转录信号传导子和激活子3信号传导通路调控选择性环氧化酶2抑制剂抗结肠癌的机制

目的探究转录信号传导子和激活子3(Stat3)信号传导通路与选择性环氧化酶2(COX-2)抑制剂抗结肠癌细胞株HT-29机制的关系,明确COX-2抑制剂抗结肠癌细胞内信号传导机制。方法将选择性COX-2抑制剂NS-398,作用于结肠癌细胞系HT-29,运用MTT法检测细胞增殖状态;流式细胞仪观察NS-398对细胞凋亡的影响,进一步用RT-PCR检测药物作用前后HT-29中COX-2mRNA的表达;ELISA法测定体系前列腺素E2(PGE2)水平;Westernblot检测药物作用前后Stat3通路相关蛋白JAK2、Stat3的磷酸化活性和cyclinD1、Bcl-2的表达。结果结肠癌细胞系HT-29中COX-2mRNA呈高表达,NS-398呈时间、剂量依赖性方式抑制HT-29细胞增殖,促进其凋亡。NS-398使HT-29细胞COX-2mRNA和PGE2表达水平显著下降。同时p-JAK2、p-Stat3、cyclinD1、Bcl-2表达水平随作用时间延长而下降。结论癌基因Stat3信号传导通路调控了NS-398抗结肠癌的细胞内信号传导机制,最终通过其下游靶基因cyclinD1、Bcl-2影响结肠癌细胞系HT-29的增殖与凋亡。     

Voltage-Gated calcium channels and nonvoltage-gated calcium uptake pathways in the rat incisor odontoblast plasma membrane

Odontoblasts participate actively in the transport and accumulation of Ca²⁺ ions to the mineralization front during dentinogenesis. These cells are known to carry membrane-bound ATP-driven pumps and Na⁺/Ca²⁺ antiports for Ca²⁺ extrusion, but little is known about Ca²⁺ influx mechanisms into these cells. It has been shown that the administration of Ca²⁺ channel blockers in vivo strongly impairs Ca²⁺ uptake in the mineral phase during dentinogenesis in the rat; the present in vitro study is aimed at further elucidating odontoblast Ca²⁺ uptake mechanisms. Dissected rat incisor odontoblasts exhibited a pronounced fluorescence when incubated with a fluorescently-labeled (STBodipy) dihydropyridine, which is specific for voltage-gated Ca²⁺ channels of the L-type, and this binding was competitively abolished by nifedipine. As assayed by fluorescence spectrometry, odontoblast Ca²⁺ uptake was enhanced by the agonistic dihydropyridine BAYK-8644 (5 μM) as well as by plasma membrane depolarization in a high K⁺ (120 mM) medium. The Ca²⁺ uptake after depolarization was impaired by nifedipine (5 μM). When treated with the Ca²⁺-ATPase inhibitor cyclopiazonic acid (CPA; 10 μM), a nonvoltage-gated uptake of ⁴⁵Ca²⁺ was identified. This uptake was not influenced by nifedipine (20 μM) but was impaired by lanthanum ions (200 μM). A nonvoltage-gated uptake of Mn²⁺ into CPA-treated cells could be traced using the fura-2 quenching technique. This CPA-induced Ca²⁺ flux was not caused by an alteration of the plasma membrane potential, as assayed with di-8-ANEPPS. The results demonstrate that Ca²⁺ flux into dentinogenically active odontoblasts occurs through voltage-gated Ca²⁺ channels of the L-type and by nonvoltage-gated, agonist-sensitive Ca²⁺ uptake pathways. Received: 6 November 1995 / Accepted: 21 February 1996     

Managed mental health care: problems and possibilities

Case management has become an established organizational approach to mental health care. However, a recent development of case management, known as 'managed care' has received only limited attention in the UK and this has been confined to acute medical or surgical hospital care. The potential of managed care as applied to mental health care is uncertain. This paper clarifies the nature of managed care and discusses its relevance to mental health care, in particular to the care of people suffering from schizophrenia. The high incidence and heavy resource demands of this user group makes these people an ideal focus for managed care. However, there are conceptual and practical problems hindering its development and implementation, including: the variability and unpredictability of the disease process of schizophrenia; challenges of outcome measurement; and problems relating to the current organization of mental health care.     

视交叉后损害的临床与图形视觉诱发电位分析

图形视觉诱发电位(P—VEP)是眼接受图形的刺激时,视路及大脑皮质枕区所产生的一系列电位变化。在视交叉后病变的诊断,病情估计及预后推测中有比较肯定的价值。 本文对17例视交叉后损害的病人进行分析。发现视交叉后病变以视皮质损害为主,表现为视物模糊,视力下降,视野改变。P—VEP检查的异常率与病变部位大小及病变性质有关。同时检查半视野刺激有助于提高阳性率。     

Chromatic pattern-reversal electroretinograms (ChPERGs) are spared in multiple system atrophy compared with Parkinson’s disease

Abstract Idiopathic Parkinson’s disease (IPD) patients have abnormal visual evoked potentials (VEPs) and pattern electroretinograms (PERGs), attributed to dopaminergic transmission deficiency in visual pathway, probably the retina. VEP abnormalities are not reported in multiple system atrophy (MSA). The aim of this study was to investigate and compare chromatic (Ch) red-green (R-G) and blue-yellow (B-Y), and luminance yellow-black (Y-Bk) PERGs in patients with MSA and IPD. We investigated 6 MSA patients (mean age: 62±7.4 years) not undergoing any pharmacological treatment, as well as 12 early IPD patients (mean age: 60.1±8.3 years) and 12 age-matched normal observers. ChPERGs were recorded monocularly in response to full-field equiluminant R-G, B-Y and Y-Bk horizontal gratings. In MSA only responses to R-G stimuli showed minimal insignificant changes (slight but not significant amplitude reduction without any significant latency delay); no significant abnormality was detected for B-Y and luminance Y-Bk stimuli. By contrast, in IPD all responses were reduced in amplitude and delayed in latency, above all for B-Y stimuli. Present data indicate that both chromatic and achromatic PERGs are virtually unaffected in MSA, whereas in early IPD they are clearly impaired, suggesting different pathogenic retinal mechanisms and a useful simple tool for distinguishing MSA from IPD.     

经食道心房程序调搏检测房室结双径路——附23例检查报告

本文通过食道心房程序调搏检测出典型房室结双径路23例,其中12例诱发室上性心动过速(占52%);占17例有心动过速发作史者的70.6%。本文着重分析了房室结双径路与室上性心动过速的关系。     

白细胞介素6、信号传导和转录活化因子3和血管内皮生长因子在人脑胶质瘤中的表达及相关性研究

目的研究人脑不同级别胶质瘤中白细胞介素（IL）-6，信号传导和转录活化因子3（STAT3）和血管内皮生长因子（VEGF）的表达，探讨IL-6、STAT3和VEGF与肿瘤病理级别和侵袭性的关系。方法采用免疫组织化学法，检测70例人脑胶质瘤，10例脑膜瘤和5例正常脑组织中IL-6、STAT3和VEGF的表达。结果胶质瘤中IL-6、STAT3和VEGF的表达水平在高级别组（Ⅲ、Ⅳ级）明显高于低级别组（Ⅰ、Ⅱ级），两组间差异有统计学意义（P〈0．01），STAT3的表达与IL-6和VEGF的表达均呈正相关（P〈0．01）。结论IL-6、STAT3和VEGF的表达与胶质瘤的恶性程度有密切关系；且三者协同在胶质瘤发生、发展过程中起重要作用。三者的相关性证实VEGF基因由STAT3蛋白调节，而STAT3又由IL-6刺激活化。     

肿瘤蛋白质组学在信号传导通路、肿瘤标志物等方面的研究

肿瘤是一个多因素的疾病 ,在其的发生、发展过程中 ,分子生物学事件的复杂性日益受到人们的重视。随着基因组全序列测定的完成 ,蛋白质组学的研究得到了广泛的关注。应用蛋白质组学的方法 ,可以对细胞生长、分化过程中的蛋白质与细胞信号传导通路上的蛋白质之间的相互作用进行更为深入的研究 ,因而有希望发现控制肿瘤生物学行为的诸多蛋白质和信号分子。