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。     

重症肌无力患者胸腺凋亡基因Bcl-2和Fas的表达水平与临床的相关性

目的研究重症肌无力(MG)患者胸腺凋亡基因Bcl-2和Fas的表达水平与临床的相关性。方法应用流式细胞仪测定43例MG和11例心脏病(对照组)患者胸腺单个核细胞Bcl-2、Fas的表达水平,并与有关临床因素进行相关性分析。结果MG胸腺增生组Bcl-2阳性细胞数显著高于对照组(P<0·01),MG胸腺瘤组Bcl-2阳性细胞数与对照组比较差异无显著性(P>0·05)。MG组与对照组Fas阳性细胞数比较差异无显著性(P>0·05)。胸腺Bcl-2与Fas阳性细胞数之间,以及与伴或不伴胸腺异常(增生或胸腺瘤)患者的血清乙酰胆碱受体抗体(AchRAb)滴度、疾病分型、年龄和性别均无相关性。结论胸腺增生MG患者胸腺凋亡基因Bcl-2表达异常增高,胸腺Bcl-2和Fas的表达之间及与临床有关因素之间无相关性。     

胸腺瘤旁胸腺组织Fas及其配体表达在重症肌无力发病中的意义

目的　探讨Fas及其配体 (FasL)蛋白表达与胸腺瘤合并重症肌无力的关系。方法利用免疫组织化学染色方法,分析各期胸腺瘤伴有和不伴有重症肌无力患者胸腺组织内Fas及FasL蛋白表达程度,利用显微图像分析系统对结果进行量化统计分析。结果　各期胸腺瘤伴有重症肌无力者胸腺组织内Fas及FasL蛋白表达(Ⅳ期分别为 1 75% ±0 85%和 4 96% ±2 01% )明显低于不伴有重症肌无力者(Ⅳ期Fas及FasL分别为 25 80%±13 43%和 25 75%±13 13% ),差异有统计学意义(P<0 01)。结论　胸腺瘤伴有重症肌无力者,胸腺内T淋巴细胞凋亡能力下降,导致自身反应性T淋巴细胞克隆清除障碍从而引发重症肌无力等自身免疫性疾病。     

重症肌无力患者血清可溶性Fas水平变化及其临床意义

目的探讨重症肌无力(MG)患者血清可溶性Fas(sFas)水平变化及其临床意义。方法采用流式细胞术及酶联免疫吸附法(ELISA)分别测定45例MG患者(MG组)及40例对照者(对照组)外周血T细胞亚群分布和血清sFas水平,并对其中24例MG患者应用糖皮质激素(GC)治疗前后的血清sFas水平进行比较。结果(1)MG组外周血中CD8 T细胞百分率为(21.50±2.21)%,明显低于对照组[(27.75±3.00)%](P<0.01);CD4 /CD8 比值(1.92±0.26)明显高于对照组(1.48±0.16)(P<0.01);血清sFas水平[(3542.06±706.23)pg/m l]显著高于对照组[(2568.18±562.48)pg/m l](P<0.01)。(2)MG组全身型血清sFas水平为(3914.23±804.81)pg/m l,极明显高于眼肌型[(2797.72±592.83)pg/m l](P<0.001);病情中、重度患者明显高于病情轻度者(均P<0.005);预后良好者[(3254.69±661.73)pg/m l]显著低于预后不良者[(4178.38±841.65)pg/m l](P<0.001)。(3)24例MG患者经GC治疗后sFas水平[(2864.59±617.43)pg/m l]较治疗前[(3539.67±705.92)pg/m l]极显著降低(P<0.001)。结论MG患者血清凋亡抑制因素sFas水平增高,并与MG类型、病情及预后相关;GC治疗可以改善MG患者的免疫功能。     

药物及胸腺切除手术治疗重症肌无力的疗效分析

目的探讨伴有不同胸腺情况的重症肌无力(MG)患者对药物及胸腺切除术(TX)的疗效。方法对我院确诊的71例MG患者进行回顾性分析,根据胸腺CT情况将患者分为胸腺CT正常组、合并胸腺增生组、合并胸腺瘤组及合并胸腺癌组,采用Fisher精确检验法比较各组对两种治疗方法的疗效。结果胸腺CT正常的MG患者多采取药物治疗,缓解率为52%,有效率为88.5%;合并胸腺增生、胸腺瘤、胸腺癌的MG患者多采取了TX治疗。合并胸腺增生组的术后缓解率(62.5%)明显高于合并胸腺瘤组(8.3%)(P<0.05);合并胸腺增生组的术后有效率(93.7%)与合并胸腺瘤组差异无显著性(83.3%)(P>0.05)。结论合并胸腺增生的MG患者TX的术后疗效优于合并胸腺瘤者。     

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。     

自身免疫调节因子在重症肌无力患者胸腺内的表达及作用分析

目的比较自身免疫调节因子(AIRE)在重症肌无力(MG)患者及正常人胸腺内的含量,分析AIRE在MG发病中的作用。方法收集濮阳市人民医院胸外科MG胸腺切除患者的胸腺组织及心脏外科手术患者的胸腺组织,将其分为MG合并胸腺异常组(A)、MG胸腺正常组(B)、对照组(C)。采用蛋白免疫印迹法及荧光定量PCR法比较3组胸腺内AIRE基因及蛋白含量。结果 C组(0.75±0.04)AIRE基因含量明显高于A(0.42±0.08)、B(0.45±0.08)两组,差异有统计学意义(P0.05);A、B两组之间AIRE基因含量差异无统计学意义(P0.05)。C组(0.72±0.05)AIRE蛋白含量较A(0.40±0.08)、B(0.50±0.05)两组高,差异有统计学意义(P0.05);A、B两组之间蛋白含量差异无统计学意义(P0.05)。结论 MG患者胸腺内AIRE基因及蛋白含量较对照组偏低,而与胸腺病理类型无关,AIRE在MG发病过程中有重要作用。     

重症肌无力与胸腺外恶性肿瘤关系的临床研究

目的研究重症肌无力(MG)与胸腺外恶性肿瘤的相关性。方法研究2350例MG患者胸腺外恶性肿瘤的发生情况,并描述伴胸腺外恶性肿瘤MG患者的临床病理学特性。结果2350例MG患者中47例(2%)发现有胸腺外恶性肿瘤,最常见的肿瘤类型是肺癌。伴胸腺瘤MG患者,其胸腺外恶性肿瘤较非胸腺瘤患者显著增高。胸腺切除术、胸腺瘤分期及MG治疗方法不影响恶性肿瘤的发生。MG发病时Osserman分型,型者胸腺外恶性肿瘤较其它型少。结论MG患者胸腺外恶性肿瘤风险增加,尤其是伴胸腺瘤的MG患者,与胸腺切除、胸腺瘤分期及治疗方法无关。伴胸腺瘤性MG即使是良性的,也应随访注意有无其它恶性肿瘤的发生。     

100例重症肌无力患者肿瘤坏死因子-α分泌活性的研究

目的比较重症肌无力(myasthenia gravis, MG)患者和正常人体内和体外经诱导后淋巴细胞分泌肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)的差别. 方法 (1) 采用ELISA法测定 100例MG患者治疗前、后及正常对照者血清TNF-α.(2)对 20例MG患者(有胸腺病变者10例,胸腺正常者10例)和20名正常对照者,于治疗前和胸腺切除/免疫治疗后分离外周血淋巴细胞,与植物血凝素(PHA)、抗乙酰胆碱受体(AChR)及空白对照共同培养后离心取上清,并以ELISA测定血清TNF-α水平. 结果 (1)血清TNF-α水平在MG组治疗前[(1.994±0.517) ng/mL]与对照组[(1.841±0.696) ng/mL]间差异无显著性.在MG组中,全身型患者血清TNF-α平均水平[(2.173±0.592) ng/mL]较眼肌型[(1.885±0.453) ng/mL]高;胸腺病变患者血清TNF-α水平[(2.210±0.583) ng/mL]较胸腺正常者[(1.787±0.495) ng/mL]高;MG患者接受胆碱酯酶抑制剂、激素或免疫抑制剂、胸腺手术等治疗后血清TNF-α水平[(1.738±0.553) ng/mL]较治疗前[(1.994±0.517) ng/mL]下降.(2)体外细胞培养结果表明MG组治疗前所产生的TNF-α水平较对照组高;胸腺病变组和胸腺正常组比较差异无显著性;经治疗后的胸腺正常组分泌的TNF-α水平较治疗前降低,胸腺病变组也降低. 结论 MG患者淋巴细胞经体外诱导后产生.TNF-α处于上调状态,在MG的发病中起作用或起促进作用.经过胸腺手术或免疫调控药物治疗(免疫相关治疗)后,TNF-α系统活跃性减低,病情好转.     

CTLA-4基因-1722位点多态性与重症肌无力的相关性研究

目的 研究细胞毒性T淋巴细胞相关抗原4(CTLA-4)基因上游启动子区域-1722位点多态性与重症肌无力(MG)患者的相关性及其与患者临床表型之间的关系.方法 应用聚合酶链反应(PCR)-限制性片断长度多态性(RFLP)方法,对166例MG患者和233名健康对照者CTLA-4基因启动子区域-1722位点进行多态性检测.结果 与健康对照组相比,MG患者中CTLA-4基因-1722位点CC基因型频率明显增高(P<0.01),C等位基因明显高于健康对照组(P<0.01).患者不同性别、合并胸腺瘤否、临床分型、发病年龄等不同组之间分型差异无统计学意义.结论 CTLA-4基因-1722位点CC基因型与MG明显相关,有必要对CTLA-4基因位点多态性进行进一步研究.     

Local nonuniformities in the syncytium of the horizontal cells of the retina in the turtle

Electrical coupling between horizontal cells of the turtle retina was investigated by means of two microelectrodes (current and recording ones) penetrating neighbouring cells at a fixed distance from each other. The morphological coupling was revealed by means of fluorescent dye Lucifer Yellow. The electrical coupling was confirmed between elements of similar type (L1--axonal terminals, or L2--cell bodies, or R/G type cells) and no coupling was found between elements of different types, though L1 and L2 are directly connected through thin axons. In the L1 syncytium the electrical coupling at small (less than or equal to 50 microns) but fixed distances between microelectrodes could differ several times depending on the minimal displacement of microelectrodes. This local nonuniformity of coupling can be explained on the basis of structural nonuniformities in the L1 (axon terminal) network. It is unlikely however that the structural nonuniformities can influence the functional properties of horizontal cell network when the retina is stimulated adequately (by light).     

Asymmetry in the structural organization of the ganglion layer of the retina in the frog

Silver-impregnated retinal preparations were used to study the distribution density and topographic features of small and large ganglionic cells (GC) of Rana ridibunda and Rana temporaria. For both species the increased density of GC (a streak) stretched higher than the naso-temporal axis passing through the optic disk. Beyond the streak the density of small GC was maximal in the central zone of the retina and decreased towards its periphery. For the upper quadrants of the retina the density of small GC was higher than that for the lower ones by 26% on the average. On the contrary, the density of large GC was higher in the lower part of the retina as compared to the upper one, the difference being more pronounced for R. temporaria. The density of large GC was also asymmetric with respect to the dorso-ventral axis being higher in nasal quadrants than in temporal ones by 40-55%. The highest density of large GC was found in the middle zone of the retina. The found structural asymmetry in the retinal output raster may bear an adaptively ecological meaning and may condition the particularities of the formation of the visually guided prey-catching and avoidance reactions.     

Inhomogeneities in the propagation of the slow wave in the stomach

The propagation of the slow wave in the stomach and its role in inducing sweeping peristaltic contractions toward the pylorus, essential for a proper digestion and emptying, have been studied for many years. Irregularities in the timing or in the pattern of propagation of the slow wave have been known to induce various gastric malfunctions and, recently, several types of gastric dysrhythmias have been described which could lead to gastric contraction abnormalities. In this study, Du et al. have analyzed the disturbances caused by a simple transmural incision in a human stomach, performed to obtain a biopsy of the muscle, on the propagation pattern of the slow wave. In addition, they show that such an incision may by itself also induce new types of gastric dysrhythmias. These results are important in demonstrating that the function of the stomach can easily be disturbed by such procedures. This mini‐review describes several ways in which inhomogeneities in propagation may affect the conduction pattern of the slow wave, including the genesis of several dysrhythmias, and what is currently known about their impact on gastric contraction and digestion.     

Early stages in the formation of the cerebellum in the frog

The formation of the cerebellum was studied during the first 6 months of the tadpole stage of the bullfrog by using standard histological methods and reconstructions from serial horizontal sections. Three major developmental phases were noted in the formation of the cerebellum. (1) During the first 5 weeks of development, the neuroepithelium proliferated and the dorsal mesencephalic plates increased in size. (2) Starting in the sixth week, a patch of neuroepithelium began to differentiate and gave rise to a small population of Purkinje cells. In subsequent weeks, the area of differentiation continued to spread and a Purkinje cell layer became established along the dorsal margin of the cerebellar plate. (3) In the 12th week, the ventrolateral part of the cerebellar plate began to increase in size and generate two populations of small cells. The lateralmost part of the neuroepithelium in this area generated a group of cells that formed an external granular layer that was one cell deep. Cells of this external granular layer migrated inward into the primitive molecular layer, and by the 26th week only a remnant of an external granular layer remained in the cerebellum. The more medially situated part of the neuroepithelium gave rise to another population of small cells that formed a column, which appeared to be continuous with the Purkinje cells, but differed from them in size. It should be noted that full maturation of the cerebellum occurs during metamorphosis, which in this species remains some 2 years away.     

Challenges in the Management of the HIV Patient in the Third Decade of AIDS

The epidemic of AIDS has been increasingly recognized as a major health and socioeconomic problem, not only in the United States or Africa, but also the rest of the world. The face of the epidemic has changed. The role that mental health providers play has also significantly grown as the epidemic continues on. Prior to the introduction of Highly Active Anti-Retroviral Therapy (HAART) and other advances in HIV care, the patients faced issues that related to death and dying. These advances brought with them renewed hope and resurrected lives. The patients fought with issues related to living new lives with HIV no longer an imminent death threat. In the third decade of AIDS, the struggles of the post-HAART era continue but bring with it more challenges. Mental health providers need to familiarize themselves with these issues so that they can better help HIV patients cope with this devastating disease.     

Analysis of the habituation-like changes in transmission in the temporodentate pathway of the rat

Habituation-like decrements in extracellular measures of synaptic activation (population EPSP) and cell discharge (population spike) were analyzed in the dentate gyrus of the rat following repetitive low-frequency stimulation of the medial and lateral entorhinal cortex. Stimulation of either subdivision of the entorhinal projection system resulted in comparable habituation-like response decrements with similar stimulation regimens. However, habituating stimulation of one subdivision did not result in decreased responsiveness to stimulation of the other. Repetitive low-frequency stimulation or even a single pulse delivered to either subdivision did, however, result in a potentiation of granule cell discharge in response to stimulation of the other subdivision (a form of heterosynaptic potentiation). This heterosynaptic potentiation of granule cell discharge was not accompanied by any increase in the extracellular EPSP. Comparisons of the relationship between the population EPSP and population spike before and during habituating stimulation revealed changes in cell discharge in response to the habituating stimulus which could not be accounted for by changes in synaptic activation alone. The results suggest that repetitive activation of the temporodentate pathway alters granule cell output as a result of two processes, a habituation-like decrement in synaptic activation, and a potentiation of granule cell discharge as a consequence of prior activation.     

Gradients of histogenesis in the ependymal lining of the third ventricle in the rabbit

Tritiated thymidine autoradiography was used to analyze the site, time of origin, and developmental gradients of the specialized lining of the ependymal surface of the third ventricle. Cells destined to form the ependyma are generated between days 15 and 22 of embryogenesis (gestation: 30 +/- 2 days), the majority of the cells undergoing final division on the 18th day of gestation. Ependymal cells originate in an orderly fashion according to 3 gradients. Two gradients of opposite direction (ventrodorsal and dorsoventral) are found in the parasaggital plane. Both gradients start at the level of the hypothalamic sulcus, progressively departing from this anatomical landmark as histogenesis progresses. A third gradient occurs in the caudorostral axis, such that cells located in caudal regions originate earlier than those located in rostral sectors. Thus, an orderly relationship exists between the time of origin of ependymal cells and their final location within the lining of the ventricular wall. These findings indicate, once again, the topographic nature of the gradients of histogenesis. The histogenic gradients displayed by the ependymal lining of the third ventricle appear strongly related to those exhibited by other diencephalic derivatives. The latter suggests that common factors govern the developmental sequence of all diencephalic derivatives as a function of their relative topographic location, independently of their functional role in the adult.