Publications
| Title | Abstract | Year(sorted ascending) Filter | PMID Filter |
|---|
| molecular analysis of cases of italian sheep scrapie and comparison with cases of bovine spongiform encephalopathy (bse) and experimental bse in sheep. | concerns have been raised about the possibility that the bovine spongiform encephalopathy (bse) agent could have been transmitted to sheep populations via contaminated feedstuffs. the objective of our study was to investigate the suitability of molecular strain typing methods as a surveillance tool for studying scrapie strain variations and for differentiating prp(sc) from sheep scrapie, bse, and sheep bse. we studied 38 italian sheep scrapie cases from 13 outbreaks, along with a british scrapie ... | 2003 | 12958236 |
| repeated challenge with prion disease: the risk of infection and impact on incubation period. | natural exposure to prion disease is likely to occur throughout successive challenges, yet most experiments focus on single large doses of infectious material. we analyze the results from an experiment in which rodents were exposed to multiple doses of feed contaminated with the scrapie agent. we formally define hypotheses for how the doses combine in terms of statistical models. the competing hypotheses are that only the total dose of infectivity is important (cumulative model), doses act indep ... | 2003 | 12960400 |
| new inhibitors of scrapie-associated prion protein formation in a library of 2000 drugs and natural products. | transmissible spongiform encephalopathies (tses) are fatal, untreatable neurodegenerative diseases associated with the accumulation of a disease-specific form of prion protein (prp) in the brain. one approach to tse therapeutics is the inhibition of prp accumulation. indeed, many inhibitors of the accumulation of prp associated with scrapie (prp(sc)) in scrapie-infected mouse neuroblastoma cells (scn(2)a) also have antiscrapie activity in rodents. to expedite the search for potential tse therape ... | 2003 | 12970413 |
| differential inhibition of prion propagation by enantiomers of quinacrine. | prion diseases are fatal neurologic disorders caused by accumulation of a pathogenic isoform (prp(sc)) of the prion protein (prp). the recent discovery of the inhibitory action of quinacrine on prp(sc) formation in scrapie-infected neuroblastoma (scn2a) cells raised the possibility of a treatment for patients with prion disease. to investigate the efficacy of quinacrine enantiomers, we measured the inhibitory effect of these isomers on prp(sc) formation in scn2a cells. (s)-quinacrine exhibited s ... | 2003 | 12808118 |
| in vivo micro magnetic resonance imaging signal changes in scrapie infected mice. | signal abnormalities on magnetic resonance imaging (mri) t2-weighted images (t2wi) have been described in patients with creutzfeldt-jakob disease; however, the pathology underlying these findings remains to be fully described. we investigated the time-course of signal alterations in a murine model of prion disease using in vivo 9.4 tesla micro magnetic resonance imaging (mumri). the topography of mumri signal changes was correlated with the accumulation of proteinase resistant prp(sc) in corresp ... | 2003 | 12809974 |
| prion diseases: infectious and lethal doses following oral challenge. | a brain homogenate prepared from a terminally ill hamster infected with scrapie strain 263k was serially diluted and administered orally to groups of hamsters. the undiluted brain homogenate led to clinical scrapie in all animals inoculated. the attack rate decreased with dilutions of the homogenate, and subclinical infections were identified among the healthy survivors at 520 days post-infection by western blotting. the number of animals succumbing to disease and the combined number of western ... | 2003 | 12810889 |
| prions, mad cow disease, and preventive measures: a critical appraisal. | 2003 | 12819966 | |
| regional heterogeneity of cellular prion protein isoforms in the mouse brain. | prion diseases are a group of invariably fatal neurodegenerative disorders that include creutzfeldt-jakob disease in humans, scrapie in sheep and goats, and bovine spongiform encephalopathy in cattle. the infectious agent or prion is largely composed of an abnormal isoform (prpsc) of a host encoded normal cellular protein (prpc). the conversion of prpc to prpsc is a dynamic process and, for reasons that are not clear, the distribution of spongiform change and prpsc deposition varies among prion ... | 2003 | 12821516 |
| evaluation of depth filtration to remove prion challenge from an immune globulin preparation. | plasma-derived therapeutic proteins have the potential to contain transmissible spongiform encephalopathy (tse) infectivity. this study evaluated the effectiveness and characterized the mechanism of abnormal prion protein removal during a depth-filtration step used in the manufacture of an immunoglobulin preparation. | 2003 | 12823726 |
| european union's rapid tse testing in adult cattle and sheep: implementation and results in 2001 and 2002. | after the discovery of variant creutzfeldt-jakob disease (vcjd), scientific advances quickly led to post-mortem tests to identify late-stage bovine spongiform encephalopathy (bse) disease. these were first used in switzerland in 1999 for active bse surveillance of a) fallen and emergency-slaughter bovines (risk stock) and b) 5% sample of routinely slaughtered cattle over 30 months of age. in 1999 and 2000, switzerland's estimated 103 bse positives per 1000000 adult cattle put it in the same bse ... | 2003 | 12828246 |
| transmissible encephalopathies: speculations and realities. | virtually all transmissible encephalopathies (tses), such as scrapie, cjd, and bse, are caused by a type of infectious particle that remains enigmatic. the language of prion theory supersedes the reality of what is, and what is not known. this review questions the predictive value, consistency and accuracy of this now dominant assumption. many people believe the normal cellular prion protein (prp) self-converts into an infectious amyloid protein or prion. although the amyloidogenic capacity of p ... | 2003 | 12828865 |
| synthesis and evaluation of analogues of congo red as potential compounds against transmissible spongiform encephalopathies. | the synthesis of analogues of the amyloid stain congo red (1) as potential compounds against transmissible spongiform encephalopathies (tses) is reported. using the direct method, aniline (2) or diamines such as 4,4'-diaminodiphenylsulfone (dapsone, 9), 3,3'-diaminodiphenylsulfone (10), benzidine (11), 3,3'-dimethoxybenzidine (12) or 3,3'-dichlorobenzidine (13) were diazotised to afford the corresponding diazonium salts, which without isolation, were directly used for coupling with a range of ar ... | 2003 | 12832128 |
| 'complex' prp genotypes identified by the national scrapie plan. | 2003 | 12833938 | |
| evaluation of quinacrine treatment for prion diseases. | based on in vitro observations in scrapie-infected neuroblastoma cells, quinacrine has recently been proposed as a treatment for creutzfeldt-jakob disease (cjd), including a new variant cjd which is linked to contamination of food by the bovine spongiform encephalopathy (bse) agent. the present study investigated possible mechanisms of action of quinacrine on prions. the ability of quinacrine to interact with and to reduce the protease resistance of prp peptide aggregates and prpres of human and ... | 2003 | 12857915 |
| mapping the antigenicity of copper-treated cellular prion protein with the scrapie isoform. | when recombinant and cellular prion protein (prp(c)) binds copper, it acquires properties resembling the scrapie isoform (prp(sc)), namely protease resistance, detergent insolubility and increased beta sheet content. however, whether the conformations of prp(c) induced by copper and prp(sc) are similar has not been studied in great detail. here, we use a panel of seven monoclonal antibodies to decipher the epitopes on full-length mouse prp(c) that are affected by exogenous copper, and to compare ... | 2003 | 12861388 |
| up-regulation of cathepsin b and cathepsin l activities in scrapie-infected mouse neuro2a cells. | prion diseases are characterized by the accumulation of an abnormal, proteinase k-resistant isoform of the prion protein, prp(sc), which is generated by a post-translational conversion of the protease-sensitive normal cell-surface glycoprotein prp(c) involving major conformational changes. the conversion is thought to occur at the plasma membrane or along the endocytic pathway towards the lysosome. prp(sc) aggregates have been found to accumulate in secondary lysosomes. in our study, the activit ... | 2003 | 12867662 |
| immunohistochemical comparison of anti-prion protein (prp) antibodies in the cns of mice infected with scrapie. | one of the pathological changes characteristic of the transmissible spongiform encephalopathies (tses) is the accumulation of disease-specific prp (prp(sc)). immunolabeling of prp(sc) was compared using a panel of monoclonal and polyclonal antibodies. to determine the effects of tissue fixation on immunostaining, we performed a supplementary investigation reviewing the fixatives formol saline and periodate-lysine-paraformaldehyde (plp). the main target sites of the antibodies were similar. howev ... | 2003 | 12871988 |
| analysis of polymorphic microsatellites within the bovine and ovine prion protein (prnp) genes. | twenty-four microsatellite sites with at least three repeats were found in the bovine prion protein gene (prnp) and 23 in the ovine prnp gene. eight microsatellite sites were polymorphic in cattle and six in sheep with up to 10 alleles per site. in many cases allelic dna fragments had variants in microsatellite sites and in flanking regions. distances between microsatellite sites in eight genes from cattle and sheep occurred on average every 0.9 kb. the numerous polymorphic microsatellite sites ... | 2003 | 12873216 |
| identification of a novel lysine-171 allele in the ovine prion protein (prnp ) gene. | 2003 | 12873221 | |
| copper modulation of ion channels of prp[106-126] mutant prion peptide fragments. | we have shown previously that the protease-resistant and neurotoxic prion peptide fragment prp[106-126] of human prp incorporates into lipid bilayer membranes to form heterogeneous ion channels, one of which is a cu(2+)-sensitive fast cation channel. to investigate the role of prp[106-126]'s hydrophobic core, agaaaaga, on its ability to form ion channels and their regulation with cu(2+), we used the lipid-bilayer technique to examine membrane currents induced as a result of prp[106-126] (aa/ss) ... | 2003 | 12879164 |
| the prion paradox: infection or polymerisation? | a weak but significant similarity was found between the prion protein (prp) and some transcription factors and zinc-finger proteins. a possible interpretation of this similarity is that the prp is a metal- (copper-) binding transcription factor and might behave like a zn-finger protein, with the cu2+ binding to its histidine and serine residues. copper-binding could create intramolecular bridges in the prpc (normal, cytoplasmic) molecule, but intermolecular bridges in the prpsc (scrapie pathogen ... | 2003 | 15130813 |
| results of a postal survey in 2002 into the occurrence of scrapie in great britain. | 2003 | 14735995 | |
| [infectious prion disease: cjd with dura mater transplantation]. | prion diseases include scrapie, bse and cwd in animals, and spontaneous, familiar and infectious creutzfeldt-jakob disease(cjd) in human. infectious prion diseases include kuru, variant cjd and iatrogenic cjd. cjd has been transmitted from human to human by contaminated cadaveric dura mater grafts and by cadaveric pituitary hormones. to date, cjd associated with dura mater grafts, reaching 156 cases, has been reported in 17 countries. more 2/3 of cases have been reported in japan. nationwide sur ... | 2003 | 15152489 |
| bovine spongiform encephalopathy (bse)--infectious, contagious, zoonotic or production disease? | in 1986, a new progressive neurological condition similar to scrapie of sheep and goats was recognised in cattle in the united kingdom (uk), and was named bovine spongiform encephalopathy (bse). there is an ongoing discussion whether bse should be classified as infectious, contagious, or zoonotic, and if it fits the definition of a production disease. the objective of this work is to briefly describe the main characteristics of transmissible spongiform encephalopathies (tse), to review the epide ... | 2003 | 15259778 |
| administration of identification boluses to sheep. | 2003 | 14620557 | |
| scrg1, a novel protein of the cns is targeted to the large dense-core vesicles in neuronal cells. | scrapie responsive gene one (scrg1) is a novel transcript discovered through identification of the genes associated with or responsible for the neurodegenerative changes observed in transmissible spongiform encephalopathies. scrg1 mrna is distributed principally in the central nervous system and the cdna sequence predicts a small cysteine-rich protein 98 amino acids in length, with a n-terminal signal peptide. in this study, we have generated antibodies against the predicted protein and revealed ... | 2003 | 14622145 |
| neuropathological characterisation of french bovine spongiform encephalopathy cases. | bovine spongiform encephalopathy (bse) in cattle is a neurodegenerative disease belonging to the transmissible spongiform encephalopathies, a group of diseases including sheep scrapie and human creutzfeldt-jakob disease. the pathological characteristics of bse are vacuolation, mild gliosis, little neuronal degeneration without inflammatory process and abnormal prion protein (prpsc) accumulation. the aim of this study was to define precisely the neuropathology of bse in french cases by assessing ... | 2003 | 14624299 |
| emerging therapeutic agents for transmissible spongiform encephalopathies: a review. | transmissible spongiform encephalopathies (tses) are a group of fatal neurodegenerative disorders associated with misfolding of prion protein, from prpc to prpsc. different types of experimental studies have resulted in a better understanding of the pathogenesis of the prion diseases. genetic and molecular properties of prp isoforms have been explained but the conformational conversion of the prpc isoform to the prpsc isoform has not yet been entirely elucidated. however, a number of possible th ... | 2003 | 14633183 |
| in situ identification of protein structural changes in prion-infected tissue. | transmissible spongiform encephalopathies (tse) are fatal neurodegenerative disorders characterized by the conversion of the normal prion protein (prp(c)) into aggregates of its pathological conformer (prp(sc)). the mechanism behind this structural conversion is unclear. we report the identification of disease-related protein structural differences directly within the tissue environment. utilizing a synchrotron infrared (ir) light source, ir images of protein structure were obtained at a subcell ... | 2003 | 14636946 |
| novel heparan mimetics potently inhibit the scrapie prion protein and its endocytosis. | during prion diseases the normal prion protein prp(c) is refolded into an abnormal conformer prp(sc). we have studied the prp(sc) inhibiting activity of a library of synthetic heparan mimetic (hm) biopolymers. hms are chemically derived dextrans obtained by successive substitutions with carboxymethyl, benzylamide, and sulfate groups on glucose residues. some hms eliminated prp(sc) from prion-infected cells after a 5 day course at 100 ng/ml and were 15 x potent than pentosan sulfate in this syste ... | 2003 | 14637161 |
| two different scrapie prions isolated in japanese sheep flocks. | two different scrapie prion strains with different characteristics were obtained from two sheep naturally infected with scrapie in japan. in mice transmission, one (tsukuba-1) showed shorter incubation periods (133+/-2 days) than the other (tsukuba-2) (288+/-5 days). spongiform changes and accumulation of an abnormal isoform of prion protein (prp(sc)) were observed throughout the brain in tsukuba-1 inoculated mice, while the lesions and the prp(sc) accumulation were localized in the brain stem o ... | 2003 | 14638998 |
| enzymatic degradation of prion protein in brain stem from infected cattle and sheep. | prions-infectious agents involved in transmissible spongiform encephalopathies-normally survive proteolytic and mild protein-destructive processes. using bacterial keratinase produced by bacillus licheniformis strain pwd-1, we tested conditions to accomplish the full degradation of prion protein (prp) in brain-stem tissue from animals with bovine spongiform encephalopathy and scrapie. the detection of prpsc, the disease-associated isoform of prp, in homogenates was done by western blotting and v ... | 2003 | 14639552 |
| copper binding to prpc may inhibit prion disease propagation. | although it has been well established that prp(c), the normal isoform of prp(sc), is a copper-binding protein, the role of this metal in the function of prp(c) as well as in prion disease pathology remains unclear. here, we show that when scrapie-infected neuroblastoma cells were cultured in the presence of copper, the accumulation of prp(sc) in these cells was markedly reduced. in addition, our results indicate that when normal neuroblastoma cells were cultured in the presence of copper ions, t ... | 2003 | 14642846 |
| epidemiological implications of the susceptibility to bse of putatively resistant sheep. | the experimental infection of sheep with bovine spongiform encephalopathy (bse) by the oral route and the likelihood that sheep were fed bse-infected meat and bone meal has led to extensive speculation as to whether or not sheep are naturally infected with bse. in response, the uk government has initiated the national scrapie plan (nsp), an ambitious pound 120 million per year project to create a bse- and scrapie-resistant national sheep flock, by selectively breeding for a genotype of sheep bel ... | 2003 | 14645932 |
| prion probing comes up with the goods. | 2003 | 14649239 | |
| the clinical neurology of scrapie in irish sheep. | one hundred twenty-nine sheep with scrapie were identified from 20 flocks in which scrapie previously had been confirmed. physical and neurologic examinations were performed on all animals. videotape recordings were made and reviewed to assess gait. these procedures were repeated in 46 sheep at 2- to 3-week intervals until recumbency or inappetence necessitated euthanasia. confirmation of scrapie was made by histopathologic and immunohistochemical examinations of brain tissue. the clinical signs ... | 2003 | 14658730 |
| first confirmed sheep scrapie with a136r154q171 genotype in slovakia. | the first confirmed evidence of scrapie in slovakia was demonstrated in one sheep of the autochthonous merino breed from the southeastern part of the country. the reported scrapie was diagnosed during compulsory transmissible spongiform encephalitis (tse) screening of sheep over 9 months of age assigned for consumption. the positive ewe was 5-year-old, which did not show any clinical signs of scrapie. the presence of the proteinase-resistant prion protein (prp) in brain was proved independently ... | 2003 | 14658850 |
| subclinical prion infection. | prion diseases are transmissible neurodegenerative disorders that include scrapie in sheep, bovine spongiform encephalopathy (bse) in cattle and creutzfeldt-jakob disease (cjd) in humans. the principal component of the infectious agent responsible for these diseases appears to be an abnormal isoform of the host-encoded prion protein (prp), designated prp(sc). prion diseases are transmissible to the same or different mammalian species by inoculation with, or dietary exposure to, infected tissues. ... | 2003 | 14659690 |
| prion gene sequence variation within diverse groups of u.s. sheep, beef cattle, and deer. | prions are proteins that play a central role in transmissible spongiform encephalopathies in a variety of mammals. among the most notable prion disorders in ungulates are scrapie in sheep, bovine spongiform encephalopathy in cattle, and chronic wasting disease in deer. single nucleotide polymorphisms in the sheep prion gene ( prnp) have been correlated with susceptibility to natural scrapie in some populations. similar correlations have not been reported in cattle or deer; however, characterizat ... | 2003 | 14722726 |
| [scrapie, proteasome and endoplasmic reticulum]. | 2003 | 14593603 | |
| sodium hydroxide renders the prion protein prpsc sensitive to proteinase k. | sodium hydroxide (naoh) solutions are widely used for the purification of contaminated equipment, as they are known to inactivate a variety of pathogens. however, information about their effect on agents causing transmissible spongiform encephalopathy (tse) is sparse and contradictory. scrapie hamster brain homogenate, containing the disease-associated form of the prion protein (prp(sc)), was exposed to naoh. kinetics studies showed that treatment of brain homogenate with millimolar concentratio ... | 2003 | 14573823 |
| transmission of murine scrapie to p101l transgenic mice. | the prp protein is central to the transmissible spongiform encephalopathies (tses), and the amino acid sequence of this protein in the host can influence both incubation time of disease and targeting of disease pathology. the n terminus of murine prp has been proposed to be important in the replication of tse agents, as mutations or deletions in that region can alter the efficiency of agent replication. to address this hypothesis and to investigate the mechanisms by which host prp sequence contr ... | 2003 | 14573822 |
| voluntary scrapie flocks scheme. | 2003 | 14690083 | |
| detection of new quantitative trait loci for susceptibility to transmissible spongiform encephalopathies in mice. | susceptibility to scrapie is largely controlled by the prnp gene in mice and in several other species. however, individuals with identical scrapie susceptibility prnp alleles may have very different incubation periods, suggesting the influence of other environmental and genetic factors. to detect loci influencing susceptibility to tse, two mouse lines carrying the same prnp genotype (c57bl and riii) were crossed to produce an f2 population inoculated intracerebrally with a mouse-adapted scrapie ... | 2003 | 14704188 |
| selective prion protein binding to synaptic components is modulated by oxidative and nitrosative changes induced by copper(ii) and peroxynitrite in cholinergic synaptosomes, unveiling a role for calcineurin b and thioredoxin. | choline acetyltransferase (chat) and choline transport are decreased after nitrosative stress. chat activity is altered in scrapie-infected neurons, where oxidative stress develops. cellular prion protein (prpc) may play a neuroprotective function in participating in the redox control of neuronal environment and regulation of copper metabolism, a role impaired when prpc is transformed into prpsc in prion pathologies. the complex cross-talk between prpc and cholinergic neurons was analyzed in vit ... | 2003 | 14713301 |
| identification of a novel ovine prp polymorphism and scrapie-resistant genotypes for st. croix white and a related composite breed. | susceptibility to scrapie is primarily controlled by polymorphisms in the ovine prion protein gene (prnp). here, we report a novel ovine exon three prnp polymorphism (snp g346c; p116), its association with the ovine arq allele (p116a136r154q171), and two new genotypes (parq/arr; parq/arq) for the st. croix white (scw) breed and a related composite (cmp) breed developed for meat production. the (p116) polymorphism occurs between the n-terminal cleavage site and the hydrophobic region of the ovine ... | 2003 | 14970684 |
| allelic variants of ovine prion protein gene (prnp) in oklahoma sheep. | 1,144 sheep belonging to 21 breeds and known crosses were sequence analyzed for polymorphisms in the ovine prnp gene. genotype and allele frequencies of polymorphisms in prnp known to confer resistance to scrapie, a fatal neurodegenerative disease of sheep, are reported. known polymorphisms at codons 136 (a/v), 154 (h/r) and 171 (q/r/h/k) were identified. the frequency of the 171r allele known to confer resistance to type c scrapie was 53.8% and the frequency of the 136a allele known to influenc ... | 2003 | 14970685 |
| exuberant cellular reaction of the optic nerves in experimental creutzfeldt-jakob disease. | we report here on the exuberant glial reaction in the optic nerves affected by prion diseases. optic nerves from cjd- and gss-, and scrapie-infected mice and hamsters showed severe pathology. these lesions were qualitatively indistinguishable from each other but were more intense in the fujisaki model than in the hamsters inoculated with echigo-1. exuberant cellular reaction comprised of macrophages containing numerous mitochondria, abundant rough endoplasmic reticulum, and secondary lysosomes f ... | 2003 | 15053254 |
| mutational analysis of topological determinants in prion protein (prp) and measurement of transmembrane and cytosolic prp during prion infection. | the prion protein (prp) can adopt multiple membrane topologies, including a fully translocated form (secprp), two transmembrane forms (ntmprp and ctmprp), and a cytosolic form. it is important to understand the factors that influence production of these species, because two of them, ctmprp and cytosolic prp, have been proposed to be key neurotoxic intermediates in certain prion diseases. in this paper, we perform a mutational analysis of prp synthesized using an in vitro translation system in or ... | 2003 | 12933795 |
| ultrastructural changes in the optic nerves of rodents with experimental creutzfeldt-jakob disease (cjd), gerstmann-sträussler-scheinker disease (gss) or scrapie. | this report describes the ultrastructural changes in the optic nerves of (1) hamsters infected with the echigo-1 strain of creutzfeldt-jakob disease (cjd), (2) hamsters infected with the 263k or 22c-h strain of scrapie, and (3) mice infected with the fujisaki strain of gerstmann-sträussler-scheinker disease (gss). vacuolation of myelinated fibres was present in the myelin sheaths, with splitting of myelin lamellae. these vacuoles contained typical secondary vacuoles and curled membrane fragments ... | 2003 | 12921728 |
| cytosolic prion protein is not toxic and protects against bax-mediated cell death in human primary neurons. | recently, it was observed that reverse-translocated cytosolic prp and prp expressed in the cytosol induce rapid death in neurons (ma, j., wollmann, r., and lindquist, s. (2002) science 298, 1781-1785). in this study, we investigated whether accumulation of prion protein (prp) in the cytosol is toxic to human neurons in primary culture. we show that in these neurons, a single prp isoform lacking signal peptide accumulates in the cytosol of neurons treated with epoxomicin, a specific proteasome in ... | 2003 | 12917444 |
| dimethyl sulfoxide delays prp sc accumulation and disease symptoms in prion-infected hamsters. | prp(sc), an aberrantly folded protein, is the only identified component of the prion, an agent causing fatal neurodegenerative diseases such as scrapie and bovine spongiform encephalopathy. dimethyl sulfoxide (dmso) has been shown to reduce the accumulation of prp(sc) in scrapie-infected (scn2a) cells, and to inhibit its aggregation in vitro. in humans, dmso was used successfully in the treatment of various peripheral amyloidotic diseases. here we show that administration of dmso to scrapie-infe ... | 2003 | 12914974 |
| characterization of 2'-fluoro-rna aptamers that bind preferentially to disease-associated conformations of prion protein and inhibit conversion. | we have isolated artificial ligands or aptamers for infectious prions in order to investigate conformational aspects of prion pathogenesis. the aptamers are 2'-fluoro-modified rna produced by in vitro selection from a large, randomized library. one of these ligands (aptamer saf-93) had more than 10-fold higher affinity for prpsc than for recombinant prpc and inhibited the accumulation of prpres in near physiological cell-free conversion assay. to understand the molecular basis of these propertie ... | 2003 | 12902353 |
| congo red analogues as potential anti-prion agents. | 'transmissible spongiform encephalopathies' (tse) are a group of degenerative, progressive and fatal disorders of cns which affect both humans and animals, characterised by a long incubation time. the pathogenetic mechanism in tse is the conversion of normal prion protein (prp(sen)) to an altered protease resistant isoform (prp(res)) that accumulates in amyloid deposits into the brain; therefore, prp(res) is the primary target for therapeutic strategies. the discovery that the sulphonated azo dy ... | 2003 | 13679188 |
| a quantitative, highly sensitive cell-based infectivity assay for mouse scrapie prions. | prions are usually quantified by bioassays based on intracerebral inoculation of mice that are slow, imprecise, and costly. we have isolated neuroblastoma n2a sublines highly susceptible to mouse prions, as evidenced by accumulation of infectivity and the scrapie form of prion protein (prpsc), and developed quantitative in vitro assays for prion infectivity. in the scrapie cell (sc) assay, susceptible n2a cells are exposed to prion-containing samples for 3 days, grown to confluence, and split 1: ... | 2003 | 14504404 |
| n-acetyl aspartate estimation: a potential method for determining neuronal loss in the transmissible spongiform encephalopathies. | neurodegenerative pathology is typical of the transmissible spongiform encephalopathies (tses), and is thought to underlie clinical disease. some morphometric studies have shown early focal neurone loss, but the full extent of tse induced neuronal loss in the central nervous system is not known, and can only be accurately estimated using intensive morphometric techniques. we have used a murine scrapie model in which we determined the levels of n-acetyl aspartate (naa), a putative neuronal marker ... | 2003 | 14507336 |
| generation of antibodies against prion protein by scrapie-infected cell immunization of prp(0/0) mice. | four monoclonal antibodies (mabs) specific for prion protein (prp) were generated by using prp-knockout mice immunized with a scrapie-infected mouse neuroblastoma cell line (n2a/22l). the mabs reacted with both the cellular form (prp(c)) and the protease k-treated form (prp(sc)) on western blotting. of the four mabs, three recognized mouse and hamster prp, while the remaining mab recognized mouse, sheep, and bovine prps. in addition, these mabs were shown to react only with the unglycosylated an ... | 2003 | 14511572 |
| monte carlo simulation of surveillance strategies for scrapie in norwegian sheep. | our aim was to compare the efficiency of different surveillance strategies for detecting scrapie-infected sheep flocks in the norwegian population using simulation modelling. the dynamic monte carlo simulation model has the flock as the unit. the input parameters include properties of the sheep population (number of flocks, flock size, age distribution, reasons for culling, breeds, prion protein-allele distribution); properties of scrapie (genotype-dependent infection rate and incubation periods ... | 2003 | 14519340 |
| copper chelation delays the onset of prion disease. | the prion protein (prp) binds copper and under some conditions copper can facilitate its folding into a more protease resistant form. hence, copper levels may influence the infectivity of the scrapie form of prion protein (prpsc). to determine the feasibility of copper-targeted therapy for prion disease, we treated mice with a copper chelator, d-(-)-penicillamine (d-pen), starting immediately following intraperitoneal scrapie inoculation. d-pen delayed the onset of prion disease in the mice by a ... | 2003 | 14519758 |
| introduction to the transmissible spongiform encephalopathies or prion diseases. | sheep scrapie has been known for at least 200 years and was described as a transmissible disease over 100 years ago. since then, three groups of transmissible spongiform encephalopathies or tse diseases have been identified in humans including familial, infectious and sporadic types. the discovery of the prion protein (prp) in the 1980s greatly accelerated knowledge of the biology and pathogenesis of tse diseases as this protein was found to play a critical role in disease susceptibility and the ... | 2003 | 14522845 |
| biochemistry and structure of prp(c) and prp(sc). | in a brief historical description, it is shown that the prion model was developed from the biochemical and biophysical properties of the scrapie infectious agent. the biochemical properties of the prion protein which is the major, if not only, component of the prion are outlined in detail. prp is a host-encoded protein which exists as prp(c) (cellular) in the non-infected host, and as prp(sc) (scrapie) as the major component of the scrapie infectious agent. an overview of the purification techni ... | 2003 | 14522846 |
| physiological and pathological functions of the prion protein homologue dpl. | a misfolded version of the prion protein prp(c), known as prp(sc), is the major component of scrapie infectivity, the pathological agent in transmissible spongiform encephalopathies. the prnp gene that encodes the cellular prp(c) protein was cloned almost 20 years ago, but remained without sequence or structural relatives for over a decade. only recently a novel protein, named doppel (dpl), was identified, which shares significant biochemical and structural homology with prp(c). when overexpress ... | 2003 | 14522847 |
| prp knock-out and prp transgenic mice in prion research. | spongiform encephalopathies such as scrapie in sheep, bovine spongiform encephalopathy (bse) in cattle or creutzfeldt-jacob disease (cjd) and gerstmann-sträussler-scheinker syndrome (gss) in humans is caused by a transmissible agent designated prion. the 'protein only' hypothesis proposes that the prion consists partly or entirely of a conformational isoform of the normal host protein prp(c), designated prp(*)(1) and that the abnormal conformer, when introduced into the organism, causes the conv ... | 2003 | 14522848 |
| prion propagation in cultured cells. | cell cultures represent relevant and useful experimental models of transmissible spongiform encephalopathies (tses). they are able to promote, upon subpassaging, stable and persistent replication of prp(sc) as well as infectivity. to date, only a few cell culture models permissive to prion replication are available. among them, mouse neuroblastoma cell lines (n2a) are most commonly used. while they correspond to homologous models supporting propagation of mouse-adapted scrapie strains, recent st ... | 2003 | 14522851 |
| tse strain variation. | studies in mice have revealed considerable strain variation in the agents causing transmissible spongiform encephalopathies (tses). tse strains interact with genetic factors in the host (in particular prp genotype) to influence characteristics of the disease such as incubation period and neuropathology. tse strains can retain their identity after propagation in different host species or prp genotypes, showing that these agents carry their own strain-specific information. it is not known whether ... | 2003 | 14522852 |
| cns pathogenesis of prion diseases. | prion diseases or transmissible spongiform encephalopathies (tses) are fatal neurodegenerative diseases, clinically characterised by cognitive decline, paralleled by severe damage to the central nervous system. prion diseases have attracted a broad interest because of their unique mechanisms of replication and propagation; however, the underlying pathogenic mechanisms are still highly speculative. in this review, current knowledge about the pathogenesis of prion diseases in the cns will be highl ... | 2003 | 14522855 |
| scrapie and experimental bse in sheep. | scrapie is a natural disease of sheep, but it can also be successfully transmitted between sheep by experimental inoculation. although bse is primarily a disease of cattle, it has also infected humans (causing vcjd) and, in addition, can be transmitted orally to sheep bringing concerns that bse might naturally have infected the uk sheep population. because of this, scrapie and bse are being compared and studied in detail in sheep. prp genotype controls sheep susceptibility and resistance to scra ... | 2003 | 14522858 |
| bovine spongiform encephalopathy (bse) and its epidemiology. | since the recognition of bse in 1986, over 180,000 cattle in the uk have developed the disease and 1-3 million are likely to have been infected with the bse agent, most of which were slaughtered for human consumption before developing signs of the disease. the origin of the first case of bse is unknown, but the epidemic was caused by the recycling of processed waste parts of cattle, some of which were infected with the bse agent, to other cattle in feed. control measures have resulted in the con ... | 2003 | 14522859 |
| other animal prion diseases. | in addition to bovine spongiform encephalopathy (bse) of cattle and scrapie of sheep and goats, a few other animal prion diseases have been reported. these include feline spongiform encephalopathy of zoological and domestic cats (fse) and transmissible spongiform encephalopathy (tse) of zoological ruminants and non-human primates, as well as chronic wasting disease of deer and elk (cwd) and transmissible mink encephalopathy of farmed mink (tme). the origins of tse in cats, zoo bovids, and non-hu ... | 2003 | 14522860 |
| caspase-12 and endoplasmic reticulum stress mediate neurotoxicity of pathological prion protein. | prion diseases are characterized by accumulation of misfolded prion protein (prp(sc)), and neuronal death by apoptosis. here we show that nanomolar concentrations of purified prp(sc) from mouse scrapie brain induce apoptosis of n2a neuroblastoma cells. prp(sc) toxicity was associated with an increase of intracellular calcium released from endoplasmic reticulum (er) and up-regulation of several er chaperones. caspase-12 activation was detected in cells treated with prp(sc), and cellular death was ... | 2003 | 14532116 |
| pathogenesis of bse. | before the emergence of bovine spongiform encephalopathy (bse) and recognition of its zoonotic potential, the major example of the transmissible spongiform encephalopathies (tses) of animals was scrapie of sheep. but there is no evidence that scrapie transmits naturally to any species other than sheep and goats. the pathogenesis of scrapie has been studied most in experimental laboratory rodent species. in most experimental models of scrapie, after peripheral non-neural routes of infection, repl ... | 2003 | 14535364 |
| animal transmissible spongiform encephalopathies and genetics. | the genotype of the host plays a crucial role in the pathogenesis of transmissible spongiform encephalopathies (tses). in this respect, the most important factor is represented by the gene of the prion protein (prp). the present work summarizes the currently available knowledge on the genetic basis of tses focusing, in particular, on sheep scrapie. interest in this disease has grown markedly following the discovery of bovine spongiform encephalopathy, both for scientific and health reasons. in i ... | 2003 | 14535366 |
| development of in vitro cell cultures for the evaluation of molecules with antiprionic activity. | 2003 | 14535427 | |
| immunisation with a synthetic prion protein-derived peptide prolongs survival times of mice orally exposed to the scrapie agent. | several lines of evidence suggest that immunisations may be helpful in the prophylaxis and treatment of neurodegenerative amyloidoses like alzheimer's disease and prion infections. we used a synthetic prion protein-derived peptide (prp105-125) and a recombinant prp fragment (prp90-230) as antigens for the active immunisation of mice, which were subsequently infected by dietary exposure to the scrapie agent. immunisation with prp105-125 prolonged the survival times significantly. in contrast, imm ... | 2003 | 14550926 |
| prevalence of scrapie infection in great britain: interpreting the results of the 1997-1998 abattoir survey. | an accurate estimate of the prevalence of scrapie infection in the great britain (gb) sheep flock is essential when assessing any potential risk to human health through exposure to sheep transmissible spongiform encephalopathies (tses). one method for assessing the prevalence is to sample sheep intended for human consumption using a diagnostic test capable of detecting infected animals prior to the onset of clinical signs. an abattoir survey conducted in great britain in 1997-1998 tested brain s ... | 2003 | 14561305 |
| positioning of follicular dendritic cells within the spleen controls prion neuroinvasion. | peripheral infection is the natural route of transmission in most prion diseases. peripheral prion infection is followed by rapid prion replication in lymphoid organs, neuroinvasion and progressive neurological disease. both immune cells and nerves are involved in pathogenesis, but the mechanisms of prion transfer from the immune to the nervous system are unknown. here we show that ablation of the chemokine receptor cxcr5 juxtaposes follicular dendritic cells (fdcs) to major splenic nerves, and ... | 2003 | 14562059 |
| prion diseases: a nucleic-acid accomplice? | 2003 | 14562085 | |
| rna molecules stimulate prion protein conversion. | much evidence supports the hypothesis that the infectious agents of prion diseases are devoid of nucleic acid, and instead are composed of a specific infectious protein. this protein, prp(sc), seems to be generated by template-induced conformational change of a normally expressed glycoprotein, prp(c) (ref. 2). although numerous studies have established the conversion of prp(c) to prp(sc) as the central pathogenic event of prion disease, it is unknown whether cellular factors other than prp(c) mi ... | 2003 | 14562104 |
| elucidation of endemic neurodegenerative diseases--a commentary. | recent investigations of scrapie, creutzfeldt-jakob disease (cjd), and chronic wasting disease (cwd) clusters in iceland, slovakia and colorado, respectively, have indicated that the soil in these regions is low in copper and higher in manganese, and it has been well-known that patients of als or parkinson's disease were collectively found in the new guinea and papua islands, where the subterranean water (drinking water) contains much al3+ and mn2+ ions. above facts suggest that these neurodegen ... | 2003 | 14577644 |
| [involvement of the immunological system in the pathogenesis of transmissible spongiform encephalopathies]. | we review the current knowledge relative to the role of different immune system components and their contribution the spread of prions throughout the infected organism. | 2003 | 14582023 |
| depleting neuronal prp in prion infection prevents disease and reverses spongiosis. | the mechanisms involved in prion neurotoxicity are unclear, and therapies preventing accumulation of prpsc, the disease-associated form of prion protein (prp), do not significantly prolong survival in mice with central nervous system prion infection. we found that depleting endogenous neuronal prpc in mice with established neuroinvasive prion infection reversed early spongiform change and prevented neuronal loss and progression to clinical disease. this occurred despite the accumulation of extra ... | 2003 | 14593181 |
| dynamics of a scrapie outbreak in a flock of romanov sheep--estimation of transmission parameters. | knowledge of epidemiological mechanisms and parameters underlying scrapie transmission in sheep flocks remains very limited at present. here we introduce a method for fitting stochastic transmission models to outbreak data to estimate bounds on key transmission parameters. we apply this method to data describing an outbreak of scrapie in a closed flock of romanov sheep. the main findings are that the relative infectiousness of infected animals in this outbreak becomes appreciable early into dise ... | 2003 | 14596544 |
| gag bioscience gmbh. | completion of the human genome project led to an explosion in available genomic information. single nucleotide polymorphisms (snps) have emerged as a versatile and powerful tool for genotyping almost all variant species. the unique technological platform developed by gag bioscience is exclusively based on snp detection and allows genotyping of up to 60,000 samples per day. an analysis robot, a mass spectrometer and a database form a practically self-controlled analysis and documentation system t ... | 2003 | 14596644 |
| diagnosis and treatment of retropharyngeal injuries in lambs associated with the administration of intraruminal boluses. | the administration of intraruminal identification boluses to a group of 76 lambs resulted in 24 (32 per cent) showing signs of pharyngeal damage. in 16 of them the bolus was found to be in the retropharyngeal region by means of a hand-held microchip scanner, radiography and endoscopy. purulent tracts were identified in the dorsal pharynx. in 13 of the 16 lambs the surgical removal of the bolus under general anaesthesia was followed by a normal clinical recovery, although the lambs did not grow a ... | 2003 | 14601795 |
| scrapie genetic susceptibility in portuguese sheep breeds. | 2003 | 14601805 | |
| experimental transmission of abnormal prion protein (prpsc) in the small intestinal epithelial cells of neonatal mice. | using an immunohistochemical method, we attempted to detect the transmission of abnormal prion protein (prpsc) to the enterocytes of the small intestine of neonatal mice by oral exposure with sheep brain affected by scrapie. five 1-day-old neonatal mice were exposed by oral inoculation to the homogenized brain of a scrapie-affected sheep. in the small intestine of all mice 1 hour after inoculation, immunoreactivity with antinormal prion protein (prpc) antibody was seen in the cytoplasm of villus ... | 2003 | 14608031 |
| [neurodegenerative diseases, antioxidative enzymes and copper. a review of experimental research.] | introduction: in almost all degenerative diseases of the brain aggregation of proteins inside neurons or extracellulary, is a common pathological phenomenon regardless of etiology. it is assumed that the biochemical pathways leading to aggregation are more harmful than the aggregations themselves and most likely imply production of free oxygen radicals. this oxidative stress is in the body met by free radical scavengers in the form of specific chemical substances and antioxidative enzymes. it ha ... | 2003 | 16940591 |
| microdissection: a method developed to investigate mechanisms involved in transmissible spongiform encephalopathy pathogenesis. | the transmissible spongiform encephalopathies (tses) are a group of neurodegenerative diseases affecting both human and animals. the neuroanatomical changes which occur in the central nervous system (cns) of tse infected animals include vacuolation, gliosis, neuronal loss and the deposition of a disease specific protein, prpsc. experimental murine models of scrapie, a tse of sheep, have revealed that pathology may be confined to specific brain areas with targeting of particular neuronal subsets ... | 2004 | 15053838 |
| involvement of gut-associated lymphoid tissue of ruminants in the spread of transmissible spongiform encephalopathies. | scrapie is a transmissible spongiform encephalopathy (tse) and its spread across the intestine of sheep is linked to the biology of intestinal peyer's patches (pps). specialized epithelial cells, m cells, would appear to be the portal of entry for the scrapie agent, prp(sc), while lymphoid nodules of pps become major sites of accumulation of prp(sc) as the infection becomes established. furthermore, evidence suggests that the enteric nervous system supplying the pps is important for neuroinvasio ... | 2004 | 15063596 |
| dendritic cells and oral transmission of prion diseases. | transmissible spongiform encephalopathies (scrapie, bse, kuru) develop as central nervous system (cns) diseases after long incubation periods, and many of which may arise following the consumption of infected material. the infectious agent is thought to be a misfolded form (scrapie associated prp (prp(sc))) of a normal host protein (cellular isoform of prp (prp(c))), which is relatively resistant to proteolytic degradation and which serves as a template, directing host prion protein (prp) to acc ... | 2004 | 15063597 |
| evaluation of rapid tests for the diagnosis of transmissible spongiform encephalopathies in sheep and goats. | in accordance with eu regulation 999/2001, rapid tests already adopted for bovine spongiform encephalopathy (bse; prionics check western, platelia-bse and enfer tse) are to be applied in all european countries to a sub-population of over 18-month-old slaughtered or dead sheep and goats to improve scrapie surveillance and to determine the possible presence of bse in sheep; however, the three tests have thus far been evaluated only for bse and no official data are available about their performance ... | 2004 | 15067554 |
| knock-down of the 37-kda/67-kda laminin receptor in mouse brain by transgenic expression of specific antisense lrp rna. | the 37-kda/67-kda laminin receptor (lrp/lr) plays a major role in the propagation of prpsc, the abnormal form of the prion protein. in order to ablate the expression of lrp/lr in mouse brain we generated transgenic mice ectopically expressing antisense lrp rna in the brain under control of the neuron-specific enolase (nse) promoter. hemizygous transgenic mice tgn(nseaslrp)2 showed a significant reduction of lrp/lr protein levels in hippocampal and cerebellar brain regions. these mice might act a ... | 2004 | 15070079 |
| conformational variation between allelic variants of cell-surface ovine prion protein. | the distribution of prion infectivity and prpsc between peripheral lymphoid tissues suggests their possible haematogenic spread during the progression of natural scrapie in susceptible sheep. since ovine pbmcs (peripheral blood mononuclear cells) express prpc, they have the potential to carry or harbour disease-associated forms of prp. to detect the possible presence of disease-associated prp on the surface of blood cells, an understanding is required of the conformations that normal ovine cell- ... | 2004 | 15070397 |
| rapid disease development in scrapie-infected mice deficient for cd40 ligand. | the inhibition of cd40-cd40l interaction-mediated signalling was suggested as a therapeutic strategy for the treatment of alzheimer's disease. conversely, cd40-deficient neurons were reported to be more vulnerable to stress associated with ageing as well as nerve growth factor-beta and serum withdrawal. we studied the scrapie infection of cd40l-deficient (cd40l(-/-)) mice to see whether ablation of the cd40l gene would be beneficial or detrimental in this model of a neurodegenerative amyloidosis ... | 2004 | 15071493 |
| detection of polymorphisms in the prion protein gene in the belgian sheep population: some preliminary data. | the development of clinical signs of tse/scrapie in sheep has been linked to polymorphisms in the prion protein (prnp) gene. the most important polymorphisms appear to be at codons 136, 154, and 171. the objective of this study was to investigate the polymorphisms at these codons in the belgian sheep population, including clinical healthy animals, healthy animals at the slaughterhouse and animals in tse/scrapie positive farms (including a nor98 farm). | 2004 | 15072136 |
| clinicopathological findings in sheep from sardinia showing neurological signs of disease. | histopathological and bacteriological examinations were performed on 178 brains from sardinian sheep which were showing neurological signs. the sheep represented the total number of sheep with neurological syndromes submitted for diagnostic investigations over a three-year period in sardinia. scrapie was detected in 57 cases, cerebrocortical necrosis in 25, intoxication by a typical mediterranean plant (cistus species) was suspected in 25, coenurosis was detected in 11 cases, listeria monocytoge ... | 2004 | 15074327 |
| slow conformational dynamics in the hamster prion protein. | although the mechanism of the conformational conversion from the cellular (prp(c)) to the scrapie (prp(sc)) form of animal prion proteins has yet to be elucidated, evidence is accumulating that may provide insight into the conversion process at atomic resolution. here we show critical aspects of the slow fluctuation dynamics of the recombinant hamster prion protein, rprp(90-231), based on nmr relaxation analysis using carr-purcell-meiboom-gill (cpmg) experiments, and compare them in detail with ... | 2004 | 15078089 |
| scrapie protein degradation by cysteine proteases in cd11c+ dendritic cells and gt1-1 neuronal cells. | dendritic cells (dc) of the cd11c(+) myeloid phenotype have been implicated in the spread of scrapie in the host. previously, we have shown that cd11c(+) dc can cause a rapid degradation of proteinase k-resistant prion proteins (prp(sc)) in vitro, indicating a possible role of these cells in the clearance of prp(sc). to determine the mechanisms of prp(sc) degradation, cd11c(+) dc that had been exposed to prp(sc) derived from a neuronal cell line (gt1-1) infected with scrapie (scgt1-1) were treat ... | 2004 | 15078959 |
| chronic wasting disease--prion disease in the wild. | 2004 | 15094817 | |
| prion protein is ubiquitinated after developing protease resistance in the brains of scrapie-infected mice. | although the key event in the pathology of prion diseases is thought to be the conversion of cellular prion protein (prp(c)) to the protease-resistant scrapie species termed prp(sc), the factors that contribute to neurodegeneration in scrapie-infected animals are poorly understood. one probable determinant could be when the accumulation of prp(sc) in infected brain overwhelms the ubiquitin-proteasome system and triggers the degenerative cascade. in the present study, it was found that in mouse b ... | 2004 | 15095484 |