Publications

biological hazards in the workplace.		1992	1455591
spongiform encephalopathy in a captive puma (felis concolor).	a captive adult puma developed ataxia, a hypermetric gait and whole body tremor. the signs progressed over a period of six weeks. histopathological examination following euthanasia demonstrated spongiform encephalopathy, gliosis and mild non-suppurative meningoencephalitis. immunostaining with a polyclonal antiserum revealed prion protein (prp) associated with these changes in sections of cervical spinal cord and medulla. this is the first confirmed case of a scrapie-like spongiform encephalopat ...	1992	1455592
assessment of western immunoblotting for the confirmatory diagnosis of ovine scrapie and bovine spongiform encephalopathy (bse).		1992	1457549
ultrastructural features of spongiform encephalopathy transmitted to mice from three species of bovidae.	the ultrastructural neuropathology of mice experimentally inoculated with brain tissue of nyala (tragelaphus angasi; subfamily bovinae), or kudu (tragelaphus strepsiceros; subfamily bovinae) affected with spongiform encephalopathy was compared with that of mice inoculated with brain tissue from cows (bos taurus; subfamily bovinae) with bovine spongiform encephalopathy (bse). as fresh brain tissue was not available for nyala or kudu, formalin-fixed tissues were used for transmission from these sp ...	1992	1462768
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 localisation 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 ...	1992	1480316
[an outbreak of scrapie].		1992	1481211
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
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
cytoprotective effect of nmda receptor antagonists on prion protein (prionsc)-induced toxicity in rat cortical cell cultures.	rat cortical cells were incubated with the scrapie prion protein, prionsc. at concentrations of 3 ng/ml of prionsc and higher, the viability of the cells decreased significantly after a 12-h incubation period. simultaneously, the degree of dna fragmentation increased. in control experiments with antibodies against prionsc, prionsc lost its deleterious effect on neurons. prionsc did not affect the viability of astrocytes. drugs known to block nmda receptor channels, such as memantine (1-amino-3,5 ...	1993	7901042
heparin-like molecules bind differentially to prion-proteins and change their intracellular metabolic fate.	prpsc is the only known component of the scrapie prion. the difference between prpsc and its normal isoform prpc is probably conformational, since no difference has been found in the amino acid sequence or postranslational modifications between both proteins. heparan sulfate (hs) has been shown to be a component of amyloid plaques in a number of diseases including the prion diseases. we now present evidence that prp can specifically bind to heparin-like compounds and that this interaction might ...	1993	7901226
ablation of the prion protein (prp) gene in mice prevents scrapie and facilitates production of anti-prp antibodies.	mice, homozygous for prion protein (prp) gene ablation (prn-p0/0), develop normally and remain well > 500 days after inoculation with murine scrapie prions. in contrast, wild-type mice developed scrapie < 165 days after inoculation and most prn-p0/+ mice, heterozygous for disruption of the prp gene, exhibited signs of central nervous system dysfunction between 400 and 465 days after inoculation. in situ immunoblots showed widespread deposition of scrapie prp (prpsc) in the brains of both wild-ty ...	1993	7902565
conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins.	prions are composed largely, if not entirely, of prion protein (prpsc in the case of scrapie). although the formation of prpsc from the cellular prion protein (prpc) is a post-translational process, no candidate chemical modification was identified, suggesting that a conformational change features in prpsc synthesis. to assess this possibility, we purified both prpc and prpsc by using nondenaturing procedures and determined the secondary structure of each. fourier-transform infrared (ftir) spect ...	1993	7902575
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
the role of antibodies to prp in the diagnosis of transmissible spongiform encephalopathies.	transmissible spongiform encephalopathies (tse) are progressive degenerative disorders of the central nervous system. efficient and accurate identification of these disorders is necessitated by their transmissibility and fatal prognosis. the availability of polyclonal and monoclonal antibodies to a tse disease-specific protein marker prpsc affords the sensitivity and specificity for immuno-diagnostic assays. the majority of prpsc antigenic sites are species-directed, involve non-self sites and a ...	1993	8270104
the research programme on transmissible spongiform encephalopathies in britain with special reference to bovine spongiform encephalopathy.	research into bovine spongiform encephalopathy (bse) commenced immediately following its discovery in november 1986. formal epidemiological studies commenced in june 1987 and were part of a large research programme set up mainly at the central veterinary laboratory weybridge and the institute for animal health, afrc/mrc neuropathogenesis unit in edinburgh. this programme also covered the clinicopathology of bse, transmission studies and molecular chemistry. research results have shown that bse i ...	1993	8270105
tse research in germany: brief statement.		1993	8270106
prions and nucleic acids: search for "residual" nucleic acids and screening for mutations in the prp-gene.	studies on prions involve nucleic acid chemistry under two headings: i) do infectious prion particles contain nucleic acids? ii) is it possible by a simple procedure to screen the prion protein (prp)-gene for mutations? the return refocusing gel electrophoresis technique was developed to detect by sensitive silver staining homogeneous and heterogeneous nucleic acids extracted from highly purified scrapie prion preparations. with this method all kinds of nucleic acids from a length of 13 nucleoti ...	1993	8270107
inactivation of the scrapie agent in a scaled-down procedure for the purification of gangliosides from brain tissue.	the inactivation of the scrapie agent in biologicals was evaluated on a scaled-down procedure currently in use on a large scale for the purification of gangliosides from bovine brain tissue. residual infectivity was determined by an in vivo animal bio-assay using hamsters as the host species and the 263k strain as the reference agent. infectivity was significantly diminished during the early stages of purification and infectivity was never detected in the final preparations. these results confir ...	1993	8270108
bovine spongiform encephalopathy and its association with the feeding of ruminant-derived protein.	the epidemic of bovine spongiform encephalopathy which is currently afflicting british cattle probably represents transmission of the sheep disease, scrapie, to bovines. epidemiological evidence suggests that the source of the infection was dietary, and implicates commercial cattle rations containing meat and bone meal. although this product is manufactured worldwide from waste animal tissues, only sporadic cases of the cattle disease have occurred outside great britain where a unique combinatio ...	1993	8270111
prion encephalopathies of animals and humans.	studies over the past decade of the infectious prions causing scrapie and other transmissible neurodegenerative diseases support the hypothesis that these pathogens are novel. after convincing evidence was obtained showing that scrapie infectivity depends upon a protein component, the term "prion" was introduced to distinguish these infectious pathogens from others, including viroids and viruses. enriching fractions from syrian hamster (sha) brain for scrapie prion infectivity led to the discove ...	1993	8270114
molecular biology of prion diseases.		1993	8270116
pathology of nonhuman spongiform encephalopathies: variations and their implications for pathogenesis.	microscopic cavitation of the central nervous system (cns) is a variable, non-specific feature of several different diseases of animals. in none, however, has it received more discussion than in scrapie, a naturally occurring disease of sheep, the clinical signs of which have been known for at least two centuries; yet consensus on the essential neurodegenerative pathology of scrapie emerged only three decades ago. the subsequent recognition of such changes in other species, including man, was a ...	1993	8270117
neuropathology of human prion diseases (spongiform encephalopathies).	the human prion diseases (spongiform encephalopathies) comprise creutzfeldt-jakob disease (cjd), gerstmann-sträussler-scheinker syndrome (gss), and kuru. their clinical characteristics are progressive neurological illness with dementia and ataxia as the most prominent signs. the typical neuropathological changes are limited to the central nervous system; they consist of spongiform degeneration, amyloid plaques, astrocytic gliosis, and nerve cell loss. the aetiology of human spongiform encephalop ...	1993	8270118
infectious cerebral amyloidosis: clinical spectrum, risks and remedies.	the clinical and pathological features of the nih series of 209 transmitted cases of sporadic creutzfeldt-jakob disease (cjd) are compared with familial and iatrogenic forms of spongiform encephalopathy. real or potential risk factors are noted, including animal sources such as scrapie and bse, iatrogenic sources such as homografts and cadaveric tissue extracts, and genetic defects in the chromosome 20 amyloid precursor gene. the paper concludes with a discussion of the means by which such risks ...	1993	8270120
creutzfeldt-jakob disease. a case report, with special attention to the electroencephalogram in this disorder and to its possible relationships to kuru, scrapie and "mad cow disease".	a case of creutzfeldt-jakob disease in a 58-year-old brazilian cattle rancher and businessman is presented. the eeg was normal, which is consistent with the fact that it was made during the first half of his illness; in a later stage suppression of normal rhythms by slow moderate voltage waves would be expected. the resemblances of kuru, scrapie and "mad cow disease" to c-j disease are discussed. in each of these 4 illnesses the patient or affected animal (scrapie and "mad cow disease") (a) has ...	1993	8274092
molecular cloning of single-stranded dna purified from scrapie-infected hamster brain.	homogenized normal and scrapie-infected hamster brains were subjected to subcellular fractionation. a single band of ssdna corresponding to about 1.2 kb was purified by alkaline gel electrophoresis from the nucleic acid content of enriched preparations of mitochondria/tubulofilamentous particles. the ssdna was synthesized into double-stranded dna using taq polymerase with four dntp for extension. the cdna synthesized was inserted in m13mp10, cloned and sequenced. an unusual palindromic six-base ...	1993	8284515
bovine spongiform encephalopathy.		1993	8288469
prevention of scrapie transmission in sheep, using embryo transfer.	reciprocal embryo transfers were made between scrapie-inoculated and scrapie-free sheep (cheviot and suffolk breeds) to measure scrapie transmission via the embryo (using offspring from embryos of scrapie-inoculated donors and scrapie-free recipients) and via the uterus (using offspring from embryos of scrapie-free donors and scrapie-inoculated recipients taken by cesarean section). two control groups of offspring, 1 from scrapie-free parents (negative) and 1 from scrapie-inoculated parents (pos ...	1993	8291764
amyloid, amyloid-inducers, cytokines and heavy metals in scrapie and other human and animal subacute spongiform encephalopathies: some hypotheses.	a number of hypotheses regarding the pathogenesis of scrapie and other human and animal spontaneous and experimental subacute spongiform encephalopathies (sse) are presented here. in particular, it is speculated that a prpsc 27-30-induced suppression of host's defense system is responsible, through the existence of the different and synergistically operating mechanisms, for the absence of any documented inflammatory or immunologic response during sse. this could be therapeutically counterparted ...	1993	8297402
a study of gabaergic system in scrapie-infected hamsters after striatal microinoculation of the agent.	experimental scrapie in hamster is a simple, reproducible model of prion diseases that occur in humans and animals. stereotaxic microinoculation (0.5 microliter) of the agent (263 k) into a specific cerebral structure (striatum) in hamster, previously developed in our group, gives the opportunity to further investigate the pathogenesis of these degenerative diseases and to more precisely define the brain areas and the groups of cells more vulnerable to the effects of the agent. in this model, ea ...	1993	8309620
risk analysis and the importation of animals and animal products.	importation of animals or animal products cannot take place without some element of risk. risk analysis is a blend of art and science and is a tool intended to provide decision-makers with an objective, repeatable and defensible assessment of the risks posed by a particular import proposal. risk analysis comprises risk identification, risk assessment, risk management and risk communication. examples are presented of risk analysis involving anthrax in green hides, slow virus diseases and sheep em ...	1993	8312612
[analysis of risk factors associated with bovine spongiform encephalopathy in argentina].	epidemiological studies conducted in the united kingdom have revealed the risk factors involved in the epidemic of bovine spongiform encephalopathy (bse). this has facilitated a detailed study of risk factors associated with the possible introduction of bse into argentina. an analysis has been made of the numbers and geographical distribution of cattle in the country, the structure of the veterinary services responsible for controlling animal diseases, the way in which cattle and sheep are slaug ...	1993	8312622
quantitative assessment of the astrocytic response in natural scrapie of sheep.	scrapie of sheep and goats belongs to the spongiform encephalopathies, a term derived from the characteristic vacuolar degeneration in the central nervous system. astrocytosis has been described, but a systematic quantitative study has not been made. such a study is important in resolving the still controversial issues as to whether the astrocytic response is caused directly by the infectious agent or represents a secondary reaction to tissue damage. in this study the numbers of astrocytes in 12 ...	1993	8315052
astrocytes are the primary source of tissue factor in the murine central nervous system. a role for astrocytes in cerebral hemostasis.	hemostasis in the brain is of paramount importance because bleeding into the neural parenchyma can result in paralysis, coma, and death. consistent with this sensitivity to hemorrhage, the brain contains large amounts of tissue factor (tf), the major cellular initiator of the coagulation protease cascades. however, to date, the cellular source for tf in the central nervous system has not been identified. in this study, analysis of murine brain sections by in situ hybridization demonstrated high ...	1993	8326003
isolation of scrapie agent from the placenta of sheep with natural scrapie in japan.	a five-month-pregnant suffolk sheep histologically diagnosed as spontaneous scrapie was studied. western blot analysis was performed with rabbit serum against the sheep scrapie-associated fibrils (saf). in the proteinase k (pk)-treated parental brain and spleen samples, three major bands (15 k, 18 k, and 23 k) were detected. these major bands were not detected from the placenta. infectious agents were isolated in mice from the brain samples but not from the placental homogenates. in another case ...	1993	8350771
ganglioside composition changes in spongiform encephalopathies: analyses of 263k scrapie-infected hamster brains.	ganglioside composition in brains of terminally ill lvg/lak golden syrian hamsters infected with the 263k strain of the scrapie agent was analyzed. results were compared to those obtained from noninfected animals matched by age, sex, and strain. gangliosides extracted from scrapie-infected animals showed little change in major components, while an increased number of new alkali-labile species appeared. additionally, the animal strain employed demonstrated a significant polymorphism in brain gang ...	1993	8371832
fibrils in brain of rocky mountain elk with chronic wasting disease contain scrapie amyloid.	chronic wasting disease (cwd), a progressive, fatal neurological disorder of captive mule deer and rocky mountain elk, is characterized neuropathologically by spongiform change in the neuropil, intraneuronal vacuolation and astrocytic hypertrophy and hyperplasia. recently, scrapie amyloid-immunoreactive plaques have been demonstrated in brain tissues of cwd-affected captive mule deer, rocky mountain elk and hybrids of captive mule deer and white-tailed deer. we now report on the presence of abno ...	1993	8372644
[persistent virus infections--mechanisms and consequences].	the establishment of persistent virus infections can be regarded as evolutionary mechanisms to protect viruses against the host immune reactions and to enable the perpetuation of virus infections. in principle, persistent or latent virus infections are known among most species of all virus families. among the different strategies which envolved during virus infections, three mechanisms leading to persistent or latent infections are chosen and discussed in greater detail in this review: masking o ...	1993	8392848
role of the prp gene in transmissible spongiform encephalopathies.	the transmissible agent that causes spongiform encephalopathies such as scrapie, the prion, is believed to be devoid of nucleic acid and identical with prpsc, a modified form of prpc. prpc is a normal host protein encoded by a single copy gene (prn-p) and is found predominantly on the surface of neurons. prpsc, in contrast to prpc, is resistant to protease and accumulates intracellularly. prusiner proposed that prpsc, when introduced into a normal host, causes the conversion of prpc or its precu ...	1993	8407244
bovine spongiform encephalopathy: an appraisal of the current epidemic in the united kingdom.	bovine spongiform encephalopathy (bse) is a food-borne infection of cattle caused by the use of contaminated meat and bone meal in concentrated feeds. the uk epidemic was initiated by a sudden exposure to infection in 1981-1982, which was associated with a dramatic reduction in the use of organic solvents in the manufacture of meat and bone meal. this change almost certainly removed two partial disinfection steps and allowed enough contamination with a scrapie-like agent to infect cattle. althou ...	1993	8407247
kinetics of infectivity are dissociated from prp accumulation in salivary glands of creutzfeldt-jakob disease agent-inoculated mice.	the protease-resistant isoform of prion protein (prp) has been implicated in the pathogenesis and transmission of creutzfeldt-jakob disease (cjd), scrapie and other related diseases, but the relationship between the infectious agent and prp awaits elucidation. in the present study, we have examined levels of infectivity together with accumulation of the protease-resistant form of prp (prpcjd) in various tissues of cjd agent-inoculated mice. accumulation of prpcjd occurred only in tissues, includ ...	1993	8409936
[a trend of molecular genetics on prion diseases and prion protein].	infectious amyloid filaments designated as prion rods or scrapie associated fibrils (saf) present in brain tissues affected by transmissible spongiform encephalopathies such as creutzfeldt-jakob disease (cjd), gerstmann-sträussler-scheinker disease (gss) and kuru of humans, and scrapie of sheep. a hydrophobic glycoprotein, prpsc is a major component of saf, and is known to be associated with the infectivity of these diseases. both prpsc and the normal isoform of this glycoprotein, prpc are encod ...	1993	8411733
increased expression of heat shock protein, transferrin, and beta 2-microglobulin in astrocytes during scrapie.	scrapie is a slow infection and neurodegenerative disease of animals characterized pathologically by formation of amyloid, astrocytosis, vacuolation and injury and death of neurons. our previous studies of scrapie point to: (i) a critical role for the astrocyte in responding to, and perhaps inadvertently contributing to, the neuropathological manifestations of infection; and (ii), the hypothesis that the astrocyte executes a programed response to neurological injury analogous to the stress respo ...	1993	8412623
perturbation of the secondary structure of the scrapie prion protein under conditions that alter infectivity.	limited proteolysis of the scrapie prion protein (prpsc) generates prp 27-30, which polymerizes into amyloid. by attenuated total reflection-fourier transform infrared spectroscopy, prp 27-30 polymers contained 54% beta-sheet, 25% alpha-helix, 10% turns, and 11% random coil; dispersion into detergent-lipid-protein-complexes preserved infectivity and secondary structure. almost 60% of the beta-sheet was low-frequency infrared-absorbing, reflecting intermolecular aggregation. decreased low-frequen ...	1993	8419912
pieces of scrapie puzzle falling into place.		1993	8420903
neuropathology of chronic wasting disease of mule deer (odocoileus hemionus) and elk (cervus elaphus nelsoni).	the pathology of the central nervous system of nine mule deer (odocoileus hemionus) and six elk (cervus elaphus nelsoni) with chronic wasting disease, a spongiform encephalopathy of mule deer and elk, was studied by light microscopy. lesions were similar in both species and were characterized by spongiform transformation of gray matter, intracytoplasmic vacuolation of neurons, neuronal degeneration and loss, astrocytic hypertrophy and hyperplasia, occurrence of amyloid plaques, and absence of si ...	1993	8442326
structural studies of the scrapie prion protein using mass spectrometry and amino acid sequencing.	the only component of the infectious scrapie prion identified to date is a protein designated prpsc. a posttranslational process converts the cellular prp isoform (prpc) into prpsc. denatured prpsc was digested with endoproteases, and the resulting fragments were isolated by hplc. by both mass spectrometry and edman sequencing, the primary structure of prpsc was found to be the same as that deduced from the prp gene sequence, arguing that neither rna editing nor protein splicing feature in the s ...	1993	8448158
multiple sclerosis and prions.	the etiology of multiple sclerosis (ms) is unknown. existing epidemiologic data suggests that ms can be an infectious disease. ms used to be classified as one of the 'slow infections'--many of these are caused by prions. prions are small, proteinaceous, infectious particles--distinguished from viruses by the absence of intrinsic nucleic acids. in a contrast to the 'classic' prional diseases (kuru, scrapie or creutzfeldt-jacob disease) that in cns affect primarily neurons, the 'target' cell in ms ...	1993	8455467
delimiting the location of the scrapie prion incubation time gene on chromosome 2 of the mouse.	scrapie is a transmissible neurodegenerative disease caused by unusual pathogens called prions. the interval between inoculation and illness for experimental mouse scrapie is dramatically influenced by an incubation time gene (prn-i) that is linked to prn-p, the structural gene for prion protein (prp). although prion proteins from mouse strains with short and long scrapie incubation times differ by two amino acids, mice with discordant disease phenotype and prn-p genotype occur in segregating cr ...	1993	8462855
neurotoxicity of a prion protein fragment.	the cellular prion protein (prpc) is a sialoglycoprotein of m(r) 33-35k that is expressed predominantly in neurons. in transmissible and genetic neurodegenerative disorders such as scrapie of sheep, spongiform encephalopathy of cattle and creutzfeldt-jakob or gerstmann-sträussler-scheinker diseases of humans, prpc is converted into an altered form (termed prpsc) which is distinguishable from its normal homologue by its relative resistance to protease digestion. prpsc accumulates in the central n ...	1993	8464494
attempts to restore scrapie prion infectivity after exposure to protein denaturants.	a wealth of experimental evidence argues that infectious prions are composed largely, if not entirely, of the scrapie isoform of the prion protein. we attempted to restore scrapie infectivity after exposure to protein denaturants including urea, chaotropic salts, and sds. none of the procedures restored infectivity. dialysis to remove slowly chaotropic ions and urea failed to restore scrapie infectivity. attempts to create monomers of the scrapie isoform of the prion protein under nondenaturing ...	1993	8464892
the enigma of slow viruses. facts and artefacts.		1993	8467225
transmissible spongiform encephalopathies and human neurodegenerative disease.	there has been a tremendous amount of publicity concerning the transmissible spongiform encephalopathies, and this has led to speculation regarding the possible risk to humans following the emergence of new forms in cattle and cats. we review the data relating to these diseases in the light of new developments, particularly in the fields of molecular biology and epidemiology.	1993	8472098
conversion of truncated and elongated prion proteins into the scrapie isoform in cultured cells.	the only known component of the infectious prion is a posttranslationally modified protein known as the scrapie isoform of the prion protein, prpsc. upon limited proteolysis, a protease-resistant fragment designated prp 27-30 is formed. using in vitro mutagenesis, we examined the role of the n and c termini in the formation of prpsc in persistently infected, mouse neuroblastoma (scn2a) cells. neither deletion of amino acids 23-88, which are also removed by proteinase k in the formation of prp 27 ...	1993	8475059
reduced rumination in bovine spongiform encephalopathy and scrapie.		1993	8480399
ultrastructural neuropathology of chronic wasting disease in captive mule deer.	chronic wasting disease (cwd), a progressive and uniformly fatal neurological disorder, is characterized neuropathologically by intraneuronal vacuolation, spongiform change of the neuropil and astrocytic hyperplasia and hypertrophy. ultrastructural neuropathological findings consist of (1) extensive vacuolation in neuronal processes, within myelin sheaths, formed by splitting at the major dense lines or within axons; (2) dystrophic neurites (dendrites, axonal preterminals and myelinated axons co ...	1993	8480515
localization of the mrna for a chicken prion protein by in situ hybridization.	the infectious agent (prion) responsible for transmissible spongiform encephalopathies in humans and animals is composed primarily of a 33- to 35-kda glycoprotein called prpsc (scrapie isoform of prion protein), which is a posttranslationally modified form of the normal cell-surface protein prpc. little is known about the function of prpc. interestingly, chprp, the chicken homologue of prpc, copurifies with a factor from brain that stimulates synthesis of acetylcholine receptors on skeletal musc ...	1993	8483948
[transmissible and non-transmissible brain amyloidoses: neurodegenerative disorders of different etiologies and the same pathogenesis].	i report here the molecular, ultrastructural and immunohistochemical similarities between transmissible (scrapie, creutzfeldt-jakob disease and gerstmann-sträussler-scheinker syndrome) and non-transmissible (alzheimer's disease, hereditary cerebral hemorrhage with amyloidosis--dutch (hchwa-d) and icelandic (hchwa-i) types) brain amyloidoses. the central pathogenic event in both types of amyloidoses is a synthesis and a processing of amyloid precursor followed by an accumulation of a final deposi ...	1993	8488078
experimental transmission of bse and scrapie to the common marmoset.	two young male common marmosets (callithrix jacchus) were injected intracerebrally and intraperitoneally with a crude brain homogenate prepared from a cow with bovine spongiform encephalopathy (bse). two other marmosets were similarly injected with brain homogenate from a sheep with natural scrapie. the two animals injected with scrapie material developed neurological signs 38 and 42 months after injection and the two animals injected with bse material developed neurological signs after 46 and 4 ...	1993	8488658