Alteration of virus entry mode: a neutralisation mechanism for Dengue-2 virus

Polyclonal antibodies derived from dengue virus immune sera and 3H5 monoclonal antibody showed potent neutralisation effect on dengue-2 virus in the plaque reduction neutralisation assay. This study demonstrated that antibodies present in immune human sera and 3H5 monoclonal antibody neutralised dengue-2 virus by altering the virus entry pathway into cells. In the presence of neutralising antibodies, dengue-2 virus was endocytosed by LLC-MK2 cells. The endocytosis process involved ruffling of antibody-coated virions by cellular pseudopodia and invagination of cell membrane. This mode of entry is atypical as compared to direct fusion of dengue-2 virus with cell membrane in the absence of antibody. The virions were internalised in the form of virion-antibody complexes consisting of single or clumps of virions. After 3 minutes of incubation, neutralised virions were detected in cellular vesicles, and signs of intra-endosomal penetration into cytoplasm were not evident even after a prolonged incubation of 10 minutes, suggesting that viral uncoating was compromised. Vesicle-bound virions were no longer detected after 20 minutes of incubation. In addition, no sign of viral replication was detected in cells infected with "neutralised" virions by immunofluorescence assay. This indicated that internalised virions had been degraded leading to abortive infection. In conclusion, antibodies present in 3H5 monoclonal antibody and human immune sera rendered dengue-2 virus non-infective by neutralising the viral fusion site and causing alteration of viral entry mode. Antibodies in immune sera but not 3H5 monoclonal antibody also exerted minimal inhibitory effect on virus binding and internalisation.     

Endoxin antagonist lessens myocardial ischemia reperfusion injury

Endoxin antagonist lessens myocardial ischemia reperfusion injury@柯永胜$Department of Cardiology, Yijishan Hospital, Wannan Medical College, Wuhu, 241001 China @王德国$Department of Cardiology, Yijishan Hospital, Wannan Medical College, Wuhu, 241001 C     

放免法测定746例地戈辛血药浓度分析

目的：监测地戈辛血药浓度。方法;采用放免法监测７４６例地戈辛治疗慢性心功能不全病人的血药浓度。结果;血药浓度在治疗范围者３２５例,偏低者９９例,高者３２２例,大于治疗范围者中有１２例出现中毒症状。结论：监测地戈辛血药浓度可作为判断药物疗效和中毒的客观指标。     

COX-2 expression is induced by UVB exposure in human skin: implications for the development of skin cancer

Extensive documentation has validated the role of UV irradiation as a tumor initiator and promoter, inducing both squamous and basal cell carcinomas. Human epidermis is a tissue which undergoes active metabolism of arachidonic acid to prostaglandins which is regulated by the action of prostaglandin H synthase (also known as cyclooxygenase). One mechanism for the promotional activity of UV light may involve its ability to induce prostaglandin formation. Work in our laboratory has demonstrated that acute exposure of human keratinocytes to UVB irradiation results in increased production of prostaglandin E2 (PGE2). When cultured human keratinocytes were examined after irradiation with 30 mJ/cm2 UVB in vitro, Western blot analysis showed a 6-fold increase in COX-2 protein which was evident at 6 h and peaked 24 h after irradiation. Furthermore, when human subjects were irradiated on sun- protected skin with up to four times their minimal erythema dosage (MED) and biopsied 24 h later, upregulation of COX-2 protein expression was observed via immunofluorescence microscopy. RNAase protection assays supported this observation, showing induction of COX-2 message which peaked at approximately 12 h following irradiation in vitro. Furthermore, human squamous cell carcinoma biopsies exhibited strongly enhanced staining for COX-2 protein via immunohistochemistry and Western analysis when compared to normal non-sun-exposed control skin. Together, these data demonstrate acute upregulation of COX-2 via UVB irradiation and suggest the need for further studies of COX-2 expression as a potential pharmacological target mediating human skin tumor development.      

DNA diagnosis of FRAXA and FRAXE in Chinese children with neurodevelopmental disorders and fragile X syndrome

Fragile X (FraX) syndrome is the most common cause of inherited mental retardation. To see whether FRAXA or FRAXE can account for the etiology of some unexplained neurodevelopmental disorders in children, we screened for trinucleotide repeat expansion in a consecutive cohort of 73 Chinese children and their mothers seen in 1995 (group 1) referred for developmental assessment due to developmental delay, language delay, attention deficit hyperactivity disorder, autistic spectrum disorder, mental retardation and/or learning disability. We also screened DNA samples of all five previously diagnosed cytogenetically-positive FraX boys, their mothers and sisters (group 2). A control group of unrelated teenagers and adults were recruited from the community (group 3). In group 1, 3 families (2 mothers and a mother and her son) were found to carry a small premutation allele at FRAXA (premutation frequency = 2%, 3/153 independent X chromosomes), but none had any expansion at FRAXE. In group 2, all 5 FraX boys had full mutation at FRAXA and normal repeat length at FRAXE. In group 3, 1 male has a premutation allele out of 18 males and 59 females tested (premutation frequency of control = 0.7%, 1 out of 136 X chromosomes). For FRAXE screening in group 3, 2 females were carriers (1.5%, 2 out of 136 X chromosomes). Thus, FRAXA and FRAXE cannot account for the etiology of neurodevelopmental disorders in our cohort of Chinese children, and the prevalence of FRAXE mutation in normal Chinese population appears to be higher than reported in the Caucasians.     

中国香港与西方儿童分泌性中耳炎发病率的比较

目的 调查中国香港儿童分泌性中耳炎发病率,并且进一步与西方的研究结果做比较。方法 1995-1998年,在中国香港特别行政区随机抽取小学、幼稚园(4-5岁)及幼儿园(2-3岁),对6872名2-7岁儿童进行检查,在校内接受由耳鼻咽喉科专家施行的耳镜检查及由听力学家执行的鼓室导抗测试。为了与西方研究结果作出标准化的比较,根据他们所采用的诊断标准重新计算。结果 在划分为2-3岁、4-5岁及6-7岁的研究对象中,若以耳镜临床诊断作标准,本研究分泌性中耳炎发病率为5.2％-21.6％;若以鼓室导抗图作诊断标准,发病率为7.3％-30.7％。同一组数据,发病率计算结果是会因为采用不同的鼓室导抗图诊断定义而有偏差,但无论是用哪种方法,结果都与西方同龄研究的发病率差异无显著性,而且发病率随年龄增加而下降。结论 香港2-3岁、4-5岁,及6-7岁中国儿童的分泌性中耳炎发病率与西方文献报告没有显著性差异。     

伊贝辛的分离和鉴定

从吉林栽培的伊贝母(Fritillaria pallidiflora Schrenk)鳞茎中分离出两种介藜芦胺类生物碱Ⅰ和Ⅱ。碱Ⅱ是一个新的甾体生物碱,定名为伊贝辛(yibeissine),结构为22,26-imino-17,23-oxidojerv-12-en-6-oxo-3β,11α-diol,碱Ⅰ是一个已知化合物,结构为11-deoxo-6-oxo-5α,6-dihydrojervine。     

免疫功能紊乱与再生障碍性贫血

免疫功能紊乱与再生障碍性贫血的发病密切相关。它不便宜接参与造血于细胞的损伤,促进造血于细胞的凋亡,而且可引发骨髓造血微环境的缺陷。本文综述了近年来这一方面的研究进展,并提出应用免疫调节剂治疗再障的重要性。