Publications
| Title | Abstract | Year Filter | PMID(sorted descending) Filter |
|---|
| 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 |
| 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 |
| [scrapie, proteasome and endoplasmic reticulum]. | 2003 | 14593603 | |
| 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 |
| [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 |
| 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 |
| 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 |
| strain-specific kinetics of prion protein formation in vitro and in vivo. | the molecular basis of prion strain diversity is proposed to be encoded by distinct conformations of the abnormal scrapie isoform of the prion protein (prp(sc)). prp(sc) formation for the hyper (hy) and drowsy (dy) strains of the transmissible mink encephalopathy (tme) agent was investigated using the cell-free prp conversion reaction to determine the role of distinct prp(sc) conformations in the rate of in vitro conversion of cellular prp into protease-resistant prp. prp conversion increased at ... | 2004 | 14573620 |
| 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 |
| prion diseases: a nucleic-acid accomplice? | 2003 | 14562085 | |
| 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 |
| 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 |
| 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 |
| development of in vitro cell cultures for the evaluation of molecules with antiprionic activity. | 2003 | 14535427 | |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| further experimental observations on scrapie. | 1961 | 14484424 | |
| distribution of the scrapie agent in the tissues of experimentally inoculated goats. | 1962 | 14484423 | |
| scrapie: a transmissible and hereditary disease of sheep. | 1962 | 14484073 | |
| the causal agent of scrapie. ii. extraction of the agent from infected goat tissue. | 1962 | 14476627 | |
| the causal agent of scrapie. i. extraction of the agent from infected sheep tissue. | 1962 | 14476626 | |
| further observations on the experimental production of scrapie in goats and sheep. | 1960 | 14430942 | |
| experimental production of scrapie in goats. | 1959 | 14430941 | |
| distribution of vacuolated neurons in brains of sheep affected with scrapie. | 1960 | 14429975 | |
| biochemical and haematological observation on the blood and cerebrospinal fluid of clinically healthy and scrapie-affected goats. | 1960 | 14422665 | |
| free and esterified cholesterol in the cerebrospinal fluid of goats affected with experimental scrapie. | 1965 | 14342649 | |
| succinic dehydrogenase, cytochrome oxidase and acid phosphatase activities in the brains of scrapie-infected goats and mice. | 1965 | 14329713 | |
| scrapie in mice. the stability of the agent to various suspending media, ph and solvent extraction. | 1965 | 14329712 | |
| experimental transmission of mouse passaged scrapie to goats, sheep, rats and hamsters. | 1965 | 14319384 | |
| resistance of the scrapie agent to formalin. | 1965 | 14317615 | |
| nitrogenous constituents of serum and urine in normal and scrapie sheep. | 1965 | 14281671 | |
| cultural characters of scrapie mouse brain. | 1965 | 14281662 | |
| studies on the heat stability and chromatographic behaviour of the scrapie agent. | 1964 | 14247749 | |
| transmission by contact of scrapie in mice. | 1964 | 14198336 | |
| genetical control of the incubation period in mice of the neurological disease, scrapie. | 1964 | 14167576 | |
| degeneration of the cerebellar and hypothalamoneurohypophysial systems in sheep with scrapie; and its relationship to human system degenerations. | 1964 | 14152208 | |
| the intracellular location of the agent of mouse scrapie. | 1964 | 14135538 | |
| experimental scrapie in goats: a modification of incubation period and clinical response following pre-treatment with normal goat brain. | 1963 | 14098502 | |
| experimental transmission of scrapie to rats. | 1963 | 14072925 | |
| the pathology of the brain of mice inoculated with tissues from scrapie sheep. | 1962 | 14003831 | |
| further observations on the experimental transmission of scrapie from sheep and goats to laboratory mice. | 1963 | 14003830 | |
| scrapie in sheep: the hereditary component in a high incidence environment. | 1962 | 13887736 | |
| cerebellar and midbrain lesions in scrapie. | 1960 | 13847683 | |
| the histopathology of the spinal cord in scrapie disease of sheep. | 1960 | 13844696 | |
| further studies on scrapie. | 1959 | 13833715 | |
| scrapie disease of sheep. | 1961 | 13788684 | |
| the histology of the spinal and sympathetic ganglia and the adrenal glands in scrapie disease of sheep. | 1961 | 13785183 | |
| scrapie produced experimentally in goats with special reference to the clinical syndrome. | 1961 | 13733383 | |
| brain glycogen- and copper-levels in normal sheep and sheep affected with scrapie. | 1961 | 13719725 | |
| encephalopathy in mice produced by inoculation with scrapie brain material. | 1961 | 13692303 | |
| 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 |
| attempts to demonstrate the transmissible agent of scrapie in experimentally infected goats by means of fluorescent antibody. | 1959 | 13663567 | |
| the histopathology of the brain stem of sheep affected with experimental scrapie. | 1958 | 13587709 | |
| the skeletal muscle of sheep affected with scrapie. | 1958 | 13525473 | |
| the histopathology of the brain stem of sheep affected with natural scrapie. | 1958 | 13525462 | |
| some clinical and histological observations on scrapie in sheep. | 1957 | 13475132 | |
| significance of vacuolated neurones in the medulla of sheep affected with scrapie. | 1957 | 13464849 | |
| vacuolated neurones in sheep affected with scrapie. | 1957 | 13418775 | |
| vacuolated neurones in sheep affected with scrapie. | 1957 | 13407753 | |
| myopathy in sheep; its relationship to scrapie and to dermatomyositis and muscular dystrophy. | 1956 | 13368509 | |
| scrapie; a study in ohio. | 1954 | 13129159 | |
| scrapie found in california sheep. | 1952 | 13022527 | |
| 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 |
| 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 |
| 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 |
| cases of scrapie with unusual features in norway and designation of a new type, nor98. | five cases of scrapie with unusual features have been diagnosed in norway since 1998. the affected sheep showed neurological signs dominated by ataxia, and had the prp genotypes homozygous a136 h154 q171/ a136h154q171 or heterozygous a136h154q171/a136r154q171, which are rarely associated with scrapie. brain histopathology revealed neuropil vacuolisation essentially in the cerebellar and cerebral cortices; vacuolation was less prominent in the brainstem, and no lesions were observed at the level ... | 2003 | 12956297 |
| effects of beta-sheet breaker peptide polymers on scrapie-infected mouse neuroblastoma cells and their affinities to prion protein fragment prp(81-145). | the effects of soto's 'beta-sheet breaker peptide' and its polymer on prpsc formation in scn2a cells were investigated. surface plasmon resonance study indicated that direct binding between prp(81-145) and the 'beta-sheet breaker peptide' is not specific and may not play a major role in the inhibition of prpsc formation. | 2003 | 12948186 |
| [gliosis as a trigger of pathomorphological changes in prion diseases]. | experiments with three cell lines revealed that the scraplecontaining cerebral extract, obtained from preliminarily infected 6-month mice, sharply induced the cellular proliferation, which was registered yet in 3 days after incubation. however, the cerebral extract of healthy 6-month mice did not virtually influence the velocity of cells' reproduction in all three cultures. the authors suggest, with respect to published data and to their independently found research results, that the gliosis of ... | 2003 | 12945205 |
| chronic wasting disease in deer and elk: scientific facts and findings. | chronic wasting disease (cwd) is a prion disease of cervids such as deer and elk in north america. unlike other transmissible spongiform encephalopathy (tse) such as scrapie, cwd occurs in both captive and wild ranging animals, but not in domestic ruminants such as sheep and cattle. in this paper, the history of the disease, pathogenesis of cwd, susceptibility of animals, its transmission mechanisms, potential origins of the disease, diagnostic methods in the field and laboratory tests, surveill ... | 2003 | 12939501 |
| variant creutzfeldt-jakob disease: pathology, epidemiology, and public health implications. | prion diseases, or transmissible spongiform encephalopathies, include creutzfeldt-jakob disease (cjd) in humans and scrapie and bovine spongiform encephalopathy (bse) in animals. these neurodegenerative diseases are invariably fatal and can be transmitted by inoculation or dietary exposure. they are associated with the accumulation of an altered, disease-associated form of the normal prion protein. pathologically, prion diseases result in neuronal cell death and a characteristic spongiform appea ... | 2003 | 12936961 |
| prophylactic and therapeutic effects of phthalocyanine tetrasulfonate in scrapie-infected mice. | the transmissible spongiform encephalopathy (tse) diseases are rare, neurodegenerative diseases that include scrapie in sheep, bovine spongiform encephalopathy, and creutzfeldt-jakob disease in humans. there are no effective treatments available for clinical use in humans. we now demonstrate that, in 2 different rodent models of scrapie, multiple pretreatments with the cyclic tetrapyrrole phthalocyanine tetrasulfonate (pcts) were as effective at delaying disease as multiple treatments starting a ... | 2003 | 12934186 |
| 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 |
| neurochemical and behavioural modifications induced by scrapie infection in golden hamsters. | scrapie-infected hamsters were tested for spontaneous motor activity and passive avoidance at various times after infection. after testing, some animals were killed and their whole brains assayed for norepinephrine, dopamine, serotonin and their metabolites. the apparent rate of turnover was estimated in terms of metabolite/amine concentrations. after 70 days, there was a decrease in passive avoidance and dopamine and serotonin. passive avoidance correlated with the apparent rate of turnover of ... | 2003 | 12932859 |
| 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 |
| experimental inoculation of scrapie and chronic wasting disease agents in raccoons (procyon lotor). | 2003 | 12918830 | |
| inducible cytokine gene expression in the brain in the me7/cv mouse model of scrapie is highly restricted, is at a strikingly low level relative to the degree of gliosis and occurs only late in disease. | the temporal course of cerebral cytokine gene expression was investigated in the me7/cv murine scrapie model to determine any association with neuropathological events. analysis by rnase protection assay (rpa) demonstrated no transcripts for ils 2, 3, 4, 5, 6, 7, 10, 12p40 and 13, granulocyte macrophage colony-stimulating factor, ifn-gamma or lymphotoxin-alpha at any time during the course of this disease. transcripts for transforming growth factor-beta 1 were constitutively expressed in both co ... | 2003 | 12917482 |
| a novel generation of heparan sulfate mimetics for the treatment of prion diseases. | the accumulation of prp(res), the protease-resistant abnormal form of the host-encoded cellular prion protein, prp(c), plays a central role in transmissible spongiform encephalopathies. human contamination by bovine spongiform encephalopathy (bse) has propelled many scientific teams on a highway for anti-prion drug development. this study reports that heparan sulfate mimetics (hms), developed originally for their effect on tissue regeneration, abolish prion propagation in scrapie-infected gt1 ce ... | 2003 | 12917481 |
| 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 |
| identification of novel proteinase k-resistant c-terminal fragments of prp in creutzfeldt-jakob disease. | the central event in the pathogenesis of prion diseases, a group of fatal, transmissible neurodegenerative disorders including creutzfeldt-jakob disease (cjd) in humans, is the conversion of the normal or cellular prion protein (prpc) into the abnormal or scrapie isoform (prpsc). the basis of the prpc to prpsc conversion is thought to involve the diminution of alpha-helical domains accompanied by the increase of beta structures within the prp molecule. consequently, treatment of prpsc with prote ... | 2003 | 12917418 |
| 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 |
| theoretical modeling of prion disease incubation. | we apply a theoretical aggregation model to laboratory and epidemiological prion disease incubation time data. in our model, slow growth of misfolded protein aggregates from small initial seeds controls the latent or lag phase; aggregate fissioning and subsequent spreading leads to an exponential growth phase. our model accounts for the striking reproducibility of incubation times for high dose inoculation of lab animals. in particular, low dose yields broad incubation time distributions, and in ... | 2003 | 12885622 |
| a short review of transmissible spongiform encephalopathies, and guidelines for managing risks associated with chronic wasting disease in captive cervids in zoos. | the transmissible spongiform encephalopathies (tses) represent an emerging group of diseases that have been labeled as "prion diseases" because of the recent characterization of the infectious agent. tses are caused by prions, which induce neurodegenerative fatal diseases in humans and animals. some tses (scrapie and kuru), have existed in both animals and humans for a very long time, whereas others such as bovine spongiform encephalopathy and variant creutzfeld-jakob disease have either recentl ... | 2003 | 12885128 |