Publications

overexpression of active syrian golden hamster prion protein prpc as a glutathione s-transferase fusion in heterologous systems.	this article describes a procedure which permits for the first time the isolation of the prion protein prpc from the syrian golden hamster in heterologous systems. using a glutathione s-transferase (gst) fusion approach, milligram amounts of stable, soluble, and homogeneous gst::prpc protein were obtained in escherichia coli and with baculovirus-infected insect cells. authentic prpc was released from the immobilized fusion protein by direct cleavage with thrombin. gst::prpc expressed in these tw ...	1995	7609044
on safari with prp: prion diseases of animals.	prions are infectious pathogens that cause fatal neurodegeneration in humans and animals and are composed largely, or entirely, of an aberrant isoform of the host-encoded prion protein (prp). a post-translational process involving a conformational change in prp is a significant feature of their replication. differences in prp sequences modify the incubation times, neuropathology and properties of prion 'strains'.	1995	7613755
production of antiserum for the diagnosis of scrapie and bovine spongiform encephalopathy using a baculovirus-expressed prion protein antigen.		1995	7619908
early loss of neurons and axon terminals in scrapie-affected mice revealed by morphometry and immunocytochemistry.		1995	7632328
different allelic effects of the codons 136 and 171 of the prion protein gene in sheep with natural scrapie.	scrapie is a transmissible degenerative disease of the central nervous system occurring naturally in sheep. it belongs to the group of prion diseases also affecting man in which an abnormal isoform of the host-encoded prion protein (prp) accumulating in the brain is responsible for neuronal death. three main polymorphisms have been described in the sheep prp gene, at positions 136, 154 and 171. a strong association between susceptibility/resistance to natural scrapie and a dimorphism at codon 13 ...	1995	7636494
intracerebral distribution of infectious amyloid protein in spongiform encephalopathy.	we studied the regional distribution of infectious amyloid protein by western immunoblots of brain tissue extracts from 37 patients with different forms of spongiform encephalopathy, i.e., 16 sporadic cases, 18 familial cases with a variety of mutations, and 3 iatrogenic cases. in sporadic and familial creutzfeldt-jakob disease, amyloid protein concentrations were usually highest in the frontotemporal regions of the cerebral cortex, whereas iatrogenic creutzfeldt-jakob disease and gerstmann-strä ...	1995	7654073
encephalopathy in cattle experimentally infected with the scrapie agent.	ten 8- to 10-month-old cattle were each inoculated intramuscularly, subcutaneously, intracerebrally, and orally with the scrapie agent to determine whether cattle are susceptible to it. two inocula, both 10% homogenates of cerebrum, were used. one inoculum was from a sheep used for the second experimental ovine passage of the agent from 4 naturally affected suffolk sheep. the other inoculum was from a goat used for the first experimental caprine passage of the agent from 2 naturally affected dai ...	1995	7661455
sulfated polyanion inhibition of scrapie-associated prp accumulation in cultured cells.	the accumulation of an abnormal, protease-resistant form of the protein prp (prp-res) in hosts with scrapie and related transmissible spongiform encephalopathies appears to be important in disease pathogenesis. to gain insight into the mechanism of prp-res accumulation and the in vivo antiscrapie activity of certain polyanions, we have studied effects of sulfated glycans on prp metabolism in scrapie-infected neuroblastoma cells. pentosan polysulfate, like the amyloid-binding dye congo red, poten ...	1993	7678300
major histocompatibility complex genes have an increased brain expression after scrapie infection.	we have examined the expression of the major histocompatibility complex (mhc) antigens and related genes in scrapie-infected hamster brain. both the class i and the class ii mhc genes as well as the class ii-associated invariant chain were found to have an increased brain expression after scrapie infection. the increased expression of the class i complex was immunohistochemically localized primarily to neurons, though some astrocytes contained much smaller amounts of the class i complex. while t ...	1993	7678332
studies on a species-specific epitope in murine, ovine and bovine prion protein.	transmissible spongiform encephalopathies are fatal neurodegenerative disorders which are linked to abnormal isoforms of the prion protein (prp), which is expressed in different cells of various mammalian species. susceptibility to disease and reduced transmission rates upon the first passage to another species are thought to be a result of functional and biochemical differences of the prp as a consequence of amino acid sequence among species. in 1985 an epidemic of bovine spongiform encephalopa ...	1993	7687651
comment on the paper of h.k. narang. 'evidence that scrapie-associated tubulofilamentous particles contain a single-stranded dna'.		1994	7698886
cholesterol depletion and modification of cooh-terminal targeting sequence of the prion protein inhibit formation of the scrapie isoform.	after the cellular prion protein (prpc) transits to the cell surface where it is bound by a glycophosphatidyl inositol (gpi) anchor, prpc is either metabolized or converted into the scrapie isoform (prpsc). because most gpi-anchored proteins are associated with cholesterol-rich membranous microdomains, we asked whether such structures participate in the metabolism of prpc or the formation of prpsc. the initial degradation of prpc involves removal of the nh2 terminus of prpc to produce a 17-kd po ...	1995	7698979
scrapie prions selectively modify the stress response in neuroblastoma cells.	the fundamental event underlying scrapie infection seems to be a conformational change in the prion protein. to investigate proteins that might feature in the conversion of the cellular prion protein (prpc) into the scrapie isoform (prpsc), we examined mouse neuroblastoma n2a cells for the expression and cellular distribution of heat shock proteins (hsps), some of which function as molecular chaperones. in scrapie-infected n2a (scn2a) cells, hsp72 and hsp28 were not induced by heat shock, sodium ...	1995	7708753
astroglial reactivity in natural scrapie of sheep.	astrogliosis is known to be a common histological feature in experimental scrapie, but astroglial reactivity in natural scrapie of sheep has not yet been precisely studied. we investigated the expression of two markers of glial plasticity, glial fibrillary acidic protein (gfap) and glutamine synthetase (gs), by western and northern blotting, in different areas of the sheep brain. we report that both gfap-mrna and gfap are overexpressed in the cerebellum and the pons. in the thalamus, overexpress ...	1994	7723656
species specificity in the cell-free conversion of prion protein to protease-resistant forms: a model for the scrapie species barrier.	scrapie is a transmissible neurodegenerative disease that appears to result from an accumulation in the brain of an abnormal protease-resistant isoform of prion protein (prp) called prpsc. conversion of the normal, protease-sensitive form of prp (prpc) to protease-resistant forms like prpsc has been demonstrated in a cell-free reaction composed largely of hamster prpc and prpsc. we now report studies of the species specificity of this cell-free reaction using mouse, hamster, and chimeric prp mol ...	1995	7732006
evidence that scrapie-associated tubulofilamentous particles contain a single-stranded dna.	unique virus-like tubulofilamentous particles, termed nemavirus, have been consistently observed in spongiform encephalopathic brains by electron microscopy in thin sections. sodium dodecyl sulphate treatment of unfixed infected brain tissue on grids revealed a twisted fibril core of tubulofilamentous particles. the unmasked fibrils were identified as scrapie-associated fibrils by immunogold labelling. both tubulofilamentous particles and scrapie-associated fibrils are not artefacts of protease ...	1993	7755662
viral particles are required for infection in neurodegenerative creutzfeldt-jakob disease.	several models have been proposed for the infectious agents that cause human creutzfeldt-jakob disease (cjd) and sheep scrapie. purified proteins and extracted nucleic acids are not infectious. to further identify the critical molecular components of the cjd agent, 120s infectious material with reduced prion protein (prp) was treated with guanidine hydrochloride or sds. particulate and soluble components were then separated by centrifugation and molecularly characterized. conditions that optimal ...	1995	7761460
neuropathology and the scrapie-kuru connection.	when their kinship was surmised 35 years ago, scrapie and kuru were linked mainly by their neuropathologic similarity. most notable were neuronal degeneration and intense astrocytosis with little, if any, inflammation. especially eye-catching in kuru were the vacuolated neurons--the histologic hall-mark of scrapie that drew me to the human disease from the start. because spongiform change in gray matter neuropil is variable and usually lacks prominence in both scrapie and kuru, it was not part o ...	1995	7767488
prion protein transgenes and the neuropathology in prion diseases.	the concept that prions are novel pathogens which are different from both viroids and viruses has received increasing support from many avenues of investigation over the past decade. enriching fractions from syrian hamster (sha) brain for scrapie prion infectivity led to the discovery of the prion protein (prp). prion diseases of animals include scrapie and "mad cow" disease; those of humans present as inherited, sporadic and infectious neurodegenerative disorders, two of which are called creutz ...	1995	7767493
the neuropathology and epidemiology of bovine spongiform encephalopathy.	bovine spongiform encephalopathy (bse), defined originally from its characteristic neuropathology, retains a place of particular interest in the scrapie-like or prion disease group, presenting uniquely an example of such diseases occurring as a nationwide food-borne epidemic in great britain. comprehensive monitoring of the epidemic, both pathologically and epidemiologically, has facilitated our present understanding of the disease. bse presents the classical neuropathological features of the tr ...	1995	7767494
early unsuspected neuron and axon terminal loss in scrapie-infected mice revealed by morphometry and immunocytochemistry.	neuronal loss is often quoted as an element of the pathology of the transmissible spongiform encephalopathies, but few data are published. to determine whether neuronal loss is a salient feature of murine scrapie, and whether there is a relationship with the other hallmark lesions of scrapie we compared the numbers of neurons, severity of vacuolation, axonal bouton density and distribution of prion protein (prp) in the dorsal lateral geniculate nucleus (dlgn) following intraocular infection of c ...	1995	7770120
[epidemiology of creutzfeldt-jakob disease].	creutzfeldt-jakob disease is a rare disease (incidence < 1 case per million inhabitants), reported in all continents. certain characteristics are constant from one country to another: mean age of onset: 65 years, duration of the disease: about 6 months, sex ratio close to 1 and approximately 10% of familial cases. the geographical sites of this disease identified in chile, israel and czechoslovakia suggest certain genetic and/or environmental risk factors. the principal environmental factor impl ...	1995	7777374
[electrophysiology of transmissible encephalopathies].	the purpose of electrophysiological studies during the evolution of spongiform encephalopathies or prion diseases is to describe the changes of spontaneous or evoked electroencephalographic activity in natural and experimental diseases (natural and experimental scrapie, kuru and creutzfeldt-jakob (cj) disease in man and in different animal models) and to establish or to propose an action mechanism of the infectious agents. in the aim, the changes of electroencephalogram (eeg) and evoked potentia ...	1995	7777375
[scrapie in sheep and transmissible encephalopathy of the mink].	scrapie in sheep and goat is the prototype of the group of the transmissible spongiform encephalopathies which affect man and some animal species, notably other ruminants with bovine spongiform encephalopathy (bse) and chronic wasting disease of wild ruminants. transmissible mink encephalopathy (tme) is a rare disease of ranch-raised mink caused by exposure to a contaminated food ingredient in the ration scrapie, unrecognised bse-like disease...). there is clinical and pathological similarities ...	1995	7777384
indicator expression directed by regulatory sequences of the glial fibrillary acidic protein (gfap) gene: in vivo comparison of distinct gfap-lacz transgenes.	an increase in the expression of the glial fibrillary acidic protein (gfap) gene by astrocytes appears to constitute a crucial component of the brain's response to injury because it is seen in many different species and features prominently in diverse neurological diseases. previously, we have used a modified gfap gene (c-339) to target the expression of beta-galactosidase (beta-gal) to astrocytes in transgenic mice (mucke et al.; new biol 3:465-474 1991). to determine to what extent the in vivo ...	1995	7782103
identification of differentially expressed genes in scrapie-infected mouse neuroblastoma cells.	in vitro cdna libraries from scrapie-infected and non-infected murine neuroblastoma cell lines were screened with cdna probes derived by subtractive hybridization from scrapie-infected and uninfected cells to identify genes with altered expression associated with scrapie infection. eleven independent recombinant clones, whose expression was either increased or decreased in scrapie-infected cells, were identified. expression of these genes was also analyzed in a panel of scrapie-infected and non- ...	1995	7783594
pathology of the transmissible spongiform encephalopathies with special emphasis on ultrastructure.	the transmissible spongiform encephalopathies are a group of genetic and infectious disorders which are exemplified by scrapie in animals and creutzfeldt-jakob disease in humans. the spongiform encephalopathies are characterized by symmetrical vacuolation of neurons and neuropil. amyloid plaque formation similar to that found in alzheimer's disease is conspicuous in many, but not all, of these diseases. the sub-cellular pathology features of the spongiform encephalopathies have been studied by c ...	1995	7788281
ultrastructural localization of cellular prion protein (prpc) in synaptic boutons of normal hamster hippocampus.	the cellular prion protein (prpc) is a membrane sialoglycoprotein synthesized in the central nervous system and extraneural tissues. its post-translational modification produces an accumulation of abnormal isoform prpsc found in brains of transmissible neurodegenerative disorders in animals (scrapie and bovine spongiform encephalopathy) and humans (kuru, creutzfeldt-jakob disease, gerstmann-sträussler-scheinker syndrome). one major unanswered question relative to prpc concerns its physiological ...	1995	7788502
non-genetic propagation of strain-specific properties of scrapie prion protein.	the infectious agents causing scrapie and other transmissible spongiform encephalopathies have been postulated to consist solely of the protease-resistant form of prion protein (prpsc). one unprecedented requirement of the protein-only model is that the 'inheritance' of pathogen strain differences must be mediated by stable variations in prpsc structure, rather than mutations in an agent-specific nucleic acid. strain differences in prpsc structure have been described for the hyper (hy) and drows ...	1995	7791905
seac reports on transmissible spongiform encephalopathies.		1995	7793019
the consistent use of organic solvents for purification of phospholipids from brain tissue effectively removes scrapie infectivity.	a procedure for the purification of phospholipids from brain tissue was evaluated for its efficacy in eliminating scrapie agent infectivity. the key feature of the process was that phospholipids were extracted and purified by exclusive use of organic solvents. experiments were done by in vivo animal bioassay on a scaled-down version of the original procedure using 263 k-infected hamster brains as source material. the absence of any detectable infectivity in the final preparations indicated that ...	1994	7811455
[epidemiology of human diseases caused by unconventional transmissible agents].	human unconventional viruses infections are scarcely found with a worldwide occurrence below 1/million inhabitants. the disease would be induced by an interaction between the patient's genetic characteristics and environmental factors. no link has been found between the occurrence of the disease in man and the presence of the animal form of the disease, i.e. scrapie. the professional risk has been pointed out for people working with animals or in the medical sector. most iatrogenic cases are sub ...	1994	7812460
[transmissible animal spongiform encephalopathies. epidemiologic aspects].	this article presents an update of data about the transmissible spongiform encephalopathies which affect some animal species, particularly bovine spongiform encephalopathy in great britain and in other countries where this disease is sporadic. the genetic susceptibility of scrapie in sheep and the natural transmission of these spongiform encephalopathies are discussed. the control measures for public health and animal health are presented.	1994	7812463
prion protein and the scrapie agent: in vitro studies in infected neuroblastoma cells.	the mouse neuroblastoma cell line n2a was persistently infected with the chandler strain of the mouse scrapie agent. although the infection did not spread to infect > 1% of the cells, clones were established that had from 50 to 100% infected cells. these clones expressed the abnormal protease-resistant form of prion protein (prp), which is believed to mediate brain degeneration in animals with scrapie and bovine spongiform encephalopathy and in humans with kuru, creutzfeldt-jakob disease, and ge ...	1994	7812655
[scrapie and bse, the status ib the netherlands].		1995	7817367
epidemiological observations on spongiform encephalopathies in captive wild animals in the british isles.	since 1986, scrapie-like spongiform encephalopathy has been diagnosed in 19 captive wild animals of eight species at or from eight zoological collections in the british isles. the affected animals have comprised members of the family bovidae: one nyala (tragelaphus angasi), four eland (taurotragus oryx), and six greater kudu (tragelaphus strepsiceros), one gemsbok (oryx gazella), one arabian oryx (oryx leucoryx), and one scimitar-horned oryx (oryx dammah), and members of the family felidae: four ...	1994	7817514
correlative light and electron microscopy studies of prp localisation in 87v scrapie.	the transmissible neurodegenerative diseases, of which scrapie is the archetype, are caused by unconventional infectious agents. prion protein (prp), a widespread host coded, cell surface sialoglycoprotein, is thought to be an essential or, controversially, sole component of these agents. during infection, disease specific accumulations of prp may be observed in immunostained brain sections of mice infected with the 87v scrapie strain as amyloid plaques or as diffuse or granular foci within the ...	1994	7820594
biology and genetics of prion diseases.	enriching fractions from syrian hamster (sha) brain for scrapie prion infectivity led to the discovery of the prion protein (prp). prion diseases include scrapie of sheep, bovine spongiform encephalopathy (bse) of cattle, as well as creutzfeldt-jakob disease (cjd), gerstmann-sträussler-scheinker disease (gss), and fatal familial insomnia (ffi) of humans. discovery of mutations in the prp genes of humans with familial cjd, gss, and ffi established that prion diseases are both genetic and infectio ...	1994	7826022
mice devoid of the glial fibrillary acidic protein develop normally and are susceptible to scrapie prions.	glial fibrillary acidic protein (gfap) is an intermediate filament protein specifically expressed in astrocytes in the cns. to examine the function of gfap in vivo, the gfap gene was disrupted by gene targeting in embryonic stem cells. mice homozygous for the mutation were completely devoid of gfap but exhibited normal development and showed no obvious anatomical abnormalities in the cns. when inoculated with infectious scrapie prions, the mutant mice exhibited neuropathological changes typical ...	1995	7826639
concentration and distribution of infectivity and prpsc following partial denaturation of a mouse-adapted and a hamster-adapted scrapie strain.	prpsc is a specific protein marker for slow infectious diseases known as the transmissible subacute spongiform encephalopathies. although prpsc is closely associated with infectivity, it is not known if it is the infectious agent itself, a component of the agent or merely adventitiously associated with infectivity. in the present study we demonstrate that the resistance of prpsc to partial denaturation and of infectivity to inactivation differs markedly for two scrapie strains. proteinase k trea ...	1994	7832637
decontamination studies with the agents of bovine spongiform encephalopathy and scrapie.	macerates of bovine brain infected with bovine spongiform encephalopathy (bse) agent, and rodent brain infected with the 263k or me7 strains of scrapie agent, were subjected to porous-load autoclaving at temperatures between 134 and 138 degrees c for < or = 60 min. bioassay in rodents showed that none of the regimens produced complete inactivation. homogenates of bse-infected bovine brain were exposed for < or = 120 min to solutions of sodium hypochlorite or sodium dichloroisocyanurate containin ...	1994	7832638
bovine spongiform encephalopathy in germany.	bovine spongiform encephalopathy (bse) has been described as an epidemic central nervous disorder in cattle from the united kingdom. the disease is thought to have emerged by an interspecies transmission of the scrapie agent of sheep to cattle, after feeding scrapie-contaminated meat and bone meal (mbm). the disease has caused substantial economic losses for the british cattle industry. because of strict veterinary regulations for the import of adult british cattle by the european union and for ...	1994	7839751
prp gene dosage determines the timing but not the final intensity or distribution of lesions in scrapie pathology.	we have produced by gene targeting a mouse line with an inactive prp gene. in animals heterozygous for this mutation, prp mrna is reduced by approximately 50% throughout the brain compared with wild type mice. the steady-state level of prpc is also significantly reduced in heterozygotes compared to wild type mice. prp mrna and protein are not detected in brains of mice homozygous for the mutation. we have infected wild type mice and mice heterozygous and homozygous for the mutation with the me7 ...	1994	7842304
a 60-kda prion protein (prp) with properties of both the normal and scrapie-associated forms of prp.	scrapie is a transmissible spongiform encephalopathy of sheep and other mammals in which disease appears to be caused by the accumulation of an abnormal form of a host protein, prion protein (prp), in the brain and other tissues. the process by which the normal protease-sensitive form of prp is converted into the abnormal protease-resistant form is unknown. several hypotheses predict that oligomeric forms of either the normal or abnormal prp may act as intermediates in the conversion process. we ...	1995	7852415
frequencies of prp gene variants in healthy cattle and cattle with bse in scotland.	bovine spongiform encephalopathy (bse) is one of a family of scrapie-like diseases which affect various mammals. polymorphisms and mutations of the prp gene have been associated with the incidence of experimental and natural scrapie in other animals and this study of the bovine prp gene was undertaken to discover whether there was a similar association with prp genotype in cattle with bse. there are two known polymorphisms of the coding region of the bovine prp gene, a silent hindii restriction ...	1994	7856030
severe autolysis does not prevent scrapie diagnosis in sheep.		1994	7858030
endosome-lysosomes and neurodegeneration.	a number of the major human and animal neurodegenerative diseases, such as alzheimer's disease and sheep scrapie, are characterised by deposits of amyloid, arising through incomplete breakdown of membrane proteins. although our knowledge concerning these diseases is increasing, they remain largely untreatable. recently, attention has focussed on the mechanisms of production of different types of amyloid and the likely involvement within cells of acid compartments called endosome-lysosomes. these ...	1994	7858158
animal spongiform encephalopathies--an update. part 1. scrapie and lesser known animal spongiform encephalopathies.	the present article (part i) reviews recent developments in animal spongiform encephalopathies (ses), with the exception of bovine spongiform encephalopathy (bse), which is dealt with in part ii. the article focuses on scrapie and describes epidemiological aspects and the prospects for a preclinical diagnosis. up to now, confirmatory diagnosis of scrapie depended on histological examination of the brain, collected during post-mortem examination from sheep with clinical signs of the disease. an a ...	1994	7871704
diagnosis of scrapie.		1994	7886893
identification of five allelic variants of the sheep prp gene and their association with natural scrapie.	scrapie is a fatal neurodegenerative disease of sheep that belongs to the group of prion diseases found in humans and animals. the host encoded prion protein (prp) plays a central role in the disease process. in the prp genes of man, mice and sheep, polymorphisms have been found that are associated with disease susceptibility and pathogenesis. we have used denaturing gradient gel electrophoresis (dgge) to detect polymorphisms in the sheep prp gene. in addition to the already described polymorphi ...	1995	7897344
morphogenesis of amyloid plaques in 87v murine scrapie.	amyloid plaques of scrapie-infected mouse brains are composed of fibrillar forms of a host coded, cell surface sialoglycoprotein called prp (prion protein). serial ultrastructural immunogold staining was performed on plaques identified by light microscopic immunocytochemistry of brains of vm mice infected with the 87v strain of scrapie. classical plaques, of a kuru-type morphology, were composed of a central core of bundles of amyloid fibrils. amyloid fibrils of classical plaques were immunoreac ...	1994	7898615
cytoprotective effect of nmda receptor antagonists on prion protein (prionsc)-induced toxicity in rat cortical cell cultures.	rat cortical cells were incubated with the scrapie prion protein, prionsc. at concentrations of 3 ng/ml of prionsc and higher, the viability of the cells decreased significantly after a 12-h incubation period. simultaneously, the degree of dna fragmentation increased. in control experiments with antibodies against prionsc, prionsc lost its deleterious effect on neurons. prionsc did not affect the viability of astrocytes. drugs known to block nmda receptor channels, such as memantine (1-amino-3,5 ...	1993	7901042
heparin-like molecules bind differentially to prion-proteins and change their intracellular metabolic fate.	prpsc is the only known component of the scrapie prion. the difference between prpsc and its normal isoform prpc is probably conformational, since no difference has been found in the amino acid sequence or postranslational modifications between both proteins. heparan sulfate (hs) has been shown to be a component of amyloid plaques in a number of diseases including the prion diseases. we now present evidence that prp can specifically bind to heparin-like compounds and that this interaction might ...	1993	7901226
ablation of the prion protein (prp) gene in mice prevents scrapie and facilitates production of anti-prp antibodies.	mice, homozygous for prion protein (prp) gene ablation (prn-p0/0), develop normally and remain well > 500 days after inoculation with murine scrapie prions. in contrast, wild-type mice developed scrapie < 165 days after inoculation and most prn-p0/+ mice, heterozygous for disruption of the prp gene, exhibited signs of central nervous system dysfunction between 400 and 465 days after inoculation. in situ immunoblots showed widespread deposition of scrapie prp (prpsc) in the brains of both wild-ty ...	1993	7902565
conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins.	prions are composed largely, if not entirely, of prion protein (prpsc in the case of scrapie). although the formation of prpsc from the cellular prion protein (prpc) is a post-translational process, no candidate chemical modification was identified, suggesting that a conformational change features in prpsc synthesis. to assess this possibility, we purified both prpc and prpsc by using nondenaturing procedures and determined the secondary structure of each. fourier-transform infrared (ftir) spect ...	1993	7902575
insights into the role of the immune system in prion diseases.		1994	7904753
alzheimer's disease and creutzfeldt-jakob disease: overlap of pathogenic mechanisms.	this article compares beta-amyloid precursor protein (beta-app) disorders exemplified by alzheimer's disease (ad), with prion protein (prp) disorders, exemplified by creutzfeldt-jakob disease (cjd) in humans and scrapie in animals. although there are obvious differences in the etiology and pathogenesis of both sets of disorders, a remarkable number of similarities exist. both sets of disorders are characterized clinically by age-related sporadic and familial diseases. in both, an abnormal form o ...	1993	7904883
thermal stability and conformational transitions of scrapie amyloid (prion) protein correlate with infectivity.	the scrapie amyloid (prion) protein (prp27-30) is the protease-resistant core of a larger precursor (prpsc) and a component of the infectious scrapie agent; the potential to form amyloid is a result of posttranslational event or conformational abnormality. the conformation, heat stability, and solvent-induced conformational transitions of prp27-30 were studied in the solid state in films by cd spectroscopy and correlated with the infectivity of rehydrated and equilibrated films. the exposure of ...	1993	7905316
effect of sinc genotype, agent isolate and route of infection on the accumulation of protease-resistant prp in non-central nervous system tissues during the development of murine scrapie.	mice congenic for the sinc gene were infected intracerebrally with two scrapie strains, me7 and 22a. at various times during the incubation period tissues were monitored for the infection-specific form of prp (prpsc). prpsc was found in brain, spleen, lymph nodes, pancreas, submaxillary gland and thymus. after intraperitoneal inoculation prpsc was found in spleen, lymph nodes, pancreas and submaxillary glands prior to its detection in brain. the kinetics of accumulation of prpsc in these tissues ...	1994	7907357
detection of prpsc in sheep at the preclinical stage of scrapie and its significance for diagnosis of insidious infection.	a field sheep insidiously infected with natural scrapie was diagnosed at the preclinical stage through detection of the core fragment of prpsc (prpcore) in peripheral lymph nodes by the biopsy method. three out of 32 euthanized healthy sheep were found positive for prpcore in the spleen and lymph nodes. mice that were inoculated with spleen homogenate of one of these sheep showed clinical signs of scrapie and were positive for prpcore in their brain samples. these results suggest that the detect ...	1994	7907466
small virus-like structure in fractions from scrapie hamster brain.	the scrapie model in hamsters has been used to search for the agents that cause creutzfeldt-jakob disease in man and similar transmissible encephalopathies in animals. we found structures that are extraordinarily small for a virus, but exhibit viral structural properties in negatively stained samples, by electron microscopy in fractions containing scrapie-associated fibrils.	1994	7908360
prp genotype and agent effects in scrapie: change in allelic interaction with different isolates of agent in sheep, a natural host of scrapie.	man and sheep are the two species in which spongiform encephalopathies occur naturally, and in which there are recognized genetic components that predispose an individual person or sheep to clinical disease. in both species mutations/polymorphisms in the prp gene have been linked to the incidence of natural disease, but only in sheep is it possible to investigate by deliberate exposure to infection whether these polymorphisms are directly correlated with survival time. cheviot sheep of different ...	1994	7909834
properties of the scrapie prion protein: quantitative analysis of protease resistance.	the disease-specific isoform of the prion protein (prpsc) is an essential part of the infectious particle which causes spongiform degeneration in various mammalian species. prpsc differs from prp of normal animals (prpc) by its relative protease resistance. the physical nature of this difference is still unknown. we analyzed the protease resistance of prpsc quantitatively using an enzyme-linked immunofiltration assay. prpsc was rendered completely protease-sensitive at alkaline ph or in > 1.5 m ...	1994	7910036
prion isolate specified allotypic interactions between the cellular and scrapie prion proteins in congenic and transgenic mice.	different prion isolates, often referred to as "strains," present an enigma because considerable evidence argues that prions are devoid of nucleic acid. to investigate prion diversity, we inoculated three "strains" of prions into congenic and transgenic mice harboring variable numbers of two different alleles, designated a and b, of the prion protein (prp) structural gene, prn-p. the length of the incubation time was inversely related to the number of prn-p(a) genes in mice inoculated with the r ...	1994	7911243
scrapie, creutzfeldt-jakob disease and bovine spongiform encephalopathy: the key role of a nerve membrane protein (prp).		1994	7911437
protease-resistant prp accumulation and scrapie agent replication: a role for sulphated glycosaminoglycans?		1994	7911438
a glycolipid-anchored prion protein is endocytosed via clathrin-coated pits.	the cellular prion protein (prpc) is a glycolipid-anchored, cell surface protein of unknown function, a posttranslationally modified isoform of which prpsc is involved in the pathogenesis of creutzfeldt-jakob disease, scrapie, and other spongiform encephalopathies. we have shown previously that chprp, a chicken homologue of mammalian prpc, constitutively cycles between the cell surface and an endocytic compartment, with a transit time of approximately 60 min in cultured neuroblastoma cells. we n ...	1994	7911471
characterisation of antisera raised against species-specific peptide sequences from scrapie-associated fibril protein and their application for post-mortem immunodiagnosis of spongiform encephalopathies.	transmissible spongiform encephalopathies (tse), such as scrapie or creutzfeldt-jakob disease (cjd), are fatal neurodegenerative diseases of the central nervous system caused by a yet unidentified virus. they are accompanied by a brain specific amyloidosis, during which a host coded protein irreversibly aggregates to form the scrapie-associated fibrils. the diagnosis of tse relies on histopathological detection of spongiform lesions, on electron microscopical detection of fibrils, or on the immu ...	1994	7911655
no propagation of prions in mice devoid of prp.		1994	7912659
structure and polymorphism of the mouse prion protein gene.	missense mutations in the prion protein (prp) gene, overexpression of the cellular isoform of prp (prpc), and infection with prions containing the scrapie isoform of prp (prpsc) all cause neurodegenerative disease. to understand better the physiology and expression of prpc, we retrieved mouse prp gene (prn-p) yeast artificial chromosome (yac), cosmid, phage, and cdna clones. physical mapping positions prn-p approximately 300 kb from ecotropic virus integration site number 4 (evi-4), compatible w ...	1994	7912827
prpsc in icelandic sheep naturally infected with scrapie.		1994	7913301
the significance of prpsc detection for the diagnosis of insidious scrapie.		1994	7913303
heterologous prp molecules interfere with accumulation of protease-resistant prp in scrapie-infected murine neuroblastoma cells.	mutations within a host cellular protein, prp, have been associated with disease in the transmissible spongiform encephalopathies. murine neuroblastoma cells persistently infected with mouse scrapie accumulate protease-resistant prp (prp-res), the abnormal form of prp associated with disease in the transmissible spongiform encephalopathies. these cells provide a controlled system in which to study the molecular interactions which are important in the formation of prp-res. we have expressed recom ...	1994	7913509
histopathological changes in the islets of langerhans in scrapie 139h-affected hamsters.	previous studies showed that the 139h strain of scrapie injected into hamsters caused obesity, a marked hypertrophy of the islets of langerhans, generalized endocrinopathy and marked hypoglycaemia-hyperinsulinaemia. in the current study, female weanling syrian hamsters (lvg/lak strain) were inoculated intracerebrally with scrapie strain 139h or 263k, or with normal hamster brain. sections of the pancreas stained with haematoxylin and eosin or gomori's one-step trichrome were examined by light mi ...	1994	7913716
genetics of prion diseases and prion diversity in mice.	linkage of the prion protein (prp) and scrapie incubation time genes in mice provided strong evidence for the central role of prp in determining susceptibility to prion disorders. considerable evidence now argues that the prion protein and incubation time genes are identical. the mouse prion protein gene (prn-p) may act both quantitatively and qualitatively in modulating prion incubation time. differences at positions 108 and 189 between prp-a and prp-b allotypes can place constraints on interac ...	1994	7913753
scrapie-associated prp accumulation and agent replication: effects of sulphated glycosaminoglycan analogues.	an abnormally protease-resistant and apparently neuropathogenic form of prp accumulates in the brains of hosts with scrapie and related transmissible spongiform encephalopathies. studies with scrapie-infected neuroblastoma cells have highlighted dramatic differences in the metabolism of the normal (protease-sensitive) and scrapie-associated (protease-resistant) isoforms of prp. furthermore, this model has been useful in identifying inhibitors of protease-resistant prp accumulation and scrapie ag ...	1994	7913757
transmission of bovine spongiform encephalopathy and scrapie to mice: strain variation and the species barrier.	transmissions of bovine spongiform encephalopathy (bse) from seven unrelated cattle sources have given remarkably uniform disease characteristics in mice, differing from over twenty previous and contemporary transmissions of sheep and goat scrapie. transmissions to mice of spongiform encephalopathy from six species (including sheep and goats) which have been experimentally or naturally infected with bse have given similar results to direct bse transmissions from cattle. therefore the bse agent h ...	1994	7913758
physicochemical and biological characterizations of distinct strains of the transmissible mink encephalopathy agent.	inoculation of the stetsonville, wisconsin source of transmissible mink encephalopathy (tme) into syrian hamsters has identified two strains of the tme agent having distinct biological properties and producing disease-specific prion proteins (prptme) having different physicochemical properties. although several strains of the sheep scrapie agent have been identified in great britain, this is the first indication that agents producing transmissible spongiform encephalopathies in the united states ...	1994	7913759
the neuropathological phenotype in transgenic mice expressing different prion protein constructs.	neuropathologic examination of transgenic (tg) mice which express different prion protein (prp) constructs is essential because spongiform (vacuolar) degeneration of neurons, the distribution of prpsc and whether prp amyloid plaques form are the phenotypes of prion diseases. in tg models of experimental scrapie, it was found that all of the parameters that define prion isolates ('strains') can be manipulated by changing the structure of prp. in those studies, further evidence that prpsc causes s ...	1994	7913760
nucleic acids in prion preparations: unspecific background or essential component?	as recently published (kellings et al. j. gen vir. 73, 1025-1029 (1992)), the analysis of purified scrapie prions by return refocusing gel electrophoresis revealed remaining nucleic acids in the size range up to 1100 nucleotides. the results defined the possible characteristics of a hypothetical scrapie-specific nucleic acid. if homogeneous in size, such a molecule would be less than 80 nucleotides in length at a particle-to-infectivity ratio (p:i) near unity; if heterogeneous, scrapie-specific ...	1994	7913761
susceptibility to scrapie in mice is dependent on prpc.	mice devoid of functional prp genes (prn-p(o/o) mice) showed normal development and behaviour. when inoculated with mouse scrapie prions they remained free of scrapie symptoms for at least 18 months whereas wild-type controls all died within 6 months. no propagation of infectivity could be detected in the prp null mice. surprisingly, heterozygous prn-p(o/+) mice also showed enhanced resistance to scrapie. after introduction of syrian hamster prp transgenes, prn-p(o/o) mice became highly suscepti ...	1994	7913762
spectroscopic characterization of conformational differences between prpc and prpsc: an alpha-helix to beta-sheet transition.	although no chemical modifications have been found to distinguish the cellular prion protein prpc from its infectious analogue prpsc, spectroscopic methods such as fourier transform infrared (ftir) spectroscopy reveal a major conformational difference. prpc is rich in alpha-helix but is devoid of beta-sheet, whereas prpsc is high in beta-sheet. n-terminal truncation of prpsc by limited proteolysis does not destroy infectivity but it increases the beta-sheet content and shifts the ftir absorption ...	1994	7913763
characterization of prp binding proteins.	prions cause spongiform degeneration in various mammalian species. the scrapie prion protein (prpsc) is part of the infectious particle and may mediate infection and spreading of the disease in the brain. it was therefore of interest to purify and analyse prp ligands (plis). plis were identified on ligand blots using either intact prp or peptides corresponding to the central portion of prp. here, characterization of a 110 and a 125 kda pli is reported. both plis were found in total membrane frac ...	1994	7913764
molecular biology and genetics of prion diseases.	scrapie was thought for many years to be caused by a virus. enriching fractions from syrian hamster (sha) brain for scrapie infectivity led to the discovery of the prion protein (prp). to date, no scrapie-specific nucleic acid has been found. as well as scrapie, prion diseases include bovine spongiform encephalopathy (bse) of cattle, as well as creutzfeldt-jakob disease (cjd) and gerstmann-sträussler-scheinker syndrome (gss) of humans. transgenic (tg) mice expressing both sha and mouse (mo) prp ...	1994	7913765
cell-free formation of protease-resistant prion protein.	the infectious agent (or 'prion') of the transmissible spongiform encephalopathies (tses) such as scrapie resembles a virus in that it replicates in vivo and has distinct strains, but it was postulated long ago to contain only protein. more recently, prpsc, a pathogenic, scrapie-associated form of the host-encoded prion protein (prp), was identified as a possible primary tse agent protein. prpsc is defined biochemically by its insolubility and resistance to proteases and is derived post-translat ...	1994	7913989
pharmacological studies of a new derivative of amphotericin b, ms-8209, in mouse and hamster scrapie.	transmissible subacute spongiform encephalopathies (tsse) are neurodegenerative diseases characterized by the presence of a modified, partially proteinase-resistant host protein, prpsc, which accumulates in the brains of infected individuals. recently it has been reported that amphotericin b (amb) treatment of hamsters infected with scrapie strain 263k prolongs the incubation period of the disease, and dissociates in vivo replication of the scrapie agent from prpsc accumulation. we report here o ...	1994	7915757
serial transmission in rodents of neurodegeneration from transgenic mice expressing mutant prion protein.	two lines of transgenic (tg) mice expressing high (h) levels of the mutant p101l prion protein (prp) developed a neurologic illness and central nervous system pathology indistinguishable from experimental murine scrapie; these mice were designated tg(moprp-p101l)h. brain homogenates from tg(moprp-p101l)h mice were inoculated intracerebrally into cd-1 swiss mice, syrian hamsters, and tg196 mice, tg mice expressing the moprp-p101l transgene at low levels. none of the cd-1 mice developed central ne ...	1994	7916462
expression of glial fibrillary acidic protein and glutamine synthetase genes in the natural scrapie of sheep.	gene expression of two astroglial markers, glial fibrillary acidic protein (gfap) and glutamine synthetase (gs), was investigated in cerebellum and brainstem from scrapie-affected sheep. the gfap and gfap-mrna concentrations were increased in the two cerebral regions studied in the scrapie-affected animals as compared to the controls. the good correlation between the increase in gfap and gfap-mrna concentrations found in scrapie-affected sheep indicates a significant de novo synthesis of gfap in ...	1994	7916768
transmissible spongiform encephalopathies or prion disorders--current views.	basic hypotheses concerning nature of an infectious agent of the transmissible spongiform encephalopathies are reported here. the agent may consist of a protein only (prpsc), and for such a molecular structure the term "prion" has been coined. it may consist of a yet-to-be-discovered small oligonucleotide and a shell protein and this is the "virino" concept. or, the agent may be a virus which has still eluded detection. the experiments with transgenic and knock-out mice proved that prpsc is cruc ...	1994	7922109
[risk assessment for importing bovine spongiform encephalopathy (bse)].	since the occurrence of bovine spongiform encephalopathy (bse) in switzerland in 1990, extensive epidemiological investigations and risk factor analyses were carried out. in this study, statistical data on meat and bone meal traded from 1985 to 1989 were analysed addressing the following questions: i) what amount of meat and bone meal was exported from great britain (gb) and where to and ii) what amount of meat and bone meal was imported into switzerland and where from? the findings led to the h ...	1994	7924970
homozygosity for prion protein alleles encoding glutamine-171 renders sheep susceptible to natural scrapie.	natural scrapie has been viewed both as a recessive trait and as a contagious disease modulated by a host locus. to address this conundrum, we determined the structure of the sheep prion protein (prp) gene, which contains three exons and extends over 20 kb of dna. in the united states 86.4% of scrapie cases occur in suffolk sheep, and within this breed 49 +/- 6% (+/- s.d., n = 69) of healthy animals carry one or more prp alleles encoding arg (r)-171. four scrapie-affected sheep were homozygous f ...	1994	7926780
amphotericin b delays both scrapie agent replication and prp-res accumulation early in infection.	amphotericin b delays the onset of clinical symptoms in hamsters infected with scrapie agent strain 263k. here we show that accumulation of a scrapie-specific isoform of the prion protein (prp-res) and agent replication were delayed early in amphotericin b-treated animals. by 8 weeks postinfection, only untreated animals exhibited clinical symptoms of scrapie infection whereas prp-res levels and titers were similar in treated and untreated animals. this suggests that although prp-res accumulatio ...	1994	7933137
small virus-like structure in brains from cases of sporadic and familial creutzfeldt-jakob disease.	we have previously observed small virus-like particles in the brain of hamsters with experimental scrapie. here we report that small virus-like structures can be isolated from brains of patients with creutzfeldt-jakob disease and identified by electronmicroscopy.	1994	7934349
transmission of creutzfeldt-jakob disease from humans to transgenic mice expressing chimeric human-mouse prion protein.	transgenic (tg) mice were constructed that express a chimeric prion protein (prp) in which a segment of mouse (mo) prp was replaced with the corresponding human (hu) prp sequence. the chimeric prp, designated mhu2mprp, differs from moprp by 9 amino acids between residues 96 and 167. all of the tg(mhu2m) mice developed neurologic disease approximately 200 days after inoculation with brain homogenates from three patients dying of creutzfeldt-jakob disease (cjd). inoculation of tg(mhu2m) mice with ...	1994	7937921
effect of infection with the 139h scrapie strain on the number, area and/or location of hypothalamic crf- and vp-immunostained neurons.	scrapie is a transmissible neurodegenerative disease which shares some characteristics with alzheimer disease (ad). recent studies show abnormal enlargement of the adrenal glands and kidneys in 139h-affected hamsters. using immunocytochemical techniques with antibodies to corticotropin-releasing factor (crf) and vasopressin (vp), we observed the following: (1) a significantly higher number of crf-immunostained neurons in the preoptic nucleus of hypothalamus of 139h-affected hamsters than control ...	1994	7941971
detection of prion protein in formalin-fixed brain by hydrated autoclaving immunohistochemistry for the diagnosis of scrapie in sheep.		1994	7948209
bovine spongiform encephalopathy surveillance in argentina.	bovine spongiform encephalopathy (bse) is a new disease of cattle first described in the united kingdom in november 1986. bse belongs to the scrapie-related group of diseases. the epidemiological studies performed in the united kingdom demonstrate that the bse epidemic was caused by feeding cattle with ruminant-derived protein contaminated by a scrapie-like agent. until june 1994, the disease had been detected in indigenous cattle in ireland, switzerland and france. three cases reported in germa ...	1994	7949355
[natural history of transmissible subacute spongiform encephalopathy (tsse)].	sheep scrapie is the archetype of esst it has been described for more than 200 years but the first scientific papers were published less than 60 years ago. the link between doctors and veterinary surgeons enabled our knowledge to develop. first, a slow virus was evoked, then hadlow dvm (usa) suggested using brain filtrates from deceased patients of kuru in order to inoculate primates or small rodents; this was carried out by the team of d.c. gajdusek. the complete absence of immune reaction has ...	1994	7953894
[transmissible animal spongiform encephalopathies].	scrapie in sheep and goats was the first animal spongiform encephalopathy diagnosed. it has since been described in a large number of species (cattle, wild and exotic ruminants, mink, cat). they form an original group of diseases because they are transmissible by a specific pathogen and they depend on the genetic predisposition of the recipient animal. transmission between species and the possibility of oral transmission underline the need to assess the risk to man.	1994	7953895
astrocyte gene expression in experimental mouse scrapie.	the biological hallmark of transmissible spongiform encephalopathies is a significant accumulation, in brain, of the scrapie prion protein (prpsc), often associated with an increased glial fibrillary acidic protein (gfap) expression. this study was focused on astrocyte gene expression during scrapie development over a period of 172 days in intracerebrally inoculated newborn mice. the levels of expression of prp and two specific astrocyte proteins, -gfap and glutamine synthetase (gs)-, were inves ...	1994	7962730