Recruitment of complement factor H-like protein 1 promotes intracellular invasion by group A streptococci

Numerous microbial pathogens exploit complement regulatory proteins such as factor H (FH) and factor H-like protein 1 (FHL-1) for immune evasion. Fba is an FHL-1 and FH binding protein expressed on the surface of the human pathogenic bacterium, Streptococcus pyogenes, a common agent of pharyngeal, skin, and soft-tissue infections. In the present study, we demonstrate that Fba and FHL-1 work in concert to promote invasion of epithelial cells by S. pyogenes. Fba fragments were expressed as recombinant proteins and assayed for binding of FHL-1 and FH by Western blotting, enzyme-linked immunosorbent assay, and surface plasmon resonance. A binding site for FHL-1 and FH was localized to the N-terminal half of Fba, a region predicted to contain a coiled-coil domain. Deletion of this coiled-coil domain greatly reduced FHL-1 and FH binding. PepSpot analyses identified a 16-amino-acid segment of Fba which overlaps the coiled-coil domain that binds both FHL-1 and FH. To localize the Fba binding site in FHL-1 and FH, surface plasmon resonance was used to assess the interactions between the streptococcal protein and a series of recombinant FH deletion constructs. The Fba binding site was localized to short consensus repeat 7 (SCR 7), a domain common to FHL-1 and FH. SCR 7 contains a heparin binding site, and heparin was found to inhibit FHL-1 binding to Fba. FHL-1 promoted entry of Fba(+) group A streptococci into epithelial cells in a dose-dependent manner but did not affect invasion by an isogenic fba mutant. To our knowledge, this is the first report of a bacterial pathogen exploiting a soluble complement regulatory protein for entry into host cells.     

机体不同状态下高压氧暴露后对脑微血流动力作用的差异性

目的 :探讨正常及急性脑缺血损伤动物高压氧暴露后大脑微循环血流动力作用的变化。方法 :成年沙土鼠 61只 ,随机分为 0 .1MPa、0 .2MPa、0 .2 5MPa高压氧暴露组 ,脑缺血损伤组和对照组。实验时动物用urethane麻醉 ,在颅骨顶开窗 ,暴露软脑膜。用阻断双侧颈总动脉造成脑缺血损伤。用LMB 1检测软脑膜细动静脉管径和流速 ,用LDF 3检测脑皮质局部血流量。动物在小型氧舱进行了实验暴露。结果 :动物在 0 .2MPa氧暴露后软脑膜细动脉比暴露前收缩 10 .1% ,细动脉血流速度比高压氧暴露前减慢 0 .58mm/s ,细静脉流速比高压氧暴露前减慢 0 .2 9mm/s ,大脑皮质血流量减少 3 4 % ,有非常显著差异 (P <0 .0 1)。而脑缺血损伤动物暴露于 0 .2 5MPa高压氧 60min ,细动脉可在颈动脉再灌流后血流速度得到一定改善的基础上净增 0 .85mm/s ,细静脉血流速度增加 0 .3 1mm /s ,脑皮质血流量在高压氧暴露后可恢复到或接近脑损伤前水平。单纯脑缺血组在实验观测期间软脑膜细动静脉血液速度和脑皮质血流量均明显减少 (P <0 .0 1)。结论 :机体不同状态 (脑缺血性损伤与正常机体 )高压氧暴露后脑血流动力作用出现的差异 ,可能与机体在不同状态下对氧的反应与需求有关。     

病毒载量和T淋巴细胞计数在HIV感染者临床治疗疗效观察中的应用

目的 研究病毒载量检测和CD4^ 计数在评价人类免疫缺陷病毒(HIV)感染者疗效中的应用效果。方法 对HIV感染者临床病例73例进行了实验室和临床观察，其中包括6例鸡尾酒治疗病例、36例中药试验性治疗病例及31例未进行治疗的感染者。主要实验室指标包括血浆病毒载量及T淋巴细胞亚群计数。结果 在进行治疗后3个月时联合治疗组的病毒载量明显低于其他两组，并且在其后保持在很低的水平，CD4^ 计数水平明显高于其他两组并在其后持续升高。在整个观察期间，中药治疗组的病毒载量检测和CD4^ 计数水平与未治疗组差异无显著性，但在临床症状观察中中药治疗组较未治疗组有明显改善。结论 病毒载量检测和CD4^ 计数试验是评价抗HIV治疗疗效的有效方法。     

The refined crystal structure of cowpea mosaic virus at 2.8 A resolution

Comoviruses are a group of plant viruses in the picornavirus superfamily. The type member of comoviruses, cowpea mosaic virus (CPMV), was crystallized in the cubic space group I23, a = 317 A and the hexagonal space group P6(1)22, a = 451 A, c = 1038 A. Structures of three closely similar nucleoprotein particles were determined in the cubic form. The roughly 300-A capsid was similar to the picornavirus capsid displaying a pseudo T = 3 (P = 3) surface lattice. The three beta-sandwich domains adopt two orientations, one with the long axis radial and the other two with the long axes tangential in reference to the capsid sphere. T = 3 viruses display one or the other of these two orientations. The CPMV capsid was permeable to cesium ions, leading to a disturbance of the beta-annulus inside a channel-like structure, suggesting an ion channel. The hexagonal crystal form diffracted X rays to 3 A resolution, despite the large unit cell. The large ( approximately 200 A) solvent channels in the lattice allow exchange of CPMV cognate Fab fragments. As an initial step in the structure determination of the CPMV/Fab complex, the P6(1)22 crystal structure was solved by molecular replacement with the CPMV model determined in the cubic cell.     

基于边界特征的乳腺肿瘤超声图像识别

通过对乳腺肿瘤边界特征的分析，得到边界的特征量似圆度，面积比率，长宽比组成的特征矢量，最后用反向传播人工神经网络（BP）的算法对经病理证实的119幅乳腺良、恶性肿块超声图像进行分类识别。BP神经网络对良、恶性肿瘤正确识别率分别为89．7％、73．5N。量化后的乳腺超声图像肿瘤轮廓特征结合BP神经网络可以比较有效的用于肿瘤的良、恶性识别。     

Analysis of the influence of therapy and viral suppression on high-risk sexual behaviour and sexually transmitted infections among patients infected with human immunodeficiency virus in Taiwan

This study examined the effects of certain characteristics of human immunodeficiency virus (HIV)-infected patients related to the risks of practising unprotected sex (UPS) among 919 HIV-infected patients who attended the sexually transmitted disease (STD) clinic of the Taipei City STD Control Center, Taiwan, during the period January–July 2004. After learning that they were HIV-positive, 517 (56%) subjects had practised UPS, 476 (52%) had a new STD diagnosis, and 106 (12%) had used some form of injected drug. UPS was reported by 76% of homosexual/bisexual males, 19% of heterosexual males and 5% of females, and was reported more often by those individuals with casual sexual partners (p < 0.001). According to multivariate logistic regression analyses, UPS was associated with male-tomale sexual intercourse (OR 2.46; 95% CI 1.26–4.86, p < 0.001), with casual sexual partners (OR 2.82; 95% CI 1.62–4.88, p < 0.001), and with an individual's knowledge of his/her HIV status for > 11 years (OR 2.06; 95% CI 1.02–4.18, p < 0.05). Although using anti-retroviral therapy to prevent sexual transmission of HIV is rational, the avoidance of at-risk sexual behaviour should also be a priority among HIV-seropositive individuals. Ongoing risk-reduction counselling related to HIV transmission is needed to reduce certain sexual behaviours associated with HIV transmission.     

Allelic loss in human papillomavirus-positive and -negative vulvar squamous cell carcinomas

Vulvar squamous cell carcinoma (VSCC) is a biologically and morphologically diverse disease, consisting of human papillomavirus (HPV)-positive and -negative tumors that differ in their morphological phenotypes and associated vulvar mucosal disorders. This study analyzed the frequencies of allelic loss (loss of heterozygosity (LOH)) in HPV-positive and -negative VSCCs to identify potential targets for the study of preinvasive diseases, to determine whether HPV status influenced patterns of LOH, and to determine whether these patterns differed from HPV-positive tumors of another genital site, cervical squamous cell carcinomas (CSCC). DNA extracted from microdissected archival sections of two index tumors, one each HPV negative and positive, was analyzed for LOH at 65 chromosomal loci. Loci scoring positive with either sample were included in an analysis of 14 additional cases that were also typed for HPV. Frequencies of LOH at loci were computed in a panel of HPV-positive and -negative VSCCs. Twenty-nine loci demonstrated LOH on the initial screen and were used to screen the remaining 14 tumors. High frequencies of LOH were identified, some of which were similar to a prior karyotypic study (3p, 5q, 8p, 10q, 15q, 18q, and 22q) and others of which had not previously been described in VSCC (1q, 2q, 8q, 10p, 11p, 11q, 17p, and 21q). With the exception of 5q and 10p, there were no significant associations between frequency of LOH and HPV status in VSCC. LOH at 3p and 11q were frequent in both VSCC and CSCC; however, allelic losses at several sites, including 5q, 8q, 17p, 21q, and 22q, were much more common in VSCC. VSCCs exhibit a broad range of allelic losses irrespective of HPV status, with high frequencies of LOH on certain chromosomal arms. This suggests that despite their differences in pathogenesis, both HPV-positive and -negative VSCCs share similarities in type and range of genetic losses during their evolution. Whether the different frequencies of LOH observed between VSCC and CSCC are real or reflect differences in stage and/or tumor size remains to be determined by further comparisons. The role of these altered genetic loci in the genesis of preinvasive vulvar mucosal lesions merits additional study.     

臂丛神经损伤的磁刺激运动诱发电位

对12例臂丛神经损伤患者进行了磁刺激运动诱发电位(MEP)的测定,并与同时进行的肌电图(EMG)、神经传导速度(NCV)进行了比较,结果发现MEP的阳性率与EMG近似,对臂丛神经损伤的定位及鉴别诊断有意义。     

B超心脏图象轮廓的自动检测

本文提出若干应用横向决策过程的动态规划及序贯模式识别的新方法，充分利用帧间心脏轮廓的动态信息，从超声图象中自动检测、分离心脏的内壁和外壁。