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[scrapie of sheep and creutzfeldt-jakob disease in iceland].scrapie of sheep and creutzfeldt-jakob disease (cjd) are both classified as prion diseases. the infectious agents of both diseases are closely related. the objectives of the study was to explore, whether sheep scrapie could be transmitted to humans and cause cjd.200818591729
western blot detection of prp sc in archived paraffin-embedded brainstem from scrapie-affected sheep.scrapie is a naturally occurring fatal neurodegenerative disease of adult sheep and goats, one of a group of mammalian diseases known as transmissible spongiform encephalopathies (tse) or prion diseases. immunoassays that identify disease-associated prion protein (prp sc) are integral to the diagnosis of scrapie and other prion diseases. results obtained by either immunohistochemistry (ihc) or western blot (wb) assay are generally adequate for the definitive diagnosis. approved or accepted metho ...200818599864
scrapie prion protein structural constraints obtained by limited proteolysis and mass spectrometry.elucidation of the structure of scrapie prion protein (prp(sc)), essential to understand the molecular mechanism of prion transmission, continues to be one of the major challenges in prion research and is hampered by the insolubility and polymeric character of prp(sc). limited proteolysis is a useful tool to obtain insight on structural features of proteins: proteolytic enzymes cleave proteins more readily at exposed sites, preferentially within loops, and rarely in beta-strands. we treated prp( ...200818621059
changes in protein structure and distribution observed at pre-clinical stages of scrapie pathogenesis.scrapie is a neurodegenerative disorder that involves the misfolding, aggregation and accumulation of the prion protein (prp). the normal cellular prp (prp(c)) is rich in alpha-helical secondary structure, whereas the disease-associated pathogenic form of the protein (prp(sc)) has an anomalously high beta-sheet content. in this study, protein structural changes were examined in situ in the dorsal root ganglia from perorally 263k scrapie-infected and mock-infected hamsters using synchrotron fouri ...200818625306
scrapie resistance in arq sheep.variation in the ovine prion protein amino acid sequence influences scrapie progression, with sheep homozygous for a(136)r(154)q(171) considered susceptible. this study examined the association of survival time of scrapie-exposed arq sheep with variation elsewhere in the ovine prion gene. four single nucleotide polymorphism alleles were associated with prolonged survival. one nonsynonymous allele (t112) was associated with an additional 687 days of survival for scrapie-exposed sheep compared to ...200818632863
delivery of single-chain antibodies (scfvs) directed against the 37/67 kda laminin receptor into mice via recombinant adeno-associated viral vectors for prion disease gene therapy.the 37/67 kda laminin receptor (lrp/lr) acts as a receptor for prions providing a promising target for the treatment of prion diseases. recently, we selected anti-lrp/lr single-chain antibodies (scfvs) and proved a reduction of the peripheral prp(sc) propagation by passive immunotransfer into scrapie-infected mice. here, we report the development of an in vivo gene delivery system based on adeno-associated virus (aav) vectors expressing scfvs-s18 and -n3 directed against lrp/lr. transduction of ...200818632978
a gamma-secretase inhibitor and quinacrine reduce prions and prevent dendritic degeneration in murine brains.in prion-infected mice, both the notch-1 intracellular domain transcription factor (nicd) and the disease-causing prion protein (prp(sc)) increase in the brain preceding dendritic atrophy and loss. because the drug ly411575 inhibits the gamma-secretase-catalyzed cleavage of notch-1 that produces nicd, we asked whether this gamma-secretase inhibitor (gsi) might prevent dendritic degeneration in mice with scrapie. at 50 d postinoculation with rocky mountain laboratory (rml) prions, mice were given ...200818647832
prion diseases are efficiently transmitted by blood transfusion in sheep.the emergence of variant creutzfeld-jakob disease, following on from the bovine spongiform encephalopathy (bse) epidemic, led to concerns about the potential risk of iatrogenic transmission of disease by blood transfusion and the introduction of costly control measures to protect blood supplies. we previously reported preliminary data demonstrating the transmission of bse and natural scrapie by blood transfusion in sheep. the final results of this experiment, reported here, give unexpectedly hig ...200818647958
prion protein amino acid determinants of differential susceptibility and molecular feature of prion strains in mice and voles.the bank vole is a rodent susceptible to different prion strains from humans and various animal species. we analyzed the transmission features of different prions in a panel of seven rodent species which showed various degrees of phylogenetic affinity and specific prion protein (prp) sequence divergences in order to investigate the basis of vole susceptibility in comparison to other rodent models. at first, we found a differential susceptibility of bank and field voles compared to c57bl/6 and wo ...200818654630
characterisation of new monoclonal antibodies reacting with prions from both human and animal brain tissues.post-mortem diagnosis of transmissible spongiform encephalopathies (prion diseases) is primarily based on the detection of a protease resistant, misfolded disease associated isoform (prp(sc)) of the prion protein (prp(c)) on neuronal cells. these methods depend on antibodies directed against prp(c) and capable of reacting with prp(sc)in situ (immunohistochemistry on nervous tissue sections) or with the unfolded form of the protein (western and paraffin embedded tissue (pet) blotting). here, high ...200818657541
prion infection of mice transgenic for human appswe: increased accumulation of cortical formic acid extractable abeta(1-42) and rapid scrapie disease development.neuropathological, epidemiological and experimental data indicate a potential interrelationship between alzheimer's disease and prion diseases. proteolytic processing of amyloid precursor protein (app) by beta-secretase was recently suggested to be controlled by prion protein expression. here, we characterized the prion infection of tg2576 mice, which overexpress the human app(swe) protein. prion infection of tg2576-mice led to an early death of the animals, which was preceded by a relatively sh ...200818662767
extending zelterman's approach for robust estimation of population size to zero-truncated clustered data.estimation of population size with missing zero-class is an important problem that is encountered in epidemiological assessment studies. fitting a poisson model to the observed data by the method of maximum likelihood and estimation of the population size based on this fit is an approach that has been widely used for this purpose. in practice, however, the poisson assumption is seldom satisfied. zelterman (1988) has proposed a robust estimator for unclustered data that works well in a wide class ...200818663764
effect of the dimethoate administration on a scrapie murine model.some authors have associated organophosphate compounds with susceptibility to transmissible spongiform encephalopathy (tse) and even with the origin of this group of diseases. nevertheless, the actual role played by these compounds still remains unclear. the aim of this study was to assess the effect of oral exposure to dimethoate (dmt) on the development of scrapie using a genetically modified murine model. a total of 70 c57bl/6 mice over-expressing the prp gene (tg20) were included in the pres ...200818667030
synthetic fibril peptide promotes clearance of scrapie prion protein by lysosomal degradation.transmissible spongiform encephalopathies are infectious and neurodegenerative disorders that cause neural deposition of aggregates of the disease-associated form of prp(sc). prp(sc) reproduces by recruiting and converting the cellular prp(c), and scn2a cells support prp(sc) propagation. we found that incubation of scn2a cells with a fibril peptide named p9, which comprises an intrinsic sequence of residues 167-184 of mouse prp(c), significantly reduced the amount of prp(sc) in 24 hr. p9 did not ...200818667034
scrapie-induced defects in learning and memory of transgenic mice expressing anchorless prion protein are associated with alterations in the gamma aminobutyric acid-ergic pathway.after infection with rml murine scrapie agent, transgenic (tg) mice expressing prion protein (prp) without its glycophosphatidylinositol (gpi) membrane anchor (gpi(-/-) prp tg mice) continue to make abundant amounts of the abnormally folded disease-associated prpres but have a normal life span. in contrast, all age-, sex-, and genetically matched mice with a gpi-anchored prp become moribund and die due to a chronic progressive neurodegenerative disease by 160 days after rml scrapie agent infecti ...200818667494
breeding for scrapie resistance in the hungarian sheep population.the first results of the hungarian sheep prion protein (prp) genotyping programme are discussed in this paper. to obtain initial genotype frequency data 10 commercial (hungarian merino, german mutton merino, merino landschaf, german blackheaded, suffolk, texel, ile de france, charollais, lacaune, british milksheep) and 4 indigenous (gyimes racka, hortobágy racka, tsigaja, cikta) breeds were sampled in 2003 and 2004, and the prp genotypes were determined by microsequencing analysis with capillary ...200818669244
[establishment of an assay for prp(sc) detection based on streptomycin precipitation].to establish a new western blotting assay for prp(sc) detection, we optimized the western blotting assay with a precipitation procedure of streptomycin sulfate. after digestion with pk, 10% scrapie infected hamster brain homogenates were incubated with 60 mmol/l streptomycin and the precipitated prp(sc) was recovered by centrifugation. the enrichment of prp(sc) by streptomycin sulfate precipitation was evaluated using western blotting assay. the results showed streptomycin could bind to pk-treat ...200818683554
small-ruminant lentivirus enhances prpsc accumulation in cultured sheep microglial cells.sheep scrapie is the prototypical transmissible spongiform encephalopathy (prion disease), which has a fundamental pathogenesis involving conversion of normal cellular prion protein (prp(c) [c superscript stands for cellular]) to disease-associated prion protein (prp(sc) [sc superscript stands for sheep scrapie]). sheep microglial cell cultures, derived from a prnp 136vv/171qq near-term fetal brain, were developed to study sheep scrapie in the natural host and to investigate potential cofactors ...200818684809
prominent pancreatic endocrinopathy and altered control of food intake disrupt energy homeostasis in prion diseases.prion diseases are fatal neurodegenerative diseases that can induce endocrinopathies. the basis of altered endocrine function in prion diseases is not well understood, and the purpose of this study was to investigate the spatiotemporal relationship between energy homeostasis and prion infection in hamsters inoculated with either the 139h strain of scrapie agent, which induces preclinical weight gain, or the hy strain of transmissible mink encephalopathy (tme), which induces clinical weight loss. ...200818434355
increase of monoamine oxidase-b activity in the brain of scrapie-infected hamsters.in the present study, the purpose is to determine activities of monoamine oxidases (mao) in the brain of 263k scrapie-infected hamsters during the development of this experimental prion disease. indeed, mao activity modifications which have already been related in aging and neurodegenerations is suspected to be involved in the neuron loss process by elevated hydrogen peroxide formation. monoamine oxidase type a (mao-a) and b (mao-b) activities were followed in the brain at different stages of th ...200818442871
pruritus is a common feature in sheep infected with the bse agent.the variability in the clinical or pathological presentation of transmissible spongiform encephalopathies (tses) in sheep, such as scrapie and bovine spongiform encephalopathy (bse), has been attributed to prion protein genotype, strain, breed, clinical duration, dose, route and type of inoculum and the age at infection. the study aimed to describe the clinical signs in sheep infected with the bse agent throughout its clinical course to determine whether the clinical signs were as variable as de ...200818445253
the key-role of tyrosine 155 in the mechanism of prion transconformation as highlighted by a study of sheep mutant peptides.prion protein is a strongly conserved and ubiquitous glycoprotein. the conformational conversion of the non-pathogenic cellular prion isoform (prp(c)) into a pathogenic scrapie isoform (prp(sc)) is a fundamental event in the onset of transmissible spongiform encephalopathies (tse). during this conversion, helix h1 and its two flanking loops are known to undergo a conformational transition into a beta-like structure. in order to understand mechanisms which trigger this transconformation, sheep pr ...200818455265
prion diseases and emerging prion diseases.transmissible spongiform encephalopathies (tses), also called prion diseases, are fatal neurodegenerative disorders. an abnormal isoform of the prion protein (prp(sc)) generated by post-translational modification of the cellular prion protein (prp(c)) is believed to be the main component of this infectious agent. prp(sc) is relatively resistant to proteinase k (pk) digestion. this characteristic has been widely accepted as the physicochemical basis for distinguishing between prp(c) and prp(sc). ...200818473798
cholesterol transporter atp-binding cassette a1 (abca1) is elevated in prion disease and affects prpc and prpsc concentrations in cultured cells.prion diseases are transmissible neurodegenerative disorders of prion protein (prp) conformation. prion replication by conversion of benign prpc isoforms into disease-specific prpsc isoforms is intimately involved in prion disease pathogenesis and may be initiated in cholesterol-rich caveolae-like domains (cld). concentrations of the cholesterol transporter atp-binding cassette a1 protein (abca1) are elevated in pre-clinical scrapie prion-infected mice and in prion-infected cells in vitro. eleva ...200818474570
effect of intraventricular infusion of anti-prion protein monoclonal antibodies on disease progression in prion-infected mice.it is well known that anti-prion protein (prp) monoclonal antibodies (mabs) inhibit abnormal isoform prp (prpsc) formation in cell culture. additionally, passive immunization of anti-prp mabs protects the animals from prion infection via peripheral challenge when mabs are administered simultaneously or soon after prion inoculation. thus, anti-prp mabs are candidates for the treatment of prion diseases. however, the effects of mabs on disease progression in the middle and late stages of the disea ...200818474571
prion propagation in mice lacking central nervous system nf-kappab signalling.prions induce highly typical histopathological changes including cell death, spongiosis and activation of glia, yet the molecular pathways leading to neurodegeneration remain elusive. following prion infection, enhanced nuclear factor-kappab (nf-kappab) activity in the brain parallels the first pathological changes. the nf-kappab pathway is essential for proliferation, regulation of apoptosis and immune responses involving induction of inflammation. the ikappab kinase (ikk) signalosome is crucia ...200818474572
virus-induced alterations of membrane lipids affect the incorporation of prp sc into cells.prion diseases are fatal neurodegenerative disorders characterized by long incubation periods. to investigate whether concurrent diseases can modify the clinical outcome of prion-affected subjects, we tested the effect of viral infection on the binding and internalization of prp(sc), essential steps of prion propagation. to this effect, we added scrapie brain homogenate or purified prp(sc) to fibroblasts previously infected with minute virus of mice (mvm), a mouse parvovirus. we show here that t ...200818478553
transmissible spongiform encephalopathy strain-associated diversity of n-terminal proteinase k cleavage sites of prp(sc) from scrapie-infected and bovine spongiform encephalopathy-infected mice.assessment of the different conformational states of the abnormal prion protein (prp(sc)) in the cns provides an established basis for distinguishing transmissible spongiform encephalopathy (tse) strains. prp(sc) conformers are variably resistant to n-terminal proteinase k (pk) digestion, and analysis of the consensus products (prp(res)) by immunoassay enables effective, but relatively low-resolution differentiation. determination of the precise n-terminal amino acid profile (n-taap) of prp(res) ...200818484354
prion early kinetics revisited using a streptomycin-based prp(res) extraction method.the use of streptomycin in the prp(sc) detection procedures represents a new and attractive way to detect more prp(sc), the best marker for the transmissible spongiform encephalopathies (tses). actually, the streptomycin prp(sc) aggregating property reported recently was established as beneficial in prp(sc) detection using immunohistochemistry in diagnostic as well as in experimental conditions. the present study reports in details how to use advantageously this original streptomycin property in ...200818489903
identification of new quantitative trait loci (other than the prnp gene) modulating the scrapie incubation period in sheep.although susceptibility to scrapie is largely controlled by the prnp gene, we have searched for additional genomic regions that affect scrapie incubation time in sheep, using two half-sib families with a susceptible prnp genotype and naturally infected by scrapie. quantitative trait loci were detected on oar6 and oar18.200818493086
antimicrobial use in the alberta sheep industry.information regarding antimicrobial use in sheep is scarce. in 2001, a scrapie surveillance program was initiated in alberta that also provided a mechanism for collecting other sheep health data including antimicrobial use information between april 2001 and april 2002. a major objective of this study was to describe antimicrobial use in the alberta sheep industry. this was done by obtaining qualitative antimicrobial use information from all flocks (n = 212) providing cull ewes to the program usi ...200818505202
transmission and detection of prions in feces.in chronic wasting disease (cwd) in cervids and in scrapie in sheep, prions appear to be transmitted horizontally. oral exposure to prion-tainted blood, urine, saliva, and feces has been suggested as the mode of transmission of cwd and scrapie among herbivores susceptible to these prion diseases. to explore the transmission of prions through feces, uninoculated syrian hamsters (shas) were cohabitated with or exposed to the bedding of shas orally infected with sc237 prions. incubation times of 14 ...200818505383
atypical scrapie in a sheep in a closed uk flock with endemic classical natural scrapie. 200818515761
polymorphisms of the prion protein gene in sheep of inner mongolia, china.polymorphisms of the prion protein gene (prnp), especially the amino acid residue alterations at codons 136, 154, and 174, in sheep have been found to be associated with susceptibility to scrapie disease. we investigated prnp polymorphisms in three local sheep breeds in inner mongolia, china. blood samples were collected from 46 ujumqin, 34 sunite, and 22 mongolian sheep. the genetic dna of blood samples was extracted, amplified and sequenced, and amino acid alignment was determined. polymorphis ...200818521732
induced neuroprotection independently from prpsc accumulation in a mouse model for prion disease treated with simvastatin.the misfolding and aggregation of specific proteins has emerged as a key feature of several neurodegenerative diseases. in prion diseases, progressive disease and neuronal loss are associated with the accumulation of prp(sc), the misfolded isoform of prp(c). previous in vitro studies suggest that cholesterol-lowering drugs inhibit the conversion of prp(c) to prp(sc) and the accumulation of the latter, possibly through the disturbance of cholesterol-rich membrane domains (lipid rafts).200818541796
different expression patterns of ck2 subunits in the brains of experimental animals and patients with transmissible spongiform encephalopathies.to address the possible alteration of casein kinase 2 (ck2) in transmissible spongiform encephalopathies (tses), the levels and patterns of ck2 in the brain tissues of hamsters or c57bl mice inoculated intracerebrally with scrapie agents 263k or 139a were evaluated by western blots, followed by quantitative analysis. specific semi-quantitative rt-pcr for evaluating the mrna transcripts of ck2 subunits was performed in parallel. compared with normal animals, the levels of ck2alpha and ck2beta in ...200818404245
high titers of mucosal and systemic anti-prp antibodies abrogate oral prion infection in mucosal-vaccinated mice.significant outbreaks of prion disease linked to oral exposure of the prion agent have occurred in animal and human populations. these disorders are associated with a conformational change of a normal protein, prp(c) (c for cellular), to a toxic and infectious form, prp(sc) (sc for scrapie). none of the prionoses currently have an effective treatment. some forms of prion disease are thought to be spread by oral ingestion of prp(sc), such as chronic wasting disease and variant creutzfeldt-jakob d ...200818407424
association of the prion protein gene with individual tissue weights in scottish blackface sheep.this study investigated associations of prion protein (prp) genotype with body composition and weight traits of scottish blackface ewes. body composition was predicted using computer tomography (ct) scans to estimate muscle, carcass fat, internal fat, and bone weights. the traits were measured at 4 key seasonal production points (pre-mating, pregnancy, midlactation, and weaning) over 4 production cycles (2 to 5 yr old). there were 2,413 records for each of the ct traits measured on 335 ewes, and ...200818407978
mouse neuroblastoma cells release prion infectivity associated with exosomal vesicles.tses (transmissible spongiform encephalopathies) are neurodegenerative disorders affecting humans and animals. prp(sc), a conformationally altered isoform of the normal prion protein (prp(c)), is thought to be the pathogenic agent. however, the biochemical composition of the prion agent is still matter of debate. the potential transmission risk of the prion agent through biological fluids has been shown, but the development of competitive diagnostic tests and treatment for tses requires a more c ...200818422484
canine mdck cell lines are refractory to infection with human and mouse prions.influenza vaccine production in embryonated eggs is associated with many disadvantages, and production in cell culture systems is a viable alternative. madin darby canine kidney (mdck) cells are permissive for a variety of orthomyxoviruses and have proven particularly suitable for vaccine mass production. however, mammalian cells harboring the prnp gene can theoretically acquire prion infections. here, we have attempted to infect mdck cells and substrains thereof with prions. we found that mdck ...200818423803
atypical scrapie in a sheep in scotland. 200818424849
scrapie transmission via milk. 200818424852
myenteric neurons of the ileum that express somatostatin are a target of prion neuroinvasion in an alimentary model of sheep scrapie.neuroinvasion of the enteric nervous system by prions is an important step in dissemination to the brain, yet very little is known about the basic process of enteric neuroinvasion. using an alimentary model of neonatal disease transmission, neuroinvasion by scrapie prions in the ileum of lambs was detected by immunohistochemical staining for the disease-associated form of the prion protein, prpsc. odds ratios (or) were determined for the frequency of prpsc staining within enteric somata categori ...200818427817
excretion of bse and scrapie prions in stools from murine models.faeces from infected animals have been suggested as a potential source of contamination and transmission of prion diseases in the environment. this work describes the development of a procedure for the detection of prp(res) in stools which is based on a detergent-based extraction and immunoprecipitation (ip). the procedure was evaluated by analyzing tse-spiked sheep and mice faeces, and proved to be specific for prp(res) with sensitivities of 5-10 microg of infected brain tissue. in order to ana ...200818395370
role of erk1/2 activation in prion disease pathogenesis: absence of ccr1 leads to increased erk1/2 activation and accelerated disease progression.prion diseases are neurodegenerative infections with gliosis and vacuolation. the mechanisms of degeneration remain unclear, but chemokines may be important. in current experiments ccr1 knock-out (ko) mice succumbed more rapidly to scrapie infection than wt controls. infected ko mice had upregulation of ccl3, a ccr1 ligand, and ccr5, a receptor with specificity for ccl3. both infected ko and wt mice had upregulation of ccr5-mediated signaling involving activation of erk1/2 in astrocytes; however ...200818396336
evidence of scrapie transmission via milk.the risk of scrapie infection increases with increased duration and proximity of contact between sheep at lambing. scrapie infectivity has not been detected in milk but cellular prion protein, the precursor of disease-associated prion protein prpd, has been found in milk from ruminants. to determine whether milk is able to transmit scrapie, 18 lambs with a prion protein genotype associated with high susceptibility to scrapie (vrq/vrq) were fed milk from twelve scrapie-affected ewes of the same g ...200818397513
tubulovesicular structures are a consistent (and unexplained) finding in the brains of humans with prion diseases.creutzfeldt-jakob disease (cjd), gerstmann-sträussler-scheinker disease (gss) and fatal familial insomnia (ffi) are slow neurodegenerative disorders classified as transmissible spongiform encephalopathies (tses) or prion diseases, which appear in sporadic, hereditary or environmentally acquired forms. tubulovesicular structures (tvs) are ultrastructural particles of unknown origin and chemical composition found in the brains of both animal and human forms of transmissible spongiform encephalopat ...200818164506
unraveling prion strains with cell biology and organic chemistry. 200818172195
observing fibrillar assemblies on scrapie-infected cells.the infectious agent in prion diseases is an aberrant-folded isoform of the cellular prion protein (prpc). this scrapie-related prion protein (prpsc) has an increased beta-sheet content, is detergent insoluble and proteinase k resistant, and accumulates in prion-infected organisms and cells. in vitro, prpsc self-aggregates into amyloid fibrils. however, there is no direct experimental proof for the occurrence of prpsc-containing fibrils in vivo or in cell cultures. applying atomic force microsco ...200818175144
semen from scrapie-infected rams does not transmit prion infection to transgenic mice.scrapie is the most common transmissible spongiform encephalopathy (tse) in livestock. natural contamination in sheep flocks is presumed to occur by maternal transmission to offspring. however, horizontal prion transmission from animal to animal exists and may be significant in sustaining and spreading contagion in the field. artificial insemination is widely used in modern farming, and as large amounts of prion protein have been found in sheep sperm membrane, epididymal fluid and seminal plasma ...200818299435
a comparison of the active surveillance of scrapie in the european union.the abattoir and the fallen stock surveys constitute the active surveillance component aimed at improving the detection of scrapie across the european union. previous studies have suggested the occurrence of significant differences in the operation of the surveys across the eu. in the present study we assessed the standardisation of the surveys throughout time across the eu and identified clusters of countries with similar underlying characteristics allowing comparisons between them. in the abse ...200818307969
simplified ultrasensitive prion detection by recombinant prp conversion with shaking. 200818309304
impy, a potential beta-amyloid imaging probe for detection of prion deposits in scrapie-infected mice.a potential single-photon emission computed tomography imaging agent for labeling of a beta plaques of alzheimer's disease, impy (2-(4'-dimethylaminophenyl)-6-iodo-imidazo[1,2-a]pyridine), would be effective in detection of prion amyloid deposits in transmissible spongiform encephalopathies (tses).200818312829
comprehensive transcriptional profiling of prion infection in mouse models reveals networks of responsive genes.prion infection results in progressive neurodegeneration of the central nervous system invariably resulting in death. the pathological effects of prion diseases in the brain are morphologically well defined, such as gliosis, vacuolation, and the accumulation of disease-specific protease-resistant prion protein (prpsc). however, the underlying molecular events that lead to the death of neurons are poorly characterised.200818315872
prion protein in sheep urine.the misfolded form of cellular prion protein (prp(c)) is the main component of the infectious agent of transmissible spongiform encephalopathies and the validated biomarker for these diseases. the expression of prp(c) is highest in the central nervous system and has been found in peripheral tissues. soluble prp(c) has been detected in cerebrospinal fluid, urine, serum, milk, and seminal plasma. in this study, attempts were made to characterize prion protein in urine samples from normal and scrap ...200818319425
adaptation and evaluation of a rapid test for the diagnosis of sheep scrapie in samples of rectal mucosa.in recent publications, it was shown that disease-associated prion protein (prp(d)) accumulates in the lymphoid tissue of the rectal mucosa of a high proportion of scrapie-infected sheep at clinical and preclinical stages, regardless of several host factors; prp(d) can also be detected in biopsy specimens of rectal mucosa, with an increased probability proportional to age or incubation period and with an efficiency almost identical to that of tonsil biopsies. rectal biopsies have the advantages ...200818319433
a real-time polymerase chain reaction assay to detect single nucleotide polymorphisms at codon 171 in the prion gene for the genotyping of scrapie susceptibility in sheep.the objective of this study was to report a reliable real-time polymerase chain reaction assay compatible with the roche lightcycler 2.0 capable of genotyping sheep for scrapie susceptibility at codon 171. the single nucleotide polymorphisms (snps) in the prion protein gene in sheep that may govern resistance to scrapie at codon 171 encode for lysine (k), histidine (h), glutamine (q), and arginine (r). a modified proteinase k method for leukocytes or whole blood was used to isolate genomic dna f ...200818319434
conformational change in hamster scrapie prion protein (prp27-30) associated with proteinase k resistance and prion infectivity.the scrapie prion protein (prp27-30) is a crucial component of the prion and is responsible for its transmissibility. structural information on this protein is limited because it is insoluble and shows aggregated properties. in this study, prp27-30 was effectively dispersed using sonication under the weak alkaline condition. subsequently, the small prp27-30 aggregates were subjected to different ph, heat, and denaturing conditions. the loss of proteinase k (pk) resistance of prp27-30 and prion i ...200818319576
detection and survival of prion agents in aquatic environments.environmental contamination is considered a potential mechanism of transmission of prion diseases. sheep scrapie and cervid chronic wasting diseases (cwd) epizootics are thought to be maintained by natural horizontal transmission through the environment. here, we describe a method for the detection of prion proteins (prpres) in aquatic environments. the procedure is based on a glycine buffer-mediated extraction, sonication, and an ultracentrifugation step. the detection limit of the method was e ...200818321558
cannabidiol: a prion therapy for mice? 200818338806
a sensitive and quantitative assay for normal prp in plasma.transmissible spongiform encephalopathies can be transmitted by blood transfusion. the risk of spreading the disease among the human population could be mitigated with the implementation of a blood screening assay. we developed a two-antibody assay for prp detection in plasma using the origen technology with a protocol modification to improve the limit of detection and to increase the sample volume assayed. in the standard 200 microl format, the assay had a detection limit of 7-10 pg of recombin ...200818339433
aggregation and amyloid fibril formation of the prion protein is accelerated in the presence of glycogen.prion diseases like creutzfeldt-jakob disease in humans or scrapie in sheep and goats are infectious neurodegenerative diseases. their infectious agent, called prion, is composed mainly of aggregated and misfolded prion protein and non-proteinaceous components. an example of such a common non-proteinaceous secondary component of natural prions is the polysaccharide scaffold. we studied the influence of such a polysaccharide on the conformational transition of prp applying an in vitro conversion ...200818341429
thr but asn of the n-glycosylation sites of prp is indispensable for its misfolding.prion protein (prp) contains two n-linked glycosylation sites. it is unknown which amino acid substitution contributes most efficiently to the abolishment of n-linked glycosylations. to define the influence of amino acid substitution at the n-linked glycosylation sites on the conversion efficiency of mouse prp, we tested each of all 19 amino acid substitutions at either one of the n-linked glycosylation sites (codon 180, 182, 196 or 198). the conversion efficiency of the mutagenized prp was high ...200818343219
a species barrier limits transmission of chronic wasting disease to mink (mustela vison).transmissible mink encephalopathy (tme) occurs as sporadic outbreaks associated with ingestion of feed presumably contaminated with some type of prion disease. mink lack a species barrier to primary oral challenge with bovine spongiform encephalopathy, whereas they have a barrier to such challenge with scrapie. we investigated whether mink have a species barrier to chronic wasting disease (cwd) by performing primary intracerebral (ic) and primary oral challenge with cwd-positive elk brain. prima ...200818343853
structural and functional analysis of the hsp90aa1 gene: distribution of polymorphisms among sheep with different responses to scrapie.scrapie is a transmissible spongiform encephalopathy in sheep and goats. susceptibility to this neurodegenerative disease is mainly controlled by point mutations at the prnp locus. other genes, apart from prnp, have been reported to modulate resistance/susceptibility to scrapie. on the basis of several studies in alzheimer and different transmissible spongiform encephalopathy models, hsp90aa1 was chosen as a putative positional and functional candidate gene that might be involved in the polygeni ...200818347938
prevalence of sheep infected with classical scrapie in great britain: integrating multiple sources of surveillance data for 2002.estimates for the prevalence of sheep infected with classical scrapie are essential for assessing the efficacy of control strategies that have been implemented in great britain (gb). here a back-calculation approach was used to estimate the prevalence in the gb national flock by integrating data on reported cases and the results of abattoir and fallen stock surveys for 2002. prevalence estimates ranged from 0.33 to 2.06%, depending on the estimates used for the frequencies of prion protein (prp) ...200818348959
chemically induced accumulation of gags delays prp(sc) clearance but prolongs prion disease incubation time.prion diseases are a group of fatal neurodegenerative diseases affecting humans and animals. the only identified component of the infectious prion is prp(sc), an aberrantly folded isoform of prp(c). glycosaminoglycans, which constitute the main receptor for prions on cells, play a complex role in the pathogenesis of prion diseases. for example, while agents inducing aberrant lysosomal accumulation of gags such as tilorone and quinacrine significantly reduced prp(sc) content in scrapie-infected c ...200818350378
distinct immunohistochemical localization in kuru plaques using novel anti-prion protein antibodies.by immunizing prnp-knockout mice with synthetic polypeptides, a panel of mabs directed to bovine prp(c) was obtained. the mab panel was characterized by the elisa method, where synthetic polypeptides were used for epitope mapping. different reactivity patterns were identified. the ability of these mabs to detect abnormal prp(sc) in cjd cases was studied by immunohistochemistry. all mabs were tested for prp(sc) in murine, bovine, monkey and human brain tissues. three mabs recognized the fragmente ...200818352909
application of one-list capture-recapture models to scrapie surveillance data in great britain.in this paper, we apply one-list capture-recapture models to estimate the number of scrapie-affected holdings in great britain. we applied this technique to the compulsory scrapie flocks scheme dataset where cases from all the surveillance sources monitoring the presence of scrapie in great britain, the abattoir survey, the fallen stock survey and the statutory reporting of clinical cases, are gathered. consequently, the estimates of prevalence obtained from this scheme should be comprehensive a ...200818355934
effects of nutrition and genotype on prion protein (prpc) gene expression in the fetal and maternal sheep placenta.for placental transmission of scrapie to occur, the normal cellular prion protein (prpc) must be converted to an abnormal infectious form known as prpsc. prpc genotype influences susceptibility to contracting scrapie, but we still do not understand whether genotype or expression levels of prpc are important in transmission of scrapie. some evidence exists that nutrition affects expression levels of prpc. thus, we evaluated the effects of genotype and nutrition on prpc mrna and protein expression ...200818358531
the efficacy of tetracyclines in peripheral and intracerebral prion infection.we have previously shown that tetracyclines interact with and reverse the protease resistance of pathological prion protein extracted from scrapie-infected animals and patients with all forms of creutzfeldt-jakob disease, lowering the prion titre and prolonging survival of cerebrally infected animals. to investigate the effectiveness of these drugs as anti-prion agents syrian hamsters were inoculated intramuscularly or subcutaneously with 263k scrapie strain at a 10(-4) dilution. tetracyclines w ...200818365024
cell death and autophagy in prion diseases (transmissible spongiform encephalopathies).neuronal autophagy, like apoptosis, is one of the mechanisms of programmed cell death. in this review, we summarize current information about autophagy in naturally occurring and experimentally induced scrapie, creutzfeldt-jakob disease and gerstmann-sträussler-scheinker syndrome against the broad background of neural degenerations in transmissible spongiform encephalopathies (tses). typically a sequence of events is observed: from a part of the neuronal cytoplasm sequestrated by concentric arra ...200818368623
subependymal plaques in scrapie-affected hamster brains--why are they so different from compact kuru plaques?we report here routine thin-section and immunogold electron microscopic studies on diffuse plaques in scrapie-affected hamster brains. these plaques were not discernible by routine he staining. ultrastructurally, plaques were recognized as areas of low electron density containing haphazardly-oriented fibrils, but not as stellate compact structures typical of mouse scrapie models; hence we labelled them "loose plaques". following immunohistochemistry at the electron microscopy level, fibrils with ...200818368625
polymorphism of the prnp gene in the main breeds of indigenous chinese goats.the polymorphism of the prnp gene plays a key role in susceptibility to prion disease. scrapie is a neurodegenerative disease affecting sheep and goats and belongs to the group of prion diseases. we isolated dna from 333 goat samples representing the main local goat breeds in six provinces in china to identify prnp polymorphisms and to determine whether these breeds were at risk for developing scrapie. two novel amino acid polymorphisms (r211g and t219i) and a novel silent mutation at codon 125 ...200818369524
ultrastructural evidence that ependymal cells are infected in experimental scrapie.during the last stage of infection in the experimental scrapie-infected hamster model, light microscopy reveals typical immunostaining of prpsc in the subependymal region and at the apical ependymal cell borders. whereas the subependymal immuno-staining is known to originate from extracellular amyloid filaments and residual membranes of astrocytes as constituents of plaque-like structures, the ultrastructural correlate of the supraependymal prpsc staining remains uncertain. to decipher this apic ...200818369649
antiprion prophylaxis by gene transfer of a soluble prion antagonist.prion diseases are untreatable neurodegenerative disorders characterized by accumulation of prp(sc), an aggregated isoform of the normal prion protein prp(c). here, we delivered the soluble prion antagonist prp-fc(2) to the brains of mice by lentiviral gene transfer. although naïve mice developed scrapie at 175 +/- 5 days postintracerebral prion inoculation (dpi), gene transfer before inoculation delayed disease onset by 72 +/- 4 days. at 170 days postintracerebral prion inoculation, prp(sc) acc ...200818372425
identification of differentially expressed genes in ileal peyer's patch of scrapie-infected sheep using rna arbitrarily primed pcr.in scrapie and prion diseases, the knowledge concerning genes involved in host response during the early infection period in the lymphoid tissues, still remains limited. in the present study, we have examined differential gene expression in ileal peyer's patches and in laser microdissected follicles of sheep infected with scrapie.200818373840
diagnosis of preclinical scrapie in live sheep by the immunohistochemical examination of rectal biopsies.in most sheep infected with a transmissible spongiform encephalopathy (tse) the disease-associated prion protein (prp(d)) accumulates in tissues of the lymphoreticular system, suggesting that it might be detected in biopsy specimens. a procedure has been developed to obtain biopsy specimens of rectal mucosa in which prp(d) has been detected by immunohistochemistry in preclinically infected sheep of all susceptible prp genotypes. it is probable that prp(d) increases with the age of sheep or perio ...200818375983
occurrence and cellular localization of prpd in kidneys of scrapie-affected sheep in the absence of inflammation.following a preliminary description of disease-associated prion protein (prpd) deposition in the kidneys of scrapie-affected sheep, detailed studies have been undertaken in order to evaluate the factors that could account for such prpd accumulation and to determine the precise location of prpd in the renal papillae. immunohistochemical (ihc) examinations for prpd were conducted in kidneys collected at post-mortem from 30 naturally and 37 experimentally infected sheep. in addition, prpd detection ...200818381605
no temporal trends in the prevalence of atypical scrapie in british sheep, 2002-2006.so-called atypical scrapie was first identified in great britain (gb) in 2002 following the introduction of wide-scale scrapie surveillance. in particular, abattoir and fallen stock surveys have been carried out in gb since 2002, with a total of 147 atypical positives identified by the end of 2006. the results of these surveys provide data with which to assess temporal trends in the prevalence of atypical scrapie in sheep in great britain between 2002 and 2006.200818384678
neuroendocrine cultured cells counteract persistent prion infection by down-regulation of prpc.cell models for prion diseases are mainly of neuronal origin. however, the pathological isoform prp(sc) of cellular prion protein (prp(c)) and prion infectivity are found in a variety of extraneural tissues in prion diseases. although many cell types are not able to propagate prp(sc), little is known about cellular mechanism counteracting prion infection. it is desirable to identify neuronal or non-neuronal cell models that restrict prp(sc) generation or propagate prp(sc) only transiently. neuro ...200818387818
tubulovesicular structures are present in brains of hamsters infected with the echigo-1 strain of creutzfeldt-jakob disease agent.tubulovesicular structures (particles; tvs) are virion-like particles 25-30 nm in diameter found by thin-section electron microscopy in brains of all prion diseases including scrapie, creutzfeldt-jakob disease (cjd) fatal familial insomnia (ffi) and gerstmann-sträussler-scheineker disease (gss) as well as in cell cultures infected with tse agents. tvs are regarded as a disease-specific ultrastructural marker for tses and, by those not completely satisfied with the prion hypothesis, they are even ...200818389013
the tubulovesicular structures - the ultrastructural hallmark for all prion diseases.tubulovesicular structures (particles - tvs) are the only ultrastructural marker for all prion diseases as seen by thin-section electron microscopy as opposed to "negative-staining" techniques. tvs are spheres or short rods of approximately 27 nm in diameter. that size of tvs is also the size of filter cut-off of infectivity as judged from the ultrafiltration studies and the size of the smallest infectious unit as recently estimated. tvs have been found in all naturally occurring and experimenta ...200818389022
rapid typing of transmissible spongiform encephalopathy strains with differential elisa.the bovine spongiform encephalopathy (bse) agent has been transmitted to humans, leading to variant creutzfeldt-jakob disease. sheep and goats can be experimentally infected by bse and have been potentially exposed to natural bse; however, whether bse can be transmitted to small ruminants is not known. based on the particular biochemical properties of the abnormal prion protein (prpsc) associated with bse, and particularly the increased degradation induced by proteinase k in the n terminal part ...200818394279
the stability and aggregation of ovine prion protein associated with classical and atypical scrapie correlates with the ease of unwinding of helix-2.susceptibility to scrapie disease in sheep, the archetypal prion disease, correlates with polymorphisms within the ovine prp (prion-related protein) gene. the vrq (val136arg154gln171) and al141rq (ala136leu141arg154gln171) allelic variants are associated with classical scrapie, whereas the arr (ala136arg154arg171), af141rq (ala136phe141arg154gln171) and ahq (ala136his154gln171) allelic variants are associated with atypical scrapie. recent studies have suggested that there are differences in the ...200817931166
retinal cell types are differentially affected in sheep with scrapie.transmissible spongiform encephalopathies (tses) are a group of fatal neurodegenerative diseases characterized microscopically by spongiform lesions (vacuolation) in the neuropil, neuronal loss, and gliosis. accumulation of the abnormal form of the prion protein (prp(sc)) has been demonstrated in the retina of natural and non-natural tse-affected hosts, with or without evidence of microscopically detectable retinal pathology. this study was conducted to investigate the effect of prp(sc) accumula ...200818061608
a monoclonal antibody (1d12) defines novel distribution patterns of prion protein (prp) as granules in nucleus.a monoclonal antibody (mab) panel to bovine prion protein (prp) was studied by immunoblotting and immunohistochemistry for scrapie and bovine spongiform encephalopathy. a mab panel recognized both normal (prp(c)) and abnormal (prp(sc)) isoforms of prp in murine, ovine and bovine brain tissues. interestingly, an anti-bovine prp mab, 1d12, prepared by immunizing prp gene-knockout mice with a synthetic polypeptides corresponding to codons 153-166 of the bovine prp gene showed novel patterns of reac ...200818068119
cell models of prion infection.due to recent renewal of interest and concerns in prion diseases, a number of cell systems permissive to prion multiplication have been generated in the last years. these include established cell lines, neuronal stem cells and primary neuronal cultures. while most of these models are permissive to experimental, mouse-adapted strains of prions, the propagation of natural field isolates from sheep scrapie and chronic wasting disease has been recently achieved. these models have improved our knowle ...200818073097
human prion diseases: from antibody screening to a standardized fast immunodiagnosis using automation.demonstration of pathological prion protein accumulation in the central nervous system is required to establish the diagnosis of transmissible subacute encephalopathies. in humans, this is frequently achieved using prion protein immunohistochemistry in paraffin-embedded tissue, a technique that requires multiple epitope retrieval and denaturing pretreatments. in addition to being time-consuming, this procedure induces tissue alterations that preclude accurate morphological examination. the aim o ...200818084251
molecular interaction between prion protein and gfap both in native and recombinant forms in vitro.gliosis of glial fibrillary acidic protein (gfap) associated astrocytes is considered to be one of the hallmarks of transmissible spongiform encephalopathies (tses). in the present study, remarkable gfap-prp(sc) or gfap-prp(c) complexes were separately detected in the brain homogenates of 263 k (scrapie)-infected or normal hamsters by co-immunoprecipitation assay. to get more exact molecular evidences for interaction between prion protein (prp) and gfap, various recombinant prp or gfap proteins ...200818087720
resistance of cell lines to prion toxicity aided by phospho-erk expression.prion diseases are fatal neurodegenerative disorders. they are characterised by neuronal loss and the accumulation of an abnormal protein in the cns. cell lines exist that express the toxic form of the prion protein (prp) with little evidence of cell death. other cell based models studying the mechanism by which cell death occurs employ exogenous application of peptides or fragments of prp. in this study, we demonstrated that full-length recombinant prp binding manganese was toxic to prp-express ...200818088369
the deletion of amino acids 114-121 in the tm1 domain of mouse prion protein stabilizes its conformation but does not affect the overall structure.a mutant of mouse prion protein (prpc) carrying a deletion of residues 114-121 (prpdelta114-121) has previously been described to lack convertibility into the scrapie-associated isoform of prp (prpsc) and to exhibit a dominant-negative effect on the conversion of wild-type prpc into prpsc in living cells. here we report the characterization of recombinantly expressed prpdelta114-121 by fourier-transformation infrared spectroscopy (ftir) and circular dichroism (cd) spectroscopy. the analysis of s ...200818088603
decontamination of surgical instruments from prions. ii. in vivo findings with a model system for testing the removal of scrapie infectivity from steel surfaces.the unusual resistance of agents causing transmissible spongiform encephalopathies (tses) to chemical or thermal inactivation requires special decontamination procedures in order to prevent accidental transmission of these pathogens by surgical instruments. in the search for effective, instrument-compatible and routinely applicable decontamination procedures, a previous study [lemmer, k., mielke, m., pauli, g. & beekes, m. (2004). j gen virol 85, 3805-3816] identified promising reagents in an in ...200818089760
pathogenesis of bovine spongiform encephalopathy in sheep.the pathogenesis of bovine spongiform encephalopathy (bse) in sheep was studied by immunohistochemical detection of scrapie-associated prion protein (prp(sc)) in the gastrointestinal, lymphoid and neural tissues following oral inoculation with bse brain homogenate. first accumulation of prp(sc) was detected after 6 months in the tonsil and the ileal peyer's patches. at 9 months postinfection, prp(sc) accumulation involved all gut-associated lymphoid tissues and lymph nodes as well as the spleen. ...200818092124
scrapie resistance and production traits in rambouillet rams: ram performance test 2002-2006.sheep possessing alleles for the prion protein with glutamine (q) or histidine, both reported as q, at codon 171 are highly susceptible to scrapie. incidence of scrapie infection is rare when animals possess at least one allele for arginine (r) at codon 171. the current usda aphis scrapie eradication program utilizes genotyping for alleles that confer resistance to scrapie. although it has not been a criterion of registration, genotyping has been utilized in the university of wyoming ram perform ...200818093625
cns delivery of vectored prion-specific single-chain antibodies delays disease onset.a unifying characteristic of prion diseases is the conversion of a normal cellular protein (prp(c)) to an abnormal pathogenic conformation, designated prp(sc). antibodies directed against prp(c), when added to scrapie-infected cell cultures or passively administered in vivo, can result in elimination of prp(sc) or prevent its replication, respectively. in our efforts to develop an approach with potential prophylactic utility we employed a recombinant adeno-associated vector type 2 (raav2) viral ...200818180775
atypical/nor98 scrapie: properties of the agent, genetics, and epidemiology.atypical/nor98 scrapie cases in sheep were diagnosed for the first time in norway in 1998. they are now identified in small ruminants in most european countries and represent an increasingly large proportion of the scrapie cases diagnosed in europe. atypical/nor98 scrapie isolates have shown to be experimentally transmissible into transgenic mice and sheep but the properties of the tse agent involved, like its biological and biochemical features, are so clearly distinct from the agent involved i ...200818187032
experimental transmission of us scrapie agent by nasal, peritoneal, and conjunctival routes to genetically susceptible sheep.scrapie is a naturally occurring fatal neurodegenerative disease of sheep and goats. this study documents incubation periods, pathologic findings, and distribution of abnormal prion proteins (prp(sc)) by immunohistochemistry in tissues of genetically susceptible sheep inoculated with us sheep scrapie agent. four-month-old suffolk lambs (qq at codon 171) were inoculated by 1 of 3 different routes (nasal, peritoneal, and conjunctival) with an inoculum (no. 13-7) consisting of a pool of scrapie-aff ...200818192568
the elk prnp codon 132 polymorphism controls cervid and scrapie prion propagation.the elk prion protein gene (prnp) encodes either methionine (m) or leucine (l) at codon 132, the l132 allele apparently affording protection against chronic wasting disease (cwd). the corresponding human codon 129 polymorphism influences the host range of bovine spongiform encephalopathy (bse) prions. to fully address the influence of this cervid polymorphism on cwd pathogenesis, we created transgenic (tg) mice expressing cervid prpc with l at residue 132, referred to as cerprpc-l132, and compar ...200818198392
comprehensive gene expression analysis in human periodontal ligaments of the mandibular third molars performing vertical movement and the maxillary second premolars with occlusal contact.the periodontal ligament (pdl) is thought to be an important tissue in vertical movement during tooth eruption, but the precise molecular mechanism is not known. thereto, comprehensive gene expression was analyzed in human pdl of mandibular third molars performing vertical movement and maxillary second premolars with occlusal contact.200818199074
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