cellular protein of the same size (prp 33-35c) is completely degraded. subcellular fractionation of hamster brain showed that both prp 33-35sc and prp 33-35c were found only in membrane fractions. nacl, edta, and osmotic shock failed to ...	1986	3085093
purification of scrapie agent from infected animal brains and raising of antibodies to the purified fraction.	the fraction (p4) containing scrapie infectivity was obtained by treatment of scrapie-infected mouse brains with the detergent sarcosyl, differential centrifugation, and proteolytic enzyme digestion. scrapie infectivity in the p4 fraction was purified 239-2,390 times with respect to protein. similar fractions were also prepared from the brain of a sheep naturally infected with scrapie. morphological observation of the p4 fractions revealed that the main components were unique rods of 3-5 x 60-20 ...	1986	3086675
creutzfeldt-jakob disease.	there has been significant advance in our understanding of cjd and similar spongiform encephalopathies in recent years. the range in clinical expression of the disease is better appreciated, and the existence of "atypical" cases of cjd is increasingly recognized. new ideas about the possible modes of natural transmission have been derived from case-control studies in different parts of the world.	1986	3086688
the nature of the scrapie agent.	there now seems little doubt that the infective agent of scrapie cannot be accommodated within current concepts of virology/molecular biology. it is proposed: that the basic infective entity is a nucleic acid fragment (oligonucleotide) of some 40 bp coupled with specific (but host encoded) protein totalling approximately 10(5) daltons, a significant proportion of which is in the form of proteolipid; that the nucleic acid fragment reprograms the host cell on the chemically switched microprocessor ...	1986	3088402
learning ability of mice infected with different strains of scrapie.	cd-1 mice were infected intraperitoneally with one of 4 different strains of scrapie and tested simultaneously at or near the end of incubation. there were no differences between any of the scrapie injected groups and controls in spontaneous motor activity, or in the shock thresholds and entry latencies measured during training in a one-trial passive avoidance test. on testing, the avoidance responses were normal for the mice infected with 22c or me7, but these mice did not show overt clinical s ...	1986	3088623
monoclonal antibodies to the cellular and scrapie prion proteins.		1986	3090160
immunoreactivity of a synthetic pentadecapeptide corresponding to the n-terminal region of the scrapie prion protein.	a pentadecapeptide with an amino acid sequence corresponding to the amino-terminal region of the scrapie prion protein was synthesized. immunization of a rabbit with the peptide conjugated with ovalbumin induced specific antibodies. the antibodies reacted with all three of the major polypeptides in a proteinase k-treated fraction obtained from brains of mice infected with the obihiro strain of scrapie agent. some peptides in the proteinase-untreated fraction also shared antigenicity with the thr ...	1986	3090197
from prions to prionic viruses.	the pathogens causing scrapie and other similar degenerative neurological diseases are called "prions" and classified either as viruses or, more often, as a novel class of pathogens. it is argued herein that prions are not the pathogens producing these diseases. the pathogens involved are endogenous viral systems inherited by the host. these endogenous parasites, tentatively named prionic viruses, produce the prions which are horizontally transmitted. the prions trigger the pathological manifest ...	1986	3090406
characterization of major peptides in creutzfeldt-jakob disease and scrapie.	in creutzfeldt-jakob disease three major peptides cosediment with the infectious agent. these distinct peptides are not present in identical fractions from uninfected brain, and bind to polyclonal antibodies raised against "prion protein" purified by protease treatment. three similar distinct peptides are also found in scrapie-infected brain fractions purified without the use of proteases. to clarify the relationships between these distinct peptides and prion protein, peptides were analyzed on i ...	1986	3090551
recent developments in scrapie and creutzfeldt-jakob disease.		1986	3092282
amyloid plaques in creutzfeldt-jakob disease stain with prion protein antibodies.	amyloid plaques are found in the brains of some patients with creutzfeldt-jakob disease (cjd) and all patients with a related transmissible disorder, gerstmann-sträussler syndrome (gss). in scrapie, a prion disease of animals, amyloid plaques have been shown to be composed of prion proteins (prp), which form filaments of relatively uniform diameter. we report here that antisera raised against hamster scrapie prp specifically stain amyloid plaques in the brains of both humans and rodents with cjd ...	1986	3092727
assignment of the human and mouse prion protein genes to homologous chromosomes.	purified preparations of scrapie prions contain one major macromolecule, designated prion protein (prp). genes encoding prp are found in normal animals and humans but not within the infectious particles. the prp gene was assigned to human chromosome 20 and the corresponding mouse chromosome 2 using somatic cell hybrids. in situ hybridization studies mapped the human prp gene to band 20p12----pter. our results should lead to studies of genetic loci syntenic with the prp gene, which may play a rol ...	1986	3094007
spread of scrapie agent to the central nervous system: study of a rat model.	invasion of scrapie agent into the central nervous system (cns) was studied in rats following intracerebral and peripheral inoculation, the latter by injection into intact or transected sciatic nerve. comparison of sleep-wakefulness alterations, neuropathological features, and time lag of electroencephalographic and clinical signs in the 3 groups suggests that hematogenous spread of infection to the cns may predominate over neural transport, and that peripheral inoculation may closely approximat ...	1986	3094830
replication of scrapie prions in hamster eyes precedes retinal degeneration.	progressive degeneration of outer retinal structures occurs in hamsters with scrapie. in order to determine the relationship between histopathologic changes and replication of the scrapie agent, hamsters were inoculated intracerebrally with approximately 10(7) id50 units. animals sacrificed at 50 days after inoculation showed no signs of neurologic dysfunction, but had high titers of the scrapie agent or prions in both neural and nonneural portions of the eye. prion titers in retina were greater ...	1986	3095759
the major polypeptide of scrapie-associated fibrils (saf) has the same size, charge distribution and n-terminal protein sequence as predicted for the normal brain protein (prp).	scrapie-associated fibrils (saf) are unique structures characteristic of the group of unconventional slow infections which includes scrapie and creutzfeldt-jakob disease. a major component of hamster fibrils has been described as a protease-resistant glycoprotein with an apparent mol. wt of 27,000-30,000 (prp27-30). however, we report here that if fibrils are prepared by procedures designed to minimise proteolysis the prp proteins co-purifying with hamster saf have mol. wts of 33,000-35,000 (prp ...	1986	3096712
purified scrapie prions resist inactivation by uv irradiation.	the development of effective purification protocols has permitted evaluation of the resistance of isolated scrapie prions to inactivation by uv irradiation at 254 nm. prions were irradiated on ice with doses of uv light ranging up to 120,000 j/m2. uv dosimetry experiments, performed with saccharomyces cerevisiae plasmid dna or eucaryotic cells, indicated that under these experimental conditions an incident uv dose of 10 j/m2 formed 2 thymine dimers per 5.1 x 10(6) daltons of eucaryotic cell dna. ...	1987	3097336
scrapie, ribosomal proteins and biological information.	consideration of the autocatalytic synthesis of ribosomal proteins leads to a criterion for the infectivity of a foreign proteinaceous species in terms of the biochemical rate constants governing the propagation of errors during the translation of genetic information in a model system. evidence pertaining to the suggestion that scrapie and its analogues are caused by proteinaceous infectious agents (prions) which replicate by invading the translation process and altering ribosomal specificity is ...	1986	3099090
biology and structure of scrapie prions.		1986	3100471
effects of different methods of purification on aggregation of scrapie infectivity.	high levels of scrapie infectivity were found in detergent-insoluble residues of hamster brain purified by either repeated pelleting in 10% nacl or by separation in nycodenz gradients. titres determined by the method of incubation interval assay were 100-fold higher than titres measured by endpoint dilution assay. the protein profiles and end-labelled rna examined by one-dimensional polyacrylamide gel electrophoresis were not different from samples prepared from uninfected brain. preparations pr ...	1987	3100716
biological evidence that scrapie agent has an independent genome.	there are many distinct strains of scrapie agent, identified by their relative incubation periods and quantitative and qualitative neuropathological properties in inbred mice of particular genotypes. when serially passaged under specified conditions of mouse strain, route of infection and dose of infectivity these properties are stable. however, they may change in a predictable manner if the passage strategy is altered. the scrapie strain 87a shows what has previously been defined as class iii s ...	1987	3100717
aids virus and scrapie protein genes.		1987	3100963
genetic control of scrapie: incubation period and plaque formation in i mice.	the host component of control of scrapie incubation period in the mouse is manifested largely through the action of the sinc gene. only one mouse strain (vm) has been found that is p7p7 (prolonged incubation for me7 agent) and two other strains have been derived from vm. all other strains, designated s7s7, have a short incubation for me7. in the present study, the i strain was shown to fulfil the criteria that are characteristic of mouse strains with the p7 allele of sinc: a comparatively long i ...	1987	3102684
[the structure of the infectious scrapie agent].		1986	3104895
scrapie, an unconventional virus: the current views.		1987	3104917
scrapie incubation periods and end-point titers in mouse strains differing at the h-2d locus.	in extending findings on the influence of the mouse h-2d locus on the scrapie incubation period, we showed that with the intracerebral (i.c.) route of injection, sjl and nzw mice (s and z alleles, respectively) had shorter incubation periods than c57bl mice (b allele) at several concentrations of two scrapie strains, me7 and 139a. the three mouse strains have the same sinc genotype, s7s7. incubation period data among the three mouse strains after intraperitoneal (i.p.) injection revealed a diffe ...	1986	3106258
characterization of scrapie infection in mouse neuroblastoma cells.	a mouse neuroblastoma cell line was successfully infected with scrapie agent. agent derived from infected mouse brain or spleen infected cultures. however, agent from infected hamsters did not infect mouse cell cultures, suggesting that species specificity influenced the infection process in vitro. positive cultures supported scrapie replication for as many as 47 passages in vitro. agent was shown to be cell-associated and between 631 and 7943 unselected culture cells constituted 1 mouse ld50. h ...	1987	3106566
scrapie and its association with 'amyloid-like' fibrils and glycoproteins encoded by cellular genes: an animal model for human dementia.		1986	3107063
photoreceptor degeneration during infection with various strains of the scrapie agent in hamsters.	hamsters were inoculated intracerebrally with the 22c, 79a, and me7 strains of the scrapie agent to compare the effects on the retina with those caused by strain 263k. the animals developed clinical signs of encephalopathy. photoreceptor degeneration occurred in all experimental animals. the changes were similar to those seen in animals infected with the 263k strain of scrapie although somewhat more variable and less extensive.	1987	3108023
purified prion proteins and scrapie infectivity copartition into liposomes.	considerable evidence indicates that the scrapie prion protein (prp 27-30) is required for infectivity. aggregates of prp 27-30 form insoluble amyloid rods that resist dissociation by nondenaturing detergents. mixtures of the detergent cholate and phospholipids were found to solubilize purified prp 27-30 in the form of detergent-lipid-protein complexes. removal of the cholate by dialysis resulted in the formation of closed liposomes. both the detergent-lipid-protein complexes and the liposomes o ...	1987	3108886
temporary and permanent modifications to a single strain of mouse scrapie on transmission to rats and hamsters.	the interspecies transmission of scrapie is frequently associated with exceptionally long incubation periods at first passage in the new host compared to later passages (the species barrier effect). the basis of this was investigated using the 139a strain of scrapie which had been cloned by three serial passages in mice at limiting infectious doses. cloned scrapie was passaged through hamsters (twice) or rats (thrice) and then reisolated in mice. large species barrier effects were encountered on ...	1987	3110370
[biology of the infectious scrapie agent].		1987	3110752
changes in the localization of brain prion proteins during scrapie infection.	prion proteins (prp) were localized in the brains of normal and scrapie-infected hamsters by immunohistochemistry and western blotting. prp monoclonal antibodies and monospecific anti-prp peptide sera, which react with both the cellular (prpc) and scrapie (prpsc) isoforms of the prion protein, were used to locate prp in tissue sections. in normal hamsters, prpc was located primarily in nerve cell bodies throughout the cns; whereas, in the terminal stages of scrapie, prp immunoreactivity was shif ...	1987	3112607
amyloid scrapie plaques in mice, and alzheimer senile plaques, share common antigens with tau, a microtubule-associated protein.	immunolabelling was performed on brain sections of scrapie-infected mice with antibodies against tau, a microtubule-associated protein, and against the paired helical filaments of alzheimer's disease. both kinds of antibodies have been shown previously to label paired helical filaments in neurons and in abnormal neurites associated with the senile plaques of alzheimer's disease. amyloid plaques in murine scrapie were labelled by both antisera. the structural substrate for the immunolabelling was ...	1987	3112659
purified scrapie prions resist inactivation by procedures that hydrolyze, modify, or shear nucleic acids.	prions were purified from scrapie-infected hamster brains and incubated for 24 hr at 65 degrees with 2 mm zn2+ or 5 mm mg2+; no loss of infectivity was observed. bacteriophage m13, tobacco mosaic virus (tmv), potato virus x, and potato spindle tuber viroid were all inactivated by divalent metal ions under these conditions. prions also resisted inactivation by prolonged digestions with dnase i, rnases a and t1, and micrococcal nuclease. prions were resistant to psoralen photoadduct formation usin ...	1987	3114950
immunochemical characterization of proteins from scrapie-infected hamster brain, using immunoblot analysis.	preparations of brain plasma membrane from scrapie-infected or noninfected hamsters were extracted with a solvent and were used to inoculate rabbits. antisera evaluated by immunoblot analysis revealed a protein of 45 kd in scrapie-infected hamster brain that had a greater signal compared with proteins of comparable relative mass in noninfected brain. this 45-kd protein was not increased in scrapie-infected mouse, sheep, or goat brain. seemingly, the 45-kd protein may be a degradation product of ...	1987	3115155
the brain fine structure in experimental scrapie. the 263k strain in golden syrian hamsters.		1987	3116454
[role of phagocytes in experimental scrapie in hamsters].	we studied the interactions between scrapie agent and hamster's phagocytic cells. macrophages which have been in contact with the scrapie agent are able to carry the infectivity of this agent. we induced variations of different parameters involved on fixation and phagocytosis and we did not observe any modification. a depletion of phagocytic cells induced in hamster at the entry of scrapie increase the incubation time of the illness. furthermore phagocytic cells cocultured with glial cells seem ...	1987	3116644
ionising radiation has no influence on scrapie incubation period in mice.	scrapie has an early non-clinical stage when replication of agent occurs in lymphoreticular organs. whole-body irradiation failed to alter the incubation or neuropathology of the disease. many experiments were carried out with different strains of scrapie agent and host, doses and timing of irradiation. the results suggest that mitotically quiescent cells are involved in agent replication.	1987	3116748
autoclaved, formol-fixed scrapie mouse brain is suitable for histopathological examination, but may still be infective.	autoclaving creutzfeldt-jakob disease (cjd)-infected brain after fixation has been proposed previously as a means of making it safe for handling in the laboratory, while preserving its microscopic integrity. however, the practice which was recommended (126 degrees c for 30 min) would be unlikely to achieve complete decontamination. autoclaving scrapie mouse brain (an analogue for cjd) to the higher, recommended standard of 134-138 degrees c for 18 min was found to lead to some tissue damage but ...	1987	3118629
[neuronal reaction of the central nervous system to infection by the scrapie agent in mice in the preclinical period of the pathogenesis of the experimental infection].		1987	3120418
[scrapie agent].		1987	3124085
characterization of prion proteins with monospecific antisera to synthetic peptides.	the prion protein (prp) 27-30 is the major macromolecular component in highly purified preparations of prions derived from scrapie-infected hamster brain. immunoblotting studies demonstrated that this protein is generated by partial protease digestion of a larger precursor (prpsc) with an apparent mr of 33 to 35 kda, and that a protease-sensitive cellular prp isoform, designated prpc, is present in normal hamster brain. to characterize the relationships among these proteins, elisa and immunoblot ...	1988	3125249
comparison of scrapie associated fibril detection and histology in the diagnosis of natural sheep scrapie.		1987	3125660
evidence for a secretory form of the cellular prion protein.	the biogenesis of hamster brain prion protein (prp) has been studied by expression of rna transcribed from a full-length prp cdna in xenopus oocytes and cell-free systems. earlier studies in the wheat germ cell-free system showed that one form of prp is a transmembrane protein that spans the bilayer at least twice [hay, b., barry, r. a., lieberburg, i., prusiner, s. b., & lingappa, v. r. (1987) mol. cell. biol. 7, 914-920]. we now report that prp can also exist as a secreted protein. sp6 prp rna ...	1987	3126796
antiheretical speculations on the "prion" protein and scrapie.		1988	3127809
scrapie agent proteins do not accumulate in grey tremor mice.	the grey tremor mouse is an autosomal recessive mutant characterized by a phenotype of unusual pigmentation, neurological abnormalities and early death. these mice have a spongiform encephalopathy similar to scrapie and creutzfeldt-jakob disease. although the disease is clearly heritable, the grey tremor mouse spongiform pathology has also been transmitted by inoculation of genetically normal mice with diseased brain homogenates. the possibility that a scrapie-like agent is involved has been pro ...	1988	3128642
evidence that dna is present in abnormal tubulofilamentous structures found in scrapie.	abnormal tubulofilamentous structures have been identified in electron micrographs of thin sections and negatively stained impression grids prepared from brains of animals with scrapie and other spongiform encephalopathies, and we showed that such tubules contain a core of filamentous structures resembling scrapie-associated fibrils (saf). we treated impression grids from brains of scrapie-infected hamsters with several substances that bind to or cleave proteins and nucleic acids to see if they ...	1988	3130630