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1.
The use of non-prion biomarkers for the diagnosis of Transmissible Spongiform Encephalopathies in the live animal 总被引：1，自引：0，他引：1
Scrapie and bovine spongiform encephalopathy (BSE) are major global concerns and the emergence of variant Creutzfeldt-Jakob disease (vCJD) has caused turmoil for blood transfusion services and hospitals worldwide. Recent reports of iatrogenic CJD (iCJD) cases following blood transfusions from Transmissible Spongiform Encephalopathies (TSE)-infected donors have fuelled this concern. Major diagnostic tests for BSE and scrapie are conducted post-mortem from animals in late stages of the disease. Although the lymphoreticular system is involved in the earlier pathogenesis of some forms of sheep scrapie and vCJD, which presents great opportunity for diagnostic development, other TSE diseases (some strains of scrapie, sporadic CJD (sCJD) and bovine BSE) do not present such a diagnostic opportunity. Thus, there is an urgent need for pre-mortem tests that differentiate between healthy and diseased individuals at early stages of illness, in accessible samples such as blood and urine using less invasive procedures. This review reports on the current state of progress in the development and use of prion and non-prion biomarkers in the diagnosis of TSE diseases. Some of these efforts have concentrated on improving the sensitivity of PrPSc detection to allow in vivo diagnosis at low abundances of PrPSc whilst others have sought to identify non-prion protein biomarkers of TSE disease, many of which are still at early stages of development. In this review we comment upon the limitations of prion based tests and review current research on the development of tests for TSE that rely on non-prion disease markers in body fluids that may allow preclinical disease diagnosis. 相似文献
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Transmissible Spongiform Encephalopathies are a group of chronic, always fatal diseases affecting the central nervous system of humans and animals. They occur in all species and are probably caused by agents called prions. In this minireview, a first part provides an overview of the various disease forms, a second part is devoted to the molecular biology of transmissible spongiform encephalopathies, and a last part deals with the specific problems of the Bovine Spongiform Encephalopathy. 相似文献
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Ganter M 《DTW. Deutsche tier?rztliche Wochenschrift》2002,109(8):342-344
The first case of Bovine Spongiform Encephalopathy (BSE) in Germany induced a profound irritation not only of the consumers but also of the farmers and the veterinarians in Germany. The following BSE-crisis accelerated the structural changes in Beef and Dairy industries. The analysis of the detected BSE-cases of the last years in Germany and Switzerland shows that the sensitivity of BSE-tests is much higher in clinically preselected BSE-suspected cases compared to BSE-tests in normal slaughter cattle. Therefore it is necessary for an effective battle against BSE that clinical cases of CNS-diseases and disturbances of the locomotion especially in cows around partus should be clarified etiologically. If intra vitam the etiology of the disease can not be diagnosed by clinical and laboratory investigation of blood, urine and liquor samples and the therapy induces no improvement, the case has to be notified at the local veterinary officer. In the same way cases of Scrapie in sheep have to be handled. In sheep genotyping gives the opportunity to select for Scrapie resistance. In contrary to cattle with BSE Scrapie can be diagnosed intra vitam already before clinical symptoms occur by immunohistochemical investigations for Scrapie prion protein of tonsillar biopsies. These two diagnostic tools open new ways for fighting against Transmissible Spongiform Encephalopathies in sheep. 相似文献
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运用风险分析理论,以科学研究为基础,同时遵循客观实际,分别从危害确认、接触评估、危害评定及风险评定几方面对含有牛源性成份的化妆品能否传播人类变异型克雅氏症的风险进行了科学评估。结果认为,由于化妆品直接与皮肤接触,而朊蛋白可以被身体许多部位吸收,所以含有牛源性蛋白的化妆品是一个潜在的暴露源,使用含牛源性蛋白的化妆品存在感染人类变异型克雅氏症的风险。然而,由于风险评估中存在许多重要的变数,因而存在许多不确定性,关于发生该病的风险所做的任何定量评估都不是很准确的,防止疯牛病病原通过化妆品传播的最可靠的做法就是化妆品生产中禁止使用高风险性牛源蛋白。 相似文献
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Transmissible spongiform encephalopathies affect a number of mammalian species. The most common spongiform encephalopathies are scrapie in sheep and Bovine Spongiform Encephalopathy (BSE) in cattle. Feline Spongiform Encephalopathy (FSE) is a related disorder in domestic cats. Because of the link between BSE and FSE, cats are put on a par with cattle, in terms of politics and regulations. In the Netherlands, when a case of BSE is found on a farm, not only the ruminants, but also the cats are taken away for post-mortem examination. So far, the cats examined have always been negative for FSE. There are no scientific reasons for destroying the cats on farms where BSE has been found. 相似文献
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构建了携带绵羊朊蛋白基因（PRNP）的重组真核转染质粒,通过脂质体转染试剂将其转染至神经胶质瘤细胞（C6）,以期为进一步研究绵羊朊蛋白的生理功能和从细胞水平研究朊蛋白疾病的发病机制奠定基础。采用PCR扩增目的基因序列,纯化后将其克隆到带有增强型绿色荧光蛋白（EGFP）报告基因的真核表达载体pEGFP-N1中,对重组质粒pEGFP-PRNP做酶切鉴定。而后采用阳离子脂质体转染法将重组质粒转染到C6细胞,荧光显微镜观察。经鉴定,绵羊PRNP基因已克隆到真核表达载体pEGFP-N1中,成功地构建了重组pEGFP-PRNP质粒,并可稳定地在C6细胞中表达。本研究为外源朊蛋白在细胞中表达提供了平台,为进一步在细胞水平研究朊病毒疾病奠定了基础。 相似文献
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David J Everest Susan Waterhouse Tina Kelly Elena Velo-Rego Maurice J Sauer 《Journal of veterinary diagnostic investigation》2007,19(5):552-557
Management of prion diseases in livestock would benefit greatly from availability of a validated blood test. A promising immunocapillary electrophoresis technique (also known as capillary electrophoresis fluoroimmunoassay) to detect abnormal prion protein in blood from live sheep is evaluated here. Capillary electrophoresis fluoroimmunoassay was applied to analysis of extracted blood from scrapie-exposed sheep (n = 87; 347 samples) at various stages of incubation, and to control sheep (n = 194; 489 samples). Overall, test values for the control and test populations were not significantly different, and a similar proportion of control (7%) and test (10%) sheep were classified as positive. Over 2-3 month intervals from birth until clinical disease, test specificity and sensitivity ranged from 66.7% to 100% and 0% to 66.7%, respectively, indicating poor diagnostic performance at all stages of pathogenesis. In routine application, in its present form, the capillary electrophoresis fluoroimmunoassay procedure proved to be insufficiently robust for use as a blood test for scrapie diagnosis. 相似文献
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Yilmaz H Turan N Gurel A Gulcubuk A Sonmez K Bozkurt HH Morgan KL 《Polish journal of veterinary sciences》2007,10(4):271-274
The aim of this study was to investigate Bovine Spongiform Encephalopathy (BSE) in Turkish cattle in the Marmara region which borders the European Union (EU). For this, cattle brought to abattoirs in Istanbul were analysed. The high risk group were selected and therefore 384 cattle above 2 years old were included in the study. They were primarily examined for the presence of any clinical signs of nervous system and also other clinical disorders. The whole brains were taken and analysed for the presence of vacuolar degeneration and prion protein by PLATELIA BSE test kit. Only 5 cattle were found to be nervous and showed aggressive behaviour. There were no cattle showing incoordination or other neurological disorders. Cysts were observed in 3 brains. Histopathologically, no vacuolar degeneration indicative of BSE was found in any cattle examined. However, in 8 brains, few vacuoles were observed in neurons in sections taken from the brain, cerebellum, medulla oblongata and medulla spinalis. Slight mononuclear cell infiltration in 9 brain, intensed mononuclear cell infiltration in 1 brain, haemorrhages in 5 brains and gliosis in 11 brains were also found. No infective prion was detected by ELISA in samples taken from 384 cattle brain. 相似文献
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Prion diseases of animal and man belong to neurological diseases with amyloidal deposition of the respective proteins. As to prion disease, the cellular prionprotein is in its abnormal isoform(s) an essential component of prionprotein aggregates found in affected tissue. In contrast to all neurodegenerative diseases like Morbus Alzheimer or Huntington's disease, prion diseases are transmissible. Therefore, prion diseases were designated Transmissible Spongiform Encephalopathies (TSE). The diseases are well known since decades. Scrapie was first described around 1750, a BSE case was reported in the 1850, most likely a misdiagnosis, and in 1920/1930 the human Creutzfeldt-Jakob disease (CJD) had been described. Transmission of CJD i.e. Kuru had been suspected in the early 1950s and erronously classified as slow virus disease. The CJD transmission posed a problem to humans when transplants from CJD cases were used for treatment. Fortunately, these iatrogenic transmissions remained limited. But with the advent of BSE and appearance of variant CJD cases in the UK and some places in Europe scientists suspected that transmission from cattle to man could have happened. From animal models we know of successful transmission via several routes. Species barriers do not completely prevent transmission. Rather transmission barriers might exist controlling individual susceptibility against prions. Modes of transmission, susceptibility for transmission, identification of receptor molecules as well as molecular mechanisms of the transmission process are intensely investigated. Current knowledge let us to assume that inapparent stages of prion infection pretend a (not existing) species barrier. This inapparent infection preceeds overt disease and, thus, most re-search focuses on the development of highly sensitive assay systems for detection of minute amounts of pathological prionprotein in suspected cases. Inapparence also should warn us to underestimate BSE or human vCJD cases; at present, 124 in Europe and one probable case in Hongkong (7 March 2002). Whether BSE had spread to other parts of the world by animal nutrition components or meat can neither be excluded nor confirmed at this time. New data on transmission and consequences of BSE for the human population are summarized in this review. 相似文献
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Construction of a microarray specific to the chicken immune system: profiling gene expression in B cells after lipopolysaccharide stimulation 
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下载免费PDF全文 Aimie J. Sarson Leah R. Read Hamid R. Haghighi Melissa D. Lambourne Jennifer T. Brisbin Huaijun Zhou Shayan Sharif 《Canadian journal of veterinary research》2007,71(2):108-118
The objective of this study was to profile gene expression in cells of the chicken immune system. A low-density immune-specific microarray was constructed that contained genes with known functions in the chicken immune system, in addition to chicken-expressed sequence tags (ESTs) homologous with mammalian immune system genes, which were systematically characterized by bioinformatic analyses. Genes and ESTs that met the annotation criteria were amplified and placed on a microarray. The microarray contained 84 immune system gene elements. As a means of calibration, the microarray was then used to examine gene expression in chicken B cells after lipopolysaccharide stimulation. Differential gene expression was observed at 6, 12, and 24 h but not at 48 h after stimulation. The results were validated by semiquantitative polymerase chain reaction. The microarray showed a high degree of reproducibility, as demonstrated by intra- and interassay correlation coefficients of 0.97 and 0.95, respectively. Thus, the low-density microarray developed in this study may be used as a tool for monitoring gene expression in the chicken immune system. 相似文献
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朊病毒研究进展 总被引：2，自引：0，他引：2
朊病毒是一种不含核酸的蛋白浸染子,主要引起人和动物的中枢神经疾病。目前,由其引起的朊病毒病在世界多国已有发生,危害严重,经济损失巨大,并对人类的健康构成很大威胁。该病毒蛋白是一种膜糖蛋白,至少有两种基本形式,即PrPc与PrPsc,PrPsc对紫外线及消毒剂有很强的抵抗力;朊蛋白基因是单拷贝基因,高度保守,但在物种间可能存在易感性相关基因。病毒的复制呈指数增长过程,需朊病毒结合因子参与。病毒的致病性在于正常的朊病毒蛋白PrPc转变为PrPsc,PrPsc是发病的直接原因。另外,对其检测和防治目前也有了新的方法及措施。文章就朊病毒概念、蛋白、基因、复制、致病机理及检测与防治作了综述。 相似文献
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Otsuka Y Ito D Katsuoka K Arashiki N Komatsu T Inaba M 《The Japanese journal of veterinary research》2008,56(2):75-84
Alpha-Hemoglobin stabilizing protein (AHSP) functions as the erythroid-specific molecular chaperon for alpha-globin. AHSP gene expression has been reported to be downregulated in hematopoietic tissues of animals suffering from prion diseases though the mechanism remains to be clarified. Herein, we demonstrate that MELhipod8 cells, a subclone of murine erythroleukemia (MEL) cells, have prion protein (PrPc) on the cell surface and have highly inducible expression of the AHSP and alpha- and beta-globin genes, resembling the expression pattern of the PrP and AHSP genes in bipotential erythroid- and megakaryocyte-lineage cells followed by erythroid differentiation in normal erythropoiesis. Moreover, MELhipod8 cells exhibit greater effective erythroid differentiation with a population of hemoglobinized normoblast-like cells than that observed for the parental MEL cells. These findings suggest that MELhipod8 cells could provide a mechanism for downregulation of the AHSP gene in prion diseases. 相似文献
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C. Darcel 《Veterinary research communications》1995,19(3):231-252
The transmissible spongiform encephalopathies of domesticated animals, scrapie in-sheep and bovine spongiform encephalopathy (BSE), and transmissible mink encephalopathy are more than a scientific curiosity; under certain circumstances their impact on commercial activities can be calamitous. Knowledge of their causation and pathogenesis is still rudimentary, but many consider than an unconventional agent, the prion (a brain protein, PrP), that is not associated with nucleic acid is involved in both. Others believe that conventional viruses, which replicate by virtue of their nucleic acid-defined genes, are involved in the causation and progression of the encephalopathies but that technical problems have prevented their identification. Others postulate even more exotic causative agents. While this paper will particularly address the possibility of a viral aetiology for these diseases, it is also emphasized that our knowledge of the state of the immune system in animals with encephalopathy needs broadening. There are remarkable gaps in our knowledge of the histopathology of these diseases, particularly the nature of the characteristic vacuoles. Much further work is needed on the biochemical changes in the brain and the serum, particularly of the latter as it could lead to an additional means of recognizing clinical cases without waiting for the animal to die with subsequent examination of the brain for characteristic lesions and the presence of protease-K-resistant PrP.Abbreviations AI
artificial insemination
- BSE
bovine spongiform encephalopathy
- CJD
Creutzfeldt-Jakob disease
- ET
embryo transfer
- GSSD
Gerstmann-Sträussler-Scheinker disease
- HDV
hepatitis delta virus
- MCF
mink cell focus
- PK
proteinase K
- PrP
prion protein
- PrPSc
scrapie prion protein
- PrP-C
the proteinase-K sensitive homologue in normal brain
- SAF
scrapie-associated fibrils
- TME
transmissible mink encephalopathy 相似文献
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Vella LJ Greenwood DL Cappai R Scheerlinck JP Hill AF 《Veterinary immunology and immunopathology》2008,124(3-4):385-393
Prion diseases are transmissible neurodegenerative disorders affecting humans and a wide variety of animal species including sheep and cattle. The transmissible agent, the prion, is an abnormally folded form (PrP(Sc)) of the host encoded cellular prion protein (PrP(C)). Distribution of the prion protein in the fluids of species susceptible to these diseases is of importance to human health and the iatrogenic spread of prion disease. Aside from blood which is confirmed to be a source of prion infectivity, it is currently unclear which other body fluids harbor a significant transmission risk. In the current study we examined two ovine fluids; pseudo-afferent lymph and cerebral spinal fluid (CSF), for the presence of exosomes and concurrent enrichment of the normal, cellular form of the prion protein (PrP(C)). Here we demonstrate the existence of exosomes in both pseudo-afferent lymph and CSF isolated from sheep. In the CSF derived exosomes we were able to show an enrichment of PrP(C) over unfractionated CSF. This experimental approach suggests that CSF derived exosomes could be used as a novel means of detecting abnormal forms of the prion protein and provide an in vivo link between these vesicles and prion disease pathogenesis. 相似文献
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Schreuder BE 《Tijdschrift voor diergeneeskunde》1999,124(6):182-184
After a discussion of the different hypotheses about the causative agent of prion diseases, various aspects of the two most important animal prion diseases, i.e. BSE and scrapie are described. This thesis focuses on the search for a preclinical diagnosis. A major breakthrough was the discovery of a new technique for detecting the disease-associated protein in tonsillar biopsies from scrapie-infected sheep long before clinical signs appeared. Another essential part of the studies described in this thesis concerned a risk analysis for BSE in a country like the Netherlands. Major risk factors were assessed, including an assessment of the efficacy of Dutch rendering procedures in the inactivation of the agents of scrapie and BSE. 相似文献
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小胶质细胞活化是朊病的病理学特征之一。朊蛋白多肽PrP106—126具神经毒性,是研究异常腕蛋白（PrPSc）的理想工具。为探讨PrP106—126对小胶质细胞氧化压力的影响。本研究以小胶质细胞BV-2为细胞模型,PrP106—126作用48h,应用MTT和流式细胞仪检测细胞的活化情况,应用分子探针技术对细胞的氧化压力（reactiveoxygenspecies,ROs）进行检测,并通过荧光定量RT—PCR对与R0s相关的酶的mRNA表达进行了测定。结果表明PrPl06—126显著促进小胶质细胞BV-2的活化,并提高胞内的ROS水平;定量RT—PCR显示,PrP106—126显著降低细胞S0D-1（P〈0．01）表达水平、提高胞内Cat（P〈0．01）的表达水平;对Grx、Trx-1、和Trx-2mRNA的表达水平有升高的趋势,但未达到显著水平（P〉0．05）,对SOd-2、GPx、GR无显著性影响（P〉0．05）。从分子水平初步阐明小胶质细胞ROS升高的机理。 相似文献
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After the decline of the Bovine Spongiform Encephalopathy (BSE) epidemic in Great Britain (GB), scrapie remains the most prevalent animal Transmissible Spongiform Encephalopathy (TSE) present in GB. A number of control measures have been implemented for classical scrapie, and since 2005 there has been a large reduction in the number of observed cases. The objective of this study is to estimate two measures of disease frequency using up to date surveillance data collected during and after the implementation of different control measures established since 2004, and breeding for resistance schemes that ran from 2001 until 2009. This would enable an assessment of the effectiveness of both the breeding for resistance programme and the compulsory eradication measures in reducing the prevalence of scrapie in GB. Evaluation of the sensitivity of the rapid post-mortem test for scrapie indicated that it detected scrapie in the last 25% of the incubation period. A back-calculation model was developed to estimate the prevalence of infection at animal and flock-level. The results of the model indicated a mean drop of infection prevalence of 31% each year, leading to a 90% drop in infection prevalence between 2005, with an estimate of 5737 infected sheep in GB in 2012. 相似文献