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invasion of the nervous system by "slow" virus: a study with scrapie agent. 19695392819
simple method of evaluating scrapie in mice.mice in advanced scrapie characteristically clasp their hindlegs together. as the disease progresses into the clasping stage, mice exhibit a sequence of identifiable hindleg reactions which have categorized and assigned relative scores permitting objective, quantitative evaluation of disease.19705466135
orientated tubules in axoplasm of cerebellar myelinated nerve fibres in the rat. a study of normal and scrapie animals. 19675624640
distribution of experimentally induced scrapie lesions in the brain. 19675625087
glycosidase histochemistry in normal and scrapie mice, rats, sheep and goats. 19685690819
inherited characteristics affecting neurotropic behaviour of scrapie. 19695767040
neurological illness after inoculation of tissue from tumour bearing animals. 19695813102
the fatty composition of brain and myelin of normal and scrapie-affected mice. 19695813348
dna synthesis in scrapie-affected mouse brain. 19676070059
ultrastructural cytochemical studies of cerebral microvasculature in scrapie infected mice.alkaline phosphatase, 5'-nucleotidase nucleoside diphosphatase and thiamine pyrophosphatase activities were studied by cytochemical method applied to electron microscopy of brain microvasculature in normal and scrapie infected mice. in control mice, the major location of all phosphatases studied was the luminal plasma membrane of the endothelial cells. in scrapie infected mice, changes in activity and distribution of the above mentioned phosphatases manifested themselves in the appearance of the ...19816111887
scrapie: strategies, stalemates, and successes. 19826122977
immunological studies of scrapie infection. 19826183292
the reticuloendothelial system in scrapie pathogenesis.a single injection of 1 mg dextran sulphate 500 per mouse considerably prolonged incubation times and produced survivors, even when given 3 days after intravenous or intraperitoneal scrapie infection. since this compound could be detected in mononuclear phagocytes of spleen and lymph nodes for up to 7 months, it is suggested that it impairs a particular step in the infectious process in these cells of the lymphoreticular system. blockage of the reticuloendothelial system by trypan blue and silic ...19846198455
scrapie agent contains a hydrophobic protein.the scrapie agent causes a degenerative nervous system disorder of sheep and goats. considerable evidence indicates that the scrapie agent contains a protein that is necessary for infectivity [prusiner, s. b., groth, d. f., cochran, s. p., masiarz, f. r., mckinley, m. p. & martinez, h. m. (1980) biochemistry 19, 4883-4891], but direct demonstration of a protein moiety has been hampered by lack of sufficiently purified preparations. employing preparations of the scrapie agent enriched 100- to 100 ...19816273882
inability to transmit scrapie by transfection of mouse embryo cells in vitro.infectivity of nucleic acid from highly infectious mouse scrapie brains was studied by transfecting the nucleic acid in vitro prior to inoculation into animals. foetal mouse brain and whole mouse embryo cultures were chosen as the cells used for the transfection. as an internal control, infectious nucleic acid was recovered from bacteriophage phi x174 and whole virus particles were obtained when cultures were transfected with herpes simplex virus dna. in contrast, none of the animals inoculated ...19826278059
scrapie-associated fibrils in creutzfeldt-jakob disease.scrapie of sheep, and creutzfeldt-jakob disease (cjd) of man belong to a group of transmissible encephalopathies which have been successfully transmitted to a variety of hosts. in susceptible hosts, these diseases are characterized by progressive degeneration of the central nervous system leading inevitably to death. the agents responsible for these diseases have not yet been identified, but they exhibit similar physicochemical characteristics. abnormal fibrils designated 'scrapie associated fib ...19836358899
[the role of animals in central nervous system diseases in man]. 19846400461
[the ola major histocompatibility complex of sheep. genetic frequencies compared in prélpe sheep with and without scrapie].the ola genic frequencies were studied in both normal "préalpe" sheep and those affected with scrapie. in the non-affected sheep of contaminated flocks, frequencies were generally decreased, compared with frequencies of the same factors in sick sheep or in non-infected controls. three ola-a genes significantly decreased; at this locus, results in "préalpe" and "ile-de-france" sheep were inversed. this observation excludes ola genes being involved in pathogeny or resistance to the disease, but su ...19846430472
occurrence of ovine scrapie in japan: clinical and histological findings in mice inoculated with brain homogenates of an affected sheep. 19846441054
an epidemiologic critique of creutzfeldt-jakob disease. 19806448751
sheep lymphocyte antigens and scrapie.the frequencies of 15 lymphocyte antigens were determined in 2 experimental flocks of herdwick sheep derived from the same foundation stock. the blue flock had been bred for resistance, and the red flock for susceptibility, to a standard dose of the ssbp/1 source of scrapie injected subcutaneously. although there were marked frequently differences between the 158 red flock and 51 blue flock sheep tested these differences could be attributed to genetic drift. within the red flock no significant f ...19846470228
[karyological characteristics of continuous mouse cell lines infected with the scrapie agent].a karyological study of murine cell line l, latently infected with different strains of the scrapie agent (compton and c-506) showed that the both variants number of chromosomes and the number of robertson's translocations of chromosomes decrease insignificantly with an increase in the time of subcultivation. the use of the c-method of differential chromosome staining revealed four new analogous chromosomes in both experimental cell lines. this phenomenon is probably specific for this infected c ...19846539520
ultrastructural morphology of amyloid fibrils from neuritic and amyloid plaques.the structure of partially purified, cns amyloid fibrils from three different sources have been compared by negative stain em. the fibrils isolated from brains with senile dementia of alzheimer type were 4-8 nm in diameter, narrowing every 30-40 nm and apparently composed of two 2-4 nm filaments. the fibrils from a gerstmann-sträussler syndrome brain were 7-9 nm in diameter, narrowing every 70-80 nm and with a suggestion that they are composed of two 3-5 nm filaments. the fibrils isolated from 8 ...19836683919
scrapie in france: some possible predisposing factors in the naturally-acquired disease of sheep.a nationwide survey of the occurrence of scrapie in france during the 12-year period 1968-1979 has shown the disease to be more widespread than previously thought. the data suggest that certain sheep raising practices, such as transhumance (nomadic grazing), pen and pasture alternations, and use of animals for milk production, may play a possible role in disease prevalence.19836685940
[epidemiology of aids]. 19846730611
replication of the scrapie agent in ocular neural tissues.optic nerves and retinas removed from hamsters experimentally inoculated with the scrapie agent contain a high titer of infectivity. ophthalmoscopic examination of these animals revealed gross lesions of retinopathy as early as 3 weeks before the onset of clinical signs of brain degeneration. these results suggest that the scrapie agent may spread centrifugally in nerve fibers after intracerebral inoculation and that the scrapie-associated retinopathy seen in hamsters is directly induced by the ...19806767244
virologic and neurohistologic findings in dairy goats affected with natural scrapie.virologic and neurohistologic findings in three dairy goats that became affected with scrapie while living with naturally infected suffolk sheep were essentially like those in affected sheep. virus, detected by mouse inoculation, was widespread in non-neural sites, particularly in lymphatic tissues and intestine. im most sites, titers of virus ranged from 3.0 to 3.5 log10 mouse intracerebral ld50/30 mg of tissue. virus was in nervous tissue in much higher titer. ranging from 5.1 to 5.8 log10, th ...19806767304
sensitivity of scrapie infectivity to detergents and 2-mercaptoethanol.exposure of fractions obtained from scrapie-infected mouse brain to triton x-100 resulted in no change in its infectivity except after sedimentation. infectivity was reduced after exposure to 2-mercaptoethanol but only in the presence of sds. these results support the view that protein is an important component of the scrapie agent and that disulfide bonds may play a part in maintaining the structural integrity of the infectious agent.19806768695
host and viral genetic determinants of the behavioral effects of scrapie encephalopathy. 19806773083
pathogenesis of mouse scrapie: evidence for neural spread of infection to the cns.the replication of infectious agent has been studied in brain, thoracic cord, and lumbar cord of compton white mice (sinc87) infected with the 139a strain of scrapie. nine experiments were carried out using four different peripheral routes of injection. a highly consistent pattern of results was obtained in which replication in the cns started in the thoracic cord after about 35% of the total incubation period had elapsed (range 25 to 42%). this was followed by the simultaneous onset of replicat ...19806780656
[hyperproduction of glial fibrillary acidic protein (gfa) during development of experimental scrapie in mice]. 19816796203
changes in the nigrostriatal system following microinjection of an unconventional agent.the effect of apomorphine, a direct dopamine receptor agonist, was studied in golden hamsters after unilateral injection of scrapie agent (strain 263k) into the nigrostriatal system. twenty-five received an injection into the left striatum and 24 into the left substantia nigra. varying volumes (5, 1 and 0.5 microliterss) and dilutions of the homogenate (10(-2), 10(-3), 10(-4)) were used. the duration of the incubation period (delay of appearance of clinical signs of the disease) was dependent on ...19826807492
experimental scrapie in golden syrian hamsters: temporal comparison of in vitro cell-fusing activity with brain infectivity and histopathological changes.golden syrain hamsters were inoculated intracerebrally with the hamster-adapted 263k strain of scrapie virus, and the evolution of in vitro cell fusing activity induced by brain suspensions was compared with brain infectivity titers and histological changes. cell-fusing activity abruptly appeared 4 weeks after inoculation, 1 week before the earliest detectable histopathological changes, at an infectivity level of 7.6 log 50% lethal doses per g of brain. cell-fusing activity was sustained through ...19826809626
optic nerve degeneration in hamsters experimentally infected with scrapie. 19826890907
[slow virus infections: the concept of chronic diseases]. 19806999335
[experimental pathology of subacute spongiform encephalopathies]. 19807011482
focal and asymmetrical vacuolar lesions in the brains of mice infected with certain strains of scrapie. 19827180387
effect of vaccinia-activated macrophages on scrapie infection in hamsters. 19817194567
perivascular infiltrates of leukocytes in brains of scrapie-infected mice. 19817198185
retinal damage in scrapie mice.retinal damages in mice infected with scrapie are reported. the effects ranged from no histopathological changes, through partial loss of the outer nuclear layer (onl) to the most severe changes with complete loss of onl cells and photoreceptors. for the most part, cells of inner nuclear and ganglion layers were spared. these changes were found in 23% of c57bl/6j mice injected with the me7 strain of scrapie and in 28.5% of vm mice injected with the 87 v strain, while no changes were found in 13 ...19827199805
western blot mapping of disease-specific amyloid in various animal species and humans with transmissible spongiform encephalopathies using a high-yield purification method.saf-protein, an amyloid, is the main constituent of scrapie-associated fibrils (saf) and a specific marker for transmissible spongiform encephalopathies (tse). using an improved extraction method and western blot detection, the disease-specific amyloid was found in various parts of the central nervous system of hamsters orally infected with scrapie, of squirrel monkeys orally infected with kuru, sporadic creutzfeldt-jakob disease (cjd) and scrapie, of human patients with sporadic cjd, of a sheep ...19957595360
a cellular form of prion protein (prpc) exists in many non-neuronal tissues of sheep.a cellular form of the prion protein (prpc) is thought to be a substrate for an abnormal isoform of th eprion protein (prpsc) in scrapie. prpc is abundant in tissues of the central nervous system, but little is known about the distribution of prpc in non-neuronal tissues of sheep, the natural host of scrapie. this study investigated the tissue distribution of prpc in sheep. although prpc was abundant in neuronal tissues, it was detected in non-neuronal tissues such as spleen, lymph node, lung, h ...19957595362
intracerebral distribution of infectious amyloid protein in spongiform encephalopathy.we studied the regional distribution of infectious amyloid protein by western immunoblots of brain tissue extracts from 37 patients with different forms of spongiform encephalopathy, i.e., 16 sporadic cases, 18 familial cases with a variety of mutations, and 3 iatrogenic cases. in sporadic and familial creutzfeldt-jakob disease, amyloid protein concentrations were usually highest in the frontotemporal regions of the cerebral cortex, whereas iatrogenic creutzfeldt-jakob disease and gerstmann-strä ...19957654073
studies on a species-specific epitope in murine, ovine and bovine prion protein.transmissible spongiform encephalopathies are fatal neurodegenerative disorders which are linked to abnormal isoforms of the prion protein (prp), which is expressed in different cells of various mammalian species. susceptibility to disease and reduced transmission rates upon the first passage to another species are thought to be a result of functional and biochemical differences of the prp as a consequence of amino acid sequence among species. in 1985 an epidemic of bovine spongiform encephalopa ...19937687651
[scrapie in sheep and transmissible encephalopathy of the mink].scrapie in sheep and goat is the prototype of the group of the transmissible spongiform encephalopathies which affect man and some animal species, notably other ruminants with bovine spongiform encephalopathy (bse) and chronic wasting disease of wild ruminants. transmissible mink encephalopathy (tme) is a rare disease of ranch-raised mink caused by exposure to a contaminated food ingredient in the ration scrapie, unrecognised bse-like disease...). there is clinical and pathological similarities ...19957777384
seac reports on transmissible spongiform encephalopathies. 19957793019
endosome-lysosomes and neurodegeneration.a number of the major human and animal neurodegenerative diseases, such as alzheimer's disease and sheep scrapie, are characterised by deposits of amyloid, arising through incomplete breakdown of membrane proteins. although our knowledge concerning these diseases is increasing, they remain largely untreatable. recently, attention has focussed on the mechanisms of production of different types of amyloid and the likely involvement within cells of acid compartments called endosome-lysosomes. these ...19947858158
identification of five allelic variants of the sheep prp gene and their association with natural scrapie.scrapie is a fatal neurodegenerative disease of sheep that belongs to the group of prion diseases found in humans and animals. the host encoded prion protein (prp) plays a central role in the disease process. in the prp genes of man, mice and sheep, polymorphisms have been found that are associated with disease susceptibility and pathogenesis. we have used denaturing gradient gel electrophoresis (dgge) to detect polymorphisms in the sheep prp gene. in addition to the already described polymorphi ...19957897344
structure and polymorphism of the mouse prion protein gene.missense mutations in the prion protein (prp) gene, overexpression of the cellular isoform of prp (prpc), and infection with prions containing the scrapie isoform of prp (prpsc) all cause neurodegenerative disease. to understand better the physiology and expression of prpc, we retrieved mouse prp gene (prn-p) yeast artificial chromosome (yac), cosmid, phage, and cdna clones. physical mapping positions prn-p approximately 300 kb from ecotropic virus integration site number 4 (evi-4), compatible w ...19947912827
hungary remains free of scrapie and bovine spongiform encephalopathy (bse).brains from 44 sheep and 43 cattle with cns clinical signs not due to rabies virus infection were collected from diagnostic institutes throughout hungary. the brains were examined for histological lesions diagnostic of scrapie/bovine spongiform encephalopathy (bse) and all were found to be negative. these findings confirm that hungary remains free of scrapie and bse.19938017235
prp genotypes and the sip gene in cheviot sheep form the basis for scrapie strain typing in sheep. 19948030950
bse awareness programme in tasmania. 19948059517
french autochthonous scrapied sheep without the 136val prp polymorphism. 19938104061
inactivation of se agents.the transmissible agents of the spongiform encephalopathies are relatively resistant to inactivation, and accidental transmission has occurred in animals and man. rigorous chemical or physical procedures are required to achieve decontamination, and their effectiveness can only be determined by bioassay in animals. the best-defined model is scrapie in mice or hamsters, and this has been used in many of the studies to establish practical inactivation procedures. although a number of techniques had ...19938137130
detection of apoptosis induced dna cleavage in scrapie-infected sheep brain.the pathogenesis and molecular basis of nerve cell death which accompanies scrapie infections in sheep are not well understood. degeneration of neurons in culture caused by prion protein fragments has recently been reported to be consistent with mechanisms of cell death by apoptosis or programmed cell death. apoptosis activation during prion-related encephalopathies has not yet been established in vivo. we report here the detection of dna damage consistent with apoptosis in the brain cells of sh ...19948138146
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 ...19938219808
scrapie control in the united states. 19938236771
bovine spongiform encephalopathy. 19938288469
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 ...19938312612
creutzfeldt-jakob disease and bovine spongiform encephalopathy. aetiology of scrapie in certain circumstances is not evidence against another aetiology in different circumstances. 19968563543
comparative study of electron microscopical techniques for the detection of scrapie-associated fibrils.samples of cervical spinal cord and four anatomical regions of the brains of 12 sheep with natural scrapie and six control sheep were examined by electron microscopy, after the tissues had been stored at 4 degrees c and -20 degrees c. the tissues were tested for the presence of scrapie-associated fibrils by a centrifugal extraction technique and by a touch-grid technique. the touch-grid technique was no better than the centrifugal extraction technique for the detection of fibrils. structures whi ...19958588101
[prion diseases. review of the literature on the light of two case reports of creutzfeldt-jakob disease].during the last ten years the diseases scrapie in sheep and bovine spongiform encephalopathy (or mad cow disease) in cattle have received increased attention. through the 1960s it became apparent that scrapie in sheep and kuru and later creutzfeldt-jakob disease in man were infectious diseases. during the last decade the appearance of mad cow disease in great britain has increased the fear that humans can develop creutzfeldt-jakob disease through their food. a special characteristic of the infec ...19968658476
strain specific and common pathogenic events in murine models of scrapie and bovine spongiform encephalopathy.the development of transmissible spongiform encephalopathies in experimental models depends on two major factors: the intracerebral accumulation of an abnormal, protease-resistant isoform of prp (prpres), which is a host protein mainly expressed in neurons; and the existence of different strains of agent. in order to make a distinction between pathogenic mechanisms depending upon the accumulation of host-derived prpres and the strain-specific effects, we quantified and compared the sequence of m ...19968758005
protease-resistant prp deposition in brain and non-central nervous system tissues of a murine model of bovine spongiform encephalopathy.infectivity within the central nervous system has been demonstrated by the transmission of bovine spongiform encephalopathy (bse) from affected cattle to inbred laboratory mice. sedimentable, protease-resistant prp (prpsc) has also been extracted from bse-affected cattle brain. both infectivity and prpsc have been reported in the lymphoreticular tissues of sheep and mice clinically and preclinically affected with scrapie. neither infectivity nor prpsc has yet been detected in non-neural tissues ...19968760446
observations on the transmission of scrapie in experiments using embryo transfer.this investigation studied the maternal transmission of scrapie in sheep by using embryo transfer to examine the viability of highly susceptible offspring derived from scrapie-affected and uninfected donors. the study also examined the effect of washing the embryos. scrapie occurred in both washed and unwashed embryo-derived sip sasa progeny from both groups of donor ewes. as a result, the earlier observation that scrapie might pass via the unwashed embryo to develop as disease in adult sheep ha ...19968795182
spongiform encephalopathies: still many unanswered questions. 19968795492
endosome-lysosomes, ubiquitin and neurodegeneration.before the advent of ubiquitin immunochemistry and immunogold electron microscopy, there was no known intracellular molecular commonality between neurodegenerative diseases. the application of antibodies which primarily detect ubiquitin protein conjugates has shown that all of the human and animal idiopathic and transmissible chronic neurodegenerative diseases, (including alzheimer's disease (ad), lewy body disease (lbd), amyotrophic lateral sclerosis (als), creutzfeldt-jakob disease (cjd) and s ...19968861020
prp genotype contributes to determining survival times of sheep with natural scrapie.several allelic variants of the sheep prp gene are associated with scrapie susceptibility. however, it is not known whether, and to what extent, the prp genotype contributes to determining survival times of scrapie sheep. we therefore determined the prp genotype and life spans of over 50 flemish and swifter sheep within a single scrapie-affected flock. eighty-three per cent of the scrapie sheep were homozygous for the prp(vq) allele (polymorphic amino acids at codons 136 and 171 are indicated) a ...19968887505
improvement of prpsc-detection in mouse spleen early at the preclinical stage of scrapie with collagenase-completed tissue homogenization and sarkosyl-nacl extraction of prpsc.scrapie in sheep has recently become again a target of control measures and eradication programs. crucial for the effectiveness of these measures is the detection of infected sheep during the long and potentially hazardous incubation period. however, routine-diagnosis is mostly limited to clinical examinations when disease becomes apparent, and to postmortem investigations. through the detection of the scrapie-specific isoform of the prion protein (prpsc) by western blot in the spleen and lymph ...19968920821
transmissible spongiform encephalopathies (tse): minimizing the risk of transmission by biological/biopharmaceutical products: an industry perspective.several guidelines and recommendations have been published on assessing the potential risk of a biological product being contaminated with an agent causing a transmissible spongiform encephalopathy (tse). basic principles which can be used during the manufacturing of biological products to minimize the risk of transmission of tse agents include the following: (i) obtaining animals, tissues or animal-derived raw materials from countries in which the relevant tse agent is reported to be absent; (i ...19969119148
biochemical typing of scrapie strains. 19979121579
[prion diseases and a new variant of creutzfeldt-jakob disease].the causal link of a new variant of cjd (v-cjd) with bovine spongiform encephalopathy (bse) has led to world-wide panic. bse emerged in 1986 through dietary products contaminated with scrapie pathogen, bse case reports increased in number up to 37,000/year in 1993, then declined in 1994 when the first case of v-cjd emerged. there is a 3-year gap between the emergence of bse and the introduction of a ban on the use of specified bovine offal in human food. people might have consumed dietary produc ...19969128415
prp genotypes and experimental scrapie in orally inoculated suffolk sheep in the united states.one-hundred and three unites states suffolk sheep were inoculated orally with a scrapie agent preparation and monitored for clinical disease and histopathological lesions characteristic of scrapie. a retrospective study of the polymorphisms at codon 171 of the prion protein (prp) gene was performed on these sheep. all 63 sheep that developed scrapie during the observation period were homozygous for the glutamine 171 (171-qq) prp allele. twelve 171-qq sheep failed to develop disease. all 5 sheep ...19979129673
[prion disease in animals and experimental prion disease]. 19979282362
syrian hamster prion protein (prp(c)) is expressed in photoreceptor cells of the adult retina.prp(c), the cellular isoform of the prion protein (prp) serves as a precursor to abnormal prp isoforms which accumulate in diseases such as scrapie in sheep, and creutzfeldt-jakob disease in humans. since prions can replicate in photoreceptors we surmised that prp(c) must be expressed in these cells. accordingly, monoclonal antisera directed against two epitopes of hamster prp(c) produced retinal immunostaining in hamsters, and in mice bearing a hamster prp transgene. immunostaining was most pro ...19979347934
an immunological approach to prion diseases.ovine scrapie and bovine spongiform encephalopathy are genetic diseases, presenting probably autoimmunity transmissible by the oral route. the absence of immune response in prion diseases indicates a tolerant state for prp(c) and prp(sc). the tolerant state against these diseases should be overcome before immunizing animals. we suggest that an early diagnosis may be possible using polyclonal and monoclonal antibodies specific for either ovine or bovine prp(sc). such reagents could be obtained by ...19989488187
[molecular pathogenesis of spongiform encephalopathy]. 19979489393
comparison of scrapie-associated fibril detection and western immunoblotting for the diagnosis of natural ovine scrapie.detergent- and proteinase k-treated extracts of grey matter were prepared from four regions of the brains of 106 sheep with scrapie, diagnosed clinically and by the demonstration of spongiform encephalopathy. the extracts were examined by electron microscopy for the presence of scrapie-associated fibrils and by western immunoblotting for the disease-specific abnormal prion protein (prpsc). as a diagnostic method, western immunoblotting proved to be more sensitive than electron microscopy, the de ...19989500237
melatonin and prolactin secretion profile in naturally occurring scrapie in ewe.the 24 hr pattern of melatonin secretion was determined in scrapie-affected ewes during the clinical course of the disease. the melatonin response to a night interruption by a 1 hr period of illumination was also measured. fourteen ewes (seven control and seven scrapie-affected ewes) were subjected to artificial short days (9l:15d). four 24 hr blood sampling sessions separated by about 10 days were performed. ewes were sacrificed when clinical signs had progressed to irreversible recumbency and ...19989510437
synthetic peptide vaccines yield monoclonal antibodies to cellular and pathological prion proteins of ruminants.transmissible spongiform encephalopathies are closely linked to the accumulation of a pathological isoform of a host-encoded prion protein (prp(c)), designated prp(sc). in an attempt to generate mono- and polyclonal antibodies to ruminant prp, 32 mice were vaccinated with peptide vaccines which were synthesized according to the amino acid sequence of ovine prp. by this approach five prp-reactive polyclonal antisera directed against four different domains of the protein were stimulated. splenocyt ...19989568991
bse: can we predict the future?prion diseases are transmissible neurodegenerative disorders of humans and animals. the prion protein (prpc) gene is expressed to some extent in many cell types but principally in neurons. normal prpc may contribute in the protection of neurons and are protease sensitive. abnormal prions consist of a post-translationally modified form of prp, prpsc, which is partly protease resistant. prpsc is a protein with high resistance to inactivation by irradiation, heat and harsh chemical treatments. it i ...19979581370
an antibody raised against a conserved sequence of the prion protein recognizes pathological isoforms in human and animal prion diseases, including creutzfeldt-jakob disease and bovine spongiform encephalopathy.antibodies to the prion protein (prp) have been critical to the neuropathological and biochemical characterization of prp-related degenerative diseases in humans and animals. although prp is highly conserved evolutionarily, there is some sequence divergence among species; as a consequence, anti-prp antibodies have a wide spectrum of reactivity (from strong immunopositivity to lack of reactivity) when challenged with prp from diverse species. we have produced an antibody (anti-prp95-108) raised a ...19989626045
scrapie.scrapie and other transmissible spongiform encephalopathies (tses) are characterized by similar pathology, biochemistry and genetics. the prp protein and its conversion to the disease-related isoform, prpsc, are crucial for the development of all tses. although scrapie is more often studied in laboratory rodents, it is not a natural disease of these animals, and much can be learned from the normal hosts, sheep. disease incidence is linked to polymorphisms and mutations of the prp gene. the compl ...19989718582
urodynamic parameters in scrapie-affected ewes and their modifications in the course of the disease.the aim of this study was to determine the urological abnormalities linked to spontaneous spongiform encephalopathy and their occurrence in the course of the disease. the animals used in this were 11 healthy and 20 scrapie-affected ewes. the scrapie-affected ewes were studied at a rate of once a month (1 to 5 measures; mean, 2.55) until they died. urodynamic explorations were performed. the bladder activity was explored using cystometry. the urethral activity was measured during cystometry and d ...19989776019
complete genomic sequence and analysis of the prion protein gene region from three mammalian species.the prion protein (prp), first identified in scrapie-infected rodents, is encoded by a single exon of a single-copy chromosomal gene. in addition to the protein-coding exon, prp genes in mammals contain one or two 5'-noncoding exons. to learn more about the genomic organization of regions surrounding the prp exons, we sequenced 10(5) bp of dna from clones containing human, sheep, and mouse prp genes isolated in cosmids or lambda phage. our findings are as follows: (1) although the human prp tran ...19989799790
a mathematical model of the dynamics of scrapie in a sheep flock.a mathematical model is developed for the dynamics of an outbreak of scrapie in a single sheep flock with the aim of assisting the interpretation of field data. the model incorporates age structure of the sheep population, both horizontal and vertical transmission, genetic predisposition to infection, variable initial load of the infectious agent, and increasing infection load during an incubation period of the same order as sheep life expectancy. this leads to system of partial differential equ ...19989825634
bovine spongiform encephalopathy: current status and possible impacts.bovine spongiform encephalopathy is an apparently new disease; first recognized in 1985, its pathological distinction was first reported in 1986. bovine spongiform encephalopathy is a member of a group of transmissible encephalopathies that includes scrapie in sheep and creutzfeldt-jakob disease in humans. early indications of its epidemiology suggested that the disease was transmitted via cattle feed containing meat and bone meals from previously infected animals. the tissues most likely to con ...19989839244
the shortest known prion protein gene allele occurs in goats, has only three octapeptide repeats and is non-pathogenic.the prion protein (prp) gene modulates the incidence and incubation periods of transmissible spongiform encephalopathies of sheep, goats, mice and man. here, a new caprine prp allele encoding the shortest naturally occurring prp protein so far described is reported. this variant contains only three instead of the usual five copies of a short peptide repeat [pro-gln/his-gly-gly-gly-(gly)-trpgly-gln] characteristic of prp, with an additional trp to gly substitution in codon 102. fifteen out of 111 ...19989880037
molecular analysis of ovine prion protein identifies similarities between bse and an experimental isolate of natural scrapie, ch1641.new variant creutzfeldt-jakob disease (vcjd) and bovine spongiform encephalopathy (bse) are caused by the same strain of pathogen and, as sheep can develop experimental bse, this has raised concern that humans may be at risk from eating mutton if bse has naturally transmitted to sheep. biochemical typing of abnormal prion proteins (prpsc) has been suggested to detect bse in sheep. although this approach is ingenuous, we can now report biochemical evidence of strain variation in contemporary and ...19999934675
experimentally induced bovine spongiform encephalopathy did not transmit via goat embryos.goats are susceptible to experimental challenge with bovine spongiform encephalopathy (bse). this study set out to investigate whether the transmission of bse could occur in goats following the transfer of embryos from experimentally infected donor females into uninfected recipient females. the results showed no evidence of transmissible spongiform encephalopathy disease in any of the offspring which developed from embryos from infected donors, nor indeed in any of the recipient females used as ...199910073715
astrocytosis and proliferating cell nuclear antigen expression in brains of scrapie-infected hamsters.scrapie is a neurodegenerative disease in sheep and goats. neuropathological examination shows astrocytosis. one issue is whether the astrocytosis seen in scrapie is a function of an increase in reactivity of individual cells, or whether there is actual replication of astrocytes. we used double-label immunohistochemistry for proliferating cell nuclear antigen (pcna) and for glial fibrillary acidic protein (gfap) to determine the mitotic state of cells and to confirm their identity as astrocytes. ...199810344795
scrapie-associated prion protein in the gastrointestinal tract of sheep with natural scrapie.the scrapie-associated prion protein (prpsc), which is closely associated with scrapie infectivity, accumulates in the brain and lymphoid tissues of sheep with natural scrapie. the most probable portal of entry of the scrapie agent in sheep is the alimentary tract; little attention, however, has been paid to the gastro-intestinal tract in scrapie research. in this study, we examined the presence and distribution of prpsc within the gastro-intestinal tract of sheep with natural scrapie and scrapi ...199910373293
risk of transmission of bovine spongiform encephalopathy to humans in the united states: report of the council on scientific affairs. american medical association.the risk of possible transmission of bovine spongiform encephalopathy (bse) in the united states is a substantial public health concern.199910386559
differences in proteinase k resistance and neuronal deposition of abnormal prion proteins characterize bovine spongiform encephalopathy (bse) and scrapie strains.prion diseases are associated with the accumulation of an abnormal isoform of host-encoded prion protein (prp(sc)). a number of prion strains can be distinguished by "glycotyping" analysis of the respective deposited prp(sc) compound. in this study, the long-term proteinase k resistance, the molecular mass, and the localization of prp(sc) deposits derived from conventional and transgenic mice inoculated with 11 different bse and scrapie strains or isolates were examined. differences were found i ...199910415165
autoantibodies to brain components and antibodies to acinetobacter calcoaceticus are present in bovine spongiform encephalopathy.bovine spongiform encephalopathy (bse) is a neurological disorder, predominantly of british cattle, which belongs to the group of transmissible spongiform encephalopathies together with creutzfeldt-jakob disease (cjd), kuru, and scrapie. autoantibodies to brain neurofilaments have been previously described in patients with cjd and kuru and in sheep affected by scrapie. spongiform-like changes have also been observed in chronic experimental allergic encephalomyelitis, at least in rabbits and guin ...199910569779
exacerbated spongiform lesions in the cerebral cortex in japanese sheep, in an outbreak of scrapie during 1984-1987.the present study dealt with the pathology of natural scrapie in japanese suffolk sheep in a certain selected area. vacuolations in the cytoplasm of neurons were conspicuous. they were particularly evident in many areas of the medulla and pons, extending into and through pedunculus cerebri and thalamus to the septal area and olfactory tubercle. proliferation of astrocytes was also easily observed with glial fibrillary acidic protein staining. neural vacuolations in the cerebral cortex were obser ...199910738362
ecosystems supporting clusters of sporadic tses demonstrate excesses of the radical-generating divalent cation manganese and deficiencies of antioxidant co factors cu, se, fe, zn. does a foreign cation substitution at prion protein's cu domain initiate tse?analyses of food chains supporting isolated clusters of sporadic tses (cwd in n colorado, scrapie in iceland, cjd in slovakia) demonstrate a consistent 2 1/2+ fold greater concentration of the pro-oxidant divalent cation, manganese (mn), in relation to normal levels recorded in adjoining tse-free localities. deficiencies of the antioxidant co factors cu/se/zn/fe and mg, p and na were also consistently recorded in tse foodchains. similarities between the clinical/pathological profile of tses and ...200010790765
protease-resistant prion protein in brain and lymphoid organs of sheep within a naturally scrapie-infected flock.the hallmark of transmissible spongiform encephalopathies (tse), such as scrapie in sheep, is the accumulation in tissues of an insoluble and protease resistant form (prpres) of the cellular prion protein. in this study, we evaluated whether the diversity in both the clinical pattern and the prp genotypes of scrapied sheep from the same flock was connected with different levels and/or glycoform patterns of the prpres in the brain and lymphoid organs of the animals. whereas the prpres levels in s ...200010839972
usda authorizes funding for scrapie eradication. 200010844956
a survey of more than 11 years of neurologic diseases of ruminants with special reference to transmissible spongiform encephalopathies (tses) in greece.the first cases of scrapie were detected in greece in a flock of sheep in october 1986. all the animals of the affected flock and all sheep in two flocks that were in contact were killed and buried. a systematic investigation of all available cases with signs indicating a neurological disease started in sheep and goats in late 1986, as well as in cattle in 1989. the investigation was based on clinical examination, necropsy or macroscopical examination of the brain and viscera, and histological e ...200010861199
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