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。     

基于椭圆方程的三维心脏超声图像的位移场估计

三维超声心动图技术能使医生直观地看到心脏整体和各部分的运动，在临床得到重视。在三维超声心动图技术中，如何定量的描述心脏中某个组织的运动状况极具临床意义。本研究提出了一种基于椭圆偏微分方程的二尖瓣三维运动估计方法。该方法直接在三维超声图像的位移场上进行了运动估计，避免了传统运动估计方法，如光流法，需要标定的缺点。本研究首先建立一个二次误差指标函数，然后利用变分法导出了三维空间下的一组椭圆型偏微分方程。这类方程有着比较成熟的数值解法，利用了有限差分法，对多个三维超声数据立方体进行了计算，结果证明这类方法是有效的。     

HLA-DR residues accessible under the peptide-binding groove contribute to polymorphic antibody epitopes

Many residues involved in polymorphic antibody-binding epitopes on class II molecules are located on the -helix of DRβ chains. Although they have received less attention, residues in the peptide-binding groove and second domain of the DRβ chain may also be critical for polymorphic anti-DR antibody epitopes. In this study, we used transfectants expressing site-directed mutations at positions in the HLA-DR β₁ and β₂ domains and flow cytometry to define the epitopes of several polymorphic anti-DR antibodies. Both DR(β 1^*0403) residues 14 and 25 were shown to be involved in the epitopes of mAbs DA6. 164, HU-20, Q5/6, and 50D6, and DR(β 1^*0701) residue 14 was shown to be critical for the epitopes of two DR7-specific mAbs, SFR16-DR7M and TAL 13. 1. Unlike most other residues shown to be important in antibody-binding epitopes, residue 14 is located in the floor of the peptide-binding groove and residue 25 is in an outer loop, each with their side chains pointing down, such that antibodies may directly contact these residues from below the binding groove. Two residues in the β₂ domain, β180 and β181, were also shown to be involved in the epitopes of three polymorphic anti-DR mAbs, NFLD.D1, NFLD.M1, and LY9. Although these two residues are close to the transmembrane domain in the linear sequence, their solvent accessibility in the DR1 structures is quite impressive. Our data provide new evidence that residues accessible under the peptidebinding groove contribute to polymorphic antibody-binding epitopes.     

Diverse locations of amino acids in HLA-DR beta chains involved in polymorphic antibody binding epitopes on DR(alpha, beta 1*0101), DR(alpha, beta 1*1101), and DR(alpha,beta 3*0202) molecules.

In a previous study, we used transfectants expressing hybrid HLA-DR(beta 1*0403)/DR(beta 1*0701) chains to map sequences involved in polymorphic antibody binding epitopes on DR(alpha, beta 1*0403) or DR(alpha, beta 1*0701) molecules. Amino acids 1-40 of the beta 1 domain were found to make the major contributions to most of the antibody binding epitopes studied. To begin to localize sequences that contribute to polymorphic antibody epitopes on DR(alpha,beta 1*0101), DR(alpha,beta 1*1101) and DR(alpha,beta 3*0202) molecules, we used indirect immunofluorescence and flow cytometry to assess the binding of mAb to transfectants expressing hybrid DR(beta 1*0101)/DR(beta 1*1101) or DR(beta 1*1101)/DR(beta 3*0202) chains that divide the DR beta chain into three segments: amino acids 1-40, 41-97, and the beta 2 domain. The results indicate that amino acids 41-97 of the beta 1 domain on DR(beta 1*0101), DR(beta 1*1101), or DR(beta 3*0202) are critical in most of the epitopes, including those recognized by human antibodies MP4 and MP12, and mouse mAb GS88.2, I-LR1, 21r5, and 7.3.19.1, whereas amino acids 1-40 of DR(beta 1*1101) are critical in the epitope recognized by the MCS-7 mAb, and both segments 1-40 and 41-97 of DR(beta 1*1101) are important in the epitopes recognized by the I-LR2 and UL-52 mAbs. Based on these data and comparison of DR beta allelic protein sequences, the residues that may play critical roles in these antibody binding epitopes are predicted.     

多发性骨髓瘤患者血清IL-6活性与急性相蛋白浓度的相关性研究

运用敏感的B_9细胞增殖试验检测了81例多发性骨髓瘤(MM)患者血清IL-6活性,同时分析了标本的几种急性相蛋白含量,结果表明,68％MM患者血清中IL-6活性大于5μ/ml(正常对照为5μ/ml以下),几种急性相蛋白中C-反应性蛋白(CRP)在MM时升高(P<0.01),平均达正常对照组的17倍以上,MM患者补体C_4与正常对照组无差异(p>0.05),C_3、白蛋白及转铁蛋白在MM时分别比正常下降24.42％、38.83％和32.80％,且与疾病分期有关,在血清IL-6大于5μ/ml的55例中,IL-6活性与CRP、C_3、白蛋白的相关系数分别为0.46,-0.34和-0.29,IL-6与转铁蛋白浓度相关不明显。本文结果提示:CRP、C_3及白蛋白等含量的变化可作为反映MM病情的简易而敏感的指标。     

不同剂量病毒唑治疗肾综合征出血热306例疗效分析

应用不同剂量病毒唑对３０６例肾综合征同血热患者进行治疗对比观察，发现两治疗组疗效无显著性差异，但两治疗组怀对照组相比，越期率高，肾功能恢复快，血小板数恢复早，病程缩短，并发症减少，病死率也有所下降，但无显著性差异。     

Favorably tipping the balance between cytopathic and regulatory T cells to create transplantation tolerance

Therapeutic application of broadly reactive anti-T cell antibodies can lead not only to potent immunosuppression but also to profound and long-lived T cell depletion. We reasoned that a strategy that almost exclusively targets activated cytopathic donor reactive T cells and spares immunoregulatory networks might prove to be an exceptionally potent and highly selective means of producing long-term engraftment and tolerance. Herein we show that the combined administration of rapamycin and agonist IL-2- and antagonist IL-15-related cytolytic fusion proteins provides for long-term engraftment/tolerance in exceptionally stringent allotransplant models by (1) limiting the early expansion of activated T cells, (2) preserving and even exaggerating their subsequent apoptotic clearance, and (3) further amplifying the depletion of these activated T cells by antibody-dependent mechanisms, while (4) preserving CD4+CD25+ T cell-dependent immunoregulatory networks.     

Fas蛋白在糖尿病大鼠局灶性脑缺血再灌注损伤后海马区的表达及意义

目的探讨Fas蛋白在糖尿病大鼠脑缺血再灌注海马区神经元损伤中的表达及意义。方法健康雄性Wister大鼠60只,随机分为4组:①正常对照组,②假手术组,③脑缺血再灌注组(NIR),④糖尿病脑缺血再灌注组(DIR组);采用STZ诱导糖尿病和线栓法建立大脑中动脉闭塞(MCAO)模型,HE法观察海马CA1神经元缺失,用免疫组化方法检测Fas在糖尿病大鼠脑缺血再灌注海马神经元损伤中的表达。结果HE染色:正常对照与假手术组未见神经元缺失和细胞凋亡,DIR组与脑缺血再灌注组均见神经元缺失和神经细胞凋亡,而DIR组比脑缺血再灌注组神经元缺失严重(P<0.05)。正常对照与假手术组极少见Fas免疫染色阳性细胞,DIR组与脑缺血再灌注组明显见Fas免疫染色阳性细胞,且DIR组比脑缺血再灌注组多(P<0.05)。结论Fas介导的细胞凋亡可能是糖尿病脑缺血再灌注损伤后海马区神经元损伤的机制之一。