狂犬病病毒致病机制研究概况

狂犬病病毒（RV）是一种高度嗜神经性病毒，由RV引发的狂犬病通常是一种急性致死性神经系统损伤性疾病。RV通过周围神经末梢和中枢神经系统（CNS）的神经元进行病毒的复制和传播。绝大多数狂犬病例CNS病理学表现为急性脑脊髓炎，常常没有显著的显微镜下改变，脑部可以轻度肿胀，脑膜和脑实质血管轻度充血并伴有少量炎症细胞浸润，这也是其他急性病毒性脑炎常见的共同表现。     

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     

单纯疱疹病毒感染与冠心病急性心肌梗死血液流变特性的相关性研究

目的　探讨单纯疱疹病毒 (HSV)感染与冠心病心肌梗死的关系。方法　测定 5 1例急性心肌梗死 (AMI)和 4 2例陈旧性心肌梗死 (OMI)患者及 31例冠脉造影正常者 (NC)的HSV - 1特异性抗体 (HSV - 1IgG、HSV - 1IgM)浓度 ,并同步观察纤维蛋白原 (Fg)、血液流变特性指标变化及其与HSV - 1感染的相关性。结果　AMI组HSV - 1IgG阳性率及平均浓度明显高于NC组 (P <0 0 5 ) ,HSV - 1DNA检测结果与之吻合。校正冠心病危险因素前后HSV - 1IgG阳性与AMI均有相关关系 (OR4 2 6 6 ,P =0 0 19;OR 3 82 1,P =0 0 32 )。AMI组IgG、Fg、血浆黏度、低 /高切全血黏度、红细胞压积、红细胞聚集指数高于 ,而红细胞变形指数低于NC组及OMI组 (P均 <0 0 5 )。AMI组中HSV - 1( )组上述指标 (除HCT外 )的改变与同组中HSV - 1( - )组及与NC、OMI组中HSV - 1( )组比较有显著性差异 (P均 <0 0 5 ) ,AMI组中HSV - 1( )组IgG与Fg、血浆黏度、低 /高切全血黏度、红细胞聚集指数呈正相关 ,而与红细胞变形指数呈负相关 ,调整冠心病的危险因素前后IgG与Fg均呈正相关。结论　HSV - 1感染与CHD(AMI)之间存在明显的相关性 ,与Fg、血液流变特性指标也存在相关性。     

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.     

pp60c-src encoded by the proto-oncogene c-src is a product of sensory neurons

The advent of recombinant DNA technology has led to the identification in the DNA of normal animal cells of over 30 proto-oncogenes that are homologous to retroviral transforming genes. One of these encodes a protein kinase (pp60c-src) of unknown function, that is preferentially synthesized in brain and neural retina. Here the expression of pp60c-src in the peripheral nervous system was examined in sensory neurons from chick dorsal root ganglia with antisera raised against the transforming protein of Rous sarcoma virus (pp60v-src) expressed in Escherichia coli carrying the cloned v-src gene. This antiserum recognizes pp60c-src specifically in normal chicken cells. Western immunoblotting showed that dorsal root ganglia of stage 30 (day 6.5) chick embryos contained elevated levels of pp60c-src. Immunoperoxidase staining of neuron-enriched cultures prepared from chick dorsal root ganglia showed pp60c-src immunoreactivity in cells with neuronal morphology; flat, fibroblastic cells contained no detectable immunoreactivity. Indirect double immunofluorescence with pp60src antibodies and monoclonal antibodies against the 200-kD subunit of neurofilament protein confirmed that the cells expressing pp60c-src were neurons. Ninety-six percent of the neurofilament-positive cells were immunoreactive with pp60src antibodies, and conversely, all pp60c-src-positive cells were immunoreactive with neurofilament antibodies. pp60c-src immunofluorescence appeared to be distributed over the cell body, processes, and growth cones. These results clearly demonstrate that pp60c-src is a product of neurons and is expressed in sensory neurons in culture.     

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.     

复方丹参注射液干扰素治疗乙肝后肝纤维化

目的探讨复方丹参注射液联合干扰素治疗慢性乙肝患者的疗效。方法110例慢性乙肝患者，按随机方法分成①对照组30例，应用普通保肝药物治疗，疗程6个月；②丹参组30例，应用复方丹参注射液（每ml含丹参、降香各1g）30ml加入10％葡萄糖溶液300ml中静脉注射1个月；③IFN组30例，应用IFN—α 3MU，隔日一次肌内注射，3个月；④联合组20例，应用复方丹参注射液30ml加10％葡萄糖溶液300ml静脉注射1个月，IFN-α 3MU，隔日一次肌内注射，3个月。丹参组，IFN组和联合组保肝药物治疗同对照组。四组病例在性别、年龄、病程，治疗前肝功能等方面均无统计学差异。治疗前检测肝功能，肝炎病毒标志，血清HA、IV—C、PCI—Ⅱ，部分病例进行肝穿病理检查。治疗开始后每月检测肝功能，3个月（治疗后）和6个月（随访时）时检测血清HA、IV—C、PCⅢ及乙肝病毒标志，治疗后1年行肝穿病理检查。结果治疗前四组患者血清HA、PCⅢ、IV—C水平无统计学差异；治疗后丹参组、IFN组、联合组血清HA、FCⅢ、IV—C水平较治疗前及对照组有不同程度的降低。结论复方丹参注射液联合IFN治疗可使血清HA、PCⅢ、IV—C有明显下降，肝组织病理改变明显改善，为目前有效的慢性乙肝治疗措施。