幽门螺杆菌ureB基因表达产物的反应原性

目的：克隆幽门螺杆菌ureB基因，并进行表达，验证表物的反应原性。方法：应用PCR技术从技术临床分离株中扩增出ureB基因，克隆入载体pGEM-7zf( ）进行测序，进一步转到友大肠杆菌表达载体pBV220进行诱导表达，以Western blot实验验证重组蛋白的反应原性。结果：测序后经同源性比较，证实扩增后得到的片断确为ureB基因，并原核表达出可被抗Hp抗体识别的非融合重组蛋白。结论：获得了有反应原性的重组ureB蛋白。     

乙肝患者血清抗心磷脂抗体的检测

目的 :了解抗心磷脂抗体 (ACA)在乙型肝炎病毒 (HBV)感染中的检出率。方法 :采用ELISA法测定 83例HBV患者和 6 6例正常对照者血清的ACA。结果 :HBV患者ACA阳性率为 16 .9% ,与正常对照组 (4.5 % )比较有显著性升高 (P <0 .0 1) ;在HBV患者中 ,肝功能异常者ACA阳性率明显高于肝功能正常者 (P <0 .0 1)。结论 :ACA可常见于乙型肝炎患者 ,并可能与乙型肝炎的病情有一定关系。     

慢性乙型肝炎中可溶性白细胞介素2受体与其它血清学指标的关系

目的 :探讨血清可溶性白细胞介素 2受体 (sIL 2R)在慢性乙型病毒性肝炎 (慢乙肝 )中的发病机制及sIL 2R与肝纤维化指标、肝功能的相关关系。方法 :对 312例肝活检病人按组织病理学炎症和纤维化程度进行分级分期 ,同时检测了病人血清sIL 2R、肝功能及肝纤维化相关指标。结果 :血清sIL 2R均值较对照组明显增高 (P <0 .0 1) ,增幅随着肝脏病理炎症和纤维化程度的加重而逐渐加大 ,各组间比较差异有显著性 (P <0 .0 5或P <0 .0 1)。sIL 2R与血清白蛋白 (A)呈显著负相关 ,与血清脯氨酸肽酶 (PLD)、Ⅳ型胶原 (CⅣ )、层粘连蛋白 (LN)、透明质酸 (HA)、Ⅲ型前胶原氨基端肽 (PⅢNP)、肝功指标中的TB、DB、G、ALT、AST、AKP、γ GT呈显著正相关 (P <0 .0 5或P <0 .0 1)。结论 :慢乙肝病人血清sIL 2R水平与A呈显著负相关 ,与PLD、CⅣ、LN、HA、PⅢNP呈显著正相关 ;sIL 2R的血清水平能反映肝脏组织学病变的程度 ,可作为判断肝组织炎症和纤维化程度的参考指标。     

儿童慢性乙型肝炎细胞免疫功能及胸腺素疗效

目的　探讨慢性乙型肝炎(CHB)患儿细胞免疫功能及胸腺素疗效。方法　6 0例CHB患儿随机分为常规组(予常规治疗)和胸腺素组(在常规治疗基础上+胸腺素) ,并以6 0例健康儿童作为正常对照组。于治疗前、疗程结束后1mo检测T细胞亚群(CD+ 3 、CD+ 4 、CD+ 8)、血清白细胞介素2 (IL 2 )及可溶性白细胞介素2受体(sIL 2R)水平;定期复查肝功能、乙肝标志物和HBV DNA。结果　与正常对照组比较,CHB组CD+ 3 与CD+ 4 的百分率、CD+ 4 /CD+ 8及血清IL 2水平明显降低(P均<0 0 1) ,CD+ 8百分率及血清sIL 2R水平明显升高(P均<0 0 1) ;与常规组比较,胸腺素组血清ALT明显下降(P <0 0 1) ,ALT复常时间明显缩短(P <0 0 1) ,HBeAg转阴率明显上升(P <0 0 5 ) ,各免疫学指标明显恢复,差异均有统计学意义(P <0 0 1或P <0 0 5 )。结论　CHB患儿细胞免疫功能低下,胸腺素能增强细胞免疫功能,有利于病毒清除和肝功能的恢复     

原发性肝癌患者乙型及丙型肝炎病毒感染的检测

目的　调查原发性肝癌患者乙型及丙型肝炎病毒感染情况。　方法　采用免疫组织化学 SP法检测15 7例原发性肝癌患者乙型肝炎病毒 (HBV)及丙型肝炎病毒 (HCV)感染情况 ,每例患者均有血清学检测资料 ,另取 30例良性肝病组织作对照 ,所有数据用卡方检验。　结果　 15 7例原发性肝癌患者中 HBV感染阳性率为31.8% (5 0 / 15 7) ,HCV感染阳性率为 5 1.0 % (80 / 15 7) ,其中 10 7例原发性肝细胞癌 HBV、HCV感染阳性率分别为39.3% (42 / 10 7) ,4 5 .8% (49/ 10 7) ,5 0例胆管细胞癌 HBV、 HCV感染阳性率分别为 16 .0 % (8/ 5 0 ) ,6 2 .0 %(31/ 5 0 ) ,原发性肝细胞癌、胆管细胞癌 HBV、HCV重叠感染率分别为 2 7.1% (2 9/ 10 7) ,14 .0 % (7/ 5 0 ) ,良性肝病组HBV、HCV感染阳性率分别为 16 .7% (5 / 30 ) ,30 .0 % (9/ 30 )。原发性肝细胞癌 HBV感染、胆管细胞癌 HCV感染率高于良性肝病组 ,差异均有显著性 (P<0 .0 5 )。原发性肝细胞癌 HBV、HCV血清学检测阳性率分别为 87.8%(94 / 10 7) ,13.1% (14 / 10 7) ,胆管细胞癌 HBV、HCV血清学检测阳性率分别为 6 8.0 % (34/ 5 0 ) ,16 .0 % (8/ 5 0 )。　结论　原发性肝癌与 HBV、HCV的感染有密切关系     

B cells as a target of immune modulation

B cells have recently been identified as an integral component of the immune system; they play a part in autoimmunity through antigen presentation, antibody secretion, and complement activation. Animal models of multiple sclerosis (MS) suggest that myelin destruction is partly mediated through B cell activation (and plasmablasts). MS patients with evidence of B cell involvement, as compared to those without, tend to have a worse prognosis. Finally, the significant decrease in new gadolinium-enhancing lesions, new T2 lesions, and relapses in MS patients treated with rituximab (a monoclonal antibody against CD20 on B cells) leads us to the conclusion that B cells play an important role in MS and that immune modulation of these cells may ameliorate the disease. This article will explore the role of B cells in MS and the rationale for the development of B cell–targeted therapeutics. MS is an immune-mediated disease that affects over 2 million people worldwide and is the number one cause of disability in young patients. Most therapeutic targets have focused on T cells; however, recently, the focus has shifted to the role of B cells in the pathogenesis of MS and the potential of B cells as a therapeutic target.     

两性霉素B微乳的制备及体外经皮渗透研究

 目的制备水包油型两性霉素B微乳,并对其进行体外经皮渗透性能考察。方法用相转变温度法制备两性霉素B微乳,用光散射粒度仪测定微乳的粒径,电子透射电镜观察微乳的形态。用药物渗透扩散仪进行两性霉素B透皮吸收研究,高效液相色谱法测定两性霉素B含量。结果用相转变温度法制备了Tween80和异丙醇重量比为1∶1,IPM和混合表面活性剂之比为1∶9,水含量64.6%,载药量为0.247%的两性霉素B微乳。所制微乳符合微乳特征,调节pH值有助于两性霉素B由分散介质向微乳表面转移。水性月桂氮酮对两性霉素B的促渗效果最好,pH值为5.12,月桂氮酮浓度为1%时,两性霉素B微乳经离体兔皮的JS为4.627μg·cm^-2·h^-1,经离体大鼠皮肤的JS为4.484μg·cm^-2·h^-1。结论开发微乳透皮给药制剂有望提高两性霉素B的疗效,降低其毒副作用。     

Novel azapeptide inhibitors of cathepsins B and K. Structural background to increased specificity for cathepsin B

Abstract: We have designed and synthesized a new series of azapeptides which act as potential inhibitors of cathepsin B and/or cathepsin K. Their structures are based upon the inhibitory sites of natural cysteine protease inhibitors, cystatins. For the synthesized azapeptides, the equilibrium constants for dissociation of inhibitor–enzyme complex, K_i, were determined. Comparison of these values indicated that all of the azainhibitors act much stronger toward cathepsin B. Z‐Arg‐Leu‐His‐Agly‐Ile‐Val‐OMe ( 7 ) proved to be approximately 500 times more potent for cathepsin B than for cathepsin K. To be able to explain the obtained experimental values we used the molecular dynamics procedures to analyze the interactions between cathepsin B and compound 7 . We also determined the structure of the most potent and selective cathepsin B azainhibitor by means of NMR studies and theoretical calculations. In this report, we describe SAR studies of azapeptide inhibitors indicating the influence of the conformational flexibility of the examined compounds on inhibition of cathepsins B and K.     

Immune reactivity towards insulin, its amyloid and protein S100B in blood sera of Parkinson's disease patients

Peripheral immune responses can be sensitive indicators of disease pathology. We evaluated the autoimmune reactions to endocrine (insulin) and astrocytical (S100B) biomarkers in the blood sera of 26 Parkinson's disease (PD) patients compared with controls by using ELISA. We found a statistically significant increase of the autoimmune responses to both antigens in PD patients compared with controls with a mean increase of 70% and 50% in the autoimmune reactions towards insulin and S100B, respectively. Heterogeneity of the immune responses observed in patients may reflect the modulating effect of multiple variables associated with neurodegeneration and also changes in the basic mechanisms of individual autoimmune reactivity. We did not detect any pronounced immune reactions towards insulin amyloid fibrils and oligomers in PD patients, indicating that an amyloid-specific conformational epitope is not involved in immune recognition of this amyloid type, while sequential epitope of native insulin is hidden within the amyloid structures. Immune reactions towards S100B and insulin may reflect the neurodegenerative brain damaging processes and impaired insulin homeostasis occurring in PD.