Notch-1与Jagged-1蛋白在大肠癌组织中的表达及其意义

目的探讨Notch-1与Jagged-1蛋白在大肠癌组织中的表达及其与临床病理特征的关系。方法应用免疫组织化学PV-9000二步法检测大肠癌组织、癌旁组织及癌远端组织中Notch1与Jagged-1蛋白的表达,并分析Notch1与Jagged-1蛋白表达与临床病理参数的关系。结果Notch-1、Jagged-1蛋白在大肠癌中表达的阳性率明显高于癌旁组织及癌远端组织（P〈0．05）;大肠癌中Jagged-1蛋白表达强度与肿瘤组织学分级、Dukes分期及淋巴结转移密切相关（r=0．355、0．385、0．248,P均〈0．05）。大肠癌中Notch-1蛋白与Jagged-1蛋白表达呈正相关（r=0．305,P〈0．05）。结论Notch．1及Jagged-1蛋白可能在大肠癌发生发展中起重要作用。     

RASSF1A基因在胃腺癌和癌前病变中的表达及意义

目的: 探讨RASSF1A与CyclinD1在胃癌发生发展中的作用.方法: 采用RT-PCR检测胃正常组织、腺瘤组织、不典型增生组织各20例及胃腺癌组织40例中RASSF1A及CyclinD1 mRNAA表达,并Western blot法检测RASSF1A蛋白表达.结果: 胃腺癌组RASSF1A的表达低于不典型增生、良性腺瘤及正常组织组(37.5%vs 80.0%,95.0%,100.0%,均P<0.05),而CyclinD1的表达高于不典型增生、良性腺瘤及正常组织组(77.5%vs 25.0%,10.0%,5.0%,均P<0.05).胃癌组织中,RASSF1A及CyclinD1 mRNA表达均与病理分级有关(χ2=4.422,8.935,均P<0.05);两者之间表达呈负相关(γ=-0.448,P<0.05);RASSF1A蛋白表达与mRNA表达一致.结论: RASSF1A与CyclinD1两种蛋白的异常表达在胃癌的发生发展中可能具有协同作用,二者联合检测能为胃癌的早期临床诊断和治疗提供有利的生物学信息.     

Expression and significance of ICAM-1 and its counter receptors LFA-1 and Mac-1 in experimental acute pancreatitis of rats

AIM: To investigate the role of intercellular adhesion molecule-1 (ICAM-1) and its counter receptors LFA-1 and Mac-1 in acute pancreatitis (AP). METHODS: SD rats were allocated to AP group and control group randomly (25 rats each). AP was induced by infusion of 5% chenodeoxycholic acid into the pancreatic duct, followed by ligation of pancreatic duct. The rats were sacrificed at 1, 3, 6, 12 and 24 h after induction of pancreatitis. Five rats were sacrificed at one time point in the two groups before the blood and specimens from pancreas and lung were obtained. Serum amylase and ascitic fluid were measured at each time point. Expression of ICAM-1 at different time points was assessed by immunohistochemistry in pancreas and lung, and the expression of LAF-1 and Mac-1 on neutrophils at different time points was detected by flow cytometer. RESULTS: Induction of AP was confirmed by the serum levels of amylase and histological studies. The expression of ICAM-1 in pancreas increased significantly than that in the control group at all time points (P < 0.05 or P < 0.01), as well as the expression in lung except at 1 h. The expression of LFA-1 and Mac-1 on neutrophil in blood increased significantly in AP group than that in control group at several time points (P < 0.05 ox P < 0.01). The amount of ascitic fluid and serum amylase level of AP group increased significantly than that of control group at all time points (P < 0.05 or P < 0.01). Parallel to these results, a significant neutrophil infiltration was found in pancreas and lung tissues of AP group rats. CONCLUSION: Our findings suggest the important role for ICAM-1, LFA-1 and Mac-1 in mediating the development of AP from a local disease to a systemic illness. Upregulation of ICAM-1, LFA-1, Mac-1 and subsequent leukocyte infiltration appear to be significant events of pancreatic and pulmonary injuries in AP.     

PD-1/PD-L1抑制途径与自身免疫性糖尿病

PD-1(CD279)是一种负性协同刺激分子,属于CD28超家族成员,呈诱导性表达于活化的T、B和自然杀伤细胞表面.PD-L1(B7-H1,CD274)和PD-L2(B7-DC,CD273)是PD-1的两个配体.PD-1和PD-L1相互作用可以使活化的自身反应性T细胞获得负性信号,抑制其对自身抗原持续的免疫应答.若PD...     

Trp-21 is important in the processing and secretion of big endothelin-1

To investigate the intracellular processing of endothelin-1 (ET-1), the synthesis and secretion of preproET-1 (PPET-1) was studied in transiently transfected COS-7 cells. Replacements at the highly conserved C-terminal region of ET-1 were made by site-directed mutagenesis, with codons for residues Ile-20 and Trp-21 being replaced by one for Ala in the PPET-1 cDNA. The mutant and wildtype PPET-1 cDNAs were expressed in COS-7 cells following transient transfection, and cell media and extracts, collected after 48 h, were assayed for ET-1 and big ET-1 by radioimmunoassay. The concentration of immunoreactive ET-1 in the medium obtained from the Ala-21-ET-1 mutant was 10-fold lower than that from PPET-1 wildtype and (Ala-20-ET-1) PPET-1 transfected cells. Moreover, Ala-21 -big ET-1 accumulated in the cells transfected with the cDNA for (Ala-21-ET-1) PPET-1, whereas there was no significant accumulation of ET-1-like or big ET-1-like immunoreactivity in the cells transfected with cDNAs for PPET-1 wildtype and (Ala-20-ET-1) PPET-1. These results suggest that Trp-21 is involved in intracellular processing and secretion of big ET-1.     

甲型H1N1流感合并肺炎的临床特点分析

目的通过对甲型H1N1流感合并肺炎的临床特点的分析。方法分析2009年月10月-2010年3月在我院入住的29例甲型H1N1流感合并肺炎患者的临床表现、实验室检查及胸部CT等资料。结果本组病例男性16例,女性13例。3例妊娠,13例合并有基础疾病。所有病例均有流感样前驱症状,呼吸道主要症状为发热、干咳少痰,严重者气短、呼吸困难、咯血。合并细菌感染时咯脓痰。肺部听诊无啰音或少啰音,合并哮喘时有哮鸣音,合并细菌感染时可有湿啰音。实验室检查65%白细胞不高或降低,41%心肌酶升高,58.6%存在低氧血症,35%呼吸衰竭。影像学表现多种多样：65.5%主要为单侧或双侧棉团样、团片样边界模糊高密度渗出影伴肺实变,其内见充气支气管征,病变沿支气管血管束分布。轻症及早期较局限,重症者及晚期病变融合呈双肺多发弥漫性改变。少数呈大叶及小叶性肺炎表现。预后大多良好,病死率6.9%。主要死亡原因为呼吸衰竭及大咯血。结论甲型H1N1流感合并肺炎是以甲型H1N1流感病毒肺炎为主要疾病的多种肺炎构成。甲型H1N1流感病毒肺炎临床表现具有流感病毒肺炎共性特点,其影像学表现有一定特征性。     

1-Naphthyl isocyanate and 1-naphthylamine as metabolites of 1-naphthylisothiocyanate

Abstract: The importance of the bioactivation of 1-naphthylisothiocyanate was studied. Forty minutes after 1-naphthylisothiocyanate administration to rats, bile was collected over a 2.5-h period; the liver was then excised and homogenized. 1-naphthylisothiocyanate and its metabolites in bile and liver of rats were identified and quantified using coupled gas chromatography-mass spectrometry. Three main compounds were found in all 1-naphthylisothiocyanate-treated animals. They were identified as 1-naphthyl isocyanate, 1-naphthylamine and the parent compound, 1-naphthylisothiocyanate. When rats were given cycloheximide, which attenuates 1-naphthylisothiocyanate toxicity, 30 min before 1-naphthylisothiocyanate (300 mg/kg), 1-naphthyl isocyanate concentration was significantly lower than in rats receiving only 1-naphthylisothiocyanate. The appearance of 1-naphthylamine was also inhibited by cycloheximide, although not to the same extent as 1-naphthyl isocyanate. On the other hand, phenobarbital, which potentiates 1-naphthylisothiocyanate hepatotoxicity, enhanced 1-naphthyl isocyanate and 1-naphthylamine formation. It is suggested that 1-naphthyl isocyanate, 1-naphthylamine and the highly reactive sulfur released from 1-naphthylisothiocyanate might be involved in the hepatotoxic effect of 1-naphthylisothiocyanate.     

Notch-1、Jagged-1及P-mTOR在胰腺癌中的表达及意义

目的 检测Notch-1、Jagged-1及p-mTOR三种蛋白在胰腺癌组织中的表达并探讨它们与临床病理特征的关系及三者之间的相关性.方法 采用免疫组织化学SP法检测40例胰腺癌组织和20例正常胰腺组织中Notch-1、Jagged-1及p-mTOR三种蛋白的表达.结果 Notch-1的阳性表达主要位于肿瘤细胞胞膜和胞浆,Jagged-1、p-mTOR的阳性表达主要位于细胞浆.Notch-1、Jagged-1及p-mTOR在胰腺癌组织中的阳性表达率分别为80%、75%和72.5%,均显著高于正常胰腺组织中的表达,差异有统计学意义(P<0.05).Notch-1、Jagged-1及p-mTOR的异常表达均与胰腺癌的淋巴结转移和TNM分期有关(P<0.05),与患者的性别、年龄、部位、分化程度和病理分型无关(P>0.05).Notch-1、Jagged-1及p-mTOR三者间的表达均呈正相关.结论 Notch-1、Jagged-1及P-mTOR的过表达促进胰腺癌的发生发展、浸润转移,Notch-1信号通路可能间接调节mTOR的活性.     

B7-H1及其受体PD-1分子在原发性肝-癌组织中的表达及临床意义

目的:分析B7-H1和PD-1分子在原发性肝癌组织中的表达,并探讨其在肝癌发生过程中的临床意义.方法:采用免疫组织化学染色和半定量逆转录聚合酶链反应(RT-PCR)检测42例原发性肝癌组织及对应的癌旁正常肝组织中B7-H1蛋白和mRNA表达,分析B7-H1分子与肝癌分化程度、有无侵袭转移的关系.分离肝组织内淋巴细胞.流式细胞仪分析PD-1分子在T细胞表面表达,以及B7-H1信号对肝癌组织内T细胞功能的影响.结果:原发性肝癌组织中B7-H1蛋白及mRNA表达水平均比癌旁组织和正常组织显著升高(85.71%vs 28.57%,7.14%:0.73±0.21vs0.35±0.12,0.23±0.07,均P<0.05),B7-H1阳性细胞与癌组织分化程度、有无侵袭转移相关(x2=7.876,8.492,均P<0.05),但与患者性别、年龄、肿瘤大小、肿块类型及AFP水平无相关关系.肝癌组织中T细胞表达PD-1水平比癌旁对照显著上高(20.15%±3.47%vs2.67%±0.53%,P<0.001).结论:肝癌中B7-H1分子表达可能抑制肝癌组织内T细胞功能,促进肝癌细胞逃避免疫监控,阻断肝癌细胞表面B7-H1/PD-1信号传导,可能成为肝癌免疫治疗的新途径.     

C57黑鼠骨关节炎模型的关节病理积分与血清及滑膜中基质金属蛋白酶-3白细胞介素-1水平的相关性研究

目的 探讨基质金属蛋白酶(MMP)-3与白细胞介素(IL)-1在骨关节炎(OA)发病中所起的作用及其用于临床判断OA早期病理变化的可能性.方法 采用C57黑鼠OA模型.在自然增龄基础上,又对小鼠进行运动负荷训练.应用形态学方法对模型关节的病理切片观察,进行OA积分评分.研究采用酶联免疫吸附试验(ELISA)的方法.检测血清及滑膜中MMP-3、IL-1的水平.采用相关性分析来检验血清和滑膜中MMP-3、IL-1水平之间的关系,以及与OA积分评分之间的相关性.结果 ①形态学观察:C57黑鼠具有自发OA特征,其OA严重程度与周龄相关,且运动负荷可加快有自发OA倾向的小鼠关节软骨病理改变.②ELISA检测:运动负荷组滑膜中MMP-3[(84±6)ng/ml]、IL-1[(48±3)ng/ml]及血清中IL-1[(38.3±5.0 mg/ml]含量高于自然增龄组[滑膜MMP-3(71±5)ng,ml;IL-1(42±3)ng/ml;血清IL-1(8.1±2.4)ng/ml],差异有统计学意义(P<0.01);血清与滑膜中MMP-3、IL-1水平、OA评分存在线性相关[r均>0.67,P均<0.01].结论 联合检测MMP-3及IL-1在OA血清中的含量,有助于疾病的诊断与病情的判断.特别是MMP-3对于OA的早期诊断具有更为重要的意义.     

代谢酶基因CYP 1A1与广西胃癌遗传易感性的关系

目的探讨代谢酶基因CYP 1A1MSP1多态性与广西地区汉族、壮族人群胃癌遗传易感性之间相关性。方法采用PCR-RFLP技术检测广西地区汉族、壮族人群中121例胃癌患者和138例健康人CYP1A1MSP1多态性的分布频率,分析其与广西地区汉族、壮族人群胃癌遗传易感性的相关性及与吸烟、饮酒在胃癌易感性中的相互作用。结果 (1)CYP 1A1MSP1三种基因型(m1/m1、m1/m2、m2/m2)分布频率在两组间比较差异无统计学意义(χ2=0.901,P=0.342);(2)携带CYP1A1MSP1突变m2基因型的个体较携带m1/m1基因型的个体患胃癌的风险增加(OR=1.509),但差异无统计学意义(P=0.342)。结论单独的CYP 1A1基因MSP1多态性与广西地区汉族、壮族人群胃癌易感性无明显相关性。     

谷胱甘肽-S-转移酶M1和T1空白基因型与肝癌遗传易感性的研究

目的谷胱甘肽－Ｓ－转移酶Ｍ１和Ｔ１（ＧＳＴＭ１和ＧＳＴＴ１）空白基因型与肝癌遗传易感性的关系。方法应用多重ＰＣＲ技术检测６３例肝癌患者和８８例健康对照的ＧＳＴＭ１和ＧＳＴＴ１空白基因型。结果病例组ＧＳＴＭ１空白基因型的频率为５７．１％，对照组则为４２．０％，二者差异无显著性（χ２＝３．３５，Ｐ＝０．０６７），处于临界水平。ＯＲ值为１．８４（９５％ＣＩ＝０．９１～３．７３）。病例组ＧＳＴＴ１非空白基因型的频率为８７．３％，对照组则为６２．５％，二者差异有非常显著性（χ２＝１１．４２，Ｐ＝０．０００７２７４），ＯＲ值为４．１３（９５％ＣＩ＝１．６４～１０．７０）。叉生分析表明，ＧＳＴＴ１非空白基因型与肝癌的关联大于ＧＳＴＭ１空白基因型，两因素在肝癌发生中存在协同作用。结论具有ＧＳＴＭ１空白基因型和ＧＳＴＴ１非空白基因型的个体，患肝癌的危险性增加。     

肿瘤-睾丸抗原MAGE-1和NY-ESO-1 mRNA在胃肠间质瘤中的表达

目的:探讨肿瘤-睾丸抗原(CTA)MAGE-1和NY-ESO-1作为胃肠间质瘤(GISTs)免疫治疗特异性靶点及MAGE-1和NY-ESO-1 mRNA作为辅助GISTs危险度分级指标的可能性.及其与GISTs生物学行为的关系.方法:采用逆转录-聚合酶链反应(RT-PCR)技术,检测30例GISTs中MAGE-1和NY-ESO-1mRNA的表达,并取正常胃肠道组织作为阴性对照组,同时分析MAGE-1和NY-ESO-1mRNA表达与病理特征的关系.结果:正常对照组中无阳性表达,30例GISTs中,18例至少表达一种CTA,MAGE-1和NY-ESO-1 mRNA在GISTs中的表达率分别为30%和47%.MAGE-1和NY-ESO-1 mRNA表达与患者年龄、性别和病理类型无关,而与肿瘤生长部位、肿瘤大小及危险度分级有关(P<0.05).MAGE-1和NY-ESO-1 mRNA在低危、中危、高危三个组中表达量随着危险度分级的升高而增高,三组间差异有统计学意义(P<0.05).MAGE-1和NY-ESO-1 mRNA在GISTs中的表达不存在相关性(r=0.018,P>0.05).结论:MAGE-1和NY-ESO-1 mRNA在GISTs中的高特异性表达,其抗原有望成为GISTs免疫治疗特异性的靶点:MAGE-1和NY-ESO-1 mRNA表达与GISTs危险度分级有关,MAGE-1和NY-ESO-1 mRNA有望成为辅助GISTs危险度分级的诊断指标.     

新甲型H1N1流感病毒与流感大流行防治研究进展

由于甲型流感病毒基因高度变异的特点,导致其对不同种属宿主亲和力、毒力、免疫原性、抗药性不断发生变化,全球新型流感大流行的风险时刻存在.因此,应加强流感特别是重症流感发病机制和有效干预措施研究,从疫苗研制、开发新型抗病毒药、加强综合治疗,特别是调节宿主免疫反应等多个方面着手,为应对可能爆发的流感大流行提供对策.     

共刺激分子B7-H1和受体PD-1在溃疡性结肠炎患者结肠黏膜中的表达及意义

目的研究共刺激分子B7-H1和受体PD-1在溃疡性结肠炎患者结肠黏膜中的表达,探讨二者在结肠黏膜炎症反应中的作用及意义。方法收集溃疡性结肠炎患者45例及正常对照者10例,结肠镜下活检结肠黏膜行免疫组织化学染色,检测结肠黏膜中B7-H1和PD-1的表达,以阳性细胞的累积光密度值（IOD值）为评价指标,比较各组差异。结果 B7-H1和PD-1主要在结肠黏膜固有层单个核细胞中表达。UC活动期患者炎症最重部位及炎症不明显部位、UC缓解期患者原炎症部位B7-H1和PD-1的表达强度（IOD值）均明显高于正常对照组。其中B7-H1表达强度最高的为UC活动期患者炎症最重部位,其后依次为UC活动期患者炎症不明显部位和UC缓解期患者原炎症部位,各组间比较差异均有统计学意义（P〈0.05）;PD-1表达强度最高的为UC活动期患者炎症不明显部位,其后依次为UC活动期患者炎症最重部位和UC缓解期患者原炎症部位,各组间比较差异均有统计学意义（P〈0.05）。结论 UC患者结肠黏膜中B7-H1和受体PD-1表达上调,且表达水平与炎症程度有关,提示二者参与了肠道的炎症反应。