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11.
构建了可在哺乳动物细胞中表达人p53蛋白的重组质粒p53─pSV2neo,分别转染猴肾细胞株CV─1及人子宫颈癌细胞株SiHa。用PCR法检测出转染细胞中的p53cDNA;用免疫组化ABC法检测出p53蛋白的表达定位于细胞核内,用Westernblot检测出转染细胞中存在p53蛋白。结果表明,外源性野生型p53基因的表达可以使SiHa细胞的细胞克隆形成效减少50%,使细胞生长速度降低,但对SiHa细胞的软琼脂克隆形成效无明显影响。提示p53基因的肿瘤抑制作用与野生型p53蛋白的量有关,并且是细胞类型特异性的。 相似文献
12.
B. R. Mclaren T. Haenel S. Stevenson S. Mukherjee B. W. S. Robinson R. A. Lake 《Internal medicine journal》2000,30(4):450-456
Background : Simian virus (SV) 40 sequences have been found in some, but not all studies of mesotheliomas. This virus is known to cause tumours in rodents but its role in human oncogenesis remains controversial.
Aims : The aim of this study therefore was to determine whether SV40 is associated with the development of mesotheliomas in Australia. The absence of the virus or its gene products in tissue derived from mesotheliomas would detract from this possibility.
Methods : We used polymerase chain reaction from three pairs of primers to amplify different regions of the large T antigen from DNA from cell lines and cDNA from both cell lines and an independent set of tumour biopsies from patients with mesothelioma.
Results : We examined five human mesothelioma cell lines that were established in our laboratories. In addition, we examined several tumour biopsies from seven different patients. SV40 like sequences were present in all the cell lines and in at least one sample from each of the patients examined.
Conclusions : The large T antigen of SV40 or an SV40 like virus is expressed in Australian mesotheliomas and therefore could be aetiologically-associated with tumourigenesis. Alternatively, these sequences could be expressed subsequent to the development of the disease. 相似文献
Aims : The aim of this study therefore was to determine whether SV40 is associated with the development of mesotheliomas in Australia. The absence of the virus or its gene products in tissue derived from mesotheliomas would detract from this possibility.
Methods : We used polymerase chain reaction from three pairs of primers to amplify different regions of the large T antigen from DNA from cell lines and cDNA from both cell lines and an independent set of tumour biopsies from patients with mesothelioma.
Results : We examined five human mesothelioma cell lines that were established in our laboratories. In addition, we examined several tumour biopsies from seven different patients. SV40 like sequences were present in all the cell lines and in at least one sample from each of the patients examined.
Conclusions : The large T antigen of SV40 or an SV40 like virus is expressed in Australian mesotheliomas and therefore could be aetiologically-associated with tumourigenesis. Alternatively, these sequences could be expressed subsequent to the development of the disease. 相似文献
13.
血栓栓塞性疾病是人类首要致死病因,临床预防血栓药物均存在出血危险。选择性的内源性凝血途径抑制剂已成为低出血倾向预防血栓药物研发的重点方向。SV是以天然岩藻糖化糖胺聚糖(FG)为先导化合物经结构优化获得的选择性内源性凝血因子Xase抑制剂(IC50=30 nm),其抑制内源性凝血活性与依诺肝素相当,在等效抗凝血剂量的倍数剂量下出血倾向显著降低。本文探讨低出血倾向的SV预防血栓药理学作用及其机制,为选择性Xase抑制剂及其新药发现研究提供参考依据。 相似文献
14.
目的:探讨利福霉素钠注射液联合利奈唑胺注射液对重症革兰阳性球菌感染患者炎症反应、血清降钙素原(PCT)水平及不良反应的影响。方法:选取2018年5月至2019年9月商丘市第一人民医院收治的重症革兰阳性球菌感染患者60例作为研究对象,按照随机数字表法分为研究组和对照组,每组30例。对照组患者给予利奈唑胺注射液治疗,研究组患者在对照组的基础上给予利福霉素钠注射液治疗。比较两组患者的临床疗效、炎症指标[白细胞计数(WBC)、超敏C反应蛋白(hs-CRP)、白细胞介素1β(IL-1β)及白细胞介素10(IL-10)]水平、血清PCT水平及不良反应发生情况的差异。结果:研究组患者的总有效率明显高于对照组[90.00%(27/30)vs.66.67%(20/30)],差异有统计学意义(P<0.05)。治疗后,两组患者血清WBC、CRP及IL-1β水平均较治疗前明显降低,血清IL-10水平较治疗前明显升高;且研究组患者血清WBC、CRP及IL-1β水平明显低于对照组,血清IL-10水平明显高于对照组,上述差异均有统计学意义(P<0.05)。治疗后,两组患者血清PCT水平均较治疗前明显降低,且研究组患者明显低于对照组,差异均有统计学意义(P<0.05)。研究组、对照组患者的不良反应发生率分别为23.33%(7/30)、26.67%(8/30),差异无统计学意义(P>0.05)。结论:利福霉素钠注射液联合利奈唑胺注射液治疗重症革兰阳性球菌感染的临床效果显著,能够有效降低患者血清PCT水平,改善炎症反应,缓解感染症状,具有一定的临床应用价值。 相似文献
15.
Haotian Gu Sahrai Saeed Andrii Boguslavskyi Gerald Carr-White John B. Chambers Phil Chowienczyk 《JACC: Cardiovascular Imaging》2019,12(1):52-63
Objectives
This study investigated the prognostic value of first-phase ejection fraction (EF1) in patients with aortic stenosis (AS), a condition in which left ventricular dysfunction as measured by conventional indices is an indication for valve replacement.Background
EF1, the ejection fraction up to the time of maximal ventricular contraction may be more sensitive than existing markers in detecting early systolic dysfunction.Methods
The predictive value of EF1 compared to that of conventional echocardiographic indices for outcomes was assessed in 218 asymptomatic patients with at least moderate AS, including 73 with moderate, 50 with severe, and 96 with “discordant” (aortic area <1.0 cm2 and gradient <40 mm Hg) AS, all with preserved EF, followed for at least 2 years. EF1 was measured retrospectively from archived echocardiographic images by wall tracking of the endocardium. The primary outcome was a combination of aortic valve intervention, hospitalization for heart failure, and death from any cause.Results
EF1 was the most powerful predictor of events in the total population and all subgroups. A cutoff value of 25% (or EF1 of <25% compared to ≥25%) gave hazard ratios of 27.7 (95% confidence interval [CI]: 13.1 to 58.7; p < 0.001) unadjusted and 24.4 (95% CI: 11.3 to 52.7; p < 0.001) adjusted for other echocardiographic measurements including global longitudinal strain, for events at 2 years in all patients with asymptomatic AS. Corresponding hazard ratios for all-cause mortality in the total population were 17.5 (95% CI: 5.7 to 53.3) and 17.4 (95% CI: 5.5 to 55.2) unadjusted and adjusted, respectively.Conclusions
EF1 may be potentially valuable in the clinical management of patients with AS and other conditions in which there is progression from early to late systolic dysfunction. 相似文献16.
Ultrastructural localization of active zone and synaptic vesicle proteins in a preassembled multi-vesicle transport aggregate 总被引:1,自引:0,他引:1
Tao-Cheng JH 《Neuroscience》2007,150(3):575-584
Although it has been suggested that presynaptic active zone (AZ) may be preassembled, it is still unclear which entities carry the various proteins to the AZ during synaptogenesis. Here, I propose that aggregates of dense core vesicles (DCV) and small clear vesicles in the axons of young rat hippocampal cultures are carriers containing preformed AZ and synaptic vesicle (SV) components on their way to developing synapses. The aggregates were positively labeled with antibodies against Bassoon and Piccolo (two AZ cytomatrix proteins), VAMP, SV2, synaptotagmin (three SV membrane proteins), and synapsin I (a SV-associated protein). Bassoon and Piccolo labeling were localized at dense material both in the aggregates and at the AZ. In addition to the SV at the synapses, the SV membrane proteins labeled the clear vesicles in the aggregate as well as many other SV-like and pleiomorphic vesicular structures in the axons, and synapsin I labeling was associated with the vesicles in the aggregates. In single sections, these axonal vesicle aggregates were approximately 0.22 by 0.13 microm in average dimensions and contain one to two DCV and five to six small clear vesicles. Serial sections confirmed that the aggregates were not synaptic junctions sectioned en face. Labeling intensities of Bassoon and Piccolo measured from serially sectioned transport aggregates and AZ were within range of each other, suggesting that one or a few aggregates, but not individual DCV, can carry sufficient Bassoon and Piccolo to form an AZ. The present findings provide the first ultrastructural evidence localizing various AZ and SV proteins in a preassembled multi-vesicle transport aggregate that has the potential to quickly form a functional active zone. 相似文献
17.
HIV-1 proteins, especially gp120 and Tat, elicit reactive oxygen species (ROS) and cause neuron apoptosis. We used antioxidant enzymes, Cu/Zn superoxide dismutase (SOD1) and glutathione peroxidase (GPx1) to study signaling and neuroprotection from Tat-induced apoptosis. SOD1 converts superoxide to peroxide; GPx1 converts peroxide to water. Primary human neurons were transduced with SV40-derived vectors carrying SOD1 and GPx1, then HIV-1 Tat protein was added. Both SV(SOD1) and SV(GPx1) delivered substantial transgene expression. Tat decreased endogenous cellular, but not transduced, SOD1 and GPx1. Tat rapidly increased neuron [Ca(2+)](i), which effect was not altered by SV(SOD1) or SV(GPx1). However, both vectors together blocked Tat-induced [Ca(2+)](i) fluxes. Similarly, neither SV(SOD1) nor SV(GPx1) protected neurons from Tat-induced apoptosis, but both vectors together did. Tat therefore activates multiple signaling pathways, in one of which superoxide acts as an intermediate while the other utilizes peroxide. Gene delivery to protect neurons from Tat must therefore target both. 相似文献
18.
A dynamic model of STAT1 degradation by the V protein of parainfluenza virus 5 (PIV5; formerly SV5) has been proposed. In it, the V protein functions as a bipartite adaptor linking DDB1, a component of a cellular SCF-like ubiquitin E3 ligase complex, to STAT2, which in turn binds STAT1 and presents STAT1 to the E3 ligase complex for ubiquitination and subsequent degradation. Furthermore, it appears that loss of STAT1 from the complex results in decreased affinity of V for STAT2 such that STAT2 either dissociates from V or is displaced by STAT1/STAT2 complexes, facilitating the cycling of the DDB1/PIV5 V containing E3 complex for further rounds of STAT1 ubiquitination and degradation. By determining the approximate number of molecules of V, DDB1, STAT1 and STAT2 present in IFN-treated 2fTGH cells, we provide additional evidence for this dynamic model of STAT1 degradation. These results show that (i) in IFN-treated cells there is approximately 4-fold less STAT2 and 15-fold less DDB1 than STAT1 per cell and thus DDB1 and STAT2 must repeatedly acquire more STAT1 for degradation to go to completion, and (ii) approximately 600 molecules of V protein per cell can target as many as 120,000 molecules of STAT1 for degradation in the absence of either viral or cellular protein synthesis. The importance of this mechanism in terms of the ability of the virus to dismantle the IFN-induced anti-viral state of cells is discussed. 相似文献
19.
Glomerular podocytes play a key role in maintaining the integrity of the glomerular filtration barrier. This function may be regulated by angiotensin II (Ang II) through activation of cell-surface receptors. Although studies suggest that podocytes express receptors for Ang II, the Ang II binding site has not been characterized with radioligand binding techniques. We therefore used iodine 125-labeled Ang II to monitor Ang II-receptor density during differentiation of a mouse podocyte cell line. Scatchard analyses of equilibrium binding data revealed a single class of high-affinity binding sites (dissociation constant approximately 3 nmol/L) in both differentiated and nondifferentiated cells. During differentiation, the density of Ang II-receptor sites increased roughly 15-fold in differentiated podocytes (maximal density of specific binding sites 881 fmol/mg protein) compared with that in nondifferentiated cells (52 fmol/mg protein; P<.005). Glomerular podocytes expressed messenger RNA for AT1A, AT1B, and AT2 receptor subtypes, and competitive binding studies found that differentiated podocytes expressed mostly AT1 receptors (approximately 75%) with lesser amounts of AT2 (approximately 25%). Up-regulation of Ang II-receptor number was associated with increased Ang II-receptor responsiveness, as evidenced by enhanced Ang II-stimulated inositol phosphate (IP) generation and incorporation of tritiated thymidine. Both [3H]thymidine incorporation and IP generation were mediated by AT1-receptor activation. These data suggest that glomerular podocytes express a high-affinity binding site for Ang II with pharmacologic characteristics of both AT1 and AT2 receptors. This receptor site is up-regulated during podocyte differentiation, and receptor activation induces both IP generation and DNA synthesis by AT1-dependent mechanisms. We speculate that activation of podocyte Ang II receptors contributes to glomerular damage in disease states. 相似文献
20.
Renal transplantation and polyomavirus infection: recent clinical facts and controversies 总被引:1,自引:0,他引:1
Abstract: Although many articles have been published on polyomavirus‐induced pathologies in transplant recipients, our knowledge regarding their clinical aspects remains relatively limited. In fact, the number of questions and controversies on the subject seems even to be increasing as new publications continue to appear. This article presents some of these controversies through a brief review of recent clinical facts about the three polyomaviruses that infect humans – JC virus, simian virus 40, and BK virus – as they relate to renal transplantation. 相似文献