Publications

total ck and ck-bb activity in serum from sheep with scrapie.	total ck and iso-enzyme ck-bb activity was measured in serum from four sheep with scrapie and in serum from four healthy control sheep. blood samples were taken weekly for about six months. there was a clear overlap between the total ck and ck-bb activity in serum from sheep with scrapie and that in serum from control sheep. thus measurement of these enzymes does not aid the clinical diagnosis of scrapie.	1992	1485407
diverse biological parameters in clinically healthy sheep from a flock with scrapie: variations, and correlations with ola antigens.	a comparison was made in the blood levels of various cell types and biochemical substances and in lymphocyte antigens between 107 healthy sheep from a flock contaminated with scrapie (hc sheep) and 93 sheep from a noncontaminated flock (nc sheep), which served as a control population. significant differences between the two groups of sheep were found in some of the levels, as had previously been found with lymphocyte antigens. the hc sheep, which included genetically resistant animals, could be ...	1992	1489554
natural scrapie in goats: neuropathology.	the brains of the 20 goats affected with natural scrapie received at the central veterinary-laboratory, weybridge, since 1975 were examined microscopically. lesions of a spongiform encephalopathy were found in the brainstem, cerebellum, diencephalon, corpus striatum, and also in the neopallium or cerebral cortex. the lesions in the neopallium have not previously been reported in natural scrapie in goats. deposits of amyloid were present in the thalamus in three of the 20 goats.	1992	1523800
natural scrapie in goats: case histories and clinical signs.	the case histories of the 20 goats affected with natural scrapie which have been examined since 1975 at the central veterinary laboratory, weybridge, are reviewed. their ages ranged from two to seven years (median three years, four months) and 85 per cent of them were between two and four years old. the most common clinical signs were hyperaesthesia, ataxia and pruritus. the histories indicated that scrapie can occur in goats which have not been in contact with sheep.	1992	1529502
from slow virus to prion: a review of transmissible spongiform encephalopathies.	spongiform encephalopathies include seven neurodegenerative diseases: three in man (creutzfeldt-jakob disease, gerstmann-sträussler-scheinker disease and kuru) and four in animals (scrapie, mink encephalopathy, bovine spongiform encephalopathy and chronic wasting disease in deer and elks). they are all transmissible to a variety of species, and man-to-man propagation of the diseases in the form of iatrogenic transmission has been well-documented. the infectious agent is highly unusual and the pa ...	1992	1531331
transmissible mink encephalopathy.	transmissible mink encephalopathy (tme) is a rare disease of ranch-raised mink caused by exposure to an as yet unidentified contaminated food ingredient in the ration. the clinical and pathological similarities between tme and scrapie, together with the indistinguishable physicochemical characteristics of their transmissible agents, suggest that sheep may be the source of infection. however, experimental testing of oral susceptibility of mink to several different sources of sheep scrapie have be ...	1992	1535524
the natural occurrence of scrapie in moufflon.	six cases of scrapie were confirmed in two separately maintained flocks of moufflon, in both of which the disease appeared to be endemic. the clinical signs and histopathology were indistinguishable from those observed in scrapie-affected domesticated sheep. the pathology included lesions in the cerebral cortex which, although commonly present in scrapie-affected sheep, have not previously been described in the natural disease.	1992	1542978
analysis of cerebrospinal fluid from field cases of some common ovine neurological diseases.	analysis of cerebrospinal fluid (csf) samples from normal sheep and from cases of some common neurological diseases revealed a significant increase (p less than 0.05) in the group mean csf protein concentration for meningitis, listeriosis and spinal abscess but not for scrapie, spinal injury, ovine pregnancy toxaemia or polioencephalomalacia. the csf white blood cell count (wbc) was significantly increased (p less than 0.05) in the meningitis group and in those cases of listeriosis which failed ...	1992	1551009
clinical observations on four cases of scrapie in goats.		1992	1557871
bovine spongiform encephalopathy: epidemiological features 1985 to 1990.	following the identification of bovine spongiform encephalopathy (bse) in the british cattle population in 1986 epidemiological studies were launched. this paper provides an updated account of the epidemiological features of bse from 1985, when the first cases, based on clinical histories, occurred, until 1990. the number of cases up to december 1989 represents an annual incidence of 3.9 confirmed cases per 1000 adult animals in great britain. many more dairy herds were affected than beef suckle ...	1992	1557877
neuronal autophagic vacuoles in experimental scrapie and creutzfeldt-jakob disease.	we report the presence of autophagic vacuoles (av) in neuronal perikarya and neuronal processes of rodents with experimental scrapie and creutzfeldt-jakob disease. av were composed of sequestrated cytoplasmic areas containing ribosomes and occasionally mitochondria and small secondary vacuoles. the formation of av may contribute to neuronal degeneration and ultimately to neuronal loss.	1992	1557945
bovine spongiform encephalopathy in northern ireland: epidemiological observations 1988-1990.	this study describes the epidemiological features of bovine spongiform encephalopathy (bse) in northern ireland where the first case occurred in november 1988. they were very similar to those observed in great britain except that the annual incidence of bse in 1990 in northern ireland, 2.3 confirmed cases per 10,000 adult cows, was approximately one 10th of that in great britain. the findings were also consistent with the current hypothesis that affected cattle had been exposed to a scrapie-like ...	1992	1561742
purification of non-infectious ganglioside preparations from scrapie-infected brain tissue.	the extraction and purification of gangliosides from brains of animals infected with the scrapie agent was evaluated by scaling-down a large-scale procedure currently used with bovine brains. inactivation experiments employed hamster brains infected with the 263 k strain of scrapie. residual infectivity was determined at different points of the procedure and in the final preparation by an in vivo animal bioassay. the efficacy of single steps, which included chemicals or physical techniques known ...	1992	1571012
[annotation to the mitochondrial genome].	after a brief explanation of the mitochondrial function, especially in the relation to the inner-cell coordination, the study analyzed the mitochondrial hypertroph-dilatative cardiomyopathy, myopathy and scrapie which were recently tied to the "d-loop fragment" of the mtdna. any primary connection between viral unconventional slow infections and the mitochondrial genome seems unlikely. it is argued in the study that this category of diseases can be much better explained through the transfer of t ...	1992	1584979
recommendations for minimizing the risk of infection by agents causing zoonoses and other animal infections in manufacture of medicinal products. the federal minister for health.		1992	1586388
scrapie-like encephalopathy in a greater kudu (tragelaphus strepsiceros) which had not been fed ruminant-derived protein.	a 19-month-old greater kudu (tragelaphus strepsiceros), whose dam had died 15 months earlier with spongiform encephalopathy, required euthanasia after developing severe ataxia and depression with an apparently sudden onset. no macroscopic abnormalities were detected on post mortem examination but a scrapie-like spongiform encephalomyelopathy was apparent on histopathological examination of brain and segments of spinal cord. negative stain electron microscopy of proteinase k-treated detergent ext ...	1992	1604783
scrapie: a clinical assessment.		1992	1604786
[spongiform encephalopathies with special reference to bovine spongiform encephalopathy].	in switzerland bovine spongiform encephalopathy (bse) was detected for the first time in november 1990. it is a transmissible disease of the central nervous system similar to creutzfeldt-jakob disease (cjd), gerstmann-sträussler-scheinker syndrome (gss) and kuru in man, and, in animals, scrapie in sheep and goats, chronic wasting disease (cwd) in captive mule deer and elk of north america and transmissible mink encephalopathy (tme) of farm reared mink. the infectious agent of the spongiform ence ...	1992	1615298
bovine spongiform encephalopathy.	a detailed account is given of the occurrence of bovine spongiform encephalopathy (bse), current research into the aetiology of this new disease of cattle, and the relationship between bse, scrapie and other similar diseases. epidemiology, clinical signs, pathology, diagnosis, prevention and control are described.	1992	1617201
scrapie.	a detailed review is presented of the history, geographical distribution, cause, epidemiology, clinical features, pathogenesis, pathology, diagnosis, prevention, control and economic effects of scrapie in sheep. brief mention is made of the disease in goats and moufflon. the nature of the agent causing scrapie, the genetic control of the incubation period in sheep and the natural transmission of scrapie in sheep and goats are discussed. national efforts to control scrapie in various countries ar ...	1992	1617202
sub-acute, transmissible spongiform encephalopathies: current concepts and future needs.	the first diagnosis of bovine spongiform encephalopathy (bse) in the united kingdom in 1986 was to stimulate the most intensive epidemiological study of any animal disease of all time in that country. it led also to the initiation of a broad-based research programme with an international flavour. this principally involved scientists and veterinarians in europe (especially the united kingdom) and the united states of america, especially those with experience of slow infections in general and expe ...	1992	1617204
bovine spongiform encephalopathy: case-control studies of calf feeding practices and meat and bonemeal inclusion in proprietary concentrates.	following the identification of meat and bonemeal as the most likely source of exposure for the occurrence of bovine spongiform encephalopathy (bse) in great britain case-control studies were initiated to investigate this hypothesis. these involved a comparison of the consumption of specific proprietary calf feedstuffs, and whether or not meat and bonemeal had been included, between animals born in 1983-84 in bse-unaffected herds and confirmed cases of bse also born in 1983-84. the feeding of pr ...	1992	1620965
bovine spongiform encephalopathy: detection of fibrils in the central nervous system is not affected by autolysis.	the effect of autolysis on the electron microscopic detection of the characteristic abnormal fibrils, originally called 'scrapie-associated fibrils', was investigated in four different areas of the central nervous system (cns) from 10 clinically suspect bse cattle after post mortem delay and compared with the histopathological diagnosis. the tissues for fibril detection were subjected to controlled incubations to simulate autolysis. fibril detection in all areas sampled from nine animals in whic ...	1992	1620966
replication of distinct scrapie prion isolates is region specific in brains of transgenic mice and hamsters.	scrapie prions are composed largely, if not entirely, of prpsc molecules. the prion isolates sc237 and 139h exhibit markedly different incubation times in syrian, armenian, and chinese hamsters, as well as in transgenic (tg) 81 mice expressing syrian hamster prp (shaprp). repassage of prions from transgenic mice or chinese hamsters into syrian hamsters revealed that the original properties of the prion isolates are retained. when syrian hamsters were first inoculated with 139h prions and subsequ ...	1992	1628828
scrapie in the central nervous system: neuroanatomical spread of infection and sinc control of pathogenesis.	following bilateral intraocular (i.o.) infection of sinc s7 mice with me7 scrapie, sequential tissue pools were taken from retina, optic nerve, superior colliculus (sc), dorsal lateral geniculate nucleus (dlgn), visual cortex and cerebellum. the infectivity levels in these pools were estimated by intracerebral (i.c.) assay in c57bl/fabtdk mice. infectivity was first detected in retina at 35 days post-injection (as an increase above residual injected inoculum), sc at 56 days, dlgn at 77 days and ...	1992	1629695
comparative ultrastructural neuropathology of naturally occurring bovine spongiform encephalopathy and experimentally induced scrapie and creutzfeldt-jakob disease.	we report the ultrastructural neuropathology of bovine spongiform encephalopathy (bse), a recently described slow virus disease first recognized in friesian/holstein cattle, and compare it to that of experimental scrapie and creutzfeldt-jakob disease. the spongiform change, which was most pronounced in the central grey matter of the midbrain, consisted of membrane-bound vacuoles within neuronal processes, containing curled membrane fragments, secondary chambers and vesicles. axons and dendrites ...	1992	1644932
ultrastructural pathology of axons and myelin in experimental scrapie in hamsters and bovine spongiform encephalopathy in cattle and a comparison with the panencephalopathic type of creutzfeldt-jakob disease.	we report the ultrastructural pathology of axons and myelin sheaths in bovine spongiform encephalopathy (bse) and experimental scrapie in hamsters and compare it with that found in a panencephalopathic model of creutzfeldt-jakob disease (cjd). intramyelinic vacuoles (myelin ballooning), dystrophic axons, phagocytic astrocytes and macrophages were found in all three models but to different degrees, while axons containing numerous cellular processes and concentric cisterns were observed only in ex ...	1992	1644933
transmission of bovine spongiform encephalopathy and scrapie to mice.	transmission from four cases of bovine spongiform encephalopathy (bse) to mice resulted in neurological disease in 100% of recipient animals, after incubation periods of between 265 and 700 days post-injection. the results from the four cases were very similar to one another. there were major differences in the incubation period between the four inbred strains of mice tested, and even between strains of the same sinc genotype, and the incubation periods of sinc heterozygote mice were much longer ...	1992	1645134
in vivo detection of metabolic changes in a mouse model of scrapie using nuclear magnetic resonance spectroscopy.	in vivo proton nuclear magnetic resonance (nmr) spectroscopy studies of scrapie in a mouse model have shown the appearance of an abnormal peak in the brain early in the incubation period. this abnormal peak was detected weeks before the detection of a protease-resistant form of a membrane protein and vacuolar histopathology in vitro, and several months before clinical signs, and the signal increased in intensity as the disease progressed. in the chronic stage of the disease, a reduction in n-ace ...	1991	1655955
clostridium difficile infection in adult hamsters.	diarrhea was encountered in a group of adult female golden syrian hamsters (mesocricetus auratus) used for titrating the scrapie agent. ninety percent of the cases occurred in animals over 210 days old even though animals of all age groups lived in the colony concurrently. the cause of diarrhea was investigated in both uninoculated animals and those receiving greater than a limiting dilution of scrapie infectivity, i.e., animals that were not expected to contract the experimental scrapie disease ...	1991	1667195
the role of protein ubiquitination in neurodegenerative disease.	ubiquitin immunocytochemistry with an antiserum which reacts with ubiquitin-protein conjugates demonstrates the presence of ubiquitinated proteins in filamentous inclusions found in neurones in the major human neurodegenerative diseases, i.e. alzheimer's disease, diffuse lewy body disease, motor neurone disease. ubiquitin immunohistochemistry has revolutionized the neuropathological diagnosis of dementia showing that diffuse lewy body disease is not, as previously supposed, a rare cause of demen ...	1991	1668896
molecular biology and pathology of scrapie and the prion diseases of humans.	scrapie and bovine spongiform encephalopathy of animals and creutzfeldt-jakob and gerstmann-sträussler-scheinker diseases of humans are transmissible and genetic neurodegenerative diseases caused by prions. infectious prion particles are composed largely, if not entirely, of an abnormal isoform of the prion protein which is encoded by a chromosomal gene. an as yet unidentified post-translational process converts the cellular prion protein into an abnormal isoform. scrapie neuropathology, incubat ...	1991	1669719
prion biology and diseases.		1991	1670551
bovine spongiform encephalopathy and man.		1991	1670807
survival of scrapie virus after 3 years' interment.	supernatant fluid from a scrapie-infected hamster brain homogenate was mixed with soil, packed into perforated petri dishes that were then embedded within soil-containing pots, and buried in a garden for 3 years. between 2 and 3 log units of the input infectivity of nearly 5 log units survived this exposure, with little leaching of virus into deeper soil layers. these results have implications for environmental contamination by scrapie and by similar agents, including those of bovine spongiform ...	1991	1671114
scrapie-associated prion protein accumulates in astrocytes during scrapie infection.	in the course of scrapie, a transmissible spongiform encephalopathy caused by an unconventional agent, a normal cellular protein is converted to an abnormal form that copurifies with infectivity and aggregates to form deposits of amyloid. we have used immunocytochemistry and methods that enhance detection of amyloidogenic proteins to investigate the types of cells in the central nervous system which are involved in the formation of the abnormal scrapie-associated protein. we show that this prote ...	1991	1671170
different forms of the bovine prp gene have five or six copies of a short, g-c-rich element within the protein-coding exon.	current models of the virus-like agents of scrapie and bovine spongiform encephalopathy (bse) have to take into account that structural changes in a host-encoded protein (prp protein) exhibit an effect on the time course of these diseases and the survival time of any man or animal exposed to these pathogens. we report here the sequence of different forms of the bovine prp gene which contain either five or six copies of a short, g-c-rich element which encodes the octapeptide pro-his-gly-gly-gly-t ...	1991	1671225
new mutation in scrapie amyloid precursor gene (at codon 178) in finnish creutzfeldt-jakob kindred.		1991	1671440
differences in the membrane interaction of scrapie amyloid precursor proteins in normal and scrapie- or creutzfeldt-jakob disease-infected brains.	the membrane interaction and hydrophobicity of the normal (prpc) and infectious isoform (prpsc/cjd) of scrapie and creutzfeldt-jakob disease amyloid precursor proteins was studied. the normal isoform of hamster and human scrapie amyloid precursor protein was found on the microsomal/synaptosomal membranes anchored solely by the c-terminal glycolipid. glycolipid cleavage resulted in dissociation from the membranes and change of behavior from a highly hydrophobic to a hydrophilic protein, susceptib ...	1991	1671680
amyloid protein of gerstmann-sträussler-scheinker disease (indiana kindred) is an 11 kd fragment of prion protein with an n-terminal glycine at codon 58.	gerstmann-sträussler-scheinker (gss) disease is a familial neurological disorder pathologically characterized by amyloid deposition in the cerebrum and cerebellum. the gss amyloid is immunoreactive to antisera raised against the hamster prion protein (prp) 27-30. this is a proteinase k-resistant glycoprotein of 27-30 kd that is derived from an abnormal isoform of a neuronal glycoprotein of 33-35 kd designated prpsc and is a molecular marker of amyloid fibrils isolated from animals with scrapie a ...	1991	1672107
the disease characteristics of different strains of scrapie in sinc congenic mouse lines: implications for the nature of the agent and host control of pathogenesis.	mouse lines which are congenic for sinc, the major gene controlling scrapie incubation period, have been produced by selective breeding from the inbred c57bl(sincs7) and vm(sincp7) strains; the s7 allele of sinc has been introduced into a vm background by 18 serial backcrosses, at each generation selecting on the basis of the incubation period with the me7 scrapie strain. the characteristics of the disease produced by seven scrapie strains have been compared in sincs7 and sincp7 congenic mice an ...	1991	1672371
clinical and molecular genetic study of a large german kindred with gerstmann-sträussler-scheinker syndrome.	we have verified, by full open reading frame sequencing, the presence of an amino-acid-altering mutation in codon 102 of the scrapie amyloid protein gene in three affected members of a large and well-documented german family with experimentally transmitted gerstmann-sträussler-scheinker syndrome. in addition, we identified the mutation by partial sequencing or dna restriction enzyme analysis in three of 12 presently healthy family members with an affected parent, and none of 12 members without a ...	1991	1672447
pre-clinical and clinical diagnosis of scrapie by detection of prp protein in tissues of sheep.	the usefulness of detecting the scrapie-associated fibrillar protein (prp) in the lymphoreticular organs of sheep as a diagnostic tool was investigated. the prp was detected by means of a rabbit-anti-sheep prp polyclonal antibody by western blot analysis. prp was detected in samples from the central nervous system (cns) of five of six sheep showing clinical signs of natural scrapie infection, in spleen samples from four of the six sheep and in lymph node samples taken from three of the sheep. pr ...	1991	1674826
evidence of ssdna in tubulofilamentous particles: their relationship to scrapie-associated fibrils.	abnormal tubulofilamentous particles were identified by electron microscopy using a simple touch negative staining technique from brains of mice infected with four strains of the scrapie agent. treatment by three proteolytic enzymes and subsequent treatment with dnase and mung bean nuclease of grids prepared from the infected animals confirmed previous observations that the tubulofilamentous particles observed in scrapie-effected brains are complex structures. the core of the tubulofilamentous p ...	1991	1674941
morphological and biochemical evidence that scrapie-associated fibrils are derived from aggregated amyloid-like filaments.	the membrane fraction from scrapie infected mouse brains was dissolved in saturated urea, centrifuged on a 10 to 50% glycerol gradient at 35,000 rpm for 24 h, and fractionated from the bottom of the tube into 11 fractions. prp was detected throughout the gradient. however, the relative prp concentrations of fractions 4 and 8 were the highest. the relative prp concentration versus protein concentration of fractions 1 to 4 was higher than that of the other fractions. scrapie infectivity also was d ...	1991	1675031
alterations in neurotransmitter-related enzyme activity in scrapie-infected pc12 cells.	enzyme activities associated with the neurotransmitter pathways in nerve growth factor-treated, 139a scrapie strain-infected pc12 cells were examined. since these cells show no morphological alterations during the time of agent replication, any scrapie-induced effects would have to be associated with non-vital cellular functions. when compared to controls, infection with the 139a scrapie strain resulted in decreased activity of the cholinergic pathway-related enzymes, choline acetyltransferase a ...	1991	1675247
restriction fragment length polymorphisms of the scrapie-associated fibril protein (prp) gene and their association with susceptibility to natural scrapie in british sheep.	we have investigated the correlation between restriction fragment length polymorphisms of the scrapie-associated fibril protein (prp) gene and the incidence of natural scrapie in british sheep during the period from july 1988 to november 1990. sixty percent of the scrapie-positive animals studied were homozygous for a 6.8 kb ecori fragment (e1) and a further 26% carried e1 as heterozygotes. this fragment is linked to susceptibility to experimental scrapie in a closed flock of cheviot sheep. twel ...	1991	1675248
molecular biology of prion diseases.	prions cause transmissible and genetic neurodegenerative diseases, including scrapie and bovine spongiform encephalopathy of animals and creutzfeldt-jakob and gerstmann-sträussler-scheinker diseases of humans. infectious prion particles are composed largely, if not entirely, of an abnormal isoform of the prion protein, which is encoded by a chromosomal gene. a posttranslational process, as yet unidentified, converts the cellular prion protein into an abnormal isoform. scrapie incubation times, n ...	1991	1675487
virus-induced amyloidosis in scrapie involves a change in covalent linkages in the preamyloid.	preparations of the preamyloid and the amyloid protein from normal and scrapie hamster brains show different solubilization behaviours towards triton x-114 extraction. the normal isoform is completely extractable from microsomal membranes by the detergent, whereas the pathological one is not. both forms can be isolated using preparative sds electrophoresis as the final step in order to remove all non-covalently associated materials. after removal of the sds these purified proteins retain their s ...	1991	1675561
scrapie-infected spleens: analysis of infectivity, scrapie-associated fibrils, and protease-resistant proteins.	scrapie-associated fibrils (saf) and protease-resistant proteins (prp) were isolated from spleens and brains of clinical animals (mice and hamsters) from three scrapie agent-host strain combinations, and their concentrations were compared with infectivity levels. the spleens of infected animals contained lower levels of infectivity, prp, and saf than did brains. regardless of the route of infection, both saf and infectivity were detected in spleen before brain. infectivity increased in brains an ...	1991	1676044
paradoxical shortening of scrapie incubation times by expression of prion protein transgenes derived from long incubation period mice.	prolonged incubation times for experimental scrapie in i/lnj mice are dictated by a dominant gene linked to the prion protein gene (prn-p). transgenic mice were analyzed to discriminate between an effect of the i/lnj prn-pb allele and a distinct incubation time locus designated prn-i. paradoxically, 4 independent prn-pb transgenic mouse lines had scrapie incubation times shorter than nontransgenic controls, instead of the anticipated prolonged incubation periods. aberrant or overexpression of th ...	1991	1676894
human and experimental spongiform encephalopathies: recent progress in pathogenesis.	the spongiform encephalopathies belong to the group of "slow virus infections" of the nervous system, characterized by a long incubation period, a protracted course and involvement of the nervous system with a lethal outcome. in contrast to the conventional virus infections, such as visna in sheep and progressive multifocal leukoencephalopathy (pml) in humans, the etiological agent for the spongiform encephalopathies has not been clearly defined. the known forms in animals are scrapie in sheep a ...	1991	1676992
homozygous prion protein genotype predisposes to sporadic creutzfeldt-jakob disease.	the human prion diseases, creutzfeldt-jakob disease (cjd) and gerstmann-sträussler syndrome (gss), are neurodegenerative diseases that are unique in being both infectious and genetic. transmission of both diseases and the animal spongiform encephalopathies (for example, scrapie and bovine spongiform encephalopathy) to experimental animals by intracerebral inoculation with brain homogenates is well documented. despite their experimental transmissibility, missense and insertional mutations in the ...	1991	1677164
secondary structure analysis of the scrapie-associated protein prp 27-30 in water by infrared spectroscopy.	a protease-resistant form of the protein prp (prp-res) accumulates in tissues of mammals infected with scrapie, creutzfeldt-jakob disease, and related transmissible neurodegenerative diseases. this abnormal form of prp can aggregate into insoluble amyloid-like fibrils and plaques and has been identified as the major component of brain fractions enriched for scrapie infectivity. using a recently developed technique in fourier transform infrared spectroscopy which allows protein conformational ana ...	1991	1678278
partial dominance of the sa allele of the sip gene for controlling experimental scrapie.		1991	1679574
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
immunohistochemical localization of prion protein in spongiform encephalopathies and normal brain tissue.	we used polyclonal antibodies raised against hamster and mouse prp27-30 as immunologic probes to study the localization of intracellular and extracellular deposits of prion protein in normal and scrapie-infected mouse and hamster brains and in creutzfeldt-jakob disease (cjd)-infected mouse brains. in addition, we examined normal human brain and brain tissues from patients with cjd, kuru, alzheimer's disease, and idiopathic chronic encephalitis. there was positive staining in the cytoplasm of neu ...	1990	1690364
pronase does not reduce the protein content of hirt supernatant of normal mouse brain.	normal mouse brain has been used as a model in experiments to explain the reduction of infectivity obtained following incubation with pronase of brain infected with the scrapie infective agent. incubation of hirt supernatants of normal mouse brain with pronase had no effect on the protein content when compared to controls similarly incubated without pronase. this points to a resistance of the proteins in the brain extract to protease or to the presence of anti-protease activity. much of the 'rna ...	1990	1693052
a simple and effective method for inactivating virus infectivity in formalin-fixed tissue samples from patients with creutzfeldt-jakob disease.	we fixed brains from hamsters infected with scrapie virus in (1) formalin, (2) phenol-saturated formalin, (3) formalin with a 1-hour immersion in formic acid, or (4) phenol-saturated formalin with a 1-hour immersion in formic acid. in addition, we used the formalin-formic acid procedure on brains from mice infected with the virus of creutzfeldt-jakob disease. formic acid proved superior to phenol in respect to both disinfection and tissue preservation, almost completely eliminating virus infecti ...	1990	1693181
scrapie prion proteins accumulate in the cytoplasm of persistently infected cultured cells.	the cellular prion protein (prpc) is a sialoglycoprotein anchored to the external surface of cells by a glycosyl phosphatidylinositol moiety. during scrapie, an abnormal prp isoform designated prpsc accumulates, and much evidence argues that it is a major and necessary component of the infectious prion. based on the resistance of native prpsc to proteolysis and to digestion with phosphatidylinositol-specific phospholipase c as well as the enhancement of prpsc immunoreactivity after denaturation, ...	1990	1693623
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
spiroplasmas and spongiform encephalopathies.		1992	1736068
are prions misfolded molecular chaperones?	a theory has been developed that could explain prion infection. prions could be molecular chaperones that are required for their own assembly. the theory has been deduced from an analysis of protein folding and consequences explored by computer simulations. thermo-kinetic analysis of protein folding shows that a misfolded chaperone gives rise to new misfolded chaperones. consequently such a protein could behave as a new kind of informative molecule and replicate misfolding according to a process ...	1991	1756852