P16MTS1、P27KIP1基因在胆管癌组织中的表达研究

目的：探讨P16^MIS1,P27^KIP1基因与胆管癌临床病理的关系。方法：采用免疫组化方法，检测48例胆管癌和8例伴慢性炎症的胆管壁组织中P16^MIS1,P27^KIP1蛋白表达情况。结果：（1）胆管癌中P16^MIS1,P27^KIP1阳性表达率分别为47．9％和35．4％，而伴炎症的胆管组织阳性表达率为100％和87．5％；（2）P16^MIS1,P27KIP1蛋白表达与胆管癌的分化程度，有无淋巴结或远处转移以及临床分期呈显著相关性。结论：P16^MIS1,P27^KIP1多基因表达异常可能与胆管癌的发生发展有关，是衡量胆管癌预后的有用指标。     

罗格列酮对多囊肾囊肿衬里上皮细胞p38促分裂原活化蛋白激酶信号通路的影响

Objective To investigate the effect of rosiglitazone on p38 mitogen-activated protein kinase (p38MAPK) pathway in polycystic kidney cyst-lining epithelial cells. Methods The cyst-lining epithelial cells (PKD cells) from human polycystic kidney were treated with rosiglitazone (10 μmol/L), peroxisome proliferator-activated receptor-γ (PPARγ) inhibitor GW9662 (10 μmol/L), rosiglitazone (10 μmol/L) +GW9662 (10 μmol/L), p38MAPK specific inhibitor SB203580 (10 μmol/L), SB203580 (10 μmol/L)+ rosiglitazone(10 μmol/L) for 2 hours followed by epidermal growth factor (EGF) stimulation. Protein expressions of p38, phuspho-p38 (p-p38) and proliferating cell nuclear antigen (PCNA) were detected by Western blot. p38 mRNA was examined by RT-PCR. Expression of c-fos and c-jun was observed by immunocytochemistry. Results (1) EGF markedly up-regulated the expressions of p38, p-p38, PCNA, c-fos anti c-jun compared with control group (P<0.01). (2) Compared with EGF treated group, rosiglitazone significantly reduced p38 activation and mRNA expression (P<0.01, respectively). Rosiglitazone, rosiglitazone+SB203580 could significantly down-regulated p-p38, PCNA, c-fos and c-jun expression (P<0.01, respectively) with no significant difference between these two groups. (3) GW9662 partially reversed the reduction effect of rosiglitazone. Conclusions Rosiglitazone can inhibit proliferation of autosomal dominant polycystic kidney disease cyst-lining epithelial cells partially through down-regulating p38 activation and reducing c-fos, c-jun and PCNA expression. The above effect of rosiglitazone is in part PPARγ-independcnt.     

氯喹敏感与抗性株恶性疟原虫对青蒿琥酯、克林霉素及其联用的体外敏感性

目的 为了解氯喹敏感和抗性株恶性疟原虫对青蒿琥酯、克林霉素及其二联用的敏感性。方法 运用Rieckmann体外微量法测定原虫对药物的敏感性。结果 氯喹敏感株恶性疟原虫对青蒿琥酯、克林霉素及青／克联用的ID50分别为2.8、3784.7及6.4/2046.6nmol/L；抗性株原虫对上述药物的ID50分别为8.1、1652.1及2.35/1409.4nmol/L。结论 抗氯喹恶性疟原虫对克林霉素无交叉抗性。青蒿琥酯与克林霉素联用在体外测定中，其抗疟作用对抗性株明显优于敏感株。     

Ki67、P53及微血管密度在大肠肿瘤中的表达

目的 研究Ki67、P53及微血管密度(microvessel density,MVD)在大肠肿瘤中的表达,探讨其与大肠肿瘤癌变的关系及作为早期癌变生物学标志物的可能性。方法 采用免疫组化技术分别测定正常大肠黏膜、大肠息肉及大肠癌组织标本中Ki67、P53及MVD值,共80例,分析其变化规律及相关性。结果 在正常黏膜、大肠息肉、大肠癌组中的Ki67标记指数逐渐增高(分别为11.00±10.70、39.64±17.70、52.96±26.40),组间比较差异显著(P=0.0001)。正常黏膜组P53蛋白均为阴性,大肠癌组P53蛋白表达的阳性率明显高于息肉组(P=0.0001)。Ki67、P53蛋白表达与性别、年龄、病程、病变部位、大小、大肠癌的病理类型、Dukes分期均无相关性。正常黏膜、大肠息肉、大肠癌组的MVD值(14.80±5.10、19.70±7.84、36.56±20.40)逐渐上升,3组差别显著(P=0.0001)。大肠癌中Dukes C、D期的MVD值(40.56±3.49)明显高于A、B期(29.50±2.45)(P=0.016)。Ki67与P53在各种组织中的表达呈正相关(r=0.5149,P=0.015)。联合检测Ki67及P53鉴别大肠良恶性病变的敏感度(70.37％)低于单侧Ki67(96.30％),但特异度(94.34％)明显增高。结论 Ki67标记指数可反映细胞增殖状态,指数高的大肠腺瘤易发生癌变。MVD值高的大肠癌易发生转移,MVD可作为判断大肠癌预后的参考指     

肝癌患者血清P-选择素测定及临床意义

目的：研究肝癌患血清P-selection(P-sel)在肝癌复发和转移中的作用。方法：采用ELISA法分别测定原发性肝癌患和对照组血清P-选择素的含量，同时测定AFP含量。结果：肝癌患P-sel含量显高于正常人，且与AFP含量呈线性正相关，术后2周浓度降低；P-sel含量以Ⅰ、Ⅲ和Ⅳ期肝癌患显高于Ⅰ期患；且大肝癌患显高于小肝癌患，有癌栓组、有肝内转移组明显高于无癌栓组和无转移组。结论：P-选择素测定在原发性肝癌的诊断和检测术后复发方面有重要价值，联合检测AFP和sP-sel可提高诊断敏感性。     

45例正常人听觉诱发电位P50的分析

目的 利用诱发电位技术探讨正常人听觉P50特征.方法 应用美国Nicolet Bravo脑电生理仪,采用条件刺激(S1)-测试刺激(S2)模式对45名健康受试者作了听觉P50检测.结果 分析了基本波型,提出了Cz和Pz区域P50诸指标平均值.结论 听觉P50电位具有抑制性特征,其变化可反映大脑正常感觉门的功能状态.P50较佳表达式是波幅S1-S2和100(1-S2/S1)两种结合,能直接显示感觉门的程度.此正常值可供抑郁症研究时参考.     

Illness-induced hyperalgesia is mediated by spinal neuropeptides and excitatory amino acids

The spinal cord dorsal horn contains neural mechanisms which can greatly facilitate pain. We have recently shown that ‘illness’-inducing agents, such as intraperitoneally administered lipopolysaccharide (LPS; bacterial endotoxin), can produce prolonged hyperalgesia. This hyperalgesic state is mediated at the level of the spinal cord via activation of the NMDA-nitric oxide cascade. However, prolonged neuronal depolarization is required before such a cascade can occur. The present series of experiments were aimed at identifying spinal neurotransmitters which might be responsible for creating such a depolarized state. These studies show that LPS hyperalgesia is mediated at the level of the spinal cord by substance P, cholecystokinin and excitatory amino acids acting at non-NMDA sites. No apparent role for serotonin or kappa opiate receptors was found.     

A study of tachykinin-immunoreactivity in the cat visual cortex

The localization of tachykinin-immunoreactivity in the cat visual cortex (area 17) was investigated using immunohistochemical methods. Strong laminar specificity was observed, with immunoreactivity highest in layer V, followed by layers I, VI, II and III, and the lowest density in layer IV. Most of the immunoreactive product was localized in neuronal processes. A few immunopositive cell bodies were also present. The immunopositive neurons were non-pyramidal, multipolar, or bipolar in shape, and mostly found in layer V. There were particularly dense immunopositive fibers and varicosities around somata in layer V. These may represent tachykinin-containing presynaptic terminals (boutons). The results provide anatomical evidence that tachykinin may primarily affect layer V neurons in the cat visual cortex.     

延髓—脊髓P物质能神经元下行通路参与毒扁豆碱的中枢升压反应

大鼠延髓腹侧面头端应用毒扁豆碱引起血压升高和心率加快,伴有延髓腹侧面头端胆碱酯酶活性降低和脊髓蛛网膜下腔灌流液中P物质样免疫反应活性升高。在延髓腹侧面头端应用阿托品或脊髓蛛网膜下腔注射P物质拮抗剂D-脯~2,D-苯丙~7,D-色~9-P物质均可阻断毒扁豆碱的心血管效应。脊髓蛛网膜下腔注射P物质抗血清或辣椒素均可减弱毒扁豆碱的升压反应。实验结果提示,毒扁豆碱作用于延髓腹侧面头端的M受体,兴奋了延髓-脊髓P物质能神经元下行通路,使之释放P物质,引起交感肾上腺髓质系统兴奋,从而使血压升高和心率加快。     

晚发性抑郁患者情绪调节机制的ERPs研究

目的采用事件相关电位探讨晚发性抑郁患者情绪调节障碍的神经生理机制。方法被试者包括16例晚发性抑郁患者（发病年龄≥60岁）与16名健康老年人。采用Go／Nogo实验范式，要求被试者对刺激序列中双个三角形进行按键反应（Go），单个三角形不反应（Nogo）。记录32导脑电。结果健康老年人中，Nogo刺激产生了明显的额中央区分布的N2Nogo和P3Nogo；与对照组相比，病例组的N2Nogo。波幅明显增高，而P3Nogo波幅显著降低，两者潜伏期无显著差异。结论晚发抑郁患者存在情绪调节障碍，其电生理学指标为N2Nogo明显增高和P3Nogo的显著降低，为晚发性抑郁的诊断和治疗提供了一定的客观评价指标。