Mechanisms underlying the antidopaminergic effect of clonazepam and melatonin in striatum

Intrastriatal injection of the GABA_A antagonist, bicuculline, caused about a 75% decrease in the inhibitory effect of the central-type benzodiazepine (BZ) agonist, clonazepam or the indoleamine hormone, melatonin, on apomorphine-induced rotation in a 6-hydroxydopamine model of dopaminergic supersensitivity. Pretreatment with the peripheral-type BZ antagonist, PK 11195 (intrastriatally or intraperitoneally), also attenuated the antidopaminergic effect of these drugs but with much less potency than bicuculline. However, the combination of both bicuculline and PK 11195, injected directly into the striatum, completely blocked the antidopaminergic action of clonazepam or melatonin. These results indicate that the antidopaminergic action of clonazepam and melatonin in the striatum involves two distinct mechanisms: (1) a predominant GABAergic activation via the BZ/GABA_A receptor complex, and (2) a secondary mechanism linked to a PK 11195- sensitive BZ receptor pathway. Recent studies indicate that PK 11195 blocks BZ-induced inhibition of the adenylyl cyclase-cyclic AMP pathway in the striatum. Since cyclic AMP has been implicated in the rotational behaviour of 6-hydroxydopamine-lesioned animals, it is possible that the antidopaminergic action of clonazepam and melatonin also involves suppression of this second messenger. All rights reserved.     

胚鼠黑质细胞悬液移植于帕金森病模型鼠侧脑室的实验研究

将胚鼠中脑腹侧组织制成细胞悬液移植于帕金森病(PD)模型鼠侧脑室,动态观察受体鼠在移植前后的行为变化。移植后16周应用诱发荧光及免疫细胞化学等方法,对移植物在受体鼠脑内的存活及生长情况进行了研究。结果,受体鼠旋转行为明显改善,侧脑室内可见黄绿色荧光细胞及酪氨酸羟化酶(TH)免疫反应阳性细胞,有的发出突起伸向室管膜及迁于尾核区.提示:移植的胚鼠黑质细胞生长良好,似作为触液神经元发挥其作用。     

Predictive power of various models for longitudinal attachment level change

Abstract Several statistical models that have been suggested in the periodontal literature for describing longitudinal attachment level changes, such as the gradual loss, single-burst, multiple-burst, and random walk models as well as other models introduced in this paper are compared by their power to predict future attachment loss. The data used in this analysis is from 1061 sites of 8 subjects, with moderate to severe periodontal disease, monitored monthly for about a year. This study found that none of the suggested models could significantly outperform the naive mean predictor, which predicts the future attachment level from the past mean. It was also found that no single model, such as the burst, gradual, or random walk, together with measurement error can fully explain the variation in the data. These results indicate that in the course of one year, the attachment level change may not follow the same model. Consequently, a model that fits well to past data cannot be accurately extended to the future.     

应激相关因素对护士生活质量作用模型的理论构建和结构方程分析

目的应用结构方程分析研究应激相关因素对护士生活质量的影响机制。方法通过随机抽样,采用生活质量综合评定问卷、压力反应问卷、生活事件量表、特质应对方式问卷、领悟社会支持量表、艾森克人格问卷对405名护士进行调查,并应用结构方程分析方法对其作用机制进行探索。结果在5个理论可行的竞争模型中获取了最佳模型(CMINDF2.344;GFI0.928;AGFI0.891;CFI0.945;RMSEA0.060),即应激相关5因素(压力反应、生活事件、社会支持、应对方式和个性特征)中除应对方式外均能直接影响生活质量,而应对方式则以其他应激相关因素为中介对生活质量产生间接影响,这5个因素均可互为中介对护士生活质量产生间接作用。结论结构方程分析方法证实应激对护士生活质量的影响是一个交叉作用系统,在干预应激对护士生活质量的影响时应综合运用直接和间接方法。     

社区卫生服务信息系统功能建模研究

理顺功能关系、理清业务流程是构建社区卫生服务信息系统的前提和基础,功能建模是理顺功能关系的一个重要手段。在研究现有的各种功能分析方法的基础上,本文以IDEF0模型方法为基础,提出了社区卫生服务信息系统功能建模方法。通过建立功能、数据和约束之间的内在联系,为系统的功能设计和数据分析提供了基础。     

人参茎叶总皂甙对实验性小鼠生殖细胞遗传物质损伤的影响

本文采用小鼠精原细胞姐妹染色单体互换（ＳＣＥ）实验方法，研究了人参茎叶总皂甙（ＧＮＳ）对丝裂霉素Ｃ（ＭＭＣ）引起的小鼠精原细胞遗传物质损伤的影响。结果表明，ＧＮＳ不能诱发小鼠精原细胞ＳＣＥ，而且在腹腔注射ＭＭＣ的同时给予ＧＮＳ，可使ＭＭＣ诱发的小鼠精原细胞ＳＣＥ频率明显降低。为此，我们认为ＧＮＳ对小鼠生殖细胞遗传物质具有保护作用。     

乳腺癌层粘连蛋白的免疫组织化学研究

本研究应用层粘连蛋白（ＬＮ）抗体，对２７例乳腺癌、５例乳腺良性病变进行了免疫组织化学研究。结果发现乳腺良性病变时，ＬＮ以均匀完整的线型阳性反应显示在乳腺导管及小叶基膜处。乳腺癌时，ＬＮ的染色表现为癌细胞胞浆内弥漫状阳性反应。２７例乳腺癌中，癌细胞ＬＮ染色强度不同，伴有转移的乳腺癌ＬＮ染色多数较强，强度在＋＋～的为７／１２（５８．３％）；不伴有转移的病例，ＬＮ染色多数较浅或为阴性，强度在＋＋～＋＋＋的病例为３／１５（２０％）。说明癌细胞内源性ＬＮ染色强弱与肿瘤转移密切相关，内源性ＬＮ的合成可能改变肿瘤细胞的浸润活性。     

Controlling for occasion-specific effects when assessing the test–retest reliability of self-report health questionnaires

OBJECTIVE: This study proposes a method for self-report health questionnaires to adjust test-retest reliability for changes during the test-retest interval based on an external measure, and to distinguish such changes from random response errors. METHODS: In our application, eighty participants completed the Symptoms of Illness Checklist (SIC) on two occasions, two weeks apart, immediately before interviews given on each occasion by one of two physicians in a crossover design. The physician interview scores served as external measures, and structural equation modeling was used to estimate the parameters of a model that corrected for the occasion-specific effect of participants' responses using information from the interviews. RESULTS: Correcting for changes in symptoms during the test-retest interval increased SIC test-retest reliability from .744 to .804 and significantly improved model fit (chi2(diff)(1) = 30.78, p < .001). CONCLUSIONS: The results suggest methods that can improve the evaluation of self-report health questionnaire test-retest reliability by identifying changes using an external measure, and distinguishing these from random response errors; these increased the estimated SIC test-retest reliability and indicated that the SIC was indeed able to measure changes over the studied time interval. This method can be applied across a broad range of questionnaires.     

Neuronal activity in the globus pallidus of multiple system atrophy patients.

The pathophysiological changes in neural activity that characterize multiple system atrophy (MSA) are largely unknown. We recorded the activity of pallidal neurons in 3 patients with clinical and radiological features of MSA who underwent unilateral microelectrode-guided pallidotomy for disabling parkinsonism. Findings in these patients were compared with 4 control patients with a clinical diagnosis of Parkinson's disease (PD). The position, firing rates, and firing patterns of single neurons in the pallidal complex were analyzed in both MSA and PD patients. The mean spontaneous firing rate of neurons in the internal segment of the globus pallidus internus (GPii) was significantly lower in MSA than in PD patients. There were no significant differences between MSA and PD patients, however, in firing rates of neurons in the external globus pallidus (GPe) or in the external segment of GPi (GPie). In addition, no significant differences in firing pattern were found between MSA and PD patients. In conclusion, this study has shown that firing rates of neurons in GPii but not in GPie and GPe are different in MSA patients compared with that in PD patients, a finding that may reflect the poor clinical results of pallidotomy reported in patients with MSA.     

Phenotypic and genetic analyses of T-cell-mediated immunoregulation in patients with Type 1 diabetes.

AIMS: To investigate the contribution of regulatory T cells and co-stimulatory molecules in CD4(+) T cells to the development of Type 1 diabetes (T1D). METHODS: Twelve patients with T1D, nine patients with systemic lupus erythematosus (SLE), and 12 age-matched healthy control subjects participated. We analysed the proportions of CD25(+)CD4(+) T cells and natural killer T cells (NKT cells), and the expression levels of Foxp3, CTLA-4, CD28, ICOS, PD-1 and BTLA in peripheral blood mononuclear cells and purified CD4(+) T cells. RESULTS: There were no significant differences in the proportions of CD25(+) CD4(+) T cells or NKT cells among the three groups. PD-1 expression levels of peripheral CD4(+) T cells from T1D patients were significantly lower than those from healthy control subjects (P = 0.00066). In contrast, PD-1 expression levels were similar in SLE patients and healthy control subjects. The expression levels of Foxp3, CTLA-4, CD28, ICOS and BTLA were similar in the three groups. CONCLUSIONS: Decreased expression of the PD-1 gene in CD4(+) T cells may contribute to the development and/or maintenance of autoimmune T1D. As the population studied was small and heterogeneous, further studies are required to confirm the findings.