多发性硬化患者中IL-12和孕酮的检测及其临床意义

目的检测IL-12和孕酮在多发性硬化(MS)患者中的水平,探讨男、女性多发性硬化患者存在的发病机制,比较男、女性MS患者在临床上发病的差异。方法采用酶联免疫(ELISA)法检测60例MS患者的脑脊液和40例患者血液中IL-12的水平,应用放射免疫法测定40例MS患者血液中孕酮的含量,并与40例正常对照组比较(以上标本男女各半)。结果男、女性MS患者血液中和脑脊液IL-12的含量明显高于正常对照组(P<0.01);女性患者血液中孕酮的含量明显低于正常对照组(P<0.01),男性患者血液中孕酮的含量与正常对照组差别不明显(P>0.05);女性患者血液中孕酮对IL-12的含量存在负相相关作用(r=-0.80,P<0.01),男性相关作用不明显(r=-0.38,P>0.05)。结论IL-12参与多发性硬化的发病过程;孕酮可能是男、女性患者发病差异性的原因之一。     

重组人白细胞介素10的融合表达及鉴定

目的 研究重组人白细胞介素10(rhIL—10)载体在大肠杆菌B121(DE3)pLyse细胞中的表达，为进一步研究IL-l0在动脉粥样硬化中的作用机制奠定基础。方法 用构建成功的IL-l0—PCRT7/NT-TOPO质粒转化大肠杆菌BL21(DE3)pLyse细胞，并通过SDS-PAGE鉴定融合表达蛋白。结果 PCRT7/NT—TOPO质粒载体成功载入rhIL-l0基因；在异丙基硫代—β-D-半乳糖苷(IPTG)诱导下表达的蛋白质主要以包涵体形式存在。结论 在IPTG诱导下，重组的IL-l0—PCRT7/NT—TOPO质粒载体在大肠杆菌BL2l(DE3)pLyse细胞内成功表达。     

IMMUNOREGULATORY EFFECT OF PANAXATRIOL GINSENOSIDE ON IMMUNE FUNCTIONS IN BONE MARROW SUPPRESSED MICE

The effect of Panaxatriol Ginsenoside (PTGS) on Immune functions in bone marrow suppressed mice induced by injection of cyclophosphamide (CY) has been studied. Bone marrow suppressed mice were made by injection of CY (150 mg/kg) parenterally. Subcutaneous injection of PTGS three days earlier partially restored the number and the activity of bone marrow cells, significantly enhanced the production of IL-1, IL- 3 and IL- 6 like substances and promoted the reactivity of murlne spleen cells to Con-A In bone marrow suppressed mice.     

白细胞介素—2胸腔灌注治疗恶性胸水24例临床分析

恶性胸腔积液能严重影响病人的呼吸循环功能,加速病人死亡。本文对24例恶性胸腔积液病人给予白细胞介素—2(IL-2)胸腔灌注治疗,取得了明显效果。其总有效率(完全缓解率 部分缓解率)较对照组有显著性差异(P<0.05),该作者认为该疗法治疗效果肯定,副作用轻,具有推广应用价值。     

Expansion of CD3+CD56+ lymphocytes correlates with induction of cytotoxicity by interleukin-2 gene transfer in human breast tumor cultures

Background: Mice immunized with murine mammary carcinoma cells genetically engineered to secrete interleukin-2 (IL-2) are rendered resistant to subsequent challenge with unmodified tumor cells, and in the case of mice bearing established tumors, the rate of development of pulmonary metastases is reduced. Despite these encouraging animal results, little is known about the induction of antitumor immunity by IL-2 gene transfer in human breast cancer. Methods: Adenovirally mediated IL-2 gene transfer was performed in 12 tumor fragment cultures established from seven primary breast cancers. Autologous tumor infiltrating lymphocytes (TILs) or peripheral blood mononuclear cells (PBMCs) were cocultured with transduced tumor fragments, and changes in phenotype and cytotoxicity were measured. Results: IL-2 was never detectable in the untransduced cultures, but it peaked at 5.0—1,324.8 ng/ml in the transduced cultures. Lymphocyte counts declined in all untransduced cultures, but they increased two- to sevenfold in four transduced cultures. CD4:CD8 ratios decreased from a mean of 2.11 at baseline to 1.27 after stimulation in coculture (p=0.03). Expansion of lymphocytes expressing the natural killer cell phenotype (CD3⁻CD56⁺) occurred in only one culture, but the CD3⁺CD56⁺ population increased in four of six cultures. Lymphocytes from four of 10 cocultures generated significant cytotoxicity against allogeneic breast cancer cells. Induction of cytotoxicity correlated with expansion of the CD3⁺CD56⁺ phenotype (R²=0.805, p=0.02). Conclusions: IL-2 gene expression by human breast cancer causes expansion of CD3⁺CD56⁺ cytotoxic lymphocytes. This phenotype is consistent with that of a non-major histocompatibility complex (MHC)-restricted cytokine induced killer cell population previously described. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the U.S. Army. Presented at the 49th Annual Cancer Symposium of The Society of Surgical Oncology, Atlanta, Georgia, March 21–24, 1996.     

白细胞介素—2新的功能位点及其中枢镇痛作用

白细胞介素－２（ＩＬ－２）不仅是重要的免疫调节因子，而且还具有重要的中枢调节作用。本实验以钾离子透入引起大鼠甩尾反应为指标，发现侧脑室注射ＩＬ—２能显著提高动物痛阈，并能被纳洛酮所阻断，表示ＩＬ－２的中枢镇痛作用可能与阿片受体有关。利用基因定位突变技术获得的无免疫活性ＩＬ－２实查体仍具有中枢镇痛作用，表明ＩＬ—２分子上发挥镇痛和免疫调节作用的功能位点是相互独立的。纳洛酮能够阻断ＩＬ—２的中枢镇痛作用，而不能影响ＩＬ—２增殖ＣＴＬＬ－２细胞的作用，提示ＩＬ－２发挥镇痛和免疫调节作用可能通过不同的受体途径。ＩＬ－２分子中第４５位Ｔｙｒ残基突变为Ｖａｌ后，虽仍保留了免疫活性，但丧失了镇痛功能，表示４５位Ｔｙｒ残基是ＩＬ—２发挥中枢镇痛功能的关键残基之一。我们推测ＩＬ—２的镇痛功能位点可能在ＩＬ—２分子中第４５位Ｔｙｒ残基附近区域。     

Effect of interleukin-8 on glomerular sulfated compounds and albuminuria

To evaluate the effect of interleukin-8 (IL8) on glomerular basement membrane (GBM) sulfated compounds and albuminuria, we infused IL8 in 1% bovine serum albumin (BSA) for 5 days into the left renal artery of Holtzman male rats at the rate of 10 μl/h using an osmotic pump. Control rats received 1% BSA. A significant increase in urinary albumin/creatinine ratio was seen on the last day of IL8 infusion (0.38±0.11, mean ± SEM) when compared with albumin/creatinine ratio prior to infusion (0.19±0.04, P = 0.04). No significant differences in urinary albumin excretion prior to and after infusion of 1% BSA were observed. On the last day of infusion, rats were injected with ³⁵sulfate (1.0 mCi/200 g body weight) intraperitoneally and killed after 8 h. Glomeruli were isolated and GBM obtained. After 5 days of IL8 administration, there was a significant increase in ³⁵sulfate uptake by GBM of the infused kidney (76±10 cpm/dry glomerular weight, mean ± SEM) compared with the uptake seen in the contralateral kidney (53±9, P = 0.05). The in vivo infusion of IL8 increased the ³⁵sulfate uptake by GBM and augmented the urinary albumin/creatinine ratio, suggesting that IL8 may induce albuminuria by altering the metabolism of the GBM sulfated compounds. This hypothesis needs to be confirmed by studies on glomerular charge selectivity and GBM anionic sites during the course of the infusion. Moreover, the persistence of the effect needs to be evaluated by prolonging the infusion for more than 5 days. Received June 3, 1996; received in revised form and accepted October 18, 1996     

The effects of maternal inflammation on neuronal development: possible mechanisms

That maternal inflammation adversely affects fetal brain development is well established. Less well understood are the mechanisms that account for neurodevelopmental disorders arising from maternal inflammation. This review seeks to begin an examination of possible sites and mechanisms of action whereby inflammatory cytokines - produced by the mother or by the fetal brain - could impact the developing fetus. We focus first on the placenta where cytokines maintain the immunological environment that prevents maternal rejection of the fetus. Following a brief examination of placental transfer of maternal cytokines, the focus turns on embryonic microglia, early and ubiquitous residents of the developing brain. Finally, a more intense examination of interleukin-6 (IL-6) and bone morphogenetic proteins (BMPs) provides examples of glial- or maternal-derived cytokines that are known to have profound effects on developing systems and that could, if dysregulated, have undesirable consequences for brain development.     

Frontotemporal dementia and parkinsonism linked to chromosome 17 with the N279K tau mutation

We present a case of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP‐17) harboring the N279K mutation in the MAPT gene from the family known as pallido‐ponto‐nigral degeneration (PPND). This 49‐year‐old man was followed for 17 years. He presented at age 41 years with left leg stiffness and en‐bloc turning. During the course of his illness he developed a constellation of symptoms including parkinsonism, pyramidal signs, vertical gaze palsy, dysphagia, dystonia, personality and cognitive dysfunction, weight loss and mutism. Gross neuropathological examination showed mild atrophy of the cerebral cortex, hippocampal formation, amygdala, thalamus, subthalamic nucleus and depigmentation of the substantia nigra. Microscopy revealed neuronal loss and gliosis in the same regions. Tau immunohistochemistry showed pretangles, numerous threads, grain‐like structures and oligodendroglial tau‐positive inclusions (“coiled bodies”). In the spinal cord the tau pathology was more abundant in gray than white matter. Pretangles and threads were present in the anterior and, to a lesser extent, in the posterior horns. FTDP‐17 should be suspected in patients with a history of familial parkinsonism combined with behavioral and cognitive changes, onset before age 65 years and an aggressive clinical course.     

溴环己胺醇预先给药对大鼠盐酸吸入性肺损伤的作用

目的 观察溴环己胺醇预先给药对大鼠盐酸吸入性肺损伤是否具有保护作用，并探讨其可能机制。方法30只健康 SD 大鼠，随机分成3组，A 组：生理盐水吸入组；B组：稀盐酸吸入组；C组：稀盐酸吸入 溴环己胺醇处理组，每组10只。C 组腹腔注射溴环己胺醇，1次/d，连续3d，A、B 组以等体积生理盐水代替。第3天注药后30min，B、C 组气管注入pH 值为1.25的稀盐酸1.2ml/kg，制成盐酸吸入性肺损伤模型，A 组气管注入生理盐水1.2ml/kg。观察注药后5h 动脉血气、氧合指数(PaO_2/FiO_2)、肺湿/干重比(W/D)、肺组织及血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-8(IL-8)水平。结果 与 A 组比较，B、C 组 PaO_2、PaO_2/FiO_2降低(P<0.01)，B、C 组W/D、B 组肺组织 TNF-α、IL-8含量、血清 IL-8浓度升高(P<0.01)。与 B 组比较，C 组 PaO_2、PaO_2/FiO_2升高(P<0.01)，C 组W/D、肺组织TNF-α、IL-8含量及血清 IL-8浓度降低(P<0.01)。结论 溴环己胺醇可能通过抑制 TNF-α、IL-8炎症因子的产生和释放机制对盐酸吸入性损伤肺产生保护作用。