Viral dynamics and their relations to baseline factors and longer term virologic responses in treatment-naive HIV-1-infected patients receiving abacavir in combination with HIV-1 protease inhibitors

From a study of 71 HIV-1-infected patients receiving abacavir in combination with 1 of 5 different HIV-1 protease inhibitors (indinavir, ritonavir, saquinavir, nelfinavir, or amprenavir), we found that the baseline HIV-1 RNA levels were highly predictive of the viral decay rates. The baseline HIV-1 RNA levels were negatively correlated with the first phase viral decay rates (r = -0.77, P < 0.001) and positively correlated with the second phase viral decay rates (r = 0.68, P < 0.001). In addition, the first phase viral decay rate was positively correlated with CD4+ cell increases. No significant correlation was found between viral decay rates and longer term (24 weeks) virologic responses, and no difference in viral decay rates was found among the 5 study regimens. These data suggest that the potency of the 5 treatment regimens was similar and was not predictive of long-term virologic failure.     

脂肝宁对大鼠脂肪性肝炎肝细胞热休克蛋白表达的影响

目的： 观察脂肝宁在预防大鼠脂肪性肝炎过程中热休克蛋白(HSP) 60、70在肝细胞中的表达。方法: 将SD大鼠随机分为脂肝宁大、小剂量组、熊去氧胆酸组、病理模型和正常对照组。除正常对照组外，其余大鼠给予高脂饲料和35%乙醇 10 mL/kg，2次/d灌胃，防治组同时给予药物预防。于第9周末处死大鼠，分别进行 ⑴ 肝组织切片常规HE染色，观察炎症反应；⑵ 免疫组化法观察肝组织热休克蛋白60、70的表达情况；⑶ 透射电镜下观察肝细胞及炎细胞的超微结构。结果: ⑴ 光镜下脂肝宁大剂量组和熊去氧胆酸组的肝组织炎症活动度显著低于病理模型组 (P<0.05)。⑵ 脂肝宁大剂量组和熊去氧胆酸组中肝组织HSP70的阳性细胞数显著多于病理模型组和正常对照组（分别为P<0.05，P<0.01），脂肝宁大剂量组中HSP60的表达显著多于模型组及正常对照组（分别为P<0.05，P<0.01）。⑶ 脂肝宁大剂量组和熊去氧胆酸组肝细胞超微结构较模型组明显改善，内无明显脂滴，线粒体嵴排列较整齐。结论: 脂肝宁、熊去氧胆酸对乙醇加高脂饮食诱发的大鼠脂肪性肝炎有较好的防治作用。提高热休克蛋白60、70的表达可能是其防治机制之一。     

精神分裂症患者G72基因表达水平的研究

目的 本工作旨在检测精神分裂症（Schizophrenia）患者外周淋巴细胞中G72基因的表达情况，进而探讨G72基因的表达与精神分裂症的相关关系。 方法 工作在56例精神分裂症患者和84名年龄性别相匹配的对照中进行，在新鲜外周血样本中抽提总RNA，反转录成cDNA，基因表达量的检测在ABI Prism7900HT型序列监测系统上进行，采用TaqMan的方法对患者及对照组样本的mRNA进行定量，采集的荧光数据经SDS2.1软件自动处理，每个样本作三次平行检测，取平均值作为该样本的最终定量。数据应用SPSS统计软件进行处理，对组间基因表达水平的差异采用独立样本的T检验，调用本实验室G72基因单核苷酸多态性（SNPs）资料，用单因素方差分析的方法分析SNP与基因表达水平的关联性。结果 1.检测得到G72基因在对照组中的表达量为0.0586±0.0114amol/ng cDNA, 在精神分裂症患者组中的表达量为0.0498±0.0121amol/ng cDNA。2.经显著性检验， G72基因的表达水平在病例和对照组间差异无统计学意义，t=-0.512，df138，P=0.609，95%CI:-4.258~2.506。3.单因素方差分析结果显示，rs947267位置上的SNP与该基因的表达水平无相关，F=0.355，df2，χ2=0.703；而rs2181953位置上的SNP与G72基因表达水平相关联，F=6.275，df2，χ2=0.004。A/A基因型的患者基因表达水平显著高于其他基因型。结论：精神分裂症患者G72基因的表达量总体上较正常人并无显著变化，但rs2181953位置上的基因型会影响精神分裂症患者该基因的表达。     

PCR analysis of egyptian respiratory adenovirus isolates, including identification of species, serotypes, and coinfections

Eighty-eight adenovirus (Ad) isolates and associated clinical data were collected from walk-in patients with influenza-like illness in Egypt during routine influenza surveillance from 1999 through 2002. Respiratory Ad distributions are geographically variable, and serotype prevalence has not been previously characterized in this region. Serotype identity is clinically relevant because it predicts vaccine efficacy and correlates strongly with both clinical presentation and epidemiological pattern. Species and serotype identities were determined using several well-validated multiplex PCR protocols culled from the literature and supplemented with a few novel primer sets designed to identify rare types. The isolates included common species B1 serotypes (Ad3 and Ad7), common species C serotypes (Ad1, Ad2, and Ad5), the less common species B2 serotype Ad11, and three isolates of the rare species B1 serotype Ad16. Two isolates that appear to be variant Ad16 were also identified. Fifteen coinfections of multiple adenoviral types, primarily AdB/AdC and Ad3/Ad7 dual infections, were detected. The majority of these were verified using redundant PCR tests targeted at multiple genes. PCR is able to resolve coinfections, in contrast to traditional serum neutralization tests. PCR is also comparatively rapid and requires very little equipment. Application of the method allowed an inclusive determination of the serotypes found in the Egyptian respiratory sample set and demonstrated that coinfections are common and may play a previously unrecognized role in adenovirus pathogenesis, evolution, and epidemiology. In particular, coinfections may influence adenoviral evolution, as interserotypic recombination has been identified as a source of emerging strains.     

Genomic analysis of the nuclear receptor family: new insights into structure, regulation, and evolution from the rat genome

Completion of the Rattus norvegicus genome sequence enabled a global inventory and analysis of the nuclear receptors (NRs) in three mammalian species. Forty-nine NR members were found in mouse, 48 in human. Forty-seven were found in the rat, with gaps at the locations expected for the other two. Pairwise comparisons of their distribution in rat, mouse, and human identified 11 syntenic NR gene blocks, including three small clusters of two or three closely related genes, each spanning 40 kb to 1700 kb. The exon structure of the ligand-binding domain suggests that exon shuffling has played a role in the evolution of this family. An invariant splice junction in all members of the NR family except LXRbeta suggests a functional role for the intron. The ligand-binding domains of PXR and CAR are among the most divergent in the family. Their higher nucleotide substitution rates may be related to the central role played by these two NRs in the metabolism of the foreign compounds and may have resulted from limited positive selection.     

PTOV-1, a novel protein overexpressed in prostate cancer,shuttles between the cytoplasm and the nucleus and promotes entry into the S phase of the cell division cycle

PTOV1 was recently identified as a novel gene and protein during a differential display screening for genes overexpressed in prostate cancer. The PTOV1 protein consists of two novel protein domains arranged in tandem, without significant similarities to known protein motifs. By immunohistochemical analysis, we have found that PTOV1 is overexpressed in 71% of 38 prostate carcinomas and in 80% of samples with prostate intraepithelial neoplasia. High levels of PTOV1 in tumors correlated significantly with proliferative index, as assessed by Ki67 immunoreactivity, and associated with a nuclear localization of the protein, suggesting a functional relationship between PTOV1 overexpression, proliferative status, and nuclear localization. In quiescent cultured prostate tumor cells, PTOV1 localized to the cytoplasm, being excluded from nuclei. After serum stimulation, PTOV1 partially translocated to the nucleus at the beginning of the S phase. At the end of mitosis, PTOV1 exited the nucleus. Transient transfection of chimeric green fluorescent protein-PTOV1 forced the entry of cells into the S phase of the cell cycle, as shown by double fluorescent imaging for green fluorescent protein and for Ki67, and also by flow cytometry. This was accompanied by greatly increased levels of cyclin D1 protein in the transfected cells. These observations suggest that overexpression of PTOV1 can contribute to the proliferative status of prostate tumor cells and thus to their biological behavior.