Publications

pathogenesis of experimental scrapie.	most of our understanding of the pathogenesis of the unconventional slow infections comes from studies of experimental scrapie in mice and hamsters. after injection by non-neural peripheral routes, pathogenesis necessarily involves the lymphoreticular system (lrs) before the central nervous system (cns). available evidence indicates haematogenous spread from the site of injection to the scrapie replication sites in the lrs; later, infection spreads along visceral autonomic nerves from the lrs to ...	1988	3137002
tubulovesicular structures in experimental creutzfeldt-jakob disease and scrapie.	tubulovesicular structures, measuring 20-50 nm in diameter, were found in dilated neuronal processes in brains from mice infected with the fujisaki strain of creutzfeldt-jakob disease virus. these particles were similar to those observed in brains from hamsters infected with scrapie. these structures are consistently present in naturally occurring and experimentally induced spongiform encephalopathies, irrespective of the host species or virus strain. their role in pathogenesis is undetermined.	1988	3137185
immunoaffinity purification and neutralization of scrapie prion infectivity.	prions are unusual infectious pathogens causing scrapie of sheep and goats as well as creutzfeldt-jakob disease of humans. biochemical and genetic studies contend that the scrapie isoform of the prion protein (prpsc) is a major component of the prion. limited proteinase k digestion of prpsc produced a protein of 27-30 kda. after dispersion of brain microsomes isolated from scrapie-infected hamsters into detergent-lipid-protein complexes, copurification of prpsc and scrapie infectivity was obtain ...	1988	3137571
purification and properties of the cellular and scrapie hamster prion proteins.	during scrapie infection an abnormal isoform of the prion protein (prp), designated prpsc, accumulates and is found to copurify with infectivity; to date, no nucleic acid has been found which is scrapie-specific. both uninfected and scrapie-infected cells synthesize a prp isoform, denoted prpc, which exhibits physical properties that differentiate it from prpsc. prpc was purified by immunoaffinity chromatography using a prp-specific monoclonal antibody cross-linked to protein-a--avidgel. prpsc w ...	1988	3138115
the unusual properties of ch1641, a sheep-passaged isolate of scrapie.	an isolate of scrapie designated ch1641 was identified from a natural case of scrapie in a cheviot sheep by passage in sheep and goats. it has not been possible to transmit scrapie to mice from this source. the sip gene which controls the incubation periods of experimental scrapie in cheviot sheep has two alleles; sa which shortens and pa which lengthens the incubation periods of most strains of scrapie after the first experimental injection in sheep (the a group of strains). the ch1641 isolate ...	1988	3140468
superovulation and embryo transfer.		1988	3140469
adrenal involvement in scrapie-induced obesity.	in previous studies we found an increase in body weight during the preclinical phase of disease in certain scrapie strain-mouse strain combinations. the effect was augmented by injection into the hypothalamus. in the present study, we found an increase in food consumption (compared to the normal mouse brain injection group) for both the 139a and me7 scrapie groups, although only the me7 group showed an increase in body weight. in a scrapie strain-mouse strain combination that showed an increase ...	1988	3141932
effects of the antiserum against a fraction enriched in scrapie-associated fibrils on the scrapie incubation period in mice.	an antiserum against a fraction enriched for scrapie-associated fibrils (saf), was examined for its effects on scrapie incubation period by inoculating mice either intraperitoneally or intracerebrally with various dilutions of the serum mixed with scrapie-infected mouse brain homogenate. after intraperitoneal inoculation the mean time of the incubation period increased with increasing concentrations of the antiserum in a statistically significant fashion, when the serum dilutions were made with ...	1988	3143050
[cytomorphologic study of a line of hybrid somatic cells persistently infected with the scrapie agent].	virological, cytological and electron microscopic methods were used to study the peculiarities of the scrapie agent persistence in the tissue culture of the mouse and human hybrid cells. a long-term persistence of the scrapie agents in the cells (658 days) has been obtained. the fact of persistence is confirmed by the results of biotest and electron microscopic studies of the mouse cns. the agent persistence promotes a decrease in the mitotic activity of the infected cells and development of the ...	1988	3143174
transmissible and non-transmissible amyloidoses: autocatalytic post-translational conversion of host precursor proteins to beta-pleated sheet configurations.		1988	3143742
incubation periods in six models of intraperitoneally injected scrapie depend mainly on the dynamics of agent replication within the nervous system and not the lymphoreticular system.	the pathogenesis of intraperitoneally injected me7 scrapie has been studied in two sinc genotypes of mice which gave predictable but widely different incubation periods. comparisons were made with three other mouse scrapie models and one model in hamsters (involving different strains of agent and an untyped isolate from sheep). average incubation periods ranged from 114 days in the fastest model (263k/hamsters) to 482 days in the slowest (me7/sincp7 mice). there were only small differences betwe ...	1988	3143808
the senile dementias: a new model.	kuru and creutzfeldt jakob disease are fatal neurological disorders in humans that are transmissible to humans and other experimental animals. largely because of their transmissibility the etiology of these diseases has been ascribed to infectious agents classified as "slow" or unconventional viruses. a related neurological disease in sheep called scrapie has also been ascribed to infection by slow viruses. despite more than 20 years of intensive research no viruses or other infectious agents ha ...	1988	3144644
breeding controls rein in scrapie in yorkshire.		1988	3176270
cerebrovascular amyloid in scrapie-affected sheep reacts with antibodies to prion protein.	in an immunohistochemical study of naturally-occurring and experimental scrapie in sheep, deposits of cerebrovascular amyloid were found to react with antibodies to hamster scrapie prion protein (prp 27-30), but not with antibodies to the amyloid beta-protein of alzheimer's disease. it is concluded that this vascular amyloid is formed from prp and is therefore closely associated with scrapie infection. it is likely that this amyloid is formed from a host precursor protein as a specific pathologi ...	1988	3185993
scrapie in sheep in central and southern italy.	seven cases of scrapie were encountered in six flocks of local breeds of sheep in central and southern italy. scrapie has never been reported in these areas, in which the great majority of the italian sheep population is concentrated. the diagnosis was based on clinical and histopathological findings.	1988	3188385
comparison of spongiform lesions in experimental scrapie and rabies in skunks.	striped skunks were inoculated intracerebrally with the scrapie agent (suspension of brain from a naturally infected suffolk sheep) or intramuscularly with street rabies virus (suspension of salivary glands from naturally infected skunks). those given the scrapie agent developed clinical signs of weakness, posterior ataxia, and emaciation after incubated periods of 8 to 23 months. those inoculated with rabies virus developed clinical signs of rabies (aggressive behavior, hyperexcitability, ataxi ...	1988	3213430
abomasal dilatation and emptying defect in a flock of suffolk ewes.	abomasal dilatation and emptying defect was identified in 14 of 130 suffolk sheep from a single flock in northern california. abomasal dilatation and emptying defect was diagnosed in 13 of the sheep between november 1986 and april 1987. all affected sheep were ewes and in all, the condition developed during the lambing season. clinical signs consisted of chronic anorexia and weight loss. laboratory data from affected ewes reflected concurrent disease and was not helpful in diagnosis of the disea ...	1988	3215813
bovine spongiform encephalopathy: epidemiological studies.	this study, initiated in june 1987, describes the epidemiology of bovine spongiform encephalopathy (bse), a recently described novel neurological disease of domestic cattle first identified in great britain in november 1986. records suggested that the earliest suspected cases occurred in april 1985. there was variability in the presenting signs and the disease course, but the majority of cases developed behavioural disorders, gait ataxia, paresis and loss of bodyweight; pruritus was not a predom ...	1988	3218047
immunostaining of scrapie cerebral amyloid plaques with antisera raised to scrapie-associated fibrils (saf).	brain sections from 16 different mouse scrapie models were immunostained with antisera to scrapie-associated fibrils (saf) from three experimental scrapie sources (hamster 263k, mouse me7 and mouse 22l). these models involved seven strains of scrapie injected intracerebrally or intraperitoneally into a range of inbred mouse strains, producing a wide variety of neuropathological changes. the only brain structures which were positively immunostained were amyloid plaque cores in those models in whi ...	1988	3221978
the occurrence of cytoplasmic lamellar bodies in scrapie-infected and normal hamster brains.		1988	3226555
prions.		1988	3251470
scrapie in sheep in sweden.		1988	3256247
can potential hazard of creutzfeldt-jakob disease infectivity be reduced in the production of human growth hormone? inactivation experiments with the 263k strain of scrapie. rapid communication.	scrapie infectivity is reduced 5-6 logs following filtration through 100,000 mw cut-off filter plus overnight treatment with 6 m urea. these steps, applied to purified human growth hormone (hgh), increase the margin of safety of hgh.	1988	3277594
scrapie-infected murine neuroblastoma cells produce protease-resistant prion proteins.	scrapie and creutzfeldt-jakob disease are transmissible, degenerative neurological diseases caused by prions. considerable evidence argues that prions contain protease-resistant sialoglycoproteins, designated prpsc, encoded by a cellular gene. the prion protein (prp) gene also encodes a normal cellular protein designated prpc. we established clonal cell lines which support the replication of mouse scrapie or creutzfeldt-jakob disease prions. mouse neuroblastoma n2a cells were exposed to mouse sc ...	1988	3282080
sheep major histocompatibility (ola) complex: linkage between a scrapie susceptibility/resistance locus and the ola complex in ile-de-france sheep progenies.	as seen on their family trees, ile-de-france sheep with scrapie show genetic susceptibility to this disease, which is transmitted via scrs, an autosomal recessive gene. scrapie occurred in homozygous recessive sheep, whereas the presence of the dominant resistance allele scrr sufficed to prevent this disease in heterozygous animals. this hypothesis, previously proposed by parry (1962), was tested in a study involving 133 crossings of sheep of different genotypes, and verified in the observed pro ...	1988	3334722
first report of ovine scrapie in cyprus.		1988	3345421
ultrastructural studies of glycoconjugates in brain micro-blood vessels and amyloid plaques of scrapie-infected mice.	lectin or glycoprotein-gold complexes and samples of scrapie-infected mouse brain embedded in lowicryl k4m were used for ultrastructural localization of glycoconjugates. the lectins tested recognize the following residues: beta-d-galactosyl [rca, ricinus communis agglutinin (aggl.) 120], n-acetyl and n-glycolyl neuraminic acid (lfa, limax flavus aggl.), n-acetyl-d-glucosaminyl and sialyl (wga, wheat germ aggl.), n-acetyl-d-galactosaminyl (hpa, helix pomatia aggl., and dba, dolichos biflorus aggl ...	1988	3348084
properties of scrapie prion protein liposomes.	purified scrapie prions contain one identifiable macromolecule, prp 27-30, which polymerizes into rod-shaped amyloids. the rods can be dissociated with retention of scrapie infectivity upon incorporation of prp 27-30 into detergent-lipid-protein complexes (dlpc) as well as liposomes. as measured by end-point titration, scrapie infectivity was increased greater than 100-fold upon dissociating the rods into liposomes. the incorporation of prp 27-30 into liposomes was demonstrated by immunoelectron ...	1988	3350818
bovine spongiform encephalopathy: time to take scrapie seriously.		1988	3394240
genetic control of scrapie in cheviot and suffolk sheep.		1988	3420785
genetics and polymorphism of the mouse prion gene complex: control of scrapie incubation time.	the mouse prion protein (prp) gene (prn-p), which encodes the only macromolecule that has been identified in scrapie prions, is tightly linked or identical to a gene (prn-i) that controls the duration of the scrapie incubation period in mice. constellations of restriction fragment length polymorphisms distinguish haplotypes a to f of prn-p. the prn-pb allele encodes a prp that differs in sequence from those encoded by the other haplotypes and, in inbred mouse strains, correlates with long scrapi ...	1988	3149717
cattle disease set for cure.		1989	2918927
age at death from natural scrapie in a flock of suffolk sheep.	this study deals with natural scrapie in a flock of suffolk sheep being bred to maximise the incidence of the disease and shows that with succeeding generations the incubation period of the disease became progressively shorter until the flock died out. the most likely explanation for this phenomenon is considered to be an increase in the load of infection.	1989	2588442
ferritin immunohistochemistry as a marker for microglia.	an immunohistochemical analysis of formalin-fixed, paraffin-embedded brain sections was performed with antisera against holoferritin and the light(l)-subunit of ferritin. sections immunostained using anti-glial fibrillary acidic protein (gfap), ricinus communis agglutinin-1 (rca-1) stain for microglia and iron stain (berlin blue stain) were compared. the l-subunit of ferritin was purified from normal human spleen according to the modified scrapie-associated fibrils purification, and the anti-ser ...	1989	2596262
bovine spongiform encephalopathy in a cow in the united kingdom.	bovine spongiform encephalopathy (bse) was diagnosed in a cow with a history of behavioral change, apprehension, hyperesthesia to auditory and tactile stimuli, wide-based stance, and marked hind limb hypermetria. myoclonus involving individual muscles was observed in the shoulder region, ventral cervical region, and upper portion of the hind limb. clonus was observed in the forelimbs. clinicopathologic findings were normal, except for high serum globulin concentration, which was attributable mai ...	1989	2599961
serial ultrastructural studies of scrapie in hamsters.	we report sequential studies of the ultrastructural neuropathology of the subcortical grey matter of hamsters infected with the 263k strain of scrapie virus. vacuolation in this model develops relatively late in the incubation period, while tubulovesicular structures appear early. furthermore, neuroaxonal dystrophy, accumulations of branching tubules, and neuronal change consisting of intracytoplasmic "whorls" of proliferating membranes constitute prominent features of scrapie-related neurodegen ...	1989	2607015
neuronal degeneration and neurofilament accumulation in the trigeminal ganglia in creutzfeldt-jakob disease.	we report the pathological and immunohistochemical changes in the first-order neurons in the trigeminal ganglia in creutzfeldt-jakob disease (cjd). degenerative changes consisted of cytoplasmic vacuolation and fenestration, abundant satellite cells, neurofilament accumulation in neurons, and axonal dystrophy with spheroid formation and torpedolike structures arising from the neuronal cytoplasm. dystrophic axons, axonal spheroids, and some ganglion cells were labeled with monoclonal antibodies to ...	1989	2643917
iatrogenic transmission of creutzfeldt-jakob disease.		1989	2657828
a novel replicating agent isolated from the human intestinal tract having characteristics shared with creutzfeldt-jakob and related agents.	a novel replicating agent (ifdo) was isolated from ileal fluid. growth occurred in vitro under aerobic and anaerobic conditions, and was faster at 37 degrees c than at room temperature. the doubling time was 15.8 min. colonies were dark brown in colour and occurred beneath the surface of agar after conventional surface inoculation. provisional data indicate that the agent may be a normal intestinal commensal. the agent was remarkably resistant to inactivation by steam at 134 degrees c, formaldeh ...	1989	2659797
bovine spongiform encephalopathy and human health.	because bovine spongiform encephalopathy (bse) has probably been caused by accidental transmission of the transmissible agent of sheep scrapie there is concern that humans may be at risk from bse. epidemiological and experimental evidence is examined which suggests that this is unlikely.	1989	2686150
neuroaxonal dystrophy: an ultrastructural link between subacute spongiform virus encephalopathies and alzheimer's disease.		1989	2690113
classic genetics of scrapie.	many years ago, observations of natural scrapie revealed differences in clinical manifestations and in the areas of the brain that showed the most intense histopathological changes. in experimental work with scrapie in mice two fundamental points were established in early studies: (1) a mouse gene, termed sinc for scrapie incubation, affects the length of the incubation period. (2) in a single strain of mice, incubation periods of different "strains" of scrapie can differ by as much as 3-4 fold, ...	1989	2690115
amyloidogenesis in alzheimer disease and scrapie.		1989	2690127
scrapie-induced diabetes mellitus in hamsters.	scrapie-infected hamsters had slightly elevated non-fasting plasma glucose levels, markedly abnormal glucose tolerance tests, and impaired release of insulin in response to a glucose load. plasma cortisol levels were essentially the same in infected and uninfected animals. histological examination of the pancreas revealed no morphological changes in infected animals with no alteration in distribution of cells secreting insulin, glucagon and somatostatin. in contrast, brains of scrapie-infected a ...	1989	2693886
the correlation of electroretinographic and histopathological findings in the eyes of mice infected with the 79a strain of scrapie.	retinal degeneration was produced using the 79a strain of scrapie injected intracerebrally into mice of the mm inbred strain, and studied by electroretinography and light and electron microscopy during the preclinical and clinical phases of the disease. the changes in the electroretinogram (erg), detectable in some mice at 118 days postinjection (d.p.i.), appeared to coincide with the earliest morphological evidence of photoreceptor damage. in the early stages there was a progressive reduction o ...	1989	2725831
scrapie and the sheep mhc: claims of linkage refuted.		1989	2731967
adenocarcinoma of the salivary gland in a white swiss mouse.	a salivary gland adenocarcinoma in a white swiss mouse used in a titration of the scrapie agent is reported. the neoplasm originated from the serous cells of the parotid salivary gland. retroviral particles were detected in the neoplastic salivary gland cells by electron microscopy.	1989	2766159
changes in brain gene expression shared by scrapie and alzheimer disease.	we have isolated two recombinant cdnas whose corresponding rnas have an increased abundance in scrapie-infected hamster brain. dna sequence analysis has shown that these two recombinants represent the genes for sulfated glycoprotein 2 and transferrin. the abundance of sulfated glycoprotein 2 rna is increased in hippocampus from patients with alzheimer disease and pick disease, whereas transferrin rna is not strongly modulated in these conditions. expression of two previously identified scrapie-m ...	1989	2780570
ovine scrapie: follow-up of sheep belonging to an endemic scrapie-infected flock.	there is a close similarity between the unconventional virus-induced ovine scrapie and human creutzfeldt-jakob disease. since infection might be transmitted orally, the ovine production of an endemically scrapie-infected farm was studied. about 80% of the annual production are sold (50% as butcher-meat, 30% as breeding animals), and scrapie appears in 20% of the sheep kept on the farm. was the same proportion of butcher-meat animals scrapie-infected? since the scrapie agent has been detected in ...	1989	2785055
primary structure of prion protein may modify scrapie isolate properties.	scrapie is an infectious neurodegenerative disease caused by unusual pathogens called prions, in which no scrapie-specific nucleic acid has been detected to date. the only known component of the prion is the scrapie isoform of prion protein (prpsc), which is encoded by a host gene (prn-p). isolates of scrapie agent were prepared by passage of infectivity through inbred strains of mice that differ in scrapie incubation time and produce prpsc molecules differing by two amino acids. both the length ...	1989	2798418
scrapie as a model for neuroaxonal dystrophy: ultrastructural studies.	neuritic degeneration is a prominent ultrastructural feature of scrapie in hamsters. to investigate the morphogenesis of neuritic degeneration, we examined brain tissues from hamsters infected with the 263k strain of scrapie virus and from age-matched controls at varying intervals following intracerebral inoculation. dystrophic neurites--defined as dendrites, axonal preterminals, and myelinated axons containing mitochondria and pleomorphic, electron-dense inclusion bodies--were found as early as ...	1989	2806455
unraveling prion diseases through molecular genetics.	prions are transmissible pathogens that cause degenerative diseases in humans and animals. unique attributes of prion diseases include infectious, sporadic and genetic manifestations, as well as progression to death, all in the absence of a detectable immune response. prions are resistant to chemical procedures that modify or destroy nucleic acids and are composed largely of a protein, designated prpsc. molecular cloning of a cognate cdna established a cellular host origin for prpsc protein and ...	1989	2473558
scrapie agent decontamination: implications for bovine spongiform encephalopathy.	bovine spongiform encephalopathy probably results from the use of commercial diets containing scrapie-contaminated ingredients. of all the chemical and physical decontamination procedures which are effective against conventional viruses, only high temperature autoclaving, high concentrations of sodium hypochlorite, and possibly molar sodium hydroxide, are useful against the group of unconventional transmissible agents which includes scrapie. the implications of this problem for the rendering ind ...	1989	2499090
the role of the spleen in the neuroinvasion of scrapie in mice.	the pathogenesis of 139a scrapie has been studied in cw mice infected intraperitoneally (i.p.), intravenously (i.v.) or subcutaneously (s.c.). in mice splenectomised before i.p. infection, the evidence points to a neuroinvasive pathway from visceral lymph nodes (and other sites of scrapie replication in the peritoneum) to the thoracic spinal cord. however, in non-splenectomised mice, the major neuroinvasive pathway is clearly from spleen to thoracic cord because i.p. incubation periods are short ...	1989	2499134
pathogenesis of scrapie in mice after intragastric infection.	infection via the gastrointestinal tract is likely to be a natural route of scrapie infection in sheep. this paper describes the pathogenesis of the 139a strain of scrapie introduced intragastrically (i.g.) into cw mice. there was an almost immediate uptake of infectivity and onset of replication in peyer's patches which preceded replication in spleen. splenectomy had no effect on incubation period suggesting that, in contrast to the intraperitoneal route, the spleen plays little or no role in t ...	1989	2499135
scrapie-induced alterations in glucose tolerance in mice.	certain scrapie strains cause obesity in several strains of mice. the potential association between obesity and altered glucose tolerance was assessed by monitoring body weight and glucose tolerance throughout the incubation period in scrapie strain-mouse strain combinations that do and do not produce obesity. virtually all obese mice showed reduced glucose tolerance as shown by significantly higher blood glucose levels 2 h after a glucose overload. mice injected with a scrapie strain that did n ...	1989	2499660
ultrastructural studies of scrapie-associated fibrils and prion protein from hamster brains infected with scrapie.	we report here about the purification of prion protein 27-30 (prp 27-30) and scrapie-associated fibrils (saf) from hamsters infected with the 263k strain of scrapie. ultrastructural analysis of fractions from scrapie-infected brains revealed numerous fibrils measuring approximately 20 nm in diameter and 100-200 nm in length. the substructure of these fibrils consisted of protofilaments which were usually straight and rarely helically arranged. we conclude that the electron microscopic appearance ...	1989	2500370
induced frameshifting mechanism of replication for an information-carrying scrapie prion.	a specific mistranslation mechanism for the replication of an infectious protein is described. the feedback mechanism requires the infectious agent to induce concerted frameshifts during the translation of a cellular gene. each module of the tandem repeat region of the gene encoding the prion protein (prp) associated with scrapie infectivity contains multiple sites of potential ribosomal frameshifting. it is proposed that some aberrant variants of prp containing frameshifted peptides within the ...	1989	2502700
the genomic identity of different strains of mouse scrapie is expressed in hamsters and preserved on reisolation in mice.	263k is the most widely used strain of agent in scrapie research because it produces very short incubation periods in golden hamsters and exceptionally high infectivity titres in clinically affected brain. 263k is also remarkable in having a very low pathogenicity for mice. evidence is presented that 263k originated as a mutant that was strongly selected on passage in hamsters. seven new passage lines have been established in hamsters using well characterized strains of mouse scrapie representin ...	1989	2504883
asparagine-linked glycosylation of the scrapie and cellular prion proteins.	post-translational modification of the scrapie prion protein (prp) is thought to account for the unusual features of this protein. molecular cloning of a prp cdna identified two potential asn-linked glycosylation sites. both the scrapie (prpsc) and cellular (prpc) isoforms were susceptible to digestion by peptide n-glycosidase f (pngase f) but resistant to endoglycosidase h as measured by migration in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. pngase f digestion of prpc yielded t ...	1989	2505674
polyclonal increase in certain igg subclasses in mice persistently infected with the 87v strain of scrapie.	eight different combinations of seven strains of scrapie agent and the three known sinc genotypes of mice were screened for changes in the concentration of igg in serum. a single radial immunodiffusion assay was used to measure igg throughout the incubation period which in different models ranged from an average of 125 days to longer than the maximum observation period of about 600 days. the only major changes occurred with the 87v strain of scrapie injected intracerebrally (i.c.) or intraperito ...	1989	2507597
acceleration of scrapie in neonatal syrian hamsters.	prions cause creutzfeldt-jakob disease, gerstmann-sträussler syndrome, and kuru of humans as well as scrapie of animals. prolonged incubation periods, from months to decades, precede clinical disease. in studies on the biochemical characteristics of prions, weanling syrian hamsters have been used extensively because they have relatively short incubation periods. in studies reported here, inoculation of neonatal hamsters significantly shortened the scrapie incubation period even further. our resu ...	1989	2507957
amphotericin b: a novel class of antiscrapie drugs.	amphotericin b (amb) has been able to lengthen the incubation period of intracerebrally (ic) scrapie-injected hamsters to 45 d. this article reports a linear relationship between amb doses and the duration of the incubation periods of ic-treated animals compared with controls, a greater effect of amb treatment administered 2 w before or the same day of ic scrapie incubation, and the ineffectiveness of mepartricin, an amb analogue, in prolonging the incubation period of ic scrapie-injected hamste ...	1989	2509571
levels of infectivity in the blood throughout the incubation period of hamsters peripherally injected with scrapie.	viremia is found in intraperitoneally scrapie-injected hamsters. the absence of a viremic peak before the beginning of scrapie replication in the brain suggests either that the spread of the agent to the brain is not via the blood or that early after infection, circulating monocytes carry the agent to the brain where it remains silent until the neural cells start replicating it.	1989	2512893
enucleation after intraocular scrapie injection delays the spread of infection.	after right intraocular infection, mice develop lesions in the contralateral retinal projections long before clinical disease occurs. enucleation up to 7 days post-infection prevented targeting of lesions to visual projections, and prolonged the incubation period. when enucleation was delayed until at least 14 days post-infection, lesion targeting and incubation periods were similar to unenucleated mice. it was concluded that infectivity took a minimum of 14 days to reach the brain via the optic ...	1989	2513087
transport and targeting of scrapie infectivity and pathology in the optic nerve projections following intraocular infection.	the initial development of scrapie lesions can be seen following intraocular infection to be directly related to sequential infection of connecting neuronal relays within the projections of the optic nerve. for example, intraocular infection of vm mice with 22a virus produces lesions in the contralateral dorsal lateral geniculate nucleus (dlgn) and superior colliculus around halfway through the incubation period of about 360 days; the next lesions appear in the visual cortex, presumably as a res ...	1989	2513583
the scrapie disease process is unaffected by ionising radiation.	the incubation period of scrapie, its degenerative neuropathology and the replication of its causal unconventional virus are all tightly controlled parameters of the experimental disease in mice. each parameter can vary depending on the strain and dose of virus, on the route of infection, and on the host genotype. exposure to whole-body gamma-irradiation from caesium 137 has no effect on the progress or development of the disease, based on the three independent indices of incubation period, neur ...	1989	2513584
sulfated glycosaminoglycans in amyloid plaques of prion diseases.	brain sections from cases of human creutzfeldt-jakob disease, gerstmann-sträussler syndrome, kuru, and hamster scrapie containing amyloid were examined for the presence of sulfated glycosaminoglycans (gags), the anionic component of proteoglycans, using the sulfated alcian blue method and alcian blue technique with 0.3 m and 0.7 m magnesium chloride. these studies suggest that sulfated glycosaminoglycans are part of the cns amyloid plaques in each of the above human prion disorders as well as in ...	1989	2523631
an electron microscopic study of inclusion bodies in synaptic terminals of scrapie-infected animals.	inclusion bodies consisting of vesicles of about 25 nm diameter and occurring in the synaptic terminals of scrapie-infected animals have been described by a number of people. in the present study these inclusion bodies were looked for in the neocortex, hippocampus and corpus callosum in a variety of strains of mice (c3h, lm, riii, im, vl) infected with different strains of scrapie agent (22c, 79a, me7, 87v) after intracerebral inoculation. in plaque-bearing models of scrapie, terminals containin ...	1989	2540611
precise targeting of the pathology of the sialoglycoprotein, prp, and vacuolar degeneration in mouse scrapie.	widespread immunostaining of prp protein was demonstrated in scrapie mouse brain, distributed diffusely in the neuropil and focally in amyloid plaques, microglia and 2-5 microns structures resembling neuronal processes. with the 87v scrapie strain, which produces focal vacuolation in particular areas, prp pathology was precisely targeted to these same areas, predating vacuolar degeneration by at least several weeks. on the other hand, both vacuolar and prp changes were widely distributed through ...	1989	2550852
prion protein biosynthesis in scrapie-infected and uninfected neuroblastoma cells.	numerous studies have indicated that a modified proteinase k-resistant form of an endogenous brain protein, prion protein (prp), is associated with scrapie infection in animals. this scrapie-associated prp modification appears to occur posttranslationally in brain, but its molecular nature is not known. to learn about the normal prp biosynthesis and whether it is altered by scrapie infection in vitro, we did metabolic labeling experiments with uninfected and scrapie-infected mouse neuroblastoma ...	1989	2562814
infectivity of unconventional viruses in dura mater.		1989	2563815
apparent non-involvement of prions in the pathogenesis of spongiform change in hiv-infected brain.	characteristic neuropathological white matter changes in the brains of patients dying from the acquired immune deficiency syndrome (aids) suggest pathogenetic involvement of either the prp27-30 gene or a scrapie-related prion; however, proteinase-k resistant scrapie-like proteins could not be detected in brain tissue from aids patients.	1989	2564045
linkage of a prion protein missense variant to gerstmann-sträussler syndrome.	gerstmann-sträussler syndrome is a rare familial neurodegenerative condition that is vertically transmitted, in an apparently autosomal dominant way. it can also be horizontally transmitted to non-human primates and rodents through intracerebral inoculation of brain homogenates from patients with the disease. the exact incidence of the syndrome is unknown but is estimated to be between one and ten per hundred million. patients initially suffer from ataxia or dementia and deteriorate until they d ...	1989	2564168
evidence of mitochondrial involvement in scrapie infection.	two cdna libraries were constructed from brain membrane and cytoskeletal preparations purified from scrapie-infected hamster brains. four recombinants strongly preferential to the scrapie cytoskeletal preparation were identified by the differential hybridization of 7,000 recombinants. these clones were not, however, preferential to total nucleic acids extracted from scrapie-infected hamster brains. dna sequence analysis revealed all four clones to have significant sequence similarities to the mo ...	1989	2564438
isolation and purification of scrapie-associated fibrils and prion protein from scrapie-infected hamster brain.	we report the purification of prion protein (prp) 27-30 and scrapie-associated fibrils (saf) from hamsters infected with the 263k strain of scrapie. sds-page of fractions purified from scrapie-infected brains revealed several bands at approximately 28.5 kda, 23.9 kda and 14.3 kda and, in one set of preparations, a protein of mr 26 kda was found in both scrapie-infected and sham-inoculated animals. the specificity of prps was confirmed by western blotting. ultrastructural analysis of fractions fr ...	1989	2565919
linkage of the gene for the scrapie-associated fibril protein (prp) to the sip gene in cheviot sheep.	the gene sip with two alleles, sa and pa, is the major gene determining the incubation period of scrapie in its natural host, sheep. two lines of cheviot sheep have been bred which differ in their response to experimental infection with ssbp/1 scrapie. the negative line have a decreased incidence of disease caused by ssbp/1 and are sippapa. the positive line have an increased incidence of disease and the majority are either sipsasa or sipsapa; it is not possible to distinguish between the two ge ...	1989	2566212
structural and biochemical evidence that scrapie-associated fibrils assemble in vivo.	scrapie-associated fibrils (saf) are a ubiquitous pathological feature of brains affected by scrapie and the other scrapie-like agents. they are composed of prp, a heterogeneous glycoprotein which is also present in normal brain but not as saf. the prp protein associated with saf is partially resistant to proteinase k, whereas the soluble form is not. it has been proposed that saf do not exist as such in vivo, but rather self-assemble from subunit structures liberated from membranes by detergent ...	1989	2567338
creutzfeldt-jakob disease and scrapie prions.	creutzfeldt-jakob disease, kuru, and gerstmann-sträussler syndrome are transmissible degenerative diseases of the central nervous system caused by novel infectious pathogens designated prions. scrapie is a neurodegenerative disease of sheep and goats and is also caused by prions. experimental scrapie has been extensively studied in hamsters and mice. the scrapie prion protein (prpsc) is the only component of the infectious scrapie prion identified, to date. scrapie infectivity and prpsc copartit ...	1989	2568118
the nature of the unconventional slow infection agents remains a puzzle.	unconventional slow infections are progressive transmissible degenerative disorders of the central nervous system. the human diseases belonging to this group are creutzfeld-jakob disease, kuru, and gerstmann-straussler syndrome. scrapie, transmissible mink encephalopathy, chronic wasting disease of mule deer and elk, and the recently discovered bovine spongiform encephalopathy are similar diseases found in animals. unusual characteristics of the unconventional slow infections clearly distinguish ...	1989	2568119
post-mortem immunodiagnosis of scrapie and bovine spongiform encephalopathy.	two polyclonal antisera were raised in rabbits against the scrapie-associated fibril protein (prp) prepared from sheep and mice which were terminally infected with experimental scrapie. the anti-mouse prp serum identifies the proteins of scrapie-associated fibrils (saf) from all the host species studied (mouse, hamster, sheep and goat) and bovine spongiform encephalopathy (bse) fibrils from cow. the anti-sheep prp serum displays species restricted immunoreactivity. while it identifies several pr ...	1989	2569471
scrapie prions.		1989	2572197
mutations in familial creutzfeldt-jakob disease and gerstmann-sträussler-scheinker's syndrome.	a host protein encoded by the gene specifying the scrapie amyloid precursor affects pathogenesis of the transmissible spongiform encephalopathies: creutzfeldt-jakob disease (cjd), gerstmann-sträussler-scheinker's syndrome (gss), and kuru in man, and scrapie in animals. we found a mutation in this gene of two patients with cjd from one family and a second mutation in the same gene in three patients with gss from another family. the mutation in two related familial cjd patients changed glutamine i ...	1989	2572450
transgenic mice expressing hamster prion protein produce species-specific scrapie infectivity and amyloid plaques.	three transgenic mouse lines designated tg 69, 71, and 81 were produced harboring a syrian hamster (ha) prion protein (prp) gene; all expressed the cellular haprp isoform in their brains. inoculation of tg 81 mice or hamsters with ha prions caused scrapie in integral of 75 days; nontransgenic control mice failed to develop scrapie after greater than 500 days. tg 71 mice inoculated with ha prions developed scrapie in integral of 170 days. both tg 71 and tg 81 mice exhibited spongiform degeneratio ...	1989	2574076
introduction to scrapie and perspectives on current scrapie research.	scrapie is the prototype of a family of six transmissible diseases which includes creutzfeldt-jakob disease, the only known transmissible human dementia. bovine spongiform encephalopathy is the most recent addition to the family. alzheimer's disease is not known to be transmissible. however the pathogenesis of both scrapie and alzheimer's disease is associated with the modification of (different) normal brain proteins to form various types of amyloid. in scrapie, the evidence suggests that a mem ...	1989	2574870
immunoaffinity purification and neutralization of scrapie prions.	the scrapie agent causes a degenerative neurologic disease and can be transmitted to laboratory rodents. the unusual properties of the scrapie agent prompted introduction of the term prion in order to distinguish this class of novel pathogens from viruses and viroids. the scrapie prion protein (prpsc) is the only component of the infectious scrapie prion identified, to date. although many biochemical and genetic lines of evidence argue that prpsc is a major component of the infectious particle, ...	1989	2574871
prpsc in scrapie-infected hamster brain is spatially and temporally related to histopathology and infectivity titer.		1989	2574872
comparative sequence analysis, in vitro expression and biosynthesis of mouse prp.	a number of studies have indicated that an endogenous brain protein, prp, is associated with transmissible agents causing spongiform encephalopathies such as scrapie, kuru, and creutzfeldt-jakob disease. it has been proposed that prp derived from scrapie brain is the scrapie agent itself. to test directly whether the prp mrna in scrapie brain tissue can encode the scrapie agent, we expressed prp cdna cloned from scrapie-infected mouse brain in vitro. the expressed prp did not transmit scrapie to ...	1989	2574873
the molecular pathology of scrapie and the biological basis of lesion targeting.	strains of scrapie virus can only be distinguished from the incubation period and neuropathology of the disease they induce in mice of different sinc genotypes. there are two main aspects of the neuropathology: a spongiosis or degenerative vacuolation associated with the replication of virus, and cerebral amyloid plaques. the relationship between these two is unclear - they can occupy topographically quite different centres in the cns and the timing of their occurrence is different. surprisingly ...	1989	2574874
bovine spongiform encephalopathy: a scrapie-like disease of british cattle.	scrapie is a cns degenerative infection of sheep and goats, which is invariably fatal after incubation periods of several months to years. related disorders are found naturally in man and other species. there is a impairment of protein catabolism in scrapie and related diseases which leads to the accumulation of sparingly-soluble protein deposits in brain. these protein aggregates may share with the amyloid of alzheimer's disease (ad) some common stage in the biochemical pathways of their format ...	1989	2574875
diversity of oligosaccharide structures linked to asparagines of the scrapie prion protein.	prion proteins from humans and rodents contain two consensus sites for asparagine-linked glycosylation near their c-termini. the asparagine-linked oligosaccharides of the scrapie isoform of the hamster prion protein (prp 27-30) were released quantitatively from the purified molecule by hydrazinolysis followed by n-acetylation and nab3h4 reduction. the radioactive oligosaccharides were fractionated into one neutral and three acidic oligosaccharide fractions by anion-exchange column chromatography ...	1989	2574992
organ distribution of proteinase-resistant prion protein in humans and mice with creutzfeldt-jakob disease.	we attempted to clarify the organ distribution of human and murine proteinase-resistant prion protein (prpcjd) in creutzfeldt-jakob disease (cjd), and to measure the concentration of prpcjd, using a semi-quantitative western blot analysis. human prpcjd was restricted to the central nervous system, whereas murine prpcjd was present in the central nervous system and in the lymphoreticular system at the end stage of cjd. prpcjd concentration in the central nervous system of mice was almost identica ...	1989	2575138
scrapie in goats in cyprus.	ovine scrapie was first recorded in cyprus in 1985. subsequently four dairy goats kept in two mixed flocks with affected sheep developed characteristic clinical signs similar to those seen in sheep. fifteen goats from the two flocks were examined histologically and neurological lesions consistent with a diagnosis of scrapie were found in the four animals and in three others which had subsequently developed early neurological signs. these lesions were similar to those of naturally-affected sheep ...	1989	16031555
scrapie: report of an outbreak and brief review.	an outbreak of scrapie in western canada is described. the disease was confirmed in seven sheep, all originating from the same flock; six were suffolk ewes and one was a hampshire ewe. the main clinical signs were pruritus with a positive "nibbling reflex", weight loss and seizures precipitated by handling or excitement. at presentation four ewes were between 35 and 38 months of age; two were approximately four years old and the oldest was six years old. no evidence of scrapie was seen in six go ...	1989	17423289
ontario. incidental neoplasia during experiments on scrapie in white swiss mice.		1990	17423668
scrapie in sheep and goats.		1990	2075694
experimental scrapie in white swiss mice.	in order to confirm the clinical and histological diagnosis of scrapie and to determine the infectivity titer of the scrapie agent in the brain of a naturally infected suffolk sheep, 123 white swiss mice were inoculated intracerebrally. from about 13 to 20 months post-inoculation, 28 mice died, and 95 that were sick were killed. in the terminal stages of disease, the mice developed weakness, gradual emaciation, posterior ataxia, and occasionally alopecia. the average infection (83%) of mice affe ...	1990	2082631
cytoskeletal messenger rna stability in human neocortex: studies in normal aging and in alzheimer's disease.	total rna was extracted from human brain temporal and parietotemporal neocortical grey matter with postmortem intervals (pmi) of up to 13.5 hours. the integrity and rank abundance of heterogeneous nuclear rna (hnrna) and messenger rna (mrna) were analyzed by northern gel dot blot hybridization with specific cloned probes of neurobiological interest: the rna messages for four cytoskeletal components including glial fibrillary acidic protein (gfap), alpha-tubulin, beta-actin and the human neurofil ...	1990	2084053
[the biology of prions, a response to the enigma of spongiform encephalopathies of sheep and humans].	prions are small proteinaceous infectious particles without nucleic acids. the prion protein arise from a cellular protein by a post-transduction event and constitute amyloid deposits. prions are the agent of animal and human spongiform encephalopathies which evolve on simultaneous infectious and genetic dependence in the absence of a detectable immune response.	1990	2094563
mad cows and englishmen: bovine spongiform encephalopathy.		1990	2096311