Characterization of erythromycin-resistant Streptococcus pneumoniae in Korea, and In Vitro activity of telithromycin against erythromycin-resistant Streptococcus pneumoniae

To characterize the phenotypes and genotypes of erythromycin-resistant clinical isolates of Streptococcus pneumoniae in Korea and to evaluate the in vitro activity of telithromycin against these erythromycin-resistant isolates, we tested a total of 676 isolates of S. pneumoniae collected from 1997 to 2002 in a tertiary hospital in Seoul, Republic of Korea. MICs for erythromycin and telithromycin were determined by the agar dilution method. The macrolide resistance phenotypes of erythromycin-resistant isolates were determined by the erythromycin- clindamycin-rokitamycin triple disk (ECRTD) and MIC induction tests, whereas their macrolide resistance genotypes were determined by PCR for the erm(B), erm(A), subclass erm(TR), and mef genes. To discriminate between mef(A) and mef(E), PCR-restriction fragment length polymorphism (RFLP) analyses were performed. Of the 676 S. pneumoniae isolates, 459 (67.9%) were resistant to erythromycin. Of the 459 erythromycin-resistant isolates, 343 (74.7%) were assigned to the cMLS phenotype, 48 (10.4%) to the iMcLS phenotype, 4 (0.9%) to the iMLS phenotype, and 64 (14.0%) to the M phenotype. The erm(B) gene was detected in 251 (54.6%) isolates, the mef gene was detected in 64 (14.0%), and both the erm(B) and mef genes were detected in 144 (31.4%) isolates. All of the mef genes detected were identified as mef(E). Of the 459 erythromycin- resistant isolates, all but one were susceptible to telithromycin. The MIC(50)/MIC(90) to telithromycin of isolates carrying erm(B), mef(E), and both genes was 0.06/0.5 microg/ml, 0.03/0.125 microg/ml, and 0.5/1.0 microg/ml, respectively. Although the MICs of telithromycin for the erythromycin-resistant isolates varied according to genotype, telithromycin was very active against these erythromycin-resistant S. pneumoniae.     

Human TLR-7-, -8-, and -9-mediated induction of IFN-alpha/beta and -lambda Is IRAK-4 dependent and redundant for protective immunity to viruses

Five TLRs are thought to play an important role in antiviral immunity, sensing viral products and inducing IFN-alpha/beta and -lambda. Surprisingly, patients with a defect of IRAK-4, a critical kinase downstream from TLRs, are resistant to common viruses. We show here that IFN-alpha/beta and -lambda induction via TLR-7, TLR-8, and TLR-9 was abolished in IRAK-4-deficient blood cells. In contrast, IFN-alpha/beta and -lambda were induced normally by TLR-3 and TLR-4 agonists. Moreover, IFN-beta and -lambda were normally induced by TLR-3 agonists and viruses in IRAK-4-deficient fibroblasts. We further show that IFN-alpha/beta and -lambda production in response to 9 of 11 viruses tested was normal or weakly affected in IRAK-4-deficient blood cells. Thus, IRAK-4-deficient patients may control viral infections by TLR-3- and TLR-4-dependent and/or TLR-independent production of IFNs. The TLR-7-, TLR-8-, and TLR-9-dependent induction of IFN-alpha/beta and -lambda is strictly IRAK-4 dependent and paradoxically redundant for protective immunity to most viruses in humans.     

Predicting intellectual outcome among children treated with 35-40 Gy craniospinal irradiation for medulloblastoma

Fifty children diagnosed with medulloblastoma completed 188 psychological evaluations using the Wechsler Intelligence Scales for Children (D. Wechsler, 1974, 1991) over a 7-year study period following 35-40 Gy postoperative craniospinal irradiation. Random coefficient models were used to predict the trend in the children's intellectual performance as a function of time since diagnosis, with both patient and treatment variables as parameters of this function. A quadratic model demonstrated a delay prior to decline in performance for older patients, whereas the younger patients showed an immediate loss of performance with a plateau at approximately 6 years postdiagnosis. A steeper decline was found for those with higher baseline performance. Clinicians may use the proposed predictive model to identify those patients who are at risk of significant intellectual decline.     

基于椭圆方程的三维心脏超声图像的位移场估计

三维超声心动图技术能使医生直观地看到心脏整体和各部分的运动，在临床得到重视。在三维超声心动图技术中，如何定量的描述心脏中某个组织的运动状况极具临床意义。本研究提出了一种基于椭圆偏微分方程的二尖瓣三维运动估计方法。该方法直接在三维超声图像的位移场上进行了运动估计，避免了传统运动估计方法，如光流法，需要标定的缺点。本研究首先建立一个二次误差指标函数，然后利用变分法导出了三维空间下的一组椭圆型偏微分方程。这类方程有着比较成熟的数值解法，利用了有限差分法，对多个三维超声数据立方体进行了计算，结果证明这类方法是有效的。     

PD-1-Expressing SARS-CoV-2-Specific CD8+ T Cells Are Not Exhausted,but Functional in Patients with COVID-19

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TGFβ1基因对血管内皮细胞细胞外基质表达及与基质黏附的影响

了解TGFβ1基因对血管内皮细胞表达细胞外基质蛋白及与基质黏附力的影响。用DOTAP脂质体转染p MAMneo TGFβ1于原代培养的脐静脉内皮细胞,经G4 18筛选,TGFβ1表达经免疫荧光鉴定。Western blot确定 型胶原、纤黏连蛋白的表达,微管吸吮系统确定内皮细胞与基质的黏附力。结果表明生理情况下的内皮细胞能表达少量的TGFβ1及胶原、纤黏连蛋白。经G4 18筛选,外源性TGFβ1在血管内皮细胞中稳定表达,能显著提高胶原、纤黏连蛋白纤维的表达及细胞与基质的黏附。说明TGFβ1在血管组织工程中促进内皮细胞的黏附具有一定的应用价值。     

丙型肝炎病毒阳性血清体外感染人肝细胞的研究

目的 研究丙型肝炎病毒(HCV)抗体(Ab)阴性,HCV-RNA阳性血清建立体外感染肝细胞模型.方法 HCV Ab阴性,HCV-RNA阳性的窗口期血清与人肝细胞共同培养,用反转录-聚合酶链反应(RT-PCR)、免疫荧光染色、Western blot、共聚焦显微镜和透射电镜等方法检测细胞内HCV核酸复制、蛋白质表达及超微结构改变.结果 细胞与病毒共同培养7～45 d,细胞内和/或培养上清中可间断检出HCV正、负链RNA;细胞浆内有HCV 核心和NS3抗原的表达;细胞超微结构有改变,并于感染后第24天时观察到类似病毒样颗粒.结论 窗口期血清中的HCV能在人肝细胞7701中复制一段时间.     

人体组织中血液灌注率和动脉血温度的无损测量研究

由于人体组织中存在血液对流传热和代谢产热，当皮肤表面绝热后，皮肤表面的温度将上升，体表温升值是人体组织中血液灌注率和动脉血温度的函数，根据实际测量的体表温升与时间的关系就可以测出活体组织的血液灌注率和动脉血温度。根据一维Pennes生物传热方程，推导出了体表绝热后人体组织中及皮肤表面温度分布的解析解，并对人体组织中的血液灌注率及动脉血温度进行了实验测量。由于测量过程中利用的只是皮肤表面的温度信息，无须引入外加热源，对人体组织完全不会造成损伤，亦避免了干扰人体组织的正常生理状态，整个测量系统也比较简单。     

恒河猴骨髓间充质干细胞分离培养及其生长特性

采用密度梯度离心和贴壁筛选方法分离纯化了恒河猴骨髓间充质干细胞(mesenchymal stem cells from bone marrow of Rhesus monkey,RhBMSCs);通过表面抗原检测和核型分析对细胞进行了初步鉴定;通过生长曲线的绘制和细胞凋亡的检测探讨了细胞的生长特点。本实验获得的RhBMSCs形态以梭型为主,核型正常,CD29表达率为99.2%,CD34、CD45、HLA-DR表达率均低于3.2%,RhBMSCs表型符合间充质干细胞的特点,且纯度较高,细胞生长旺盛,但倍增时间有随传代数的增加而逐渐延长的趋势。本实验探讨了RhBMSCs的体外分离、扩增培养及鉴定的方法,并对其生长特点进行了初步观察,这不仅有助于进一步了解与之近似的人的骨髓间充质干细胞的相关特性,而且为以猕猴为对象的BMSC定向分化和组织修复等动物体内实验打下了基础。