CiteSeerX - Document Details (Isaac Councill, Lee Giles, Pradeep Teregowda): Abstract. The misfolded form of cellular prion protein (PrPC) is the main component of the infectious agent of transmissible spongiform encephalopathies and the validated biomarker for these diseases. The expression of PrPC is highest in the central nervous system and has been found in peripheral tissues. Soluble PrPC has been detected in cerebrospinal fluid, urine, serum, milk, and seminal plasma. In this study, attempts were made to characterize prion protein in urine samples from normal and scrapie-infected sheep. Urine samples from scrapie-infected sheep and age-matched healthy sheep were collected and analyzed by Western blot following concentration. A protease K-sensitive protein band with a molecular weight of approximately 27-30 kDa was visualized after immunoblotting with anti-PrP monoclonal antibodies to a C-terminal part of PrPC, but not after immunoblotting with monoclonal antibodies to an N-terminal epitope of PrPC
Prions, infectious agents causing transmissible spongiform encephalopathy (TSE), are composed primarily of the pathogenic form (PrPSc) of the host-encoded prion protein. Although very low levels of infectivity have been detected in urine from scrapie-infected rodents, no reports of urinary PrPSc have been substantiated. Studies on the dynamics of urinary PrPSc during infection are needed to ensure the safety of urine-derived biopharmaceuticals and to assess the possible horizontal transmission of prion diseases. Using the protein misfolding cyclic amplification technique, a time-course study of urinary excretion and blood levels of PrPSc was performed in Sc237-infected hamsters and a high rate of PrPSc excretion was found during the terminal stage of the disease. Following oral administration, PrPSc was present in all buffy coat samples examined; it was also present in most of the plasma samples obtained from hamsters in the symptomatic stage. PrPSc was excreted in urine for a few days after oral
Groundbreaking research from the University of Alberta has identified the structure of the infectious prion protein, the cause of "mad cow disease" or BSE, chronic wasting disease in deer and elk and Creutzfeldt-Jakob disease in humans, which has long remained a mystery.. The infectious prion protein is a misfolded protein, which makes it very difficult to purify and study. Since it clumps together, standard structural biology techniques cannot be used to study it. Since the protein was first purified in the 1980s researchers have made limited insights into the structure of the protein.. The collaborative study, published in PLOS Pathogens, used electron cryomicroscopy to collect high-resolution electron micrographs. This was the first time this technology has been used on amyloid fibrils of the infectious prion, which are a special form of clumped-together proteins that form fibrils.. "The recent advances to electron cryomicroscopy technology are certainly a breakthrough," says Holger Wille, ...
Prion diseases are fatal neurodegenerative diseases characterized by the accumulation of PrPSc, the infectious and protease-resistant form of the cellular prion protein (PrPC). We generated lentivectors expressing PrPC-specific short hairpin RNAs (shRNAs) that efficiently silenced expression of the prion protein gene (Prnp) in primary neuronal cells. Treatment of scrapie-infected neuronal cells with these lentivectors resulted in an efficient and stable suppression of PrPSc accumulation. After intracranial injection, lentiviral shRNA reduced PrPC expression in transgenic mice carrying multiple copies of Prnp. To test the therapeutic potential of lentiviral shRNA, we used what we believe to be a novel approach in which the clinical situation was mimicked. We generated chimeric mice derived from lentivector-transduced embryonic stem cells. Depending on the degree of chimerism, these animals carried the lentiviral shRNAs in a certain percentage of brain cells and expressed reduced levels of PrPC. ...
Prion diseases are fatal neurodegenerative diseases characterized by the accumulation of PrPSc, the infectious and protease-resistant form of the cellular prion protein (PrPC). We generated lentivectors expressing PrPC-specific short hairpin RNAs (shRNAs) that efficiently silenced expression of the prion protein gene (Prnp) in primary neuronal cells. Treatment of scrapie-infected neuronal cells with these lentivectors resulted in an efficient and stable suppression of PrPSc accumulation. After intracranial injection, lentiviral shRNA reduced PrPC expression in transgenic mice carrying multiple copies of Prnp. To test the therapeutic potential of lentiviral shRNA, we used what we believe to be a novel approach in which the clinical situation was mimicked. We generated chimeric mice derived from lentivector-transduced embryonic stem cells. Depending on the degree of chimerism, these animals carried the lentiviral shRNAs in a certain percentage of brain cells and expressed reduced levels of PrPC. ...
Supplementary MaterialsFigure S1: PrPC in PMCA substrate prepared using brain from different mouse lines. infected individuals the prevalence of the disease in the population remains uncertain. In that context, the risk MK-0822 reversible enzyme inhibition of vCJD blood borne transmission is considered as a serious concern by health authorities. In this study, appropriate conditions and substrates for highly efficient and specific amplification of vCJD/BSE agent using Protein Misfolding Cyclic Amplification (PMCA) were first identified. This showed that whatever the origin (species) of the vCJD/BSE agent, the ovine Q171 PrP substrates provided the very best amplification shows. These outcomes indicate the fact that homology of PrP amino-acid series between your seed as well as the substrate isnt the key determinant from the vCJD agent propagation amplification of vCJD agent by Proteins Misfolding Cyclic Amplification (PMCA). In vCJD pet versions (sheep and primate), the identification was ...
Lesion profiles are considered to be an important tool for the comparison of the various animal and human spongiform encephalopathies and to obtain information upon prion strain variations. Histological and immunohistochemical reactions (PrPsc, GFAP) in 13 brain areas at 4 levels in the brainstem from 135 BSE-positive and 45 BSE-negative cases were retrospectively evaluated. In this retrospective study a lesion profile based on histological features was worked out on the basis of BSE cases originating from Switzerland over a period of ten years. They were confirmed post mortem by histology and immunohistology. Our findings were reviewed in comparison with lesion profiles published in England. No striking differences comparing type and quality of lesions in the relevant areas between the Swiss and the English cases were evident. Moreover, the lesion profiles and the character of the lesions did not differ between animals born before or after the offal feeding ban, which supports the hypothesis ...
Different is the case of vCJD. vCJD has been observed in 12 different countries, but in every registered case the same clinical and pathological characteristics have been found.39 In particular, the PrPSc responsible of the vCJD shows a peculiar WB profile, with the unglycosylated form of the protease-resistant PrPSc of 19 kDa (type 2) and a higher representation of the diglycosilated PrPSc (PrPSc 2B) compared with sCJD.39 Nevertheless, using specific antibodies against type 1 PrPSc, a small amount of PrPSc type 1 with a high percentage of diglycosilated form can be detected in association with PrPSc 2B.98 The 2B type is a useful marker for identifying the replication of BSE prions also in other species, including non-human primates.99 In addition, unlike sporadic and genetic CJD, in vCJD the same biological marker (2B type) has been found in all the analyzed brain areas.100 This strong biochemical and pathological homogeneity is in agreement with the hypothesis of the existence of a unique ...
Different is the case of vCJD. vCJD has been observed in 12 different countries, but in every registered case the same clinical and pathological characteristics have been found.39 In particular, the PrPSc responsible of the vCJD shows a peculiar WB profile, with the unglycosylated form of the protease-resistant PrPSc of 19 kDa (type 2) and a higher representation of the diglycosilated PrPSc (PrPSc 2B) compared with sCJD.39 Nevertheless, using specific antibodies against type 1 PrPSc, a small amount of PrPSc type 1 with a high percentage of diglycosilated form can be detected in association with PrPSc 2B.98 The 2B type is a useful marker for identifying the replication of BSE prions also in other species, including non-human primates.99 In addition, unlike sporadic and genetic CJD, in vCJD the same biological marker (2B type) has been found in all the analyzed brain areas.100 This strong biochemical and pathological homogeneity is in agreement with the hypothesis of the existence of a unique ...
y fresh recMoPrPc 2331 (open squares, black line). Upon seeding with 5% PrP fibrils the fibril content grows logarithmically (grey circles, grey line)17 kDa band that is certainly located in PrPsc that has been PK digested immediately after deglycosylation [15]. Actually, a 17 kDa band can also be seen in recombinant PrPsc generated by way of PMCA and POPG/RNA that has been PK digested [18]. However in these situations, the 17 kDa fragment, from PK digested PrPsc, is frequently as abundant at the 12/ 13 kDa bands. Offered that the ,17 kDa PK resistant fragment seems to become characteristic of infectious prions and provided that the 12/13 kDa fragments are typically located in non-infectious prions, we are now working on modifying our shaking conversion protocol to find out if we are able to boost the proportion from the 17 kDa fragment. This could cause the generation of a self-propagating type equivalent to that described by Deleault et al., [21]. We also tested the PK resistance of fibrils ...
Beringue, V, Vilette, D, Mallinson, G, Archer, F, Kaisar, M, Tayebi, M, Jackson, GS, Clarke, AR, Laude, H, Collinge, J and Hawke, S (2004) PrPSc binding antibodies are potent inhibitors of prion replication in cell lines. ...
Citation: Herrmann, L.M., Cheevers, W.P., Davis, W.C., Knowles, Jr., D.P., ORourke, K.I. 2005. CD21 positive follicular dendritic cells: A possible source of PrPSc in lymph node macrophages of scrapie-infected sheep. American Journal of Pathology. 162(4):1075-1081. Interpretive Summary: Natural sheep scrapie is part of a group of neurodegenerative diseases called transmissible spongiform encephopathies (TSEs) and continues to be spread in flocks in the United States. The presence of prion protein (PrPSc) in germinal centers of lymphoid tissues of scrapie-infected sheep is a marker for scrapie. But, little information exists regarding the specific cell types in lymphoid tissue that accumulate PrPSc. Using dual immunohistochemistry, follicular macrophages cells involved in the immune response of lymph nodes from scrapie-infected sheep were found to accumulate PrPSc. Technical Abstract: Natural sheep scrapie is a prion disease characterized by the accumulation of PrPSc in brain and lymphoid ...
Author Summary The transmissible agent of prion disease consists of a prion protein in its abnormal conformation (PrPSc), which replicates itself according to the template-assisted mechanism. This mechanism postulates that the folding pattern of a newly recruited polypeptide chain accurately reproduces that of a PrPSc. The current study reports that infectious prions and transmissible prion disease can be triggered in wild type animals by amyloid fibrils produced from recombinant prion prtotein, which are structurally different from PrPSc and lacks any detectable PrPSc particles. This work introduces a new hypothesis that transmissible prion diseases can be induced by prion protein structures different from that of authentic PrPSc and suggests that a new mechanism for triggering PrPSc formation different from the classical templating exists. The current work provides important new insight into the mechanisms underlying genesis and evolution of the transmissible states of the prion protein and has
Prion diseases are classically characterized by the accumulation of pathological prion protein (PrPSc) with the protease resistant C-terminal fragment (PrPres) of 27-30 kDa. However, in both humans and animals, prion diseases with atypical biochemical features, characterized by PK-resistant PrP internal fragments (PrPres) cleaved at both the N and C termini, have been described. In this study we performed a detailed comparison of the biochemical features of PrPSc from atypical prion diseases including human Gerstmann-Sträussler-Scheinker disease (GSS) and variably protease-sensitive prionopathy (VPSPr) and in small ruminant Nor98 or atypical scrapie. The kinetics of PrPres production and its cleavage sites after PK digestion were analyzed, along with the PrPSc conformational stability, using a new method able to characterize both protease-resistant and protease-sensitive PrPSc components. All these PrPSc types shared common and distinctive biochemical features compared to PrPSc from classical prion
Sunday, February 2, 2014 The Presence of Disease-Associated Prion Protein in Skeletal Muscle of Cattle Infected with Classical Bovine Spongiform Encephalopathy NOTE Pathology http://bovineprp.blogspot.com/2014/02/the-presence-of-disease-associated.html kind regards,
As for the variance between the presence of PrPsc deposits and presentation of clinical signs found in some mice, PrPsc concentration used for inoculation could affect the results but also other explanations arise on this matter [42]. The possibility of a transmission of the disease without neurological signs [43] or a possible non-exclusive relationship between PrPsc and infectivity [44-46] and neurodegeneration [47], among them. Besides, the demonstration of the existence of animals as persistent carriers [48] or with a subclinical state of the disease [47], already described in mice with high titers of infection but no symptoms [49], should be borne in mind. This same lack of correlation between PrPsc and infectivity could be reflecting in the animals with symptoms but no PrPsc deposits [50], considering in this case that the disease might be transmitted without detectable PrPsc [44], even with high titers [51]. Further studies with non-diagnostic aims but for identification of astrocytes ...
During pathogenesis of transmissible spongiform encephalopathies (TSEs) an abnormal form (PrPSc) of the host encoded prion protein (PrPC) accumulates in insoluble fibrils and plaques. The two forms of PrP appear to have identical covalent structures, but differ in secondary and tertiary structure. Both PrPC and PrPSc have glycosylphospatidylinositol (GPI) anchors through which the protein is tethered to cell membranes. Membrane attachment has been suggested to play a role in the conversion of PrPC to PrPSc, but the majority of in vitro studies of the function, structure, folding and stability of PrP use recombinant protein lacking the GPI anchor. In order to study the effects of membranes on the structure of PrP, we synthesized a GPI anchor mimetic (GPIm), which we have covalently coupled to a genetically engineered cysteine residue at the C-terminus of recombinant PrP. The lipid anchor places the protein at the same distance from the membrane as does the naturally occurring GPI anchor. We ...
We now show that a protease-resistant PrP isoform can also be detected in the urine of hamsters, cattle, and humans suffering from transmissible spongiform encephalopathies. Most important, this PrP isoform (UPrPSc) was also found in the urine of hamsters inoculated with prions long before the appearance of clinical signs. Interestingly, intracerebrally inoculation of hamsters with UPrPSc did not cause clinical signs of prion disease even after 270 days, suggesting it differs in its pathogenic properties from brain PrPSc. We propose that the detection of UPrPSc can be used to diagnose humans and animals incubating prion diseases, as well as to increase our understanding on the metabolism of PrPSc in vivo ...
The uptake of proteins from soil into plants has been documented for many years and we have been investigating the uptake of prions into plants in vitro. Using laser scanning confocal microscopy, we observed root uptake of fluorescently-tagged, abnormal prion protein in the model plant thale cress or mouse-eared cress (_Arabidopsis thaliana_), as well as the crop plants alfalfa (_Medicago sativa_), barley (_Hordeum vulgare_), and tomato _(Solanum lycopersicum_). Using serial protein misfolding cyclic amplification, a sensitive biochemical prion detection method, we have found evidence of prions in aerial tissues from these species, as well as maize (_Zea mays_). Both stems and leaves of _A. thaliana_ grown in culture media containing prions are infectious when injected into mice and oral bioassays are underway for _A. thaliana_ and other plants. Our results suggest that prions are taken up by plants and that contaminated plants may represent a previously unrecognized risk of human, domestic ...
Different is the case of vCJD. vCJD has been observed in 12 different countries, but in every registered case the same clinical and pathological characteristics have been found.39 In particular, the PrPSc responsible of the vCJD shows a peculiar WB profile, with the unglycosylated form of the protease-resistant PrPSc of 19 kDa (type 2) and a higher representation of the diglycosilated PrPSc (PrPSc 2B) compared with sCJD.39 Nevertheless, using specific antibodies against type 1 PrPSc, a small amount of PrPSc type 1 with a high percentage of diglycosilated form can be detected in association with PrPSc 2B.98 The 2B type is a useful marker for identifying the replication of BSE prions also in other species, including non-human primates.99 In addition, unlike sporadic and genetic CJD, in vCJD the same biological marker (2B type) has been found in all the analyzed brain areas.100 This strong biochemical and pathological homogeneity is in agreement with the hypothesis of the existence of a unique ...
Different is the case of vCJD. vCJD has been observed in 12 different countries, but in every registered case the same clinical and pathological characteristics have been found.39 In particular, the PrPSc responsible of the vCJD shows a peculiar WB profile, with the unglycosylated form of the protease-resistant PrPSc of 19 kDa (type 2) and a higher representation of the diglycosilated PrPSc (PrPSc 2B) compared with sCJD.39 Nevertheless, using specific antibodies against type 1 PrPSc, a small amount of PrPSc type 1 with a high percentage of diglycosilated form can be detected in association with PrPSc 2B.98 The 2B type is a useful marker for identifying the replication of BSE prions also in other species, including non-human primates.99 In addition, unlike sporadic and genetic CJD, in vCJD the same biological marker (2B type) has been found in all the analyzed brain areas.100 This strong biochemical and pathological homogeneity is in agreement with the hypothesis of the existence of a unique ...
PrPSc distribution and content in brain of bovine spongiform encephalopathy (BSE)-infected rhesus macaques. A) Paraffin-embedded tissue blot of striatum and c
subtypes. in both BSE-affected and unaffected countries in the. light of these ndings. If human BSE prion infection can. result in propagation of type 2 PrPSc, it would be expected. that such cases would be indistinguishable on clinical,. pathological and molecular criteria from classical CJD. It. may also be expected that such prions would behave. biologically like those isolated from humans with sporadic. CJD with type 2 PrPSc. The transmission properties of. prions associated with type 2 PrPSc from BSE-inoculated. 129MM Tg35 mice are being investigated by serial. passage.. We consider these data inconsistent with contamination. of some of the 129MM Tg35 mice with sporadic CJD. prions. These transmission studies were performed according. to rigorous biosafety protocols for preparation of. inocula and both the inoculation and care of mice, which. are all uniquely identi ed by sub-cutaneous transponders.. However, crucially, the same BSE inocula have been used. on 129VV Tg152 and 129MM Tg45 ...
An assay comprises contacting cells containing a conformationally altered protein with test compound and determining if the altered protein is cleared. The cells may be scrapie-infected neuroblastoma cells. Another assay comprises contacting organ or tissue homogenate (at pH 5.0 or less) with test compound to determine if altered protein in the homogenate is cleared. The homogenate may be brain homogenate from a transgenic mouse infected with human prions. Compounds which are found to clear the altered protein are useful in preventing, arresting and/or reversing (i.e. treating) a disease associated with the conformationally altered protein.
Prion diseases are infectious neurodegenerative disorders that affect humans and other mammals and are inevitably fatal. The infectious agent in prion disease (PrPSc) is an abnormal isoform of an endogenous host protein ...
Well, the zombie-biting thing has taken off in earnest. I find myself missing my life as a medicine resident. Its weird, actually, sort of a cross between working in the MICU and going to the dentist. I mean, Ive been present at more crazy codes than probably the average IM physician sees in their entire…
Prion Trafficking Model.Immune cells encounter prions in the PC and MedLN. Mφ, DCs, monocytes, neutrophils, B and T cells have all been shown to associate with
understand natures ground rules. Thats exactly what prions have done to scientists understanding of the ground rules for infectiousdiseases. Prions
bovine spongiform encephalopathy - Find news stories, facts, pictures and video about bovine spongiform encephalopathy - Page 1 | Newser
The amyloidotic form of bovine spongiform encephalopathy (BSE) termed BASE is caused by a prion strain whose biological properties differ from those of typical BSE, resulting in a clinically and pathologically distinct phenotype. Whether peripheral tissues of BASE-affected cattle contain infectivity is unknown. This is a critical issue since the BASE prion is readily transmissible to a variety of hosts including primates, suggesting that humans may be susceptible. We carried out bioassays in transgenic mice overexpressing bovine PrP (Tgbov XV) and found infectivity in a variety of skeletal muscles from cattle with natural and experimental BASE. Noteworthy, all BASE muscles used for inoculation transmitted disease, although the attack rate differed between experimental and natural cases (~70% versus ~10%, respectively). This difference was likely related to different prion titers, possibly due to different stages of disease in the two conditions, i.e. terminal stage in experimental BASE and ...
Prion diseases are fatal and incurable neurodegenerative diseases of humans and animals. Despite years of research, no therapeutic agents have been developed that can effectively manage or reverse disease progression. Recently it has been identified that recombinant prion proteins (rPrP) expressed in bacteria can act as inhibitors of prion replication within the in vitro prion replication system Protein Misfolding Cyclic Amplification (PMCA). Here, within PMCA reactions amplifying a range of ruminant prions including distinct Prnp genotypes/host species and distinct prion strains, recombinant ovine VRQ PrP displayed consistent inhibition of prion replication and produced IC50 values of 122 and 171 nM for ovine scrapie and bovine BSE replication, respectively. These findings illustrate the therapeutic potential of rPrPs with distinct TSE diseases.. ...
Bovine Spongiform Encephalopathy is a progressive, fatal disease of the nervous system of cattle. It is what is known as a transmissible spongiform encephalopathy (TSE).
IMPORTANCE: The diagnosis of autoimmune and neurodegenerative conditions can be unclear. Treatments such as removing the associated tumor, if present, and immunosuppression can halt or often reverse the progression of autoimmune conditions, but there is no curative treatment for neurodegenerative conditions. The presence of autoantibodies can sometimes be misleading. This report illustrates potential difficulties in differentiating autoimmune encephalopathies from sporadic Creutzfeldt-Jakob disease. OBSERVATIONS: In a clinical follow-up of an older man with rapidly evolving encephalopathy at a neuroscience center, unsuccessful treatment with immunosuppression based on the incorrect presumptive diagnosis of Morvan syndrome was followed by the correct histological diagnosis of sporadic Creutzfeldt-Jakob disease. CONCLUSIONS AND RELEVANCE: Autoimmune encephalopathies raise important treatment options and potential for recovery. However, since neuronal antibodies may be positive in prion disease,
Sporadic Creutzfeldt-Jakob disease (sCJD) is the commonest form of human prion diseases, accounting for about 85% of all cases. Current criteria for intra vitam diagnosis include a distinct phenotype, periodic sharp and slow-wave complexes at electroencephalography (EEG), and a positive 14-3-3-protein assay in the cerebrospinal fluid (CSF). In sCJD, the disease phenotype may vary, depending upon the genotype at codon 129 of the prion protein gene (PRNP), a site of a common methionine/valine polymorphism, and two distinct conformers of the pathological prion protein. Based on the combination of these molecular determinants, six different sCJD subtypes are recognized, each with distinctive clinical and pathologic phenotypes. We analyzed CSF samples from 127 subjects with definite sCJD to assess the diagnostic value of 14-3-3 protein, total tau protein, phosphorylated181 tau, and amyloid beta (Aβ) peptide 1-42, either alone or in combination. While the 14-3-3 assay and tau protein levels were the most
Introduction. Scrapie is a fatal, infectious neurodegenerative disease that affects sheep and goats. The disease results from infection with pathogenic agents known as "prions" which change the normal prion protein (PrPC) to the improperly folded, disease-associated form (PrPSc). The abnormal PrPSc is resistant to the protein turnover process and forms deposits in the central nervous system and some peripheral tissues that lead to progressive neurodegeneration. Goat scrapie is similar to a group of prion diseases that includes Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy (BSE) in cattle, sheep scrapie and chronic wasting disease in cervids. The disease impacts animal health and welfare, animal movement and trade. Natural mutations (also called variants or alleles) in the prion protein gene (PRNP) of sheep and goats have been identified which confer susceptibility or resistance to scrapie. In the goat, S146 and K222 variants have been confirmed, experimentally and in the ...
Prions are misfolded proteins that propagate by corrupting properly folded versions of themselves. The prion protein PrP (known as PrPSC in its misfolded form) causes deadly transmissible spongiform encephalopathies, including bovine spongiform encephalopathy (BSE) in cows, scrapie in sheep, and Creutzfeldt-Jakob disease (CJD) in humans. PrPSC molecules attach to and convert normal PrP proteins into the toxic form, accelerating the formation of PrPSC aggregates and fibrils. When these aggregates break apart, each fragment becomes a seed that can corrupt new PrP molecules. This break-up process is what senior author Adriano Aguzzi of the University of Zurich aimed to target. "That is the most important moment in the life of a prion fibril, just like mitosis is for a cancer cell," Aguzzi told Alzforum. As his weapon of choice, Aguzzi chose a group of compounds already known for their amyloid-smothering properties. Luminescent conjugated polythiophenes (LCPs) are fluorescent molecules that ...
Bovine spongiform encephalopathy (BSE) is a progressive fatal neurodegenerative disease of cattle, first recognised in 1986 in the UK.1 An early study indicated that BSE was consistent with exposure of cattle to a scrapie-like agent via cattle feedstuffs containing ruminant-derived protein.2 Transmission mainly occurs during calfhood, with the time of infection ranging between 0 and 18 months of age and a typical incubation period of five years.3 4 In dairy cattle, the age-dependent risk of infection is highest during the first six months of life.5 Since 1987, 28 countries in Europe, Asia and North America have reported cases of BSE. The International Organisation for Animal Health (OIE) assigns a BSE disease status to member countries, and in 2016 categorised 46 countries as having a negligible BSE risk and 8 as having a controlled BSE risk.6. In Ireland, the first case of BSE was diagnosed in 1989.7 By December 31, 2016, 1660 cases of BSE had been confirmed in Ireland, including four atypical ...
BACKGROUND: With respect to sporadic Creutzfeldt-Jakob disease (sCJD), six molecular subtypes (MM1, MM2, MV1, MV2, VV1, and VV2) have been described, which vary with respect to age at disease onset, disease duration, early symptoms, and neuropathology. MRI signal alterations were reported to correlate with distinct Creutzfeldt-Jakob disease (CJD) subtypes. This multicenter, international study aimed to describe the brain MRI findings associated with each of the sCJD molecular subtypes. METHODS: Pathologically confirmed sCJD cases with codon 129 genotype (MM, MV, and VV), PrP(Sc) type, and fluid-attenuated inversion recovery (FLAIR) or diffusion-weighted imaging (DWI) were collected in seven countries. All MRI scans were assessed for signal changes according to a standard protocol encompassing seven cortical regions, basal ganglia, thalamus, and cerebellum. RESULTS: MRI scans were evaluated in 211 CJD patients (98 MM1, 23 MM2, 19 MV1, 30 MV2, 9 VV1, and 32 VV2). Basal ganglia hyperintensities ...
Following intracerebral or peripheral inoculation of mice with scrapie prions, infectivity accumulates first in the spleen and only later in the brain. In the spleen of scrapie-infected mice, prions were found in association with T and B lymphocytes and to a somewhat lesser degree with the stroma, which contains the follicular dendritic cells (FDCs) but not with non-B, non-T cells; strikingly, no infectivity was found in lymphocytes from blood of the same mice. Transgenic PrP knockout mice expressing PrP restricted to either B or T lymphocytes show no prion replication in the lymphoreticular system. Therefore, splenic lymphocytes either acquire prions from another source or replicate them in dependency on other PrP-expressing cells. The essential role of FDCs in prion replication in spleen was shown by treating mice with soluble lymphotoxin-β receptor, which led to disappearance of mature FDCs from the spleen and concomitantly abolished splenic prion accumulation and retarded neuroinvasion ...
Article that explores the causes of Mad Cow disease, what happens when science faces an unknown pathogen, and the implications for public health. ...
Bovine Spongiform Encephalopathy (BSE) in livestock has gained much of the worlds attention with its identification in Western and Eastern Europe, Israel, Japan and North America. BSE and other TSEs are considered serious animal health concerns. BSE has also become a public health issue as a result of the connection that has been made between BSE in cattle and variant Creutzfeld-Jakob Disease (vCJD) in humans. Public confidence in the beef supply is potentially affected each time another case of BSE in cattle is identified. Many questions remain that can only be resolved through further research, on-going evaluation and assessing the risks involved. Maintaining an adequate food safety system while additional knowledge is obtained remains a primary objective.. NASDA supports a policy which assures that the U. S. actions are supported by the best available science-a policy that embraces research as a method to advance current knowledge and understanding, is based on risk analysis, is able to ...
Heart rates of healthy cows and cows suspected of having bovine spongiform encephalopathy were measured by auscultation and by a portable cardiac monitor. Bradycardia was demonstrated in suspect cases which were confirmed histopathologically. Disturbances in cardiac rhythm were also evident in some cases. Healthy cows deprived of food exhibited bradycardia. The administration of pharmacological doses of atropine indicated that bradycardia in BSE was mediated by increased vagal influence, suggesting that the cardioinhibitory reflexes in the caudal brainstem were functionally altered by the disease.. ...
Learn about the veterinary topic of Overview of Bovine Spongiform Encephalopathy. Find specific details on this topic and related topics from the Merck Vet Manual.
Creutzfeldt-Jakob disease (CJD) is the best known of the human prion diseases. Creutzfeldt-Jakob Disease is caused by an infectious prion protein...
Friday, November 23, 2012 sporadic Creutzfeldt-Jakob Disease update As at 5th November 2012 UK, USA, AND CANADA http://creutzfeldt-jakob-disease.blogspot.com/2012/11/sporadic-creutzfeldt-jakob-disease.html kind regards, terry
Transmissible spongiform encephalophies (TSEs) affect humans and domesticated animals such as sheep (scrapie) and cattle (BSE). TSEs can be genetic (inherited mutations in the prion gene), infectious (dietary or accidental exposure to prions as in iatrogenic cases or consumption of prion-infected food) or sporadic v.g. sporadic Cruetzfeld-Jacob Disease (CJD). Prions have properties that are maintained upon transmission from one host to the next, allowing different strains to be distinguished. Strains cause specific phenotypes, such as different symptoms, incubation time, and tissue distribution of PrPSc. Differentiation of strains is of paramount importance: as an example, the strain of sheep PrPSc that causes scrapie is not transmissible to humans, while the strain that causes ovine BSE presumably is. By SDS-PAGE analysis, PrPSc from different strains maintain specific ratios of non-, mono-, and di-glycosylated glycoforms and different size of the proteinase K (PK) resistent core. However, ...
in Journal of Clinical Microbiology (2005), 43(2), 862-9. A retrospective epidemiological study (n = 7,875) of neurologically expressed disorders (NED) in ruminants before the onset of the bovine spongiform encephalopathy epidemic (years studied, 1980 to 1997 ... [more ▼]. A retrospective epidemiological study (n = 7,875) of neurologically expressed disorders (NED) in ruminants before the onset of the bovine spongiform encephalopathy epidemic (years studied, 1980 to 1997) was carried out in Belgium. The archives of all veterinary laboratories and rabies and transmissible spongiform encephalopathy (TSE) epidemiosurveillance networks were consulted. For all species, a significantly higher number of NED with virological causes (rabies) was reported south of the Sambre-Meuse Valley. During the period 1992 to 1997, for which the data were complete, (i) the predicted annual incidence of NED varied significantly as a function of species and area (higher numbers in areas where rabies was present) but ...
Team:Valencia/head}} ,div id="HomeCenter"> ,div id="Titulos"> Regulating Mars temperature ,br> ,br> using a prion switch ,/div> ,br> ==Prions== In 1982 Stanley B. Prusiner created the term "prion" (or proteinacius infectious particle) to name the exclusively proteic infectious agent responsible of the transmissible spongiform encephalopathies (TSEs), a group of mammalian neurodegenerative disorders. According to the widely supported "protein-only" model, the prion mechanism of transmissibility arise from the ability of the prion form of the protein to promote the conformational change of the normal cellular form to the infectious prion forms (Prusiner, 1998). The infectious forms are mis-folded proteins that induce by polymerization the formation of an amyloid fold constituted by tightly packed beta sheets. These aggregates are insoluble fibrils that display resistance to proteolytic digestion and have affinity for aromatic dyes. ===Fungal prions=== In 1994 Reed Wickner proposed the prion nature ...
Maddening cow disease might be a better name, so frustrating is the causative agent with its apparent ability to move among species. Not to mention the public- health dilemmas facing authorities in Great Britain, where a cattle disease called bovine spongiform encephalopathy, or mad cow disease, may have infected humans.
We describe analyses of two data sets relating to maternal risk enhancement: data from a seven- year cohort study (Wilesmith et al. 1997, Donnelly et al. 1997a) of the offspring of BSE- affected dams and their matched controls and identification data on the dams of BSE cases born after the introduction of the ruminant feed ban in July 1988 (Donnelly et al. 1997b). Our aim is to characterize the maternal transmission rate (as a function of maternal incubation stage where possible) and genetically variable susceptibility using a range of genetic models including that suggested by the one study to date to find any differences in the PrP gene between BSE- affected and unaffected cows (Neibergs et al. 1994). Results indicate significant heterogeneity in susceptibility to feed infection. ...