17β-雌二醇对子宫内膜异位症患者在位子宫内膜间质细胞β-catenin mRNA和蛋白表达的影响

目的研究17β-雌二醇(17β-E2)对子宫内膜异位症(内异症)患者在位子宫内膜间质细胞β-catenin mRNA和蛋白表达的影响,探讨Wnt/β-catenin信号通路在介导雌激素促进内异症发生发展的作用。方法体外分离培养内异症患者在位子宫内膜间质细胞。用不同浓度17β-E2处理子宫内膜间质细胞48 h;此后选用10-10mol/L 17β-E2处理子宫内膜间质细胞12、24和48 h,逆转录聚合酶链反应(RT-PCR)和免疫印迹法(Western blotting)检测17β-E2处理前后子宫内膜间质细胞β-catenin mRNA和蛋白的表达水平。同法分析雌激素受体拮抗剂ICI182,780(10-6mol/L)对17β-E2促进β-catenin mRNA和蛋白表达的影响。免疫组织化学染色观察17β-E2作用后β-catenin在子宫内膜间质细胞中的定位。结果17β-E2能明显促进内异症患者在位子宫内膜间质细胞β-catenin mRNA和蛋白的表达,并呈剂量和时间依赖性,于10-10mol/L作用48 h最明显。雌激素受体拮抗剂ICI182,780能明显抑制17β-E2对子宫内膜间质细胞β-catenin mRNA和蛋白的表达。免疫组织化学染色发现17β-E2能促进β-catenin在子宫内膜间质细胞核内的表达。结论雌激素可能通过激活Wnt/β-catenin信号通路促进内异症在位子宫内膜的异位种植。     

Association between cord blood IgE and genetic polymorphisms of interleukin-4, the β-subunit of the high-affinity receptor for IgE, lymphotoxin-α, and tumor Necrosis factor-α

High cord blood immunoglobulin E (cbIgE) is known to be associated with increased risks of atopic diseases in childhood. The relationship between genetic polymorphisms and high cbIgE has not been well documented. A cross-sectional study was conducted to assess the association between cbIgE and genetic polymorphisms of interleukin (IL)-4 -590C/T, the beta-subunit of the high-affinity receptor for IgE (FcepsilonRI-beta) E237G, lymphotoxin (LT)-alphaNcoI alleles, and tumor necrosis factor (TNF)-alpha -308G/A. A total of 320 mother-neonate pairs were recruited from four maternity hospitals from different locations of Taiwan. Cord blood was obtained and assayed for cbIgE. Polymerase chain reaction followed by restriction fragment length polymorphism was used to assess the genotypes. Three hundred pairs of mothers and neonates were included in the final analysis. Infants with IL-4 -590 C allele were found to have higher risk of elevated cbIgE (> or =0.35 IU/ml, 24.3%) (p = 0.004). After adjusting for gender, birth order, maternal age, and history of allergic disease in maternal and paternal families, odds ratios for CC and CT genotypes were 4.41 and 3.16 (95% confidence interval 0.78-22.67, and 1.66-6.13), respectively, using TT genotype as reference. The genotypes of FcepsilonRI-beta, LT-alpha, and TNF-alpha were not associated with cbIgE before or after the adjustment. Our finding suggested a significant association of cbIgE with genetic polymorphism of IL-4 -590C/T, but not with the genotypes of FcepsilonRI-beta, LT-alpha, and TNF-alpha.     

Asymmetric dimethyl-arginine (ADMA) response to inflammation in acute infections.

BACKGROUND AND METHODS: The endogenous inhibitor of nitric oxide synthase (NOs) asymmetrical dimethyl-arginine (ADMA) has been implicated as a possible modulator of inducible NOs during acute inflammation. We examined the evolution in the plasma concentration of ADMA measured at the clinical outset of acute inflammation and after its resolution in a series of 17 patients with acute bacterial infections. RESULTS: During the acute phase of inflammation/infection, patients displayed very high levels of C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin and nitrotyrosine. Simultaneous plasma ADMA concentration was similar to that in healthy subjects while symmetric dimethyl-arginine (SDMA) levels were substantially increased and directly related with creatinine. When infection resolved, ADMA rose from 0.62 +/- 0.23 to 0.80 +/- 0.18 micromol/l (+29%, P = 0.01) while SDMA remained unmodified. ADMA changes were independent on concomitant risk factor changes and inversely related with baseline systolic and diastolic pressure. Changes in the ADMA/SDMA ratio were compatible with the hypothesis that inflammatory cytokines activate ADMA degradation. CONCLUSIONS: Resolution of acute inflammation is characterized by an increase in the plasma concentration of ADMA. The results imply that ADMA suppression may actually serve to stimulate NO synthesis or that in this situation plasma ADMA levels may not reflect the inhibitory potential of this methylarginine at the cellular level.     

Pharmacokinetics of the 13C labeled anticancer agent temozolomide detected in vivo by selective cross-polarization transfer

The anticancer agent temozolomide labeled with ¹³C (8-Carbamoyl-3-13C-methylimidazo-[5,1-d]-1,2,3,5-tetrazin-4-(3H)-one), was noninvasively detected in subcutaneous RIF-1 tumors by a selective cross polarization ¹³C NMR method, at a field strength of 9.4T. Pharmacokinetics of the drug, at a dose of 150 mg/kg, were determined for intravenous and intraperitoneal modes of administration (three animals per mode). The half-life of the drug in the tumors was approximately 60 min. The uptake and clearance of the drug, however, varied significantly between individual hosts, for both modes of administration. These results demonstrate the feasibility of obtaining pharmacokinetics of anticancer agents for individual tumors without the need for a label that might modify drug activity (e.g., fluorine). The variability of the in vivo measurements, even within the same tumor model, demonstrates the necessity of directly monitoring the tumor to evaluate drug pharmacokinetics.     

免疫抑制因子对佐剂关节炎的影响

目的；研究免疫抑制因子对佐剂关节炎发病的影响。方法：检测对照组与实验组对正常小鼠淋巴细胞转化的影响。结果：脑室注射ＩＬ１的关节炎大鼠在第０、７、１４、２８、３５ｄ的血清具有明显的抑制淋巴细胞转移化的作用。关节炎症状加重，病程延长。结论：免疫抑制蛋白可能参与佐剂关节炎的发病，有可能是造成关节炎的原因之一。     

Effects of interleukin-1α on platelet-derived growth factor release from bovine cerebral microvascular endothelial cells

ThepreviousworkofourlabshowedthatILlastimulatedtheproliferationofbovinecerebralmicrovascularsmoothmusclecells(BCMSMC);",butthemechanismremainsunknown.EarlierreportsshowedthatIL--1stimulatedendothelialcellstosecretesomefactorswhichweremitogenictothevascularsmoothmusclecells[2].Amongthosefactors,platelet--derivedgrowthfactor(PDGF)wasthemainone[3j.OurexperimentwasdesignedtoinvestigatetheeffectofPDGFonproliferationofbovinecerebralmicrovascularsmoothmusclecells(BCMSMC)stimulatedbyIL--la.…     

Inadequate Erythropoietin Response to Anaemia in HIV Patients: Relationship to Serum Levels of Tumour Necrosis Factor-Alpha, Interleukin-6 and Their Soluble receptors

Severe anaemia is a frequent complication in advanced HIV infection. In our study we investigated the interaction between cytokine network, HIV infection and erythropoietin (Epo) response with increasing anaemia levels. No correlations could be established between circulating tumour necrosis factor (TNF)-alpha and any of the examined parameters. However, a negative correlation was found between haemoglobin values and soluble TNF receptor levels (sTNF-R-I: r  = −0.54; P  < 0.001; sTNF-R II: r  = −0.47; P  < 0.001) as well as interleukin-6 levels ( r  = −0.29; P  < 0.001). In contrast, no significant increase in log[Epo], counterbalancing haemoglobin decline and paralleling the rise in sTNF receptors, was found. In patients classified as stage III, according to the Centers for Disease Control (CDC) classification, the erythropoietin response was significantly more impaired than in patients from CDC groups I and II ( P  < 0.001). The results of this study suggest that similar to its action in vitro , activation of the TNF/TNF-R system may impair erythropoietin production in HIV-associated anaemia. Due to the brief half-life of TNF-α, this activation is particularly reflected by elevations of soluble TNF receptor levels.     

Sensory neuropeptides are not directly involved in bronchial hyperresponsiveness induced by interleukin-8 in guinea-pigs in vivo

Background Interleukin-8 (IL-8) hus been shown to be a chemotactic factor for netitrophils, T-lymphocytes and eosinophils. Repeated intranasal administration of IL-8 enhances bronchial responsiveness to inhaled histamine in guinea-pigs. Neuropeptides which arc released trotn C-fibre nerve-endings have been postulated to induce bronchial hyperresponsiveness through neurogenic inflammation. Objective This study was conducted to examine whether sensory neuropeptides are involved in the IL-8-induced bronchial hyperresponsiveness. Methods IL-8 at a dose of 5μg/kg was administered intranasally to guinea-pigs twice a week for 3 weeks. One day after the last administration, animals were anesthetized and artificially ventilaled through tracheal cannula, and lateral pressure at the tracheal cannula (Pao) was measured as an overall index of airway responses lo increasing concentrations of inhaled histamine (25, 50, 100, and 200 μg/mL). A NKI and NK2 dual antagonist FK224(10mg/kg), a selective NK1 antgonist FK888 (10mg/kg) or vehicle was intravenously administered 10min before measurement of bronchial responsiveness. Result The IL-8 treatment significantly enhanced bronchial responsiveness to histamine (ANOVA P < 0.01). FK224 or FK888 did not alter the IL-8-induced bronchial hyperresponsiveness. Conclusion We conclude that repeated intranasal administratioti of IL-8 causes bronchial hyperresponsiveness (BHR) and that neuropeptides such as neurokinin A and substance P do not directly contribute to the development of BHR induced by IL-8.     

人IL-10基因重组复制缺陷型腺病毒DNA的构建

目的 构建人IL-10基因的重组腺病毒并进行体外表达和检测。方法从质粒pcDNA3IL-10的CMV启动子下游完整切下IL-10 cDNA的片段,将其定向插入Gateway载体,在克隆酶的作用下将阳性克隆质粒转入目的腺病毒载体。PacI酶线性化IL-10腺病毒DNA后阳离子质脂体转染293A细胞,获得人IL-10的复制缺陷型重组腺病毒。体外感染人胰腺癌细胞株Bxpc-3和大鼠胰腺细胞株AR-42J;Western blot检测人IL-10的表达。结果 成功地构建人IL-10重组腺病毒,病毒滴度达2×109PFU/mL。体外感染的细胞株均检测到IL-10的表达。结论 构建复制缺陷型重组腺病毒能够介导IL-10的基因表达,为细胞因子的抗炎冶疗奠定实验基础。     

羊水粪染与羊膜腔感染的关系

【摘要】 目的 :探讨羊水粪染与羊膜腔感染的关系。方法 :选择未临产且胎膜完整的剖宫产产妇 5 6例 ,根据术中所见羊水性状分为羊水清亮组、羊水Ⅰ～II度粪染组和羊水III度粪染组。于剖宫产术中取羊水用双抗体夹心ELISA法测IL 6含量 ,取胎盘胎膜做病理检查以了解有无炎性细胞浸润 ,并记录新生儿Apgar评分 ,观察产妇术后有无产褥感染。结果 :3组羊水中IL 6含量差异无显著性 ,3组胎盘标本病理检查示炎性细胞浸润之差异亦无显著性 ,而羊水粪染组新生儿窒息发生率较清亮组明显增加 (P <0 .0 5 )。结论 :羊水粪染尤其是III度粪染是胎儿窘迫的标志 ,而与羊膜腔感染无明显相关性。