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排序方式: 共有97条查询结果,搜索用时 31 毫秒
1.
Release of the cellular prion protein from cultured cells after loss of its glycoinositol phospholipid anchor 总被引:3,自引:0,他引:3
Borchelt David R.; Rogers Mark; Stahl Neil; Telling Glenn; Prusiner Stanley B. 《Glycobiology》1993,3(4):319-329
Secreted forms of the sialoglycoprotein designated cellularprion protein (PrPC) have been identified that cannot be explainedby alternative splicing. We report that secreted forms of PrPCderive from precursors that are bound to the plasma membraneby glycoinositol phospholipid (GPI) anchors. Secreted PrPC slowlyappeared in the culture medium of metabolically radiolabelledcells after incubations of 824 h. Digestion of nascentPrPC with phosphatidylinositol-specific phospholipase C (PIPLC)prevented the appearance of secreted PrPC. Secreted PrPc partitionedinto the aqueous phase of Triton X114 like PIPLC-releasedPrPC. While the Mr of PIPLC-released PrPC was reduced 24kDa after treatment with aqueous hydroflouric acid, which removesthe entire GPI anchor modification, the Mr of secreted PrPCwas unchanged. Both PIPLC-released and secreted PrPc were recognizedby antiserum raised against a synthetic C-terminal peptide correspondingto residues 220233 (amino acid 231 is the site of GPIattachment). We conclude that GPI-anchored PrPC is post-translationallyprocessed to remove most, if not all, of the GPI modificationand then shed into culture medium. Whether PrPC is shed afterproteolysis near the C-terminus remains to be established. Aminority of PrPC in normal Syrian hamster brain partitionedinto the aqueous phase of Triton X114 like shed PrPCsuggesting physiological significance. post-translational prion protein secretion sialoglycoprotein 相似文献
2.
GC Wood 《New Zealand journal of zoology.》2013,40(3):186-195
Abstract The Westland petrel (Procellaria westlandica) is an endemic New Zealand species and one of the very few burrowing seabird species still breeding on mainland New Zealand. It nests only on a series of coastal ridgelines near to Punakaiki on the West Coast of the South Island. Between 2002 and 2005, surveys were undertaken at 28 of the 29 known colonies. The area occupied by the colonies was 73 ha; most colonies had fewer than 50 burrows, but six colonies had 201–500 burrows and four colonies had more than 1000 burrows. We find that the current breeding range of Westland petrel and the location of individual colonies are similar to those reported in both the 1950s and 1970s. Based on total burrow counts at 28 colonies and burrow occupancy rates determined by annual monitoring, the annual breeding population is estimated to be between 2954 and 5137 breeding pairs. 相似文献
3.
4.
Telling GC 《Genome biology》2004,5(5):222-3
Studies of mammalian prion diseases such as bovine spongiform encephalopathy have suggested that different strains consist of prion proteins with different conformations. Two recent studies of yeast prions have now formally demonstrated that multiple stable protein conformations are the basis of strain variation. 相似文献
5.
Background
Patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) commonly require hospitalization and admission to intensive care unit (ICU). It is useful to identify patients at the time of admission who are likely to have poor outcome. This study was carried out to define the predictors of mortality in patients with acute exacerbation of COPD and to device a scoring system using the baseline physiological variables for prognosticating these patients.Methods
Eighty-two patients with acute respiratory failure secondary to COPD admitted to medical ICU over a one-year period were included. Clinical and demographic profile at the time of admission to ICU including APACHE II score and Glasgow coma scale were recorded at the time of admission to ICU. In addition, acid base disorders, renal functions, liver functions and serum albumin, were recorded at the time of presentation. Primary outcome measure was hospital mortality.Results
Invasive ventilation was required in 69 patients (84.1%). Fifty-two patients survived to hospital discharge (63.4%). APACHE II score at the time of admission to ICU {odds ratio (95 % CI): 1.32 (1.138–1.532); p < 0.001} and serum albumin (done within 24 hours of admission) {odds ratio (95 % CI): 0.114 (0.03-0.432); p = 0.001}. An equation, constructed using the adjusted odds ratio for the two parameters, had an area under the ROC curve of 91.3%. For the choice of cut-off, sensitivity, specificity, positive and negative predictive value for predicting outcome was 90%, 86.5%, 79.4% and 93.7%.Conclusion
APACHE II score at admission and SA levels with in 24 hrs after admission are independent predictors of mortality for patients with COPD admitted to ICU. The equation derived from these two parameters is useful for predicting outcome of these patients. 相似文献6.
One of us remembers sitting in a high school biology class in 1977 being taught about scrapie, a naturally occurring disorder
of sheep. The teacher had no particular interest in agriculture, but was pointing out some peculiar characteristics of this
disease as a biological curiosity on a wet Friday afternoon. The prion disorders captured the imagination of a range of biologists
(including that teacher) well before the epidemic of bovine spongiform encephalopathy (BSE) and the appearance of a new variant
of the human prion disease, Creutzfeldt Jakob disease (CJD), in the UK, because of their extraordinary biology and the unique
properties of the infectious agent. We review the results of studies leading to a convergence of evidence that the causative
infectious agent, the `prion', is devoid of nucleic acid and is composed of an abnormal isoform of a host-encoded protein,
the prion protein (PrP).
Received: 2 March 1998 / Accepted: 2 March 1998 相似文献
7.
Lisa C Willcocks Paul A Lyons Andrew J Rees Kenneth GC Smith 《Arthritis research & therapy》2010,12(1):202
The aetiology of anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis has not been well defined. Here
we review two factors which may play a role in the pathogenesis of the disease: genetics and infection. In particular, we
discuss the role of autoantibodies to LAMP-2, which may arise following infection with Gram-negative bacteria, and may contribute
to the development of ANCA-associated systemic vasculitis in genetically susceptible individuals. 相似文献
8.
9.
Background
Current techniques used to obtain lung samples have significant limitations and do not provide reproducible biomarkers of inflammation. We have developed a novel technique that allows multiple sampling methods from the same area (or multiple areas) of the lung under direct bronchoscopic vision. It allows collection of mucosal lining fluid and bronchial brushing from the same site; biopsy samples may also be taken. The novel technique takes the same time as standard procedures and can be conducted safely.Methods
Eight healthy smokers aged 40–65 years were included in this study. An absorptive filter paper was applied to the bronchial mucosa under direct vision using standard bronchoscopic techniques. Further samples were obtained from the same site using bronchial brushings. Bronchoalveolar lavage (BAL) was obtained using standard techniques. Chemokine (C-C Motif) Ligand 20 (CCL20), CCL4, CCL5, Chemokine (C-X-C Motif) Ligand 1 (CXCL1), CXCL8, CXCL9, CXCL10, CXCL11, Interleukin 1 beta (IL-1β), IL-6, Vascular endothelial growth factor (VEGF), Matrix metalloproteinase 8 (MMP-8) and MMP-9 were measured in exudate and BAL. mRNA was collected from the bronchial brushings for gene expression analysis.Results
A greater than 10 fold concentration of all the biomarkers was detected in lung exudate in comparison to BAL. High yield of good quality RNA with RNA integrity numbers (RIN) between 7.6 and 9.3 were extracted from the bronchial brushings. The subset of genes measured were reproducible across the samples and corresponded to the inflammatory markers measured in exudate and BAL.Conclusions
The bronchoabsorption technique as described offers the ability to sample lung fluid direct from the site of interest without the dilution effects caused by BAL. Using this method we were able to successfully measure the concentrations of biomarkers present in the lungs as well as collect high yield mRNA samples for gene expression analysis from the same site. This technique demonstrates superior sensitivity to standard BAL for the measurement of biomarkers of inflammation. It could replace BAL as the method of choice for these measurements. This method provides a systems biology approach to studying the inflammatory markers of respiratory disease progression.Trial registration
NHS Health Research Authority (13/LO/0256). 相似文献10.
Nazor KE Kuhn F Seward T Green M Zwald D Pürro M Schmid J Biffiger K Power AM Oesch B Raeber AJ Telling GC 《The EMBO journal》2005,24(13):2472-2480
The absence of infectivity-associated, protease-resistant prion protein (PrPSc) in the brains of spontaneously sick transgenic (Tg) mice overexpressing PrP linked to Gerstmann–Sträussler Scheinker syndrome, and the failure of gene-targeted mice expressing such PrP to develop disease spontaneously, challenged the concept that mutant PrP expression led to spontaneous prion production. Here, we demonstrate that disease in overexpressor Tg mice is associated with accumulation of protease-sensitive aggregates of mutant PrP that can be immunoprecipitated by the PrPSc-specific monoclonal antibody designated 15B3. Whereas Tg mice expressing multiple transgenes exhibited accelerated disease when inoculated with disease-associated mutant PrP, Tg mice expressing mutant PrP at low levels failed to develop disease either spontaneously or following inoculation. These studies indicate that inoculated mutant PrP from diseased mice promotes the aggregation and accumulation of pre-existing pathological forms of mutant PrP produced as a result of transgene overexpression. Thus, while pathological mutant PrP possesses a subset of PrPSc characteristics, we now show that the attribute of prion transmission suggested by previous studies is more accurately characterized as disease acceleration. 相似文献