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transmission and adaptation of chronic wasting disease to hamsters and transgenic mice: evidence for strains.in vitro screening using the cell-free prion protein conversion system indicated that certain rodents may be susceptible to chronic wasting disease (cwd). therefore, cwd isolates from mule deer, white-tailed deer, and elk were inoculated intracerebrally into various rodent species to assess the rodents' susceptibility and to develop new rodent models of cwd. the species inoculated were syrian golden, djungarian, chinese, siberian, and armenian hamsters, transgenic mice expressing the syrian gold ...200717287284
the spread of prions through the body in naturally acquired transmissible spongiform encephalopathies.transmissible spongiform encephalopathies are fatal neurodegenerative diseases that are caused by unconventional pathogens and affect the central nervous system of animals and humans. several different forms of these diseases result from natural infection (i.e. exposure to transmissible spongiform encephalopathy agents or prions, present in the natural environment of the respective host). this holds true also for scrapie in sheep, bovine spongiform encephalopathy in cattle, chronic wasting disea ...200717288548
resistance to chronic wasting disease in transgenic mice expressing a naturally occurring allelic variant of deer prion protein.prion protein (prp) is a required factor for susceptibility to transmissible spongiform encephalopathy or prion diseases. in transgenic mice, expression of prion protein (prp) from another species often confers susceptibility to prion disease from that donor species. for example, expression of deer or elk prp in transgenic mice has induced susceptibility to chronic wasting disease (cwd), the prion disease of cervids. in the current experiments, transgenic mice expressing two naturally occurring ...200717314157
fate of prions in soil: detergent extraction of prp from soils.the transmissible spongiform encephalopathies (tses) are caused by infectious agents whose structures have not been fully characterized but include abnormal forms of the host protein prp, designated prp(sc), which are deposited in infected tissues. the transmission routes of scrapie and chronic wasting disease (cwd) seem to include environmental spread in their epidemiology, yet the fate of tse agents in the environment is poorly understood. there are concerns that, for example, buried carcasses ...200717328187
colorado surveillance program for chronic wasting disease transmission to humans: lessons from 2 highly suspicious but negative cases.to describe 2 patients with rapidly progressive dementia and risk factors for exposure to chronic wasting disease (cwd) in whom extensive testing negated the possible transmission of cwd. design/200717353391
johne's disease (paratuberculosis) in goats: a report of eight cases in quebec.johne's disease (paratuberculosis) is reported in eight goats. clinical signs were mainly those of a chronic wasting disease which lead to emaciation, severe weakness, prostration and death. soft pasty stool and/or profuse diarrhea were observed only after several weeks of illness, in the terminal stages of the disease, in six of the eight goats. gross lesions were characterized by emaciation and mesenteric lymphadenopathy with more or less extensive areas of caseous necrosis and calcification. ...198217422111
adsorption of pathogenic prion protein to quartz sand.management responses to prion diseases of cattle, deer, and elk create a significant need for safe and effective disposal of infected carcasses and other materials. furthermore, soil may contribute to the horizontal transmission of sheep scrapie and cervid chronic wasting disease by serving as an environmental reservoirforthe infectious agent. as an initial step toward understanding prion mobility in porous materials such as soil and landfilled waste, the influence of ph and ionic strength (l) o ...200717438782
chronic wasting disease of deer and elk in transgenic mice: oral transmission and pathobiology.to study the pathogenesis of chronic wasting disease (cwd) in deer and elk, transgenic (tg) mice were generated that expressed the prion protein (prp) of deer containing a glycine at amino acid (aa) 96 and a serine at aa 225 under transcriptional control of the murine prp promoter. this construct was introduced into murine prp-deficient mice. as anticipated, neither non-tg mice nor prp ko mice were susceptible when inoculated intracerebrally (i.c.) or orally with cwd brain material (scrapie pool ...200717451773
a meta-baci approach for evaluating management intervention on chronic wasting disease in mule deer.advances in acquiring and analyzing the spatial attributes of data have greatly enhanced the potential utility of wildlife disease surveillance data for addressing problems of ecological or economic importance. we present an approach for using wildlife disease surveillance data to identify areas for (or of) intervention, to spatially delineate paired treatment and control areas, and then to analyze these nonrandomly selected sites in a meta-analysis framework via before-after-control impact (bac ...200717479841
good and bad news about transmissible spongiform encephalopathies (prion diseases). 200717488582
prion protein genes in caribou from alaska.prion protein genes were sequenced in free-ranging alaska caribou (rangifer tarandus grantii). caribou prion alleles are identical or nearly so to those of wapiti, white-tailed deer, and mule deer. five single-nucleotide polymorphisms were detected with substitutions at residues 2 (v-->m), 129 (g-->s), 138 (s-->n), 146 (n-->n), and 169 (v-->m). the 138n codon had been previously reported only in prion pseudogenes of other cervids. in caribou, the 138s and 138n alleles are present at frequencies ...200717495306
a natural case of chronic wasting disease in a free-ranging moose (alces alces shirasi).chronic wasting disease (cwd) was diagnosed in a free-ranging moose (alces alces shirasi) killed by a hunter in jackson county, colorado, usa, in september 2005. the diagnosis was based upon immunohistochemistry (ihc) demonstrating the presence of accumulations of cwd-associated prion protein (prp(cwd)) in tissue sections of medulla oblongata at the level of the obex (dorsal motor nucleus of the vagus) and in retropharyngeal lymph node (rpln); additional testing by ihc revealed deposits of prp(c ...200717495319
scrapie agent (strain 263k) can transmit disease via the oral route after persistence in soil over years.the persistence of infectious biomolecules in soil constitutes a substantial challenge. this holds particularly true with respect to prions, the causative agents of transmissible spongiform encephalopathies (tses) such as scrapie, bovine spongiform encephalopathy (bse), or chronic wasting disease (cwd). various studies have indicated that prions are able to persist in soil for years without losing their pathogenic activity. dissemination of prions into the environment can occur from several sour ...200717502917
levels of abnormal prion protein in deer and elk with chronic wasting disease.chronic wasting disease (cwd) of deer and elk is a widespread health concern because its potential for crossspecies transmission is undetermined. cwd prevalence in wild elk is much lower than its prevalence in wild deer, and whether cwd-infected deer and elk differ in ability to infect other species is unknown. because lymphoid tissues are important in the pathogenesis of some transmissible spongiform encephalopathies such as sheep scrapie, we investigated whether cwd-affected elk and deer diffe ...200717553219
efficient in vitro amplification of chronic wasting disease prpres.chronic wasting disease (cwd) of cervids is associated with conversion of the normal cervid prion protein, prp(c), to a protease-resistant conformer, prp(cwd). here we report the use of both nondenaturing amplification and protein-misfolding cyclic amplification (pmca) to amplify prp(cwd) in vitro. normal brains from deer, transgenic mice expressing cervid prp(c) [tg(cerprp)1536 mice], and ferrets supported amplification. pmca using normal tg(cerprp)1536 brains as the prp(c) substrate produced > ...200717553879
prpcwd in rectal lymphoid tissue of deer (odocoileus spp.).the utility of rectal lymphoid tissue sampling for the diagnosis of chronic wasting disease (cwd) infections in mule deer (odocoileus hemionus) and white-tailed deer (odocoileus virginianus) was evaluated. cwd-associated prion protein (prp(cwd)) deposits were observed in the rectal mucosa from 19 orally inoculated mule deer by 381 days post-inoculation (p.i.); similarly, 45 out of 50 naturally infected mule deer had prp(cwd) in their rectal mucosa. in orally inoculated white-tailed deer, the pre ...200717554043
special issue: prion-related disorders. 200717562431
susceptibility of cattle to first-passage intracerebral inoculation with chronic wasting disease agent from white-tailed deer.fourteen, 3-month-old calves were intracerebrally inoculated with the agent of chronic wasting disease (cwd) from white-tailed deer (cwdwtd) to compare the clinical signs and neuropathologic findings with those of certain other transmissible spongiform encephalopathies (tse, prion diseases) that have been shown to be experimentally transmissible to cattle (sheep scrapie, cwd of mule deer [cwdmd], bovine spongiform encephalopathy [bse], and transmissible mink encephalopathy). two uninoculated cal ...200717606510
effect of time and temperature on prpcwd immunoreactivity as evidenced by western blot.the protease-resistant infectious prion protein, prpres, that causes transmissible spongiform encephalopathies, is remarkably resistant to conventional physical and chemical sterilization methods, including heat. it was hypothesized that thermal-dependent prpres degradation has been underestimated, and the effect of prolonged incubation at 37 degrees c, 55 degrees c, and 80 degrees c on prpres detection was examined using brain homogenates from chronic wasting disease-affected elk and mule deer ...200717609348
polymorphisms of the prion gene promoter region that influence classical bovine spongiform encephalopathy susceptibility are not applicable to other transmissible spongiform encephalopathies in cattle.two regulatory region polymorphisms in the prion gene of cattle have been reported to have an association with resistance to classical bovine spongiform encephalopathy (bse). however, it is not known if this association also applies to other transmissible spongiform encephalopathies (tse) in cattle. in this report, we compare the relationship between these 2 polymorphisms and resistance in cattle affected with naturally occurring atypical bse as well as in cattle experimentally inoculated with e ...200717709775
spiroplasma spp. from transmissible spongiform encephalopathy brains or ticks induce spongiform encephalopathy in ruminants.spiroplasma, small motile wall-less bacteria, are linked by molecular and serological studies to the transmissible spongiform encephalopathies (tses), which include scrapie in sheep, chronic wasting disease (cwd) in deer and creutzfeldt-jakob disease in humans. in this study, two experiments were undertaken to determine the role of spiroplasma in the pathogenesis of tse. in experiment 1, spiroplasma mirum, a rabbit tick isolate that had previously been shown to experimentally induce spongiform e ...200717761489
applicability of current bovine spongiform encephalopathy (bse) diagnostic procedures for chronic wasting disease (cwd).chronic wasting disease (cwd) in cervids is one of the transmissible spongiform encephalopathies ; however, its risk to humans is still obscure. an increase in number of diseased deer in north america has raised concerns regarding the cwd risk to humans. we demonstrated that the con-firmatory procedures and the commercial diagnostic kits for bovine spongiform encephalopathy (bse) can be adopted for the diagnosis of cwd. no cwd case was confirmed in the surveillance of 558 cervids that were exami ...200717951994
direct detection of soil-bound prions.scrapie and chronic wasting disease are contagious prion diseases affecting sheep and cervids, respectively. studies have indicated that horizontal transmission is important in sustaining these epidemics, and that environmental contamination plays an important role in this. in the perspective of detecting prions in soil samples from the field by more direct methods than animal-based bioassays, we have developed a novel immuno-based approach that visualises in situ the major component (prp(sc)) o ...200717957252
species barriers for chronic wasting disease by in vitro conversion of prion protein.chronic wasting disease (cwd) is a transmissible spongiform encephalopathy that can affect north american cervids (deer, elk, and moose). using a novel in vitro conversion system based on incubation of prions with normal brain homogenates, we now report that prp(cwd) of elk can readily induce the conversion of normal cervid prp (prp(c)) molecules to a protease-resistant form, but is less efficient in converting the prp(c) of other species, such as human, bovine, hamster, and mouse. however, when ...200717964288
elk use of wallows and potential chronic wasting disease transmission.deposition of prions into the environment by infected animals may contribute to transmission and spread of chronic wasting disease (cwd) among free-ranging cervids, and identification of such environmental sources may provide an avenue for managing cwd. we evaluated the role that wallow use by elk (cervus elaphus) may play in cwd transmission by monitoring wallows with animal-activated cameras throughout their period of use. we monitored 39 wallows from 5 august 2005 to 14 october 2005. elk visi ...200717984281
age-related lesions in laboratory-confined raccoons (procyon lotor) inoculated with the agent of chronic wasting disease of mule deer.this communication documents age-associated pathologic changes and final observations on experimental transmission of chronic wasting disease (cwd) by the intracerebral route to raccoons (procyon lotor). four kits were inoculated intracerebrally with a brain suspension from mule deer with cwd. two uninoculated kits served as controls. one cwd-inoculated raccoon was humanely killed at 38 months after inoculation, and 1 control animal died at 68 months after inoculation. both animals had lesions t ...200717998557
elk with a long incubation prion disease phenotype have a unique prpd profile.the transmissible spongiform encephalopathies (tses) invariably result in fatal neurodegeneration and accumulation of prp, an abnormal form of the host prion protein prp, encoded by the prnp gene. a naturally occurring polymorphism (methionine/valine) at prnp codon 129 is associated with variation in relative disease susceptibility, incubation time, clinical presentation, neuropathology, and/or prp biochemical characteristics in a range of human tses. a methionine/leucine polymorphism at the cor ...200718007190
anti-prion activity generated by a novel vaccine formulation.chronic wasting disease (cwd) is a transmissible spongiform encephalopathy (tse) of domestic and wild cervids in north america. to address possible prevention regimens for cwd, we have used a mouse model system and the rocky mountain laboratory (rml) mouse-adapted scrapie prion strain to screen efficacy of potential vaccine candidates. three peptides derived from the primary amino acid sequence of the prion protein were conjugated to blue carrier protein (bcp) and formulated in an adjuvant conta ...200718023980
prion strain discrimination using luminescent conjugated polymers.the occurrence of multiple strains of prions may reflect conformational variability of prp(sc), a disease-associated, aggregated variant of the cellular prion protein, prp(c). here we used luminescent conjugated polymers (lcps), which emit conformation-dependent fluorescence spectra, for characterizing prion strains. lcp reactivity and emission spectra of brain sections discriminated among four immunohistochemically indistinguishable, serially mouse-passaged prion strains derived from sheep scra ...200718026110
molecular characterization of the rocky mountain elk (cervus elaphus nelsoni) prnp putative promoter.chronic wasting disease (cwd) is a transmissible spongiform encephalopathy (tse) affecting deer (odocoileus spp.), moose (alces alces), and rocky mountain elk (cervus elaphus nelsoni). leucine homozygosity at elk prnp codon 132 has been associated with reduced cwd susceptibility. however, naturally acquired cwd has been detected in elk possessing the 132 leu/leu genotype. recent human and bovine studies indicate that prnp regulatory polymorphisms may also influence tse occurrence. therefore, we ...200718032463
prions and prion diseases: fundamentals and mechanistic details.prion diseases, often called transmissible spongiform encephalopathies (tses), are infectious diseases that accompany neurological dysfunctions in many mammalian hosts. prion diseases include creutzfeldt-jakob disease (cjd) in humans, bovine spongiform encephalopathy (bse, "mad cow disease") in cattle, scrapie in sheep, and chronic wasting disease (cwd) in deer and elks. the cause of these fatal diseases is a proteinaceous pathogen termed prion that lacks functional nucleic acids. as demonstrate ...200718051314
cell models of prion infection.due to recent renewal of interest and concerns in prion diseases, a number of cell systems permissive to prion multiplication have been generated in the last years. these include established cell lines, neuronal stem cells and primary neuronal cultures. while most of these models are permissive to experimental, mouse-adapted strains of prions, the propagation of natural field isolates from sheep scrapie and chronic wasting disease has been recently achieved. these models have improved our knowle ...200818073097
landscape genetics and the spatial distribution of chronic wasting disease.predicting the spread of wildlife disease is critical for identifying populations at risk, targeting surveillance and designing proactive management programmes. we used a landscape genetics approach to identify landscape features that influenced gene flow and the distribution of chronic wasting disease (cwd) in wisconsin white-tailed deer. cwd prevalence was negatively correlated with genetic differentiation of study area deer from deer in the area of disease origin (core-area). genetic differen ...200818077240
comparison of retropharyngeal lymph node and obex region of the brainstem in detection of chronic wasting disease in white-tailed deer (odocoileus virginianus).chronic wasting disease (cwd) in wisconsin was first identified in february 2002. by april 2005, medial retropharyngeal lymph node (rln) tissues had been examined from over 75,000 white-tailed deer for the presence of cwd by either immunohistochemical (ihc) staining for the prion protein associated with cwd (prp(res)) or by using enzyme-linked immunosorbent assays with confirmation of positives by ihc staining and had been detected in 469 animals. obex tissue was also available from 438 of the c ...200818182509
epidemiology of an outbreak of chronic wasting disease on elk farms in saskatchewan.an outbreak of chronic wasting disease (cwd) in farmed elk in saskatchewan from 1996 to 2002 was reviewed to 1, determine the progression of cwd from infection to death in farmed elk; 2, assess animal risk factors for cwd infection in farmed elk; 3, assess farm management and exposure risk factors for within herd cwd transmission; and 4, assess the suitability of the canadian food inspection agency's (cfia) current disease control policy for cwd in light of the findings. the results from animal ...200718189044
the elk prnp codon 132 polymorphism controls cervid and scrapie prion propagation.the elk prion protein gene (prnp) encodes either methionine (m) or leucine (l) at codon 132, the l132 allele apparently affording protection against chronic wasting disease (cwd). the corresponding human codon 129 polymorphism influences the host range of bovine spongiform encephalopathy (bse) prions. to fully address the influence of this cervid polymorphism on cwd pathogenesis, we created transgenic (tg) mice expressing cervid prpc with l at residue 132, referred to as cerprpc-l132, and compar ...200818198392
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 ...200818284908
adaptation and evaluation of a rapid test for the diagnosis of sheep scrapie in samples of rectal mucosa.in recent publications, it was shown that disease-associated prion protein (prp(d)) accumulates in the lymphoid tissue of the rectal mucosa of a high proportion of scrapie-infected sheep at clinical and preclinical stages, regardless of several host factors; prp(d) can also be detected in biopsy specimens of rectal mucosa, with an increased probability proportional to age or incubation period and with an efficiency almost identical to that of tonsil biopsies. rectal biopsies have the advantages ...200818319433
preliminary observations on the experimental transmission of chronic wasting disease (cwd) from elk and white-tailed deer to fallow deer.to determine the transmissibility of chronic wasting disease (cwd) to fallow deer (dama dama) and to provide information about clinical course, lesions and suitability of currently used diagnostic procedures for detection of cwd in this species, 13 fawns were inoculated intracerebrally with cwd brain suspension from elk (n=6) or white-tailed deer (n=7). three other fawns were kept as uninfected controls. three cwd-inoculated deer were killed 7.6 months post-inoculation (mpi). none had abnormal p ...200818336829
a species barrier limits transmission of chronic wasting disease to mink (mustela vison).transmissible mink encephalopathy (tme) occurs as sporadic outbreaks associated with ingestion of feed presumably contaminated with some type of prion disease. mink lack a species barrier to primary oral challenge with bovine spongiform encephalopathy, whereas they have a barrier to such challenge with scrapie. we investigated whether mink have a species barrier to chronic wasting disease (cwd) by performing primary intracerebral (ic) and primary oral challenge with cwd-positive elk brain. prima ...200818343853
a prion disease of cervids: chronic wasting disease.chronic wasting disease (cwd) is a prion disease of deer, elk, and moose, initially recognized in colorado mule deer. the discovery of cwd beyond the borders of colorado and wyoming, in canada and as far east as new york, has led to its emergence as a prion disease of international importance. epidemiological studies indicate that cwd is horizontally transmitted among free-ranging animals, potentially indirectly by prion-containing secreta or excreta contaminating the environment. experimental c ...200818381058
experimental chronic wasting disease (cwd) in the ferret.chronic wasting disease (cwd), a prion disease of north american deer, elk and moose, affects both free-ranging and captive cervids. the potential host range for cwd remains uncertain. the susceptibility of the ferret to cwd was examined experimentally by administering infectious brain material by the intracerebral (ic) or oral (po) route. between 15 and 20 months after ic inoculation, ferrets developed neurological signs consistent with prion disease, including polyphagia, somnolence, piloerect ...200818387626
high titers of mucosal and systemic anti-prp antibodies abrogate oral prion infection in mucosal-vaccinated mice.significant outbreaks of prion disease linked to oral exposure of the prion agent have occurred in animal and human populations. these disorders are associated with a conformational change of a normal protein, prp(c) (c for cellular), to a toxic and infectious form, prp(sc) (sc for scrapie). none of the prionoses currently have an effective treatment. some forms of prion disease are thought to be spread by oral ingestion of prp(sc), such as chronic wasting disease and variant creutzfeldt-jakob d ...200818407424
prp genotypes of free-ranging wapiti (cervus elaphus nelsoni) with chronic wasting disease.variation in prp prion gene sequence appears to modulate susceptibility to chronic wasting disease (cwd), a naturally occurring prion disease affecting four north american species of the family cervidae. wapiti (cervus elaphus nelsoni) prp is polymorphic at codon 132 [methionine (m) or leucine (l)]. we genotyped 171 samples, collected between 2002 and 2005 from cwd-infected and uninfected wapiti from three free-ranging populations in colorado, usa, to study influences of prp polymorphisms on cwd ...200818420812
experimental transmission of chronic wasting disease (cwd) of elk (cervus elaphus nelsoni), white-tailed deer (odocoileus virginianus), and mule deer (odocoileus hemionus hemionus) to white-tailed deer by intracerebral route.to compare clinical and pathologic findings of chronic wasting disease (cwd) in a natural host, 3 groups (n = 5) of white-tailed deer (wtd) fawns were intracerebrally inoculated with a cwd prion of wtd, mule deer, or elk origin. three other uninoculated fawns served as controls. approximately 10 months postinoculation (mpi), 1 deer from each of the 3 inoculated groups was necropsied and their tissues were examined for lesions of spongiform encephalopathy (se) and for the presence of abnormal pri ...200818487485
transmission and detection of prions in feces.in chronic wasting disease (cwd) in cervids and in scrapie in sheep, prions appear to be transmitted horizontally. oral exposure to prion-tainted blood, urine, saliva, and feces has been suggested as the mode of transmission of cwd and scrapie among herbivores susceptible to these prion diseases. to explore the transmission of prions through feces, uninoculated syrian hamsters (shas) were cohabitated with or exposed to the bedding of shas orally infected with sc237 prions. incubation times of 14 ...200818505383
experimental transmission of bovine spongiform encephalopathy to european red deer (cervus elaphus elaphus).bovine spongiform encephalopathy (bse), a member of the transmissible spongiform encephalopathies (tse), primarily affects cattle. transmission is via concentrate feed rations contaminated with infected meat and bone meal (mbm). in addition to cattle, other food animal species are susceptible to bse and also pose a potential threat to human health as consumption of infected meat products is the cause of variant creutzfeldt-jakob disease in humans, which is invariably fatal. in the uk, farmed and ...200818507844
infectious disease in cervids of north america: data, models, and management challenges.over the past two decades there has been a steady increase in the study and management of wildlife diseases. this trend has been driven by the perception of an increase in emerging zoonotic diseases and the recognition that wildlife can be a critical factor for controlling infectious diseases in domestic animals. cervids are of recent concern because, as a group, they present a number of unique challenges. their close ecological and phylogenetic relationship to livestock species places them at r ...200818566093
risk behaviors in a rural community with a known point-source exposure to chronic wasting disease.the emergence and continuing spread of chronic wasting disease (cwd) in cervids has now reached 14 u.s. states, two canadian provinces, and south korea, producing a potential for transmission of cwd prions to humans and other animals globally. in 2005, cwd spread for the first time from the midwest to more densely populated regions of the east coast. as a result, a large cohort of individuals attending a wild game feast in upstate new york were exposed to a deer that was subsequently confirmed p ...200818577220
risks of transmitting ruminant spongiform encephalopathies (prion diseases) by semen and embryo transfer techniques.early experiments suggested that scrapie transmission via sheep embryos was a possibility, and gave rise to much controversy. however, when account is taken of the complex genetic effects on ovine susceptibility to scrapie, and of the several different scrapie strains with different clinical and pathological effects, the overall conclusion now is that transmission of classical scrapie by embryo transfer is very unlikely if appropriate precautions are taken. recent embryo transfer studies have co ...200818586320
bovine viral diarrhea virus multiorgan infection in two white-tailed deer in southeastern south dakota.the susceptibility of wild ruminants, especially cervids, to bovine viral diarrhea virus (bvdv) has remained an enigma. two white-tailed deer (odocoileus virginianus) were submitted to the animal disease research and diagnostic laboratory (adrdl) in the fall of 2003 by the south dakota game fish and parks for chronic wasting disease (cwd) testing. both animals were cwd negative. the animals were necropsied and histopathology, viral antigen detection, and virus isolation were performed. a noncyto ...200818689667
accelerated high fidelity prion amplification within and across prion species barriers.experimental obstacles have impeded our ability to study prion transmission within and, more particularly, between species. here, we used cervid prion protein expressed in brain extracts of transgenic mice, referred to as tg(cerprp), as a substrate for in vitro generation of chronic wasting disease (cwd) prions by protein misfolding cyclic amplification (pmca). characterization of this infectivity in tg(cerprp) mice demonstrated that serial pmca resulted in the high fidelity amplification of cwd ...200818769716
persistent bovine viral diarrhea virus infection in wild cervids of colorado.bovine viral diarrhea virus (bvdv) is a significant viral pathogen of domestic cattle. worldwide, there is evidence of bvdv exposure and infection in wild ungulates; however, the frequency and significance of such events are unknown. to determine the prevalence and distribution of colorado deer, elk, and moose persistently infected (pi) with bvdv, a cross-sectional study was conducted using full-thickness ear tissue samples collected from animals presented to the colorado division of wildlife fo ...200818776103
chronic wasting disease in a wisconsin white-tailed deer farm.in september 2002, chronic wasting disease (cwd), a prion disorder of captive and wild cervids, was diagnosed in a white-tailed deer (odocoileus virginianus) from a captive farm in wisconsin. the facility was subsequently quarantined, and in january 2006 the remaining 76 deer were depopulated. sixty animals (79%) were found to be positive by immunohistochemical staining for the abnormal prion protein (prp(cwd)) in at least one tissue; the prevalence of positive staining was high even in young de ...200818776116
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 ...200818800532
in vitro strain adaptation of cwd prions by serial protein misfolding cyclic amplification.we used serial protein misfolding cyclic amplification (spmca) to amplify the d10 strain of cwd prions in a linear relationship over two logs of d10 dilutions. the resultant pmca-amplified d10 induced terminal tse disease in cwd-susceptible tg(cerprp)1536 mice with a survival time approximately 80 days shorter than the original d10 inoculum, similar to that produced by in vivo sub-passage of d10 in tg(cerprp)1536 mice. both in vitro-amplified and mouse-passaged d10 produced brain lesion profiles ...200818952250
wasting and neurologic signs in a white-tailed deer (odocoileus virginianus) not associated with abnormal prion protein.a captive adult male white-tailed deer (odocoileus virginianus) with wasting and neurologic signs similar to chronic wasting disease (cwd) was evaluated by histopathology, histochemistry, and immunohistochemistry (ihc) for disease-associated prion protein (prp(d)). on histologic examination, the brainstem had areas of vacuolation in neuropil and extensive multifocal mineralization of blood vessels with occasional occlusion of the lumen. some of the clinical and pathologic features of this case w ...200818957666
prp antibody binding-induced epitope modulation evokes immunocooperativity.we have characterized the antibody-antigen binding events of the prion protein (prp) utilizing three new prp-specific monoclonal antibodies (mabs). the degree of immunoreactivity was dependent on the denaturation treatment with the combination of heat and sds resulting in the highest levels of epitope accessibility and antibody binding. interestingly however, this harsh denaturation treatment was not sufficient to completely and irreversibly abolish protein conformation. the mabs differed in the ...200818977037
disease-specific motifs can be identified in circulating nucleic acids from live elk and cattle infected with transmissible spongiform encephalopathies.to gain insight into the disease progression of transmissible spongiform encephalopathies (tse), we searched for disease-specific patterns in circulating nucleic acids (cna) in elk and cattle. in a 25-month time-course experiment, cnas were isolated from blood samples of 24 elk (cervus elaphus) orally challenged with chronic wasting disease (cwd) infectious material. in a separate experiment, blood-sample cnas from 29 experimental cattle (bos taurus) 40 months post-inoculation with clinical bovi ...200919059996
alkaline hydrolysis of mouse-adapted scrapie for inactivation and disposal of prion-positive material.prion diseases such as bovine spongiform encephalopathy, chronic wasting disease, and scrapie pose serious risks to human and animal health due to a host of disease-specific factors, including the resistance of infectious prions (prp(sc)) to natural degradation and to most commercial inactivation procedures. in an attempt to address this concern, a mouse model was used to compare the efficacy of an alkaline hydrolysis process with a simulated continuous-flow rendering treatment for disposal of p ...200919098230
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 ...200819098442
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.200819107193
antemortem detection of prpcwd in preclinical, ranch-raised rocky mountain elk (cervus elaphus nelsoni) by biopsy of the rectal mucosa.antemortem biopsy of the rectal mucosa was evaluated as a method for the preclinical diagnosis of chronic wasting disease (cwd) in a herd of ranch-raised rocky mountain elk (cervus elaphus nelsoni) quarantined because of exposure to cwd. biopsy samples were obtained from 41 elk during the winter of 2005-2006 and from 26 elk from that herd still alive and available for testing during the winter of 2006-2007. samples were examined for prp(cwd), the protein marker for cwd infection, by immunohistoc ...200919139496
chronic wasting disease.chronic wasting disease (cwd) is the only known prion disease affecting free-ranging animals and has become a serious epidemic in north america. although any case was reported from europe, the spread of the disease to other continents and regions cannot be excluded, because the transmission of cwd is the most efficient among prion diseases. this article reviews the host range of cwd including experimentally infected animals, models for potential transmissibility to humans, clinical signs of the ...200819143476
prion sequence polymorphisms and chronic wasting disease resistance in illinois white-tailed deer (odocoileus virginianus).nucleic acid sequences of the prion gene (prnp) were examined and genotypes compiled for 76 white-tailed deer from northern illinois, which previously tested positive for chronic wasting disease (cwd), and 120 negative animals selected to control for geographic location and age. nine nucleotide polymorphisms, seven silent and two coding, were found in the sampled population. all observed polymorphisms except two of very low frequency were observed in both negative and positive animals, although ...200819164895
recent advances in prion chemotherapeutics.the transmissible spongiform encephalopathies are rapidly progressive and invariably fatal neurodegenerative diseases for which there are no proven efficacious treatments. many approaches have been undertaken to find ways to prevent, halt, or reverse these prion diseases, with limited success to date. however, as both our understanding of pathogenesis and our ability to detect early disease increases, so do our potential therapeutic targets and our chances of finding effective drugs. there is in ...200919200018
cryptic peptides of the kringle domains preferentially bind to disease-associated prion protein.prion diseases are a group of fatal neurodegenerative disorders characterized by the accumulation of a misfolded form (prp(sc)) of the cellular prion protein (prp(c)) in the brains of affected individuals. the conversion of prp(c) to prp(sc) is thought to involve a change in protein conformation from a normal, primarily alpha-helical structure into a beta-sheet conformer. few proteins have been identified that differentially interact with the two forms of prp. it has been reported that plasminog ...200919221431
validation of use of rectoanal mucosa-associated lymphoid tissue for immunohistochemical diagnosis of chronic wasting disease in white-tailed deer (odocoileus virginianus).the examination of rectoanal mucosa-associated lymphoid tissue (ramalt) biopsy specimens for the diagnosis of transmissible spongiform encephalopathies has been described in sheep, elk, and small numbers of mule and white-tailed deer. previous sample numbers have been too small to validate examination of this type of tissue as a viable antemortem diagnostic test. in this study, we examined ramalt collected postmortem from 76 white-tailed deer removed from a farm in wisconsin known to be affected ...200919261781
transmission of scrapie and sheep-passaged bovine spongiform encephalopathy prions to transgenic mice expressing elk prion protein.chronic wasting disease (cwd) is a transmissible, fatal prion disease of cervids and is largely confined to north america. the origin of cwd continues to pose a conundrum: does the disease arise spontaneously or result from some other naturally occurring reservoir? to address whether prions from sheep might be able to cause disease in cervids, we inoculated mice expressing the elk prion protein (prp) transgene [tg(elkprp) mice] with two scrapie prion isolates. the ssbp/1 scrapie isolate transmit ...200919264659
trans-species amplification of prp(cwd) and correlation with rigid loop 170n.chronic wasting disease (cwd) is an efficiently transmitted spongiform encephalopathy of cervids. whether cwd could represent a threat to non-cervid species remains speculative. here we show that brain homogenates from several cwd-susceptible non-cervid species, such as ferrets and hamsters, support amplification of prp(cwd) by spmca, whereas brain homogenates from cwd-resistant species, such as laboratory mice and transgenic mice expressing human prp(c) [tg(huprp) mice], do not. we also investi ...200919269662
detection of cwd prions in urine and saliva of deer by transgenic mouse bioassay.chronic wasting disease (cwd) is a prion disease affecting captive and free-ranging cervids (e.g. deer, elk, and moose). the mechanisms of cwd transmission are poorly understood, though bodily fluids are thought to play an important role. here we report the presence of infectious prions in the urine and saliva of deer with chronic wasting disease (cwd). prion infectivity was detected by bioassay of concentrated, dialyzed urine and saliva in transgenic mice expressing the cervid prp gene (tg[cerp ...200919293928
identification of problems developing an ultrasensitive immunoassay for the ante mortem detection of the infectious isoform of the cwd-associated prion protein.ante-mortem assays exist for some transmission spongiform encephalopathies (tse). these assays facilitate our understanding of disease pathology and epidemiology; however, the limitations of these ante-mortem assays include the inability to quantify protein amount, poor sensitivity, and/or limited robustness. here, we utilize a bioinformatics approach to report on problems associated with developing a more sensitive immunoassay for tses including: 1) the lack of specific and sufficiently sensiti ...200919330640
chronic wasting disease prions in elk antler velvet.chronic wasting disease (cwd) is a contagious, fatal prion disease of deer and elk that continues to emerge in new locations. to explore the means by which prions are transmitted with high efficiency among cervids, we examined prion infectivity in the apical skin layer covering the growing antler (antler velvet) by using cwd-susceptible transgenic mice and protein misfolding cyclic amplification. our finding of prions in antler velvet of cwd-affected elk suggests that this tissue may play a role ...200919402954
surround optical fiber immunoassay (sofia): an ultra-sensitive assay for prion protein detection.we describe the development of a new technology (sofia) and demonstrate its utility by establishing a sensitive and specific assay for prp(sc). sofia is a surround optical fiber immunoassay which is comprised of a set of specific monoclonal antibodies and comprehensive capture of high energy fluorescence emission. in its current format, this system is capable of detecting less than 10 attogram (ag) of hamster, sheep and deer recombinant prp. approximately 10 ag of prp(sc) from 263 k-infected ham ...200919442839
genetic variability of the prion protein gene (prnp) in wild ruminants from italy and scotland.the genetics of the prion protein gene (prnp) play a crucial role in determining the relative susceptibility to transmissible spongiform encephalopathies (tses) in several mammalian species. to determine the prnp gene variability in european red deer (cervus elaphus), roe deer (capreolus capreolus) and chamois (rupicapra rupicapra), the prnp open reading frame from 715 samples was analysed to reveal a total of ten single nucleotide polymorphisms (snps). in red deer, snps were found in codons 15, ...200919461206
state-of-the-art review of goat tse in the european union, with special emphasis on prnp genetics and epidemiology.scrapie is a fatal, neurodegenerative disease of sheep and goats. it is also the earliest known member in the family of diseases classified as transmissible spongiform encephalopathies (tse) or prion diseases, which includes creutzfeldt-jakob disease in humans, bovine spongiform encephalopathy (bse), and chronic wasting disease in cervids. the recent revelation of naturally occurring bse in a goat has brought the issue of tse in goats to the attention of the public. in contrast to scrapie, bse p ...200919505422
infectious prions in pre-clinical deer and transmission of chronic wasting disease solely by environmental exposure.key to understanding the epidemiology and pathogenesis of prion diseases, including chronic wasting disease (cwd) of cervids, is determining the mode of transmission from one individual to another. we have previously reported that saliva and blood from cwd-infected deer contain sufficient infectious prions to transmit disease upon passage into naïve deer. here we again use bioassays in deer to show that blood and saliva of pre-symptomatic deer contain infectious prions capable of infecting naïve ...200919529769
host culling as an adaptive management tool for chronic wasting disease in white-tailed deer: a modelling study.emerging wildlife diseases pose a significant threat to natural and human systems. because of real or perceived risks of delayed actions, disease management strategies such as culling are often implemented before thorough scientific knowledge of disease dynamics is available. adaptive management is a valuable approach in addressing the uncertainty and complexity associated with wildlife disease problems and can be facilitated by using a formal model.we developed a multi-state computer simulation ...200919536340
space-time bayesian survival modeling of chronic wasting disease in deer.the primary objectives of this study are to describe the spatial and temporal variation in disease prevalence of chronic wasting disease (cwd), to assess the effect of demographic factors such as age and sex on disease prevalence and to model the disease clustering effects over space and time. we propose a bayesian hierarchical survival model where latent parameters capture temporal and spatial trends in disease incidence, incorporating several individual covariates and random effects. the model ...200919552977
prion infectivity in fat of deer with chronic wasting disease.chronic wasting disease (cwd) is a neurodegenerative prion disease of cervids. some animal prion diseases, such as bovine spongiform encephalopathy, can infect humans; however, human susceptibility to cwd is unknown. in ruminants, prion infectivity is found in central nervous system and lymphoid tissues, with smaller amounts in intestine and muscle. in mice, prion infectivity was recently detected in fat. since ruminant fat is consumed by humans and fed to animals, we determined infectivity tite ...200919570855
immunohistochemical and biochemical characteristics of bse and cwd in experimentally infected european red deer (cervus elaphus elaphus).the cause of the bovine spongiform encephalopathy (bse) epidemic in the united kingdom (uk) was the inclusion of contaminated meat and bone meal in the protein rations fed to cattle. those rations were not restricted to cattle but were also fed to other livestock including farmed and free living deer. although there are no reported cases to date of natural bse in european deer, bse has been shown to be naturally or experimentally transmissible to a wide range of different ungulate species. moreo ...200919635142
spatial and temporal patterns of chronic wasting disease: fine-scale mapping of a wildlife epidemic in wisconsin.emerging infectious diseases threaten wildlife populations and human health. understanding the spatial distributions of these new diseases is important for disease management and policy makers; however, the data are complicated by heterogeneities across host classes, sampling variance, sampling biases, and the space-time epidemic process. ignoring these issues can lead to false conclusions or obscure important patterns in the data, such as spatial variation in disease prevalence. here, we applie ...200919688937
prionet canada: a network of centres of excellence for research into prions and prion diseases.prionet canada's strength in basic, applied, and social research is helping to solve the food, health safety, and socioeconomic problems associated with prion diseases. prion diseases are transmissible, fatal neurodegenerative diseases of humans and animals. examples of prion diseases include bovine spongiform encephalopathy (bse, commonly known as "mad cow" disease), creutzfeldt-jakob disease in humans, and chronic wasting disease (cwd) in deer and elk. as of march 31, 2008, prionet's interdisc ...200919697232
chronic wasting disease (cwd) potential economic impact on cervid farming in alberta.chronic wasting disease (cwd) was found in wild deer populations in the province of alberta, canada, in 2005, and there is concern that this finding could create significant costs related to the farmed elk and deer industry. these potential costs or "values at risk" can be used to assess the economic returns from cwd containment and eradication programs. cost estimates of cwd to cervid farms range from $12 million for additional farm fencing to hundreds of millions of dollars in payments by gove ...200919697234
surveillance for transmissible spongiform encephalopathy in scavengers of white-tailed deer carcasses in the chronic wasting disease area of wisconsin.chronic wasting disease (cwd), a class of neurodegenerative transmissible spongiform encephalopathies (tse) occurring in cervids, is found in a number of states and provinces across north america. misfolded prions, the infectious agents of cwd, are deposited in the environment via carcass remains and excreta, and pose a threat of cross-species transmission. in this study tissues were tested from 812 representative mammalian scavengers, collected in the cwd-affected area of wisconsin, for tse inf ...200919697235
polymorphisms at the prnp gene influence susceptibility to chronic wasting disease in two species of deer (odocoileus spp.) in western canada.chronic wasting disease (cwd) is increasingly prevalent in multiple wild mule (odocoileus hemionus) and white-tailed deer (o. virginianus) herds in north america. cwd was first found in canadian wild mule deer in saskatchewan in 2000 and has since spread into the neighboring province of alberta. the infectious agent for cwd is a misfolded prion protein encoded by the prnp gene. previous studies revealed association between prnp genotype and susceptibility to cwd in both mule and white-tailed dee ...200919697236
influence of prion strain on prion protein adsorption to soil in a competitive matrix.it is likely that the soil environment serves as a stable reservoir of infectious chronic wasting disease (cwd) and scrapie prions, as well as a potential reservoir of bovine spongiform encephalopathy (bse, or "mad cow" disease). prion adsorption to soil may play an important role in prion mobility, proteolysis, and infectivity. differences in prp environmental fate are possible due to the strain- and species-dependent structure of prp(sc). kinetic and isothermal studies of prp adsorption to san ...200919708348
genetic susceptibility to chronic wasting disease in free-ranging white-tailed deer: complement component c1q and prnp polymorphisms.the genetic basis of susceptibility to chronic wasting disease (cwd) in free-ranging cervids is of great interest. association studies of disease susceptibility in free-ranging populations, however, face considerable challenges including: the need for large sample sizes when disease is rare, animals of unknown pedigree create a risk of spurious results due to population admixture, and the inability to control disease exposure or dose. we used an innovative matched case-control design and conditi ...200919723593
asymptomatic deer excrete infectious prions in faeces.infectious prion diseases-scrapie of sheep and chronic wasting disease (cwd) of several species in the deer family-are transmitted naturally within affected host populations. although several possible sources of contagion have been identified in excretions and secretions from symptomatic animals, the biological importance of these sources in sustaining epidemics remains unclear. here we show that asymptomatic cwd-infected mule deer (odocoileus hemionus) excrete cwd prions in their faeces long be ...200919741608
susceptibilities of nonhuman primates to chronic wasting disease.chronic wasting disease (cwd) is a transmissible spongiform encephalopathy, or prion disease, that affects deer, elk, and moose. human susceptibility to cwd remains unproven despite likely exposure to cwd-infected cervids. we used 2 nonhuman primate species, cynomolgus macaques and squirrel monkeys, as human models for cwd susceptibility. cwd was inoculated into these 2 species by intracerebral and oral routes. after intracerebral inoculation of squirrel monkeys, 7 of 8 cwd isolates induced a cl ...200919788803
visual pathology in animal prion diseases.prion diseases, also known as the transmissible spongiform encephalopathies (tses), are a group of slowly developing neurodegenerations occurring in human and animals. prion diseases can be transferred between animals, humans, from humans to animals, and from animals to humans. as a result, the central nervous system is attacked, resulting in microglia activation, astrocytosis, prion plaque deposition, and neuronal degeneration. prion also targets on the eye and brain visual system. in scrapie-i ...200919795355
detection of protease-resistant cervid prion protein in water from a cwd-endemic area.chronic wasting disease (cwd) is the only known transmissible spongiform encephalopathy affecting free-ranging wildlife. although the exact mode of natural transmission remains unknown, substantial evidence suggests that prions can persist in the environment, implicating components thereof as potential prion reservoirs and transmission vehicles.(1-4) cwd-positive animals may contribute to environmental prion load via decomposing carcasses and biological materials including saliva, blood, urine a ...200919823039
chronic wasting disease (cwd) susceptibility of several north american rodents that are sympatric with cervid cwd epidemics.chronic wasting disease (cwd) is a highly contagious always fatal neurodegenerative disease that is currently known to naturally infect only species of the deer family, cervidae. cwd epidemics are occurring in free-ranging cervids at several locations in north america, and other wildlife species are certainly being exposed to infectious material. to assess the potential for transmission, we intracerebrally inoculated four species of epidemic-sympatric rodents with cwd. transmission was efficient ...201019828611
mountain lions prey selectively on prion-infected mule deer.the possibility that predators choose prey selectively based on age or condition has been suggested but rarely tested. we examined whether mountain lions (puma concolor) selectively prey upon mule deer (odocoileus hemionus) infected with chronic wasting disease, a prion disease. we located kill sites of mountain lions in the northern front range of colorado, usa, and compared disease prevalence among lion-killed adult (> or =2 years old) deer with prevalence among sympatric deer taken by hunters ...201019864271
impact of age and sex of rocky mountain elk (cervus elaphus nelsoni) on follicle counts from rectal mucosal biopsies for preclinical detection of chronic wasting disease.to determine if the number of rectal lymphoid follicles decreases with respect to age and sex relative to diagnosis of chronic wasting disease (cwd), rectal biopsies (n = 1,361) were taken from captive rocky mountain elk (cervus elaphus nelsoni) at 4 ranches in the western united states between 2005 and 2008. rectal tissues were stained with a monoclonal antibody (f99/97.6.1), which selectively stains the abnormal isoform of the prion protein associated with cwd of elk. the number of lymphoid fo ...200919901292
surveillance to detect chronic wasting disease in white-tailed deer in wisconsin.chronic wasting disease (cwd), a prion disease affecting north american cervids, has been discovered in at least 12 states and provinces throughout the continent. since 2002, a number of states and provinces have initiated surveillance programs to detect cwd in native cervid populations. however, many questions remain about the appropriate methods, geographic scope, and number of samples required for an effective cwd surveillance program. we provide an improved statistical method to calculate th ...200919901375
detection of sub-clinical cwd infection in conventional test-negative deer long after oral exposure to urine and feces from cwd+ deer.chronic wasting disease (cwd) of cervids is a prion disease distinguished by high levels of transmissibility, wherein bodily fluids and excretions are thought to play an important role. using cervid bioassay and established cwd detection methods, we have previously identified infectious prions in saliva and blood but not urine or feces of cwd+ donors. more recently, we identified very low concentrations of cwd prions in urine of deer by cervid prp transgenic (tg[cerprp]) mouse bioassay and seria ...200919956732
monitoring and investigating natural disease by veterinary pathologists in diagnostic laboratories.many emerging diseases in animals are initially recognized by diagnostic pathologists in animal health laboratories using routine laboratory submissions, in conjunction with clinical veterinarians and wildlife biologists. familiar recent examples are chronic wasting disease, bovine spongiform encephalopathy, west nile encephalomyelitis in north america, and postweaning multisystemic wasting syndrome in pigs. the recognition of new diseases in animals requires that the curiosity of diagnosticians ...201020080483
a weighted surveillance approach for detecting chronic wasting disease foci.a key component of wildlife disease surveillance is determining the spread and geographic extent of pathogens by monitoring for infected individuals in regions where cases have not been previously detected. a practical challenge of such surveillance is developing reliable, yet cost-effective, approaches that remain sustainable when monitoring needs are prolonged or continuous, or when resources to support these efforts are limited. in order to improve the efficiency of chronic wasting disease (c ...201020090025
surveys for disease agents in introduced elk in arkansas and kentucky.surveys for disease agents were conducted in introduced free-ranging elk (cervus elaphus nelsoni) in arkansas and kentucky. elk had been captured in colorado and nebraska and released in arkansas during 1981-1985. from 1997 through 2002 elk were captured in arizona, kansas, north dakota, new mexico, oregon, and utah and released in southeastern kentucky. specimens were collected from 170 hunter-killed elk in arkansas during 1998-2006, and 44 elk in kentucky during 2001-2004. significant findings ...201020090032
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