Publications

inactivation of the unconventional agents of scrapie, bovine spongiform encephalopathy and creutzfeldt-jakob disease.	scrapie, bovine spongiform encephalopathy (bse) and creutzfeldt-jakob disease (cjd) are the best known of the transmissible degenerative encephalopathies (tde) that affect animals and man. among the unusual properties of the unconventional causal agents is their relative resistance to standard decontamination procedures, and this has resulted in accidental transmission. scrapie in sheep is the most common of these diseases and, through laboratory studies, is the best understood. as the model for ...	1991	1679777
proteinase-resistant prion protein accumulation in syrian hamster brain correlates with regional pathology and scrapie infectivity.	multiple lines of evidence indicate that prpsc, found only in scrapie, is a necessary component of the infectious scrapie agent. equally compelling is the evidence that its accumulation in the brain causes the neuropathology characteristic of scrapie. we measured the regional concentration of prpsc in nine brain regions throughout the course of scrapie in the syrian hamster following intrathalamic inoculation of prions. prpsc was compared to the regional concentration of glial fibrillary acidic ...	1991	1679911
distribution and activity of alternatively spliced alzheimer amyloid peptide precursor and scrapie prp mrnas on rat brain polysomes.	mammalian brains contain low levels of the alzheimer amyloid precursor variants (aapps) and the normal form of the scrapie agent protease-resistant protein (prpc); however, their mrnas are readily detectable. to understand these discrepancies we have investigated some aspects of the translational regulation of these mrnas. an accurate blot-hybridization procedure was developed to measure absolute amounts of mrna. rat brain contains the following mrna levels (ng/g tissue) aapp(695), 170; aapp(751 ...	1991	1680310
the scrapie-associated form of prp is made from a cell surface precursor that is both protease- and phospholipase-sensitive.	a common feature of scrapie and related transmissible spongiform encephalopathies is the accumulation of an abnormal protease-resistant form of prp which may be the major component of the infectious agent. while it is known that both the normal (protease-sensitive) prp and protease-resistant prp are encoded by the same endogenous gene, the nature of the disease-associated modification of prp is not understood. to study the cellular events leading to the formation of protease-resistant prp, we ha ...	1991	1680859
different scrapie-associated fibril proteins (prp) are encoded by lines of sheep selected for different alleles of the sip gene.	the incubation period of scrapie in sheep is controlled by the sip gene which has two alleles (sa and pa). following experimental challenge with ssbp/1 scrapie, a short incubation period is conferred by the partially dominant sa allele. restriction fragment length polymorphisms of the scrapie-associated fibril protein (prp) gene are associated with the sip alleles. by sequencing the protein coding region of the prp gene in cheviot sheep selected for differing sip genotypes, we have found four pr ...	1991	1681027
regulation of the glial fibrillary acidic protein, beta actin and prion protein mrnas during brain development in mouse.	developmental regulation in mrnas of three brain proteins has been investigated by northern blot evaluation in c57bl/6 mice. the mrnas of two cytoskeletal components, glial fibrillary acidic protein (gfap) and beta actin, varied significantly, and differently, during brain development (0-56 days postnatal). the beta actin mrnas peaked at day 1 after a slight increase, then dropped rapidly during the first 15 days postnatal, and thereafter remained at a level which was strictly maintained through ...	1991	1681406
immunolocalization of scrapie amyloid (prp27-30) in chronic wasting disease of rocky mountain elk and hybrids of captive mule deer and white-tailed deer.	scrapie amyloid-immunoreactive plaques are present in brain tissues of captive mule deer with chronic wasting disease (cwd), a progressive neurological disorder characterized neuropathologically by widespread spongiform change of the neuropil, intracytoplasmic vacuolation in neuronal perikarya and astrocytic hypertrophy and hyperplasia. we report here the immunolocalization of scrapie amyloid (prp27-30) in plaques observed in brain tissues of rocky mountain elk (cervus elaphus nelsoni) and hybri ...	1991	1681473
n-terminal truncation of the scrapie-associated form of prp by lysosomal protease(s): implications regarding the site of conversion of prp to the protease-resistant state.	scrapie and related transmissible spongiform encephalopathies result in the accumulation of a protease-resistant form of an endogenous brain protein called prp. as an approach to understanding the scrapie-associated modification of prp, we have studied the processing and sedimentation properties of protease-resistant prp (prp-res) in scrapie-infected mouse neuroblastoma cells. like brain-derived prp-res, the neuroblastoma cell prp-res aggregated in detergent lysates, providing evidence that the ...	1991	1682507
[molecular biology of subacute spongiform encephalitis].	subacute spongiform encephalitis is a pathology that is common to 4 human and 4 animal diseases. these diseases are characterized by the neurological lesions they share and by the fact that they can be transmitted to animals. an abnormal isoform of an endogenous central nervous system protein has been identified. it might be the sole pathogenic agent, but it is certain that it plays a major role in the expressivity of the disease.	1991	1682916
playing clue with prion disease.		1991	1684400
ultrastructural localization of scrapie prion proteins in cytoplasmic vesicles of infected cultured cells.	infectious scrapie prions are composed largely, if not entirely, of an abnormal isoform of the prion protein (prp) designated prpsc. in scrapie-infected mouse neuroblastoma (scn2a) and hamster brain (schab) cells, prpsc accumulates primarily within the cell cytoplasm, whereas cellular prp (prpc) is anchored to the external surface of the plasma membrane by a glycoinositol phospholipid moiety. to determine the subcellular localization of prpsc, scrapie-infected cells were grown to approximately 7 ...	1991	1684401
molecular biology and transgenetics of prion diseases.	considerable progress has been made deciphering the role of an abnormal isoform of the prion protein (prp) in scrapie of animals and gerstmann-sträussler syndrome (gss) of humans. some transgenic (tg) mouse (mo) lines that carry and express a syrian hamster (ha) prp gene developed scrapie 75 d after inoculation with ha prions; non-tg mice failed to show symptoms after greater than 500 d. brains of these infected tg(haprp) mice featured protease-resistant haprpsc, amyloid plaques characteristic f ...	1991	1684745
the transmissible amyloidoses: genetical control of spontaneous generation of infectious amyloid proteins by nucleation of configurational change in host precursors: kuru-cjd-gss-scrapie-bse.	kuru, creutzfeld-jakob disease, gerstmann-sträussler syndrome, scrapie, and bovine spongiform encephalopathy are caused by so-called unconventional viruses which are really replicating proteins which induce by auto nucleation and autopatterning a configurational change in the precursor protein to produce an infectious amyloid form. crystallography and nmr may eventually determine how amyloid precursor protein is converted to this infectious form by configurational changes in all tertiary and qua ...	1991	1684758
copurification of sp33-37 and scrapie agent from hamster brain prior to detectable histopathology and clinical disease.	studies were conducted to determine whether accumulation of the scrapie agent protein sp33-37 in brain correlated with the appearance of the scrapie agent or with pathology. the concentrations of the scrapie agent and sp33-37 were measured in purified fraction p5 isolated from hamster brains at weekly intervals after inoculation. the scrapie agent concentration in fraction p5 was approximately 10(-1) ld50/g brain 1 day post-inoculation and increased to 10(9.4) ld50/g at day 77. sp33-37 was first ...	1991	1684986
cerebral amyloid plaques in alzheimer's disease but not in scrapie-affected mice are closely associated with a local inflammatory process.	complement proteins of the classical pathway can be immunohistochemically identified in cerebral amyloid plaques in alzheimer's disease. microglial cells in and around amyloid plaques express class ii major histocompatibility (mhc) antigens and complement receptors cr3 and cr4. negative immunostaining for immunoglobulins and for t-cell subsets in the brain parenchyma demonstrates a lack of evidence for the involvement of specific immune responses (such as an immune complex-mediated complement ac ...	1991	1685040
a mutation in the prion protein gene in creutzfeldt-jakob disease in jewish patients of libyan, greek, and tunisian origin.	a modified host protein encoded by the gene specifying the scrapie amyloid precursor is critically involved in the pathogenesis of transmissible spongiform encephalopathies such as creutzfeldt-jakob disease (cjd), gerstmann-straussler-scheinker's syndrome, and kuru. a mutation in the open reading frame of this gene was recently described in a cluster of patients with cjd in slovakia. this mutation at codon 200 changes glutamic acid coded by gag to lysine coded by aag. we examined the prevalence ...	1991	1685643
molecular biology of prions causing infectious and genetic encephalopathies of humans as well as scrapie of sheep and bse of cattle.	considerable progress has been made in deciphering the role of an abnormal isoform of the prion protein (prp) in scrapie of animals and gerstmann-sträussler syndrome (gss) of humans. transgenic (tg) mice expressing both syrian hamster (ha) and mouse (mo) prp genes, which encode proteins differing at 16 residues out of 254, 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 after ha prion in ...	1991	1686599
electrospray mass spectrometry of the glycosylinositol phospholipid of the scrapie prion protein.		1991	1686992
production and characterization of antibodies to mouse scrapie-amyloid protein elicited by non-carrier linked synthetic peptide immunogens.	two polyclonal antibodies were raised by immunizing rabbits with two non carrier-linked synthetic peptides whose amino acid sequences corresponded to codons 89-107 (peptide p1) and 219-233 (peptide p2) of the translated cdna sequence of murine prp protein. these free peptides, whose structural characteristics in solution were studied by circular dichroism, elicited a reasonable immunologic response in animals. both antibodies still recognized the corresponding immunogens after affinity chromatog ...	1991	1687353
the human spongiform encephalopathies: kuru, creutzfeldt-jakob disease, and the gerstmann-sträussler-scheinker syndrome.		1991	1687378
genetics of prion diversity and host susceptibility.		1991	1687380
the scrapie agent: "a virus by any other name".		1991	1687381
novel properties and biology of scrapie prions.		1991	1687382
identifying and mapping changes in gene expression involved in the neuropathology of scrapie and alzheimer's disease.		1991	1687383
purification of scrapie agents: how far have we come?		1991	1687384
the scrapie fibril protein and its cellular isoform.	proteins need help to fold and attain their functional conformation (ellis and hemmingsen 1989), and mechanisms have evolved to prevent the accumulation of misfolded protein aggregates within cells (pelham 1988). these mechanisms fail to prevent the formation of protease-resistant, misfolded forms of prp (scprp) during the development of scrapie and other transmissible spongiform encephalopathies, and scprp is a biochemical marker of these diseases. much is now known about the structure and expr ...	1991	1687385
in vitro expression and biosynthesis of prion protein.	in addition to whatever function prp may have normally, its involvement in scrapie-like neurodegenerative diseases has become clearer in recent years. in vitro studies have made important contributions to the understanding of normal prp biosynthesis and turnover and how they can be influenced by scrapie infection. cell-free transcription and translation experiments have indicated that prp gene translation products are capable of assuming two different topologies, one spanning microsomal membrane ...	1991	1687386
bovine spongiform encephalopathy: a neuropathological perspective.	the occurrence of bovine spongiform encephalopathy (bse), recognition that it is a new scrapie-like disease epidemic in domestic cattle in the united kingdom and concern of a remote zoonotic potential has, in four years, produced a plethora of documented information. while much of this information has been communicated outwith the scientific literature, this review attempts to summarise, from a neuropathological viewpoint, the main findings to emerge. the initial studies established the nosologi ...	1991	1688299
chemoprophylaxis of scrapie in mice.	three applications of the polyanion pentosanpolysulphate about 2 months before infection of mice with scrapie completely protected animals infected with up to 100 ld50, and considerably prolonged the lifespan of those infected with 100 to 10,000 ld50. the clinical diagnosis was confirmed by immunoblot analysis for the protein of scrapie-associated fibrils.	1991	1704414
scrapie prion rod formation in vitro requires both detergent extraction and limited proteolysis.	scrapie prion infectivity can be enriched from hamster brain homogenates by using limited proteolysis and detergent extraction. purified fractions contain both scrapie infectivity and the protein prp 27-30, which is aggregated in the form of prion rods. during purification, prp 27-30 is produced from a larger membrane protein, prpsc, by limited proteolysis with proteinase k. brain homogenates from scrapie-infected hamsters do not contain prion rods prior to exposure to detergents and proteases. ...	1991	1704926
molecular location of a species-specific epitope on the hamster scrapie agent protein.	scrapie is a transmissible neurodegenerative disease of sheep and goats. an abnormal host protein, sp33-37, is the major protein component of the scrapie agent and the only known disease- or agent-specific macromolecule. two monoclonal antibodies (mabs), 4h8 (immunoglobulin g2b [igg2b]) and 6b11 (igg1), produced by immunizing mice with the intact hamster 263k scrapie agent protein, sp33-37ha, were found to have species specificity similar to that reported previously for mab 3f4 (igg2a), which wa ...	1991	1710287
topographic distribution of scrapie amyloid-immunoreactive plaques in chronic wasting disease in captive mule deer (odocoileus hemionus hemionus).	chronic wasting disease (cwd), a progressive neurological disorder of captive mule deer, black-tailed deer, hybrids of mule deer and white-tailed deer and rocky mountain elk, is characterized neuropathologically by widespread spongiform change of the neuropil, intracytoplasmic vacuolation in neuronal perikarya and astrocytic hypertrophy and hyperplasia. we report the topographic distribution of amyloid plaques reactive to antibodies prepared against scrapie amyloid in cwd-affected captive mule d ...	1991	1713390
[the use of electron microscopy for diagnosing spongiform encephalopathies].	the authors suggest an unsophisticated approach to laboratory diagnosis of spongiform encephalopathies induced by unconventional prion viruses, consisting in electron microscopic detection of abnormal helical scrapie-associated fibrils. these fibrils are detectable in human and animal brain tissue samples and in cell cultures.	1991	1715430
epitope mapping of the syrian hamster prion protein utilizing chimeric and mutant genes in a vaccinia virus expression system.	the cellular prion protein (prpc) is a host-encoded sialoglycoprotein bound to the external surface of the cell membrane by a glycosyl phosphatidylinositol anchor. a posttranslationally modified prp isoform (prpsc) is a component of the infectious particle causing scrapie and the other prion diseases. mab have been raised against the protease-resistant core of syrian hamster (sha) prpsc designated prp 27-30. to map the epitopes within prp reacting to these antibodies, we have expressed wild-type ...	1991	1719082
scrapie and gss--the importance of protein.		1991	1720577
demonstration of amyloid beta-protein in a 32-year-old man with progressive dementia.	we report the immunolocalization of extensive amyloid beta-protein in senile plaques, cerebrovascular amyloid deposits, neurofibrillary tangles and preamyloid in a 32-year-old man with progressive dementia not due to trisomy 21 or trauma. these amyloid deposits were non-reactive to antibodies directed against scrapie amyloid. our data indicate that the presence of amyloid beta-protein is not limited to normal aging, alzheimer's disease and related disorders but is also found in younger individua ...	1991	1723832
evidence for biological and structural diversity among scrapie strains.		1991	1725770
ultrastructural studies of prions.		1991	1725771
transgenic modelling of neurodegenerative events gathers momentum.		1991	1726340
prince edward island. scrapie in prince edward island.		1991	17423824
prion diseases and the frame-shifting hypothesis.	a group of neurological diseases, which includes scrapie, bovine spongiform encephalopathy and creutzfeldt-jakob disease, is caused by prion agents which appear to be comprised solely of an abnormal variant of a cellular protein, prp. infectious agents which contain no genetic material pose a conundrum for molecular biologists. theoretical analysis of the gene encoding prp has suggested a possible mechanism of replication for this proteinaceous infectious agent. the putative mechanism involves f ...	1991	16031617
spiroplasmas and spongiform encephalopathies.		1992	1736068
feline spongiform encephalopathy: fibril and prp studies.	the brains from 18 cats were examined for the presence of the fibrils and modified prp protein which are molecular diagnostic markers for scrapie-like diseases. thirteen cats were referred with clinical neurological signs potentially indicative of feline spongiform encephalopathy (fse). of these, five had histopathological changes of fse, five had other lesions of the central nervous system, and in three the brain was normal. the remaining five cats had no clinical neurological signs and were se ...	1992	1279883
[prion encephalopathies].	spongiform encephalopathies, also called prion encephalopathies, are characterized, in human as well as in animals, by (1) their clinical picture which indicates strict localisation in central nervous system, (2) their histological aspect: spongiform degeneration and neuronal loss, and (3) their transmissibility in the same animal species but also from man to animal. the nature of the pathogenic agent is still debated. this agent could be one isoform of the prion protein which, probably because ...	1992	1288542
new insight into the nature of scrapie from old radiation results.		1992	1290682
[human transmissible dementia: prion diseases?].	subacute transmissible spongiform encephalopathies (stse) represent a cause of presenile dementias, found in man (creutzfeldt-jakob disease, gerstmann-straussler syndrome, kuru), in sheep and goats (scrapie), in cattle (bovine spongiform encephalopathy) and in various mammals. it seems that the frequency of the human spongiform encephalopathy (hse) is more frequent than thought up to now and an alimentary origin is not to be discarded. many discussions are held concerning the nature of the trans ...	1992	1300226
immunoreactivity to ubiquitin-protein conjugates is present early in the disease process in the brains of scrapie-infected mice.	brains from mice infected with either the 87v or the me7 strains of mouse-passaged sheep scrapie were taken at stages during the disease process and immunostained to show the localization of ubiquitin-protein conjugates. in both models, conjugates were seen as fine, dot-like structures; as coarser, granular lesions within or adjacent to neurones; and in areas surrounding plaques. the dot-like structures were visible at 28 days post-me7 infection and at 55 days in 87v-infected mice. in both model ...	1992	1334140
scrapie-associated tubulofilamentous particles in scrapie hamsters.	examination of thin sections from the cerebral cortex of scrapie-infected hamster brains revealed characteristic circular 26-30 nm diameter tubulofilamentous particles, identical to those previously described in both experimentally induced scrapie in mice, hamsters and natural scrapie of sheep, bovine spongiform encephalopathy and human creutzfeldt-jakob disease and mice and chimpanzees infected with creutzfeldt-jakob disease. longitudinal forms of tubulofilamentous particles were also observed ...	1992	1338060
chimeric prion protein expression in cultured cells and transgenic mice.	the efficient expression of exogenous prion protein (prp) molecules in mouse neuroblastoma cells that are chronically infected with murine scrapie prions (scn2a cells; butler, d.a., et al., 1988, j. virol. 62, 1558-1564) and in transgenic mice is described. this technology allows investigation of the prp molecule for structural regions involved in determining species specificity, as well as ablation experiments designed to address the functionality of particular regions of the prp molecule. prev ...	1992	1338978
creutzfeldt-jakob disease with tubulovesicular structures: an ultrastructural study.	tubulovesicular structures (tvs) have been consistently observed in brain tissue of the transmissible spongiform virus encephalopathies such as natural and experimental scrapie, bovine spongiform encephalopathy and experimentally induced creutzfeldt-jakob disease (cjd). tvs were recently demonstrated in 3 cases of naturally occurring cjd. we report here the presence of tvs in another human brain with cjd, as detected in all 3 specimens by thin section electron microscopy. their occurrence in all ...	1992	1340922
nearly ubiquitous tissue distribution of the scrapie agent precursor protein.	the "modified host protein" model of scrapie proposes that the transmissible agent is composed of the degradation-resistant protein, sp33-37, and that clinical and pathologic signs result from neurotoxic accumulations of this protein. sp33-37 is an abnormal, amyloidogenic isoform of the normally occurring cellular protein cp33-37. this study investigated the tissue distribution of cp33-37 in hamster. in brain, cp33-37 was most concentrated in the hippocampal formation. immunohistochemical studie ...	1992	1346470
biochemical and physical properties of the prion protein from two strains of the transmissible mink encephalopathy agent.	transmissible mink encephalopathy (tme) has been transmitted to syrian golden hamsters, and two strains of the causative agent, hyper (hy) and drowsy (dy), have been identified that have different biological properties. during scrapie, a tme-like disease, an endogenous cellular protein, the prion protein (prpc), is modified (to prpsc) and accumulates in the brain. prpsc is partially resistant to proteases and is claimed to be an essential component of the infectious agent. purification and analy ...	1992	1347795
recommendations of the international roundtable workshop on bovine spongiform encephalopathy.	recommendations of the working party were summarized as follows: determine the status in all countries of their national cattle herds with respect to bse. attempt to develop a test to recognize bse-infected animals before they become clinically ill. establish procedures to prevent spread of bse agent into the cattle populations, especially by eliminating feeds containing rendered ruminant proteins. review the rendering processes, identify the sources and destinations of rendered products, and su ...	1992	1348501
spongiform encephalopathies. prp and the scrapie agent.		1992	1348569
amphotericin b treatment dissociates in vivo replication of the scrapie agent from prp accumulation.	scrapie and related animal and human disorders are neurodegenerative diseases characterized by the formation of a modified, partly proteinase-resistant protein (prp) of the host, which tends to aggregate as amyloid fibrils and accumulate in the brain of infected individuals. there is a general consensus that the pathological form of prp (prpsc) is essential for the clinical appearance of the disease, but whether it is part of the scrapie agent or a by-product of viral infection is still controve ...	1992	1348570
studies on maternal transmission of scrapie in sheep by embryo transfer.	the technique of embryo transfer was used to investigate the maternal transmission of scrapie in sheep. embryo donor ewes were experimentally infected with scrapie (all eventually developing the disease) and artificially inseminated six months later with semen from an uninfected scrapie-susceptible ram. embryos were harvested five and six days after insemination and transferred by laparoscopy, unwashed, into recipient ewes which had been genetically selected for very low susceptibility to scrapi ...	1992	1350694
glycosylinositol phospholipid anchors of the scrapie and cellular prion proteins contain sialic acid.	the only identified component of the scrapie prion is prpsc, a glycosylinositol phospholipid (gpi)-linked protein that is derived from the cellular isoform (prpc) by an as yet unknown posttranslational event. analysis of the prpsc gpi has revealed six different glycoforms, three of which are unprecedented. two of the glycoforms contain n-acetylneuraminic acid, which has not been previously reported as a component of any gpi. the largest form of the gpi is proposed to have a glycan core consistin ...	1992	1350920
natural scrapie in british sheep: breeds, ages and prp gene polymorphisms.	one hundred and sixty-seven sheep of 32 breeds and crossbreeds affected by natural scrapie throughout britain were tested for the presence of restriction fragment length polymorphisms of the prp gene observed when their dna was digested with ecori or hindiii. these polymorphisms have already been associated with different susceptibilities to experimental scrapie (controlled by alleles of the sip gene) in a flock of cheviot sheep. in two studies 86 to 92 per cent of the sheep were found to carry ...	1992	1351694
accumulation of transcripts coding for prion protein in human astrocytes during infection with human immunodeficiency virus.	the abnormal isoforms of the normal cellular prion protein (prp), also termed scrapie-associated fibril protein, are assumed to be one causative factor of spongiform encephalopathies. the mrna of prp contains stem-loop structures which are very similar to the human immunodeficiency virus-1 (hiv-1) cis-acting sequence tar within the ltr; both structures contain the pentanucleotide cuggg in the loop, and the uridine- and adenine-bulge in the stem. in this study, using purified hiv-encoded trans-ac ...	1992	1351748
molecular biology of scrapie-like agents.	a detailed account is given of the nature of the causal agent of scrapie and other transmissible spongiform encephalopathies, with reference to proteinase-resistant protein and its gene, subviral particles and the prion hypothesis.	1992	1352155
biological activity of subfractions from scrapie-associated fibrils.	subfractions, a nucleic acid fraction and a prp fraction consisting of prp17-25, a core fragment of prpsc, were prepared from the scrapie-associated fibril-enriched fraction from scapie-affected mouse brains. the nucleic acid fraction consisted mainly of variously fragmented dna and no scrapie-specific nucleic acid was detected in the fraction by sds polyacrylamide gel electrophoresis. to examine the biological activity, the nucleic acid fraction was either first introduced into mouse l-929 cell ...	1992	1352653
diagnostic implications of detection of proteinase k-resistant protein in spleen, lymph nodes, and brain of sheep.	brain, spleen, and selected lymph nodes from sheep with clinical signs of scrapie were analyzed for presence of proteinase k-resistant protein (prp-res). diagnosis of scrapie on the basis of detection of prp-res was compared with diagnosis on the basis of histologic evaluation of the brain from clinically affected or exposed sheep. proteinase k-resistant protein was found in every brain that was histologically positive for scrapie, and in addition, was found in the brain of several clinically po ...	1992	1352664
variations in prion protein and glial fibrillary acidic protein mrnas in the brain of scrapie-infected newborn mouse.	to begin to understand the molecular basis of cases of creutzfeldt-jakob disease recently described in young children, the expression of prion protein and glial fibrillary acidic protein (gfap) mrnas was investigated during the development of the brain of scrapie-infected newborn mice. changes in the time course of expression were identified by northern blot quantification between days 1 and 172. although scrapie-infected and control animals showed no detectable changes in brain development (fir ...	1992	1352797
potent inhibition of scrapie-associated prp accumulation by congo red.	transmissible spongiform encephalopathies (prion diseases), alzheimer's disease, and other amyloidoses result in the accumulation of certain abnormally stable proteins that are thought by many to play central roles in disease pathogenesis. using scrapie-infected neuroblastoma cells as a model system, we found that congo red, an amyloid-binding dye, potently inhibits the accumulation of the scrapie-associated, protease-resistant isoform of protein prp without affecting the metabolism of the norma ...	1992	1352803
further analysis of nucleic acids in purified scrapie prion preparations by improved return refocusing gel electrophoresis.	although increasingly unlikely, the possibility of a scrapie-specific nucleic acid carried by infectious prion particles is still unresolved. return refocusing gel electrophoresis was developed to detect homogeneous and heterogeneous nucleic acids extracted from highly purified scrapie prion preparations. this method was improved with respect to the size range from 13 to 1100 nucleotides (nt) over which analyses could be performed. the yield of nucleic acid, particularly of small dna oligonucleo ...	1992	1353106
immunohistochemical study of kuru plaques using antibodies against synthetic prion protein peptides.	prion protein (prp) is a protein closely associated with the transmission of scrapie and creutzfeldt-jakob disease (cjd). kuru plaques are composed of this protein. prp33-35 is converted to protease-resistant prp27-30 by proteinase k digestion. it has not yet been determined which of these prps is present in kuru plaques in vivo. accordingly we synthesized two peptides (peptide-n and peptide-m) that, respectively, corresponded to the protease-sensitive and protease-resistant portions of prp33-35 ...	1992	1353279
the prion protein gene: a role in mouse embryogenesis?	the neural membrane glycoprotein prp (prion protein) has a key role in the development of scrapie and related neurodegenerative diseases. during pathogenesis, prp accumulates in and around cells of the brain from which it can be isolated in a disease-specific, protease-resistant form. although the involvement of prp in the pathology of these diseases has long been known, the normal function of prp remains unknown. previous studies have shown that the prp gene is expressed tissue specifically in ...	1992	1353438
spontaneous conversion of prpc to prpsc.	octa-repeats of prion proteins (prp) contain histidine and tryptophan residues which are known to function as ligands for transition metals. it is proposed that the spontaneous conversion of the prpc (cellular) isoform into prpsc (scrapie) isoform may be triggered by the coordination of these metals.	1992	1353727
evidence for synthesis of scrapie prion proteins in the endocytic pathway.	infectious scrapie prions are composed largely, if not entirely, of an abnormal isoform of the prion protein (prp) which is designated prpsc. a chromosomal gene encodes both the cellular prion protein (prpc) as well as prpsc. pulse-chase experiments with scrapie-infected cultured cells indicate that prpsc is formed by a post-translational process. prp is translated in the endoplasmic reticulum, modified as it passes through the golgi, and is transported to the cell surface. release of nascent pr ...	1992	1353761
regional mapping of prion proteins in brain.	scrapie is characterized by the accumulation of a protease-resistant isoform of the prion protein prpsc. limited proteolysis and chaotropes were used to map the distribution of prpsc in cryostat sections of scrapie-infected brain blotted onto nitrocellulose membranes, designated histoblots. proteolysis was omitted in order to map the cellular isoform of the prion protein (prpc) in uninfected brains. compared with immunohistochemistry, histoblots increased the sensitivity for prpsc detection and ...	1992	1354357
possible cell-free prion replication.	spongiform encephalopathies, such as scrapie or bovine spongiform encephalopathy in animals, or kuru, creutzfeld-jakob disease (cjd) and gerstmann-sträussler-scheinker disease (gss) in man, seem to be caused by a transmissible agent whose nature is still a matter of debate. the properties of this agent which has been designated as prion, differ from those of any other known infectious agents, including viruses and viroids. several lines of evidence suggest that the prion is devoid of nucleic aci ...	1992	1355257
the infectivity of spongiform encephalopathies: does a modified membrane hypothesis account for lack of immune response?	scrapie, the prototype of a group of diseases which have the unique property of being both hereditary and infectious, is also exceptional in that it fails to evoke an immune response. purification of crude scrapie preparations revealed a strong association of infectivity with a membrane protein ('prpsc'); but a protein with the same amino acid sequence ('prpc') was subsequently also found in normal mammalian nervous tissue. it is postulated by some investigators that 'prpsc' is itself the infect ...	1992	1355344
lysosomes as key organelles in the pathogenesis of prion encephalopathies.	the causation, structural origin, and mechanism of formation of spongiform lesions in transmissible encephalopathies are unknown. we have used immunogold electron microscopy to locate ubiquitin conjugates, hsp 70, and beta-glucuronidase (markers of the lysosomal compartment) and prion protein (prp) in both control and scrapie-infected mouse brain. in scrapie-infected brain, lysosomes and lysosome-related structures (multivesicular and tubulovesicular dense bodies) are present in abnormally high ...	1992	1355530
attempts to convert the cellular prion protein into the scrapie isoform in cell-free systems.	the scrapie prion protein (prpsc) is derived from a cellular isoform (prpc) that acquires protease resistance posttranslationally. we have used several different experimental approaches in attempts to reconstitute in vitro the processes leading to protease-resistant prpsc molecules. in the first study, we performed mixing experiments by adding mouse prp 27-30 (moprp27-30), the protease-resistant core of prpsc, to prpc and then incubating the mixture to investigate the possibility of heterodimer ...	1992	1356161
synthesis and trafficking of prion proteins in cultured cells.	scrapie prions are composed largely, if not entirely, of the scrapie prion protein (prpsc) that is encoded by a chromosomal gene. scrapie-infected mouse neuroblastoma (scn2a) and hamster brain (schab) cells synthesize prpsc from the normal prp isoform (prpc) or a precursor through a posttranslational process. in pulse-chase radiolabeling experiments, we found that presence of brefeldin a (bfa) during both the pulse and the chase periods prevented the synthesis of prpsc. removal of bfa after the ...	1992	1356522
are sinc and the prp gene congruent? evidence from prp gene analysis in sinc congenic mice.	congenic mouse strains vm/dk and vm-sincs7/dk differ at the sinc gene, which controls the incubation period of scrapie in mice; vm/dk mice are sincp7p7 and vm-sincs7/dk mice are sincs7s7. restriction fragment length polymorphism and dna sequencing analysis demonstrated that the prp genes also differ in these strains, confirming the close genetic linkage of sinc and prp. using the restriction enzyme hhai, we have shown that at least 100 kb of dna flanking the prp gene differs between the two stra ...	1992	1357080
a role for lysosomes in scrapie pathogenesis.		1992	1358723
demonstration of scrapie strain diversity in infected pc12 cells.	scrapie strain replication in the nerve growth factor-induced, differentiated pc12 cell culture system was examined. differences in replication between mouse-derived agents were demonstrated, with the 139a scrapie strain yielding 100- to 1000-fold higher levels of infectivity than the me7 scrapie strain. replication was not detected in pc12 cells infected with either the hamster-derived 263k or rat-derived 139r scrapie strains. studies on the neurotransmitters in infected pc12 cells demonstrated ...	1992	1359002
polymorphisms of a scrapie-associated fibril protein (prp) gene and their association with susceptibility to experimentally induced scrapie in cheviot sheep in the united states.	the duration of the incubation period for scrapie, a fatal transmissible neurodegenerative disorder of sheep and goats, is mainly determined by the sip gene, which has 2 alleles (sa--susceptible and pa--resistant). a diagnostic test is not available to detect scrapie in live animals. we analyzed genomic dna extracted from frozen sheep brains collected from cheviot sheep of the united states that had been inoculated with the ssbp/1 scrapie inoculum. digestion of the dna with ecori or hindiii foll ...	1992	1360777
a specific rflp type associated with the occurrence of sheep scrapie in japan.	we have investigated restriction fragment length polymorphism (rflp) on the prp gene and the frequencies of rflp patterns in 35 healthy suffolk sheep randomly collected. according to the combinations of prp encoding dna fragments generated by restriction enzymes eco ri and hind iii, the rflp patterns were classified into six types and designated as types i to vi. the frequencies of these types were as follows: i, 8.6%; ii, 11.4%; iii, 17.6%; iv, 11.4%; v, 28.6%; and vi, 22.9%. in 10 sheep diagno ...	1992	1360795
detection of proteinase k-resistant prion protein and infectivity in mouse spleen by 2 weeks after scrapie agent inoculation.	the sequential accumulation of the protease-resistant form of the endogenous prion protein (prp-res) was compared to levels of scrapie infectivity in the spleen and brain of scrapie-infected mice at various times after inoculation. in mouse spleen prp-res was detected 1 week after inoculation, and increased 65-fold between 1 and 3 weeks post-inoculation and an additional 15-fold during the next 17 weeks. infectivity in spleen reached a maximum plateau level by 3 weeks. in contrast, in mouse brai ...	1992	1361522
immunodetection of a disease specific prp fraction in scrapie-affected sheep and bse-affected cattle.		1992	1362015
comparative sequence analysis and expression of bovine prp gene in mouse l-929 cells.	a cdna clone encoding bovine scrapie-associated fibril protein, prp, from a bovine brain cdna library and six amplified genomic dna clones of bovine prp were characterized. these clones possessed specific characteristics observed in other animal prp genes. however, the bovine prp was divided into two types by the number of repeats. one possessed four octapeptide repetitive sequences, like other animal prp genes, and consisted of 256 amino acids; the other had five such repetitive sequences and 2 ...	1992	1362024
prp protein is associated with follicular dendritic cells of spleens and lymph nodes in uninfected and scrapie-infected mice.	abnormal forms of a host protein, prp, accumulate in the central nervous system in scrapie-affected animals. here, prp protein was detected immunocytochemically in tissue sections of spleen, lymph node, peyer's patches, thymus, and pancreas from uninfected mice and from mice infected with a range of mouse-passaged scrapie strains and bovine spongiform encephalopathy (bse). in the spleen, lymph node and peyer's patches, prp-positive cells were identified as follicular dendritic cells (fdc) by the ...	1992	1362440
prpsc causes nerve cell death and stimulates astrocyte proliferation: a paradox.		1992	1363148
relationship of protease-resistant protein, scrapie-associated fibrils and tubulofilamentous particles to the agent of spongiform encephalopathies.	tubulofilamentous particles and scrapie-associated fibrils (saf) are ultrastructural markers, while protease-resistant protein (prp) is a molecular biological marker for all spongiform encephalopathies. review of all published work has suggested that prp molecules aggregate to form a three-dimensional saf. further reports have suggested that a single-stranded dna wraps round saf and acquires an outer protein coat to form tubulofilamentous particles. as incubation period increases in the infected ...	1992	1363618
scrapie-associated tubulofilamentous particles in human creutzfeldt-jakob disease.	scrapie-associated fibrils (saf) were demonstrated by a simple negative staining method for electron microscopy from fresh and frozen brains with naturally occurring human creutzfeldt-jakob disease (cjd). the findings confirm that saf occur as an internal part of a larger three-layer particle. the two outer coats of saf can be disrupted by detergent alone or can be digested in two stages by a combination of proteolytic enzymes and subsequent treatment with dnase and mung bean nuclease. examinati ...	1992	1363619
purification and properties of the cellular prion protein from syrian hamster brain.	the cellular prion protein (prpc) is encoded by a chromosomal gene, and its scrapie isoform (prpsc) features in all aspects of the prion diseases. prior to the studies reported here, purification of prpc has only been accomplished using immunoaffinity chromatography yielding small amounts of protein. brain homogenates contain two prpc forms designated prpc-i and -ii. these proteins were purified from a microsomal fraction by detergent extraction and separated by immobilized cu2+ ion affinity chr ...	1992	1363897
hidden amyloidoses.	the pathogenesis as well as the genetic disposition to develop clinical symptoms in transmissible spongiform encephalopathies (e.g. creutzfeldt-jakob disease, scrapie, bovine spongiform encephalopathy) relate these diseases to classical noninfectious amyloidoses (familial amyloidotic polyneuropathy as an example) and to alzheimer's disease. this is not obvious to the nonexpert at first glance. this communication tries to elucidate this association, to reveal which immunochemical techniques have ...	1992	1364008
bovine spongiform encephalopathy (bse): a stimulus to wider research.	the severity of the epidemic of bovine spongiform encephalopathy which is currently afflicting cattle in the british isles has stimulated a considerable research effort, much of which is directed toward understanding the aetiology and pathogenesis of the bovine disease. however, a significant thrust has also been orchestrated to address more fundamental issues such as the nature of the uncharacterized causal agents of the wider range of unusual animal and human diseases which share similar chara ...	1992	1364085
sulphate polyanions prolong the incubation period of scrapie-infected hamsters.	the effect of the organic sulphated polyanions, pentosan sulphate (sp54), dextran sulphate 500 (ds500) and suramin, have been tested on golden syrian hamsters infected with the 263k strain of scrapie by the intraperitoneal (i.p.) or the intracerebral route. sp54 had the greatest effect in prolonging the incubation period of the disease when administered within 2 h of the i.p. inoculum. the same amount of sp54 given 24 h after scrapie inoculation had a potent effect in some animals and no effect ...	1992	1372039
normal development and behaviour of mice lacking the neuronal cell-surface prp protein.	prpc is a host protein anchored to the outer surface of neurons and to a lesser extent of lymphocytes and other cells. the transmissible agent (prion) responsible for scrapie is believed to be a modified form of prpc. mice homozygous for disrupted prp genes have been generated. surprisingly, they develop and behave normally for at least seven months, and no immunological defects are apparent. it is now feasible to determine whether mice devoid of prpc can propagate prions and are susceptible to ...	1992	1373228
molecular cloning of a mink prion protein gene.	transmissible mink encephalopathy (tme) is a rare disease which is presumably transmitted to ranch-raised mink from scrapie-infected sheep offal or bovine spongiform encephalopathy-infected cattle products. although the infectious agent of tme has not been isolated, there is circumstantial evidence that tme is caused by prions. the experimental host range of tme includes sheep, cattle, monkeys and hamsters. however, tme has never been transmitted to mice. since experiments in transgenic animals ...	1992	1383401
recently described scrapie-like encephalopathies of animals: case definitions.	since 1986, naturally occurring scrapie-like encephalopathies have been described in the united kingdom in domestic cattle, in five species of captive exotic bovids and in domestic cats. the disease in domestic cattle, bovine spongiform encephalopathy, has been characterised by all currently available diagnostic criteria as a transmissible spongiform encephalopathy or 'prion' disease, and has been shown to have a dietary origin. the pathology in the other species is also entirely consistent with ...	1992	1410804
tubulovesicular structures in creutzfeldt-jakob disease.	by electron microscopy tubulovesicular structures (tvs) have been consistently observed in brain tissue of transmissible spongiform encephalopathies such as natural and experimental scrapie, bovine spongiform encephalopathy and experimentally induced, but not naturally occurring, creutzfeldt-jakob disease (cjd). for the first time we report here the presence of tvs in human brains with cjd as detected by transmission electron microscopy. tvs were observed in all three cjd specimens (two biopsies ...	1992	1414277
natural and experimental prion diseases of humans and animals.	prions cause transmissible and genetic neurodegenerative diseases. infectious prion particles are composed largely, if not entirely, of an abnormal isoform of the prion protein (prpsc), which is encoded by a chromosomal gene. although the prp gene is single copy, transgenic mice with both alleles of the prp gene ablated develop normally. a post-translational process, as yet unidentified, converts the cellular prion protein (prpc) into prpsc. scrapie incubation times, neuropathology and prion syn ...	1992	1422120
predicted alpha-helical regions of the prion protein when synthesized as peptides form amyloid.	by comparing the amino acid sequences of 11 mammalian and 1 avian prion proteins (prp), structural analyses predicted four alpha-helical regions. peptides corresponding to these regions of syrian hamster prp were synthesized, and, contrary to predictions, three of the four spontaneously formed amyloids as shown by electron microscopy and congo red staining. by ir spectroscopy, these amyloid peptides exhibited secondary structures composed largely of beta-sheets. the first of the predicted helice ...	1992	1438300
[suspicion of visna in a sheep from graubünden canton].	a lentivirus belonging to the group of retroviridae causes a chronic progressive interstitial pneumopathy (maedi) or a demyelinating encephalo-myelitis (visna) in sheep and goats. pulmonary lesions of maedi as well as sero-positive, clinically healthy animals can be observed in switzerland; visna, which even in countries with endemic infection does not occur frequently, is extremely rare. the head and cervical spine of an ewe with severe nervous troubles suspected of scrapie were submitted for p ...	1992	1439707
[the interrelationship of the causative agents of subacute transmissible spongiform encephalopathies].	virological, histological, and electron microscopy methods were used to study the features of the infectious process in minks infected with scrapie agent as compared with that in minks infected with the agent of mink transmissive encephalopathy and in mice infected with scrapie. the results of the study showed the similarity in the clinical picture and the pattern of histological and ultramicroscopic lesions in minks infected with either of the agents. on the basis of the authors' own data and t ...	1992	1441441
the role of perivascular and microglial cells in fibrillogenesis of beta-amyloid and prp protein in alzheimer's disease and scrapie.		1992	1455056