白细胞介素-37与自身免疫性疾病

白细胞介素(interleukin,IL)-37是新近发现的IL-1家族细胞因子,对固有免疫和适应性免疫均有抑制作用.IL-37主要表达于中性粒细胞、淋巴细胞、巨噬细胞、单核细胞、组织上皮细胞、角质形成细胞和树突状细胞.最近大量研究显示,IL-37在许多自身免疫性疾病患者或动物模型中表达异常并发挥关键作用,如系统性红斑狼疮、炎症性肠病、强直性脊柱炎、支气管哮喘、银屑病、Graves病以及类风湿性关节炎等.深入研究IL-37的生物学功能、信号转导途径及作用机制将为IL-37在自身免疫性疾病的治疗提供新思路和靶点.     

Tim3/HMGB1在肿瘤免疫逃逸中的机制研究进展

T细胞免疫球蛋白黏蛋白分子3(Tim-3)是一种1型膜表面蛋白分子,主要在Th1细胞表达,与天然型配体半乳糖凝集素9(galectin-9)反应参与适应性负性免疫调节。此外,Tim-3也在单核-巨噬细胞、自然杀伤细胞以及树突状细胞(DC)表达,参与免疫调节。Tim-3在肿瘤浸润DC高表达,并可与配体高迁移率族蛋白1(HMGB1)结合,通过阻断Toll样受体3(TLR3)、TLR7、TLR9及细胞质中DNA和RNA相关的免疫反应,来抑制核酸介导的固有免疫反应,导致肿瘤免疫逃逸,减弱DNA预防治疗及化疗的效果。本文就Tim-3在肿瘤浸润DC高表达以及Tim-3与配体HMGB1结合参与肿瘤免疫逃逸方面进行综述。     

高迁移率族蛋白B1的研究进展

高迁移率族蛋白B1(HMGB1)是一种非组蛋白核蛋白,普遍存在于真核细胞中,因其在聚丙烯酰胺凝胶电泳中迁移率快而得名。研究表明,HMGB1是一种重要的炎症介质,与自身免疫性疾病、肿瘤等多种疾病的发病机制密切相关。HMGB1广泛的参与妇产科相关疾病。HMGB1的异常表达,与妊娠相关疾病如妊娠期高血压疾病、胎膜早破等以及卵巢癌、子宫内异位症等生殖系统疾病相关。     

钙网蛋白的生物学功能及其与自身免疫疾病的关系

钙网蛋白(Calreticulin,CRT)最初被认为是内质网Ca2+结合蛋白,近年研究发现在细胞外也有表达,具有多种生物学功能,包括蛋白加工、细胞内钙调节、抗原递呈等。抗CRT抗体在多种自身免疫性疾病患者血清中存在,CRT可能是自身免疫性疾病致病因素之一。本文对CRT的生物学功能和它与自身免疫性疾病的关系作一综述。     

核酸酶与自身免疫性疾病

核酸酶在DNA损伤修复和基因组稳定性中起重要作用,而近年发现一些核酸酶的功能异常与多种自身免疫性疾病的发病机制相关。现重点就核酸酶TREX1和Mre11复合物(MRN)等在常见的自身免疫性疾病中的研究进展做一综述。     

钙网蛋白的生物学功能及其与自身免疫疾病的关系

钙网蛋白(Calreticulin，CRT)最初被认为是内质网Ca^2 结合蛋白，近年研究发现在细胞外也有表达，具有多种生物学功能，包括蛋白加工、细胞内钙调节、抗原递呈等。抗CRT抗体在多种自身免疫性疾病患者血清中存在，CRT可能是自身免疫性疾病致病因素之一。本文对CRT的生物学功能和它与自身免疫性疾病的关系作一综述。     

HMGB1半胱氨酸残基氧化还原状态与其功能

高迁移率族蛋白1(High Mobility Group box 1,HMGB1)是一种非组蛋白核蛋白,在许多疾病中发挥重要作用。现有越来越多的研究表明HMGB1蛋白第106位点上半胱氨酸残基的氧化还原状态与其     

Foxp3基因与自身免疫性疾病

自身免疫性疾病系由于机体免疫系统失衡,产生针对自身组织的免疫应答并导致自身组织、器官损害的一类疾病.调节性T淋巴细胞(Regulatory T cell,Treg )具有免疫应答低下和免疫抑制特性,在维持机体免疫耐受和免疫应答稳态方面具有非常重要的作用,Treg的异常与多种自身免疫性疾病有关[1].Foxp3特异性表达于CD4 CD25 Treg细胞,与其发育、成熟以及抑制功能关系密切.本文拟就Foxp3基因的研究进展及与多种自身免疫性疾病的关系作一综述.     

转录因子FOXP3与自身免疫性疾病

Foxp3是Forkhead/winged helix家族的新成员,定位于X染色体上,通过forkhead结构域与DNA特定位点结合,调节目的基因的活化与表达。其编码产物为scurfin蛋白,可能是CD4 CD25 调节性T细胞(简称CD4 CD25 Treg)特异性标志,对CD4 CD25 Treg的增殖分化及功能发挥起重要作用。CD4 CD25 Treg同时表达CD4和CD25,介导机体特异性免疫耐受,抑制机体自身免疫性疾病、肿瘤、病毒感染及器官移植免疫等。Foxp3基因突变或缺失可引起风湿、类风湿、系统性红斑狼疮、X-相关综合征等疾病;Foxp3基因过表达可诱导机体对肿瘤、病毒及器官移植等产生免疫耐受。Foxp3表达上调,可维持免疫耐受、抑制排斥反应和自身免疫性疾病;Foxp3表达下调,降低机体免疫耐受,可治疗肿瘤、器官移植及慢性病毒感染。     

高迁移率族蛋白1在类风湿性关节炎发生中的作用

高迁移率族蛋白1（HMGB1）是一种非组蛋白核蛋白,是一个具有双重功能的警报素,其免疫活性取决于细胞定位。在细胞内,HMGB1结合DNA调节转录;在细胞外,HMGB1具有和TNF相似的细胞因子活性。HMGB1参与许多免疫介导疾病的发病过程包括类风湿性关节炎（RA）。因而,研究炎症性关节炎新的发病机制可以提供新的治疗靶点。     

陕北地区临床遗传病调查研究

本文对陕北地区一个地区级医院、六个县级医院从１９８１～１９９０年十年间临床所见的遗传病作了调查分析。共查阅病历１８８，９４３份，其中遗传病２３，４１８份，占总病历数的１２．３９％；男性遗传病１３，８００例，女性９．１８１例，男：女＝１．５：１。以发病年龄看，婴幼儿多于青少年，青少年多于中老年；按年度计算，前５年明显少于后５年。共发现遗传病种类１３１种，其中单基因病６７种、３５６３例，占遗传病例１５．２１％；多基因病４８种，１８４８２例，占遗传病例７８．９２％；染色体病１６种，１３７３例，占遗传病例５．８６％。从本资料可见，多基因病最多，而且随年度出现率增高。其次隐性遗传病和染色体病较多，这可能与陕北地区自然条件差和科学文化发展慢以及通婚圈小等有关。     

心理干预对复发性尖锐湿疣患者情绪与免疫的影响

目的：探讨适当的心理干预对复发性尖锐湿疣（CA）患者的情绪及免疫是否存在积极的调节作用。方法：对一组CA患者术后采取适当的心理干预,及时调整患者的不良心理状态,同时测定了心理干预前后不同期间患者的外周血T淋巴细胞亚群分布,并与未加心理干预的CA手术病人作对照。结果：心理干预后的患者,心身健康水平明显好于未干预患者,其T淋巴细胞亚群也相应升高,至术后一个月已恢复正常,而未加心理干预的患者则无明显变化。结论：适当的心理干预对CA的预防复发及免疫功能调节存在积极的作用。     

Binswanger病和Alzheimer病的临床与脑电地形图分析

观察了３０例Ｂｉｎｓｗａｎｇｅｒ病（ＢＤ）和３０例Ａｌｚｈｅｉｍｅｒ病（ＡＤ）患者的脑电地形图（ＢＥＡＭ）变化。结果发现，ＢＤ患者和ＡＤ患者的ＢＥＡＭ阳性率均高于脑电图（ＥＥＧ）。ＢＤ患者ＢＥＡＭ局灶性和阵发性改变阳性率明显高于ＡＤ患者，并且双侧脑电功率谱不对称，以额、中央、枕区θ波多见，而ＡＤ患者双侧功率谱基本对称，以额、颞、顶区δ波多见。ＢＤ患者长谷川简易智力量表分值与ＢＥＡＭ异常改变程度有显著相关性。提示ＢＥＡＭ检查对ＢＤ的鉴别诊断和病情监测具有一定意义。     

Childhood neuronal ceroid-lipofuscinoses in Argentina

We report on 30 cases of neuronal ceroid lipofuscinoses (NCL), mainly diagnosed in 1985–1993 in Argentina, whose population is predominantly of European descent. Twenty-four cases were late infantile Jansky-Bielschowsky (LINCL) and 6 were juvenile Spielmeyer-Vogt (JNCL). Sex ratio was female: male, 20:10. Age range and mean at onset and at diagnosis for the LINCL cases were 1–6 years, mean 3.1, and 2–11 years, mean 5.5, and for the JNCL cases, 5–9 years, mean 7, and 9–18 years, mean 13, respectively. Cases were referred for biopsy after neurological examination, and most included complete electrophysiological [electroencephalography (EEG) with photic stimulation, electroretinography (ERG), and visual-evoked potential (VEP)], neuroimaging, and neurometabolic investigation. NCL was the first suspected clinical diagnosis, followed by mitochondrial encephalopathy in some cases of recent onset. Except for 1 case, clinical findings were homogeneous in LINCL, characterized by refractive epilepsy, mental regression and progressive deterioration, ataxia, myoclonia, and visual loss. Abnormal VEP, ERG, and EEG, with polyphasic high-voltage spikes when photic stimulation was performed at low frequency, were observed. Visual impairment and retinitis pigmentosa were early manifestations in 4/6 JNCL, followed by mental abnormalities, motor deterioration, and myoclonic jerks, while 2/4 followed an atypical course. In both variants inheritance was autosomal-recessive. Five out of 27 families had more than 1 affected member, 3 of whom were included in our series. Diagnosis was initially performed in conjunctival biopsy in 3 cases, skin in 5, muscle in 17, and brain in 5, though most cases had a concomitant biopsy from another tissue including nerve, and there was a single brain autopsy. In the LINCL variant, storage material was mainly curvilinear, also exhibiting dense areas and electron-lucent vacuoles in 1 case. In addition to fingerprint profiles in 4/6 cases, JNCL biopsies presented curvilinear profiles in a skin biopsy in 1 case, and electronlucent vacuoles in 2 cases in a muscle and brain biopsy coexisting within the same inclusion, with the curvilinear profiles surrounded by a unit membrane, while the other 2/6 had granular osmiophilic inclusions with poorly defined rectilinear areas. The purpose of this report is to describe NCL in a country mainly populated by European descendants, in order to contribute data for further collaborative research. © 1995 Wiley-Liss, Inc.     

先天性遗传性疾病108例分析

１０８例均为１９９４年一年内来我院遗传门诊就诊者，包括遗传病咨询者。其中出生即为死胎者１４例，余９４例患者接受专科检查，病例分类如下；染色体病２８便，常隐４７例，常显３例，Ｘ连锁隐性７例，多基因遗传病２３例。本文复述了遗传概念、传递方式及其特点，有助于我们向患者提供充分的遗传学咨询，达到优生优良的目的。     

High frequency of low-risk human leukocyte antigen class II genotypes in latent celiac disease

Human leukocyte antigen (HLA) class II genotypes in latent celiac disease, a clinical variant of celiac disease (CD) have been scarcely studied. The aim of this work was to investigate whether latent CD and CD share similar frequencies of HLA class II genotypes. HLA class II genotypes of CD patients compared with controls were subdivided in the following at-risk groups: DQB1*02/DQB1*02 (43.0%, odds ratio [OR] 8.02, p < 0.0001), DQB1*0302/DQB1*02 (12.2%, OR 2.77, p = 0.0002), DQB1*02/DQB1*X (39.2%, OR 1.23, p = 0.1903), DQB1*0302/DQB1*X (3.4%, OR 0.35, p = 0.0064) and DQB1*X/DQB1*X (0.8%, OR 0.01, p = 0.0001) where X is neither DQB1*0302 nor DQB1*02. Next, HLA class II genotypes of 21 latent CD patients were compared with the above at-risk groups. Only one latent CD patient (4.8%) was found in the high risk DQB1*02/DQB1*02 group, three (14.3%) were DQB1*0302/DQB1*02, one (4.8%) was DQB1*0302/DQB1*X and the remaining 16 (76.2%) showed the DQB1*02/DQB1*X genotype. Noteworthy, the only 1 patient with the DQB1*02/DQB1*02 high risk genotype did not carry the DR3-DQB1*02/DR3-DQB1*02 or the DR3-DQB1*02/DR7-DQB1*02 but the uncommon DR3-DQB1*02/DR4-DQB1*02 genotype. These data suggest that latent CD is prevalently associated with low-risk HLA class II genotypes.     

河南农村地区阿尔茨海默病筛查的神经心理和功能测验

目的 :了解神经心理测试量表和功能量表在农村地区阿尔茨海默病 (AD)筛查诊断中的应用特点。方法 :应用FULD物体记忆测验 (FOM)、言语流畅性测验 (RVR)、韦氏数字广度测验 (DS)、积木测验 (BD)、无肌力减退的运动障碍测验 (APRAXIA)和PFEFFER功能活动量表 (POD)进一步检查那些简易智力检查表 (MMSE)筛查阳性的农村 50岁以上人群。结果 :发现FOM的各项单项分 ,在AD组、血管性痴呆 (VaD)组、混合性痴呆 (AD VD)组、抑郁症组和非痴呆组间有显著性差异。其中有关记忆的项目特异度一般 70 %以上 ,以FOM总分的敏感度和特异度最高。而RVR、APRAXIA敏感度均较低 ,DS、BD的特异度较低 ,POD的敏感度和特异度均不高。FOM的各项回忆因子分与RVR总分的相关性较好 ,而FOM各项与DS总分和BD总分的相关系数不如与RVR总分高。结论 :FOM在AD的诊断中有重要的地位 ,而其它神经心理测验有辅助作用     

Celiac disease: diagnosis,autoimmune mechanisms and treatment

Celiac disease is a systemic autoimmune disorder triggered by the ingestion of gluten found in wheat and related grains. Once considered rare, celiac disease is now thought to affect more than one in 100 individuals, and is commonly associated with other autoimmune disorders. It predisposes patients to an increased risk of malignancy if left untreated. Celiac disease is HLA restricted as only HLA-DQ2 and -DQ8 are able to bind deamidated gluten with sufficient affinity to trigger an immune response. Both cellular and humoral immune activation occur, leading to local tissue damage and antibody formation. These antibodies, primarily to tissue transglutaminase, are the basis for highly accurate serologic testing, although the gold standard for celiac disease diagnosis remains small intestinal biopsy. Currently, the only treatment for celiac disease is a life-long gluten-free diet, although multiple novel therapeutic modalities are being studied. Although most individuals with celiac disease respond completely to gluten withdrawal, 10–20% have persistent symptoms at some point during their course and less than 1% develop refractory celiac disease, an entity of substantial morbidity.     

Prevalence of type I spinal muscular atrophy in North Dakota

In order to establish the incidence and prevalence of type I spinal muscular atrophy (SMA Werdnig-Hoffmann disease) in North Dakota, we reviewed the death certificates for the past 8 years. Between 1980 and 1987 the prevalence of was 1.5 per 10,000. The incidence was 1 in 6,720. This suggests a carrier frequency of 1 in 41 in North Dakota with a gene frequency of 0.0122. In North Dakota, type I spinal muscular atrophy appears to be 3 to 10 times more common than in other locations.