Aminoglycoside antibiotics: old drugs and new therapeutic approaches

Aminoglycoside antibiotics kill bacteria by binding to the ribosomal decoding site and reducing fidelity of protein synthesis. Since the discovery of these natural products over 50 years ago, aminoglycosides have provided a mainstay of antibacterial therapy of serious Gram-negative infections. In recent years, aminoglycosides have become important tools to study molecular recognition of ribonucleic acid (RNA). In an ingenious exploitation of the aminoglycosides’ mechanism of action, it has been speculated that drug-induced readthrough of premature stop codons in mutated messenger RNAs might be used to treat patients suffering from certain heritable genetic disorders. Received 23 January 2007; received after revision 25 February 2007; accepted 29 March 2007     

Targeted inhibition of Livin resensitizes renal cancer cells towards apoptosis

Cancer cells are typically characterized by apoptosis deficiency. In order to investigate a possible role for the anti-apoptotic livin gene in renal cell cancer (RCC), we analyzed its expression in tumor tissue samples and in RCC-derived cell lines. In addition, we studied the contribution of livin to the apoptotic resistance of RCC cells by RNA interference (RNAi). Livin gene expression was detected in a significant portion of RCC tumor tissue specimens (13/14, 92.9%) and tumor-derived cell lines (12/15, 80.0%). Moreover, targeted inhibition of livin by RNAi markedly sensitized RCC cells towards proapoptotic stimuli, such as UV irradiation or the chemotherapeutic drugs etoposide, 5-fluorouracil, and vinblastine. These effects were specific for livin expressing tumor cells. We conclude that livin can contribute significantly to the apoptosis resistance of RCC cells. Targeted inhibition of livin could represent a novel therapeutic strategy to increase the sensitivity of renal cancers towards pro-apoptotic agents. Received 30 November 2006; received after revision 22 February 2007; accepted 20 March 2007     

高核酸高蛋白酵母选育及发酵生态学研究

通过紫外线嘧啶复合处理选育到一株高核酸高蛋白酵母，并进行了营子及其它培养条件的选择性试验，确定了优化的培养条件，摇瓶培养核酸１４．７５％，蛋白质含量达６３．６７％。１．５Ｌ发酵罐发酵试验能很好地重现摇瓶效果及冰箱保存活试验证明该菌株有好的遗传稳定性。     

慢性萎缩性胃炎与正常胃活检组织RNA分布的研究

采用异硫氰酸荧光素（FITC）标记的核糖核酸酶（FITC－RNase）作为探针，结合半薄切片技术，观察了慢性萎缩性胃炎与正常胃活检组织中RNA的分布变化，结果表明：慢性萎缩性胃啖腺体细胞内RNA明显减少，分布部位与正常胃腺体细胞差异较大，这些结果于慢性萎缩性胃炎的病理诊断提供了一些依据，对进一步从分子水平上研究慢性萎缩性胃炎的病理变化及其与胃癌的关系具有一定的意义。     

Adrenocortical metabolism and plasma corticosterone in soman intoxicated rabbits

Summary The organophosphate neurotoxin soman produced impairments in adrenocortical RNA and protein metabolism. Fasciculate and reticular cell RNA and protein contents were supporessed with sublethal to acutely lethal dosages (20, 30 and 40 g/kg, s.c.) during the acute excitatory phase of intoxication and at 6–8 h post injection. All three dosages produced ca 90% inactivation of plasma cholinesterase. A transient elevation of plasma corticosterone occurred with 20 g/kg soman whereas there was a protracted increase with 30 g/kg. Corticosterone was not significantly elevated with 40 g/kg, but death occurred at 13±4 min. Thus, the magnitude and/or nature of soman-induced metabolic impairments does not appear to prevent adrenal activation.Supported by US Army Medical Research and Development Command Contract DAMD 17-81-C-1202.     

Maternal vitamin A restriction alters biochemical development of the brain in rats

Summary The biochemical development of the fetal brain in relation to maternal vitamin A restriction was studied in rats. The vitamin A status of pregnant rats was varied by supplying low, medium and adequate amounts (6, 40, and 100 g retinol/day/kg body weight, respectively) of vitamin A during pregnancy and suckling. The maternal vitamin A restriction caused an altered brain development in terms of tissue weight, DNA, RNA and protein levels, and biosynthesis of DNA and protein from [³H]-thymidine and [³H]-leucine, respectively. A dose-dependent effect of maternal vitamin A restriction on the metabolism of DNA, RNA and protein was noticed in the developing fetal brain of rats.     

反义基因逆转肿瘤细胞多药耐药性和诱导细胞凋亡的研究

探讨克服肿瘤细胞多药耐药（ＭＤＲ１）性的方法,提高化疗效果。本文采用多药耐药反义基因（ＭＤＲ１－ＲＳＰＳ－ＯＤＮ）逆转Ｋ５６２／ＡＤＭ肿瘤细胞的ＭＤＲ１,诱导肿瘤细胞凋亡,发现ＭＤＲ１－ＡＳＰＳ－ＯＤＮ诱导Ｋ５６２／ＡＤＭ细胞株细胞产生大量ＤＮＡ断片,ＦＡＣＳ检测发现几乎全部ＭＲＤ＋Ｋ５６２／ＡＤＭ细胞发生凋亡。其结果表明ＤＭＤＲ１－ＡＳＰＳ－ＯＤＮ能有效、特异地抑制ＭＤＲ１基因表达,逆转肿瘤细胞的ＭＤＲ１,促进阿霉素诱导ＭＤＲ＋１Ｋ５６２／ＡＤＭ细胞凋亡,为其临床应用提供理论依据     

Stability of the Sarcin/Ricin domain of 28S RNA in rat ribosome under hydrostatic pressure

Under 2 100 bar of hydrostatic pressure, KNA N-glycosidase can still cleave the N-C bond of adenosine at position 4324 in R/S domain of 28S RNA in rat ribosome, demonstrating that high pressure has no effect on the tertiary structure of S/R domain.     

免疫沉淀法分离纯化感染细胞中的甲肝病毒RNA

本研究采用抗血清（多抗血清）沉淀甲肝病毒,并用盐酸胍酸性酚,氯仿一步法分离纯化病毒ＲＮＡ．此方法能排除非病毒ＲＮＡ的污染,操作简单,要求条件较低,ＲＮＡ的纯度和完整性都较好