Role of tumour necrosis factor-alpha receptor p75 in cigarette smoke-induced pulmonary inflammation and emphysema.

Chronic obstructive pulmonary disease (COPD) is characterised by a local pulmonary inflammatory response to respiratory pollutants and by systemic inflammation. Tumour necrosis factor (TNF)-alpha has been implicated in systemic effects of COPD and operates by binding the p55 (R1) and p75 (R2) TNF-alpha receptors. To investigate the contribution of each TNF-alpha receptor in the pathogenesis of COPD, the present study examined the effects of chronic air or cigarette smoke (CS) exposure in TNF-alpha R1 knockout (KO) mice, TNF-alpha R2 KO mice and wild type (WT) mice. CS was found to significantly increase the protein levels of soluble TNF-alpha R1 (by four-fold) and TNF-alpha R2 (by 10-fold) in the bronchoalveolar lavage of WT mice. After 3 months, CS induced a prominent pulmonary inflammatory cell influx in WT and TNF-alpha R1 KO mice. In TNF-alpha R2 KO mice, CS-induced pulmonary inflammation was clearly attenuated. After 6 months, no emphysema was observed in CS-exposed TNF-alpha R2 KO mice in contrast to WT and TNF-alpha R1 KO mice. CS-exposed WT and TNF-alpha R1 KO mice failed to gain weight, whereas the body mass of TNF-alpha R2 KO mice was not affected. These current findings suggest that both tumour necrosis factor-alpha receptors contribute to the pathogenesis of chronic obstructive pulmonary disease, but tumour necrosis factor-alpha receptor-2 is the most active receptor in the development of inflammation, emphysema and systemic weight loss in this murine model of chronic obstructive pulmonary disease.     

10对联体双胎分离术后的远期结果

背景／目的：从1978-2000年，有10对联体双胞胎成功接受了手术分离，结果14人存活。其中6对是因为他们的联体同胞死亡或濒临死亡而接受紧急分离手术。剩余的4对，每对至少一个同胞接受至少一次的急诊手术后，才接受联体分离手术。方法：对这一独特的队列进行包含6个项目的问卷调查。问题的设计是开放式的，为父母／家庭提供有关信息的最大机会。对每个家庭就相同的问题也进行了当面的问卷调查。医师询问了与身体健康和疾病相关的一些问题。而社会工作询问了与发育、教育、社会心理和家庭功能相关的问题。结果：前面提及的14人存活的双胞胎中，4人大学毕业，1人于1981年完成中学学业，剩余9人正在上学。14人在最初的手术后，还需要接受再次手术，尤其是需要矫正泌尿系统、畸形、神经外科和小儿外科的问题。结论：通过超声检查对联体双胎进行宫内诊断，可以使医师和胎儿父母在孕早期决定在终止妊娠时是进行双胎分离还是保全其中一个。这些病例报道通过描述14例手术存活的长期体格检查和心理学检查结果，为医师和父母在关键时刻做出决定提供了另外有助的依据。     

Bacteroides forsythus ATCC43037菌体蛋白与人类唾液酸性富脯蛋白的相互作用

目的：探讨福赛类杆菌与人类唾液富脯蛋白相互作用的蛋白分子。方法：Western—blot方法。将人工合成唾液富脯蛋白用生物素标记，福赛类杆菌全菌蛋白凝胶电泳，半干转移至纤维膜上，观察二者的相互作用。结果：富脯蛋白能与分子量为85KD、65KD、60KD、以及49KD的福赛类杆菌蛋白发生结合。结论：福赛类杆菌存在与人类唾液富脯蛋白相互结合的粘附素。     

Oral beta2-agonist use by preschool children with asthma in East and Central Harlem, New York.

Although studies have documented underuse of controller medications and overuse of short-acting inhaled ss(2)-agonist among children with persistent asthma in disadvantaged communities, the persistence of oral ss(2)-agonist use in pediatric practice has not been studied since inhaled short-acting ss(2)-agonists became widespread. We describe medications used to treat asthma among children 3 to 5 years of age at 10 Head Start and other subsidized preschool centers in East and Central Harlem, New York City. We interviewed 149 parents/guardians of children who were identified as having probable asthma based on physician's diagnosis, persistent symptoms, hospitalization, and medication use. We classified 86 of the 149 children (58%) as having current persistent asthma. Only 15 of them (17%) were reported to have used controller medications at least 5 days/week in the last 4 weeks-only 2 of whom used inhaled corticosteroids. By contrast, 53 children (62%) used oral ss(2)-agonist in the last 4 weeks, often (72%) in conjunction with nebulized or inhaled short-acting ss(2)-agonist. Use of oral ss(2)-agonist was associated with more severe symptoms. This study documents the continued widespread use of oral ss(2)-agonist for treatment of children in a low-income community with high prevalence of asthma.     

How neurosecretory vesicles release their cargo.

Neurons and related cell types often contain two major classes of neurosecretory vesicles, synaptic vesicles (SVs) and dense-core granules (DCGs), which store and release distinct cargo. SVs store and release classic neurotransmitters, which facilitate propagation of action potentials across the synaptic cleft, whereas DCGs transport, store, and release hormones, proteins, and neuropeptides, which facilitate neuronal survival, synaptic transmission, and learning. Over the past few years, there has been a major surge in our understanding of many of the key molecular mechanisms underlying cargo release from SVs and DCGs. This surge has been driven largely by the use of fluorescence microscopy (especially total internal reflection fluorescence microscopy) to visualize SVs or DCGs in living cells. This review highlights some of the recent insights into cargo release from neurosecretory vesicles provided by fluorescence microscopy, with emphasis on DCGs.     

补充维生素D预防骨折——随机对照试验汇总分析

背景：对于脊椎以外的骨折而言，补充口服维生素D的预防作用和用量仍无定论。 目的：评估补充维生素D在预防老年髋骨骨折和非脊椎骨折方面的效果。 数据来源：使用MEDLINE、Cochrance对照试验记录（1960～2005年）以及EMBASE（1991-2005年），对英文和非英文文章进行系统回顾。通过与临床专家接触，通过检索美国社会骨和骨矿研究协会提供的参考文献和摘要（1995～2004年）．进一步寻找更多的研究。检索词包括随机对照试验（randomized controlled trial，RCT）、临床对照试验、随机分配、双盲法、维生素D3、维生素D2；25-羟基维生素D、骨折、人类、老年、摔倒和骨密度。 研究选取：纳入的研究仅限于口服补充维生素D（维生素D3、维生素D2、补钙或不补钙）与补钙或安慰剂比较的双盲RCTs。试验于检查髋部骨折或非脊椎骨折的老年人（年龄≥60岁）中进行。数据提取：两位作者根据预先规定独立提取相关数据，其中包括研究质量指标。 数据综合：所有的汇总分析均以随机效应模型为基础。5项有关髋部骨折的RCTs（n=9294）和7项有关非脊椎骨折危险的RCTs（n=9820）符合我们的纳入标准。所有试验均使用了维生素D3。对髋部和非脊椎骨折预防研究的异质性亦进行观察，用低剂量（400IU／d）和高剂量（700～800IU／d）分别合并RCTs后异质性消失。与补钙或安慰剂相比，每天服700～800IU的维生素D可使髋部骨折的相对危险（relative risk，aa）下降26％（3项RCTs共计5572人；RR，0．74；95％可信区间[confidence interval，CI]，0．61～0．88），使非脊椎骨折的相对危险下降23％（5项RCTs共计6098人；RR，0．77；95％CI，0．68～0．87）。每天服400IU的维生素D（2项RCTs共计3722人；髋部骨折RR，1．15；95％CI，0．88～1．50；非脊椎骨折RR，1．03；95％CI，0．86—1．24）未见明显获益。 结论：口服补充维生素D（700～800IU／d）可以降低尚能活动的老人或慈善机构收容的老年人发生髋部骨折和脊椎以外骨折的危险，每天口服400IU维生素D并不足以预防骨折。