Diabetic vascular disease: it's all the RAGE

The major consequence of long-term diabetes is the increased incidence of disease of the vasculature. Of the underlying mechanisms leading to disease, the accumulation of advanced glycation end products (AGEs), resulting from the associated hyperglycemia, is the most convincing. Interaction of AGEs with their receptor, RAGE, activates numerous signaling pathways leading to activation of proinflammatory and procoagulatory genes. Studies in rodent models of macro- and microvascular disease have demonstrated that blockade of RAGE can prevent development of disease. These observations highlight RAGE as a therapeutic target for treatment of diabetic vascular disease.     

Hypothalamus-brain stem circuitry responsible for vagal efferent signaling to the pancreas evoked by hypoglycemia in rat

Circulating glucose levels significantly affect vagal neural activity, which is important in the regulation of pancreatic functions. Little is known about the mechanisms involved. This study investigates the neural pathways responsible for hypoglycemia-induced vagal efferent signaling to the pancreas and identifies the neurotransmitters involved. Vagal pancreatic efferent nerve activities were recorded in anesthetized rats. Insulin-induced hypoglycemia, a decrease of blood glucose levels from 114 +/- 5 to 74 +/- 6 mg dl(-1), stimulated an increase in pancreatic efferent nerve firing from a basal rate of 1.1 +/- 0.3 to 19 +/- 3 impulses 30 s(-1). In contrast, vagal primary afferent neuronal discharges recorded in the nodose ganglia were unaltered by systemic hypoglycemia. Vagal afferent rootlet section plus splanchnicotomy had no effect on hypoglycemia-induced vagal efferent firing, suggesting a central site of action. Decerebration reduced the increase in nerve firing stimulated by hypoglycemia from 21 +/- 4 to 9.6 +/- 2 impulses 30 s(-1). Chemical ablation of the lateral hypothalamic area, but not the arcuate nucleus, inhibited pancreatic nerve firing evoked by hypoglycemia. Microinjection of the orexin-A receptor antagonist SB-334867 into the dorsal motor nucleus of the vagus (DMV) inhibited pancreatic nerve firing evoked by insulin-induced hypoglycemia by 56%. In contrast, injection of orexin-A (20 pmol) into the DMV elicited a 30-fold increase in pancreatic nerve firing. We concluded that systemic hypoglycemia stimulates pancreatic efferent nerve firing through a central mechanism. Full expression of pancreatic nerve activities during hypoglycemia requires both the forebrain and the brain stem. In addition to activating neurons in the brain stem, central neuroglucopenia activates subpopulations of neurons in the lateral hypothalamic area that contain orexin. The released orexin acts on DMV neurons to stimulate pancreatic efferent nerve activities and thus regulate pancreatic functions.     

Development and characterisation of neutralising monoclonal antibody to the SARS-coronavirus

There is a global need to elucidate protective antigens expressed by the SARS-coronavirus (SARS-CoV). Monoclonal antibody reagents that recognise specific antigens on SARS-CoV are needed urgently. In this report, the development and immunochemical characterisation of a panel of murine monoclonal antibodies (mAbs) against the SARS-CoV is presented, based upon their specificity, binding requirements, and biological activity. Initial screening by ELISA, using highly purified virus as the coating antigen, resulted in the selection of 103 mAbs to the SARS virus. Subsequent screening steps reduced this panel to seventeen IgG mAbs. A single mAb, F26G15, is specific for the nucleoprotein as seen in Western immunoblot while five other mAbs react with the Spike protein. Two of these Spike-specific mAbs demonstrate the ability to neutralise SARS-CoV in vitro while another four Western immunoblot-negative mAbs also neutralise the virus. The utility of these mAbs for diagnostic development is demonstrated. Antibody from convalescent SARS patients, but not normal human serum, is also shown to specifically compete off binding of mAbs to whole SARS-CoV. These studies highlight the importance of using standardised assays and reagents. These mAbs will be useful for the development of diagnostic tests, studies of SARS-CoV pathogenesis and vaccine development.     

酵母双杂合系统AD端阴离子交换蛋白C-末端表达质粒的构建

利用PCR方法，从阴离子交换蛋白1（AE1）全长cDNA中扩增出约350bp c末端cDNA片段，测序后将其克隆至pGADT7载体上，用醋酸锂法构建好的pADT7-AE1-c末端转染酵母菌HA109，观察其在选择性培养基上的表达情况。结果表明，获得了530bp AE1c－末端cDNA,pGADT7-AE1-c末端对酵母无毒性，不能激活检测基因，可作为酵母双杂合系统中的靶基因。     

足筋膜间隙综合征相关肌肉磁刺激运动诱发电位的临床研究

目的:探讨足筋膜间隙综合征患者相关肌肉的磁刺激运动诱发电位(MEP)的特征及其临床意义.方法:对21例确诊为单侧足筋膜间隙综合征患者,在双侧腘窝上缘用磁刺激坐骨神经,同心圆针电极插入双侧足部各筋膜间隙内相应的肌肉中,记录各自MEP的潜伏期及波幅变化,并计算其比值,分析该比值与足筋膜间隙综合征发生的相关性.结果:正常足部各筋膜间隙内相应的肌肉磁刺激MEP先正后负,潜伏期相对恒定,但波幅不够稳定;当间隙内压大于30mmHg时,间隙内相应肌肉MEP潜伏期明显延长,为健侧的(1.9l±0.23)倍.统计学分析显示,筋膜间隙综合征的发生与磁刺激MEP波幅比值降低之间无相关性(P＞0.05),而与相应肌肉MEP潜伏期比值的变化之间存在着明显相关性(P＜0.01).结论:磁刺激MEP作为诊断足筋膜间隙综合征的客观指标具有重要的价值.     

物理学在医学影像中的应用

物理学对医学的贡献是巨大的，物理学与医学等学科的交叉碰撞在医学领域中产生了许多丰硕成果，现代的医学影像就是其中的成果之一。本文阐述了物理学在现代四大医学影像中的应用。     

喉癌细胞中S100A8新的相互作用蛋白质的鉴定

目的探索S100A8相互作用蛋白在喉癌发生、发展中的可能机制。方法应用抗S100A8抗体通过免疫沉淀的方法从喉癌细胞系Hep-2中分离与S100A8相互作用的蛋白质。用基质辅助激光解析电离飞行时间质谱仪分析目的蛋白条带。根据这些目的蛋白条带的肽指纹谱,用Mascot软件预测其相应的蛋白质。用P-Match软件预测这些蛋白质的NF-kappa B结合位点。用免疫共沉淀方法证实其中一个蛋白质与S100A8相互结合的能力。结果获得了4种与S100A8相互作用的新的蛋白质,它们分别是假想蛋白质LOC80154（hypothetical protein LOC80154）、MHCclass Ⅰ HLA-B、T-box1异构体C相似蛋白质（similar to T-box1 isoformC）和肌纤维膜相关蛋白1（sarcolemmal associated protein 1）。这4种蛋白质均具有NF-kappa B的结合位点,其中MHCclass Ⅰ HLA-B是NF-kappa B通路中的一个成员,我们首次证实该蛋白质具有结合S100A8的能力。结论本研究获得的S100A8新的伴侣可能是NF-kappa B通路的成员。MHCclass Ⅰ HLA-B与S100A8的结合提示S100A8可能作为新成员与包括HLA-B在内的其他蛋白质在NF-kappa B通路中发挥作用。这些发现为进一步研究S100A8在喉癌发生中的分子机制提供了新线索。     

综合ICU中低年资护士培训方法探讨

目的探讨为综合ICU培养合格的护理人员的方法。方法根据ICU护士应具备的素质及低年资护士的特点,采用定期集中培训、一对一带教、参加护理查房等方法,对基础理论和基本技能进行强化,重点加强了ICU专科护理知识地训练。结果通过客观考核和主观考核,效果良好。结论经过为期12个月两个时段较规范的岗位培训,低年资护士能较好的适应ICU工作。     

Myoblasts fail to stimulate T cells but induce tolerance

Recent interest in myoblast transfer and in the use of myoblastsas vehicles in gene therapy has made it important to understandthe potential immunogenicity of allogeneic or neoantlgen-expresslngmyoblasts. Given the problems of producing a pure populationof myoblasts, In this study we used a tumour-derived musclecell line (TE671), with phenotyplc features of myoblasts, whichwe transfected to express HLA-DR1. However, this cell line wasunable to stimulate either established HLA-DR1-specific alloreactlveT cell clones or a primary alloresponse. Nor could it presenthaemagglutlnln peptide HA 306–324 to DR1-restricted, HA306–324-speciflc T cell clones or lines. Indeed, prelncubatlonwith DR1-expressing TE671 and HA 306–324 rendered suchT cells tolerant as Judged by their subsequent inability toproliferate in response to a DR1⁺ B cell line plus peptide HA306–324. These results imply that myoblasts do not providecostlmulatory signals, and are therefore unlikely to stimulateallospeclfic T cells following myoblasts transplantation orto initiate neoantlgen-speclfic immune responses following Invivo transfection.