代谢产物非“废物”——新的代谢分子调节系统北大核心CSCD

机体自稳态是在神经、内分泌和免疫这三大调节系统相互作用下实现的。其中神经系统主要通过递质、调质以反射弧的方式进行调节,内分泌系统通过激素进行体液调节,而免疫系统则通过体液和细胞免疫和产生细胞因子等而发挥作用[1]。对上述三大系统研究的成果有力地推动了生理学和相关疾病发病机制研究与防治的进展。     

溃疡性结肠炎的微生物学研究现状与展望

溃疡性结肠炎 (ulcerative colitis,UC)又称慢性非特异性溃疡性结肠炎 (chronic nonspecific ulcerative colitis) ,是一种病因不明的直肠和结肠慢性炎症疾病 ,病情轻重不等 ,多反复发作 ,可发生在任何年龄 ,多见于青壮年 ,亦可见于儿童或中年 ,男女发病率无明显差别。目前认为本病的发病涉及免疫异常 ,是一种自体免疫性疾病 ,和变态反应及遗传、感染、细胞因子、氧自由基、神经内分泌肽等因素有关 ,尤其是在微生物学研究方面 ,近几年取得的成绩非常喜人。现就有关 UC微生物学研究现状及展望作一综述。1　微生物学研究现状1.1　细菌学　 U…     

促性腺激素释放激素的免疫调节功能

随着对神经与免疫系统相互作用研究的深入,神经激素在免疫系统中的作用越来越多地被关注。由下丘脑合成的促性腺激素释放激素(gonadotropin-releasing hormone,Gn RH)及其受体均在免疫细胞中被发现,表明Gn RH在免疫系统内具有自分泌或旁分泌作用,对机体免疫反应、免疫细胞的活性与增殖、免疫介质释放和细胞功能具有免疫调节作用,对自身免疫疾病也有一定的影响。Gn RH可能是免疫系统调节的重要组成部分,在调节免疫介导的疾病中发挥作用,对于构建神经、免疫、内分泌三大系统互相调节网络起到了重要的作用。     

神经内分泌系统与免疫系统间的联系

神经内分泌系统与免疫系统间有密切的双向调节联系。免疫细胞上有多种神经内分泌激素受体,多种激素会影响免疫功能,免疫细胞也可以合成神经递质样物质和激素影响内分泌系统。     

Th17/Treg 细胞在银屑病的发病机制研究进展

Th17细胞和Treg细胞是CD4+T细胞在不同细胞因子环境中分化出的新亚群,发挥不同的生物学效应,使机体的免疫系统处于平衡状态.Th17/Treg细胞失衡可引起一系列自身免疫性疾病.银屑病是与遗传、免疫异常有关的皮肤炎症性疾病,其发病机制尚不清楚.越来越多的研究发现,Th17细胞增多和Treg细胞减少及其分泌的细胞因子在银屑病的发病中有着重要作用.本文围绕这一机制综述了近年来有关Th17细胞、Treg细胞在银屑病发病机制中作用的研究,帮助我们更深入地了解银屑病的发病机制并为今后临床诊断和治疗提供依据.     

Toll样受体4在实验性自身免疫性葡萄膜炎发病中的作用

目的:研究常见感染菌菌壁成份脂多糖(LPS)在自身免疫性眼病-葡萄膜炎的致病作用.方法:用视网膜抗原IRBP和福氏完全佐剂免疫B10.RⅢ小鼠,诱发实验性自身免疫性葡萄膜炎(EAU),在免疫动物同时添加LPS.免疫19天后检查迟发型变态反应(DTH);21天处死小鼠,收集腹股沟淋巴结和髂动脉淋巴结细胞,检测抗原特异性T淋巴细胞增殖和炎症细胞因子的分泌.结果:LPS加重B10.RⅢ小鼠EAU的发病;增强DTH反应;增加抗原特异性T淋巴细胞增殖和IL-17、IFN-γ的分泌.结论:LPS能够促进EAU发病,从而证明病原微生物感染可能参与如葡萄膜炎等自身免疫性疾病的发生.     

免疫性血小板减少症与机体免疫失衡

免疫性血小板减少症(ITP)是一种自身免疫性出血性疾病,多种免疫相关机制参与其中.B细胞产生抗血小板抗体介导巨噬细胞吞噬血小板被认为是ITP经典的发病机制.T细胞亚群以及相关细胞因子介导的细胞免疫失衡在ITP中也逐渐被证实.此外,抗原提呈细胞、间充质干细胞等免疫细胞失衡、基因表达异常、感染、代谢等因素造成的免疫微环境失...     

自身免疫性疾病治疗性疫苗研究进展

自身免疫性疾病的发生与体内自身反应性T／B细胞的异常活化有关。病理性自身免疫应答是多发性硬化、重症肌无力等自身免疫性疾病的主要致病原因。针对已感染致病原的无症状携带者或发病的患者的自身免疫性疾病治疗性疫苗能特异性地调节异常的免疫应答,具有重要的理论价值和应用前景。     

β-溶血型链球菌与银屑病发病、发生及发展的研究现状

银屑病的发病与链球菌感染的相关性近年来得到人们的密切关注.银屑病是一类由T细胞介导的自身免疫性疾病,链球菌抗原可在易感人群中诱发或加重银屑病并使银屑病慢性持续存在.从β-溶血型链球菌诱发银屑病相关的细胞壁、细胞膜、CpG DNA序列及其他相关蛋白的自身抗原及β-溶血型链球菌通过活化T细胞、抗原抗体反应途径、通过作用机体的基因改变遗传易感性诱发银屑病的可能作用途径几方面,阐述β-溶血型链球菌与银屑病发病、发生及发展的研究现状.     

神经内分泌和免疫系统之间的相互调节作用(一)

我们一般认为机体各器官、系统的功能都处于神经系统和内分泌系统的调节和控制之下。神经系统和内分泌系统是机体内起主导作用的调节系统。它们密切联系 ,互相配合 ,维持内环境相对稳定。这一传统的观念近年来受到了挑战。新的观点认为 ,免疫系统也是机体内一个重要感受和调节系统。神经内分泌和免疫系统之间的相互作用 ,对机体在不同条件下稳态的维持起有决定性的作用。因此 ,在谈到机体的功能调节时 ,如果不谈免疫系统的作用 ,将是一种缺陷。目前这方面的研究已经发展成为一门独立的边缘学科 :神经免疫调节学、神经免疫内分泌学或神经免疫…     

抽动秽语综合征遗传学研究

抽动秽语综合症(Gilles de la Tourette’s syndrome,GTS,TS)是一种慢性复杂性神经精神障碍,多起病于儿童期,以多发性运动性抽动伴不自主发声为主要临床表现,并伴多种并发症及神经行为障碍.目前已有大量关于TS遗传学研究报道,但其主要遗传学基础尚未鉴定.在此就抽动秽语综合征的遗传学研究做一介绍.     

Tourette syndrome in a pedigree with a 7;18 translocation: identification of a YAC spanning the translocation breakpoint at 18q22.3.

Tourette syndrome is a neuropsychiatric disorder characterized by the presence of multiple, involuntary motor and vocal tics. Associated pathologies include attention deficit disorder and obsessive-compulsive disorder (OCD). Extensive linkage analysis based on an autosomal dominant mode of transmission with reduced penetrance has failed to show linkage with polymorphic markers, suggesting either locus heterogeneity or a polygenic origin for Tourette syndrome. An individual diagnosed with Tourette syndrome has been described carrying a constitutional (7;18) chromosome translocation (Comings et al. 1986). Other family members carrying the translocation exhibit features seen in Tourette syndrome including motor tics, vocal tics, and OCD. Since the disruption of specific genes by a chromosomal rearrangement can elicit a particular phenotype, we have undertaken the physical mapping of the 7;18 translocation such that genes mapping at the site of the breakpoint can be identified and evaluated for a possible involvement in Tourette syndrome. Using somatic cell hybrids retaining either the der(7) or the der(18), a more precise localization of the breakpoints on chromosomes 7 and 18 have been determined. Furthermore, physical mapping has identified two YAC clones that span the translocation breakpoint on chromosome 18 as determined by FISH. These YAC clones will be useful for the eventual identification of genes that map to chromosomes 7 and 18 at the site of the translocation.     

Tourette syndrome: clinical and psychological aspects of 250 cases.

Tourette syndrome is a common hereditary neuropsychiatric disorder consisting of multiple tics and vocal noises. We summarize here clinical aspects of 250 consecutive cases seen over a period of 3 years. The sex ratio was four males to one female, and the mean age of onset was 6.9 years. Only 10% were Jewish, indicating that it is not more prevalent in Ashkenazi Jews. Only 33% had compulsive swearing (coprolalia), indicating that this is not necessary for the diagnosis. The most frequent initial symptoms were rapid eye-blinking, facial grimacing, and throat-clearing. In this series, it was clear that Tourette syndrome is a psychiatric as well as a neurological disorder. Significant discipline problems and/or problems with anger and violence occurred in 61%, and 54% had attention-deficit disorder with hyperactivity. Some degree of exhibitionism was present in 15.9% of males and 6.1% of females. Obsessive-compulsive behavior was seen in 32%. Other than tics and vocal noises, the most common parental complaints were of short temper and everything being a confrontation. There were no significant clinical differences between familial and sporadic cases. Whenever a child presents with a learning disorder, attention-deficit disorder, or significant discipline or emotional problems, the parents should be questioned about the presence of tics or vocal noises in the patient and other family members.     

Increased Thalamic Gamma Band Activity Correlates with Symptom Relief following Deep Brain Stimulation in Humans with Tourette's Syndrome

Tourette syndrome (TS) is an idiopathic, childhood-onset neuropsychiatric disorder, which is marked by persistent multiple motor and phonic tics. The disorder is highly disruptive and in some cases completely debilitating. For those with severe, treatment-refractory TS, deep brain stimulation (DBS) has emerged as a possible option, although its mechanism of action is not fully understood. We performed a longitudinal study of the effects of DBS on TS symptomatology while concomitantly examining neurophysiological dynamics. We present the first report of the clinical correlation between the presence of gamma band activity and decreased tic severity. Local field potential recordings from five subjects implanted in the centromedian nucleus (CM) of the thalamus revealed a temporal correlation between the power of gamma band activity and the clinical metrics of symptomatology as measured by the Yale Global Tic Severity Scale and the Modified Rush Tic Rating Scale. Additional studies utilizing short-term stimulation also produced increases in gamma power. Our results suggest that modulation of gamma band activity in both long-term and short-term DBS of the CM is a key factor in mitigating the pathophysiology associated with TS.     

A family study of Gilles de la Tourette syndrome.

Previous studies have demonstrated that Gilles de la Tourette syndrome (TS) is a familial disorder and that chronic tics (CT) and obsessive compulsive disorder (OCD) appear to be etiologically related to the syndrome. In the present study we report the results from a study of 338 biological relatives of 86 TS probands, 21 biologically unrelated relatives of adopted TS probands, and 22 relatives of normal subjects. The 43 first-degree relatives of the adopted TS and normal probands constituted a control sample. The rates of TS, CT, and OCD in the total sample of biological relatives of TS probands were significantly greater than in the relatives of controls. In addition, the morbid risks of TS, OCD, and CT were not significantly different in families of probands with OCD when compared to relatives of probands without OCD. These findings provide further evidence that OCD is etiologically related to TS.     

A controlled study of Tourette syndrome. II. Conduct.

To assess conduct in Tourette syndrome (TS), 47 controls, 246 TS patients, 17 attention-deficit-disorder (ADD), and 15 ADD patients with minor tics or a family history of TS (ADD 2(0) TS) were compared for the following behaviors: running away from home, lying, stealing, starting fires, vandalism, being in trouble with the law, fighting, shouting at parents or peers, attacking others, lack of respect for adults, short temper, hurting animals, feeling full of hate, being unable to stop fighting, and problems with drugs and alcohol. With the exception of running away from home and being in trouble with the law, TS patients were significantly different from controls in all other behaviors. When the components were combined for a total conduct score, only one (2.1%) of the controls had a score greater than 13, and he had TS. By contrast, 35% of the TS patients had scores greater than 13 (P less than .0005). The correlation coefficient between the total conduct score and ADD score was .48. Although the presence of ADD was an important factor in determining conduct in TS, other factors such as depression and compulsive behavior also played a contributing role. There was little correlation between the total conduct score and the number of tics. It is estimated that among non-economically disadvantaged children, 10%-30% of conduct disorder may be due to the presence of a TS gene.     

Detection of major gene for Gilles de la Tourette syndrome

The families of 250 consecutive, unselected patients with Tourette syndrome (TS) were analyzed. If the parents had either motor or vocal tics, but not both, there was an increased risk of both TS and tics in the offspring. The mode of inheritance of the combined tic-Tourette trait was evaluated in both nuclear families and extended pedigrees. Complex segregation analysis was carried out allowing for possible contributions from both a major autosomal locus and multifactorial inheritance of variation in the background of each genotype. The most likely mode of inheritance was a major semidominant gene, Ts, with low heritability of the multifactorial background variation. This was true regardless of assumptions about the prevalence of the disorder. The hypothesis of strict multifactorial inheritance could not be rejected with nuclear family data alone. However, the hypothesis of no major gene effect was rejected using data on 3 generations for any estimate of lifetime risk less than 12 per 1,000 in the general population. A pure recessive major gene effect was also rejected. With a gene frequency of approximately .5%, the penetrance was estimated to be about 94% in abnormal Ts/Ts homozygotes, 50% in Ts/ts heterozygotes, and less than 0.3% in normal ts/ts homozygotes. More than two of every three cases are heterozygotes, and nearly all other cases are phenocopies or new mutations. This is the first demonstration by segregation analysis of a major gene in a human neuropsychiatric disorder with a frequency approaching 1% of the population.     

Before your very eyes: illness, agency, and the management of Tourette Syndrome

In this article, I examine the ways that people with Tourette Syndrome (TS) manage the motor and vocal tics characteristic of this neurological disorder. To mitigate the powerful stigmas associated with TS, individuals must either remove tics from public view or strive to recast the way that they are perceived. Drawing on ethnographic research with TS sufferers in Indiana, I elaborate three strategies by which this is done, strategies referred to here as displacement, misattribution, and contextualization. These processes strongly affect both the symptoms themselves and the subjective experience of the illness. They also affect the perception of TS in the larger culture, associating the disease with florid symptoms like cursing--symptoms that, although not at all typical of TS, are the ones most resistant to these kinds of management. These patterns highlight how individual agency may actively shape the cultural construction of illness.     

Progress in the search for genetic linkage with Tourette syndrome: An exclusion map covering more than 50% of the autosomal genome

Gilles de la Tourette syndrome is a neuropsychiatric disorder with an autosomal dominant mode of inheritance and reduced penetrance at a single genetic locus. Several research groups have genetic linkage studies underway to detect the chromosomal location of the gene that predisposes for this disorder. Strong and clear evidence of linkage has not yet been produced for Tourette syndrome. This paper presents an overview of the methods and progress of the groups centered at Yale University and Erasmus University in excluding linkage from a large portion of the genome. Our labs have screened 228 genetic marker loci for linkage with a gene for this disorder in a series of affected families in the United States, Canada, The Netherlands, and Norway. More than 50% (and perhaps as much as 66%) of the autosomal genome has now been excluded on the assumption that genetic heterogeneity is not an important factor in the Tourette syndrome pedigrees pooled for this summary.