人脑胶质瘤中表皮生长因子受体表达的研究

目的：探讨表皮生长因子受体（ＥＧＦＲ）基因表达与胶质瘤恶性程度的关系。方法：采用Ｎｏｒｔｈｅｒｎ印迹杂交及免疫组织化学技术从ｍＲＮＡ及蛋白水平检测了５０例人脑胶质瘤、４个体外恶性胶质瘤细胞系及８例正常脑组织的ＥＧＦＲ的基因表达。结果：免疫组化检测高恶度胶质瘤（ＷＨＯⅢ－Ⅳ级）ＥＧＦＲ表达６９％（２０／２９），而低恶度胶质瘤（ＷＨＯⅠ－Ⅱ级）表达率为３３％（７／２１），差异显著（Ｐ＜０．０１）；４例细胞系阳性表达１００％；８例正常脑组织无ＥＧＦＲ蛋白表达。ＷＨＯ分级与ＥＧＦＲ蛋白表达呈正相关（ｒ＝０．５５９７，Ｐ＜０．００１）。对５０例胶质瘤进行Ｎｏｒｔｈｅｒｎ印迹杂交，其结果与免疫组化检测结果一致，ＥＧＦＲｍＲＮＡ也随胶质瘤恶性程度的增加而表达增高。结论：ＥＧＦＲ可能在恶性胶质瘤的发生发展中起重要作用，ＥＧＦＲ过表达与胶质瘤分级相关性为从分子水平评估肿瘤的恶性程度及选择基因治疗的靶基因提供了参考。     

P16基因改变与脑胶质瘤生物学特性相关性的研究

目的 研究Ｐ１６基因改变与脑胶质瘤恶性程度分级及肿瘤细胞增殖活性之间的关系。方法 检测４１例不同级别脑胶质瘤标本和７例正常脑组织Ｐ１６基因改变和ＰＣＮＡ蛋白表达情况。结果 实验组Ｐ１６基因缺失和突变２２例（５４％），ｍＲＮＡ和蛋白表达缺失分别为２３例（５６％）和２７例（６６％），三者改变非一对一关系。Ｐ１６基因改变和ＰＣＮＡ指数随脑胶质瘤恶性程度级别增高呈上升趋势（Ｐ〈０．０５）。Ｐ１６基因改变与     

脑胶质瘤P16基因分子病理研究

目的：检测１５例脑胶质瘤中Ｐ１６基因及蛋白的存在状况。方法：用复合ＰＣＲ和免疫组织化学技术检测１５例脑胶质瘤。结果：显示Ｐ１６基因与Ｐ１６蛋白丢失率均为６０．０％（９／１５）；Ｐ１６基因和蛋白丢失主要见于Ⅲ级（８５．７％）和Ⅳ级（１００％）脑胶质瘤。结论：本文结果间接提示Ｐ１６基因和蛋白的丢失可能与脑胶质瘤的发生和演化有关。     

p53,CerbB—2和PCNA在脑胶质瘤中表达的意义及其 …

目的 研究７６例脑质瘤的ｐ５３ＣｅｒｂＢ－２和ＰＣＮＡ表达意义及其相关性。方法 应用ＳＰ微波免疫组化技术和统计学分析。结果 （１）在７６例脑胶质瘤组织中；ｐ５３，ＣｅｒｂＢ－２和ＰＣＮＡ的阳性表达率分别是４４．７４％（３４／７６），３４．２１％（２６／７６）和８０．２６％（６１／７６）。（２）ｐ５３的表达强度与胶质瘤的组织学类型和恶性程度呈显著正相关（Ｐ〈０．０１）。（３）ｐ５３ＣｅｒｂＢ－２和Ｐ     

儿童恶性脑胶质瘤P53与细胞增殖核抗原表达的预后价值

目的探讨Ｐ５３与细胞增殖核抗原（ＰＣＮＡ）在儿童恶性脑胶质瘤表达的预后价值。方法采用ＡＢＣ免疫组化方法对３３例儿童恶性脑胶质瘤Ｐ５３与ＰＣＮＡ表达进行回顾性研究。结果３３例儿童恶性脑胶质瘤中Ｐ５３表达阳性１５例（４５％），ＰＣＮＡ表达阳性２９例（８８％）。间变性星形细胞瘤、胶质母细胞瘤及髓母细胞瘤Ｐ５３蛋白表达的阳性比例分别为５／１２、９／１６、１／５，肿瘤Ｐ５３蛋白阴性者其细胞增殖活性均较阴性者高（Ｐ＜００５）；ＰＣＮＡ标记指数与肿瘤的恶性程度呈正相关（Ｐｅａｒｓｏｎ列联系数＝０．５６，Ｐ＜００１）。Ｐ５３或ＰＣＮＡ表达阳性者存活率分别显著低于Ｐ５３或ＰＣＮＡ表达阴性者（Ｐ＜００５，Ｐ＜００１）。结论Ｐ５３基因突变以及由此导致的细胞异常增殖与儿童恶性脑胶质瘤的发生和发展有关；ＰＣＮＡ能较好地反映胶质瘤的恶性程度，其表达检测对临床预后判定有重要参考价值。     

人脑胶质瘤微血管数与病理级别及预后关系的初步研究

目的探讨人脑胶质瘤微血管数（ＭＶＱ）与病理级别、术后复发、生存期及患者年龄、性别、肿瘤生长部位的关系。方法应用免疫组织化学ＡＢＣ法检测６３例人脑胶质瘤组织中Ⅷ因子相关抗原（ＦⅧＲＡｇ）的表达,计数ＭＶＱ。结果高恶性度（Ⅲ、Ⅳ级）胶质瘤ＭＶＱ高于低恶性度（Ⅰ、Ⅱ级）胶质瘤（Ｐ＜０．０５）。术后１８个月内复发及生存期小于３年者ＭＶＱ均明显高于对应组（Ｐ均＜０．０１）。ＭＶＱ与患者性别、年龄及肿瘤生长部位无关。结论人脑胶质瘤ＭＶＱ与病理级别、术后复发及生存期关系密切,可作为一项独立的预后指标     

人脑胶质瘤WAF1／CIP1表达的研究

目的检测抑癌基因ＷＡＦ１／ＣＩＰ１在人脑胶质瘤中的表达。方法取４６例胶质瘤组织及１２例脑外伤组织，提取其ｍＲＮＡ，用ＷＡＦ１／ＣＩＰ１作为模板进行逆转录ＰＣＲ（ＲＴ－ＰＣＲ）。结果４６例胶质瘤中有１４例有ＷＡＦ１／ＣＩＰ１蛋白表达（１４／４６），表达率为３０．４％，１２例脑外伤标本全部表达（１２／１２），表达率为１００％，两组比较有显著差异（Ｐ＜０．０１）。结论ＷＡＦ１／ＣＩＰ１的缺失是脑胶质瘤发生及进展的原因之一。     

TNF—α／Vp16系统对胶质瘤基因治疗的实验研究

目的 在体外水平（ｉｎ ｖｉｔｒｏ）建立对胶质瘤有杀伤作用的ＴＮＦ－α基因／Ｖｐ１６系统,研究该系统的有效性及可行性。方法 用逆转录病毒载体将ＴＮＦ－α基因转染人胶质瘤细胞株ＳＨＧ－４４,经生长抑制试验,比较转ＴＮＦ－α基因前后ＳＨＧ－４４细胞对Ｖｐ１６的敏感性。结果 生长抑制试验表明,转染ＴＮＦ－α基因后的ＳＨＧ－４４细胞对Ｖｐ１６的敏感性是转基因前细胞的１０倍（Ｐ〈０．０１）,ＩＣ５０为０．８     

小儿脑胶质瘤p16基因的表达

目的：检测２０例小儿脑软质瘤中Ｐ１６基因及其蛋白的存在情况。方法用聚合酶链式反应－单链构象多态性分析和免疫组织化学技术检测了２０例１－１４岁小儿脑胶质瘤。成果显示Ｐ１６基因和Ｐ１６蛋白的丢失率分别为５０％（１０／２０％）及（５／２０）。结论本结果提示Ｐ１６基因和蛋白缺失可能与部分小儿脑有质瘤发生,发展有关。     

针对胶质瘤发生发展组织芯片中表皮生长因子受体基因表达分析

目的探讨表皮生长因子受体（EGFR）基因在针对胶质瘤发生，发展相关组织芯片中的表达及意义。方法采用事先制作好的布有不同恶性程度胶质瘤临床标本、裸小鼠移植瘤标本、体外细胞系球体、脑肿瘤干细胞球体和相应对照标本共118例的组织芯片，进行EGFR的SABC法免疫组化染色，分析其表达率及表达强度。同时运用荧光实时定量PCR技术检测芯片中包含的几个细胞系EGFRmRNA表达量，对芯片中蛋白水平的研究进一步验证。结果EGFR染色主要位于细胞胞膜。在71例人脑胶质瘤组织中，EGFR阳性表达率为46．5％，各级别人脑胶质瘤组织中EGFR阳性表达率分别为Ⅰ级11．1％，Ⅱ级28．0％，Ⅲ级60．9％，Ⅳ级78．6％；各级别阳性率比较差异有显著性意义（X^2=15．668，P=0．001）；并且EGFR的阳性表达率与病理级别呈直线正相关（r=0．991，P=0．009）。在正常人脑组织、正常裸小鼠骨髓及神经干细胞球体中EGFR均呈阴性表达；在裸小鼠皮下移植瘤、人脑胶质瘤体外细胞系球体及脑肿瘤干细胞球体中EGFR均呈阳性表达。荧光实时定量PCR检测显示EGFR mRNA在人脑胶质瘤体外细胞系球体及脑肿瘤干细胞球体中表达含量高，在神经干细胞球体中表达含量极低，与芯片中蛋白水平的检测相一致。结论EGFR在正常组织和神经干细胞中未见表达，而在肿瘤中特别是脑肿瘤干细胞中高表达，并且是随着肿瘤恶性程度的增高而表达量增加。因此可作为胶质瘤发生发展的分子病因作进一步研究。     

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.