Expression of the chemokine receptors CCR4, CCR5, and CXCR3 by human tissue-infiltrating lymphocytes.

Differential expression of adhesion molecules and chemokine receptors has been useful for identification of peripheral blood memory lymphocyte subsets with distinct tissue and microenvironmental tropisms. Expression of CCR4 by circulating memory CD4(+) lymphocytes is associated with cutaneous and other systemic populations while expression of CCR9 is associated with a small intestine-homing subset. CCR5 and CXCR3 are also expressed by discrete memory CD4(+) populations in blood, as well as by tissue-infiltrating lymphocytes from a number of sites. To characterize the similarities and differences among tissue-infiltrating lymphocytes, and to shed light on the specialization of lymphocyte subsets that mediate inflammation and immune surveillance in particular tissues, we have examined the expression of CCR4, CXCR3, and CCR5 on CD4(+) lymphocytes directly isolated from a wide variety of normal and inflamed tissues. Extra-lymphoid tissues contained only memory lymphocytes, many of which were activated (CD69(+)). As predicted by classical studies, skin lymphocytes were enriched in CLA expression whereas intestinal lymphocytes were enriched in alpha(4)beta(7) expression. CCR4 was expressed at high levels by skin-infiltrating lymphocytes, at lower levels by lung and synovial fluid lymphocytes, but never by intestinal lymphocytes. Only the high CCR4 levels characteristic of skin lymphocytes were associated with robust chemotactic and adhesive responses to TARC, consistent with a selective role for CCR4 in skin lymphocyte homing. In contrast, CXCR3 and CCR5 were present on the majority of lymphocytes from each non-lymphoid tissue examined, suggesting that these receptors are unlikely to determine tissue specificity, but rather, may play a wider role in tissue inflammation.     

介绍一种制备特异性TF和特异性iRNA的方法

以乙肝疫苗、人喉癌细胞膜抗原为抗原，猪脾细胞为效应细胞，经体外免疫后收集应答细胞，制备ＰＳＨＢＶ－ＴＦ ＰＳＡＣ－ｉＲＮＡ。通过抗原特异性细胞免疫功能试验证实，ＰＳＨＢＶ－ＴＦ和ＰＳＡＣ－ｉＲＮＡ都能转移特异性细胞免疫功能。采用体外免疫法制备ＰＳＨＢＶ－ＴＦ和ＰＳＡＣ－ｉＲＮＡ是可行的，并且具有诸多优点。     

A constrained tracking algorithm to optimize plug patterns in multiple isocenter gamma knife radiosurgery planning

We developed a source blocking optimization algorithm for Gamma Knife radiosurgery, which is based on tracking individual source contributions to arbitrarily shaped target and critical structure volumes. A scalar objective function and a direct search algorithm were used to produce near real-time calculation results. The algorithm allows the user to set and vary the total number of plugs for each shot to limit the total beam-on time. We implemented and tested the algorithm for several multiple-isocenter Gamma Knife cases. It was found that the use of limited number of plugs significantly lowered the integral dose to the critical structures such as an optical chiasm in pituitary adenoma cases. The main effect of the source blocking is the faster dose falloff in the junction area between the target and the critical structure. In summary, we demonstrated a useful source-plugging algorithm for improving complex multi-isocenter Gamma Knife treatment planning cases.     

切应力作用下肾近端小管上皮细胞纤溶酶原激活物(tPA和uPA)表达的变化及意义

检测切应力作用下肾近端小管上皮细胞纤溶酶原激活物tPA和uPA mRNA表达的变化,探讨糖尿病肾病早期小管间质细胞外基质重塑的可能机制.用5 dyn/cm2和10 dyn/cm2的切应力处理肾近端小管上皮细胞(NRK-52E),作用时间分别为1、3和6 h,用RT-PCR法检测tPA及uPA mRNA的表达.结果表明:切应力呈大小和时间依赖性下调肾小管上皮细胞tPA及uPA mRNA的表达.在糖尿病肾病早期,高滤过引起的切应力增加可抑制肾近端小管上皮细胞tPA和uPA mRNA表达,导致肾小管间质纤维蛋白溶解活性降低,参与小管间质细胞外基质的重塑.     

Intramucosal Helicobacter pylori in the human and murine stomach: its relationship to the inflammatory reaction in human Helicobacter pylori gastritis

Intramucosal Helicobacter pylori (H. pylori) has been described in biopsy tissues and culture systems. However, the association of intramucosal H. pylori with histopathologic features has not been evaluated. The purpose of this study is to investigate the relationship between intramucosal H. pylori and inflammatory reactions in H. pylori infection. In 113 randomly selected human gastric biopsies and 20 murine stomachs, which were inoculated with SSI every day for a week, immunohistochemical analysis for intramucosal H. pylori was done and correlated with histologic parameters. Electron microscopic examination was done on murine stomachs. H. pylori infection was present in 104 gastric biopsies and 17 murine stomachs. Intraepithelial immunopositivity for H. pylori was detected in 27 of 104 (26%) biopsies and in 11 of 17 (65%) murine stomachs. Lamina proprial immunopositivity for H. pylori was present in 51 of 104 (48%) biopsies. Neutrophil-associated immunopositivity for H. pylori was observed in 22 of 90 (24%) biopsies with H. pylori chronic active gastritis. Lamina proprial and neutrophil-associated immunopositivity for H. pylori correlated significantly with the density of H. pylori and the grade of acute inflammatory reaction in H. pylori gastritis. Intramucosal location of H. pylori itself or its antigen is closely associated with acute inflammatory reactions and may play an important role in establishing a persistent infection in chronic H. pylori gastritis. Furthermore, lamina proprial and/or neutrophil-associated H. pylori appears to be more important than intraepithelial H. pylori in acute inflammatory reactions of H. pylori gastritis.     

DNA错配修复基因甲基化在肝细胞癌发生发展中的作用

目的探讨DNA错配修复基因(MMR)hMLH1,hMSH2和hMSH3甲基化在肝细胞癌(HCC)发生发展中的作用。方法采用甲基化特异性聚合酶链反应(MSP)法对38例新鲜HCC组织,相应非肿瘤肝组织,2例正常的捐肝组织及6种肝癌细胞系的hMLH1,hMSH2和hMSH3基因启动子CpG岛甲基化进行检测;培养6种肝癌细胞系,MSP法检测加入5-aza-2‘-deoxycytidine前后hMSH2基因在HCC中的甲基化状态改变;逆转录．聚合酶链反应(RT-PCR)方法检测加入5-aza-2’-deoxycytidine前后hMSH2在肝癌细胞株中的mRNA表达改变。结果HCC标本中13．2％(5／38)发生了hMLH1启动子甲基化,68．4％(26／38)发生了hMSH2启动子甲基化;相应的非肿瘤肝组织中hMLH1,hMSH2启动子甲基化阳性率分别为2．6％(1／38),55．3％(21／38);2例正常肝组织中未发现甲基化;6株肝癌细胞系中有5株发生了hMSH2启动子甲基化,而未发现有MLH1启动子甲基化。所有标本中均未发现有hMSH3启动子甲基化。5-aza-2‘-deoxycytidine处理细胞株后,可部分或完全逆转hMSH2启动子甲基化,各细胞株的mRNA均有不同程度的表达增加。结论hMSH3基因启动子CpG岛甲基化与HCC的发生发展关系不大。hMSH2基因甲基化与mRNA表达密切相关,是基因表达调节的一种重要方式。hMLH1和hMSH2基因启动子CpG岛的高甲基化在HCC中是一个常见的基因改变,DNA错配修复基因尤其是hMSH2基因启动子甲基化在HCC的发生中起了重要作用,是早期事件,其可能为临床诊断HCC提供新的检测指标。     

Human growth hormone 1 (GH1) gene expression: complex haplotype-dependent influence of polymorphic variation in the proximal promoter and locus control region

The proximal promoter region of the human pituitary expressed growth hormone (GH1) gene is highly polymorphic, containing at least 15 single nucleotide polymorphisms (SNPs). This variation is manifest in 40 different haplotypes, the high diversity being explicable in terms of gene conversion, recurrent mutation, and selection. Functional analysis showed that 12 haplotypes were associated with a significantly reduced level of reporter gene expression whereas 10 haplotypes were associated with a significantly increased level. The former tend to be more prevalent in the general population than the latter (p<0.01), possibly as a consequence of selection. Although individual SNPs contributed to promoter strength in a highly interactive and non-additive fashion, haplotype partitioning was successful in identifying six SNPs as major determinants of GH1 gene expression. The prediction and functional testing of hitherto unobserved super-maximal and sub-minimal promoter haplotypes was then used to test the efficacy of the haplotype partitioning approach. Electrophoretic mobility shift assays demonstrated that five SNP sites exhibit allele-specific protein binding. An association was noted between adult height and the mean in vitro expression value corresponding to an individual's GH1 promoter haplotype combination (p=0.028) although only 3.3% of the variance of adult height was found to be explicable by reference to this parameter. Three additional SNPs, identified within sites I and II of the upstream locus control region (LCR), were ascribed to three distinct LCR haplotypes. A series of LCR-GH1 proximal promoter constructs were used to demonstrate that 1) the LCR enhanced proximal promoter activity by up to 2.8-fold depending upon proximal promoter haplotype, and that 2) the activity of a given proximal promoter haplotype was also differentially enhanced by different LCR haplotypes. The genetic basis of inter-individual differences in GH1 gene expression thus appears to be extremely complex.     

大学生性行为及性道德观发展研究

目的 了解当代大学生性行为及性道德观念的发展变化。方法 自制问卷，对全国9所高校的2000余名大学生进行调查，并用SPSS10．0对结果进行统计处理。结果 大学生性交行为发生率呈逐年上升趋势，且随年级上升而增加；大学生认可性交行为道德观的5个雏度，但各年级之间有差异；大学生边缘性行为和独自性行为发生率随年级显著上升，认可度也随年级增加而上升；大学生对同性性接触基本持排斥态度，但排斥态度则趋于下降。结论 大学生性行为和性道德随年级上升而明显变化，应加强学校教育和引导。     

Prognostic factors of the long-term survival after transjugular intrahepatic portosystemic shunt in the treatment of gastric and esophageal variceal bleeding

Transjugular intrahepatic portosystemic shunt (TIPSS) is a promising method of treatment for gastric or esophageal variceal bleeding. This study was performed to determine the prognostic factors contributing to the survival of patients after TIPSS for gastric or esophageal variceal bleeding. One hundred and fifty-five patients who underwent TIPSS between September 1991 and March 2001 were followed up by clinical examination, upper gastrointestinal endoscopy, and Duplex sonography. The mean portohepatic pressure gradient prior to TIPSS was 20.5+/-9.93 mmHg and dropped to 10.7+/-6.62 mmHg after TIPSS (p<0.001). The cumulative survival rate was 75.1% at 6 months, 66.6% at 1 yr, 58.4% at 2 yr, and 38.1% at 5 yr. Survival after TIPSS was inversely related to the Child-Pugh classification (p<0.05). The rebleeding rate was 18.3% at 6 months, 21.0% at 1 yr, 32.8% at 2 yr, and 53.1% at 5 yr. The causes of deaths were hepatic failure (53.5%), recurrent variceal bleeding (11.6%), pneumonia (4.6%), sepsis (3.5%), hepatic encephalopathy (2.3%), and unknown (17.4%). Multivariate analysis (Cox proportional hazard model) revealed that the Child-Pugh classification and age were statistically significant independent prognostic factors. In conclusion, TIPSS is an effective method of treatment for variceal bleeding in cases where other treatment modalities including endoscopic therapy are unsuccessful and the most important prognostic factors are preprocedural hepatic reserve (Child-Pugh class) and age.     

复杂胸椎骨折中CT图像三维重建的应用探讨

目的直观立体地显示复杂胸椎骨折的图像，探讨螺旋CT医学图像三维重建在复杂胸椎骨折诊断中的价值及其对手术的指导意义。方法对92例胸椎骨折患者采用螺旋CT进行薄层扫描和三维重建进行诊断。CT扫描全部采用Siemens SOMATOM Sensation16型多排高速螺旋CT机，1．0mm层厚。扫猫所得断层资料通过网络传送至计算机工作站进行处理，采用Window．NT3．51平台上Insisht三维重建软件进行三维重建。结果三维CT图像能够围绕X轴和Z轴任意旋转、切割以从不同角度观察，能够清晰显示复杂的胸椎骨折和狭窄椎管的解剖形态特点。结论三维CT重建在胸椎骨折方面具有很大的临床应用价值，有助于提高脊柱骨折手术的安全性和精确性并对患者预后的估计提供帮助。