抗CD40配体单克隆抗体干预重症肌无力的研究

目的研究抗CD40配体单克隆抗体(CD40LmcAb)干预重症肌无力(MG)患者外周血单个核细胞(PBMC)的效果并探讨其机制。方法MG患者25例和健康对照组16名,分离培养外周血单个核细胞,分别用植物血凝素(PHA)和美洲商陆原(PWM)进行刺激,并用CD40LmcAb进行干预。PHA刺激组培养后收集上清检测γ干扰素(IFN γ)和白细胞介素4 (IL 4);PWM刺激组培养后收集上清检测抗乙酰胆碱受体抗体(AchRab)和抗突触前膜受体抗体(PsmRab)。比较MG患者两组中CD40LmcAb干预与否的差异并与健康对照组比较。结果MG患者PBMC体外诱生AchRab(0 32±0 11)、PsmRab(0 28±0 11)、IFN γ[ (36 24±10 47)pg/ml]和IL 4水平[ (263 08±35 95)pg/ml]对比健康对照组显著增高[分别为(0 10±0 02), (0 15±0 03), (17 56±2 94)pg/ml和(190 00±6 50)pg/ml,P<0 01),CD40LmcAb干预后MG组的上述四项指标均基本降至健康对照组水平(P>0 05)。结论CD40LmcAb在体外能有效干预MG患者PBMC诱生AchRab、PsmRab、IFN γ和IL 4的水平。     

重症肌无力患者酪氨酸激酶抗体的检测

目的探讨酪氨酸激酶抗体（MuSKAb）在血清阴性重症肌无力（SNMG）发病中的作用。方法采用放射免疫法检测198例重症肌无力（MG）患者血清中抗乙酰胆碱受体抗体（AChRAb）水平，筛选出SNMG血清样本再行MuSKAb水平检测。结果MG患者血清AChRAb浓度明显高于对照组（P〈0．05），其阳性率为81．3％，SNMG患者血清MuSKAb均为阴性。结论MuSKAb可能在中国SNMG患者中的检出率较低。     

血清阴性和阳性重症肌无力被动转移动物模型的对比观察

目的:通过对血清阴性重症肌无力(SNMG)和血清阳性重症肌无力(SPMG)被动转移动物模型的对比观察,探讨SNMG和SPMG发病机理的异同。方法:分别采用SNMG和SPMG患者血清制作重症肌无力被动转移小鼠模型,观察其临床表现及电生理改变。结果:SNMG和SPMG患者血清均可诱导C57BL/6小鼠出现肌无力症状,其成功率分别为90％、85％;但SNMG组小鼠肌无力症状较SPMG组明显为轻(症状级别均值分别为1.55、2.15,P<.05),电刺激衰减率(40％)和平均衰减幅度(14％)均较后者(分别为75％、21％)为低(P<0.05)。结论:SNMG和SP-MG均是自身抗体介导的自身免疫病,SNMG血清中亦存在致病因子。     

重症肌无力被动转移动物模型的研究

目的 :探讨血清阳性 (SPMG)和阴性重症肌无力 (SNMG)被动转移动物模型 (P EAMG)的异同。方法 :用ELISA法将重症肌无力 (MG)患者分为SNMG和SPMG两组 ,然后分别用两组患者血清制作P EAMG ,观察两组小鼠的临床表现、电生理及神经肌接头(NMJ)的改变。结果 :SPMG和SNMG组小鼠均表现出明显的肌无力症状 ,低频重复电刺激出现明显衰减反应 ,但SNMG组小鼠肌无力症状较SPMG组明显为轻 ,SPMG和SNMG组小鼠NMJ处棕黄色沉积物明显减少、变细短。结论 :SNMG和SPMG均是自身抗体介导的自身免疫性疾病 ,但两者不完全相同     

血清阴性重症肌无力研究进展

乙酰胆碱受体(acetylcholine receptor,AChR)抗体阴性的重症肌无力(myasthenia gravis,MG)称为血清阴性重症肌无力(SNMG)。SNMG在发病机制、临床表现和治疗上都与AChR抗体阳性MG不同。近年来研究者在SNMG患者血清中发现多种MG相关抗体,如肌肉特异性酪氨酸激酶(muscle-specific receptor tyro-sine kinase,MuSK)抗体、低亲和力AChR抗体、低密度脂蛋白受体相关蛋白4(low density lipoprotein receptor-related protein 4,LRP4)抗体等。本文就SNMG发病机制与临床表现的研究进展做一简要综述。     

血清AChRab、PsMab和CAEab检测在胸腺异常患者中的诊断意义

目的探讨血清抗乙酰胆碱受体抗体(AChRab)、抗突触前膜抗体(PsMab)和柠檬酸提取物相关抗体(CAEab)在胸腺异常患者中的诊断价值。方法回顾性收集2009—2016年作者医院收治的经病理检查证实存在胸腺异常的患者152例,同时收集健康体检者45名(NC组)和其他神经系统疾病患者35例(OND组)作为对照组。采用ELISA方法检测各组AChRab、PsMab和CAEab水平,比较各组不同抗体阳性率的差异,并进一步比较不同胸腺异常者间各抗体阳性率差异。结果 (1)胸腺瘤、胸腺增生组血清AChRab、PsMab和CAEab阳性率明显高于NC及OND组(均P0.01),且胸腺瘤组上述3种抗体阳性率高于胸腺囊肿组(P0.01或P0.05)。胸腺囊肿组与NC及OND组各抗体阳性率比较无统计学差异(P0.05)。CAEab对胸腺瘤患者诊断灵敏度为60.6%,特异度为88.8%。(2)重症肌无力合并胸腺瘤(MGT)组PsMab阳性率高于非合并MG胸腺瘤(NMGT)组(P0.05),而其AChRab及CAEab阳性率与NMGT组比较无统计学差异(P0.05)。(3)MGT组中,MGT-全身型组血清AChRab阳性率较MGT-眼肌型组增高(P0.05)。(4)胸腺瘤不同病理分型患者间各抗体阳性率比较无统计学差异(均P0.05)。结论 (1)CAEab检测结合CT检查可作为临床可疑胸腺瘤、胸腺增生患者术前辅助诊断指标之一。(2)AChRab阳性可能与MGT患者重症肌无力严重程度有关,PsMab阳性可能跟MGT患者致病有关。     

肌肉特异性酪氨酸激酶在重症肌无力中的作用(综述)

约有20％重症肌无力(MG)患者血清中检测不到乙酰胆碱受体抗体(AChRAb)，称之为“血清反应阴性MG”(seronegative MG，SNMG)。有报道71％的SNMG患者血清中存在肌肉特异性酪氨酸激酶(MUSK)抗体(MuSKAb)，MuSKAb阳性SNMG患者的流行病学特征、If缶床特点和治疗效果与由AChRAb介导的MG(seropositive MG，SPMG)有所不同，存在较大争议。     

CD40配体在重症肌无力发病机制中的作用探讨

目的　研究 CD4 0配体 (CD4 0 L)在重症肌无力 (MG)患者主要致病因素产生中的作用 ,从而探讨CD4 0 L 在 MG发病机制中的作用。方法　 MG急性期组 10例 ,MG非急性期组 15例 ,设健康对照组 16例。分离外周血单个核细胞 (PBMC) ,分组用植物血凝素 (PHA)和美洲商陆原 (PWM)刺激剂刺激进行单个核细胞培养 :(1)PHA组 :即用 PHA刺激。培养后收集上清检测 γ-干扰素 (IFN- γ)和白细胞介素 4 (IL- 4 ) ;(2 ) PWM组 :即用 PWM刺激。培养后收集上清检测抗乙酰胆碱受体抗体 (Ach Rab)和抗突触前膜受体抗体 (Psm Rab)。比较两组中抗CD4 0 L 单克隆抗体 (CD4 0 L m c Ab)干预与否的差异并与健康对照组比较。结果　无论 MG急性期组或 MG非急性期组 ,刺激后 Ach Rab、Psm Rab、IFN- γ和 IL- 4水平均比健康对照组显著增高 (P<0 .0 0 1)。MG急性期组 IFN- γ高于 MG非急性期组 (P<0 .0 5 ) ,MG非急性期组 IL- 4高于 MG急性期组 (P<0 .0 5 ) ,CD4 0 L mc Ab干预后 4种因素均基本降至健康对照组水平 (P>0 .0 5 )。结论　在 MG的发生、发展过程中 Th细胞亚类出现不平衡 ,CD4 0 -CD4 0 L 共刺激因子均起重要作用     

肌肉特异性酪氨酸激酶抗体、血清阴性能否解释重症肌无力

20％～40％的重症肌无力（MG）病人在他们的血清中没有发现乙酰胆碱受体抗体（AchRab），被称为血清阴性重症肌无力的病人（Seronegative MG，SNMG）。Hoch等最近在血清阴性重症肌无力体内发现了一个新特殊抗原——肌肉特异性酪氨酸激酶（MuSK）。Lyanagi等发现38％～70％的血清阴性重症肌无力病人体内有肌肉特异性酪氨酸激酶抗体（MusKab）。随后，Scudefi等报道66％AchR阴性重症肌无力病人可用免疫沉淀法检查出MusK。但Jon Lindstrom提出了这样一个问题：抗MusK自身抗体能够解释血清阴性的重症肌无力吗？     

重症肌无力患者血清学标志物检测及临床意义

目的探讨血清抗乙酰胆碱受体(ACh R)抗体、抗连接素(Titin)抗体和抗Ryanodine受体(Ry R)抗体对重症肌无力的诊断价值。方法采用酶联免疫吸附试验分别检测182例重症肌无力患者(MG组)、105例其他神经系统疾病患者(OND组)和62例正常对照者(对照组)血清抗ACh R抗体、抗Titin抗体和抗Ry R抗体水平。结果重症肌无力患者血清抗ACh R抗体、抗Titin抗体和抗Ry R抗体阳性率分别为68.13%(124/182)、64.29%(117/182)和67.03%(122/182),高于OND组(均P=0.000)和对照组(均P=0.000);3种血清学标志物同时阳性,诊断重症肌无力的灵敏度为41.21%,特异度达99.40%。其中,早发型与晚发型重症肌无力亚组血清抗ACh R抗体、抗Titin抗体和抗Ry R抗体阳性率差异无统计学意义(均P0.05);伴胸腺瘤的重症肌无力亚组仅血清抗ACh R抗体阳性率高于不伴胸腺瘤的重症肌无力亚组(P=0.004),而抗Titin抗体和抗Ry R抗体阳性率差异无统计学意义(均P0.05);不同改良Osserman分型亚组中仅全身型重症肌无力(Ⅱa和Ⅱb型)血清抗ACh R抗体阳性率高于眼肌型重症肌无力(Ⅰ型;P=0.005,0.012),而抗Titin抗体和抗Ry R抗体阳性率差异无统计学意义(均P0.05)。结论血清抗ACh R抗体、抗Titin抗体和抗Ry R抗体均有助于诊断重症肌无力,对于3种生物学标志物同时呈阳性的患者,应高度怀疑重症肌无力,其中,眼肌型重症肌无力患者血清抗ACh R抗体水平较高,有可能进展为全身型重症肌无力,应积极治疗。     

Denervation study of synapses of organ of corti of old world monkeys

Fine structural characteristics of synapses in the spiral organ of Corti were examined, with reference to differences between inner and outer haircell systems, and to location of neurons of origin of efferent axons. Surgical interruption of crossed olivocochlear bundle, of vestibular nerve, of facial nerve, and excision of superior cervical ganglia were used to determine the pathways of efferent axons. Interruption of the vestibular nerve near the brainstem results in degeneration of all efferent terminals on outer hair cells. Mid-line lesions at, and caudal to, the facial colliculus result in degeneration of about half of these efferent terminals. Efferent synaptic bulbs to the inner hair-cell system are small, of the order of one micron, and form type 2 junctions with afferent dendrites. They tend to have more large dense-core vesicles (about 80 nm) than the large efferent terminals of the outer hair-cell system, and appear to be the terminals of axons in the habenula perforata, which exhibit varicosities laden with large dense core vesicles. The varicosities are unaffected by excision of the superior cervical ganglia. So far as our material can reveal, it appears that the varicosities in the habenula perforata do not survive vestibular root interruption, nor do the efferent processes in the internal spiral bundle or at the base of inner hair cells. Most interestingly, the afferent processes of the inner hair-cell system, as identified for example by their relation to pre-synaptic bodies in the inner hair cells, are subject to a trans-synaptic reaction after severance of the vestibular root. They undergo a dramatic cytological transformation, characterized by increase of volume, engorgement with microtubules, microfilaments, microvesicles of various sizes, and clusters of lysosomes. Thus, both the efferent and afferent terminals of the inner hair-cell system show marked cytological differences from the corresponding terminals of the outer hair cell system.     

Mechanism of action of tubocurarine on nicotinic cholinoreceptors of neurons of the sympathetic ganglia of rats

Tubocurarine (Tc) effect on membrane currents elicited by acetylcholine (ACh) was studied in isolated superior cervical ganglion neurons of rat using patch-clamp method in the whole-cell recording mode. The "use-dependent" block of ACh current by Tc was revealed in the experiments with ACh applications, indicating that Tc blocked the channels opened by ACh. Mean lifetime of Tc-open channel complex, tau, was found to be 9.8 +/- 0.5 s (n = 7) at -50 mV and 20-24 degrees C. tau exponentially increased with membrane hyperpolarization (e-fold change in tau corresponded to the membrane potential shift by 61 mV). Inhibition of the ACh-induced current by Tc (3-30 microM/1) was completely abolished by membrane depolarization to the level of 80-100 mV. Inhibition of ACh-induced current was augmented at increased ACh doses. It is concluded that the open channel block produced by Tc is likely to be the only mechanism for Tc action on nicotinic acetylcholine receptors in superior cervical ganglion neurons of rat.     

The effect of age of onset of PD on risk of dementia

Background Dementia occurs in the majority of patients with Parkinson’s disease (PD). Late onset of PD has been reported to be associated with a higher risk for dementia. However, age at onset (AAO) and age at baseline assessment are often correlated. The aim of this study was to explore whether AAO of PD symptoms is a risk factor for dementia independent of the general effect of age. Methods Two community-based studies of PD in New York (n = 281) and Rogaland county, Norway (n = 227) and two population-based groups of healthy elderly from New York (n = 180) and Odense, Denmark (n = 2414) were followed prospectively for 3–4 years and assessed for dementia according to DSM-IIIR. All PD and control cases underwent neurological examination and were followed with neurological and neuropsychological assessments. We used Cox proportional hazards regression based on three different time scales to explore the effect of AAO of PD on risk of dementia, adjusting for age at baseline and other demographic and clinical variables. Findings In both PD groups and in the pooled analyses, there was a significant effect of age at baseline assessment on the time to develop dementia, but there was no effect of AAO independent of age itself. Consistent with these results, there was no increased relative effect of age on the time to develop dementia in PD cases compared with controls. Interpretation This study shows that it is the general effect of age, rather than AAO that is associated with incident dementia in subjects with PD. Received in revised form: 22 December 2005     

Limits of deinstitutionalization--perspectives of relatives of psychiatric patients

After a hopeful beginning, the social process of the reintegration of those with severe mental illness has come to a standstill. I am led to wonder whether "the community" really wants to live together with people suffering from severe mental illness, and if so, how closely? As long as the medical treatment of mental illness provided by the general practitioners is fundamentally deficient, as they are not able to prescribe the necessary interventions--such as out-patient psychiatric nursing, and service providers in the out-patient sector are content with offering increasingly intensive forms of care for the less seriously ill at the cost of the Social Welfare System--the reintegration of those with serious mental illness remains an illusion--which is mainly to the benefit of providers of residential care in homes and hostels.