Apoptosis and diseases: regulation and clinical relevance

It is increasingly clear that apoptosis plays a central role in the pathogenesis of several human diseases. For instance, an increase in apoptosis leads to cell loss accompanied by neurodegenerative diseases, whereas we know that genetically determined defects of apoptosis result in deregulated cell proliferation, typical of cancer. Hence, apoptosis may be relevant as therapeutic targets for many human diseases. This article reviews briefly the regulation and the clinical relevance of apoptotic mechanisms in several different human diseases.     

嗜酸性粒细胞凋亡在支气管哮喘中的调控及意义

该文阐述了影响支气管哮喘嗜酸性粒细胞凋亡的相关机制,提出中药促进嗜酸性粒细胞凋亡的意义及在哮喘治疗中的多环节、多靶点的作用.     

钙离子和细胞凋亡及药物调控

细胞凋亡不足或过度能引发诸多疾病.细胞内Ca2+过度升高造成的Ca2+超载是细胞凋亡的重要成因.本文针对Ca2+超载引起细胞凋亡的机制,提出与Ca2+有关的药物调控细胞凋亡的作用靶点,以利于调控药物的研发和应用.     

死亡蛋白酶与细胞凋亡调控及机制

细胞凋亡 (Ａｐｏｐｔｏｓｉｓ)又称程序性死亡 (Ｐｒｏ ｇｒａｍｍｅｄＣｅｌｌＤｅａｔｈ ,ＰＣＤ)。ＰＣＤ由Ａｓｐ特异性半胱氨酸蛋白酶 (Ｃａｓｐａｒｔａｔｅ -ｓｐｅｃｉｆｉｃｃｙｓｔｅｉｎｙｌ ｐｒｏｔｅｉｎａｓｅ ,Ｃａｓｐａｓｅ或Ｃａｓｐ)家族介导 ,活化的Ｃａｓｐ触发酶级联效应 ,引起染色体ＤＮＡ的降解及细胞解体[1] 。Ｃａｓｐ家族是ＰＣＤ过程的关键元件 ,它的激活与超常表达均引起细胞凋亡 ,因此又称死亡蛋白酶 ,他们通过与众多蛋白质因子的相互作用调控ＰＣＤ[1] 。1　Ｃａｓｐ家族及生物学特性Ｃａｓｐ最初表达为蛋…     

Origins and clinical relevance of child death review teams.

Interagency child death review teams have emerged in response to the increasing awareness of severe violence against children in the United States. Since 1978, when the first team originated in Los Angeles, Calif, child death review teams have been established across the nation. Approximately 100 million Americans or 40% of the nation's population now live in counties or states served by such teams; most have been formed since 1988. Multiagency child death review involves a systematic, multidisciplinary, and multiagency process to coordinate and integrate data and resources from coroners, law enforcement, courts, child protective services, and health care providers. This article provides an introduction to the unique factors and magnitude of suspicious child deaths, and to the concept and process of interagency child death review. Future expansion of this process should lead to more effective multiagency case management and prevention of future deaths and serious injuries to children from child abuse and neglect.     

Drug and neurotransmitter receptors. New perspectives with clinical relevance

Our understanding of drug and neurotransmitter receptors has been greatly advanced by receptor binding techniques. The theme of multiple-receptor subtypes with clinical relevance is highlighted by calcium antagonist and benzodiazepine receptors. Numerous drugs may exert therapeutic and untoward effects via calcium channels. Examples include effects of loperamide hydrochloride on diarrhea, the phenothiazine thioridazine hydrochloride on cardiac and ejaculatory function, and the neuromuscular toxicity of aminoglycosides. Elevated numbers of calcium antagonist receptors in hypertrophic cardiomyopathy may be involved in the pathophysiology of this disease. Benzodiazepines act via discrete central and peripheral receptors. At central receptors, benzodiazepines facilitate the inhibitory effects of the neurotransmitter gamma-aminobutyric acid. Peripheral benzodiazepine receptors are localized to mitochondria and enriched in several endocrine glands where they are influenced by therapeutic blood levels of benzodiazepines such as diazepam.     

嗜酸粒细胞性食管炎临床病理分析

目的探讨疑难食管溃疡性病变——嗜酸粒细胞性食管炎患者临床病理学表现及免疫组化特点。方法对9例术后诊为嗜酸粒细胞性食管炎患者标本进行临床病理学分析,采用HE染色、甲苯胺蓝染色、硫堇染色及免疫组化S-P法染色等。结果9例嗜酸粒细胞性食管炎病变特征均呈溃疡型改变,溃疡及其周围黏膜各层及肉芽组织中,见到未释放型和释放型2种肥大细胞;嗜酸粒细胞集中区也是肥大细胞聚集区。结论本病的发生与变态反应有关,病变过程中可形成溃疡,手术前易误诊为食管癌。     

嗜酸性粒细胞与慢性阻塞性肺疾病的临床研究进展

慢性阻塞性肺疾病(简称慢阻肺)是一种常见的以持续性呼吸道症状和气流受限为特征的可以预防和治疗的异质性疾病,它是呼吸系统的常见病、多发病,预计到2020年将成为全球第三大死亡原因[1]。王辰等[2]最新发表在Lancet上的一项大规模流行病学研究报道我国慢阻肺总体患病率为8.6%(95%CI 7.5~9.9),总人数近1亿(95%CI 0.763~1.357),已构成重大疾病负担。既往认为慢阻肺气道慢性炎症以中性粒细胞为特征,但近年来发现慢阻肺也存在嗜酸性粒细胞(eosinophil,EOS)炎症。Brightling等[3]研究发现,高达40%的慢阻肺患者EOS计数≥3%,其比例取决于所使用的EOS阈值及研究的具体人群。本文主要对EOS在慢阻肺炎症中的作用,及其作为生物标志物评估慢阻肺急性加重、肺功能下降和肺炎的风险以及提供个体化治疗决策的潜力作一综述。     

Plasma ferritin concentrations: their clinical significance and relevance to patient care.

In healthy persons the plasma ferritin concentration is a sensitive index of the size of body iron stores. It has been successfully applied to large-scale surveys of the iron status of populations. It has also proved useful in the assessment of clinical disorders of iron metabolism. A low plasma ferritin level has a high predictive value for the diagnosis of uncomplicated iron deficiency anemia. It is of less value, however, in anemia associated with infection, chronic inflammatory disorders, liver disease and malignant hematologic diseases, for which a low level indicates iron deficiency and a high level excludes it, but intermediate levels are not diagnostic. Measuring the plasma ferritin concentration is also useful for the detection of excess body iron, particularly in idiopathic hemochromatosis, but again it lacks specificity in the presence of active hepatocellular disease. If iron overload is suspected in these circumstances determination of the iron content of a percutaneous liver biopsy specimen is required. In families with idiopathic hemochromatosis the combined determination of the plasma ferritin concentration and the transferrin saturation is a sufficient screen to identify affected relatives; however, estimation of the hepatic iron concentration is required to establish the diagnosis.     

小分子干扰RNA在细胞凋亡调控中的应用研究进展

细胞凋亡是由细胞内预存的细胞死亡程序引发的高度精密调节的、能量依赖性的、有序的细胞自杀过程,这一过程对消除机体内老化细胞及具有潜在性异常生长的细胞,以及保持机体处于稳态等中起着重要作用。细胞凋亡受相关基因调控,如果调控机制发生紊乱则可使机体发生多种疾病。小分子干扰RNA(siRNA)技术是将靶基因沉默的一种方法,它能够较简便且准确地产生与基因剔除相似的作用。本文着重介绍运用siRNA技术对凋亡诱导基因或抑制基因进行调控,及其在癌症、病毒感染性疾病及肺损伤等治疗中的研究进展,展望siRNA作为一种新型基因封闭工具的应用前景。     

兔血吸虫病肝细胞的凋亡及其调控

目的：研究血吸虫病兔肝细胞的凋亡及其调控，并探讨凋亡在血吸虫肝病发病机制中的意义。方法：以腹部敷贴法建立家兔血吸虫病模型。以感染尾蚴12周的兔20只为实验组，正常家兔5只为对照组。采用普通病理学，透射电镜，TNF－α、C－Fos和iNOS免疫组化染色及流式细胞术。结果：免疫组化：TNF－α、C－Fos和iNO强阳性反应均位于细胞浆内，阳性细胞呈弥漫性分布，以虫卵和虫卵肉芽肿周围多见，透射电镜可见典型的凋亡细胞及凋亡小体形成，流式细胞术元血吸虫病兔肝细胞凋亡百分数显著高于对照组（P＜0．01）。结论：血吸虫病兔肝细胞坏死外，同时还胡有肝细胞凋亡。TNF－α、C－Fos和iNOS参与血吸虫病时肝细胞凋亡的调控和作反传导信号。     

细胞凋亡及其基因调控在脑血管痉挛中的研究

凋亡不同于坏死,是细胞自主的有序性死亡。最近的研究表明蛛网膜下腔出血后脑血管痉挛存在内皮细胞凋亡,而且痉挛血管壁的细胞凋亡在血管痉挛形成的机制中有重要的作用。凋亡受到半胱天冬蛋白酶家族(caspases)、p53、即刻早期基因(lEGs)、Bcl-2家族、细胞凋亡受体Fas等多种相关基因的调控。上述基因已经被证实在痉挛血管壁组织中存在表达。延缓或阻止凋亡的发生和发展,有望为脑血管痉挛防治找到一条新的途径。     

YAP调节细胞增殖和凋亡作用机制的研究进展

Hippo信号通路首先在果蝇属中发现,在哺乳动物高度保守,通过调节细胞增殖和凋亡维持器官大小和机体内环境的稳态。Yes相关蛋白(YAP)是Hippo信号通路的关键效应分子,作为转录共激活因子扮演着癌基因和抑癌基因的矛盾角色。YAP去磷酸化后活化,入核参与细胞增殖和凋亡的调节;其中涉及哺乳动物雷帕霉素靶蛋白(m TOR)、磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)、Wnt/β联蛋白(Wnt/β-catenin)等信号通路。该文对哺乳动物Hippo-YAP信号通路调节细胞增殖和凋亡作用机制的研究进展予以综述。     

骨肉瘤发生中p53蛋白表达对细胞凋亡的调节

目的研究骨肉瘤发生中p53蛋白表达对细胞调亡的调节。方法利用原位脱氧核糖核酸末端转移酶(In situ terminal deoxynucleotide transferase;ISTdT)标记技术和SP免疫组织化学方法分别检测骨肉瘤和良性骨肿瘤组织中凋亡细胞和p53蛋白的表达。结果骨肉瘤中p53蛋白的阳性率(76.9%,50/65)和阳性表达强度明显高于良性骨肿瘤组织(21.1%,4/19)(分别为P＜0.01和P＜0.05),但4种亚型之间差异无显著性(P＞0.05)。骨肉瘤组织中凋亡细胞密度均明显低于良性骨肿瘤组织(P＜0.01),但各亚型之间两者亦均无明显差异(P＞0.05);骨肉瘤和良性骨肿瘤组织中p53蛋白表达与凋亡细胞密度呈明显的线性负相关(r=-0.8954,P＜0.01),其表达增强则凋亡细胞密度逐渐降低。结论在骨肉瘤发生中p53基因突变可能是一种频发事件。突变型p53基因可能是通过其蛋白过度表达抑制肿瘤细胞凋亡,导致骨肉瘤的发生和发展。     

氟伐他汀对心肌细胞凋亡的调控作用及其可能机制研究

目的 以大鼠胚胎来源的心肌细胞为模型,观察氟伐他汀对心肌细胞凋亡的调控作用,并探讨其可能机制.方法 通过MTT检测法检测细胞活性,用流式细胞仪检测细胞凋亡,用实时定量PCR以及Western Blot方法检测转化生长因子β1(TGF-β1)及其受体的表达.结果 氟伐他汀能够以浓度依赖性的方式降低H9c2细胞的活性,10 μM 氟伐他汀处理H9c2细胞后其凋亡率增加,处理4 d后H9c2细胞凋亡率为54.9%;氟伐他汀能够上调 TβRⅡ mRNA 和蛋白的表达,而对TGF-β1及TβRⅠ的表达无明显的上调作用.结论 氟伐他汀能够诱导H9c2细胞的凋亡,这种凋亡诱导作用可能与氟伐他汀对TβRⅡ的上调作用有关.