p38丝裂原活化蛋白激酶信号级联在炎症反应中的作用

在急、慢性疾病中，细胞释放的炎症介质可以活化多种信号转导级联反应，丝裂原活化蛋白激酶(MAPK)信号转导通道在招募白细胞于炎症部位聚集起着重要的作用。同时，p38MAPK异构体的活化可以激活致炎细胞因子，而后刺激白细胞活化。然而，p38MAPK引起的白细胞招募这一系列的功能过程包括：粘附、游走和效应器的功能如氧化爆发以及p38MAPK介导的复杂细胞因子网络在炎症中的作用仍有待研究。针对减少炎症介质产生和以p38MAPK为治疗靶点的研究正在进行中，不远的将来可能会成为治疗炎症疾病的新策略。     

血管通透性的调节和游离微血管技术在其研究中的应用

Vascular hyperpermeability is a cardinal feature of inflammation or bum in which an array of inflammatory mediators can cause such changes in the microvessels. The fimctional measures of microvascular exchange that represent the properties of microvascular wails are the permeability coefficients which have been reported from measurements on intact whole organisms (including human subjects}, on perfused tissues and organs, on single perfused microvessels, and on monolayers of cultured microvascular endothelial cells. In this review, we summarize some experiments of vascular permeability in individually isolated perfused microvessels.     

Raf-1 kinase,epidermal growth factor receptors,and mutant ras proteins in colonic carcinomas

Epidermal growth factor receptors (EGFR) andras mutations are known to play a significant role in controlling cell growth and tumor promotion. Both of them transmit mitogenic signals to the nucleus by activation of Raf-1 kinase. In this study, the expression of EGFR and mutant Ras proteins, and, for the first time, the expression, phosphorylation and kinase activity of Raf-1 kinase have been determined in paired samples of colorectal cancer and mucosa. The tumor and mucosa samples did not differ significantly with regard to Raf-1 kinase content and activity. A major difference between tumors and mucosa was found, however, in the phosphorylation of Raf-1. Most of the mucosa samples (13/20), but only 1/20 of the cancer samples, contained hyperphosphorylated Raf-1. EGFR were significantly (p=0.0025) decreased in the tumors. The decreased phosphorylation of Raf-1 in colonic carcinomas could be the result of activation of Raf-1 phosphatases or inactivation of kinases phosphorylating Raf-1. New forms of treatment based on EGFR overexpression do not seem to be suitable for the majority of colonic cancers.This work was supported by the state of Baden-Württemberg (Verbundforschungsprojekt: Aufklärung von Mechanismen der Tumorentstehung und Tumorabwehr).     

外源性三磷酸腺苷对肾小管上皮细胞增殖的影响

观察外源性三磷酸腺苷（ＡＴＰ）对肾小管上皮细胞株ＬＬＣＰＫ１增殖的影响。方法通过测定３Ｈ－胸腺嘧啶掺入、细胞计数以及细胞内丝裂素活化蛋白激酶活性，并与表皮生长因子（ＥＧＦ）的作用比较。结果发现ＡＴＰ呈浓度依赖性促进细胞的ＤＮＡ合成，并可使细胞计数增加，同时激活细胞内的丝裂素活化蛋白激酶，其作用与ＥＧＦ相似。腺苷与ＡＴＰ有类似作用，但较弱。核苷酸转运蛋白抑制剂对４－硝基苯６－硫基甙并不能抑制ＡＴＰ及腺苷的作用。结论细胞外ＡＴＰ可促进肾小管上皮细胞增殖，并可增强ＥＧＦ的促增殖作用，这一作用可能是通过膜受体介导的细胞内丝裂素活化蛋白激酶活化而实现的     

房室折返性心动过速RP‘时距的特征及对旁道定位的意义

应用食管调搏，检测６４例旁道参与的房室折返性心速患者Ⅰ、Ⅱ、Ⅴ１和食管导联的室房时距、Ｐ＇ｖ，Ｐｅｔ时距。发现左侧ＡＰ者ＲＰ＇１较ＲＰ＇Ｖ１短（Ｐ＜０．０１），而右侧ＡＰ时较ＲＰ＇ｖ１长（Ｐ＜０．０１）。     

细胞内钙信号的变化调节血管平滑肌细胞增殖

目的探讨细胞内钙信号的变化对大鼠血管平滑肌细胞(VSMC)增殖作用的影响及其对细胞内信号转导机制的变化。方法以培养的大鼠VSMC为模型,用雷尼丁(RY)剌激VSMC内贮Ca2 释放入胞浆,用3H亮氨酸及3H胸腺嘧啶掺入量作为反应VSMC增殖的指标,加入不同的细胞内信号转导阻断剂,观察对RY效应的影响。结果与对照组相比,RY浓度依赖性地促进细胞内游离钙浓度的增高,差异显著(P<0.05或0.01)。RY剌激组蛋白核酸合成速率明显增高,与对照组相比差异显著(P<0.01);尼卡地平(Nicardipine),蛋白激酶C抑制剂(H7),钙调素激酶(CaMPK)抑制剂(W7)和丝裂素活化蛋白激酶(MAPK)抑制剂(PD98059)能明显抑制RY介导的VSMC蛋白核酸合成速率增高,与RY剌激组相比差异显著(P<0.01)。结论细胞内钙信号的变化明显促进VSMC增殖,但其效应可能通过Ca2 、PKC、MAPK来介导。钙离子拮抗剂可抑制血管平滑肌细胞增殖。     

上矢状窦旁脑膜瘤致上矢状窦阻塞时侧支静脉通路的意义

目的 分析上矢状窦旁脑膜瘤致上矢状窦(SSS)阻塞时其侧支静脉通路的建立情况，确定其在肿瘤切除术中的意义。方法 总结归纳86例上矢状窦旁脑膜瘤行MRA及DSA检查时的静脉系表现。结果 27例发生SSS完全阻塞，59例部分阻塞。18例在阻塞的SSS周围出现了由表浅皮层静脉所形成的侧支静脉环；通过表浅皮层静脉与蝶顶窦及小脑幕静脉系建立端—端吻合的16例；通过与Troland或Labbe静脉建立吻合的14例；通过大脑镰与下矢状窦吻合的9例；通过脑膜静脉并经板障静脉引流到颈外静脉系的17例；混合型12例。结论 上矢状窦旁脑膜瘤致SSS阻塞时，肿瘤周围存在广泛侧支静脉通路，术中应注意保护。脑DSA及MRA检查对术前了解SSS通畅性及侧支静脉通路建立有帮助。     

磷脂酶C与生殖

磷脂酶C(PLC)是磷脂酰肌醇信号转导途径中一个关键酶。目前确认的哺乳类PLC共有PLC β、PLC γ、PLC δ、PLC ε和最近新发现的PLC ζ 5种亚型 ,12种同工酶。不同亚型的结构、调控和组织分布各有差异。PLC在调控信号转导通路中的特性使其在顶体反应、卵子激活中发挥了巨大的作用。本文综述了PLC家族 5种亚型的结构、调控机制及PLC在男性生殖领域的相关内容 ,包括PLC引起卵子发生Ca2 + 振荡、激活卵子、促进胚胎发育等 ,并进一步探讨了PLC在临床上可能的应用前景。     

Singularities explained: Response to Klein.

Klein [Klein, A. S. (2006). Separating transducer nonlinearities and multiplicative noise in contrast discrimination. Vision Research, 46, 4279-4293] questions the existence of intrinsic singularities in two-alternative force-choice (2AFC) Signal Detection Theory (SDT) models, suggesting that the singularities found in Katkov et al. [Katkov, M., Tsodyks, M., & Sagi, D. (2006a). Singularities in the inverse modeling of 2AFC contrast discrimination data. Vision Research, 46, 259-266; Katkov, M., Tsodyks, M., & Sagi, D. (2006b). Analysis of two-alternative force-choice Signal Detection Theory model. Journal of Mathematical Psychology, 50, 411-420] are due to discarding higher order terms in the Taylor expansion of d' and/or limited to steep psychometric functions. Here we provide some simple intuitive examples that illustrate the results described in Katkov et al. (2006a, 2006b). We show, for the constant noise model, that singularities exist when exact values of d' are computed and that the singularities are not limited to steep psychometric functions. In these cases the disambiguation of the different models requires millions of trials.