维持性血液透析病人NK—IL—2—IFNr系统的动态观察

本文检测了４０例维持性血液透析（ＭＨＤ）患者自然杀伤细胞（ＮＫ）活性，并同时检测了患者外周血单个核细胞（ＰＢＭＣ）在植物血凝素（ＰＨＡ）刺激下白细胞介素２（ＩＬ－２）和免疫干扰素（ＩＦＮｒ）产生水平。结果发现ＭＨＤ患者ＮＫ活性、ＩＬ－２活性和ＩＦＮｒ水平均显著低于正常对照组（Ｐ〈０．０１）；单次血液透析后ＭＨＤ患者的ＮＫ活性、ＩＬ－２和ＩＦＮｒ诱生水平均有不同程度的升高；长期血液透析对ＮＫ活性、Ｉ     

BCG－PSN、rIFN－r对膀胱癌患者T细胞MHCⅡ类抗原及IL－2R表达的诱导作用

采用鼠单克隆抗体间接免疫荧光技术观察了卡介苗多糖核酸（ＢＣＧ－ＰＳＮ）、重组免疫干扰素（ｒＩＦＮ－ｒ）在体外对膀胱癌患者外周静脉血Ｔ淋巴细胞主要组织相容性复合体（ＭＨＣ）Ⅱ类抗原及白细胞介素－２受体（ＩＬ－２Ｒ）表达的影响。结果表明；两者均能诱导病人Ｔ细胞ＤＲ抗原ＩＬ－２Ｒ的表达（Ｐ＜０．０５），而对正常人Ｔ细胞表达的影响无统计学意义。提示ＢＣＧ和ｒＩＦＮ－ｒ防治膀胱癌的作用可能与其诱导ＤＲ抗原、ＩＬ－２Ｒ的表达有关。     

氧化低密度脂蛋白刺激人肾小球系膜细胞产生单核细胞趋化蛋白-1由核因子-κB活化调控

目的 研究核因子ＫＢ（ＮＦ－ＫＢ）在氧化低密度脂蛋白（Ｏｘ- ＬＤＬ）诱导的体外培养的人肾小球系膜细胞表达单核／巨噬细胞趋化蛋白－１（ＭＣＰ－１）中的作用。方法 采用凝胶迁移率变动分析检测ＮＦ－ＫＢ的ＤＮＡ结合活性变化，以免疫组织化学观测细胞内ｐ６５的核转位，用细胞ＥＬＩＳＡ法检测细胞内 ＭＣＰ－１及ＩＫＢα蛋白含量变化。结果 不同浓度（１０、２５、５０、１００μｇ／ｍｌ）Ｏｘ－ＬＤＬ刺激肾小球系膜细胞均可引起细胞ＮＦ-ＫＢ的ＤＮＡ结合活性增强、ＩＫＢα蛋白表达下降以及ＭＣＰ－１蛋白表达增强，以５０μｇ／ｍｌ刺激１ｈ ＮＦ－ＫＢ活化及ＩＫＢα表达减弱最明显，作用２４ｈＭＣＰ-１表达水平最高。ＮＦ－ＫＢ俯活化的同时伴有ｐ６５核转位。上述效应可被ＮＦ－ＫＢ特异性抑制剂吡咯二硫氨基甲酸酯（ＰＤＴＣ）所抑制。结论Ｏｘ－ＬＤＬ刺激人肾小球系膜细胞产生ＭＣＰ－１是由ＮＦ－ＫＢ调控，ＮＦ－ＫＢ参与了脂质肾损害的发病过程。     

白细胞介素10抑制核因子кB介导的肾小管上皮细胞表达细胞间黏附分子1

目的研究白细胞介素１０（ＩＬ－１０）对人近端肾小管上皮细胞（ＨＫ－２细胞）在促炎症因子肿瘤坏死因子α（ＴＮＦα）作用下表达细胞间黏附分子１（ＩＣＡＭ－ｌ）及其相关核转录途径的影响。方法 用ＨＫ－２细胞作靶细胞，用细胞酶联免疫吸附法（ＥＩＪＳＡ）和Ｎｏｒｔｈｅｒｎ杂交观察ＩＣＡＭ－１的蛋白和基因的表达，以电泳迁移率变动法测定转录因子核因子ｋＢ （ＮＦｋＢ）和激活蛋白 Ｉ（ＡＰ－１）的活性。结果ＴＮＦα呈剂量依赖地诱导ＨＫ－２细胞ＮＦｋＢ的活化及ＩＣＡＭ－１的基因和蛋白表达，这些作用可以被ＮＦｋＢ的抑制剂对甲苯磺－Ｌ－苯丙氨酸氯甲基甲酮（ＴＰＣＫ）所抑制，但ＴＮＦα对ＨＫ－２细胞的ＡＰ－１活性无影响。 ＩＬ－１０（１～ ２０ｎｇ／ｍｌ）可抑制 ＴＮＦα诱导的 ＨＫ－２细胞 ＩＣＡＭ－ｌ基因和蛋白表达及 ＮＦｋＢ的活化。结论ＴＮＦα诱导人肾小管上皮细胞ＨＫ－２的ＮＦｋＢ活化，进而促进ＩＣＡＭ－ｌ基因和蛋白表达，ＩＬ－１０可抑制ＴＮＦα诱导的上述炎症效应。     

体外循环对风心病瓣膜替换病人细胞免疫功能的影响

对２５例风湿性心脏病（ＲＨＤ）换瓣病和５例先天性心脏病（ＣＨＤ）病人体外循环（ＣＰＢ）前后外周血自然杀伤细胞（ＮＫ）和抗体依赖细胞毒细胞（ＡＤＣＣ）活性、Ｔ细胞亚群、白细胞介素２（ＩＬ－２）和γ－干扰素（ＩＦＮ－γ）产生能力进行动态对照研究。结果表明：ＮＫ、ＡＤＣＣ活性、ＯＫＴ４细胞、ＩＬ－２和ＩＦＮ－γ产生能力于术后下降，以ＲＨＤ组中心功能Ⅲ级和双瓣替换为著。文中对上述指标下降原因及临床意义进行     

白细胞介素－6在老年女性原发性骨质疏松症发病中的作用

为探讨白细胞介素－６（ＩＬ－６）在老年女性原发性骨质疏松症（ｏｓｔｅｏｐｏｒｏｓｉｓＯＰ）发病中的作用，本文采用ＩＬ－６依赖性细胞株ＭＨ６０．ＢＳＦ增殖反应ＭＴＴ法检测了３０例老年女性骨质疏松性骨折患者和２４例正常者以及１４例健康绝经前女性外周血单核细胞培养上清（ＰＢＭＣ）ＩＬ－６水平以及血清雌激素（Ｅ２）、骨钙素（ＢＧＰ）等水平的变化。结果：绝经后妇女ＩＬ－６水平高于绝经前，而ＯＰ组又高于ＮＯＰ组。以ＯＰ组ＩＬ－６为因变量的多元回归分析发现：ＩＬ－６与年龄无明显相关关系，与前臂骨密度（ＢＭＤ）和Ｅ２呈负相关，与ＢＧＰ和尿钙与尿肌酐比值（Ｃａ／Ｃｒ）呈正相关。结果提示老年女性骨丢失属于高转换型，雌激素水平减少使分泌ＩＬ－６细胞活化，ＩＬ－６分泌增多，从而刺激骨吸收，骨吸收超过骨形成就会导致ＯＰ的发生     

体外循环手术前后病人血清sIL-2R水平和T淋巴细胞亚群、NK细胞的变化及临床意义

目的：通过检测心脏体外循环（ＣＰＢ）手术前后病人血清中可溶性白介素２－受体（ｓＩＬ－２Ｒ）、Ｔ细胞亚群、自然杀伤细胞（ＮＫ），观察分析心脏ＣＰＢ手术病人细胞免疫的影响及其临床意义。方法：选择２４例风心病择期换瓣病人，术前、ＣＰＢ１０分钟、ＣＰＢ２小时、术后第１天、３天、５天检测血清ｓＩＬ－２Ｒ水平、Ｔ细胞亚群及ＮＫ细胞活性。术后第１天血清ｓＩＬ－２Ｒ水平升高，ＣＯ４（辅助细胞）活性明显降低，ＣＤ４／ＣＤ８（辅助细胞／抑制细胞）比值下降，ＮＫ活性降低；并且ｓＩＬ－２Ｒ与ＣＤ４、ＮＫ活性呈负相关。结论：低温心脏ＣＰＢ手术对病人免疫机能有不良影响，临床应采取相应措施，改善术后病人的免疫机能。     

维持性血液透析患者T淋巴细胞对外源性IL－2的增殖反应

报告１８例维持性血液透析（ＭＨＤ）患者Ｔ淋巴细胞对外源性白细胞介素－２（ＩＬ－２）的增殖反应。结果显示：ＭＨＤ患者Ｔ淋巴细胞对外源性ＩＬ－２的增殖反应较正常对照组明显下降（Ｐ＜０．００１）。与单次血透前比较，单次血透后ＭＨＤ患者的Ｔ淋巴细胞对外源性ＩＬ－２的增殖反应虽有明显提高（Ｐ＜０．０５），但仍显著低于正常对照组（Ｐ＜０．０１）。     

胸腔肿瘤患者围术期外周血NK活力血浆SIL－2R表达水平的动态监测

对２１例胸腔恶性肿瘤和８例胸腔良性肿瘤二组患者围术期作ＮＫ细胞活力、血浆ＳＩＬ－２Ｒ表达水平的动态监测结果表明：胸腔恶性肿瘤患者ＮＫ细胞活力明显低于良性肿瘤组（Ｐ＜０．０５），血浆ＳＩＬ－２Ｒ表达水平明显高于良性肿瘤组（Ｐ＜０．００１）；二组患者在术始２～３小时ＮＫ活性均明显升高，术后３～５天则显著回落，而ＳＩＬ－２Ｒ水平则表现为一反向变化。结果提示胸腔恶性肿瘤患者抗肿瘤免疫功能严重受损；术中ＮＫ细胞活性一过性升高可能对手术操作引起的肿瘤细胞播散有遏制作用，但术后免疫功能的抑制对防止肿瘤的复发和转移是不利的，应引起重视     

白细胞介素—6在老年女性原发性骨质疏松症发病中的作用

为探讨白细胞介素－６（ＩＬ－６）在老年女性原发性骨质疏松症（ＯＰ）发病中的作用，本文采用ＩＬ－６依赖性细胞株ＭＨ６０．ＢＳＦ增殖反应ＭＴＴ法检测了３０例老年女性骨质疏松性骨折患者和２４例正常者以及１４例健康绝经前女性外周血单核细胞培养上清（ＰＢＭＣ）ＩＬ－６水平以及血清雌激素（Ｅ２）、骨钙素（ＢＧＰ）等水平的变化。结果：绝经后妇女ＩＬ－６水平高于绝经前，而ＯＰ组又高于ＮＯＰ组。以ＯＰ组ＩＬ－６为因     

Immunological findings in patients with superficial bladder cancer during human alpha-2-interferon treatment

6 patients with recurrent high grade superficial bladder cancer were treated with human recombinant alpha-2-Interferon (alpha 2-IFN). After initial transurethral electroresection of macroscopically visible tumor, human recombinant alpha 2-IFN was administered by daily intramuscular injections for a period of 6 weeks. The influence of IFN on the patients' immune reactivity was assessed by determination of the natural killer (NK) cell activity. Within the first week, in all the patients an increase of the NK cell activity was noted. This, however, was only a short-term effect. An increase of the IFN dosage did not lead to further NK cell stimulation. Determination of the IFN serum levels during IFN treatment revealed maximum levels of 260 IU/ml. They were measured 2 weeks after therapy begin. During treatment no further increase of IFN serum levels were found. The augmentation of the NK cell activity does not seem to depend on IFN serum levels. The amount of IFN found in patients' sera did not effect tumor cell growth in vitro.     

The response to interferon of NK and K cells from conventionally immunosuppressed and cyclosporine-treated renal allograft recipients

Interferon is a potent stimulator of natural killer (NK) and killer (K) cell activity in human beings, both these cytotoxic functions representing host defense mechanisms against viral infections and lymphoid malignancy. Both NK and K cell functions are markedly impaired in conventionally immunosuppressed allograft recipients but coincubation of lymphocytes from these patients with purified human lymphoblastoid interferon considerably augments both these activities. Cyclosporine immunosuppression causes only a moderate, but significant, impairment of NK activity--but K cell activity appears to be normal. Again IFN increases NK activity of the lymphocytes of these patients but produces a fall or only moderate increases in K cell activity. We conclude that these data support the functional distinction between NK and K cells and suggest that immunosuppressive agents act at the pre-NK/K cell stage of maturation, though possibly via different mechanisms.     

Natural killer cell subsets in long-term renal allograft recipients. A phenotypic and functional study

Natural Killer cell subsets were studied in 39 long-term renal allotransplant recipients receiving conventional immunosuppression and 26 normal controls. Two-color flow cytometry analysis was used to determine coexpression of 2 surface antigens known to allow a phenotypic and functional discrimination of NK cells--Leu-7 a marker of large granular lymphocytes, and Leu-11c directed against the FcgammaR. In 11 patients and controls, these NK cell subsets were compared with actual NK activity assessed by killing of K562 target cells. Our data clearly show that, in long-term kidney recipients, the absolute number of NK cells (Leu-11c+) is significantly decreased compared with that of the control group. Furthermore, the most cytotoxic NK cell subset (Leu-7-/Leu-11c+ phenotype) is markedly diminished in the transplant population, whereas the less cytotoxic subset (Leu-7+/Leu-11c+) is unchanged. Finally, actual NK cell activity closely correlates with both relative and absolute numbers of these 2 NK cell subsets. These data provide convincing evidence that NK activity is impaired in long-term kidney recipients because of a diminished number of NK effector cells.     

Negative effect of uraemia and cuprophane haemodialysis on natural killer cells

The evidence indicating the important role of natural killer (NK) cells in immune surveillance against tumours and certain infections is accumulating. Uraemic and dialysed patients are known to be at greater risk of infections and malignant diseases. NK cells were analysed in patients with advanced uraemia, and in patients treated with different dialysis techniques. Number of NK cells was morphologically identified as large granular lymphocytes in blood smears. NK activity was determined as mononuclear cell cytotoxicity against K562 cells. In a group of uraemic patients, large granular lymphocyte number was reduced to 39%, and NK activity to 41%-52% of control values. Large granular lymphocyte number and NK activity in patients haemodialysed on cuprophane membranes was significantly reduced, compared to corresponding values in controls and uraemic patients, declining to 17% and 8%-16% of respective control values. In a group of patients treated by CAPD, and in a group haemodialysed on polyacrylonitrile membranes, NK activity was close to values in the uraemic group, but significantly greater than those of cuprophane-haemodialysed patients. Haemodialysis on cuprophane membranes has an additional negative effect on NK cells, which are already seriously depressed by the uraemic state.     

Single agent therapy of interferon for brain tumours: Correlation between natural killer activity and clinical course

Summary The anti-tumour effect of mouse interferon (IFN) on an intracranially transplanted 203-glioma in C 57 BL mice and the natural killer (NK) activity of spleen cells were studied. As a clinical trial, five patients with glioblastomas were treated with human fibroblast IFN and the anti-tumour effect of IFN and the NK activity of peripheral blood lymphocytes were also studied. The NK activity increased after the beginning of IFN therapy but there was no remarkable antitumour effect of IFN in both mouse and human studies. There was no marked correlation between the increased NK activity and the anti-tumour effect of IFN in this study.     

The characterization of peritoneal and pleural exudate cells from malignant effusions

The immune function of peripheral blood cells and cells from the pleural and abdominal effusions of patients with advanced cancer was compared to that of peripheral blood cells from controls. The parameters examined included lymphocyte subsets, natural killer (NK) cell activity, and anti-Daudi and lymphokine-activated killer (LAK) cell activity. The percentage of CD4⁺ pleural and peritoneal exudate cells (PEC) was significantly higher than the percentage of peripheral blood mononuclear cells (PBMC) in the patients. The percentage of CD8⁺CD11⁺ PEC and PBMC, being the suppressor T-cells, of the patients was increased compared with controls, while the percentage of CD8⁺CD11^– PEC, being the cytotoxic T-cells, was identical to the PBMC of both patients and controls. The NK activity of PEC was significantly lower than that of PBMC in both patients and controls, and there was no correlation between the NK activity of PBMC and PEC. Although the anti-Daudi activity of PEC was markedly low, LAK cells with high activity could be induced by culture with interleukin-2 for 4 days. These results suggest that the immune function of cells in malignant effusions may be depressed due to a low population of cytotoxic T cells, low NK activity and increased suppressor T cells, while the local administration of interleukin-2 may induce LAK cells. Therefore, effective local immunotherapy for malignant effusions should not only augment effector cells, but also inhibit supprssor cells.     

Physical activity levels in patients on hemodialysis and healthy sedentary controls

BACKGROUND: Patients on dialysis have reduced exercise tolerance compared with age-matched sedentary controls. The reasons for this debility have not been fully elucidated, but physical inactivity could be a contributing factor. The purpose of the current study was to determine whether patients on hemodialysis are less active than healthy sedentary controls and to explore clinical correlates of physical activity level in a group of hemodialysis patients. METHODS: Thirty-four hemodialysis patients and 80 healthy sedentary individuals participated in the study. Physical activity was measured for seven days with a three-dimensional accelerometer and with an activity questionnaire. RESULTS: Vector magnitude values from the accelerometer for the dialysis and control subjects were 104,718 +/- 9631 and 161,255 +/- 6792 arbitrary units per day, respectively (P < 0.0001, mean +/- SEM). The estimated energy expenditure values derived from the questionnaire were 33.6 +/- 0.5 kcal/kg/day and 36.2 +/- 0.5 kcal/kg/day (P = 0.002). The difference between patients on dialysis and controls increased with advancing age. Among the dialysis subjects, some measures of nutritional status correlated with physical activity level, including serum albumin concentration (r = 0.58, P = 0.003), serum creatinine concentration (r = 0.37, P = 0. 03), and phase angle derived from bioelectrical impedance analysis (r = 0.40, P = 0.02). CONCLUSIONS: Patients on hemodialysis are less active than healthy sedentary controls, and this difference is more pronounced among older individuals. There is an association between the level of physical activity and nutritional status among patients on dialysis. These findings are of great concern, given the trend toward increasing age in incident dialysis patients and the well-known association between inactivity and increased mortality in the general population.     

Influence of interferon alfa-2c on the kinetics of spontaneous cell-mediated cytotoxicity in Urothelial carcinoma in vivo and in vitro

Summary It was demonstrated that patients with superficial bladder cancer displayed a raised spontaneous cellmediated cytotoxicity (SCMC) compared to patients with advanced bladder cancer and healthy control subjects. By use of recombinant interferon alfa-2c, the activity of the spontaneous cell-mediated cytotoxicity at the level of the individual cell could be increased both in vitro and in vivo. In vitro, this was the case in patients with superficial bladder cancer as well as in patients with advanced bladder carcinoma, and in healthy control subjects. The kinetics of cytolysis were not affected by recombinant human interferon (rHu IFN) alfa-2c. After in-vivo application of rHu IFN, there was an elevation of the target binding cells (TBC) and the number of active natural killer (NK) cells within 24 h, but this was only detected for a brief period of time.     

Preliminary trial of nonrecombinant interferon alpha in recurrent squamous cell carcinoma of the head and neck

Fourteen patients with recurrent squamous cell carcinoma of the head and neck (SCCHN) were treated with 10 x 10(6) U of nonrecombinant interferon alpha (IFN) intramuscularly (IM) daily for 3 days every 28 days. There were 11 men and 3 women, with ages ranging from 48 to 74 years. Patients had previously been treated with surgery (9 patients), radiotherapy (13 patients), or chemotherapy (8 patients). All patients had measurable disease by physical exam and radiologic evaluation and a performance status of less than or equal to 2 (ECOG). Patients were treated for a minimum of 3 months and continued on therapy until disease progression. The dose and treatment schedule of IFN was well-tolerated. Toxicities included low-grade fever, mild anorexia, and malaise. Treatment was stopped in 1 patient due to the development of atrial fibrillation. One death occurred as a complication of aspiration pneumonia 2 weeks following the onset of therapy and was not felt to be related to IFN therapy. Of the 14 patients treated, there was 1 complete response (30+ months) of a base of tongue primary. Two patients had stabilization of disease (SD, 8 and 12 months). One patient had a mixed response with resolution of subcutaneous nodules. The remaining 10 patients died of progressive disease. Immunological assessment was performed on 8 patients. The 1 patient who had a complete response was noted to have markedly low pretreatment natural killer (NK) cell activity and a subsequent sharp rise in activity after initial treatment. We conclude that low-dose cyclic IFN is well-tolerated in patients with recurrent SCCHN and has potential antitumor activity.     

BCG灌注对外周血免疫细胞的调节及其功能的影响

应用单克隆抗体免疫组化，细胞培养及放免分析方法对３４例膀胱癌患者ＢＣＧ灌注前后外周血免疫细胞的构成，Ｔ细胞转化水平、刺激指数、ＮＫＣ活性，ＩＬ－２诱生与活性进行了比较研究。结果表明，ＢＣＧ灌注能有效的提高外周血免疫细胞构成与活性功能。在Ｔ刺激指数、转化水平及ＮＫＣ活性调节中Ｔ４细胞数量及Ｔ４／Ｔ８比值及ＩＬ－２活性水平起重要作用。实验结果显示，ＢＣＧ灌注的抗肿瘤活性可能是细胞介导的局部免疫与宿主免疫系统功能增强的共同结果。