树突状细胞及相关细胞因子在重症肌无力患者胸腺中的变化

目的探讨胸腺树突状细胞及相关细胞因子在重症肌无力(MG)发病中的作用。方法采用免疫荧光双标法对11例胸腺瘤伴MG患者、6例单纯胸腺瘤、5例正常胸腺组织中S100(+)、HLADR(+)的树突状细胞进行检测,同时用组织匀浆、ELISA法检测胸腺组织中IL2、IL12含量。结果(1)树突状细胞主要分布在胸腺皮质、皮髓交界处,在胸腺瘤伴MG患者胸腺髓质也有一定分布。(2)S100(+)、HLADR(+)树突状细胞数量在胸腺瘤伴MG患者与单纯胸腺瘤患者间、单纯胸腺瘤患者与正常胸腺之间差异有显著性(P<005)。(3)IL2、IL12含量在胸腺瘤伴MG患者与正常胸腺之间差异有显著性(P<005);IL12含量在胸腺瘤伴MG患者与单纯胸腺瘤患者间亦有显著性差异(P<005)。结论胸腺树突状细胞以多种形式参与MG发病。     

重症肌无力患者胸腺微环境内树突状细胞的免疫组织化学变化

目的 探讨重症肌无力（MG）胸腺微环境内树突状细胞、淋巴细胞和上皮细胞的免疫组织学变化。方法 （1）25例MG病人（胸腺滤泡性增生者13例，无增生者12例）、7例先天性心脏病和1例新生儿胸腺组织，常规石蜡包埋切片，HE染色，光镜观察。（2）免疫化学标记S－100、CD1a、CD4、CD8、CD20、CD45RO、细胞角蛋白（CKPan)、上皮细胞膜抗原（EMA）和癌胚抗原（CEA），光镜观察，对其中S－100，CD1a阳性的树突状细胞半定量计数，t检验，统计分析。结果 （1）在胸腺淋巴滤泡性增生组和非增生组，胸腺单位面积内（100m^2)表达S－100阳性的树突状细胞数是23．5和47.5,CD1a为2．1和3．8，两组t检验，P＜0．05）。（2）胸腺质皮细胞和淋巴滤泡性增生的髓质分别表达CD1a、CD8和CD45RO，胸腺小体、血管周围淋巴细胞极少表达CD1a，胸腺髓质和生发中心内淋巴细胞表达CD20。（3）胸腺被膜下、皮质、胸腺小体和髓质内有表达CKPan的上皮细胞，但EMA和CEA阴性。结论 （1）MG时胸腺髓质无论有无淋巴滤泡性增生，都表达多量抑制T细胞和CD20淋巴细胞；生发中心内有多量表达CD20和少量CD8细胞。（2）MG时胸腺微环境内这些抗体的表达和树突状细胞数量的变化，将影响T、B淋巴细胞增生和淋巴滤泡形成；胸腺内树突状细胞与其基质细胞在MG的发病中起重要作用。     

重症肌无力胸腺和外周血抗原特异性单个核细胞IFN-γ、IL-4的转录及表达

目的为了解重症肌无力(MG)胸腺细胞免疫状态,对10例行胸腺摘除(Tx)的MG患者及4例先天性心脏病行开胸手术患者的胸腺和外周血单个核细胞经特异性抗原乙酰胆碱受体(AChR)刺激后,其细胞IFN-γ和IL-4的mRNA转录和细胞培养上清液中的蛋白表达情况进行了检测.方法采用RT-PCR结合狭缝印迹杂交检测IFN-γ、IL-4 mRNA转录,采用ELISA检测IFN-γ和IL-4的表达情况.结果 10例MG患者的胸腺和外周血单个核细胞经AChR刺激后IFN-γ和IL-4的mRNA转录增高,其中8例胸腺增生者胸腺细胞和外周血细胞的IFN-γ mRNA转录、外周血细胞的IFN-γ表达均高于健康对照组(P＜0.05);胸腺细胞IL-4 mRNA转录和表达均高于健康对照,差异有显著性(分别为P＜0.01和P＜0.05),而外周血细胞IL-4 mRNA转录和表达与健康对照差异无显著性(P＞0.05);另2例伴胸腺瘤者,此两种细胞因子无论mRNA转录还是蛋白表达均很低.外周血细胞与胸腺细胞IL-4 mRNA转录有一定的相关性,基本反映胸腺的免疫学变化.结论胸腺增生MG患者的细胞免疫(Th1和Th2)高度活跃,PBMC的有些免疫学参数能反映MG患者胸腺的免疫学改变,但有待进一步累积更多资料.伴胸腺增生与伴胸腺瘤的MG发病机制可能不同,Tx是必要的.     

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。     

重症肌无力患者相关基因差异片段N9在肌肉和胸腺中的表达

目的　筛选并鉴定重症肌无力 (MG)的相关基因。方法　测定由差别显示PCR(DDPCR)获得的、来自于正常人骨骼肌的cDNA差异片段 (暂命名为N9)的序列并进行同源性分析。运用半定量RT PCR方法分析该片段在MG病人和正常人胸腺与骨骼肌中的表达差异。结果　N9片段与GeneBank中已知非小细胞肺癌和肝癌的抑癌基因同源性高达 99% ;半定量RT PCR揭示 ,该基因在正常人和MG伴胸腺增生病人的肌肉中表达上调 ,而在MG伴胸腺瘤病人的肌肉中表达下调 ;正常人和病人的胸腺中均有该基因表达 ,但在伴胸腺瘤MG患者中的表达高于伴胸腺增生MG患者和正常人。结论　N9可能是已知的基因片段 ,它可能在伴不同类型胸腺异常MG的发病或发展中起某种作用 ,其具体作用还有待于进一步研究     

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。     

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。     

伴胸腺异常的重症肌无力临床研究

目的:研究伴胸腺异常重症肌无力(MG)的临床特点。方法:回顾性分析1990-2002年诊治的伴胸腺异常21例MG,病例资料并与同期无胸腺异常59例MG对比。结果:胸腺异常组男女比例为1:0.91,胸腺正常组男女比例为:1:2.11,按改良Osserman临床分型胸腺异常组临床多表现为Ⅱa、Ⅱb型,胸腺正常组多表现为Ⅰ、Ⅱa,胸腺异常以胸腺瘤和恶性胸腺瘤为主。胸腺异常组危象发生率23.3%,死亡率40%,胸腺正常组危象发生率13.6%,死亡率12.5%。结论:胸腺异常组男性患者明显增加,发病年龄以30-49岁为主。伴胸腺瘤MG临床症状重,胸腺瘤是MG危象的一个重要危险因素。     

重症肌无力患者甲状腺功能和甲状腺抗体情况的临床分析

目的　了解重症肌无力 ( MG)患者甲状腺功能及甲状腺抗体的情况。方法　回顾性分析了 2 67例临床确诊 MG患者的甲状腺素水平 ,对其中 2 64例患者检测了甲状腺球蛋白抗体 ( TGAb)和甲状腺过氧化物酶抗体( TPOAb)或甲状腺微粒体抗体 ( TMAb)。结果　 5 5例 ( 2 0 .6% )患者有甲状腺功能异常 ,48例 ( 1 8.2 % )至少有 1项上述抗体阳性。甲状腺功能异常的 MG患者中 , 、 、 型抗体阳性者较多 ( P <0 .0 1 )。甲状腺抗体阳性者较抗体阴性者 MG发病晚 ( P <0 .0 5 ) ;甲状腺抗体阴性 MG患者有甲状腺功能障碍者 MG发病早于功能正常组 ( P <0 .0 5 )。甲状腺功能异常、抗体阳性的 MG患者病程较抗体阴性者长 ( P <0 .0 5 ) ;甲状腺抗体阳性者伴发胸腺增生或胸腺瘤的几率明显增高 ( P <0 .0 5 )。结论　MG合并甲状腺功能异常并不少见 ,甲状腺抗体阳性、功能异常的 MG患者病程长 ,伴发胸腺增生或胸腺瘤的几率高 ,临床应予以重视。     

Neuroimaging in epilepsy in tropics

Epilepsy is a major public health problem in many tropical countries. Also, some of the tropical diseases are major contributors to the higher prevalence of epilepsy in these countries. The etiologic factors responsible for epilepsy in these countries are quite different from those in the developed world. This article discusses the etiologic factors and neuroimaging of epilepsy in light of the conditions in these tropical countries.     

癫痫与抑郁关系的研究进展

抑郁是癫痫患者中常见的精神障碍,严重地影响了患者的生活质量。传统的观点认为癫痫患者因为存在着诸多社会学问题易出现抑郁倾向,癫痫和抑郁是单向的联系,但大量的研究已经证明癫痫和抑郁之间存在双向的联系,一种异常状态的存在可能易转化为另一种异常状态的发展。癫痫和抑郁存在着共同的发病机制。本文主要就癫痫和抑郁的双向联系以及抗抑郁药物在癫痫患者中的应用进行阐述。     

Sudanophilic lipid accumulation in astrocytes in periventricular leukomalacia in monkeys

Summary Sudanophilic lipid accumulation is a characteristic feature of periventricular leukomalacia (PVL) of infants. At least two types of lipid-containing cells have been identified, one being the macrophage, the other the pre-myelin glial cell. A third type of lipid-containing cell has been seen in two monkeys with spontaneous PVL. Electron microscopically this cell appears to be an astrocyte. This probably represents a reaction of the astrocyte to hypoxia and may be the equivalent of the hypertrophic astrocytes found in human infants.Supported in part by NIH grant HDO 8633 and the Regional Primate Research Center Grant RR-00166     

Increase in cathepsin D activity in rat brain in aging

Cathepsin D-like activity in homogenates of five brain areas of 3-month-old and 24-month-old Fischer 344 rats was measured. With hemoglobin as substrate at pH 3.2, more than 90% of the activity was inhibited by pepstatin. In each area studied, activity was more than twice as high in the old rat brain: 140-160% higher in the cortex, cerebellum, pons-medulla, and striatum and 90-100% higher in the hippocampus and spinal cord. The greatly increased metabolic capacity in the absence of an increase in protein turnover may have a role in age-related pathological degeneration in the brain.     

Characteristics of nociceptors in the periodontium--an in vitro study in rats

Recent studies have indicated that nociceptors can be classified into various types according to their physiological properties. These studies have clarified that the frequency distribution of various nociceptor types is different among body sites and animal species. In the present study, we investigated the physiological properties of rat's periodontal nociceptors in an in vitro jaw-nerve preparation. Responses were recorded from functional single filaments in the inferior alveolar nerve. To determine the nociceptor type, calibrated von Frey filaments, heat, and bradykinin (BK) stimuli were used. We found five subtypes of nociceptors in the periodontal ligaments of the lower incisor: Adelta-high threshold mechanonociceptors (Adelta-HTM, n=28), Adelta-mechanoheat nociceptors (Adelta-MH, n=6), Adelta-polymodal nociceptors (Adelta-POLY, n=26), C-high threshold mechanonociceptors (C-HTM, n=3) and C-polymodal nociceptors (C-POLY, n=4). Most nociceptors were Adelta-innervated, while only a small number of C-innervated nociceptors were found. The present results suggest that periodontal nociceptors transmit mainly fast pain, and may thus play a role in rapid detection of injure-related stimuli during mastication.     

Gender in Voice Perception in Autism

Deficits in the perception of social stimuli may contribute to the characteristic impairments in social interaction in high functioning autism (HFA). Although the cortical processing of voice is abnormal in HFA, it is unclear whether this gives rise to impairments in the perception of voice gender. About 20 children with HFA and 20 matched controls were presented with voice fragments that were parametrically morphed in gender. No differences were found in the perception of gender between the two groups of participants, but response times differed significantly. The results suggest that the perception of voice gender is not impaired in HFA, which is consistent with behavioral findings of an unimpaired voice-based identification of age and identity by individuals with autism. The differences in response times suggest that individuals with HFA use different perceptual approaches from those used by typically developing individuals.     

Defects in Bioenergetic Coupling in Schizophrenia

Synaptic neurotransmission relies on maintenance of the synapse and meeting the energy demands of neurons. Defects in excitatory and inhibitory synapses have been implicated in schizophrenia, likely contributing to positive and negative symptoms as well as impaired cognition. Recently, accumulating evidence has suggested that bioenergetic systems, important in both synaptic function and cognition, are abnormal in psychiatric illnesses such as schizophrenia. Animal models of synaptic dysfunction demonstrated endophenotypes of schizophrenia as well as bioenergetic abnormalities. We report findings on the bioenergetic interplay of astrocytes and neurons and discuss how dysregulation of these pathways may contribute to the pathogenesis of schizophrenia, highlighting metabolic systems as important therapeutic targets.     

Ethnic disparities in problem behaviour in adolescence contribute to ethnic disparities in social class in adulthood

BACKGROUND: It is important for prevention of social class disparities to know how ethnic disparities in social class arise among migrant children. We contribute to this understanding by examining the role of problem behaviour in adolescence. METHODS: Prospective observational study with 753 Dutch native and 217 Turkish migrant adolescents (11-18 year) followed for 10 years. Internalising and externalising problems were assessed in adolescence and employment status and occupational level were assessed in adulthood. The difference in odds ratios (OR) before and after adjustment for internalising and externalising problems was an indication of the predictive value of disparities in internalising and externalising problems for the development of social class disparities. RESULTS: A total of 135 (62%) of the Turkish and 602 (80%) of the Dutch adults were employed. Internalising and externalising problems were not associated with employment status. Of the employed, 65 (48%) Turkish and 179 (30%) Dutch adults worked in low-level occupations (p < 0.0001). Internalising and externalising problems were associated with both ethnicity and occupation. The OR for low-level occupation for Turkish adults was 1.78 (1.19-2.65), indicating ethnic disparities. Adjustment for internalising problems lowered the OR with 36% to 1.50 (0.97-2.31), and adjustment for externalising problems lowered it with 8% to 1.72 (1.15-2.57). Findings were similar for men and women and did not vary by age. CONCLUSIONS: Ethnic disparities in occupational level in adulthood could partly be attributed to disparities in mental health between Turkish migrants and Dutch natives in adolescence. Prevention of ethnic disparities in mental health at young age may therefore also contribute to the prevention of occupational differences in adulthood.     

Progress in neuroprotection in Parkinson's disease

Slowing or aborting the progress of neurodegeneration in Parkinson's disease (PD) remains the most important unmet need of this disorder. There are several recent developments in trial design and also in drugs under investigation for possible neuroprotective effect. Emphasis has been placed on clinical as opposed to imaging end-points and these include change in a clinical rating scale, e.g. United Parkinson's disease Rating Scale (UPDRS), or time to additional therapy. The introduction of the delayed-start, or wash-in, trial design adds an additional dimension to drug evaluation for neuroprotection. Compounds that have been recently tested in clinical trial include the monoamine oxidase-B inhibitor rasagiline, the anti-apoptotic agents TCH346 and CEP1347, and the promitochondrial agent creatine. The dopamine agonists have been evaluated for a neuroprotective effect using imaging end-points. Perhaps the most important and simplest concept for neuroprotection has been the theory that early dopaminergic support for the degenerating dopaminergic system per se provides significant long-term clinical benefit for PD patients.     

Changes in parasympathetic system in medulla oblongata in male pigs in the course of tachycardia-induced cardiomyopathy

Background

Autonomic imbalance constituting a fundamental feature of heart failure (HF) has been assessed mainly at the periphery. Changes in the functioning of autonomic centers in the brain remain unclear. We investigated the molecular elements of parasympathetic system, i.e. α7 nicotinic acetylcholine receptor (α7nAChR) and enzymes metabolizing acetylcholine (acetylcholinesterase, AChE, choline acetyltransferase, ChAT) in medulla oblongata (MO) of male pigs with chronic tachycardia-induced cardiomyopathy.

Methods

The mRNA levels of AChE, ChAT, α7nAChR and X-box binding protein 1 (spliced form, XBP1s) in MO were analyzed using qPCR, AChE and ChAT activities using spectrophotometry, proteasome activity using fluorometry, and the protein level of α7nAChR using Western blotting.

Results

The development of systolic HF was accompanied by an increase in circulating catecholamines, a decrease in the AChE and α7nAChR mRNA in MO, an increase in AChE activity (all p < 0.05), and no change in either the mRNA or activity of ChAT. Both circulating catecholamine levels and AChE activity were inversely related to systolic function of left myocardial ventricle (p < 0.05). The level of α7nAChR protein in MO and its cytoplasmatic fraction were higher in pigs with moderate and severe HF as compared to the other animals (p < 0.01). There was no difference in proteasome activity in MO between diseased and healthy animals, whereas the XBP1s mRNA decreased during HF progression (p < 0.05).

Conclusions

Molecular elements of parasympathetic system are changed within the medulla oblongata during the progression of systolic non-ischemic heart failure in male pigs, indicating a functional link between MO and heart in HF.