Studies on the mechanisms of Ni2(+)-induced cell injury: I. Effects of Ni2+ on microtubules

Cytoskeletal perturbations have been associated with exposures to a variety of toxic agents as well as a number of human pathological conditions. We have observed dramatic alterations in the organization of microtubules (MT), a major component of the cytoskeleton, in 3T3 cells exposed to Ni2+. Severe perinuclear bundling and aggregation of MT occurred in both a time- and dose-dependent fashion, and this MT damage was reversible upon removal of Ni2+ from the culture media. To understand the mechanism of the Ni2(+)-induced MT change, we investigated the effect of Ni2+ (0.01 to 3.0 mM) on in vitro tubulin polymerization. Ni2+ at lower concentrations (0.01 to 1.0 mM) had little or no significant effect on the kinetics of MT polymerization. In contrast, in the presence of 1.5 to 2.0 mM Ni2+, a significant promoting effect on both the rate and the final extent of polymerization was observed. However, at Ni2+ concentrations higher than 2.0 mM, such stimulatory effect on the rate and the final extent of tubulin polymerization declined. Furthermore, the promoting effects of Ni2+ on MT polymerization were accompanied by a significant decrease in the lag period. Electron microscopic examination of samples of the polymerization product showed that MT, polymerized in the presence of 2.0 mM Ni2+, appeared more numerous and shorter (1.10 +/- 1.02 microns) than those of control (3.81 +/- 2.29 microns; p less than 0.005). This was probably a direct result of an increase in the number of initiation centers in the presence of Ni2+ as a consequence of the decreased critical concentration (7%, p less than 0.05) necessary for polymerization to occur. Our results suggest that Ni2+ may exert its toxic effect on MT in cultured cells by altering the normal kinetics of MT polymerization.     

The effect of individual HLA-A and -B mismatches on the generation of cytotoxic T lymphocyte precursors

In order to study the correlation between HLA mismatches and the cytotoxic T lymphocyte precursor frequency, we used a limiting dilution analysis to determine the CTLp frequencies against individual mismatched HLA-A and -B alloantigens in 21 patients waiting for a renal transplant. Altogether, thirty-three mismatched HLA-A antigens and 55 HLA-B antigens were tested. The CTLp frequencies against mismatches of HLA-B locus antigens were found to be significantly higher than those against HLA-A antigens (P less than 0.002). This may explain why matching for HLA-B antigens is more important for a good renal allograft survival than matching for HLA-A antigens.     

Effects of an anti-interleuktn-6 (IL-6) murine monoclonal antibody in a patient with acute monoblastic leukemia

Because IL-6 has been involved in the pathogenesis of acute monoblastic leukemia, we investigated thein vitro anti-proliferative effect and thein vivo anti-tumoral effect of an anti-IL-6 murine monoclonal antibody (mAb) in a patient with MSB type acute leukemia. In the current study, we clearly show the IL-6 dependence of monoblastic cell viability and proliferationin vitro in short-term cultures of malignant cells and the clinical activity of the anti-IL-6 murine mAb. The complete neutralization of IL-6in vivo was associated with a transient but complete disappearance of malignant monoblastic cells in the peripheral blood, with improvement or even normalization of several other biological parameters of disease activity, No immunization against the anti-IL-6 murine mAb was observed.     

肺移植急性排斥反应及其控制实验研究

观察了大鼠实验性肺移植术后急性排斥反应的病理改变。异系间移植术后２ｄ，移植肺内小血管及支气管周围出现单核细胞浸润。４ｄ上述细胞浸润波及肺泡壁，导致肺泡壁增厚，肺内小静脉系及毛细血管管腔变窄，血流不畅。术后６ｄ，血液循环严重障碍处，肺泡完全坏死，环抱素Ａ可使上述排斥反应得到明显抑制。     

TPA诱导的血小板聚集的研究

应用不同浓度ＴＰＡ诱发血小板聚集，观察２０名正常人血小板的聚集率。结果显示：ＴＰＡ从５ｎｇ／ｍｌ到１０ｎｇ／ｍｌ之间，随着浓度的增加，血小板聚集率逐渐增加，最佳浓度为１０ｎｇ／ｍｌ。当ＴＰＡ浓度〉１０ｍｇ／ｍｌ时，继续增加ＴＰＡ浓度，血小板聚集率将不再升高，且于２０ｍｇ／ｍｌ时出现明显的解聚现象。     

恩施土家族人眼的表面形态特征

按随机抽样原则选择湖北恩施土家族人５９８名观测了眼的表面形态。该民族大部分人两眼位置适中，虹膜褐色，眼裂水平，开度中等，无蒙古褶，双睑；多为细窄眼型或中等眼型；眼的各径男大于女，一般存在性别差异；随年龄增加，眼型由中等型向细窄型转化，根据眼外形特征和聚类分析推测，土家人眼属于南、北方民族间的过渡型。     

刺激视上核对大鼠痛阈及电针镇痛的影响

以钾离子透引起的大鼠甩尾反应为痛指标，观察了电和化学刺激视上核（ＳＯＮ）对大鼠痛阈（ＰＴ）和电针（ＥＡ）镇痛的影响。电刺激ＳＯＮ后，ＰＴ明显高于假刺激组（Ｐ＜０．０５～０．００１），电刺激ＳＯＮ后电针足三里，镇痛效应明显提高，并有明显的量效关系。电刺激ＳＯＮ的近旁部位（０．５—１ｍｍ）对ＰＴ及电针镇痛无明显影响。ＳＯＮ内注射Ｌ－谷氨酸（Ｌ－Ｇｌｕ）后痛阈和电针镇痛效应都明显对照组，也有明显的量效关     

雌激素,胎盘生乳素,钙,磷与妊高征的关系

目的：探讨雌激素，胎盘生乳素，钙在妊高征发病中的作用及其相互关系，方法：采用放射免疫法及离心分析钙试剂，测定了４２例妊高征患者血清雌二醇，胎盘生乳素，钙，磷及尿钙，磷的含量，３４例同期门诊正常孕妇作为对照组，结果：轻度妊高征患者血清雌二醇明显增加（Ｐ〈０．０５）。重度妊高征患者血清胎盘生乳素显著减少（Ｐ〈０．０５），轻，中，重度妊高征患者血钙，尿钙含量显著降低（Ｐ〈０．０５，Ｐ〈０．０１，Ｐ〈０．     

胃癌组织内微血管定量的意义

目的：研究胃癌组织中微血管数量（MVC）与临床病理因素及预后的关系。方法：材料取自瑞金医院1988年～1991年胃癌手术切除标本，共128例。抗因子Ⅷ相关抗原（F-ⅧRAg）的单克隆抗体和免疫组化试剂盒购自Dako公司。研究方法按LSAB法免疫组织化学操作技术常规进行；微血管定量以镜下200倍，肿瘤内5个最高微血管密度区的MVC均数表示；分析MVC与临床病理因素之间关系，并对有完整5年随访资料的86例胃癌患者预后与MVC关系进行探讨。结果：所有胃癌组织中的平均MVC为16.5±8．5，MVC随TNM分期增加而增加，有淋巴结转移患者的MVC（18．3±8.7）明显高于无淋巴结转移患者（13．8±7．4）（P＜0．01），高MVC（≥16）胃癌患者比低MVC（＜16）患者预后明显为差，5年生存率分别为42.5％和58．7％（P＜0．05）。结论：MVC在胃癌患者是一个有意义的预后指标．