The effect of TGFβ1 on murine tumor growth following direct intratumoral injection of plasmid DNA

In order to investigate TGFβ1 gene expression and its effect on murine tumor growth following direct intratumoral injection of naked plasmid DNA encoding human TGFβ1, LM₃ murine lung adenocarcinoma cells were inoculated subcutaneously to T₇₃₉ mice and grew to tumor nodules in 2 weeks. Multiple direct intratumoral injection of plasmid DNA, PMAMneo- TGFβ1, were given and compared with saline or vector plasmid administration groups. The growth of tumor was observed till the 8th week when the mice were killed for Northern blot analysis and histopathological study of tumoral tissue. The results showed that the growth of tumor was boosted in the TGFβ1 gene treated mice as compared with the control groups, whereas there was no significant difference in the metastatic behavior. Northern blot showed efficient expression of TGFβ1 mRNA in the treated group. The present study indicated that TGFβ1 may stimulate tumor growthin vivo through certain mechanisms. And direct intra-tumoral injection of nude plasmid DNA may be a promising gene transfer strategyin vivo. This work was supported by the National Natural Science Foundation of China (No. 39370761).     

大鼠原位肝移植及术后肝细胞超微结构观察

用５１只Ｗｉｓｔａｒ大鼠建立了新的大鼠原位肝移植手术模型,手术成功率为９２．１％,周存活率为８６．２７％。手术要点是术前供肝冷灌注;受体肝只建立门静脉血供,静脉吻合分别采用“双袖套”式吻合和“８”字外翻缝合;胆管重建采用单管支架总胆管对端吻合法。移植术后肝细胞超微结构动态观察表明：术后２周是控制免疫排斥反应的关键时期,术后８周实验鼠产生免疫耐受性,移植肝脏成活。     

12-Lipoxygenases and 12(S)-HETE: role in cancer metastasis

Arachidonic acid metabolites have been implicated in multiple steps of carcinogenesis. Their role in tumor cell metastasis, the ultimate challenge for the treatment of cancer patients, are however not well-documented. Arachidonic acid is primarily metabolized through three pathways, i.e., cyclooxygenase, lipoxygenase, and P450-dependent monooxygenase. In this review we focus our attention on one specific lipoxygenase, i.e., 12-lipoxygenase, and its potential role in modulating the metastatic process. In mammalian cells there exist three types of 12-lipoxygenases which differ in tissue distribution, preferential substrates, and profile of their metabolites. Most of these 12-lipoxygenases have been cloned and sequenced, and the molecular and biochemical determinants responsible for catalysis of specific substrates characterized. Solid tumor cells express 12-lipoxygenase mRNA, possess 12-lipoxygenase protein, and biosynthesize 12(S)-HETE [12(S)-hydroxyeicosatetraenoic acid], as revealed by numerous experimental approaches. The ability of tumor cells to generate 12(S)-HETE is positively correlated to their metastatic potential. A large collection of experimental data suggest that 12(S)-HETE is a crucial intracellular signaling molecule that activates protein kinase C and mediates the biological functions of many growth factors and cytokines such as bFGF, PDGF, EGF, and AMF. 12(S)-HETE plays a pivotal role in multiple steps of the metastatic cascade encompassing tumor cell-vasculature interactions, tumor cell motility, proteolysis, invasion, and angiogenesis. The fact that 12-lipoxygenase is expressed in a wide diversity of tumor cell lines and 12(S)-HETE is a key modulatory molecule in metastasis provides the rationale for targeting these molecules in anti-cancer and anti-metastasis therapeutic protocols.     

大鼠三叉神经本体觉中枢传导通路的电生理学证明

近年来形态学上发现了三叉神经领域本体感觉中枢通路,在此基础上,本文用电生理学方法,通过电刺激咬肌神经和压下颌,观察了由四级神经元组成的此通路的二级（三叉神经脊束核吻侧亚核背内侧部及邻接的网状结构）、三级（沿三叉神经感觉主核内缘存在的“带状区”）中继核团以及作为最后驿站的丘脑腹后内侧核等处的单位放电反应;另外又分别刺激或损毁二、三级中继核团,观察了丘脑腹后内侧核的单位放电变化,结果证明电刺激咬肌神经和压下颌,在上述核团都出现对本体觉冲动反应的单位放电,包括兴奋性反应单位、抑制性反应单位和无关单位三种类型,以兴奋性单位为主,占神经元单位放电总数的５２．９％～６７．７％．分别刺激二和三级神经元的所在核团,在丘脑腹后内侧核处发生相应的单位放电效应;损毁二和三级核团,本体觉传入冲动被阻断。本研究结果从电生理学上确证了形态学上发现的三叉神经本体感觉中枢通路的客观存在,从定性研究方面支持了定位研究的结果,并填补了以往生理学上只证明初级传入核团与丘脑腹后内侧核之间存在着一条多突触联系的本体觉传递通路但未能判断其具体行径和中继部位的空白,本研究并对方法论以及一些有关问题进行了讨论．     

Crystal Structure of 2-Debenzoyl, 2-Acetoxy Paclitaxel (Taxol®): Conformation of the Paclitaxel Side-Chain

Crystals of the C2-acetate analog of paclitaxel, grown from a mixture of isopropyl alcohol and methanol, belong to the space group P2_l with a = 9.058(3), b = 18.306(5), c = 15.043(1) , = 97.09(1)°, Z = 2, V = 2475.1(9)³, D _calc = 1.269 gcm^–3 and µ = 0.75 cm^–1. The structure was determined by direct methods and refined to R(F) = 0.054 and wR(F) = 0.057 for 605 variables and 3496 observed reflections. The paclitaxel side chain possesses a conformation similar to that observed in the crystal structure of docetaxel (Taxotere^®). A three dimensional network of hydrogen bonds is formed through solvent molecules and stabilizes the crystal lattice.     

Use of Drug Kinetics in Dermis to Predict in VivoBlood Concentration After Topical Application

Purpose. To use the drug kinetics in dermis to predict the in vivo blood concentration after topical administration. Methods. A two-step pharmacokinetic model was established. The first step was to calculate the drug input rate or flux from the skin to the systemic circulation using the drug kinetic parameters in dermis. These parameters include (a) distance over which the drug concentration declines by 50%, (b) drug concentration at the epidermal-dermal junction, and (c) minimal plateauing drug concentration in the muscle layer. These parameters were experimentally determined from the drug concentration-tissue depth profiles in the dermis, after the application of a topical dose of ddI (200 mg/kg) to rats. The second step was to use the drug input rate together with the systemic disposition pharmacokinetics of ddI in rats to predict the plasma concentration-time profiles. The model-predicted plasma concentration-time profiles were compared with the observed profiles, to determine the validity of the proposed pharmacokinetic model. Results. The observed steady state concentration (C_ss) in individual animals (n = 6) deviated from the predicted values by 3 to 55% with 3 of 6 rats showing a <15% deviation. The mean observed C_ss of all animals deviated from the mean predicted values by less than 15%. Conclusions. The close agreement between the observed and the model-predicted drug concentrations indicates that the systemic drug input can be calculated from the drug kinetics in the dermis.     

106例肺切除术分析

1982年3月～1994年12月,我们为各类肺部疾病进行肺切除术106例。术中、术后发生并发症23例次占21．6％,术后30日内死亡2例占1．8％．文内着重对支气管胸膜瘘、血胸、肺血管损伤大出血、癌栓脱入对侧肺支气管、肺静脉癌栓脱入股动脉及心跳聚停等并发症的防治及紧急处理进行了讨论。此外,作者认为,肺叶切除术目前在大多数病例仍是肺癌外科的“标准术式”,但在心肺功能允许并由于技术或肿瘤学原因非行全肺切除术才能达到根治性切除时,就要果断地行全肺切除,心包外处理肺血管有困难时,要毫不迟疑地采取心包内途径。     

总粉尘浓度转换为呼吸性粉尘浓度的两种方法学研究

目的探讨流行病学研究中历史性总粉尘浓度转换成呼吸性粉尘浓度的理论方法。方法采用两种方法：一种通过体积直接计算;另一种用ＨａｔｃｈＣｈｏａｔｅ方程计算,推导出计数百分比和计量百分比的转换关系。结果得到总粉尘浓度与呼吸性粉尘浓度的理论转换系数,其中,用ＨａｔｃｈＣｈｏａｔｅ方程计算结果偏低。结论体积直接计算法更适用。     

北京地区啮齿动物种类和地理分布调查

目的：了解北京地区啮齿动物种类和地理分布。方法：依据历年积累资料、标本、文献记载及近几年实地调查。结果：有２７种啮齿动物,隶属于２目５科１７属及４种生态类型、５种不同水热型。结论：北京地区啮齿动物的分布随生态类型和水热型不同而有所不同。     

儿童肥胖与高血压关系的研究

目的了解儿童肥胖与高血压的关系.方法运用病例对照研究的方法,在包头市小学生中对161对单纯性肥胖儿童及其相应对照进行了研究.结果单纯性肥胖儿童的收缩压、舒张压和高血压患病率均显著高于对照组.肥胖儿童中,肥胖程度越重,高血压患病率越高.结论在儿童时期,预防、控制肥胖是降低高血压及心血管疾病发生的重要措施.