Publications

'prion' diseases.		1994	7965986
distinct prp properties suggest the molecular basis of strain variation in transmissible mink encephalopathy.	the molecular basis of strain variation in scrapie diseases is unknown. the only identified component of the agent is the posttranslationally modified host prion protein (prpsc). the biochemical and physical properties of prp from two strains of transmissible mink encephalopathy (tme), called hyper (hy) and drowsy (dy), were compared to investigate if prp heterogeneity could account for strain diversity. the degradation rate of prptme digested with proteinase k was found to be strain specific an ...	1994	7966576
murine scrapie-infected neurons in vivo release excess prion protein into the extracellular space.	an originally heretical proposition that the transmissible spongiform encephalopathies are caused by a host-coded protein (the prion hypothesis) is now current dogma. indeed these disorders are commonly called prion diseases but the prion hypothesis provides no readily acceptable explanation for the source of the informational component of the agent necessary to code for the diversity of strains of scrapie. ultrastructural immunolocalisation of prion protein (prp) in murine scrapie shows that pr ...	1994	7970151
scrapie associated fibrils in found dead sheep.		1994	7975058
neurodegeneration in humans caused by prions.	prion diseases include kuru, creutzfeldt-jakob disease, gerstmann-sträussler-scheinker disease, and fatal familial insomnia of humans as well as scrapie and bovine spongiform encephalopathy of animals. for many years, the prion diseases were thought to be caused by viruses despite evidence to the contrary. the unique characteristic common to all of these disorders, whether sporadic, dominantly inherited, or acquired by infection, is that they involve aberrant metabolism of the prion protein. in ...	1994	7975565
the association of a codon 136 prp gene variant with the occurrence of natural scrapie.	incidence of both experimental and natural scrapie in sheep has been associated with polymorphisms of the prp gene. in case/control studies the prp allele which encodes valine at codon 136 (val136) is found in 96-100% of naturally infected scrapie sheep of shetland, scottish halfbred and blue du maine breeds. in contrast, in healthy animals from the same flocks, the most frequent allele encodes ala136 (91-100% of sheep). however val136 does not correlate with incidence of scrapie in two other fl ...	1994	7979991
capillary electrophoresis of the scrapie prion protein from sheep brain.	scrapie in sheep and goats causes a progressive, degenerative disease of the central nervous system and is the prototype of other transmissible spongiform encephalopathies (tse) found in humans and in animals. in samples of tse-affected brains, unique rod-shaped structures are found and are infectious. these rods are composed of a protease-resistant, post-translationally modified cellular protein (prpsc) that has a molecular mass of ca. 27,000 on sodium dodecyl sulfate-polyacrylamide gel electro ...	1994	7981826
electron microscopic findings in brain of rocky mountain elk with chronic wasting disease.	we report here the electron microscopic findings in brain of rocky mountain elk with chronic wasting disease (cdw), a progressive and fatal neurological disorder of wild ruminants characterized neuropathologically by intraneuronal vacuolation, spongiform change of the neuropil and astrocytic hypertrophy and hyperplasia. ultrastructural findings included membrane-bound vacuoles in neuronal elements, increased number of glial filaments, dystrophic neurites, numerous neuritic plaques, hirano bodies ...	1994	7982031
congo red prolongs the incubation period in scrapie-infected hamsters.	in scrapie-infected cells, congo red inhibits both the replication of the infectious agent and accumulation of the protease-resistant form of prp (prp-res). in this report, we show that congo red prolongs the incubation periods of hamsters experimentally infected with two different strains of scrapie.	1995	7983747
cytokines, prostaglandins and lipocortin-1 are present in the brains of scrapie-infected mice.	the presence of cytokines, prostaglandins and lipocortin-1 was investigated in terminally affected mice in two models of scrapie. there was marked induction of glial interleukin-1 beta, tumour necrosis factor alpha, prostaglandin e2, prostaglandin f2 alpha and lipocortin-1 immunoreactivity in those areas of the brain showing the characteristic vacuolation of scrapie. a comparison of these staining patterns with those of gfap and f4/80 showed that their expression occurred predominantly in astroc ...	1994	7987669
[unconventional disease agents--a danger for humans and animals?].	the occurrence of bovine spongiform encephalopathy (bse) in great britain in 1985/86, has focused again the public concern as well as scientific interest to the scrapie disease of sheep and goat known more than 150 years. the agents of scrapie and bse are characterized by unusual biological and physical-chemical properties, especially their high tenacity. therefore, they are also designated "unconventional agents of viruses". different theories have been proposed about their infectious character ...	1994	7993336
prp in pathology and pathogenesis in scrapie-infected mice.	prp accumulation in the brains of mice infected with scrapie takes several different forms: amyloid plaques, widespread accumulation in neuropile, and perineuronal deposits. prp is also sometimes detected within microglia and in or around astrocytes. there are dramatic and reproducible differences between scrapie strains in the relative prominence of these changes and their distribution in the brain. depending on the scrapie strain, prp pathology is targeted precisely to particular brain areas, ...	1994	7999306
inhibition of scrapie-associated prp accumulation. probing the role of glycosaminoglycans in amyloidogenesis.	accumulation of an abnormal, protease-resistant form of an endogenous protein, prp, is a characteristic feature of scrapie and related transmissible spongiform encephalopathies. this abnormal isoform is also present in the amyloid plaques that are often observed in these diseases. in mouse neuroblastoma cells persistently infected with scrapie, the abnormal protease-resistant isoform of prp is derived from an operationally normal protease-sensitive precursor. conversion of prp to the protease-re ...	1994	7999307
129/ola mice carrying a null mutation in prp that abolishes mrna production are developmentally normal.	the neural membrane glycoprotein prp is implicated in the pathogenesis of the transmissible spongiform encephalopathies; however, the normal function of prp and its precise role in disease are not understood. recently, gene targeting has been used to produce mice with neo/prp fusion transcripts, but no detectable prp protein in the brain (1). here we report the use of a different targeting strategy, to produce inbred mice with a complete absence of both prp protein and mrna sequences. at 7 mo of ...	1994	7999308
scrapie strain infection in vitro induces changes in neuronal cells.	pc12 cells, in the presence of nerve growth factor (ngf), support replication of the mouse-derived scrapie strains 139a and me7, with the former yielding 100-1000-fold higher levels of infectivity. infectivity remained cell-associated and cells did not show any gross morphological alterations, although changes were observed by electron microscopy in the form of an increased number of lipid droplets in 139a-infected cultures. analysis of phospholipid metabolism in 139a infected cells indicated th ...	1994	7999309
survey of natural scrapie in japan: analysis of rflp types of the prp gene and detection of prpsc mainly in suffolk sheep.	we examined the brains, spleens and/or lymph nodes of 197 mainly suffolk sheep collected from hokkaido, and the tohoku, kanto and chubu districts to detect prpsc and thus to estimate scrapie contamination in japan. sixteen sheep in hokkaido and 2 sheep in other districts that were introduced from hokkaido were positive for prpsc. by comparison of the frequencies of the restriction fragment length polymorphism (rflp) types of these 18 scrapie sheep with 128 healthy sheep, we confirmed the associa ...	1994	7999881
a neurotoxic prion protein fragment induces rat astroglial proliferation and hypertrophy.	prion-related encephalopathies are characterized by the accumulation of an abnormal prion protein isoform (prpsc) and the deposition of prp amyloid in the brain. this process is accompanied by neuronal loss and astrogliosis. we recently showed that a synthetic peptide corresponding to residues 106-126 of human prp is amyloidogenic and causes neuronal death by apoptosis in vitro. in the present study we investigated the effects of 1- and 14-day exposures of rat astroglial cultures to micromolar c ...	1994	8000566
hungary remains free of scrapie and bovine spongiform encephalopathy (bse).	brains from 44 sheep and 43 cattle with cns clinical signs not due to rabies virus infection were collected from diagnostic institutes throughout hungary. the brains were examined for histological lesions diagnostic of scrapie/bovine spongiform encephalopathy (bse) and all were found to be negative. these findings confirm that hungary remains free of scrapie and bse.	1993	8017235
alkaloidal glycosidase inhibitors (agis) as the cause of sporadic scrapie, and the potential treatment of both transmissible spongiform encephalopathies (tses) and human immunodeficiency virus (hiv) infection.	agis are produced by plants and microorgansims in the environment. they are absorbed from the gut, distributed throughout the body and are concentrated inside cells. agis alter the glycan chains of cellular glycoproteins (cgp) during their formation so that the same cgp produced by different clones of cells (and hence with different glycan chains) becomes structurally the same. prion protein (prp), a cgp, is rendered indestructable to cellular mechanisms (as prpi) by the tse infective process; i ...	1994	8022334
bovine spongiform encephalopathy. epidemiology, low dose exposure and risks.	bse has occurred in the u.k. as an extended common source epidemic since 1985/86. the vehicle of infection was concentrated feeds containing meat and bone meal produced by the rendering of ovine, bovine and other animal wastes. the epidemic was probably initiated in 1981/82 when a sudden decline in the use of solvents in rendering allowed a low incidence of scrapie-like infection to occur in cattle. however, the presence in feed of bovine material that, from 1984/85 (or earlier), was increasingl ...	1994	8030941
the nature of the scrapie agent. biological characteristics of scrapie in different scrapie strain-host combinations.		1994	8030943
prp-deficient mice are resistant to scrapie.	prusiner proposed that the infectious agent of scrapie, the prion, is prpsc, a modified form of the normal host protein prpc. prn-p0/0 mice devoid of prpc showed normal development and behavior. when inoculated with mouse scrapie prions they remained free of scrapie symptoms for at least 16 months while wild type controls all died within 6 months. propagation of infectivity in the prp null mice, if any, was less than 10(-5) that in wild type animals. surprisingly, heterozygous prn-p0/+ mice also ...	1994	8030944
the nature of the scrapie agent: the virus theory.		1994	8030946
dementias, neurodegeneration, and viral mechanisms of disease from the perspective of human transmissible encephalopathies.	our transmission experiments with human cjd emphasize the centrality of an exogenous infectious pathogen that can exist in symbiosis with its host for extended periods. many latent or persistent viruses can cause neurodegenerative disease and may have a role in late onset dementias. there are reasons to believe that cjd infections may share properties with some of these latent viruses in causing dementia, and several retroviral mechanisms may be operative in cjd. in order to clarify viral-like a ...	1994	8030947
the nature of the scrapie agent: the evolution of the virino.		1994	8030948
scrapie-associated prp accumulation and its inhibition: revisiting the amyloid-glycosaminoglycan connection.	an abnormal protease-resistant isoform of the protein prp accumulates in the brain of hosts with transmissible spongiform encephalopathies (tses) and appears to be centrally involved in tse pathogenesis. studies with scrapie-infected tissue culture cells have indicated that this abnormal prp is formed from an apparently normal precursor on the plasma membrane or along an endocytic pathway to the lysosomes. inhibitors of protease-resistant prp accumulation might serve as tools for studying the ba ...	1994	8030949
prp genotypes and the sip gene in cheviot sheep form the basis for scrapie strain typing in sheep.		1994	8030950
evidence that homologous ssdna is present in scrapie, creutzfeldt-jakob disease, and bovine spongiform encephalopathy.	homogenized brain tissue from scrapie-infected hamsters and uninfected hamsters was subjected to sub-cellular fractionation to isolate nemavirus. nucleic acid was extracted from these fractions, which also contained mitochondria. agarose-gel electrophoresis revealed a band corresponding to the size of circular hamster mtdna in both infected and uninfected samples, but slower migrating bands were observed only in samples from scrapie-infected brain. a single band of ssdna corresponding to about 1 ...	1994	8030952
infection-specific prion protein (prp) accumulates on neuronal plasmalemma in scrapie-infected mice.	prion protein (prp) is an abundant membrane-associated host protein which accumulates in abnormal, relatively protease-resistant forms in the brains of animals with scrapie and related diseases. using correlative light and electron microscopy we determined the sites of subcellular localization of prp in mice infected with the 87v strain of scrapie. disease-specific accumulation of prp was observed at light microscopy as amyloid plaques or as diffuse or granular staining within the neuropil, ofte ...	1994	8030953
replication of scrapie strains in vitro and their influence on neuronal functions.		1994	8030954
unsuspected early neuronal loss in scrapie-infected mice revealed by morphometric analysis.	this study was undertaken to determine to what extent neuronal loss is a feature of scrapie pathology, using an experimental model in which infectivity and subsequent vacuolar lesions are well characterized but in which neuronal loss has not been previously identified. intraocular infection with me7 scrapie directs infection through the major projections of the optic nerve, which include the dorsal lateral geniculate nucleus (dlgn) on the contralateral side to the infected eye. infectivity can b ...	1994	8030955
cerebral amyloidosis in natural scrapie of icelandic sheep is of rare occurrence.		1994	8030956
an electrophysiological study of scrapie-infected dorsal lateral geniculate neurons in vitro.		1994	8030959
interaction of scrapie agent and cells of the lymphoreticular system.	the current study focused on the role of lymphoid elements of the lymphoreticular system in scrapie pathogenesis. in the first experiment, adherent and non-adherent splenocytes from mice infected with the 139a scrapie strain were prepared. the level of infectivity on a per cell basis was significantly higher in the adherent cell population. in a second set of experiments, thymocytes, unfractionated splenocytes, t-cell enriched and t-cell depleted fractions of splenocytes were infected in vitro w ...	1994	8031232
scrapie amyloid (prion) protein has the conformational characteristics of an aggregated molten globule folding intermediate.	the scrapie amyloid (prion) protein (prp27-30) is a host-derived component of the infectious scrapie agent; the potential to replicate, propagate, and form amyloid is a result of the posttranslational event or conformational abnormality. in low concentrations of guanidine hydrochloride (gdn.hcl), prp27-30 dissociates into a compact equilibrium intermediate with a substantial portion of secondary structure, partially denatured tertiary structure, and tryptophan residues in an apolar environment [ ...	1994	8031772
prion protein is necessary for normal synaptic function.	the prion diseases are neurodegenerative conditions, transmissible by inoculation, and in some cases inherited as an autosomal dominant disorder. they include creutzfeldt-jakob disease in humans and scrapie and bovine spongiform encephalopathy in animals. the prion consists principally of a post-translationally modified form of a host-encoded glycoprotein (prpc), designated prpsc (ref. 1); the normal cellular function of prpc is, however, unknown. although prp is highly conserved among mammals a ...	1994	8035877
hyperplasia and hypertrophy of b cells in the islets of langerhans in hamsters infected with the 139h strain of scrapie.	previous studies showed that in hamsters the 139h, but not the 263k, scrapie strain caused a marked increase in pancreatic size and led to obesity, hypoglycaemia and striking hyperinsulinaemia. in the preceding paper (ye et al., 1994), the islets of langerhans in 139h-affected hamsters showed cellular atrophy, fibrosis, cytoplasmic vesicles and nuclear pathological changes. in the present study, the profiles of pancreatic islets were classified into three sizes with an image analyzer. the number ...	1994	8040383
an epidemiologist's view of bovine spongiform encephalopathy.	bovine spongiform encephalopathy was first recognized in great britain in 1986 and was the result of infection with a scrapie-like agent surviving in meat and bone meal used in feedstuffs. this effective exposure commenced in 1981-82 and was associated with a reduction in the use of hydrocarbon solvents in the manufacture of meat and bone meal. the epidemiological features are consistent with sheep scrapie as the original source, but the epidemic was amplified by the recycling of infected cattle ...	1994	8041802
bse awareness programme in tasmania.		1994	8059517
relationship of microglia and scrapie amyloid-immunoreactive plaques in kuru, creutzfeldt-jakob disease and gerstmann-sträussler syndrome.	kuru, creutzfeldt-jakob disease (cjd) and gerstmann-sträussler syndrome (gss) are transmissible dementias affecting humans characterized neuropathologically by intraneuronal vacuolation, spongiform change, astrocytic hypertrophy and hyperplasia and the variable presence of amyloid plaques. it has been suggested that microglia are amyloid-forming cells, which play an essential role in amyloid plaque formation. to study the relationship between microglia and amyloid plaques in kuru, cjd and gss, c ...	1994	8059606
correlation between the results of a histopathological examination and the detection of abnormal brain fibrils in the diagnosis of bovine spongiform encephalopathy.	a statistical comparison was made between the results of the statutory neurohistopathological method for the post mortem diagnosis of bovine spongiform encephalopathy (bse) and the detection of abnormal brain fibrils (saf). a total of 773 suspect cases was examined by both methods; it comprised 531 animals born before the feeding of ruminant-derived protein to ruminant species was prohibited and 242 born after the ban. the relative sensitivities and specificities of the methods were calculated f ...	1994	8073187
experimental infection of mink with bovine spongiform encephalopathy.	to determine whether the aetiological agent of bovine spongiform encephalopathy (bse) is pathogenic for mink, standard dark mink were inoculated with coded homogenates of bovine brain from the u.k. two homogenates were from cows affected with bse. the third was from a cow that came from a farm with no history of having had bse or having been fed ruminant-derived, rendered by-products, the proposed vehicle for introduction of the bse agent. each homogenate was inoculated intracerebrally into sepa ...	1994	8077914
mechanism of scrapie replication.		1994	8079159
the tails of two proteins: the scrapie prion protein and the ciliary neurotrophic factor receptor.	many proteins with a variety of functions have proven to have glycosylphosphatidylinositol (gpi)-linkages; two members of this family are the scrapie prion protein and the receptor for ciliary neurotrophic factor (cntf). the scrapie prion protein has two isoforms: prpc is found in brain cells from normal animals, while prpsc is an abnormal isoform that is only found in scrapie-infected animals. prpsc is the only identified component of the prion, an infectious agent that apparently does not cont ...	1994	8081242
biosynthesis of the prion proteins in scrapie-infected cells in culture.	prions are small proteinaceous particles that transmit scrapie and other fatal encephalopathies of humans and animals, and that appear to be devoid of nucleic acids. the only known--and perhaps the sole--component of the scrapie prion is an abnormal host-encoded protein, the scrapie prion protein prpsc. the biosynthesis of this pathological protein in the host cell, which is thus of paramount importance to prion replication, is still poorly understood. we are studying the biosynthesis and degrad ...	1994	8081243
spontaneous generation of infectious nucleating amyloids in the transmissible and nontransmissible cerebral amyloidoses.	the unconventional viruses of the transmissible subacute spongiform encephalopathies (kuru-cjd-gss-ffi-scrapie-bse) are nucleants spontaneously generated from host precursor proteins altered to beta-pleated sheet configuration that polymerize into insoluble infectious amyloid fibrils. the de novo conversion to infectious amyloids is facilitated or accelerated by many different point mutations causing amino acid changes, a stop codon, or octapeptide inserts that increase the likelihood of spontan ...	1994	8086124
induction of beta (a4)-amyloid in primates by injection of alzheimer's disease brain homogenate. comparison with transmission of spongiform encephalopathy.	amyloid plaques, associated with argyrophilic dystrophic neurites, and cerebral amyloid angiopathy (caa), but no neurofibrillary tangles, were found in the brains of three middle-aged marmoset monkeys that had been injected intracerebrally (ic) 6-7 yr earlier with brain tissue from a patient with early-onset alzheimer's disease. such changes were not found in the brains of three age-matched control marmosets. immunochemically the amyloid plaques and caa stained with antibody to beta (a4)-protein ...	1994	8086126
[viruses and cell therapy. evaluation of cell therapy from the virologic viewpoint].	the risks of cell therapy as seen by the microbiologist and virologist, are not calculable. numerous viruses with longterm persistence in the host cells, cannot be detected on the basis of an acute disease in the host. this applies, for example to herpesviruses, lentiviruses, retroviruses, hepatitis c virus, borna disease virus and the so-called unconventional viruses. there are two reasons why testing of the donor animal ist not possible, the first being the great number of potential pathogens, ...	1994	8088689
brain regional distribution of prion protein prp27-30 in mice stereotaxically microinjected with different strains of scrapie.	stereotaxic inoculation was used to examine the role of scrapie agent strain, inoculum, and injection site on the brain regional distribution of the prion protein, prp27-30. neither the type of inoculum nor the injection site influenced the distribution of prp27-30 in brains of mice. among the parameters examined, only the strain of agent affected the pattern of distribution and the yield of prp27-30. although mice injected into the cerebellum had the shortest incubation period, the cerebellum g ...	1993	8093365
prp polymorphisms associated with natural scrapie discovered by denaturing gradient gel electrophoresis.	scrapie is a transmissible degenerative disease of the central nervous system occurring naturally in sheep and goats. an abnormal protease-resistant form of the host-encoded prion protein (prp) accumulates in the brains of affected animals. as sip, a gene controlling the incubation period of experimental and natural scrapie, is linked to the single-copy sheep prp gene, we sought prp coding sequence polymorphisms in flocks from the romanov and ile-de-france breeds endemically affected with natura ...	1993	8094373
kinetics of expression of prion protein in uninfected and scrapie-infected n2a mouse neuroblastoma cells.	the scrapie prion protein, prpsc, is formed from its isoform, the cellular prpc. there is evidence available indicating that prpsc is a necessary component of the infectious prion particle to cause a series of transmissible spongiform encephalopathies. we have used immunocytochemistry and rna blotting techniques to investigate if infection with prions results in an increased prp gene expression. for the experiments we used n2a cells which had been infected with prions (scn2a cells). we demonstra ...	1993	8095862
transgenetic investigations of 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 ...	1993	8097053
somatic cell mapping of the bovine prion protein gene and restriction fragment length polymorphism studies in cattle and sheep.	brains affected by the progressive neurological disease bovine spongiform encephalopathy (bse) contain scrapie-associated fibrils and the protease-resistant isoform of prion protein. the gene encoding the normal host prion protein (prnp) has been mapped to human chromosome 20 and mouse chromosome 2 with the hamster cdna probe pea974. using this probe and a panel of bovine-rodent hybrid somatic cells, we have mapped prnp to bovine syntenic group u11 (100% concordancy). prnp restriction fragment l ...	1993	8098922
propagation of prions with artificial properties in transgenic mice expressing chimeric prp genes.	transgenic mice expressing chimeric prion protein (prp) genes derived from syrian hamster (sha) and mouse (mo) prp genes were constructed. one sha/moprp gene, designated mh2m prp, contains five amino acid substitutions encoded by shaprp, while another construct, designated mhm2 prp, has two substitutions. transgenic (tg) (mh2m prp) mice were susceptible to both syrian hamster and mouse prions, whereas three lines expressing mhm2 prp were resistant to syrian hamster prions. the brains of tg(mh2m ...	1993	8098995
swaledale sheep affected by natural scrapie differ significantly in prp genotype frequencies from healthy sheep and those selected for reduced incidence of scrapie.	prp glycoprotein gene polymorphisms were examined in swaledale sheep affected by natural scrapie, in healthy sheep and in swaledales selected for low susceptibility to scrapie. the three groups differed significantly in frequencies of prp genotypes detected by the restriction enzymes ecori, hindiii and bsphi, the latter being indicative of a prp protein amino acid difference at codon 136. these frequency differences were confirmed in a single-flock study and present good evidence that scrapie su ...	1993	8099602
ubiquitin immunocytochemistry in human spongiform encephalopathies.	the distribution of ubiquitin was studied by immunocytochemistry in eight cases of human spongiform encephalopathy and compared with the findings in seven age- and sex-matched cases of alzheimer's disease and six non-demented control cases. the results were also compared with the immunocytochemical distribution of prion protein and the lysosomal aspartic protease cathepsin d. in the human spongiform encephalopathies, ubiquitin immunoreactivity was found in a punctate distribution at the peripher ...	1993	8100355
mice devoid of prp are resistant to scrapie.	s.b. prusiner proposed that the infectious agent of scraple, the prion, is prpsc, a modified form of the normal host protein prpc. prn-p0/0 mice devoid of prpc showed normal development and behavior. when inoculated with mouse scrapie prions, they remained free of scrapie symptoms for at least 13 months while wild-type controls all died within 6 months. surprisingly, heterozygous prn-p0/+ mice also showed enhanced resistance to scrapie. after introduction of syrian hamster prp transgenes, prn-p0 ...	1993	8100741
three scrapie prion isolates exhibit different accumulation patterns of the prion protein scrapie isoform.	to investigate the molecular basis of prion diversity, we inoculated transgenic mice expressing the syrian hamster prion protein (prp) with three distinct prion isolates. we compared the three isolates designated sc237, 139h, and me7h in tg(shaprp)7 mice with clinical signs of scrapie because the incubation times with these mice are considerably shorter than the times found with hamsters. each prion isolate produced a distinctive pattern of the scrapie isoform of prp (prpsc) accumulation, as det ...	1993	8101989
immunolocalization of scrapie amyloid in non-congophilic, non-birefringent deposits in golden syrian hamsters with experimental transmissible mink encephalopathy.	transmissible mink encephalopathy (tme), a naturally occurring subacute spongiform encephalopathy in commercially ranch-reared mink (mustela vision), is characterized neuropathologically by spongiform changes in the neuropil, intracytoplasmic neuronal vacuolation and astrocytic hypertrophy and hyperplasia. amyloid deposits have not been observed in brain tissue sections from animals with natural and experimental tme using conventional histochemical stains such as congo red. to determine if amylo ...	1993	8103204
congo red inhibition of scrapie agent replication.	congo red inhibits the accumulation of protease-resistant prp in scrapie-infected mouse neuroblastoma cells. here we show that congo red also inhibits the replication of scrapie infectivity in these cells. this observation is consistent with the idea that protease-resistant prp is a vital component of the scrapie agent or that agent replication depends on the presence of protease-resistant prp in the cell.	1993	8103804
immunohistochemical detection of prion protein in sheep with scrapie.	prion protein (prp), which is involved in the pathogenesis of scrapie, occurs in 2 forms. the form extracted from scrapie brain is protease resistant (prp-res), whereas prp from normal brain is protease sensitive (prp-sen). this study examined whether prp-res could be detected in brains of sheep with scrapie by immunohistochemistry (ihc). a suitable ihc procedure was developed using brain tissue from hamsters that had been inoculated with the transmissible mink encephalopathy agent. tissue sampl ...	1993	8104039
french autochthonous scrapied sheep without the 136val prp polymorphism.		1993	8104061
conformational transitions, dissociation, and unfolding of scrapie amyloid (prion) protein.	the infectious form of the scrapie amyloid (prion) precursor, prpsc, is a host-derived protein and a component of the infectious agent causing scrapie. prpsc and the carboxyl-terminal proteinase k resistant core, prp27-30, have the potential to form amyloid as a result of a post-translational event or conformational abnormality. we have studied the conformational transitions of both proteins reconstituted into liposomes, associated in solid state in thin films, and dissociated by guanidine hcl. ...	1993	8104185
the scrapie enigma: insights from radiation experiments.	scrapie is the prototype of the spongiform encephalopathies (ses), now often referred to as "prion diseases." they are unique in being both familial and transmissible, even between species. proof of transmissibility led to the assumption that the agent was a slow virus, but standard virological techniques failed to determine its size. using radiation target theory, we found that, if the agent were nucleic acid, it is too small to code for even a single protein. concurrently we found that the age ...	1993	8104352
familial scrapie cases with shortened incubation periods.	two familial scrapie cases successively occurred in 29-month-old and 30-month-old corriedale dams and in three of their offspring as early as 10-19 months of age in a small flock. they showed ataxy but no pruritus. histopathological and immunochemical examinations of those sheep revealed vacuolation of nerve cells in brain tissue and presence of prpsc, a component of scrapie-associated fibrils, in brain, spleen and lymph node tissues. we discuss about shortened incubation periods and lacking pru ...	1993	8104506
synthetic peptides homologous to prion protein residues 106-147 form amyloid-like fibrils in vitro.	gerstmann-sträussler-scheinker disease (gss) is a prion-related encephalopathy pathologically characterized by massive deposition of prion protein (prp) amyloid in the central nervous system. the major component of amyloid fibrils isolated from patients of the indiana kindred of gss (gss-ik) is an 11-kda fragment of prp spanning residues 58 to approximately 150. these patients carry a missense mutation of the prnp gene, causing a phe-->ser substitution at codon 198. we investigated fibrillogenes ...	1993	8105481
london meeting explores the ins and outs of prions.		1993	8105534
genetic and infectious prion diseases.	enriching fractions from syrian hamster (sha) brain for scrapie prion infectivity led to the discovery of the prion protein (prp). prion diseases include scrapie of sheep and bovine spongiform encephalopathy of cattle as well as creutzfeldt-jakob disease (cjd) and gerstmann-sträussler-scheinker syndrome (gss) of humans. transgenic (tg) mice expressing both sha and mouse (mo) prp genes were used to probe the molecular basis of the species barrier and the mechanism of scrapie prion replication. bi ...	1993	8105771
intracerebral transmission of scrapie to cattle.	to determine if sheep scrapie agent(s) in the united states would induce a disease in cattle resembling bovine spongiform encephalopathy, 18 newborn calves were inoculated intracerebrally with a pooled suspension of brain from 9 sheep with scrapie. half of the calves were euthanatized 1 year after inoculation. all calves kept longer than 1 year became severely lethargic and demonstrated clinical signs of motor neuron dysfunction that were manifest as progressive stiffness, posterior paresis, gen ...	1994	8133096
overview of the transmissible spongiform encephalopathies: prion protein disorders.	the subacute transmissible spongiform encephalopathies (tse) are a complex group of neurodegenerative disorders which includes genetic, infectious and sporadic forms exemplified by scrapie in animals and creutzfeldt-jakob disease in humans. an extensive mass of data indicate that the infectious agents which transmit these diseases as well as the pathogenic mechanisms leading to clinical signs are related to abnormalities of a single cellular protein, designated the prion protein (prp). the goals ...	1993	8137126
scrapie pathogenesis.	there is no specific marker for scrapie infectivity, and therefore no means other than prolonged bioassay for estimating levels of infection in tissues. our knowledge of replication dynamics depends on precise rodent models which have enabled us to determine how the disease spreads and in which cells it replicates. we know, firstly, that infection replicates in the lymphoreticular system, and can identify a candidate cell; secondly, the factors which control the length of the disease process, an ...	1993	8137128
diversity in the neuropathology of scrapie-like diseases in animals.	the main diagnostic histology in the spongiform encephalopathies consists of a degenerative and usually symmetrical vacuolation of neurons and a spongiform lesion in the neuropil. sometimes there can be asymmetry. this pathology is usually confined to grey matter, but an additional white matter vacuolation is sometimes typical. the degeneration can progress to neuronal necrosis, with reactive glial changes. photoreceptor loss in the retina occurs in some experimental models. cerebral amyloidosis ...	1993	8137129
inactivation of se agents.	the transmissible agents of the spongiform encephalopathies are relatively resistant to inactivation, and accidental transmission has occurred in animals and man. rigorous chemical or physical procedures are required to achieve decontamination, and their effectiveness can only be determined by bioassay in animals. the best-defined model is scrapie in mice or hamsters, and this has been used in many of the studies to establish practical inactivation procedures. although a number of techniques had ...	1993	8137130
scrapie strain variation and mutation.	there are many strains of scrapie, distinguishable by their disease characteristics in genetically-defined mice. numerous distinct strains have been isolated in the same mouse strain, indicating that scrapie agents have an informational molecule, independent of the host. strain characteristics are stable on serial mouse passage under constant passaging conditions. however, changes in the species or mouse genotype used for passage may lead to changes in properties which are consistent with the se ...	1993	8137131
scrapie associated prp accumulation and its prevention: insights from cell culture.	transmissible spongiform encephalopathies (tses), alzheimer's disease and other amyloidoses result in the accumulation of abnormally stable, potentially amyloidogenic proteins that appear to play central roles in disease pathogenesis. scrapie-infected tissue culture cells have become well-developed models for studying how the tse-specific protein, protease-resistant prp, is made from its apparently normal precursor. the conversion of prp to the protease-resistant state occurs on the plasma membr ...	1993	8137133
epidemiology and control of bovine spongiform encephalopathy (bse).	bse is a new disease of cattle. the first clinical case occurred in april 1985 but the existence of a new disease was first confirmed microscopically in november 1986. epidemiological studies show that cattle suddenly became effectively exposed to a scrapie-like agent in ruminant-derived feed in the form of meat and bone meal in 1981/2. most cases have occurred in holstein friesian dairy cattle and have been exposed as calves. there is no evidence that cattle to cattle transmission sufficient to ...	1993	8137136
detection of apoptosis induced dna cleavage in scrapie-infected sheep brain.	the pathogenesis and molecular basis of nerve cell death which accompanies scrapie infections in sheep are not well understood. degeneration of neurons in culture caused by prion protein fragments has recently been reported to be consistent with mechanisms of cell death by apoptosis or programmed cell death. apoptosis activation during prion-related encephalopathies has not yet been established in vivo. we report here the detection of dna damage consistent with apoptosis in the brain cells of sh ...	1994	8138146
activation of cerebral cytokine gene expression and its correlation with onset of reactive astrocyte and acute-phase response gene expression in scrapie.	the pathogenesis of scrapie, a transmissible subacute spongiform encephalopathy, is unclear. however, certain aspects of the known cellular and molecular neuropathology in scrapie led us to hypothesize that cytokines could mediate cerebral pathological changes in this neurodegenerative disease. therefore, expression of multiple cytokine genes in the brain and peripheral organs of scrapie-infected mice was examined. late in the course of scrapie, expression of tumor necrosis factor alpha (tnf-alp ...	1994	8139024
endogenous viral complexes with long rna cosediment with the agent of creutzfeldt-jakob disease.	a class of viruslike agents that induces creutzfeldt-jakob disease (cjd) and scrapie remains undefined at the molecular level. several investigators believe this infectious agent is constituted by a single host protein or 'prion', and have emphasized data that would seem to exclude the presence of any viral nucleic acids. however, more rigorous evaluations in scrapie have shown reasonably abundant nucleic acids. additionally, in highly purified 120s cjd preparations that have been treated with n ...	1994	8152913
human prion diseases.	the prion diseases, sometimes referred to as the "transmissible spongiform encephalopathies," include kuru, creutzfeldt-jakob disease, and gerstmann-sträussler-scheinker disease of humans as well as scrapie and bovine spongiform encephalopathy of animals. for many years, the prion diseases were thought to be caused by viruses despite intriguing evidence to the contrary. the unique characteristic common to all of these disorders, whether sporadic, dominantly inherited, or acquired by infection, i ...	1994	8154865
risk factors and surveillance for bovine spongiform encephalopathy in the united states.		1994	8163424
scid mouse spleen does not support scrapie agent replication.	balb/c and severe combined immunodeficiency (scid) mice were inoculated intracerebrally or intraperitoneally with scrapie agent strain me7 to examine the role of functional lymphocytes and follicular dendritic cells in splenic infectivity and prpsc accumulation. intracerebrally inoculated balb/c and scid mice developed the clinical signs and microscopic lesions characteristic of scrapie. spleens from terminally affected balb/c mice contained prpsc which was detectable by immunoblot analysis; sci ...	1994	8207418
characterization of the microglial response in murine scrapie.	the nature of the glial and inflammatory cell responses to infection in scrapie-affected brains was studied in terminally-affected mice of five scrapie models. there were marked astrocytic and microglial responses. microglia showed increased staining of the surface antigens f4/80, leucocyte-common antigen, type 3 complement receptor, and elevated endocytotic and lysosomal activity. in all models, the astrocytic and microglial responses were largely restricted to anatomical regions of the brain s ...	1994	8208340
bovine spongiform encephalopathy in cattle mimics ultrastructurally experimental scrapie and creutzfeldt-jakob disease in rodents.	we report a comparison of the ultrastructural pathology of bovine spongiform encephalopathy, experimental scrapie in hamsters and a panencephalopathic model of creuzfeldt-jakob disease (cjd) in mice. vacuoles in dendrites, intramyelinic vacuoles (myelin ballooning), dystrophic axons, phagocytic astrocytes and macrophages, differing in extent, were found in all three models. we conclude, that this axonal and myelin pathology is a phenomenon common to the three models of ssve studied, and the diff ...	1993	8208436
[scrapie from the clinical aspect].	the first cases of scrapie in the federal republic of germany since 1945 occurred in 1990 and 1991. the disease was found in three flocks of suffolk sheep and it was probably brought to germany by breeding sheep from france. scrapie is a transmissible degenerative disease of the central nervous system with a slowly progressing but always fatal course. the scrapie agent is highly resistant against environmental influences as well as against disinfectants. incubation period and clinical signs of s ...	1994	8209358
the biology and molecular biology of scrapie-like diseases.	the transmissible spongiform encephalopathies (tse's) are degenerative diseases of the central nervous system which naturally affect man (creutzfeldt-jakob disease [cjd], gerstmann-sträussler syndrome [gss], kuru), sheep and goats (scrapie), cattle (bovine spongiform encephalopathy [bse]), mink (transmissible mink encephalopathy), mule deer, elk and antelope (chronic wasting disease). spongiform encephalopathies have also been diagnosed in captive species of zoo antelope and in domestic cats. mu ...	1993	8219804
analysis of nucleic acids in purified scrapie prion preparations.	amount, type, and size of nucleic acid molecules associated with purified prion preparations were analyzed. return refocusing gel electrophoresis (rrge) was developed to detect homogeneous and heterogeneous nucleic acids extracted from highly purified scrapie prion preparations. with this method all types of nucleic acids in the size range from 13 to several thousand nucleotides could be analyzed. the recovery of all nucleic acids, after deproteinization and two-phase extraction was higher than ...	1993	8219805
bovine spongiform encephalopathy: a new disease of cattle?	bovine spongiform encephalopathy (bse) was first recognized in great britain in 1985. most believe that the disease is of recent origin initiated by feeding rendered animal protein from scrapie-infected sheep to cattle, then perpetuated by feeding rendered infected cattle to other cattle. this paper explores an alternative hypothesis that bse existed in cattle populations in an unrecognized form for a much longer time until amplified by changes in the rendering process that allowed cattle to cat ...	1993	8219807
human prion diseases (spongiform encephalopathies).	prion diseases (spongiform encephalopathies) in humans are creutzfeldt-jakob disease (cjd), gerstmann-sträussler-scheinker syndrome (gss), and kuru. clinically, they are characterized by an inexorably progressing neurological illness with dementia and ataxia as the most prominent signs. the classical neuropathological changes are limited to the central nervous system and consist of spongiform degeneration, amyloid plaques, astrocytic gliosis, and nerve cell loss. the human spongiform encephalopa ...	1993	8219808
the dangers of disease transmission by artificial insemination and embryo transfer.	this review summarizes the major infectious diseases of the three major agricultural species (cattle, sheep and pigs) and horses, and presents the evidence for and against the possibility of infectious agents being transmitted between animals via the venereal route or by the use of semen or early embryos in commercial artificial insemination (ai) or embryo transfer (et). cattle feature most prominently in the widespread distribution of frozen semen, and national and international organizations h ...	1993	8221041
scrapie prions alter receptor-mediated calcium responses in cultured cells.	the molecular basis of neurologic dysfunction in prion diseases is unknown. spongiform degeneration of neurons is the most characteristic neuropathologic change which raises the possibility of abnormal ion channel function. here we examined the regulation of ca2+ fluxes in two cell lines chronically infected with scrapie prions, designated scn2a (scrapie-infected mouse neuroblatoma) and schab (scrapie-infected hamster brain) cells. in uninfected hab cells, bradykinin caused increases in intracel ...	1993	8232952
scrapie associated fibril detection on decomposed and fixed ovine brain material.	samples of cerebral cortex from eight scrapie affected sheep and two unaffected control sheep were stored for up to nine days at temperatures ranging from 18 degrees c to 29 degrees c. scrapie associated fibrils (saf) could be detected in proteinase k treated brain extracts from all the eight scrapie affected animals after five days storage and in six out of the eight after nine days storage. saf could not be detected in any brain extracts from the two control animals. formol saline fixed brain ...	1993	8235083
transmission of bovine spongiform encephalopathy to sheep and goats.	spongiform encephalopathy has been confirmed in both 'positive' and 'negative' lines of cheviot sheep (selected for their differential response on experimental exposure to scrapie) after intracerebral injection or oral dosing with brain homogenate derived from cattle with bovine spongiform encephalopathy (bse). with either challenge the incubation period of the disease ranged from 440 to 994 days in both lines of sheep. in a similar experiment, three anglo-nubian goats developed the disease 506 ...	1993	8236676
prevalence and incidence of scrapie in the netherlands: a questionnaire survey.	two independent nationwide surveys of randomly selected sheep farmers were conducted: in one a questionnaire was mailed to farmers and in the other the farmers were interviewed. the questionnaire was designed to obtain data on the occurrence of scrapie in the national sheep flock of the netherlands. farmers owning 30 or more ewes were selected from a database at the ministry of agriculture, nature management and fisheries, resulting in 10,000 addresses. two lists of names were compiled at random ...	1993	8236724
scrapie control in the united states.		1993	8236771
analysis of host genetic control of scrapie-induced obesity.	the potential for induction of obesity during the preclinical phase of scrapie disease in mice was previously shown to be a function of both the strain of scrapie and the strain of inbred mouse. in the present study, host control of obesity induction by a scrapie strain was examined to determine if the effect were dependent on a single gene or multiple genes. the approach used was assessment of the pattern of weight induction in f1 and f2 crosses of parental inbred mouse strains that did or did ...	1993	8240003
analysis of bse risk factors in argentina.		1993	8270098
scrapie control in the united states: a review of the past with an emphasis on the present flock certification program.		1993	8270099
epidemiologic and experimental studies on transmissible mink encephalopathy.	transmissible mink encephalopathy (tme) is a rare foodborne disease of ranch-raised mink produced by an as yet unidentified contaminated feed ingredient. because of the clinicopathologic similarities to scrapie and the indistinguishable physicochemical properties of their transmissible agents, it was initially assumed that tme was caused by feeding mink scrapie-infected sheep. however, subsequent studies testing the oral susceptibility of mink to scrapie were unsuccessful. epidemiologic investig ...	1993	8270100
foreign prp expression and scrapie infection in tissue culture cell lines.	prp expression and scrapie infectivity was studied in a group of tissue culture cell lines from mice, hamsters, rats and humans. cell surface prp protein was detected in seven of ten cell lines from a variety of tissues and showed both cell surface and cytoplasmic perinuclear distributions. mouse n2a neuroblastoma cells could be persistently infected with scrapie in vitro, but obl-21 mouse neuroma cells were never successfully infected. foreign prp molecules including hamster prp, mutant hamster ...	1993	8270103