大剂量卡铂化疗的药物毒性观察

6例肺癌患者接受了大剂量卡铂并自体骨髓移植治疗 ,卡铂剂量从 5 60～ 1375 mg/ m2 ,5例加用 VP～ 1630 0 mg,1例并用 MMC6mg和 VCR2 mg;主要毒性反应为白细胞、中性粒细胞、血小板减少和脱发 ( WHO毒性反应 ～ 级 )其次是贫血、皮肤粘膜出血、呕吐和可逆性肝功能损害 ,口腔粘膜溃疡及轻度发烧各 2例 ,一过性蛋白尿、室上性心动过速和便秘各 1例 ,尿素氮和肌酐未见升高 ;全部患者骨髓均获解救 ,从自体骨髓回输到骨髓造血功能重建成功平均 2 6.67( 17～ 32 )天     

尖吻蝮蛇毒引起类DIC病因的研究

本文借助 DEAE-sephadex A-50和 Sephadex G-75柱层析从尖吻蝮蛇毒(AAV)内分离并纯化出一种类凝血酶(TLE).这种 TLE 以1.5U/Kg 体重注入麻醉狗的静脉后,观察到血凝筛选试验 Fgn、BPC、PT、TT 和血清 FDP 全部异常;但凝血因子Ⅱ(Quick 二期法)、AT-Ⅲ以及纤维结合蚤白(Fn)含量仍在正常范围内.这提示实验狗血循环内未有凝血酶形成的证据,从而说明 AAV-TLE是 AAV 中毒患者并发类 DIC 综合征的主要病因.     

Anti-leukemia effect of perillyl alcohol in Bcr/Abl-transformed cells indirectly inhibits signaling through Mek in a Ras- and Raf-independent fashion.

PURPOSE: Perillyl alcohol (POH) displays preventive and therapeutic activity against a wide variety of tumor models, and it has been suggested that this might be associated with the ability of POH to interfere with Ras prenylation. POH also selectively induces G(1) arrest and apoptosis in Bcr/Abl-transformed hematopoietic cells. Because signaling through Ras is necessary for Bcr/Abl transformation, we examined whether POH induces its anti-leukemia effect by inhibiting Ras signaling. EXPERIMENTAL DESIGN: The ability of POH to inhibit posttranslational farnesylation and signaling from Ras as well as signaling through the Raf-Mek-Erk cascade was examined in Bcr/Abl-transformed and mock-transformed cells and related to the anti-leukemia effect of POH. RESULTS: POH does not affect Ras prenylation or Ras activity, but it blocks signaling downstream of Ras by reversing the state of activation of the Erk kinase, Mek. POH affects Mek activity only when it is added to intact cells. Treatment of either cell lysates or of purified Mek with POH has no effect on Mek activity. Inhibition of the Mek-Erk pathway seems to be related to the POH anti-leukemia effect for the following reasons: (a) the concentration of POH needed to block the Erk pathway, as well the kinetics with which POH inhibits this signaling cascade, both correlate with the anti-leukemia effect of POH; (b) both U0126 (a specific Mek inhibitor) and POH induce similar anti-leukemia effects; and (c) mock-transformed hematopoietic cells are simultaneously resistant to POH anti-leukemia effects and inhibition of the Mek-Erk pathway. CONCLUSION: Blocking Mek is sufficient to induce growth arrest and apoptosis in Bcr/Abl-transformed cells; therefore, POH represents a novel small molecule inhibitor of Mek that might be effective for treating Bcr/Abl leukemias.     

Ⅲ型、Ⅳ型胶原在慢性胰腺炎组织中的表达

目的检测Ⅲ、Ⅳ型胶原在CP及正常胰腺组织中的表达水平,研究其在胰腺间质纤维化形成中的作用。方法免疫组织化学方法检测16例CP标本及6例正常胰腺组织中Ⅲ、Ⅳ型胶原的表达。结果16例CP中,Ⅲ型、Ⅳ型胶原表达均为轻度以上深染,其中重度深染50%（8/16）,中度深染31.25%（5/16）;而正常胰腺组织Ⅲ、Ⅳ型胶原表达均为浅染。正常胰腺组织中Ⅲ、Ⅳ型胶原表达于基底膜、间质纤维、导管壁、血管壁,Ⅲ型胶原以间质纤维表达最明显,Ⅳ型胶原以基底膜表达最明显。CP组织中Ⅲ型胶原表达于基底膜、间质纤维、导管壁、血管壁,以间质纤维最明显;Ⅳ型胶原表达于基底膜、间质纤维、导管壁、血管壁,以基底膜最明显。结论Ⅲ、Ⅳ型胶原的表达增强在胰腺纤维化的形成中可能有重要作用。     

胸水CYFRA21-1、CEA及NSE联合测定对肺癌的诊断价值

目的　通过胸水CYFRA2 1 1(细胞角蛋白片段 )、CEA(癌胚抗原 )及NSE(神经烯醇化酶 )的检测 ,探讨各指标对肺癌诊断特异性及联合分析对肺癌的诊断价值和临床意义。方法　对 12 3例肺良性疾病组患者和 15 6例肺癌组患者胸水进行上述肿瘤标志物测定。将肺癌患者又根据病理类型分成腺癌组 (81例 )、鳞癌组 (5 0例 )、小细胞癌组 (12例 )和未定性癌组 (13例 )对各指标分别进行对照分析。结果　肺癌组胸水CYFRA2 1 1、CEA及NSE含量 (ng/ml)分别为 5 5 34± 37 44、5 7 11± 5 2 6 5及 16 99± 2 9 2 2 ,而肺良性疾病组的含量则分别为 9 0 8± 7 5 4、9 92± 6 2 8和 7 30±6 2 9,各指标的统计学检验均有极显著差异 (P <0 0 0 1)。CYFRA2 1 1在肺鳞癌组最高 ,与小细胞肺癌组相比有显著差异 (P <0 0 5 ) ,而与腺癌组和未定型癌组相比无显著差异 (P <0 0 5 ) ;CEA主要在腺癌组的含量均比其他肺癌组有极明显增高 (P <0 0 0 1) ;NSE则在小细胞癌组最高 ,其含量与其他肺癌组相比有极明显增加 (P <0 0 0 1)。结论　胸水CYFRA2 1 1,CEA及NSE在不同组织类型肺癌中的含量明显不同 ;三者联合测定对肺癌的诊断有重要的临床参考价值     

糖尿病合并冠心病的概述

从糖尿病合并冠心病的流行病学、病理基础、发病机理及临床、治疗五个方面论述了糖尿病合并冠心病的现代基础研究,并对其中西医结合治疗提出了方法.     

Effects of beta 1- and beta 1 + beta 2-antagonists on training-induced myocardial hypertrophy and enzyme adaptation

The effects of beta 1- and beta 1 + beta 2-antagonists on the myocardial adaptation to exercise training were investigated in male Sprague-Dawley rats randomly divided into trained (treadmill, 1 hr/day, 5 days/week for 10 weeks at 27 m/min, 15% grade) without drug (TC), sedentary without drug (SC), trained treated with atenolol (TA) (10 mg/kg body wt, i.p.), trained treated with propranolol (TP, 30 mg/kg body wt, i.p.), and sedentary propranolol. Doses of both beta-antagonists were titrated to decrease the exercise heart rate by 25% compared to the controls. The heart weight and heart/body weight ratio were significantly greater in TC (1.28 +/- 0.07 g (P less than 0.01); 296 +/- 12 mg/100 g body wt (P less than 0.05) respectively) than in SC (1.09 +/- 0.04 g and 268 +/- 11 mg/100 g body wt), or in TP and TA. Myocardial mitochondrial protein was unchanged by training or beta-blockade. Citrate synthase and beta-hydroxyacyl CoA dehydrogenase activities were not altered. Carnitine palmitoyltransferase activity was increased in SP compared to SC. Training increased hexokinase activity only in TC (5.22 +/- 0.12 vs 4.26 +/- 0.23 mumol/min/g wet wt, P less than 0.01). Lactate dehydrogenase activity increased significantly (P less than 0.01) in both TC (383 +/- 14 mumol/min/g wet wt) and TA (372 +/- 14 mumol/min/g wet wt) compared to SC (276 +/- 14 mumol/min/g wet wt), but not in TP versus SP. These data indicate that (1) beta-adrenergic blockade prevents training-induced cardiac hypertrophy; (2) beta-antagonists have little effect on the myocardial oxidative capacity; and (3) while the training induction of myocardial hexokinase is inhibited by both beta 1- and beta 1 + beta 2-antagonists, myocardium may increase its ability to utilize lactate during exercise with training despite beta 1-blockade.     

Poly(L-lysine)-g-poly(D,L-lactic-co-glycolic acid) micelles for low cytotoxic biodegradable gene delivery carriers.

Poly(lactic-co-glycolic acid) (PLGA)-grafted poly(L-lysine) (PLL) (PLL-g-PLGA) was synthesized to demonstrate its micelle-forming property in an aqueous solution. The micelles were used as a gene delivery carrier. The hydrodynamic diameter of PLL-g-PLGA micelles in an aqueous solution was ca. 149 nm with a narrow size distribution. Critical micelle concentration (cmc) was 9.6 mg/l. The PLL-g-PLGA micelles could be used to produce compact nanoparticulate complexes with plasmid DNA, which could efficiently protect the complexed DNA from enzymatic degradation by DNase I. The micelle/DNA complexes had highly compacted structure sized between 200-300 nm with a positive surface charge value. The PLL-g-PLGA micelles exhibited much higher transfection efficiency with lower cytotoxicity than PLL. Here, we demonstrated that biodegradable and cationic PLL-g-PLGA micelles could be used as an effective DNA condensation carrier for gene delivery system.     

在"医学教育国际标准研讨会"开幕式上的讲话

本次会议对经济全球化时代尤其是加入世界贸易组织之后,全面提升中国医学教育水平和质量,提高中国医学教育国际合作与竞争能力,具有十分重要的意义.要在国际竞争中立于不败之地,中国的高等医学教育必须增强紧迫感和危机感,加强国际交流与合作,加速高等医学教育国际化进程,积极研究并学习和借鉴医学教育国际标准,加快改革与发展,全面提高中国高等医学教育的综合实力.医学教育国际标准的引入,为我们重新审视和制定我国医学教育质量标准提供了十分有价值的参考.     

3-硝基三氮唑类衍生物体外放射增敏作用的生物学评价

探讨３－硝基三氮唑衍生物的放射增敏作用，并对其生物学效应作出评价。方法本文用克隆形成法研究了２２个３－硝基－１，２，４－三氮唑衍生物的体外放射增敏活性和乏氧、富氧细胞毒性。结果两个化合物的活性胜过ＭＩＳＯ，有三个化合物与ＭＩＳＯ和ＳＲ－２５０８相当，其余的其活性均较低。３－硝基三唑衍生物也像２－硝基咪唑类那样，其放射增敏活性与电子亲和性（用半波还原电位Ｅ１／２表示）有关。亲和性越大，即Ｅ１／２值越偏正，增敏活性越强。环核Ｎ１位和５位上取代基的结构和性质影响着化合物的Ｅ１／２、分配系数ｐ和细胞毒性。结论３－硝基三唑衍生物对乏氧和富氧（空气）细胞的毒性差别是很有限的，所以它们不是有效的乏氧调节细胞毒剂。但某些的放射增敏作用是值得深入研究的。