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81.
Inhibition of lymphokine-activated killer- and natural killer-mediated cytotoxicities by neutrophils 总被引:2,自引:0,他引:2
Peripheral blood polymorphonuclear neutrophils (PMN) can significantly inhibit lymphokine-activated killer- (LAK) mediated cytotoxicity when added to a cytotoxicity assay of IL-2-activated PBL and target cells. The inhibition by resting PMN is resistant to blocking with catalase and superoxide dismutase, suggesting that reactive oxygen species are not involved. The addition of TNF greatly enhanced the PMN-mediated inhibition of LAK effector functions. This TNF-enhanced inhibition is reversed by catalase, but not by superoxide dismutase, implicating hydrogen peroxide in the augmented inhibition. Separation of PMN from effector cells and target cells totally abrogates the inhibition by both resting PMN and TNF-treated PMN. Formalin-fixed PMN, heat-treated PMN, PMN lysates, and PMN membrane all fail to mediate any inhibition of LAK. These results suggest that contact with intact viable PMN is needed for inducing LAK inhibition. However, pretreatment of LAK cells with PMN also decreases their cytotoxicity in subsequent chromium release assays. PMN can also inhibit NK cytotoxicity of fresh PBL. However, NK activity is much less sensitive to inhibition by resting PMN than is LAK. TNF also augments PMN inhibition of NK, and there is no significant difference between LAK and NK in sensitivity to the TNF-enhanced inhibition. Our results indicate that PMN can significantly influence the destruction of tumor targets by LAK and NK, and suggest that approaches to circumvent such regulation may be important in the outcome of immunotherapies with IL-2 and LAK cells. 相似文献
82.
Depletion of NK cells with the lysosomotropic agent L-leucine methyl ester and the in vitro generation of NK activity from NK precursor cells 总被引:2,自引:0,他引:2
Human natural killer (NK) cell activity in peripheral blood lymphocytes (PBL) is totally inhibited by pretreatment of the effector cells with a lysosomotropic agent, L-leucine methyl ester (LeuOMe). This treatment specifically eliminates cells expressing the NK cell markers HNK-1, OKM1, B73.1, or Leu-11b, but has minimal effect on viability of cells with T cell markers Leu-1, OKT3, Leu-2a, or Leu-3a. LeuOMe also drastically decreased the proportion of K562 target-binding lymphocytes among PBL. PBL pretreated with LeuOMe respond normally in thymidine uptake to stimulation by phytohemagglutinin or allogeneic lymphocytes as long as irradiated autologous accessory cells are provided, indicating that the treatment is not toxic to T cells. NK activity can be regenerated in the NK cell-depleted PBL population by incubation with IL 2 or by mixed lymphocyte cultures, but not by alpha-interferon. Cells responsible for regeneration of such NK activity are probably large agranular lymphocytes, because they are resistant to LeuOMe treatment but have the same low buoyant density as NK cells in Percoll density gradient separation. The in vitro-generated NK is still sensitive to LeuOMe inhibition, but a higher concentration of the reagent is required to achieve total inhibition of the activity. 相似文献
83.
Wen-Yi Hung Chew-Wun Wu Pen-Hui Yin Chun-Ju Chang Anna Fen-Yau Li Chin-Wen Chi Yau-Huei Wei Hsin-Chen Lee 《Biochimica et Biophysica Acta (BBA)/General Subjects》2010
Background
Somatic mutation in mitochondrial DNA (mtDNA) has been proposed to contribute to initiation and progression of human cancer. In our previous study, high frequency of somatic mutations was found in the D-loop region of mtDNA of gastric cancers. However, it is unclear whether somatic mutations occur in the coding region of mtDNA of gastric cancers.Methods
Using DNA sequencing, we studied 31 gastric cancer specimens and corresponding non-cancerous stomach tissues. Moreover, a human gastric cancer SC-M1 cell line was treated with oligomycin to induce mitochondrial dysfunction. Cisplatin sensitivity and cell migration were analyzed.Results
We identified eight somatic mutations in the coding region of mtDNAs of seven gastric cancer samples (7/31, 22.6%). Patients with somatic mutations in the entire mtDNA of gastric cancers did not show significant association with their clinicopathologic features. Among the eight somatic mutations, five point mutations (G3697A, G4996A, G9986A, C12405T and T13015C) are homoplasmic and three mutations (5895delC, 7472insC and 12418insA) are heteroplasmic. Four (4/8, 50%) of these somatic mutations result in amino acid substitutions in the highly conserved regions of mtDNA, which potentially lead to mitochondrial dysfunction. In addition, in vitro experiments in SC-M1 cells revealed that oligomycin-induced mitochondrial dysfunction promoted resistance to cisplatin and enhanced cell migration. N-acetyl cysteine was effective in the prevention of the oligomycin-enhanced migration, which suggests that reactive oxygen species generated by defective mitochondria may be involved in the enhanced migration of SC-M1 cells.General Significance
Our results suggest that somatic mtDNA mutations and mitochondrial dysfunction may play an important role in the malignant progression of gastric cancer. 相似文献84.
85.
Mechanisms involved in agonist-induced hyperaggregability of platelets from normal pregnancy 总被引:2,自引:0,他引:2
Dr. Joen-Rong Sheu George Hsiao Wen-Yi Lin Tzeng-Fu Chen Yi-Yi Chien Chien-Huang Lin Chiu-Ruey Tzeng 《Journal of biomedical science》2002,9(1):17-25
There is substantial evidence of increased platelet reactivity in vivo and in vitro during pregnancy. Platelet activation occurs in pregnancy with a risk of the development of preeclampsia. In this study, platelet behavior was studied during 28-40 weeks of gestation in a group of women who remained normotensive and a group of nonpregnant female controls. Platelet aggregation and ATP release stimulated by agonists (i.e. collagen and adenosine 5'-diphosphate) were markedly enhanced in washed platelets from pregnant subjects. Furthermore, the collagen-evoked increase in intracellular Ca(2+) ([Ca(2+)](i)) mobilization in fura-2-AM-loaded platelets was also enhanced in pregnant subjects. Moreover, the binding activity of fluorescein isothiocyanate-triflavin toward the platelet glycoprotein IIb/IIIa complex did not significantly differ between the nonpregnant and pregnant groups. In addition, the amount of thromboxane A(2) (TxA(2)) formation from pregnant subjects was significantly greater than that from nonpregnant subjects in both resting and collagen-activated platelets. On the other hand, prostaglandin E(2) formation in the presence of imidazole in either resting or arachidonic acid (100 microM)-treated platelets did not significantly differ between these two groups. The levels of cyclic AMP formation in both resting and prostaglandin E(1) (10 microM)-treated platelets from pregnant subjects were significantly lower than those in nonpregnant subjects. Nitric oxide production was measured by a chemiluminescence detection method in this study. The extent of nitrate production in either resting or collagen-stimulated platelets from pregnant subjects did not significantly differ from that of platelets from the nonpregnant group. We conclude that the agonist-induced hyperaggregability of platelets from normal pregnancy may be due, at least partly, to an increase in TxA(2) formation and a lowering of the level of cyclic AMP formation, which leads to increased [Ca(2+)](i) mobilization and finally to enhanced platelet aggregation and ATP release. 相似文献
86.
基于质谱的蛋白质组学结果不仅具有重复性差和覆盖率低等缺陷,并且针对数十至百个差异表达蛋白质分子的分析非常具有挑战性,而蛋白质与蛋白质相互作用网络(protein-protein interaction network, PPIN)分析能够在一定程度上弥补上述不足,使各种组学研究结果具有一致性和可比性。本研究应用同位素标记相对和绝对定量(iTRAQ)联用串联质谱技术鉴定了与食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)相关的差异表达蛋白质244个(ESCC中,升高和降低的蛋白质分别为119个和125个),基因本体论(gene ontology, GO)富集与肿瘤十大特征相关的17个GO条目|以该17个条目包含的117个蛋白质为种子蛋白搜索STRING(http: //www.string-db.org)数据库,构建包含96个存在相互作用的PPIN和21个离散蛋白质。用CytoHubba算法确定34个中心节点蛋白质和36个瓶颈蛋白质,非重复49个中心节点和/或瓶颈蛋白质中含7个目前已报道的癌基因表达蛋白(PPP2R1A、CTNNB1、ENO1、EZR、TPM4、COL1A1、TPM3),确定与该7个癌蛋白直接相互作用的4个蛋白质(FN1、ITGB1、TAGLN和YWHAZ)可能为参与食管癌变的关键蛋白质,并应用Western印迹实验验证了 FN1、ITGB1、TAGLN和YWHAZ等4个关键蛋白质在ESCC中具有显著的表达差异,表明PPIN分析是确定具有重要生物学意义分子的有效途经之一。 相似文献
87.
森林生物量碳储量的空间分布及其变化信息, 对揭示地表空间变化规律及驱动因子、分析评价森林生产力及生态功能具有重要意义。该文以20世纪70年代、80年代、90年代和21世纪初4个时期的遥感数据和同期的森林资源清查样地数据为基础, 应用遥感信息模型, 估算了黑龙江长白山地区的森林生物量, 分析了该地区森林生物量的时空动态变化, 以及森林生物量随高程、坡度和坡向的变化规律。结果表明: 该地区4个时期的森林平均生物量分别为81.56、44.27、48.27和54.82 t·hm-2。4个时期总的森林生物量分别为5.37 × 10 8、2.83 × 10 8、3.06 × 10 8和3.46 × 10 8 t。20世纪70年代到21世纪初森林平均生物量和总的森林生物量都呈现出先降低后增加的趋势, 呈先下降趋势的主要原因是20世纪70-80年代以森林采伐为主, 后增加趋势的主要原因是实施天然林保护工程起到了很大的作用。该地区4个时期森林生物量随高程、坡度和坡向都表现出一致性的变化规律, 森林生物量随高程和坡度变化都呈先增加后减少的趋势, 导致这一现象的主要原因是, 高程、坡度和坡向变化引起了局地气候条件的变化, 从而直接影响森林生长环境, 造成森林分布的变化。森林生物量在200-400 m高程所占的比例最大, 约为35%, 在坡度5°-15°所占的比例接近50%。森林生物量在南坡和西南坡所占的比例最小, 为7%; 平坡所占的比例最大, 为28%; 南坡次之, 为19%。 相似文献
88.
Huung Weei Piring; Lin T'ai Lang; Ren Shau Shi; Chen Jia Chyuan; Chen Yung Reui; Kao Ching Huei 《Plant & cell physiology》1988,29(1):27-31
Changes of stomatal aperture during the course of developmentof rice leaves were directly observed with a scanning electronmicroscope. The stomata reached their maximal aperture sizeafter senescence began in seedling leaves and the flag leafof mature plants. The small stomatal aperture observed priorto senescence seems to be the normal size of stomata in riceleaves, and thus stomata closure does not seem to be the causeof leaf senescence in rice plants. The stomata retain theircapability of movement during senescence, suggesting that guardcells tend to live longer than mesophyll cells.
4Present address: Tobacco Taiwan, Republic of China ResearchInstitute, Taichung, Taiwan, Republic of China (Received March 12, 1987; Accepted September 30, 1987) 相似文献
89.
Zing Tsung-Yeh Tsai Wen-Yi Chu Jen-Hao Cheng Huai-Kuang Tsai 《Nucleic acids research》2014,42(2):739-747
Non-B DNA structures are abundant in the genome and are often associated with critical biological processes, including gene regulation, chromosome rearrangement and genome stabilization. In particular, G-quadruplex (G4) may affect alternative splicing based on its ability to impede the activity of RNA polymerase II. However, the specific role of non-B DNA structures in splicing regulation still awaits investigation. Here, we provide a genome-wide and cross-species investigation of the associations between five non-B DNA structures and exon skipping. Our results indicate a statistically significant correlation of each examined non-B DNA structures with exon skipping in both human and mouse. We further show that the contributions of non-B DNA structures to exon skipping are influenced by the occurring region. These correlations and contributions are also significantly different in human and mouse. Finally, we detailed the effects of G4 by showing that occurring on the template strand and the length of G-run, which is highly related to the stability of a G4 structure, are significantly correlated with exon skipping activity. We thus show that, in addition to the well-known effects of RNA and protein structure, the relative positional arrangement of intronic non-B DNA structures may also impact exon skipping. 相似文献
90.
Li-Ya Wang Wen-Yi Zhang Fan Ding Wen-Biao Hu Ricardo J. Soares Magalhaes Hai-Long Sun Yi-Xing Li Wen Zou Yong Wang Qi-Yong Liu Shen-Long Li Wen-Wu Yin Liu-Yu Huang Archie C. A. Clements Peng Bi Cheng-Yi Li 《PLoS neglected tropical diseases》2013,7(6)