自身免疫与糖尿病大血管病变

糖尿病大血管病变是以动脉粥样硬化为主要病理特征的糖尿病慢性并发症之一.近年来,自身免疫因素在动脉粥样硬化发病中的作用越来越受到关注,多种自身抗体、自身抗原和免疫系统成分参与动脉粥样硬化的发生和发展.检测血液中几种自身抗原及其抗体,如氧化型低密度脂蛋白、p2糖蛋白Ⅰ、热休克蛋白的变化,可间接预测糖尿病患者动脉粥样硬化的发生、发展.对糖尿病大血管病变相关自身免疫更深入的研究,将为糖尿病大血管病变的早期诊断、监测和治疗开辟一条新的途径.     

氧化低密度脂蛋白自身抗体与动脉粥样硬化

动脉粥样硬化是一种炎性疾病.氧化低密度脂蛋白(oxLDL)作为自身抗原诱发体内特异性免疫反应.oxLDL的自身抗体在动脉粥样硬化病变的发生发展中可能具有预防和致病的双重作用.     

低密度脂蛋白自身免疫在动脉粥样硬化发生中的作用

体液免疫和细胞免疫同时参与了动脉粥样硬化的发生和发展，修饰低密度脂蛋白、自身抗体及其循环免疫复合物在体内均可检测出，且同疾病的程度相关。低密度脂蛋白及自身抗体形成的免疫复合物可高效地引起细胞内胆固醇酯的堆积，并促进天然低密度脂蛋白受体表达和细胞因子合成增加，具一系列致病作用。     

自身免疫性血管炎与动脉粥样硬化的关系

本文综述了系统性红斑狼疮(SLE)、幼年型类风湿性关节炎(JRA)与动脉粥样硬化(AS)发生的关系及其可能机制.重点强调以自身免疫性血管炎为特征的一组风湿性疾病,可能是AS和缺血性心脏病发生的新的危险因素.     

感染免疫与炎症在动脉粥样硬化中的作用

新近大量研究表明 ,动脉粥样硬化 (AS)是一种慢性炎性疾病 ,自身免疫在AS中可能发挥着重要作用〔1〕,而感染则可能是炎症和自身免疫的激发因子之一。感染、免疫与炎症三者共同作用 ,可明显增加AS的危险性〔2〕。因而抗炎和免疫调节治疗将有望成为防治AS的重要手段之一。1　自身免疫和炎症与AS有关的证据界定一种疾病为自身免疫性炎性病变应满足以下条件 :①在患者的血液及受累的组织中存在炎性递质或免疫物质 ;②在患者体内检出自身抗体 ;③在受累组织中可见参与自身免疫的特异细胞。许多研究表明AS患者血液中炎性递质水平明显升高 ,其…     

中国动脉粥样硬化病理生理学研究近况

近四五年来，中国在动脉粥样硬化的病理生理学方面做了大量的研究工作，发表了一定数量的研究论文。综述这些研究论文，主要有四个方面：(1)动脉粥样硬化模型的复制，正向小型化发展。如引进了载脂蛋白E基因敲除鼠模型；大量维生素D加喂高脂饲料建立动脉粥样硬化大鼠模型；炎症免疫相关模型，以及基因工程型模型等。(2)在动脉粥样硬化病因学方面的工作集中在载脂蛋白基因多态性、脂蛋白脂肪酶等相关基因多态性、动脉粥样硬化遗传易感性、家族性高胆固醇血症，以及动脉粥样硬化的危险因素等方面。(3)关于动脉粥样硬化的发病学，许多作者认为，氧化型低密度脂蛋白起到主导作用：损伤血管内皮、刺激平滑肌细胞增殖、致血管壁细胞凋亡等；此外，在泡沫细胞形成、血液因素致动脉粥样硬化作用和斑块稳定性方面也做了大量工作。(4)关于抗动脉粥样硬化因素研究，除了继续探索高密度脂蛋白、过氧化体增殖物激活型受体、L精氨酸—一氧化氮酶等因素的抗动脉粥样硬化作用外，还发现了ATP结合盒转运体A1、溶血卵磷脂和小凹蛋白1等因素的抗动脉粥样硬化作用。总之，中国在动脉粥样硬化病理生理学的研究进步很大．但离完全阐明动脉粥样硬化病因发病学的目标还有较大路程。     

热休克蛋白在动脉粥样硬化进程中的作用及其应用

动脉粥样硬化(AS)被认为是一种多因素参与的慢性炎症、自身免疫性疾病。热休克蛋白(HSP)作为一种应激蛋白,能够维持细胞免受应激损害,通过抗炎症,抗氧化,抗凋亡的作用制止AS的发生,然而HSP作为一种炎症因子和自身抗原,在AS的进程中发挥不同的作用。血清中HSP的水平可为早期预测或诊断AS提供重要的依据;利用HSP的免疫抗原性质,能诱导机体的免疫耐受,抵抗AS的发生;给予具有保护作用的外源性HSP能抑制AS的进程。     

自身免疫性血管炎与动脉粥样硬化的关系

本文综述了系统性红斑狼疮(SLE)、幼年型类风湿性关节炎(JRA)与动脉粥样硬化(AS)发生的关系及其可能机制。重点强调以自身免疫性血管炎为特征的一组风湿性疾病，可能是AS和缺血性心脏病发生的新的危险因素。     

动脉粥样硬化发病机理

由于日本饮食习惯等生活方式的欧美化,使疾病的组成发生变化,动脉粥样硬化疾病有所增多。此种改变对死因产生很大影响,特别在高龄老人中死于动脉粥样硬化疾病者显著增多。直到现在这已被看作是高龄老人的特点,因为除了动脉中层钙化或小动脉硬化症以外,最近老年人动脉粥样硬化病亦在增多。因此,本文将以动脉粥样硬化疾病病因为重点,并结合以往的研究加以讨论。动脉粥样硬化危险因素的研究及其与发病机理的关系根据对来自动脉粥样硬化的缺血性心脏     

颅内动脉粥样硬化的危险因素

颅内动脉粥样硬化是缺血性卒中的重要病因之一.由于颅内、外动脉在结构和血流动力学方面存在差异,传统血管危险因素,如性别、年龄、高血压、糖尿病等对颅内、外动脉粥样硬化的影响也有所不同.及早识别颅内动脉粥样硬化的危险因素,对于积极防治颅内动脉粥样硬化和降低缺血性卒中发病率具有重要意义.然而,针对危险因素和颅内动脉粥样硬化相关性的许多研究结论并不一致.文章对颅内动脉粥样硬化危险因素的研究现状做了综述.     

Leptin and cellular and innate immunity in abstinent alcoholics and controls

BACKGROUND: Basic studies indicate that in vitro and in vivo doses of leptin modulate cellular immune responses. Given evidence that concentrations of leptin are altered in alcoholics who also show immune abnormalities, this study examined the relationships between circulating levels of leptin and markers of cellular and innate immunity. METHODS: Circulating levels of leptin, natural killer cell (NK) activity, interleukin-2 (IL-2)-stimulated NK activity, and concanavalin A-stimulated production of IL-2, IL-6, IL-10, and IL-12 were compared between abstinent DSM-IV alcohol-dependent men (n = 27) and age- and gender-matched controls (n = 34). RESULTS: As compared with controls, alcoholics showed lower NK activity (p < 0.01) and a trend for lower levels of leptin (p = 0.055). In the total sample, leptin predicted NK activity (beta = 0.33; p < 0.05) after controlling for the confounding influence of body mass index, alcohol intake, and smoking. Leptin was not correlated with any of the cytokine measures. To examine whether the effects of leptin were mediated by its direct action on NK, additional studies examined in vitro effects of leptin on NK activity in healthy volunteers (n = 10); leptin doses (0.1, 1, and 10 nM) yielded levels of NK activity comparable to those with media alone. CONCLUSIONS: These data show that circulating levels of leptin are associated with NK activity in humans and suggest that abnormal in vivo concentrations of leptin may contribute to the declines of NK activity in alcoholics who are at risk for infectious diseases.     

Biofilms and Helicobacter pylori: Dissemination and persistence within the environment and host

The presence of viable Helicobacter pylori(H. pylori) in the environment is considered to contribute to the levels of H. pylori found in the human population, which also aids to increase its genetic variability and its environment adaptability and persistence. H. pylori form biofilms both within the in vitro and in vivo envi-ronment. This represents an important attribute that assists the survival of this bacterium within environ-ments that are both hostile and adverse to prolifera-tion. It is the aim of this paper to review the ability of H. pylori to form biofilms in vivo and in vitro and to address the inherent mechanisms considered to sig-nificantly enhance its persistence within the host and in external environments. Furthermore, the dissemi-nation of H. pylori in the external environment and within in the human body and its impact upon infec-tion control shall be discussed.     

ADH and ALDH Polymorphisms and Alcohol Dependence in Mexican and Native Americans

Background: Ethanol is primarily metabolized in the liver by two rate-limiting reactions: conversion of ethanol to acetaldehyde by alcohol dehydrogenase (ADH) and subsequent conversion of acetaldehyde to acetate by aldehyde dehydrogenase (ALDH). ADH and ALDH exist in multiple isozymes that differ in their kinetic properties. Notably, polymorphisms within the genes that encode for these isozymes vary in their allele frequencies between ethnic groups, and thus, they have been considered as candidate genes that may differentially influence risk for the development of alcohol dependence across ethnic groups. Objectives and methods: Associations between alcohol dependence and polymorphisms in ADH1B, ADH1C, and ALDH2 were compared in a community sample of Native Americans (n 791) living on reservations and Mexican Americans (n 391) living within the same county. Results: Two Mexican Americans and no Native Americans possessed one ALDH2*2 allele. Presence of at least one ADH1B*2 allele was found in 7% of the Native Americans and 13% of the Mexican Americans, but was only associated with protection against alcohol dependence in the Mexican Americans. Presence of at least one ADH1B*3 allele was found in 4% of the Native Americans and 2% of the Mexican Americans, but was associated with protection against alcohol dependence only in the Native Americans. No associations between alcohol dependence and polymorphisms in ADH1C were found. Conclusions and Scientific Significance: Polymorphisms in ADH1B are protective against alcoholism in these two populations; however, these findings do not explain the high prevalence of alcoholism in these populations.     

ERCP and MRCP--when and why

Since the introduction of endoscopic retrograde cholangiopancreatography (ERCP) in the 1970s, gastroenterologists have a wide spectrum of diagnostic and therapeutic options in the biliopancreatic ductal system at their disposal. With its arrival in the 1990s, magnetic resonance cholangiopancreatography (MRCP) developed as a potent diagnostic tool in biliopancreatic pathology. Currently, MRCP is widely replacing diagnostic ERCP and thereby avoiding complications related to endoscopic technique.We summarize evidence-based data and demonstrate indications and differential indications for MRCP and ERCP in pancreatic disease. Complications related to the procedures and possible medical prevention are discussed. The feasibility of interventional endoscopy in pancreatic disease is reported in detail. The role of gastroenterologists in performing MRCP is outlined on the basis of practical examples.     

Of worms and women: sarcopenia and its role in disability and mortality

The loss of muscle mass during aging has been termed sarcopenia. Sarcopenia results in a decrease in physical strength during aging that results in important consequences for more severely affected individuals in terms of function and as a marker for disability and increased mortality. Despite the clinical importance of this condition, the pathophysiology leading to the development of sarcopenia is not well understood, and few treatments exist to prevent or reverse the condition. Recently, sarcopenia has been found to occur during aging in the nematode Caenorhabditis elegans, which is an organism increasingly used to study genetic and biochemical events involved in aging. Like in humans, sarcopenia in C. elegans leads to declines in mobility and serves as a marker for increased mortality. Interestingly, mutations affecting the age-1 gene, which slows aging of the animal, result in significant delays in the development of sarcopenia, suggesting a direct causal relationship between organismal aging and sarcopenia. These findings suggest that, in humans and worms, sarcopenia may represent a biomarker for the biological age, as opposed to chronological age, of the individual. These findings also suggest that C. elegans will develop into an important model system in which to study the biochemical and genetics events responsible for sarcopenia and to test therapeutics designed to prevent or reverse sarcopenia.     

Genomic and proteomic comparisons between bacterial and archaeal genomes and related comparisons with the yeast and fly genomes

Bacterial, archaeal, yeast, and fly genomes are compared with respect to predicted highly expressed (PHX) genes and several genomic properties. There is a striking difference in the status of PHX ribosomal protein (RP) genes where the archaeal genome generally encodes more RP genes and fewer PHX RPs compared with bacterial genomes. The increase in RPs in archaea and eukaryotes compared with that in bacteria may reflect a more complex set of interactions in archaea and eukaryotes in regulating translation, e.g., differences in structure requiring scaffolding of longer rRNA molecules, expanded interactions with the chaperone machinery, and, in eukaryotic interactions with endoplasmic reticulum components. The yeast genome is similar to fast-growing bacteria in PHX genes but also features several cytoskeletal genes, including actin and tropomyosin, and several signal transduction regulatory proteins from the 14.3.3 family. The most PHX genes of Drosophila encode cytoskeletal and exoskeletal proteins. We found that the preference of a microorganism for an anaerobic metabolism correlates with the number of PHX enzymes of the glycolysis pathway that well exceeds the number of PHX enzymes acting in the tricarboxylic acid cycle. Conversely, if the number of PHX enzymes of the tricarboxylic acid cycle well exceeds the PHX enzymes of glycolysis, an aerobic metabolism is preferred. Where the numbers are approximately commensurate, a facultative growth behavior prevails.     

COPD and erythropoiesis: interactions and consequences

Erythropoiesis is modified in chronic obstructive pulmonary disease (COPD). Tobacco smoke, hypoxaemia, systemic inflammation, and infectious exacerbations are the main factors involved. Polymorphisms in genes involved in the regulation of erythropoiesis probably explain the individual susceptibility and variability in the response. The roles of comorbidities related to COPD and the impact of treatment on erythropoiesis are important confounding factors. While polycythaemia is often related to tobacco smoke and hypoxaemia, it has become less common due to the improvement of COPD follow-up and especially the initiation of long-term oxygen therapy. The control of the main causes is often sufficient, but in cases of severe polycythaemia an erythrapheresis is indicated. Anaemia has recently been reported as a more common and serious complication. It increases dyspnoea and reduces physical activity and quality of life. Its impact on survival and the requirements for healthcare has recently been confirmed. The main approach to the management of anaemia remains exclusion of any curable causes, reducing exacerbations and systemic inflammation, and controlling the comorbidities. Though erythropoietin has some benefits in the so-called "anaemia of chronic disease", this still remains to be confirmed in patients with COPD.     

T淋巴细胞亚群及炎性细胞因子与慢性浅表性胃炎和十二指肠球部溃疡的关系

目的:检测慢性浅表性胃炎和十二指肠球部溃疡患者外周血T淋巴细胞亚群水平的变化及炎性细胞因子白细胞介素-6(IL-6)和白细胞介索-8(IL-8)的血清含量,分析其与幽门螺杆菌(Hp)的关系,探讨可能的发病机制.方法:收集91例经内镜检查证实慢性浅表性胃炎和十二指肠球部溃疡患者的血清标本,用流式细胞仪测T淋巴细胞亚群值,用酶联免疫吸附法(ELISA)检测IL-6和IL-8含量,并分析其与Hp的关系.结果:慢性浅表性胃炎和十二指肠球部溃疡患者外周血CD8及CD4/CD8与正常对照组比较差异有显著性(P＜0.01).血清IL-6含量与正常对照组比较差异有显著性(P＜0.01).血清IL-8含量与正常对照组比较差异有显著性(P＜0.01).Hp阳性者IL-6含量低于Hp阴性者(P＜0.01).Hp阳性者IL-8含量高于Hp阴性者.结论:慢性浅表性胃炎和十二指肠球部溃疡患者CD8细胞数较正常人显著升高,CD4/CD8比值较正常人显著降低.血清IL-6、IL-8含量明显增高.Hp阳性者IL-8含量增高而IL-6含量下降.     

Stress and reproduction: controversies and challenges

Inhibition of reproductive function by the activation of the stress-response has been observed since times of antiquity, however delineating a molecular mechanism by which this occurs in vertebrates continues to present a major challenge. Because recent genome sequencing programs have identified the presence of numerous paralogous peptides and receptors, our understanding of the complexity of the interaction between the reproductive and stress axes has expanded. At the neuroendocrine level, numerous studies have focused on the interaction between the corticotropin-releasing factor (CRF) and gonadotropin-releasing hormone (GnRH) systems in vertebrates. Moreover, most of these studies have been performed using rodent models and may not be completely relevant for non-mammalian vertebrates. A further problem lies in the variation of the functional expression of paralogous genes in the different taxa. In particular, the urocortin 2 and GnRH-II systems have been lost in some lineages, where its function has been taken over by urocortin 3 and GnRH-I, respectively. Establishing an integrated model that incorporates all paralogous systems for both the stress and reproductive system remains to be achieved.     

中美结直肠癌流行病学特征对比及防控策略分析

《中国肿瘤登记年报》作为我国肿瘤登记数据和统计结果的汇总，被广泛应用于肿瘤的研究及防控工作，为我国癌症的防治和研究提供了基础参考数据。而结直肠癌作为我国常见的恶性肿瘤之一，越来越受到外界的关注。尤其是近20年，结直肠癌在以美国为代表的发达国家的发病率呈明显的下降，但在我国却表现为升高趋势，这一增长变化值得我们关注并进行深入地分析。因此笔者结合年报的数据，分析我国结直肠癌流行病学特征，并针对在疾病管控中制定的策略及采取的措施，探寻具有中国特色的结直肠癌防诊治的新方向。