Bcl—2蛋白在64例大肠癌中的分析

本文采用流式细胞术（ＦＣＭ）研究了Ｂｃｌ－２蛋白在大肠癌中的表达。结果显示肿瘤的Ｂｃｌ－２蛋白表达量（１．３１±０．４１）明显高地正常粘膜细胞（１．０±０．１５），Ｐ〈０．００１；粘液腺癌、腺刺细胞癌和低分化腺癌的Ｂｃｌ－２蛋白表达量（１．４５±０．２１）高于中分化腺癌（１．３１±０．２２），Ｐ〈０．０５；低分化腺癌的Ｂｃｌ－２蛋白表达量（１．４８±０．０８），高于中、高分化腺癌（１．３１±０．２     

全身性非特异性免疫反应对大鼠睾丸功能的影响——睾丸形态学的变化

本实验以ＳＤ雄性大鼠为实验对象，采用血管内注射碳粒的方法，给动物造成一种全身性的非特异性免疫反应状态，以观察在此免疫反应情况下动物睾丸的生精功能有何变化。动物经每天１次共１０次的注射，实验组动物血白细胞计数（４．０９×１０４±１．２２×１０４／ｍｍ３）明显高于对照组（１．５８×１０４±０．４１×１０４／ｍｍ３，Ｐ＜０．００１）。此时实验组动物的睾丸呈不同程度的萎缩或充血，睾丸重量（０．６５１±０．１０２ｇ／１００ｇ体重）明显低于对照组（０．７９３±０．１６２ｇ，Ｐ＜０．０５）。镜下观察可见实验组动物睾丸内有的曲细精管生精细胞发生选择性脱落，生精上皮内生精细胞常呈现错位排列；另有的小管生精上皮细胞呈空竭状态或管内所有的细胞均发生固缩。此时睾丸间质内的细胞数量却明显增多。作者认为碳粒注射诱发的全身性非特异性免疫反应可以给睾丸的生精功能造成损害，这种影响可能是通过多种途径实现的。     

精子与宫颈粘液相互作用在预测宫颈性不育的价值

为了解精子与宫颈粘液相互作用预测生育的价值，对２７例不明原因不孕妇女进行性交后试验（ＰＣＴ）和精子穿透试验（ＳＭＰＴ）。１年后按有无妊娠分为妊娠组（ｎ＝１４）和非妊娠组（ｎ＝１３）。两组宫颈粘液评分无显著性差异（Ｐ＞０．０５）；妊娠组在性交后２和４小时精子数（１９．３±３．３及２２．２±４．４个／Ｈｐ）明显高于非妊娠组（５．０±２２及２．９±１．４个／Ｈｐ）（Ｐ＜０．０１）；妊娠组ＰＣＴ正常率（７１％）明显高于非妊娠组（０％），（Ｐ＜０．０１）；ＳＭＰＴ结果与ＰＣＴ结果基本一致。提示ＰＣＴ是有价值的预测生育指标，ＰＣＴ正常可排除男方因素及宫颈性不孕，ＰＣＴ异常则可选择人工授精提高妊娠率     

全身性非特异性免疫反应对大鼠睾丸功能的影响──Ⅱ.激素水平的变化

本实验以ＳＤ雄性大鼠为实验对象，采用碳粒血管内注射的方法，给动物造成一种全身性的非特异性免疫反应状态，以观察在这种状态下睾丸和垂体的激素分泌情况。动物经每天１次，共１０天的碳粒鼠尾静脉注射后，血浆睾酮的水平（０．８９６±０．３５８ｎｇ／ｄｌ，ｎ＝５）明显低于对照组（２．６５６±０．９９３ｎｇ／ｄｌ，ｎ＝７，Ｐ＜０．００５）；血浆ＬＨ（３．６７６±１．３５０ｍＩＵ／ｍｌ，ｎ＝９，４．６２７±２．５３９ｍＩＵ／ｍｌ，ｎ＝１０）两组比较无显著差异（Ｐ＞０．０５）；ＦＳＨ实验组（３．３６２±０．９２６ｍＩＵ／ｍｌ，ｎ＝９）与对照组相比明显降低（４．８９４±１．２３６ｍＩＵ／ｍｌ，ｎ＝１０，Ｐ＜０．０１）。实验组动物睾丸间质内ＡＣＰ阳性反应细胞增多，而β－羟基甾体脱氢酶反应消失。作者认为全身性的免疫反应既可以通过垂体也可以直接的作用于睾丸内的相关细胞，从而影响睾丸的功能。     

颈椎病，腰椎间盘突出症与血浆血管紧张素Ⅱ关系研究

目的：探讨脊柱退变性疾病体液因素的改变及其意义。方法：利用放免测定法对２３例健康成人和４０例颈椎病，腰椎间盘突出症患者血浆血管紧张素Ｉ（ＡｎｇＩ）含量进行了检测分析。结果：患者组血浆ＡｎｇＩＩ含量为６９１±３２５ｐｇ／ｍｌ，显著高于正常（Ｐ＜０００１）；其中颈椎病为６８７±３４７ｐｇ／ｍｌ（ｘ＋ｓｄ），腰椎间盘突出症患者为７０１±３１５ｐｇ／ｍｌ（ｘ＋ｓｄ），均显著高于正常，而两者之间无显著差异（Ｐ＞００５）结论ＡｎｇＩ分泌的增加是机体交感神经纤维的兴奋效应，并对这一效应的意义作了探讨。     

生精固本丸对小鼠免疫功能的影响

Ｐ＜０．０１结果如表２所示，生精固本丸在２．５ｇ／ｋｇ、５ｇ／ｋｇ、１０ｇ／ｋｇ的剂量体内用药，对ＣｏｎＡ诱导的小鼠的Ｔ细胞的增殖反应有增强作用，而对ＬＰＳ诱导的小鼠Ｂ细胞的增殖反应效果不显著。香菇多糖是已知的免疫增强剂，生精固本丸与之相比作用相似。２．３生精固本丸对小鼠游泳耗竭的影响结果见表３。表３生精固本丸对小氧游泳耗竭的影响注：与对照组相比＊Ｐ＜０．０５，Ｐ＜０．００１结果表明，动物给药５ｇ／ｋｇ、１０ｇ／ｋｇ，连用４ｄ，游泳耗竭时间分别为１５．１±３．５及３５．０±５．３ｍｉｎ，与对照组相比均有显著性差异，表明本品具有较强的抗疲劳作用。而给药２．５ｇ／ｋｇ时，与对照组相比则无明显差异，提示本品具有明显的量效关系。     

多囊卵巢综合征患者外周血生长激素水平测定

为了解多囊卵巢综合征肌（ＰＣＯＳ）患者生长激素（ＧＨ）水平，对２１例（肥胖１０例，非肥胖１１例）ＰＣＯＳ患者进行外周血ＧＨ测定，并以２６名（肥胖１２名、非肥胖１４名）正常月经周期妇女作对照。结果：（１）ＰＣＯＳ患者ＧＨ含量（肥胖组０．９１±０．３５ｐｇ／Ｌ，非肥胖组１．３４±０．４９μｇ／Ｌ）较相应正常对照组（肥胖组１．８６±０．５８μｇ／Ｌ，非肥胖组２．１１±０．８８μｇ／Ｌ）降低（Ｐ＜０．０１，Ｐ＜０．０５）。（２）ＰＣＯＳ患者肥胖组较非肥胖组ＧＨ明显降低。认为ＰＣＯＳ患者伴ＧＨ相对不足，可能与下丘脑生长抑素活性、肥胖和高胰岛素血症有关     

异丙酚对冠状动脉旁路术病人术前血流动力学的影响

目的和方法：对１９例择期冠状动脉旁路术病人麻醉诱导前各静注异丙酚１～２ｍｇ／ｋｇ（１．７ｍｇ／ｋｇ），观察其后２、４、８ｍｉｎ血流动力学效应。结果：用药后２ｍｉｎ平均动脉压（Ｐ＜０．００１）、肺动脉压（Ｐ＜０．００２）、外周血管阻力（Ｐ＜０．００１）、心每搏量（Ｐ＜０．０５）、每搏指数（Ｐ＜０．０２）和左心室搏出功指数（Ｐ＜０．００１）均比对照组降低非常显著；由于心率明显增快（Ｐ＜０．００１），故心输出量和心脏指数无改变。上述各血流动力学参数至４ｍｉｎ已恢复至对照值。结论：异丙酚扩张血管、降低外周阻力，从而短暂降低血压，用于冠状动脉旁路术的麻醉时，应依病人年龄、ＡＳＡ等选择剂量。     

大鼠胰腺生长抑素含量与结肠癌的关系

用放射免疫测定，动态观察大鼠结肠癌产生过程中胰腺生长抑素样免疫活性物（ＳＬＩ）的含量变化。结果：结肠癌组ＳＬＩ含量为５．９９±０．３１（ｎｇ／ｍｇ蛋白），明显高于粘膜乳头增生组（３．５６±０．０８）和正常对照组（１．８１±０．０７）Ｐ＜０．０ｌ）；结肠癌中管状腺癌组ＳＬＩ高于粘液腺癌组（Ｐ＜０．０１）；癌肿浸润达深肌层或浆膜层时ＳＬＩ含量明显低于粘膜层或浅肌层（Ｐ＜０，０１）；有淋巴转移组ＳＬＩ含量明显低于无淋巴转移组（Ｐ＜０．０１）。     

门静脉内注射PVA制作犬肝内型门脉高压症模型

杂交犬１４只，采用门静脉插管法，门脉内反复注射聚乙烯醇（ＰＶＡ），３个月后制成肝纤维化门脉高压症动物模型，出现脾大、腹水、食管静脉曲张等表现，门静脉造影显示门一体侧枝循环大量形成，病理检查显示肝细胞变性、坏死，肝纤维化形成。实验前后，分别测定门静脉压为９４．５±９．１ｍｍＨ２Ｏ（０．９３±０．０９ｋｐａ）和３０５．８±５７．９ｍｍＨ２Ｏ（３．００±０．５７ｋｐａ）（Ｘ±ｓ，ｎ＝１０，提示门脉高压症形成后，门脉压力明显升高（Ｐ＜０．００１）。结果与肝硬化门脉高压症临床表现相一致。为进一步研究肝内型门脉高压症发病机制提供了极为理想的动物模型。     

Th1/Th2 balance and CD45-positive T cell subsets in primary nephrotic syndrome

T cells are involved in the pathogenesis of nephrotic syndrome (NS). The aim of the study was to determine whether the activity of T-helper-1 (Th1) and T-helper-2 (Th2) cells and the distribution of the lymphocyte subsets, namely CD45RA+CD4+ (”naive” helper T cells, suppressor-inducer), CD45RA+CD8+ (”naive” suppressor T cells, suppressor-effector), CD45RO+CD4+ (”memory” helper T cells), are predictive for steroid sensitivity in children with primary NS. These parameters were assessed at the onset of disease, before initiation of steroid therapy. Two groups of NS children were retrospectively formed according to steroid sensitivity (SS) or resistance (SR). The activity of Th1 and Th2 cells was defined by the production of interleukin-2 (IL-2), interferon-γ, IL-4, and IL-10 in the supernatants of CD4+ T cell cultures activated with autologous monocytes presenting tetanus toxoid (TT). Peripheral lymphocyte subsets were determined using double- or triple-color flow cytometry. In SS children with NS we found a decreased proliferative response of CD4+ T cells to TT stimulation, cytokine synthesis indicating the predominance of Th2 activity, and an increased percentage of activated suppressor-inducer (CD45RA+ CD4+CD25+, 5.18±0.8, P<0.001) and suppressor-effector (CD45RA+CD8+CD25+, 2.05±0.6, P<0.01) cells, with the concomitant reduction of activated memory cells (CD45RO+CD4+CD25+, 0.2±0.1, P<0.001). In children with SRNS we found an increased proliferative response of CD4+ T cells to TT, a rise in activated memory (CD45RO+CD4+CD25+, 3.82±0.7, P<0.01) and suppressor-inducer peripheral T cells (CD45RA+ CD4+CD25+, 3.85±0.6, P<0.01), but a low percentage of activated suppressor-effector (CD45RA+CD8+ CD25+, 0.5±0.2, P<0.05) T cells. We conclude that prior to treatment the distribution of lymphocyte subpopulations in peripheral blood together with Th1 and Th2 cell activity provides a useful tool for evaluating the likelihood of steroid sensitivity in patients with primary NS. Received: 3 November 1998 / Revised: 1 September 1999 / Accepted: 8 September 1999     

Th1/Th2 balance in childhood idiopathic nephrotic syndrome

AIMS: In view of the conflicting evidence of helper T cell type 1 (Th1) or type 2 (Th2) pattern of cytokine synthesis in childhood idiopathic nephrotic syndrome (INS) this study examined the balance of Th1 and Th2 which are characterized by intracellular cytokine production of interferon-gamma (IFNgamma) and interleukin-4 (IL-4), respectively. SUBJECTS AND METHODS: Sixteen children with steroid-sensitive INS (mean age 9.0 years) were included in this study, together with 15 healthy normal children (mean age 7.9 years) for the control group. Intracellular production of both IFNgamma and IL-4 in helper T cell (CD4+ cell) was investigated by a 3-color flow cytometry. RESULTS: The cross-sectional data showed no significant differences of percentages of Th0 (IFNgamma+ IL-4+ CD4+ cell), Th1 (IFNgamma+ lL-4- CD4+ cell) and Th2 (IFNgamma- IL-4+ CD4+ cell) in CD4+ cells (p > 0.05). The Th1/Th2 ratio during nephrotic relapse did not differ from those during nephrotic remission and in normal healthy children (p > 0.05). CONCLUSION: We conclude that there is no significant skew of Th1/Th2 balance in childhood INS and that the cardinal immunological abnormality does not lie in helper T cells but in other cells, such as suppressor/cytotoxic T cells, natural killer cells or monocytes/macrophage. To clarify the pathogenesis of INS, comprehensive studies for these cells would be worthwhile.     

T-cell activation follows Th1 rather than Th2 pattern in haemodialysis patients.

BACKGROUND: Patients on chronic intermittent haemodialysis (HD) show an impaired cellular and humoral immune response that clinically appears with frequent infectious complications and low vaccination responses. This immune defect strongly correlates with reduced in vitro proliferative responses of T cells. The defect is localized in antigen presenting cells, which show a decreased co-stimulatory activity. Furthermore, the impaired immune response correlates with an increased production of pro-inflammatory cytokines. In response to primary activation, CD4 positive T helper (Th) cells mainly differentiate into either Th1 or Th2 cells. Th1 cells support cell mediated immunity whereas Th2 cells enhance humoral immune responses. Since both types of responses mutually inhibit each other, the impaired humoral immune response seen in HD patients could either be due to a reduced number of Th2 cells or to a predominant Th1 response. METHODS: We analysed the Th cell profile in HD patients using flow cytometry. Monocytic cytokine expression was analysed using both flow cytometry and enzyme linked immunoadsorbant assays. RESULTS: Our data demonstrate that the cytokine differentiation profile in circulating T cells from HD patients is dysregulated and characterized by an increase in Th1 cells, but a normal amount of Th2 cells. Moreover, the skewed helper cell responses correlate with a higher percentage of monocytes capable of secreting the Th1 promoting cytokine interleukin 12 (IL-12). CONCLUSIONS: Our findings contribute to a better understanding of the pathogenesis of impaired cellular immune functions in dialysis patients and, in particular, the decreased antibody production after vaccination. They provide a link between overproduction of pro-inflammatory cytokines (IL-12) and imbalanced T-cell activation.     

Characteristic cytokine products of Th1 and Th2 cells in hemodialysis patients.

Dysfunction of the host defense against infection in hemodialysis (HD) patients has major clinical and socioeconomic implications. T helper type 1 (Th1) and type 2 (Th2) cytokines are implicated in regulating the immune responses and, therefore, may be involved in impaired status. The present study was designed to examine Th1 and Th2 cytokine profiles in 22 stable HD patients (aged 63 +/- 11 years) and 22 healthy controls (aged 60 +/- 6 years). The T cell activity was significantly retarded in HD patients as compared with normal persons. The proportions of T cytotoxic/suppressor cells and natural killer cells were significantly higher in HD patients than in controls. In contrast, the proportions of T helper/inducer and B cells were significantly lower in HD patients than in controls. The production of interleukin (IL) 2, which is involved in cell-mediated immune responses, and the production of IL-4 and IL-10, which affect humoral immunity, were significantly lower in patients than in controls. The production of IL-12 by macrophages and of interferon gamma by Th1 cells was significantly higher in HD patients than in controls. The concentration of plasma sIL-2R was significantly higher in patients than in controls. These results suggest that both cellular immunity induced by Th1 and humoral immunity induced by Th2 decrease in HD patients, but that improved IL-12 secretion by macrophages activated natural killer cells to produce interferon gamma, which in turn induced macrophage activity.     

调节性及辅助性T细胞在人类IgA肾病中的表达及意义

目的 探讨CD4+CD25high调节性T细胞（Treg）及辅助性T细胞亚群（Th1、Th2）比例失衡在IgA肾病（IgAN）免疫发病机制中的作用。 方法 用流式细胞仪检测IgAN患者外周血Treg及Th1、Th2的比例。以胞内染色技术检测叉头框蛋白3（FOXP3）的表达。Treg及Th1、Th2的比例与IgAN各项临床病理指标的相关性分析采用Spearman或Pearson相关分析法。 结果 IgAN患者外周血中Treg比例明显高于健康人[（2.14±0.82）％比（1.59±0.53）％，P ＜ 0.05]，与血IgA水平呈正相关（r = 0.397，P ＜ 0.05），与eGFR呈负相关（r = -0.376，P ＜ 0.05）。IgAN患者外周血中Th2细胞比例显著高于健康对照组[（2.57±0.72）％比（1.81±1.10）％，P ＜ 0.05]，与血IgA水平呈正相关（r = 0.468，P ＜ 0.05）。IgAN患者Th1/Th2比值显著低于健康对照组（5.75±1.89比12.73±9.79，P ＜ 0.05），但与临床各指标间没有相关性。 结论 IgAN患者体内存在T细胞亚群表达紊乱。Treg在外周血中的增多以及以Th2为优势的Th1/Th2失衡可能在IgAN的发病中起重要作用。     

卵巢早衰患者血清抗透明带抗体和肿瘤坏死因子-α、γ-干扰素及白细胞介素-2的分析

目的 :探讨抗透明带抗体 ( Azp Ab)和肿瘤坏死因子 -α( TNF-α) ,γ-干扰素( IFN-γ)及白细胞介素 -2 ( IL-2 )在卵巢早衰 ( POF)发病中的作用及其临床意义。方法 :以定量酶联免疫吸附试验 ( EL ISA)测定 POF患者血清中 Azp Ab水平 ,放射免疫测定 IFN-γ、IL-2和 TNF-α的水平。结果 :POF组 Azp Ab明显高于正常对照组 ( P<0 .0 0 1 ) ,TNF-α和 IL -2显著降低 ( P<0 .0 0 1 ) ,IFN-γ明显升高 ( P<0 .0 1 )。 POF患者中 ,Azp Ab阳性组 ,以上三种细胞因子水平均明显高于 Azp Ab阴性组。结论 :Azp Ab,TNF-α,IFN-γ和IL-2在自身免疫性 POF的发病中起着重要作用。     

Th2 cytokine profile in infants predisposes to improved graft acceptance after liver transplantation

BACKGROUND: The T helper cell type 1 (Th1) cytokines interleukin (IL)-2 and interferon (IFN)-gamma are mediators of acute graft rejection after liver transplantation and Th2 cytokines, such as IL-4 and IL-10, may have a protective role and correlate with graft acceptance. To test the hypothesis that infants aged <1 year have an immunological advantage with regard to graft acceptance because of a partially immature immune system with a physiological balance toward a Th2 cytokine profile, we conducted the present study. METHODS: We compared the T helper serum cytokine profiles in 105 infants and children after liver transplantation with or without acute graft rejection and analyzed the normal age-distributed concentrations of T helper cytokines in 51 healthy controls. RESULTS: The incidence of acute graft rejection was as follows: 0 to 12 months, 26.8%; 1 to 3 years, 40.0%; and >3 years, 71.8%. There was a significantly lower incidence of acute rejection in infants 0 to 12 months of age compared with children >1 year (11/41 vs. 38/64; P=0.001). In healthy infants, significant increasing Th1 cytokine concentrations and decreasing Th2 cytokine concentrations were found with increasing age. Patients with acute rejection had significantly higher values of Th1 cytokines compared with nonrejecting subjects, who had significantly higher concentrations of Th2 cytokines. A longitudinal analysis of serum cytokines from patients showed that changes of the cytokine patterns in the follow-up did not differ significantly from preoperative values, except in the 4 weeks posttransplant. CONCLUSIONS: We conclude from the data that the physiological balance toward a Th2 cytokine profile of infants in the first months of life predisposes to improved graft acceptance. Transplantation of children with biliary atresia as early as possible, avoiding Th1 stimulation by recurrent infections and vaccinations, may have a positive impact on overall tolerance.     

Predominant Th1 and Cytotoxic Phenotype in Biopsies from Renal Transplant Recipients with Transplant Glomerulopathy

Transplant glomerulopathy (TGP) appears to be a pathogenic feature of chronic antibody-mediated rejection, but the pathogenesis of this histologic entity is still poorly understood. Previous studies suggest the involvement of lymphocytes but the phenotypes of these cells have never been analyzed. Here, we report the first study of mRNAs for specific markers of CD4+ T cells including Th1 (T-bet and INFγ), Th2 (IL4 and GATA3), Treg (Foxp3) and Th17 (IL-17 and RORγt) subsets, cytotoxic CD8 T cells (Granzyme B) and B-cell markers (CD20) in renal biopsies from renal transplant recipients suffering interstitial fibrosis and tubular atrophy (IF/TA) with or without TGP but with a similar inflammatory score and controls including transplant recipients with normal renal function. Only INFγ, T-bet (both functionally defined markers of Th1 CD4 T cells) and granzyme B (a CD8 cytotoxic marker) were significantly more strongly expressed in patients with TGP than in patients without TGP and normal controls. These results indicate a role of an active T-mediated inflammatory and cytotoxic process in the pathogenesis of TGP.     

Cyclosporine A Drives a Th17‐ and Th2‐Mediated Posttransplant Obliterative Airway Disease

Calcineurin‐inhibitor refractory bronchiolitis obliterans (BO) represents the leading cause of late graft failure after lung transplantation. T helper (Th)2 and Th17 lymphocytes have been associated with BO development. Taking advantage of a fully allogeneic trachea transplantation model in mice, we addressed the pathogenicity of Th cells in obliterative airway disease (OAD) occurring in cyclosporine A (CsA)‐treated recipients. We found that CsA prevented CD8⁺ T cell infiltration into the graft and downregulated the Th1 response but affected neither Th2 nor Th17 responses in vivo. In secondary mixed lymphocyte cultures, CsA dramatically decreased donor‐specific IFN‐γ production, enhanced IL‐17 production and did not affect IL‐13. As CD4⁺ depletion efficiently prevented OAD in CsA‐treated recipients, we further explored the role of Th2 and Th17 immunity in vivo. Although IL‐4 and IL‐17 deficient untreated mice developed an OAD comparable to wild‐type recipients, a single cytokine deficiency afforded significant protection in CsA‐treated recipients. In conclusion, CsA treatment unbalances T helper alloreactivity and favors Th2 and Th17 as coexisting pathways mediating chronic rejection of heterotopic tracheal allografts.     

血栓痔病人外周血Th1／Th2分析

为探讨血栓痔发病与T淋巴细胞活化及释放的Th1／Th2细胞因子失衡状态的关系,对32例血栓痔（实验组）和30例健康人（对照组）的外周血单个核细胞（PBMC）,经PMA诱导培养后,用流式细胞术测定CD3^＋标记T细胞内自细胞介素-4（IL-4）和干扰素-γ（IFN-γ）含量和CD8^-标记T细胞内IL-4和IFN-γ的含量,进行比较分析,从而估计Th1／Th2细胞的漂移状态。结果显示,实验组的IL-4和IFN-γ含量均显著高于对照组（P〈0．001）;且实验组IL-4^＋含量高于IFN-γ含量（P〈0．05）。结果表明,血栓痔病人发病时,体内的T淋巴细胞免疫系统被激活,且以Th2细胞为主,这种Th1／Th2细胞因子失衡可能在血栓痔发病过程中起到重要作用。