Sequencing of the alpha-synuclein gene in a large series of cases of familial Parkinson's disease fails to reveal any further mutations. The European Consortium on Genetic Susceptibility in Parkinson's Disease (GSPD)

A mutation in exon 4 of the human alpha-synuclein gene was reported recently in four families with autosomal dominant Parkinson's disease (PD). In order to examine whether mutations in this exon or elsewhere in the gene are common in familial PD, all seven exons of the alpha- synuclein gene were amplified by PCR from index cases of 30 European and American Caucasian kindreds affected with autosomal dominant PD. Each product was sequenced directly and examined for mutations in the open reading frame. No mutations were found in any of the samples examined. We conclude that the A53T change described in the alpha- synuclein gene is a rare cause of PD or may even be a rare variant. Mutations in the regulatory or intronic regions of the gene were not excluded by this study.      

应用免疫组化技术检测胃癌组织p53、c-erbB-2、p21、nm23基因表达产物及其临床意义

目的：为探讨胃癌组织p53、c-erbB-2、p21、nm23联合基因表达产物对胃癌诊断与治疗方面的价值。方法：应用免疫组化技术检测了手术切除胃癌组织p53、c-erbB-2、p21、nm23基因产物表达。结果：p53蛋白表达阳性率37．6％-46．2％，c-erbB-2为34．6％-56．8％，p21为37．8％。61．5％，nm23为30．8％-70．3％；非胃癌组织(胃、十二指肠溃疡、胃息肉、重度不典型增生)未见c-erbB-2、p21、nm23基因表达。c-erbB-2、p21的表达与胃癌的分化程度有关，p21、nm23基因表达与肿瘤浸润深度、肿瘤转移程度有关。p53、c-erbB-2、p21、nm23四种肿瘤蛋白在胃镜活检标本和手术切除标本中表达是一致的，无显著性差异。结论：对胃癌组织检测p53、c-erbB-2、p21、nm23基因表达产物在胃部的良恶性肿瘤鉴别、非手术临床分期的判断及指导胃癌的临床诊断与治疗等方面具有一定价值。     

Prognostic value of vascular endothelial growth factor expression in primary lung carcinoma

To investigate whether an association exists between vascular endothelial growth factor (VEGF) expression and tumor prognosis in primary lung carcinoma, we used immunohistochemical techniques to analyze microvessel density and VEGF expression in lung carcinoma tissue from 98 patients. Tissue had been fresh-frozen at the time of operation and preserved for more than 5 years. The results indicated that VEGF expression was positive for 50 of the 98 patients (51.0%), with 27 (27.6%) being weakly positive and 23 (23.5%) being strongly positive. The microvessel density in tissue showing weakly positive and strongly positive VEGF expression was significantly higher than that in VEGF-negative tumor tissue (P < 0.05: negative vs. weakly positive, P < 0.01: negative vs. strongly positive), we showed demonstrating that VEGF expression was significantly associated with intratumoral microvessel density. The 5-year survival rates were 8.7% for strongly VEGF-positive patients, 43.9% for weakly VEGF-positive patients and 79.2% for VEGF-negative patients, respectively (P < 0.01: negative vs. weakly positive or strongly positive). Furthermore, multivariate analysis employing multiple regression analysis indicated that VEGF expression correlates highly with the overall survival rates of patients with primary lung carcinoma. Two variables, N status and VEGF expression, were found to be significant prognostic factors (P < 0.01). The results of this study suggest that VEGF expression is associated with intratumoral microvessel density. VEGF expression may constitute important independent prognostic evidence that can help us in predicting the outcomes of patients with primary lung carcinomas.     

脂联素、核因子-kB在胰岛素抵抗大鼠表达

目的 观察炎症相关因子脂联素、核因子-kB（NF—kB）在胰岛素抵抗大鼠的表达。方法 20只Wistar大鼠随机分为空白对照组与胰岛素抵抗组，分别给予基础饮食和高糖高脂饮食8周，应用高血浆胰岛素-正常血糖钳夹技术证明胰岛素抵抗的存在。用全自动生化分析仪测定各组血脂、脂联素等，并应用免疫组化技术测定NF-kB在血管内皮细胞的表达。结果 ①应用钳夹技术证明，胰岛素抵抗组存在胰岛素抵抗，而空白对照组未出现胰岛素抵抗；②胰岛素抵抗组甘油三酯、胆固醇、低密度脂蛋白、高密度脂蛋白较空白对照组明显升高（P〈0．05），而保护性因子脂联素浓度则明显降低（P〈0．05）；③免疫组化显示，胰岛素抵抗组大鼠血管内皮细胞NF-kB阳性细胞百分率明显多于空白对照组（P〈0．05）；④脂联素浓度与NF—kB的表达呈明显负相关（r=-0．854，P〈0．05）；结论 胰岛素抵抗时，脂联素浓度降低，NF—kB过表达，二者呈明显负相关。     

Expression and characterization of the human YWK-II gene, encoding a sperm membrane protein related to the alzheimer betaA4-amyloid precursorprotein

The YWK-II cDNA, RSD-2, encoding a sperm membrane protein was isolated from a rat testis cDNA expression library. Using the RSD-2 insert in combination with rapid amplification of cDNA ends (RACE), the corresponding human gene was isolated from a human testis cDNA expression library. The human testis cDNA, HSD-2, is 3654 bp in length and contains an open reading frame of 763 codons. Hydropathicity analysis showed that the deduced polypeptide is a single strand transmembrane protein. The deduced polypeptide has partial homology with the amyloid precursor protein (APP) and high homology with the amyloid precursor homologue, APLP2/APPH. The YWK-II gene was mapped and assigned to human chromosome locus: 11q24-25. Northern blotting of various human tissue RNAs using the HSD-2 cDNA as a probe showed that the gene is transcribed ubiquitously. The cytoplasmic domain of HSD-2 was expressed in Escherichia coli. In-vitro studies showed that the recombinant polypeptide bound to a GTP-binding protein (G(o)) and was phosphorylated by protein kinase C and cdc2 kinase. In mammalian F11 cells, the recombinant polypeptide was found to be coupled to G(o). Thus, the YWK-II component has the characteristics of a G(o)-coupled receptor and may be involved in G(o)-mediated signal transduction pathway. Protein kinase C and cdc2 kinase may regulate this pathway in spermatozoa by phosphorylating the cytoplasmic domain of the YWK-II component.     

The interaction of the SARS coronavirus non-structural protein 10 with the cellular oxido-reductase system causes an extensive cytopathic effect.

The pathological mechanism of SARS-CoV infection was investigated. The gene for the SARS-CoV non-structural protein 10, which is located in the open reading frame of pp1a/pp1ab gene, was synthesized and used to screen for the specific cellular gene coding for the protein interacting with this nsp10 protein in a human embryo lung cDNA library using a yeast trap method. The results indicated that apart from the two subunits of cellular RNA polymerase complex, BTF3 and ATF5, this nsp10 protein was also able to interact specifically with the NADH 4L subunit and cytochrome oxidase II. Further study revealed that the activity of the NADH-cytochrome was altered and the inner mitochondrial membrane was depolarized in the transfected human embryo lung fibroblast by the nsp10 protein gene. The cytopathic effect of the Coronavirus 229E strain appeared more extensive in these cells than in the control cells.     

高糖对腹膜巨噬细胞诱导型一氧化氮合酶的作用

目的：探讨在体外葡萄糖对SD大鼠腹膜巨噬细胞诱导型一氧化氮合酶（iNOS）mRNA的表达及蛋白的合成。方法:取雄性SD大鼠腹腔巨噬细胞培养，培养的巨噬细胞分为5组：(1)正常对照组；(2)30 mmol/L甘露醇组；(3)90 mmol/L甘露醇组；(4)30 mmol/L葡萄糖组；(5)90 mmol/L葡萄糖组。每组6个培养孔，24 h后提取细胞RNA及蛋白，分别做RT-PCR及Western blotting以检测腹膜巨噬细胞iNOS mRNA的表达及蛋白的合成。结果:30 mmol/L及90 mmol/L甘露醇刺激腹膜巨噬细胞iNOS mRNA的表达及蛋白的合成均不明显， 30 mmol/L及90 mmol/L葡萄糖能明显刺激腹膜巨噬细胞iNOS mRNA的表达及蛋白的合成，90 mmol/L葡萄糖与30 mmol/L的葡萄糖相比更能刺激巨噬细胞iNOS mRNA的表达及蛋白的合成。结果:葡萄糖能明显刺激SD大鼠腹膜巨噬细胞iNOS mRNA的表达及蛋白的合成。     

广东汉族人β2-肾上腺素能受体基因Gln27Glu多态性

目的 探讨β2-AR 16位点基因多态性在广东汉族人群中的分布．方法 应用聚合酶链反应技术对122例正常人β2-肾上腺素能受体基因Gln27Glu进行扩增并进行图谱分析．并结合文献进行了不同种族间的分析比较．结果 广东汉族人群β2-AR基因27位点多态性分布频率：Gln／Gln基因型占36．88％，Gln／Glu基因型占52．46％，Glu／Glu基因型占10．66％．结论 广东汉族人群存在出β2-AR Gln27Glu基因多态性，其分布频率与英美高加索人群有一定差异．     

肝纤维化门静脉压力改变与血清ET-1/NO关系的实验研究

目的制作兔肝纤维化模型，观察血管活性物质与门静脉压力变化的关系。方法40只家兔采用口服硫代乙酰胺方法造模，分别于造模第8、12、16、20周时检测内皮素（ET-1）及NO浓度，超声观察胆囊壁及肝脏血流动力学指标，直接穿刺测量不同时期门静脉压力。分析血管活性物质与肝脏血流动力学指标及门静脉压力变化间的关系。结果胆囊壁增厚是肝纤维化阶段的二维超声表现；随着纤维化程度的加重，血清ET-1、NO浓度逐渐增加，且以ET-1／N0比值增加更为明显；门静脉内压力、肠系膜上动脉、脾动脉搏动指数（PI）随纤维化程度逐渐增加，实验组与对照组间差异有统计学意义（P〈0．05），且与ET-1／NO值呈正相关（P〈0．01）。结论通过超声可无创检测肝脏血流动力学变化，对肝纤维化临床诊断及治疗效果的观察，具有积极的作用。