Publications
| Title | Abstract | Year(sorted ascending) Filter | PMID Filter |
|---|
| the epidemiology of creutzfeldt-jakob disease: conclusion of a 15-year investigation in france and review of the world literature. | during the 15-year period 1968-1982, a total of 329 patients dying of creutzfeldt-jakob disease (cjd) were identified in continental france. annual mortality rates stabilized at 0.5 to 0.6 cases per million (1.1 to 1.2 cases per million in paris). six percent of cases were familial. although the frequency of cjd was related to population density, no contacts could be established among the great majority of patients. no association with socioeconomic factors, preceding trauma or surgery (exceptin ... | 1987 | 3295589 |
| immunoblotting of creutzfeldt-jakob disease prion proteins: host species-specific epitopes. | creutzfeldt-jakob disease (cjd) is a rare dementia that is generally found in older people and is caused by unusual infectious pathogens or prions. using rabbit antisera raised against hamster scrapie prion proteins (haprpsc), we identified by immunoblotting human cjd prion proteins (huprpcjd) in the brains of 14 patients dying of cjd. extracts from 6 of the patients were transmitted to mice after prolonged incubation. the rabbit antisera raised against haprpsc also reacted with the mouse cjd pr ... | 1987 | 3300520 |
| [creutzfeldt-jakob disease: report of a case]. | a case of creutzfeldt-jakob disease (cjd) in a 76 year-old man is presented. the clinical picture included a rapid progressive dementia associated with ataxia, global aphasia, myoclonus and pyramidal signs; death occurred after about 4 months. there was an antecedent of chemical trauma caused by plant liquid on right eye 12 to 18 months before. the electroencephalogram showed diffuse slow activity and the neuropathological findings were typical. the detection of a protein called "prion" or prp27 ... | 1987 | 3300614 |
| iatrogenic creutzfeldt-jakob disease. | over the past 2 years, creutzfeldt-jakob disease (cjd) has affected several patients who received cadaver pituitary-derived growth hormone (pit-hgh) and one patient who received a cadaveric dura mater graft. the risk of iatrogenic transmission of cjd has long been recognized, but until recently, the low prevalence of the disorder and minimal use of therapeutic products derived from human tissues may have limited the risk. from 1963 to 1985, approximately 10,000 children received pit-hgh. these p ... | 1987 | 3306455 |
| tubulofilaments in negatively stained scrapie-infected brains: relationship to scrapie-associated fibrils. | a simple method was devised for negative-stain transmission electron microscopy of brain infected with the agent of scrapie. brains of infected hamsters contained large masses of tubulofilamentous structures with irregular fuzzy surfaces. brains of mice infected with creutzfeldt-jakob disease agent contained similar tubulofilaments in smaller numbers. the abnormal tubulofilaments resembled but were distinguished from normal microtubules. on grids soaked in sodium dodecyl sulfate the abnormal tub ... | 1987 | 3313402 |
| molecular and genetic aspects of the pathogenesis of viral infections of the central nervous system. | viral pathogenesis can be defined in terms of a series of successive interactions between a virus and its target host. in order for a virus to injure a target organ such as the central nervous system (cns), it must first enter the host animal, replicate in some primary site near its place of entry, spread from this site to the cns and infect and injure specific populations of cells within the cns. at each of these steps, the virus must avoid or overcome a variety of immunological and nonimmunolo ... | 1987 | 3315238 |
| the comparative immunoreactivities of brain amyloids in alzheimer's disease and scrapie. | an antibody was raised to a synthetic peptide corresponding to a published sequence for the first 24 residues of a cerebrovascular amyloid peptide (cvap). immunohistochemical staining of tissue sections revealed that the antibody bound extensively to cerebrovascular amyloid in alzheimer disease (ad/sdat) and down's syndrome cases. the antibody bound less extensively to neuritic plaques (primitive and mature) and indetectably to neurofibrillary tangles. the antibody did not label scrapie plaques, ... | 1987 | 3318271 |
| [slow viruses]. | 1987 | 3321384 | |
| characterization of scrapie infection in mouse neuroblastoma cells. | a mouse neuroblastoma cell line was successfully infected with scrapie agent. agent derived from infected mouse brain or spleen infected cultures. however, agent from infected hamsters did not infect mouse cell cultures, suggesting that species specificity influenced the infection process in vitro. positive cultures supported scrapie replication for as many as 47 passages in vitro. agent was shown to be cell-associated and between 631 and 7943 unselected culture cells constituted 1 mouse ld50. h ... | 1987 | 3106566 |
| scrapie, an unconventional virus: the current views. | 1987 | 3104917 | |
| effects of different methods of purification on aggregation of scrapie infectivity. | high levels of scrapie infectivity were found in detergent-insoluble residues of hamster brain purified by either repeated pelleting in 10% nacl or by separation in nycodenz gradients. titres determined by the method of incubation interval assay were 100-fold higher than titres measured by endpoint dilution assay. the protein profiles and end-labelled rna examined by one-dimensional polyacrylamide gel electrophoresis were not different from samples prepared from uninfected brain. preparations pr ... | 1987 | 3100716 |
| biological evidence that scrapie agent has an independent genome. | there are many distinct strains of scrapie agent, identified by their relative incubation periods and quantitative and qualitative neuropathological properties in inbred mice of particular genotypes. when serially passaged under specified conditions of mouse strain, route of infection and dose of infectivity these properties are stable. however, they may change in a predictable manner if the passage strategy is altered. the scrapie strain 87a shows what has previously been defined as class iii s ... | 1987 | 3100717 |
| aids virus and scrapie protein genes. | 1987 | 3100963 | |
| genetic control of scrapie: incubation period and plaque formation in i mice. | the host component of control of scrapie incubation period in the mouse is manifested largely through the action of the sinc gene. only one mouse strain (vm) has been found that is p7p7 (prolonged incubation for me7 agent) and two other strains have been derived from vm. all other strains, designated s7s7, have a short incubation for me7. in the present study, the i strain was shown to fulfil the criteria that are characteristic of mouse strains with the p7 allele of sinc: a comparatively long i ... | 1987 | 3102684 |
| comparison of scrapie associated fibril detection and histology in the diagnosis of natural sheep scrapie. | 1987 | 3125660 | |
| evidence for a secretory form of the cellular prion protein. | the biogenesis of hamster brain prion protein (prp) has been studied by expression of rna transcribed from a full-length prp cdna in xenopus oocytes and cell-free systems. earlier studies in the wheat germ cell-free system showed that one form of prp is a transmembrane protein that spans the bilayer at least twice [hay, b., barry, r. a., lieberburg, i., prusiner, s. b., & lingappa, v. r. (1987) mol. cell. biol. 7, 914-920]. we now report that prp can also exist as a secreted protein. sp6 prp rna ... | 1987 | 3126796 |
| photoreceptor degeneration during infection with various strains of the scrapie agent in hamsters. | hamsters were inoculated intracerebrally with the 22c, 79a, and me7 strains of the scrapie agent to compare the effects on the retina with those caused by strain 263k. the animals developed clinical signs of encephalopathy. photoreceptor degeneration occurred in all experimental animals. the changes were similar to those seen in animals infected with the 263k strain of scrapie although somewhat more variable and less extensive. | 1987 | 3108023 |
| purified prion proteins and scrapie infectivity copartition into liposomes. | considerable evidence indicates that the scrapie prion protein (prp 27-30) is required for infectivity. aggregates of prp 27-30 form insoluble amyloid rods that resist dissociation by nondenaturing detergents. mixtures of the detergent cholate and phospholipids were found to solubilize purified prp 27-30 in the form of detergent-lipid-protein complexes. removal of the cholate by dialysis resulted in the formation of closed liposomes. both the detergent-lipid-protein complexes and the liposomes o ... | 1987 | 3108886 |
| temporary and permanent modifications to a single strain of mouse scrapie on transmission to rats and hamsters. | the interspecies transmission of scrapie is frequently associated with exceptionally long incubation periods at first passage in the new host compared to later passages (the species barrier effect). the basis of this was investigated using the 139a strain of scrapie which had been cloned by three serial passages in mice at limiting infectious doses. cloned scrapie was passaged through hamsters (twice) or rats (thrice) and then reisolated in mice. large species barrier effects were encountered on ... | 1987 | 3110370 |
| [biology of the infectious scrapie agent]. | 1987 | 3110752 | |
| changes in the localization of brain prion proteins during scrapie infection. | prion proteins (prp) were localized in the brains of normal and scrapie-infected hamsters by immunohistochemistry and western blotting. prp monoclonal antibodies and monospecific anti-prp peptide sera, which react with both the cellular (prpc) and scrapie (prpsc) isoforms of the prion protein, were used to locate prp in tissue sections. in normal hamsters, prpc was located primarily in nerve cell bodies throughout the cns; whereas, in the terminal stages of scrapie, prp immunoreactivity was shif ... | 1987 | 3112607 |
| amyloid scrapie plaques in mice, and alzheimer senile plaques, share common antigens with tau, a microtubule-associated protein. | immunolabelling was performed on brain sections of scrapie-infected mice with antibodies against tau, a microtubule-associated protein, and against the paired helical filaments of alzheimer's disease. both kinds of antibodies have been shown previously to label paired helical filaments in neurons and in abnormal neurites associated with the senile plaques of alzheimer's disease. amyloid plaques in murine scrapie were labelled by both antisera. the structural substrate for the immunolabelling was ... | 1987 | 3112659 |
| purified scrapie prions resist inactivation by procedures that hydrolyze, modify, or shear nucleic acids. | prions were purified from scrapie-infected hamster brains and incubated for 24 hr at 65 degrees with 2 mm zn2+ or 5 mm mg2+; no loss of infectivity was observed. bacteriophage m13, tobacco mosaic virus (tmv), potato virus x, and potato spindle tuber viroid were all inactivated by divalent metal ions under these conditions. prions also resisted inactivation by prolonged digestions with dnase i, rnases a and t1, and micrococcal nuclease. prions were resistant to psoralen photoadduct formation usin ... | 1987 | 3114950 |
| immunochemical characterization of proteins from scrapie-infected hamster brain, using immunoblot analysis. | preparations of brain plasma membrane from scrapie-infected or noninfected hamsters were extracted with a solvent and were used to inoculate rabbits. antisera evaluated by immunoblot analysis revealed a protein of 45 kd in scrapie-infected hamster brain that had a greater signal compared with proteins of comparable relative mass in noninfected brain. this 45-kd protein was not increased in scrapie-infected mouse, sheep, or goat brain. seemingly, the 45-kd protein may be a degradation product of ... | 1987 | 3115155 |
| the brain fine structure in experimental scrapie. the 263k strain in golden syrian hamsters. | 1987 | 3116454 | |
| [role of phagocytes in experimental scrapie in hamsters]. | we studied the interactions between scrapie agent and hamster's phagocytic cells. macrophages which have been in contact with the scrapie agent are able to carry the infectivity of this agent. we induced variations of different parameters involved on fixation and phagocytosis and we did not observe any modification. a depletion of phagocytic cells induced in hamster at the entry of scrapie increase the incubation time of the illness. furthermore phagocytic cells cocultured with glial cells seem ... | 1987 | 3116644 |
| ionising radiation has no influence on scrapie incubation period in mice. | scrapie has an early non-clinical stage when replication of agent occurs in lymphoreticular organs. whole-body irradiation failed to alter the incubation or neuropathology of the disease. many experiments were carried out with different strains of scrapie agent and host, doses and timing of irradiation. the results suggest that mitotically quiescent cells are involved in agent replication. | 1987 | 3116748 |
| autoclaved, formol-fixed scrapie mouse brain is suitable for histopathological examination, but may still be infective. | autoclaving creutzfeldt-jakob disease (cjd)-infected brain after fixation has been proposed previously as a means of making it safe for handling in the laboratory, while preserving its microscopic integrity. however, the practice which was recommended (126 degrees c for 30 min) would be unlikely to achieve complete decontamination. autoclaving scrapie mouse brain (an analogue for cjd) to the higher, recommended standard of 134-138 degrees c for 18 min was found to lead to some tissue damage but ... | 1987 | 3118629 |
| [neuronal reaction of the central nervous system to infection by the scrapie agent in mice in the preclinical period of the pathogenesis of the experimental infection]. | 1987 | 3120418 | |
| [scrapie agent]. | 1987 | 3124085 | |
| purified scrapie prions resist inactivation by uv irradiation. | the development of effective purification protocols has permitted evaluation of the resistance of isolated scrapie prions to inactivation by uv irradiation at 254 nm. prions were irradiated on ice with doses of uv light ranging up to 120,000 j/m2. uv dosimetry experiments, performed with saccharomyces cerevisiae plasmid dna or eucaryotic cells, indicated that under these experimental conditions an incident uv dose of 10 j/m2 formed 2 thymine dimers per 5.1 x 10(6) daltons of eucaryotic cell dna. ... | 1987 | 3097336 |
| predicted secondary structure and membrane topology of the scrapie prion protein. | the integral membrane sialoglycoprotein prpsc is the only identifiable component of the scrapie prion. scrapie in animals and creutzfeldt-jakob disease in humans are transmissible, degenerative neurological diseases caused by prions. standard predictive strategies have been used to analyze the secondary structure of the prion protein in conjunction with fourier analysis of the primary sequence hydrophobicities to detect potential amphipathic regions. several hydrophobic segments, a proline- and ... | 1987 | 2907134 |
| isolation and characterization of macrophages from scrapie-infected mouse brain. | we have isolated and characterized a population of brain macrophages from normal and scrapie-infected mice. the cells are phagocytic, possess fc-igg receptors, mac-1 surface antigen and proliferate in the presence of macrophage colony stimulating factor. they resemble microglia in that they have a plasmalemmal distribution of the enzyme nucleoside diphosphatase, a property tht is characteristic of microglia in situ. in two of the three combinations of scrapie agent and mouse strain examined, the ... | 1987 | 3031922 |
| experimental infection of sheep and goats with transmissible mink encephalopathy virus. | in a study to learn more about the pathogenicity of transmissible mink encephalopathy virus for the natural hosts of scrapie, 20 cheviot sheep and 19 dairy goats were inoculated intracerebrally with the idaho strain of the virus. five sheep and nine goats became affected with a progressive neurological disease. the incubation period in the sheep varied from 45 to 80 months (mean, 65 months) and in the goats from 31 to 40 months (mean, 35 months). except for degeneration of the cerebral cortex (n ... | 1987 | 2952237 |
| photoreceptor degeneration in experimental transmissible mink encephalopathy of hamsters. | hamsters were inoculated intracerebrally with the agent of transmissible mink encephalopathy and developed clerical signs of encephalopathy. photoreceptor degeneration occurred in all animals examined histologically. the changes were similar to those in scrapie, although less extensive. the findings suggest that either transmissible mink encephalopathy is a mink-adapted form of scrapie or, in rodents, photoreceptor degeneration is a characteristic of infection with agents of the spongiform encep ... | 1987 | 2953620 |
| temporal distribution of transmissible mink encephalopathy virus in mink inoculated subcutaneously. | information was sought on the temporal distribution of transmissible mink encephalopathy virus in royal pastel mink inoculated subcutaneously with 10(3.0) 50% intracerebral lethal doses of the idaho strain. as determined by intracerebral assay in mink, extremely little replication of the virus occurred during the preclinical stage of infection. it seemed largely limited to lymph nodes draining the site of inoculation. virus first appeared in the central nervous system (cns) at 20 weeks, when all ... | 1987 | 2957510 |
| antisera to scrapie-associated fibril protein and prion protein decorate scrapie-associated fibrils. | scrapie-associated fibrils (saf) are an infection-specific structure observed in the unconventional-agent diseases. polyclonal antisera raised to scrapie proteins were used to test the antigenic relationship between purified fibrils and saf isolated from non-protease-treated synaptosomal-mitochondrial preparations. the experimental design utilized fibrils from scrapie strain 263k-infected hamsters, scrapie strain 139a-infected mice, and scrapie strain me7-infected mice. preparations were examine ... | 1987 | 2878092 |
| prions causing nervous system degeneration. | 1987 | 2882063 | |
| persistence of the scrapie agent in glial cells from rat gasserian ganglion. | persistence of the scrapie agent in glial cell monolayers from rat gasserian ganglion have been studied by electron microscopy, virologic and histologic methods. under chosen experimental conditions the scrapie agent had been shown to persist in cells for over 2 years. the infected cells appeared to be infectious for balb/c mice throughout. persistence of the scrapie agent was associated with development of a marked proliferative effect with increasing mitotic index of the cells. changes similar ... | 1987 | 2883856 |
| prp and the nature of the scrapie agent. | 1987 | 2884041 | |
| detection of scrapie-associated fibrils (saf) and saf proteins from scrapie-affected sheep. | scrapie-associated fibrils (saf) were detected by negative-stain electron microscopy in the brains (by two different isolation procedures) and spleens of sheep naturally and experimentally infected with scrapie. although the numbers of saf varied from case to case, the yield of saf from brains of naturally affected sheep was lower than that from experimentally affected sheep. saf-specific, protease-resistant proteins (prps) were detected by silver staining and western blot analysis in most sampl ... | 1987 | 2885382 |
| linkage of the scrapie-associated fibril protein (prp) gene and sinc using congenic mice and restriction fragment length polymorphism analysis. | sinc, with two alleles p7 and s7, is the major gene determining the incubation period of all strains of scrapie in mice. the major protein (prp) of scrapie-associated fibrils is encoded by a cellular gene and we have used a cdna copy of the hamster prp mrna to carry out restriction fragment length polymorphism (rflp) analysis of different inbred mouse strains including vm(sincp7) and vm(sincs7) congenic mice. in vm(sincp7) mice, a 5.5 kb xbai fragment hybridized to the prp cdna sequence whereas ... | 1987 | 2889794 |
| cloning of rat "prion-related protein" cdna. | rat prion-related protein (prp) cdna has been cloned and sequenced. comparison of this cdna with those from human, hamster, and mouse indicates extremely high conservation (about 95%). the deduced partial rat prp possesses: (a) a highly conserved region composed of repetitive sequences in what is presumably an extracellular domain, (b) a hydrophobic transmembrane domain, (c) a highly charged region which should stop membrane transfer, (d) a substantial cytoplasmic domain (which contains all of t ... | 1987 | 2889848 |
| no evidence for involvement of plasma proteins or blood-borne cells in amyloid plaque formation in scrapie-affected mice. an immunohistoperoxidase study. | the present study was designed to investigate blood-brain permeability and the possible involvement of plasma proteins and blood-borne cells in amyloid plaque formation in scrapie-affected mice. no abnormal extravasation of intravenously injected horseradish peroxidase (hrp) was found and with immunocytochemical techniques no plasma proteins were detected in neuropil from scrapie-affected mice. in contrast to an earlier report, these findings suggest that the blood-brain barrier is essentially i ... | 1987 | 2890238 |
| isolation and structural studies of the intact scrapie agent protein. | purification of the scrapie agent by methods using digestion with proteinase k yields a protein product, prp-27-30, with an apparent mass of 27-30 kda (d. c. bolton et al. (1982) science 218, 1309-1311; s. b. prusiner et al. (1982) biochemistry 21, 6942-6950). in contrast, a 33-37 kda glycoprotein, hasp33-37, was the major protein component isolated from scrapie-affected hamster brain by a procedure that did not use protease digestion. the purified fractions containing hasp33-37 had greater than ... | 1987 | 2890330 |
| distinct prion proteins in short and long scrapie incubation period mice. | the prn-i gene, controlling scrapie incubation period, is linked to or congruent with the murine prion protein (prp) gene, prn-p. in prototypic mouse strains with long (l/ln) and short (nzw) incubation periods, prn-p transcription is initiated at similar multiple sites. the predicted nzw and l/ln prp proteins differ at codons 108 and 189. codon 189, highly conserved in mammals, lies within a polymorphic bstell site that is retained in 17 mouse strains known to have short or intermediate incubati ... | 1987 | 2890436 |
| the burden of proof in linking aids to scrapie. | 1987 | 2891035 | |
| immuno-gold localization of prion filaments in scrapie-infected hamster brains. | the brains of scrapie-infected hamsters have been examined for the presence of structures antigenically related to the prion protein (prp 27-30). glutaraldehyde-perfused hamster brains, 72 days postinfection, were immunostained using rabbit monospecific antisera raised against synthetic peptides corresponding to the n-terminal 13 or 15 amino acids of prp 27-30, and using rabbit antisera raised against infectious prions or prp 27-30 purified from scrapie-infected hamster brains. antisera to the s ... | 1987 | 2891874 |
| antiserum to scrapie-associated fibril protein cross-reacts with spiroplasma mirum fibril proteins. | protease-resistant fibril proteins purified from spiroplasma mirum and from creutzfeldt-jakob disease-infected brain tissues reacted with antisera to scrapie-associated fibrils on western immunoblot analysis. these data suggest that there are conformational similarities among spiroplasma proteins and infection-specific proteins of the transmissible spongiform encephalopathies. | 1987 | 2892856 |
| amphotericin b delays the incubation period of scrapie in intracerebrally inoculated hamsters. | the scrapie-infected hamster has been considered an excellent model for the study of slow virus diseases of man (creutzfeldt-jakob disease) and animals. at the moment no therapy is available for the cure of these fatal central nervous system diseases, although several drugs have been tested. we found that amphotericin b (amb), a polyene antibiotic, increased the incubation time of scrapie disease in animals infected by either the intraperitoneal or intracerebral route. hamsters inoculated with a ... | 1987 | 2433387 |
| is scrapie prp 27-30 related to aids virus? | 1987 | 2433599 | |
| impairment of the cortical and thalamic electrical activity in scrapie-infected rats. | cortical and thalamic eeg and somatosensory evoked potential (sep) induced by stimulation of the somesthetic radiations were studied in scrapie-infected rats. animals were inoculated intracerebrally with a rat-adapted strain (originating in the c506 m3 mouse scrapie strain). eeg and sep were recorded from 9 to 17 months after inoculation (ti). abnormalities (paroxysmal bursts, isolated spikes) first occurred in the cortex (parietal areas) and later in the thalamus, where they were usually less m ... | 1987 | 2434315 |
| formic acid pretreatment enhances immunostaining of cerebral and systemic amyloids. | the purpose of this study was to design a method by which immunoperoxidase staining can be applied to formalin-fixed, paraffin-embedded tissue sections to demonstrate amyloid deposits in cerebral and systemic amyloidotic tissues. we used anti-prion protein, anti-beta-protein, anti-amyloid a, and anti-prealbumin antisera. the tissue sections were first treated with 100% formic acid for 5, 20, or 60 minutes and the unlabeled immunoperoxidase method (biotin-streptavidin system reagents) was used. t ... | 1987 | 2441141 |
| developmental expression and regional distribution of the scrapie-associated protein mrna in the rat central nervous system. | the scrapie associated protein (sap) has been shown to be a normal brain protein of yet undefined function. this study demonstrates that rat brain sap mrna levels undergo a transcriptionally dependent increase during normal development. the interregional variation in the adult rat central nervous system (cns) is roughly 10 fold, with highest levels in the basal ganglion/thalamus and lowest levels in the spinal cord. | 1987 | 2443218 |
| scrapie prion protein contains a phosphatidylinositol glycolipid. | the scrapie (prpsc) and cellular (prpc) prion proteins are encoded by the same gene, and their different properties are thought to arise from posttranslational modifications. we have found a phosphatidylinositol glycolipid on both prpc and prp 27-30 (derived from prpsc by limited proteolysis at the amino terminus). ethanolamine, myo-inositol, phosphate, and stearic acid were identified as glycolipid components of gel-purified prp 27-30. prp 27-30 contains 2.8 moles of ethanolamine per mole. incu ... | 1987 | 2444340 |
| mouse polyclonal and monoclonal antibody to scrapie-associated fibril proteins. | antibody response in mice to scrapie-associated fibril proteins (protease-resistant proteins [prps]) was generated to different epitopes depending on the source of antigen. mice responded differently to prps isolated from scrapie-infected animals of homologous (mouse) versus heterologous (hamster) species. an enzyme-linked immunosorbent assay established to monitor this antibody response in mice immunized with prps was unable to detect such a response in scrapie-infected mice. a monoclonal antib ... | 1987 | 2446004 |
| autoclaving does not decontaminate formol-fixed scrapie tissues. | 1988 | 2455203 | |
| isolation of cdnas of scrapie-modulated rnas by subtractive hybridization of a cdna library. | we have developed a subtractive cloning procedure based on the hybridization of single-stranded cdna libraries constructed in pi h3m, a vector containing the phage m13 origin of replication. we have used this strategy to isolate three transcripts whose abundance is increased in scrapie-infected brain. dna sequence analysis showed that they represent glial fibrillary acidic protein, metallothionein ii, and the b chain of alpha-crystallin; the latter two may represent a response to stress. | 1988 | 2456582 |
| antiserum to scrapie-associated fibril protein reacts with amyloid plaques in familial transmissible dementia. | scrapie-associated fibrils (saf) are disease-specific markers for the unconventional agent-induced, transmissible spongiform encephalopathies. polyclonal rabbit antiserum to saf protein was reacted with brain sections from scrapie-infected mice, two familial cases of transmissible dementia, and three cases of alzheimer's disease (ad). specific immunostaining of cerebral amyloid plaques occurred in the scrapie-infected mice and in the two familial cases of transmissible dementia. no immunoreactiv ... | 1988 | 2892894 |
| molecular pathology of scrapie-associated fibril protein (prp) in mouse brain affected by the me7 strain of scrapie. | scrapie-associated fibrils (saf) are disease-specific structures found in extracts of the brains of animals affected with scrapie. these structures are pathological aggregates of a normal host protein (prp). abnormal post-translational modification of prp has been suggested to explain its aberrant properties in scrapie-affected brains and although there is a form of prp in saf indistinguishable in size from the protein in uninfected brain, lower-molecular-mass variants of prp are also found in s ... | 1988 | 2894984 |
| detection of prion protein mrna in normal and scrapie-infected tissues and cell lines. | prion protein (prp) forms the fibrils or prion rods isolated from scrapie-infected brain and has been proposed as the major component of the infectious agent of this slowly progressive spongiform encephalopathy. in previous northern blot analyses prp-specific mrnas have been found in both normal and scrapie-infected brains but not in spleen, an organ which harbours large titres of infectivity. in the present study, mouse prp dna was used to probe for prp mrna in assorted tissues and cells. a ree ... | 1988 | 2895163 |
| western blot detection of scrapie-associated fibril protein in tissues outside the central nervous system from preclinical scrapie-infected mice. | we describe a method of sample preparation to detect scrapie-associated fibril (saf) proteins in small amounts of scrapie-infected mouse tissues by western blot analysis using an antiserum to a synthetic peptide that corresponds to the n-terminal region of hamster prion protein. saf proteins were efficiently detected in brain tissue by this procedure. the proteins were also detected in preparations from spleen and lymph node. saf proteins were detected in brain samples at 24 weeks after intraper ... | 1988 | 2895800 |
| influence of stereotaxically injected scrapie on neurotransmitter systems of mouse cerebellum. | the 22l strain of scrapie was injected stereotaxically into the cerebellum of c57bl/6j mice to determine its effect on several cerebellar neurotransmitter systems during the early clinical stages of the disease. in this model vacuolar lesions are restricted to the cerebellum with no evidence of vacuolization in other brain regions. although vacuolar lesions develop throughout all cell layers of the cerebellum, they are most severe in the granule cell layer. modest but significant (p less than 0. ... | 1988 | 2897224 |
| in vitro expression in eukaryotic cells of a prion protein gene cloned from scrapie-infected mouse brain. | it has been proposed that the causative agent of scrapie represents a class of infectious particle that is devoid of nucleic acid and that an altered form of the endogenous prion protein (prp) is the agent. however, it has been difficult to exclude the possibility that prp purified from scrapie tissues might be contaminated with a more conventional viral agent. to obtain prp uncontaminated by scrapie-infected tissues, prp cdna cloned from a scrapie-infected mouse brain was expressed in mouse c12 ... | 1988 | 2898780 |
| replication of the scrapie agent in hamsters infected intracerebrally confirms the pathogenesis of an amyloid-inducing virosis. | following intracerebral infection of hamsters with scrapie agent replication started with or without a very short lag phase. infectivity titres increased exponentially within 35 to 40 days post-infection to a maximum level of 3 x 10(9) ld50 per brain and then remained constant until death. minimal detectable amounts of scrapie-associated fibrils (saf) appeared at 42 days and reached high levels 56 days after inoculation. the first clinical symptoms were diagnosed at about 65 days and animals die ... | 1988 | 2899129 |
| analyses of frequency of infection, specific infectivity, and prion protein biosynthesis in scrapie-infected neuroblastoma cell clones. | scrapie, a spongiform encephalopathy of sheep and goats, is caused by a poorly understood transmissible agent in which no nucleic acid has been conclusively identified. biochemical characterization of agent derived from animal tissues has not been precise because of the tenacious association of the agent with tissue components. as an approach toward obtaining homogeneous preparations of agent generated in vitro, we cloned scrapie-infected neuroblastoma cells. by frequency analysis, nearly every ... | 1988 | 2899175 |
| immunological analysis of host and agent effects on creutzfeldt-jakob disease and scrapie prion proteins. | creutzfeldt-jakob disease (cjd) and scrapie are degenerative neurological diseases caused by unusual infectious pathogens. the term prion has been introduced to underscore the apparent distinctness of these agents from viruses and viroids. the only macromolecule shown to be associated with the infectious agent, the cjd or scrapie prion protein (prpcjd or prpsc, respectively), is encoded by the same gene as a normal cellular protein. in several studies biochemical differences have been reported i ... | 1988 | 2900341 |
| developmental regulation of prion protein mrna in brain. | during development of the hamster brain, synthesis of the cellular isoform of the scrapie prion protein (prpc) was found to be regulated. low levels of prp poly(a)+ mrna were detectable one day after birth. prp poly(a)+ mrna reached maximal levels between 10 and 20 days post-partum; thereafter, no change in its level could be detected at ages up to 13 months. in contrast, myelin basic protein poly(a)+ mrna was shown to reach maximal levels by 30 days of age and thereafter steadily declined in ad ... | 1988 | 2900716 |
| scrapie: a virus-induced amyloidosis of the brain. | we have studied the pathogenesis of scrapie in hamsters, in particular the increase of infectivity and the formation of scrapie-associated fibrils in relation to clinical disease. the results of such studies after intraperitoneal or intracerebral infection are consistent with the idea that transmissible spongiform encephalopathies are a type of virus-induced, brain-specific amyloidosis. therefore, an appropriate name for the class of viruses that cause these diseases might be amyloid-inducing vi ... | 1988 | 2900717 |
| scrapie-associated fibrils, prp protein and the sinc gene. | scrapie-associated fibrils (saf) are disease-specific structures found in extracts of the brains of animals affected with scrapie. these structures are pathological aggregates of a normal host protein called prp. in collaboration with konrad beyreuther (heidelberg), we have characterized the multiple forms of prp found in saf fractions from mouse brain affected by the me7 strain of scrapie. there is no in vivo n-terminal cleavage of the most abundant forms of prp. however, n-terminal cleavage of ... | 1988 | 2900718 |
| properties of scrapie prion proteins in liposomes and amyloid rods. | the scrapie prion protein (prp 27-30) has been demonstrated to be required for infectivity. aggregates of prp 27-30 form insoluble amyloid rods which resist dissociation by non-denaturing detergents. mixtures of the detergent cholate and phospholipids were found to solubilize prp 27-30 with full retention of scrapie prion infectivity. no evidence for a prion-associated nucleic acid could be found when the phospholipid vesicles with prp 27-30 were digested with nucleases and zn2+. under digestion ... | 1988 | 2900719 |
| novel mechanisms of degeneration of the central nervous system--prion structure and biology. | prion is a term for the novel infectious agents which cause scrapie and creutzfeldt-jakob disease; these infectious pathogens are composed largely, if not entirely, of prion protein (prp) molecules. no prion-specific polynucleotide has been identified. considerable evidence indicates that prp 27-30 is required for and inseparable from scrapie infectivity. prp 27-30 is derived from a larger protein, denoted prpsc. a cellular isoform, designated prpc, and prpsc are both encoded by a single copy ch ... | 1988 | 2900720 |
| genetic control of prion incubation period in mice. | the prion gene complex (prn) is located on mouse chromosome 2 between the beta-2-microglobulin (b2m) and agouti (a) genes. within this complex are the prion protein gene (prn-p), which encodes the only identified macromolecule (prp) that purifies with infectious scrapie agent, and a scrapie incubation time gene (prn-i). using a variety of restriction endonucleases, six allelic forms of the prn-p gene have been distinguished by their patterns of restriction fragment length polymorphisms. we had p ... | 1988 | 2900721 |
| bse and scrapie: agents for change. | 1988 | 2900982 | |
| cns amyloid proteins in neurodegenerative diseases. | the amyloid plaques found in neurodegenerative diseases show considerable morphologic diversity. two amyloidogenic proteins have been isolated from the brains of humans and animals with neurodegenerative diseases--beta-protein from alzheimer's disease (ad) and down's syndrome, and prion protein (prp) from scrapie and creutzfeldt-jakob disease (cjd). using monoclonal antibodies to a synthetic peptide corresponding to a portion of beta-protein and rabbit antiserum to hamster scrapie prp 27-30, we ... | 1988 | 2901696 |
| messenger rnas of beta-amyloid precursor protein and prion protein are regulated by nerve growth factor in pc12 cells. | the effect of the neurotrophic factor ngf on the expression of two genes involved in the accumulation of amyloid deposits in neurodegenerative disorders was studied in a clonal cell line, pc12. use of hybridization methods showed that ngf increased the cellular pool of the mrna of the prion protein, a macromolecule known to generate fibrillary aggregates in the brain of scrapie-infected animals. maximal levels of prion mrna were obtained after 7 days of treatment, but a significant increase was ... | 1988 | 2903615 |
| fibrils from brains of cows with new cattle disease contain scrapie-associated protein. | during the past two years, more than 1,000 cases of a neurological disorder of cattle, bovine spongiform encephalopathy (bse), have been confirmed from farms throughout great britain. the neurological signs and brain pathology of bse resemble those produced in other species by the pathogens of scrapie and related disorders. the discovery of fibrils similar to scrapie-associated fibrils in detergent extracts o bse-affected brain supported the clinical and pathological diagnosis of the disease, bu ... | 1988 | 2904126 |
| purification and partial characterization of the normal cellular homologue of the scrapie agent protein. | the scrapie agent protein (sp33-37) is a degradation-resistant protein that aggregates into fibrils and amyloid plaques. this protein is derived from a normal cellular protein (cp33-37). understanding the mechanism responsible for the conversion of cp33-37 to sp33-37 may explain scrapie agent replication. cp33-37 was extracted from normal hamster brain and purified 2700-fold by an immunoaffinity method. both cp33-37 purified from normal hamster brain and sp33-37 purified from scrapie-affected ha ... | 1988 | 2904472 |
| nerve growth factor increases mrna levels for the prion protein and the beta-amyloid protein precursor in developing hamster brain. | deposition of amyloid filaments serves as a pathologic hallmark for some neurodegenerative disorders. the prion protein (prp) is found in amyloid of animals with scrapie and humans with creutzfeldt-jakob disease; the beta protein is present in amyloid deposits in alzheimer disease and down syndrome patients. these two proteins are derived from precursors that in the brain are expressed primarily in neurons and are membrane bound. we found that gene expression for prp and the beta-protein precurs ... | 1988 | 2904679 |
| molecular structure, biology, and genetics of prions. | 1988 | 2906782 | |
| pathogenesis of amyloid formation in alzheimer's disease, down's syndrome and scrapie. | paired helical filaments (phf) are abnormal fibrous structures found in human nerve cells and their processes. ultrastructural studies of the proto-filaments that make up the phf revealed that the individual proto-filaments have a different substructure from normal neurofilaments or any other known fibrous profiles. studies using immunological and biochemical methods suggested that abnormally phosphorylated tau, ubiquitin and neurofilament peptides are part of the phf. deposits of amyloid fibres ... | 1988 | 2970373 |
| [prions]. | 1988 | 2972052 | |
| growth factor production by creutzfeldt-jakob disease cell lines. | creutzfeldt-jakob disease (cjd), a progressive dementia of humans, is caused by an infectious agent that is closely related to the scrapie agent of sheep. although the molecular nature of these "unconventional" agents is still a matter of speculation and controversy, even less is known concerning the mechanism(s) of their effects on the central nervous system. to gain insight into the cellular effects of these agents, we have examined a series of cell lines derived directly from cjd-infected ham ... | 1988 | 3043023 |
| neuropathology of unconventional virus infections: molecular pathology of spongiform change and amyloid plaque deposition. | to the triad of neuronal loss, gliosis and spongiform change as characteristic morphological changes associated with infection of the central nervous system, one can now add the presence of scrapie-associated filaments (saf)/prp rods. while the host's immune response is conspicuous by its absence, the vigorous astrocytic response is presumptive evidence of the host's ability to recognize and respond to the primary neuronal insult. we assume that the spongiform change and vacuolation of neurons a ... | 1988 | 3044707 |
| genetic aspects of unconventional virus infections: the basis of the virino hypothesis. | the properties of genes involved directly or indirectly in the pathogenesis of scrapie and other unconventional (ucv) virus infections are reviewed. reasons are presented for assigning paramount importance to the sinc gene in mice and the sip gene in sheep (the likely homologue of sinc). the rationale is given for concluding that the agents of ucv infections have their own genomic molecules coding for strain differences. the virino hypothesis, which proposes that the infective form of the agent ... | 1988 | 3044709 |
| hypotheses concerning the aetiology of alzheimer's disease. | theories on the aetiology and pathogenesis of alzheimer's disease (ad) are revised. after discussing senile involution, the principal characteristic alterations of ad are presented. these pathological changes include involutive morphological phenomena (neurofibrillar tangles, senile neuritic plaques with varying = amyloid content) and functional phenomena (alterations in energy metabolism, in protein synthesis, and in the neurotransmitter metabolism). currently it is assumed that the neurons mos ... | 1988 | 3064109 |
| fifty years with scrapie: a personal reminiscence. | 1988 | 3066007 | |
| [has scrapie of sheep and goats a role in the transmission of creutzfeldt-jakob disease?]. | 1988 | 3068726 | |
| prion protein gene expression in cultured cells. | a single copy gene encodes both the scrapie (prpsc) and cellular (prpc) isoforms of the prion protein (prp). cultured cell lines were found to express the endogenous prp mrna at levels comparable to those observed in the brains of adult rodents; however, these cells were invariably found to express greatly reduced levels of prp. in all the cell lines examined, prp was undetectable by western immunoblot analysis. these cells were also poor recipients for expression constructs linking the hamster ... | 1988 | 2908139 |
| the scrapie agent and the prion hypothesis. | 1988 | 2908696 | |
| characterization of prion proteins with monospecific antisera to synthetic peptides. | the prion protein (prp) 27-30 is the major macromolecular component in highly purified preparations of prions derived from scrapie-infected hamster brain. immunoblotting studies demonstrated that this protein is generated by partial protease digestion of a larger precursor (prpsc) with an apparent mr of 33 to 35 kda, and that a protease-sensitive cellular prp isoform, designated prpc, is present in normal hamster brain. to characterize the relationships among these proteins, elisa and immunoblot ... | 1988 | 3125249 |
| antiheretical speculations on the "prion" protein and scrapie. | 1988 | 3127809 | |
| scrapie agent proteins do not accumulate in grey tremor mice. | the grey tremor mouse is an autosomal recessive mutant characterized by a phenotype of unusual pigmentation, neurological abnormalities and early death. these mice have a spongiform encephalopathy similar to scrapie and creutzfeldt-jakob disease. although the disease is clearly heritable, the grey tremor mouse spongiform pathology has also been transmitted by inoculation of genetically normal mice with diseased brain homogenates. the possibility that a scrapie-like agent is involved has been pro ... | 1988 | 3128642 |
| evidence that dna is present in abnormal tubulofilamentous structures found in scrapie. | abnormal tubulofilamentous structures have been identified in electron micrographs of thin sections and negatively stained impression grids prepared from brains of animals with scrapie and other spongiform encephalopathies, and we showed that such tubules contain a core of filamentous structures resembling scrapie-associated fibrils (saf). we treated impression grids from brains of scrapie-infected hamsters with several substances that bind to or cleave proteins and nucleic acids to see if they ... | 1988 | 3130630 |
| scrapie prion liposomes and rods exhibit target sizes of 55,000 da. | scrapie is a degenerative neurologic disease in sheep and goats which can be experimentally transmitted to laboratory rodents. considerable evidence suggests that the scrapie agent is composed largely, if not entirely, of an abnormal isoform of the prion protein (prpsc). inactivation of scrapie prions by ionizing radiation exhibited single-hit kinetics and gave a target size of 55,000 +/- 9000 mol wt. the inactivation profile was independent of the form of the prion. scrapie agent infectivity in ... | 1988 | 3130718 |
| a chronological study of experimental scrapie in mice. | the development of scrapie-associated particles and lesions in four regions of the brain was studied in mice over a period of 30 weeks. characteristic tubulovesicular particles, identical to those previously described, were first found about half way through the incubation period in mice inoculated by four different routes. the particles are found in brains with scrapie and other spongiform encephalopathies; they have never been seen in other conditions, and potentially represent the infectious ... | 1988 | 3131975 |
| [relation between slow virus infection of animals and man, their pathogenicity and resistance to therapy]. | besides conventional slow viruses, a category of pathogens exist, called "unconventional slow viruses". the latter evoke laughing death syndrome, creutzfeldt-jakob disease (resp. its special form of gerstmann-sträussler's syndrome) in man, in animal scrapie, infectious encephalopathy of the mink, and chronic wasting disease. they all are relatives, and their characteristics are longtime incubation, lacking immune reactions, high chemical and physical resistance, no proof of nucleic acids till no ... | 1988 | 3136063 |
| a modified host protein model of scrapie. | the scrapie agent is still not completely characterized biochemically and ultrastructurally, but its requirement for a functional protein has been established. purification of the scrapie agent by methods using digestion with proteinase k yields a glycoprotein with an apparent mass of 27-30 kda (prp 27-30). in contrast, a 33-37 kda glycoprotein, called sp33-37, is the major protein component isolated from scrapie-affected brain when protease digestion is not used. sp33-37 is the product of a nor ... | 1988 | 3136999 |
| in vitro expression of cloned prp cdna derived from scrapie-infected mouse brain: lack of transmission of scrapie infectivity. | a cdna for the prion protein (prp) derived from scrapie-infected mouse brain was expressed in c127 mouse cells in vitro under the control of the mouse metallothionein promoter. prp synthesis was detected by immunoprecipitation using a rabbit antibody specific for a 15 amino acid prp peptide. homogenates of cells expressing the cloned prp cdna inoculated into weanling mice failed to induce clinical scrapie during 190 days of observation. we conclude that either prp is not the transmissible agent ... | 1988 | 3137000 |
| search for a scrapie-specific nucleic acid: a progress report. | scrapie agent contains a proteinaceous component as well as an 'informational' molecule (suggested by the existence of distinct strains of scrapie). these operationally defined entities may be the same molecule, an infectious protein, or distinct, in which case a nucleic acid might encode the genetic information. purification of scrapie agent enriched a protein, prpsc, by virtue of its relative protease resistance. there is only a single prp gene and the primary translation product of prp mrna i ... | 1988 | 3137001 |