Publications
| Title | Abstract | Year(sorted descending) Filter | PMID Filter |
|---|
| 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 ... | 2008 | 18397513 |
| high incidence of subclinical infection of lymphoid tissues in scrapie-affected sheep flocks. | prion diseases are characterized by a long incubation period. in scrapie, sheep may incubate and spread the infection for several years before clinical signs evolve. we have previously studied the occurrence of subclinical infection in the brain. now, we have studied the occurrence of subclinical infection in the brain and several lymphoid tissues in two scrapie-affected icelandic sheep flocks by immunohistochemistry for prp(sc), a molecular marker for infectivity, and correlated this with resul ... | 2008 | 18227967 |
| intriguing nucleic-acid-binding features of mammalian prion protein. | in transmissible spongiform encephalopathies, the infectious material consists chiefly of a protein, the scrapie prion protein prp(sc), that carries no genetic coding material; however, prions are likely to have accomplices that chaperone their activity and promote the conversion of the cellular prion protein prp(c) into the disease-causing isoform (prp(sc)). recent studies from several laboratories indicate that prp(c) recognizes many nucleic acids (nas) with high affinities, and we correlate t ... | 2008 | 18243708 |
| 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 ... | 2008 | 18073097 |
| blood clearance of the prion protein introduced by intravenous route in sheep is influenced by host genetic and physiopathologic factors. | the risk of transmissible spongiform encephalopathy (tse) transmission by blood transfusion is dependent on the blood concentrations of the pathologic isoform of prion protein (prpsc) but may also be influenced by blood concentrations of cellular prp (prpc). these concentrations are controlled by the blood clearance of prp, which has never been evaluated. | 2008 | 18248567 |
| tse pathogenesis in cattle and sheep. | many studies have been undertaken in rodents to study the pathogenesis of transmissible spongiform encephalopathies (tse). only a few studies have focused on the pathogenesis of bovine spongiform encephalopathy (bse) and scrapie in their natural hosts. in this review, we summarize the most recent insights into the pathogenesis of bse and scrapie starting from the initial uptake of tse agents and crossing of the gut epithelium. following replication in the gut-associated lymphoid tissues (galt), ... | 2008 | 18258167 |
| progress and limits of prp gene selection policy. | classical scrapie has proved to be a notoriously difficult disease to control due to a poor understanding of its natural history. the recognition of disease risk linkage to prp genotype has offered the prospect of a disease control strategy, viz. genotyping and selective breeding, novel to veterinary medicine when first considered in the 1990s. the uk spongiform encephalopathy advisory committee recommended the exploitation of this approach in a voluntary, national programme to control classical ... | 2008 | 18258168 |
| binding of 14-3-3 proteins to a single stranded oligodeoxynucleotide aptamer. | a synthetic library of ca. 10(13) single stranded oligodeoxynucleotides, each comprising a randomized 40mer sequence and homogeneous 10mer flanking regions, was screened for binding to recombinant human 14-3-3gamma. a single aptamer, which showed similar affinities (k(d) approximately 10(-8)m) for six isoforms of the protein, has been shown to bind to undenatured 14-3-3 protein in the cerebral spinal fluid of scrapie infected sheep. | 2008 | 18279908 |
| copper-induced structural changes in the ovine prion protein are influenced by a polymorphism at codon 112. | prion diseases are associated with conformational change in the copper-binding protein prp. the copper-binding sites in prp are located in the n-terminal region of the molecule and comprise a series of tandem repeats of the sequence phgggwgq together with two histidines at residues 96 and 111 (human prp numbering). the co-ordination of copper ions within the non-octapeptide repeat metal ion-binding site involves met109 (human numbering, which corresponds with met112 in ovine prp) and the binding ... | 2008 | 18280261 |
| the evidence of associations between prion protein genotype and production, reproduction, and health traits in sheep. | the eu commission issued a regulation in 2003, which requires all member states to implement a breeding programme for resistance to transmissible spongiform encephalopathies in sheep by selecting for specific alleles of the prion protein (prp) gene. a key concern with regard to this regulation was that the intensive selection programmes, designed to increase resistance to scrapie, may have a negative impact on a range of other economically important production, reproduction, and disease traits i ... | 2008 | 18284907 |
| prp genetics in ruminant transmissible spongiform encephalopathies. | scrapie, bovine spongiform encephalopathy (bse), and chronic wasting disease (cwd) are prion diseases in ruminants with considerable impact on animal health and welfare. they can also pose a risk to human health and control is therefore an important issue. prion protein (prp) genetics may be used to control and eventually eradicate animal prion diseases. the prp gene in sheep and other representatives of the order artiodactyles has many polymorphisms of which several are crucial determinants of ... | 2008 | 18284908 |
| 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 ... | 2008 | 18347938 |
| 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) ... | 2008 | 18348959 |
| 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 ... | 2008 | 18164506 |
| 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 ... | 2008 | 18352909 |
| 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 ... | 2008 | 18355934 |
| 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 ... | 2008 | 18358531 |
| 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 ... | 2008 | 18365024 |
| unraveling prion strains with cell biology and organic chemistry. | 2008 | 18172195 | |
| 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 ... | 2008 | 18175144 |
| 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 ... | 2008 | 18369524 |
| 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 ... | 2008 | 18299435 |
| 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 ... | 2008 | 18307969 |
| 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 ... | 2008 | 18084251 |
| 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 ... | 2008 | 18087720 |
| 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 ... | 2008 | 18088369 |
| 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 ... | 2008 | 18319425 |
| 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 ... | 2008 | 18319433 |
| 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 ... | 2008 | 18319434 |
| 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 ... | 2008 | 18088603 |
| 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 ... | 2008 | 18321558 |
| 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 ... | 2008 | 18089760 |
| 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. ... | 2008 | 18092124 |
| 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 ... | 2008 | 18341429 |
| 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 ... | 2008 | 18093625 |
| atypical status of bovine spongiform encephalopathy in poland: a molecular typing study. | the aim of this study was to analyze molecular features of protease-resistant prion protein (prp(res)) in western blots of bse cases diagnosed in poland with respect to a possible atypical status. confirmed cases were analyzed by western blotting with several monoclonal antibodies directed at n-terminal and core epitopes of prion protein (prp). most cases showed the classical glycoprofile characterized by the dominance of the di- over the monoglycosylated prp(res) band, yielding di-/mono- ratios ... | 2008 | 17896076 |
| protective effect of prion protein via the n-terminal region in mediating a protective effect on paraquat-induced oxidative injury in neuronal cells. | transmissible spongiform encephalopathies are a group of neurodegenerative disorders caused by a posttranslational, conformational change in the cellular isoform of the prion protein (prp(c)) into an infectious, disease-associated form (prp(sc)). increasing evidence supports a role for prp(c) in the cellular response to oxidative stress. we investigated the effect of oxidative stress mediated by paraquat exposure on sh-sy5y neuroblastoma cells. a loss of mitochondrial membrane potential and subs ... | 2008 | 17896796 |
| prp n-terminal domain triggers prp(sc)-like aggregation of dpl. | transmissible spongiform encephalopathies are fatal neurodegenerative disorders thought to be transmitted by self-perpetuating conformational conversion of a neuronal membrane glycoprotein (prp(c), for "cellular prion protein") into an abnormal state (prp(sc), for "scrapie prion protein"). doppel (dpl) is a protein that shares significant biochemical and structural homology with prp(c). in contrast to its homologue prp(c), dpl is unable to participate in prion disease progression or to achieve a ... | 2008 | 17997980 |
| gene expression profile of quinacrine-cured prion-infected mouse neuronal cells. | prion diseases are transmissible fatal neurodegenerative diseases of humans and animals, characterised by the presence of an abnormal isoform (scrapie prion protein; prp(sc)) of the endogenous cellular prion protein (prp(c)). the pathological mechanisms at the basis of prion diseases remain elusive, although the accumulation of prp(sc) has been linked to neurodegeneration. different genomic approaches have been applied to carry out large-scale expression analysis in prion-infected brains and cel ... | 2008 | 18036195 |
| 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 ... | 2008 | 18187032 |
| 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 ... | 2008 | 18192568 |
| 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 ... | 2008 | 18198392 |
| 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. | 2008 | 18199074 |
| experimental transmission of scrapie agent to susceptible sheep by intralingual or intracerebral inoculation. | scrapie, a transmissible spongiform encephalopathy (tse), is a naturally occurring fatal neurodegenerative disease of sheep and goats. this study documents survival periods, pathological findings, and the presence of abnormal prion protein (prp(sc)) in genetically susceptible sheep inoculated with scrapie agent. suffolk lambs (aa/rr/qq at codons 136, 154, and 171, respectively) aged 4 mo were injected by the intralingual (il) or intracerebral (ic) route with an inoculum prepared from a pool of s ... | 2008 | 18214164 |
| 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 ... | 2008 | 18061608 |
| genetic variability of the prnp gene in goat breeds from northern and southern italy. | to determine the variability of the prion protein gene (prnp) in goats from northern and southern italy. | 2008 | 18217941 |
| 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 ... | 2008 | 18068119 |
| prion proteins: physiological functions and role in neurological disorders. | stanley prusiner was the first to promote the concept of misfolded proteins as a cause for neurological disease. it has since been shown by him and other investigators that the scrapie isoform of prion protein (prp(sc)) functions as an infectious agent in numerous human and non-human disorders of the central nervous system (cns). interestingly, other organ systems appear to be less affected, and do not appear to lead to major co-morbidities. the physiological function of the endogenous cellular ... | 2008 | 17707411 |
| prion removal by nanofiltration under different experimental conditions. | manufacturing processes used in the production of biopharmaceutical or biological products should be evaluated for their ability to remove potential contaminants, including tse agents. in the present study, we have evaluated scrapie prion protein (prp sc) removal in the presence of different starting materials, using virus removal filters of different pore sizes. following 75 nm filtration, prp sc was detected in the filtrate by western blot (wb) analysis when a "super-sonicated" microsomal frac ... | 2008 | 17890100 |
| 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 ... | 2008 | 17931166 |
| the role of parvalbumin and calbindin d28k in experimental scrapie. | prion diseases are generally characterized by pronounced neuronal loss. in particular, a subpopulation of inhibitory neurones, characterized by the expression of the calcium-binding protein parvalbumin (pv), is selectively destroyed early in the course of human and experimental prion diseases. by contrast, nerve cells expressing calbindin d28 k (cb), another calcium-binding protein, as well as pv/cb coexpressing purkinje cells, are well preserved. | 2008 | 18005331 |
| the importance of the prp genotype in active surveillance for ovine scrapie. | surveillance activities for ovine scrapie have expanded in the 21st century, following concerns about the potential for a hidden epidemic of bovine spongiform encephalopathy in european sheep populations. large-scale surveys have been used to estimate the prevalence of scrapie infection. in this study we analyse data from the surveys in great britain between 2002 and 2004. when we estimate genotype-specific prevalences for each of the two screening tests used a difference is observed. one test u ... | 2008 | 17588284 |
| lack of prp(sc) immunostaining in intracranial ectopic lymphoid follicles in a sheep with concomitant non-suppurative encephalitis and nor98-like atypical scrapie: a case report. | during active surveillance for transmissible spongiform encephalopathies (tses) in sheep, an initial reactor was detected using a rapid test on a brain sample. immunohistochemistry confirmed an atypical tse presentation that closely resembled the previously described nor98 cases. sequencing of the prnp gene confirmed the arq/ahq genotype with the l141f mutation at codon 141 associated with this phenotype. the head, including the brain and cranial lymphoid tissues, was sampled and examined thorou ... | 2008 | 17574883 |
| single chain fv antibodies directed against the 37 kda/67 kda laminin receptor as therapeutic tools in prion diseases. | transmissible spongiform encephalopathies are a group of neurological disorders associated with the deposition of prp(sc), an abnormal form of the cellular prion protein prp(c). the 37 kda/67 kda laminin receptor (lrp/lr) has been identified as a prion receptor and several lines of evidence strongly suggest that this protein plays a role during prion pathogenesis. here we report the selection of recombinant single chain antibodies (scfvs) directed against lrp from naïve and synthetic phage scfv ... | 2008 | 17576014 |
| analysis of prion protein genotypes in relation to reproduction traits in local and cosmopolitan german sheep breeds. | due to the genetic determination of susceptibility to scrapie and other forms of transmissible spongiform encephalopathy (tse) in sheep breeding to the less susceptible prion protein (prp) genotype arr/arr was advanced within eu. in 4961 ewes of nine german sheep breeds (coburg fox sheep, gray horned heath sheep, merinoland sheep, rhoen sheep, german blackheaded mutton sheep, shropshire, suffolk, texel and white east friesian milk sheep) representing local and cosmopolitan breeds the reproductiv ... | 2008 | 17204379 |
| prion propagation in vitro: are we there yet? | prion diseases are caused by proteinaceous pathogens termed prions. although the details of the mechanism of prion propagation are not fully understood, conformational conversion of cellular prion protein (prp(c)) to misfolded, disease-associated scrapie prion protein (prp(sc)) is considered the essential biochemical event for prion replication. currently, studying prion replication in vitro is difficult due to the lack of a system which fully recapitulates the in vivo phenomenon. over the last ... | 2008 | 19015743 |
| impact of strong selection for the prp major gene on genetic variability of four french sheep breeds(open access publication). | effective selection on the prp gene has been implemented since october 2001 in all french sheep breeds. after four years, the arr "resistant" allele frequency increased by about 35% in young males. the aim of this study was to evaluate the impact of this strong selection on genetic variability. it is focussed on four french sheep breeds and based on the comparison of two groups of 94 animals within each breed: the first group of animals was born before the selection began, and the second, 3-4 ye ... | 2008 | 18990357 |
| a mirna signature of prion induced neurodegeneration. | micrornas (mirnas) are small, non-coding rna molecules which are emerging as key regulators of numerous cellular processes. compelling evidence links mirnas to the control of neuronal development and differentiation, however, little is known about their role in neurodegeneration. we used microarrays and rt-pcr to profile mirna expression changes in the brains of mice infected with mouse-adapted scrapie. we determined 15 mirnas were de-regulated during the disease processes; mir-342-3p, mir-320, ... | 2008 | 18987751 |
| a rapid accurate culture assay for infectivity in transmissible encephalopathies. | the molecular and structural features of infectious agents that cause cjd, scrapie and bse remain controversial. a major impediment for agent resolution is the very long and expensive animal assays of infectivity. it is crucial to develop a rapid and broadly applicable cell culture assay to titer and compare different tse agent strains. because we found gt1 hypothalamic cells, unlike neuroblastoma n2a clones, were highly susceptible to a variety of tse agents, and could stably produce high agent ... | 2008 | 18989813 |
| kuru likened to scrapie: the story remembered. | 2008 | 18849258 | |
| reduction of prion infectivity in packed red blood cells. | the link between a new variant form of creutzfeldt-jakob disease (vcjd) and the consumption of prion contaminated cattle meat as well as recent findings showing that vcjd can be transmitted by blood transfusion have raised public health concerns. currently, a reliable test to identify prions in blood samples is not available. the purpose of this study was to evaluate the possibility to remove scrapie prion protein (prp(sc)) and infectivity from red blood cell (rbc) suspensions by a simple washin ... | 2008 | 18851948 |
| accelerated prion replication in, but prolonged survival times of, prion-infected cxcr3-/- mice. | prion diseases have a significant inflammatory component. glia activation, which is associated with increased production of cytokines and chemokines, may play an important role in disease development. among the chemokines upregulated highly and early upregulated during scrapie infections are ligands of cxcr3. to gain more insight into the role of cxcr3 in a prion model, cxcr3-deficient (cxcr3(-/-)) mice were infected intracerebrally with scrapie strain 139a and characterized in comparison to sim ... | 2008 | 18842729 |
| reduced translocation of nascent prion protein during er stress contributes to neurodegeneration. | during acute stress in the endoplasmic reticulum (er), mammalian prion protein (prp) is temporarily prevented from translocation into the er and instead routed directly for cytosolic degradation. this "pre-emptive" quality control (pqc) system benefits cells by minimizing prp aggregation in the secretory pathway during er stress. however, the potential toxicity of cytosolic prp raised the possibility that persistent pqc of prp contributes to neurodegeneration in prion diseases. here, we find evi ... | 2008 | 18804434 |
| docosahexaenoic and eicosapentaenoic acids increase prion formation in neuronal cells. | the transmissible spongiform encephalopathies, otherwise known as prion diseases, occur following the conversion of the cellular prion protein (prpc) to an alternatively folded, disease-associated isoform (prpsc). recent studies suggest that this conversion occurs via a cholesterol-sensitive process, as cholesterol synthesis inhibitors reduced the formation of prpsc and delayed the clinical phase of scrapie infection. since polyunsaturated fatty acids also reduced cellular cholesterol levels we ... | 2008 | 18789130 |
| assessing the presence of bse and scrapie in slaughterhouse wastewater. | this paper describes a procedure for evaluating the presence and the stability of the proteinase k-resistant form of the prion protein (prp(res)) in slaughterhouse wastewater. | 2008 | 19146499 |
| environmentally-relevant forms of the prion protein. | scrapie and chronic wasting disease (cwd) are prion diseases of particular environmental concern as they are horizontally transmissible and can remain infectious after years in the environment. recent evidence suggests that the n-terminus of prpsc, the infectious conformation of the prion protein, plays an important role in the mechanism of sorption to soil particles. we hypothesize that, in a prion-infected animal carcass, a portion of the n-terminus of prpsc could be cleaved by proteinases in ... | 2008 | 18800532 |
| [from the mad cow to the scrapie of the european sheep]. | 2008 | 19127901 | |
| the effects of prion protein proteolysis and disaggregation on the strain properties of hamster scrapie. | native mammalian prions exist in self-propagating strains that exhibit distinctive clinical, pathological and biochemical characteristics. prion strain diversity is associated with variations in prp(sc) conformation, but it remains unknown precisely which physical properties of the prp(sc) molecules are required to encipher mammalian prion strain phenotypes. in this study, we subjected prion-infected brain homogenates derived from three different hamster scrapie strains to either (i) proteinase ... | 2008 | 18796735 |
| lipids in the assembly of membrane proteins and organization of protein supercomplexes: implications for lipid-linked disorders. | lipids play important roles in cellular dysfunction leading to disease. although a major role for phospholipids is in defining the membrane permeability barrier, phospholipids play a central role in a diverse range of cellular processes and therefore are important factors in cellular dysfunction and disease. this review is focused on the role of phospholipids in normal assembly and organization of the membrane proteins, multimeric protein complexes, and higher order supercomplexes. since lipids ... | 2008 | 18751913 |
| prions in milk from ewes incubating natural scrapie. | since prion infectivity had never been reported in milk, dairy products originating from transmissible spongiform encephalopathy (tse)-affected ruminant flocks currently enter unrestricted into the animal and human food chain. however, a recently published study brought the first evidence of the presence of prions in mammary secretions from scrapie-affected ewes. here we report the detection of consistent levels of infectivity in colostrum and milk from sheep incubating natural scrapie, several ... | 2008 | 19079578 |
| excretion of transmissible spongiform encephalopathy infectivity in urine. | the route of transmission of most naturally acquired transmissible spongiform encephalopathy (tse) infections remains speculative. to investigate urine as a potential source of tse exposure, we used a sensitive method for detection and quantitation of tse infectivity. pooled urine collected from 22 hamsters showing clinical signs of 263k scrapie contained 3.8 +/- 0.9 infectious doses/ml of infectivity. titration of homogenates of kidneys and urinary bladders from the same animals gave concentrat ... | 2008 | 18760007 |
| a bagging-based correction for the mixture model estimator of population size. | estimation of a population size by means of capture-recapture techniques is an important problem occurring in many areas of life and social sciences. we consider the frequencies of frequencies situation, where a count variable is used to summarize how often a unit has been identified in the target population of interest. the distribution of this count variable is zero-truncated since zero identifications do not occur in the sample. as an application we consider the surveillance of scrapie in gre ... | 2008 | 19089886 |
| the effect of fenton reaction on protease-resistant prion protein (prpsc) degradation and scrapie infectivity. | in prion diseases, metal imbalances in brain and/or metal substitutions for copper in prion protein suggest that metal-catalyzed oxidation (mco) and oxidative stress may affect cellular function and accumulation of protease-resistant prion protein (prp(sc)). we examined the effect of metal-induced oxidative stress by fenton reaction on prion protein with regard to its degradation, insolubility, and infectivity. precipitation and insolubility of prion protein were induced by fenton reaction in sc ... | 2008 | 18771660 |
| prion interference with multiple prion isolates. | co-inoculation of prion strains into the same host can result in interference, where replication of one strain hinders the ability of another strain to cause disease. the drowsy (dy) strain of hamster-adapted transmissible mink encephalopathy (tme) extends the incubation period or completely blocks the hyper (hy) strain of tme following intracerebral, intraperitoneal or sciatic nerve routes of inoculation. however, it is not known if the interfering effect of the dy tme agent is exclusive to the ... | 2008 | 19098442 |
| epidemiological characteristics of classical scrapie outbreaks in 30 sheep flocks in the united kingdom. | most previous analyses of scrapie outbreaks have focused on flocks run by research institutes, which may not reflect the field situation. within this study, we attempt to rectify this deficit by describing the epidemiological characteristics of 30 sheep flocks naturally-infected with classical scrapie, and by exploring possible underlying causes of variation in the characteristics between flocks, including flock-level prion protein (prp) genotype profile. in total, the study involved prp genotyp ... | 2008 | 19098982 |
| accumulation of citrullinated proteins by up-regulated peptidylarginine deiminase 2 in brains of scrapie-infected mice: a possible role in pathogenesis. | peptidylarginine deiminases (pads), which are a group of posttranslational modification enzymes, are involved in protein citrullination (deimination) by the conversion of peptidylarginine to peptidylcitrulline in a calcium concentration-dependent manner. among the pads, pad2 is widely distributed in various tissues and is the only type that is expressed in brain. to elucidate the involvement of protein citrullination by pad2 in the pathogenesis of brain-specific prion diseases, we examined the p ... | 2008 | 18787103 |
| [analyses of the expressions of gfap in the brain tissues of hamsters infected with various amounts of scrapie strain 263k at terminal stage]. | to investigate whether gliosis in the brain tissues of the hamsters infected with various amounts of scrapie strain 263k is correlated with the inoculation doses or the incubation times. | 2008 | 19105331 |
| lions and prions and deer demise. | contagious prion diseases--scrapie of sheep and chronic wasting disease of several species in the deer family--give rise to epidemics that seem capable of compromising host population viability. despite this prospect, the ecological consequences of prion disease epidemics in natural populations have received little consideration. | 2008 | 19107193 |
| quantitative recovery of scrapie agent with minimal protein from highly infectious cultures. | there are few reports on the isolation, quantitative recovery, and relative purification of infectious particles that cause scrapie, creutzfeldt-jakob disease (cjd) and epidemic bovine spongiform encephalopathy (bse). because pure prion protein (prp) has failed to show significant infectivity, it is critical to find other molecules that are integral agent components. only complex diseased tissues such as degenerating brain have been fractionated, and agent recoveries have been quite low in conce ... | 2008 | 18788938 |
| involvement of glypican-1 autoprocessing in scrapie infection. | the copper-binding cellular prion protein (prp(c)) and the heparan sulphate (hs)-containing proteoglycan glypican-1 (gpc-1) can both be attached to lipid rafts via their glycosylphosphatidylinositol anchors, and copper ions stimulate their cointernalization from the cell surface to endosomes. the prion protein controls cointernalization and delivers copper necessary for s-nitrosylation of conserved cysteines in the gpc-1 core protein. later, during recycling through endosomal compartments, nitri ... | 2008 | 18717736 |
| atypical prpsc distribution in goats naturally affected with scrapie. | the brain and spinal cord of 48 goats from two greek herds in which scrapie had been reported were examined. all animals were symptomless at the time of euthanasia. notably, no lesions were observed either at the level of the obex or at other regions of the brain and spinal cord. immunohistochemical examination revealed prpsc labelling of the linear and fine punctuate types, mainly in the cerebral cortices, of 36 goats. twenty-seven of them were negative by elisa (designed to detect proteinase-r ... | 2008 | 18295782 |
| lactoferrin induces cell surface retention of prion protein and inhibits prion accumulation. | prion diseases are fatal neurodegenerative disorders, and the conformational conversion of normal cellular prion protein (prp(c)) into its pathogenic, amyloidogenic isoform (prp(sc)) is the essential event in the pathogenesis of these diseases. lactoferrin (lf) is a cationic iron-binding glycoprotein belonging to the transferrin (tf) family, which accumulates in the amyloid deposits in the brain in neurodegenerative disorders, such as alzheimer's disease and pick's disease. in the present study, ... | 2008 | 18717818 |
| creb-dependent gene regulation by prion protein: impact on mmp-9 and beta-dystroglycan. | corruption of the normal function of the cellular prion protein (prp(c)) by the scrapie isoform (prp(sc)) emerges as a critical causal event in transmissible spongiform encaphalopathies (tse) pathogenesis. however, prp(c) physiological role remains unclear. by exploiting the properties of the 1c11 neuroectodermal cell line, able to convert into 1c11(5-ht) serotonergic or 1c11(ne) noradrenergic neuronal cells, we assigned a signaling function to prp(c). here, we establish that antibody-mediated p ... | 2008 | 18718863 |
| detection of prion infectivity in fat tissues of scrapie-infected mice. | distribution of prion infectivity in organs and tissues is important in understanding prion disease pathogenesis and designing strategies to prevent prion infection in animals and humans. transmission of prion disease from cattle to humans resulted in banning human consumption of ruminant nervous system and certain other tissues. in the present study, we surveyed tissue distribution of prion infectivity in mice with prion disease. we show for the first time detection of infectivity in white and ... | 2008 | 19057664 |
| [establishment of a prion disease prp(sc) panel from the brain tissues of experimental hamsters infected with scrapie agent 263k]. | to establish a prion disease prp(sc) panel from the brain tissues of experimental hamsters and to address the stability of the panel conserved under the specific condition, for evaluating the diagnostic techniques of human and animal's prion diseases. | 2008 | 19469162 |
| prions in the environment: occurrence, fate and mitigation. | scrapie and cwd are horizontally transmissible, and the environment likely serves as a stable reservoir of infectious prions, facilitating a sustained incidence of cwd in free-ranging cervid populations and complicating efforts to eliminate disease in captive herds. prions will enter the environment through mortalities and/or shedding from live hosts. unfortunately, a sensitive detection method to identify prion contamination in environmental samples has not yet been developed. an environmentall ... | 2008 | 19242120 |
| transmissible spongiform encephalopathies. | 2008 | 19046027 | |
| urinary alpha1-antichymotrypsin: a biomarker of prion infection. | the occurrence of blood-borne prion transmission incidents calls for identification of potential prion carriers. however, current methods for intravital diagnosis of prion disease rely on invasive tissue biopsies and are unsuitable for large-scale screening. sensitive biomarkers may help meeting this need. here we scanned the genome for transcripts elevated upon prion infection and encoding secreted proteins. we found that alpha(1)-antichymotrypsin (alpha(1)-act) was highly upregulated in brains ... | 2008 | 19057641 |
| a patient with mv2 subtype of sporadic creutzfeldt-jakob disease and atypical clinical presentation. | we report the case of a 71-year-old woman with progressive dementia over the course of 4 years, characterized by prominent pyramidal signs and by the lack of ataxia and other cerebellar signs. creutzfeldt-jakob disease (cjd) was not suspected during the patient's life. autopsy brain tissue showed severe spongiform encephalopathy with kuru-like, but not florid, plaques in neocortex and cerebellum. massive synaptic diffuse and plaque-like prp(sc) deposition was found in the cerebral cortex, striat ... | 2008 | 19130739 |
| pathologic prion protein infects cells by lipid-raft dependent macropinocytosis. | transmissible spongiform encephalopathies, including variant-creutzfeldt-jakob disease (vcjd) in humans and bovine spongiform encephalopathies in cattle, are fatal neurodegenerative disorders characterized by protein misfolding of the host cellular prion protein (prp(c)) to the infectious scrapie form (prp(sc)). however, the mechanism that exogenous prp(sc) infects cells and where pathologic conversion of prp(c) to the prp(sc) form occurs remains uncertain. here we report that similar to the mec ... | 2008 | 19390657 |
| norwegian farmers' vigilance in reporting sheep showing scrapie-associated signs. | scrapie is a chronic neurodegenerative disease affecting small ruminants and belongs to the transmissible spongiform encephalopathies. scrapie is considered a serious animal disease and it has been notifiable in norway since 1965. the clinical signs of scrapie might be vague and the farmers, if familiar with the signs of scrapie, are often in the best position for detecting scrapie suspects. in 2002, an anonymous questionnaire survey was conducted in order to assess norwegian sheep farmers' vigi ... | 2007 | 18076757 |
| prion strain discrimination in cell culture: the cell panel assay. | prions are thought to consist mainly or entirely of misfolded prp, a constitutively expressed host protein. prions associated with the same prp sequence may occur in the form of different strains; the strain phenotype is believed to be encoded by the conformation of the prp. some cell lines can be persistently infected by prions and, interestingly, show preference for certain strains. we report that a cloned murine neuroblastoma cell population, n2a-pk1, is highly heterogeneous in regard to its ... | 2007 | 18077360 |
| anti-lrp/lr antibody w3 hampers peripheral prpsc propagation in scrapie infected mice. | we identified the 37kda/67kda laminin receptor (lrp/lr) as a cell surface receptor for the cellular prion protein (prp(c)) and the infectious prion protein (prp(sc)). recently, we showed that anti-lrp/lr antibody w3 cured scrapie infected n2a cells. here, we demonstrate that w3 delivered by passive immunotransfer into c57bl/6 mice reduced the prp(sc) content in the spleen significantly by 66%, demonstrating an impairment of the peripheral prp(sc) propagation. in addition, we observed a 1.8-fold ... | 2007 | 19164931 |
| infectious fold and amyloid propagation in podospora anserina. | amyloid protein aggregation is involved in serious neurodegenerative disorders such as alzheimer's disease and transmissible encephalopathies. the concept of an infectious protein (prion) being the scrapie agent was successfully validated for several yeast and fungi proteins. ure2, sup35 and rnq1 in saccharomyces cerevisiae and het-s in podospora anserina have been genetically and biochemically identified as prion proteins. studies on these proteins have revealed critical information on the mech ... | 2007 | 19164904 |
| yeast prions: evolution of the prion concept. | prions (infectious proteins) analogous to the scrapie agent have been identified in saccharomyces cerevisiae and podospora anserina based on their special genetic characteristics. each is a protein acting as a gene, much like nucleic acids have been shown to act as enzymes. the [ure3], [psi(+)], [pin(+)] and [het-s] prions are self-propagating amyloids of ure2p, sup35p, rnq1p and the het-s protein, respectively. the [beta] and [c] prions are enzymes whose precursor activation requires their own ... | 2007 | 19164928 |
| the evolution of internet-based map server applications in the united states department of agriculture, veterinary services. | the internet is used increasingly as an effective means of disseminating information. for the past five years, the united states department of agriculture (usda) veterinary services (vs) has published animal health information in internet-based map server applications, each oriented to a specific surveillance or outbreak response need. using internet-based technology allows users to create dynamic, customised maps and perform basic spatial analysis without the need to buy or learn desktop geogra ... | 2007 | 20422551 |
| prp genotypes in a pedigree flock of santa inês sheep. | 2007 | 17351175 | |
| changes in the expression pattern of the nitrergic system of ovine cerebellum affected by scrapie. | the constitutive and inducible isoforms of nitric oxide synthase (nos) and the end-product of nitration, nitrotyrosine, were analyzed by immunohistochemistry, western blotting, and enzymatic activity in sheep at different stages of the prion disease, scrapie. four groups were studied: 1) nonaffected (control), 2) preclinical, 3) clinical, and 4) terminal. constitutive neuronal nos (nnos) was the most abundant isoform present in cerebellar neurons of the sheep. expression of nnos increased in pre ... | 2007 | 17356381 |
| scrapie strain transmission studies in ovine prp transgenic mice reveal dissimilar susceptibility. | the tg(ovprp4) mouse line, expressing the sheep prion protein, is a sensitive model crucial for the identification of the bovine spongiform encephalopathy agent possibly present in natural sheep spongiform encephalopathies. it was also previously demonstrated as susceptible to infection with natural scrapie isolates from sheep harbouring various genotypes. the performance of this new transgenic mouse line in scrapie strain characterization was further assessed by intracranial inoculation of five ... | 2007 | 17361441 |
| is there a relationship between prion protein genotype and ovulation rate and litter size in sheep? | the identification of an association between polymorphisms of the prion protein (prp) gene and susceptibility to scrapie has enabled the development of breeding programmes to increase natural resistance to scrapie. it is, however, imperative to identify if such selection would affect important reproduction and production traits. the objective of this study was to determine if there is a relationship between polymorphisms at codons 136, 154 and 171 of the prp gene and ovulation rate or litter siz ... | 2007 | 17204381 |