胸腺瘤患者胸腺淋巴细胞Fas表达与重症肌无力的相关性

目的 探讨胸腺瘤患者发生重症肌无力(myasthenia gravis,MG)的机制及Fas基因在MG发病中的作用.方法 收集131例胸腺瘤患者,按是否合并MG分为合并MG组(70例)和不合并MG组(61例)两组.应用免疫组织化学、蛋白电泳、聚合酶链反应和酶联免疫吸附等方法检测两组患者胸腺淋巴细胞Fas蛋白表达和血清可溶性Fas(sFas)水平,应用DNA测序技术检测Fas基因结构变异.结果 胸腺瘤合并MG组患者胸腺淋巴细胞Fas表达水平明显低于胸腺瘤不合并MG组,sFas含量[(3879.06±706.51) pg/mL]明显高于胸腺瘤不合并MG组[(1868.18±391.46) pg/mL] (P＜0.01);胸腺瘤合并MG组胸腺淋巴细胞Fas基因第6外显子16和21位点T→G置换突变发生率分别为65％和75％,明显高于胸腺瘤不合并MG组(两位点均为5％)(P＜0.05).结论 胸腺淋巴细胞Fas基因外显子6某些位点发生突变,所编码的Fas蛋白跨膜区变异或缺乏跨膜区而导致Fas结构和功能的改变可能是MG发生的主要原因.     

眼肌型及全身型重症肌无力患者外周血T淋巴细胞Fas的表达

目的 探讨Fas介导的细胞凋亡与眼肌型(ocular myasthenia gravis,OMG)及全身型重症肌无力(generalized myasthenia gravis,GMG)发病的关系.方法 采用流式细胞技术检测4例OMG、13例GMG患者及13例健康对照组外周血淋巴细胞中CD4、CD8及Fas的表达.结果 OMG、GMG组与对照组外周血T淋巴细胞表面CD4、CD8分子表达的差异无统计学意义(P>0.05).GMG组与对照组外周血T淋巴细胞中Fas+细胞比例的差异有统计学意义(41.72%±8.73%、31.22%±13.00%,P:0.017).GMG组与对照组Fas表达增高者比例的差异有统计学意义(61.5%、15,4%,P=0.041).Fas表达增高的GMG患者病情较重.病程较长.胸腺瘤发生率较高.OMG与GMG组外周血T淋巴细胞中Fa8+、CD4+Fas+、CD8+Fas+细胞比例差异无统计学意义(P>0.05).结论 GMG患者外周血T淋巴细胞中Fas的表达升高,OMG与GMG患者外周血T淋巴细胞中Fas的表达无显著差异,二者可能同属一种系统性疾病.     

重症肌无力患者胸腺细胞及外周血淋巴细胞Fas表达研究

目的 探讨重症肌无力(MG)的发病机制。方法 采用流式细胞术(FCM)分别检测MG患者胸腺细胞、外周血淋巴细胞(PBL)及地塞米松培养胸腺细胞的Fas表达。结果 MG患者PBL CD4、CD8细胞Fas表达率(分别为49％，34％；39％，34％)与对照组(分别为58％，25％；49％,24％)相比差异无显著性；MG患者胸腺细胞Fas表达率(11．20％，6．13％)较对照组(6．15％，1．84％)明显增高；地塞米松培养组Fas表达率MG组、正常人组分别为11．54％、8．62％和7．08％、3．13％，与空白对照组(MG组、正常人组分别为11．36％、6．87％和7．22％、2．86％)相比差异无显著性。结论 MG患者PBI，CD4、CD8细胞Fas表达率无明显增高，可能与自身反应淋巴细胞Fas和PBL FasL结合，发生程序化死亡有关。MG患者胸腺细胞Fas表达增高，可能参与MG发病初制。     

胸腺切除对重症肌无力患者T淋巴细胞亚型的影响

目的：观察胸腺切除(Tx)术对重症肌无力(MG)病人的临床疗效及对T淋巴细胞亚型的影响。方法：用许氏评分法观察30例伴胸腺增生或胸腺瘤的MG患者的病情严重程度及Tx术后2个月的临床疗效;采用直接免疫荧光染色和流式细胞仪技术测定60名志愿健康者和30例伴胸腺增生或胸腺瘤的MG患者Tx术前及术后2个月T淋巴细胞亚型的变化。结果：伴胸腺增生或胸腺瘤的MG病人Tx术前外周血中CD4＋T淋巴细胞的百分率较正常人显著增多(P＜0．01),CD8＋T淋巴细胞的百分率较正常人显著减少(P＜0．01),CD4＋/CD8＋T细胞的比例明显增高(P＜0．01)。伴胸腺增生MG病人Tx术后随着临床症状的改善,CD8＋T淋巴细胞的百分率较术前显著升高(P＜0．05),CD4＋/CD8＋T细胞的比例较术前显著下降(P＜0．05)。伴胸腺瘤MG病人Tx术后随着临床症状的改善,CD4+T淋巴细胞的百分率较术前显著下降(P＜0．05),CD4＋/CD8＋T细胞的比例较术前显著下降(P＜0．05)。结论：重症肌无力患者T淋巴细胞亚型的测定既可以为MG免疫病理学的发病机理的研究提供实验依据,也能为Tx治疗MG提供一个客观的实验室指标,为判断疾病的转归提供实验依据。     

胸腺与重症肌无力

重症肌无力(MG)作为一种典型的自身免疫性疾病,其发病与患者胸腺内发生的异常免疫反应密切相关,大约80%左右的MG患者胸腺异常,包括胸腺增生、胸腺瘤等。因此,探索MG的发生、发展及其与胸腺内发生的免疫反应之间的关系,可为MG的治疗提供实验依据和新的思路。现就胸腺细胞及其表达的分子与MG的相关性做一综述。     

伴胸腺瘤重症肌无力发病机制研究进展

重症肌无力(myasthenia gravis,MG)是以胸腺为靶器官的器官特异性自身免疫性疾病,伴胸腺瘤MG与不伴胸腺瘤MG发病机制不同。近年来发现伴胸腺瘤MG在T细胞数量和功能、自身抗体的种类以及遗传学等方面与不伴胸腺瘤MG存在差异。本文旨在结合文献从胸腺微环境、T细胞发育、自身抗体及遗传学等方面在伴胸腺瘤MG发病机制中作用进行综述。     

重症肌无力伴胸腺瘤患者胸腺组织蛋白4.1R mRNA的表达研究

目的探讨蛋白4.1R在重症肌无力(myasthenia gravis,MG)伴胸腺瘤患者胸腺组织中的表达情况。方法运用半定量RT-PCR方法检测7例胸腺瘤MG与7例正常对照组胸腺组织中蛋白4.1R的表达。结果胸腺瘤MG组胸腺组织中蛋白4.1R mRNA的相对表达水平为0.84±0.46,与对照组0.43±3.69相比明显增高,差异有统计学意义(P0.05)。结论蛋白4.1R在胸腺瘤MG患者胸腺组织中mRNA水平表达异常,可能干扰胸腺细胞的信号传导,从而影响胸腺细胞的增殖和活化,参与了MG的发生。     

GSTM3 mRNA在重症肌无力患者胸腺组织中的表达

目的 探讨谷胱甘肽S-转移酶m3(GSTM3mRNA在重症肌无力患者及正常人胸腺组织中的表达情况.方法 利用荧光定量聚合酶链反应(FQ-PCR)方法定量分析GSTM3 mRNA在重症肌无力胸腺与正常胸腺组织中的表达水平.结果 GSTM3 mRNA在重症肌无力患者和正常人胸腺组织中的表达水平分别为0.67±0.10和0.58±0.05,两者比较差异有统计学意义(P<0.01.结论 GSTM3 mRNA在MG胸腺组织中高表达,可能与MG的发生、发展密切相关.     

55例重症肌无力胸腺MRI表现与临床病理对照分析

目的分析总结重症肌无力胸腺MRI特点,并与临床病理对照,探讨MRI对重症肌无力胸腺病变的诊断价值。方法回顾分析手术切除胸腺治疗55例重症肌无力患者的MRI表现及与临床病理对照。结果55例重症肌无力术前MRI诊断胸腺增生32例,胸腺瘤19例,胸腺正常4例;术后病理诊断胸腺增生32例,胸腺瘤20例,胸腺正常2例,萎缩1例。MRI对重症肌无力患者胸腺疾病诊断的敏感度为96.23%,特异度为100.00%,准确度为96.34%。MRI对胸腺增生、胸腺瘤、胸腺正常诊断的敏感度分别为93.75%、90.00%(50%;特异度分别为91.30%、97.12%、50%)。结论重症肌无力胸腺MRI表现有一定特点,MRI对重症肌无力胸腺病变有较高诊断价值,但对胸腺正常诊断有一定局限性。     

胸腺瘤WHO新分类与重症肌无力的关系

此文概述了胸腺瘤世界卫生组织(WHO)分类的病理学特点.在此新分类中指出,发生重症肌无力者以B型胸腺瘤居多;肿瘤上皮组织相关抗原减少、自身免疫性T细胞的释放可能参与胸腺合并重症肌无力的发生机制.     

Macrophage contribution to the response of the rat organ of Corti to amikacin

Transdifferentiation of nonsensory supporting cells into sensory hair cells occurs naturally in the damaged avian inner ear. Such transdifferentiation was achieved experimentally in the cochlea of deaf guinea pigs through Atoh 1 gene transfection. Supporting cells may therefore serve as targets for transdifferentiation therapy. Supporting cells rapidly degenerate after hair cell disappearance, however, limiting the therapeutic window for gene transfer. We studied the time course of ultrastructural and phenotypical changes occurring in Deiters cells (hair cell supporting cells) after ototoxic treatment in the rat. The presence of macrophages in the cochlea was also investigated, to study any deleterious effects they may have on pathologic tissues. One week after treatment most hair cells had disappeared. Deiters cells no longer expressed the glial marker vimentin but instead displayed typical hair cell markers, the calcium binding proteins calbindin and parvalbumin. This suggests that a process of transdifferentiation of Deiters cells into hair cells was activated. By 3 weeks post-treatment, however, the Deiters cells began to degenerate and by 10 weeks post-treatment the organ of Corti was degraded fully. Interestingly, a marked increase in macrophage density was seen after the end of amikacin treatment to 10 weeks post-treatment. This suggests chronic inflammation is involved in epithelium degeneration. Consequently, early treatments with anti-inflammatory factors might promote supporting cell survival, thus improving the efficacy of more specific strategies aimed to regenerate hair cells from nonsensory cells.     

Hypohidrosis Related to the Administration of Topiramate to Children

PURPOSE: Topiramate (TPM) is an antiepileptic agent, first licensed in the United Kingdom in 1994, that is used in the treatment of patients with refractory seizure disorders. TPM is a monosaccharide d-fructose derivate, with sulfamate function, and so far, few adverse side effects have been reported. METHODS: We describe three patients with epilepsy who were treated with TPM and developed hypohidrosis, heat and exercise intolerance, as well as fever. The sudomotor function was assessed after peripheral stimulation with pilocarpine iontophoresis. RESULTS: Sweat response was reduced in all three patients. Signs and symptoms ceased after drug suppression. CONCLUSIONS: This side effect associated with TPM, which has not been described previously, can be clinically significant during heat stress and exercise challenge.     

Live to the rhythm, slave to the rhythm

Circadian rhythms in health and disease have most often been described in terms of their phases and amplitudes, and how these respond to a single exposure to stimuli denoted as zeitgebers. The present paper argues that it is also important to consider the 24-h regularity in the repeated occurrence of the zeitgebers. The effect of the regularity of stimulation by light, melatonin, physical activity, body temperature, corticosteroids and feeding on synchronization within and between the central circadian clock and peripheral oscillators is discussed. In contrast to the phase shifts that can be recorded acutely after a single zeitgeber pulse, the effects of irregularly versus regularly timed zeitgeber can be studied only in long-term protocols and may develop slowly, which is a possible reason why they have received relatively little attention. Several observations indicate a reciprocal relation between the robustness of the endogenous circadian timing system and its dependency on regularly timed zeitgebers. Especially at old age and in disease, proper functioning of the circadian timing system may become more dependent on regularly timed exposure to zeitgeber stimuli. in such conditions, regularly timed exposure to zeitgeber appears to be highly important for health. After a concise introduction on inputs to the central and peripheral oscillators of the circadian timing system, the paper discusses the responses of the circadian timing system and health to (1) a chronic lack of zeitgeber stimuli; (2) fragmented or quasi-ultradian stimuli and (3) repeated phase shifts in stimuli. Subsequently, the specific relevance to aging is discussed, followed by an overview of the effects of experimentally imposed regularly timed stimuli. Finally, a possible mechanism for the gradually evolving effects of repeated regularly timed stimuli on the circadian timing system is proposed.