灯盏花素对大鼠脑缺血后细胞间粘附分子-1及其mRNA表达的影响

目的:灯盏花素对大鼠脑缺血后细胞间粘附分子-1(ICAM-1)及其mRNA表达的影响。方法:复制大鼠大脑中动脉闭塞/再灌注模型,应用RT-PCR及免疫组织化学的方法,观察各组大鼠脑缺血后细胞间粘附分子-1 mRNA及其蛋白的表达。结果:ICAM-1在假手术组大鼠脑组织呈低表达;单纯缺血组(缺血90 min)ICAM-1表达上调(P＜0.05);缺血再灌注组(缺血90 min再灌24 h)脑组织ICAM-1表达显著高于假手术组和单纯缺血组(P＜0.01);灯盏花素治疗组于相同时限ICAM-1表达与单纯缺血、缺血再灌注组相比显著下调(P＜0.01)。大鼠脑组织ICAM-1 mRNA在假手术组呈低表达;单纯缺血组ICAM-1 mRNA水平显著上调(P＜0.01);药物治疗组于相同时限ICAM-1 mRNA水平显著低于单纯缺血组及缺血再灌注组(P＜0.01)。结论:灯盏花素下调细胞间粘附分子-1mRNA及其蛋白的表达,减轻缺血后再灌注损伤,从而发挥脑保护作用。     

The intercellular adhesion molecule (ICAM) family of proteins

Macromolecular adhesive associations between cells are important for transmitting spatial and temporal information that is critical for immune system function. One such group of proteins, the intercellular adhesion molecules (ICAMs), has grown as newly identified members are revealed. In addition, the functions of the ICAMs, in general, have begun to be better understood, including intracellular signaling events. This information has led to the design of novel therapeutic agents that may prove effective in a variety of disease states.     

Mechanisms Involved in the Binding of Thymocytes to Rat Thymic Dendritic Cells

The effects of monoclonal antibodies (mAbs) to cell-surface molecules, divalent cations, and various cell-signaling and metabolic inhibitors on the binding of thymocytes to rat thymic dendritic cells (TDC) were studied using a rosette assay. It was found that TDC/thymocyte adhesion was stronger and faster at 37°C than at 4°C. Flow cytometric analysis demonstrated that bound thymocytes were predominantly CD4⁺CD8⁺ and CD4⁺CD8^-, but in comparison to the phenotype of whole thymocytes, they were enriched in the mature TCRαβ^hi subset. The binding of thymocytes to TDC at 37°C was almost completely dependent on Ca²⁺ and Mg²⁺ and partly on an intact cytoskeleton and calmodulin-dependent protein kinase. The adhesion was independent of new protein synthesis and the activities of protein kinases A and C, tyrosine kinases, as well as phosphotyrosine protein phosphatases. The TDC/thymocyte adhesion at 37°C was partly blocked by anti-LFA-1 (WT.1), anti-CD18 (WT.3), and anti-ICAM-1 (1A29) mAb. MAbs to class II MHC (OX-3 and OX-6), CD4 (W3/25), CD8 (OX-8), and αβTCR (R73) stimulated the adhesion via an LFA-1-dependent pathway, whereas an anti-CD45 mAb (G3C5) stimulated the rosette formation independently of LFA-1. MAbs to CD2 (OX-34), CD11b (ED7), CD11b/c (OX-42), and class I MHC (OX-18) were without significant effects on the adhesion process.     

Adhesion of carcinoma cells to rat hepatocytes and rat fibronectin is inhibited by the OPAR monoclonal antibody,which is directed against a rat liver-specific carbohydrate epitope

The OPAR mouse monoclonal antibody (mAb) directed against rat hepatocytes was previously shown to inhibit adhesion of TA3/Ha mammary carcinoma cells to hepatocytes. The antigen is abundantly present at the surface of hepatocytes beneath the endothelium of liver capillaries where we have observed invasion of carcinoma cells to occur. The OPAR mAb reacted with three major bands on a Western blot of liver plasma membrane proteins. The same proteins were also seen upon immunoprecipitation from iodinated liver plasma membrane proteins. We have isolated OPAR antigens by lectin wheat germ agglutinin (WGA) and OPAR affinity chromatography. Amino acid sequence analysis revealed that two of the bands were 1-macroglobulin and C4-binding protein, which are serum components produced by hepatocytes. The presence of the epitope on distinct proteins and our previous observation that it can be detected in the Golgi apparatus but not in the endoplasmic reticulum, suggested that OPAR reacts with a liver-specific glycoconjugate. Loss of OPAR reactivity after neuraminidase and N-glycosidase F treatment showed that the epitope contains sialic acid residues on N-linked sugar moieties. OPAR also reacted with rat fibronectin, and inhibited adhesion of TA3/St cells to fibronectin. This explains the inhibition by the OPAR mAb of TA3/St cell adhesion to hepatocytes, which we have shown to be due mainly to interaction with hepatocyte surface-associated fibronectin. However, adhesion of the related TA3/Ha cells to hepatocytes, which is mediated by the ₆P4 integrin, and does not involve binding to fibronectin, is also inhibited. This suggests that ₆₄ on liver-metastasizing carcinoma cells binds to an OPAR epitope-carrying glycoprotein produced by hepatocytes.     

Relationship Between Architecture and Adhesion in Polyurethane‐Based Copolymers, 2

Summary: This study describes the chain extension, with polycaprolactone diols, of polyurethane‐graft‐poly(butyl acrylate)s which were first prepared by the step growth polymerization of a mixture of diphenylmethane‐4,4′‐diisocyanate (MDI) and α,α′‐dihydroxyl‐poly(butyl acrylate)s. The success of the chain extension reaction was studied and confirmed by ¹H NMR, SEC and DSC analysis. The incorporation of polycaprolactone sequences in the polyurethane chains modified their specific adhesive properties, bringing cohesion to the material, as demonstrated by tack measurements.

PUR‐graft‐PBA extended with PCL.     

Loss of the CD5+ and CD45RAhi B cell subsets in alcoholics

Chronic alcoholics are frequently immunodeficient, have polyclonal hypergammaglobulinaemia, and often have autoantibodies. Recent work in other diseases has shown that functional distinctions of possible relevance to autoimmunity and immunodeficiency can be found among the B cell subsets defined by differential expression of the surface markers CD5 and CD45RA. Therefore, we have evaluated the CD5,CD45RA B cell subsets of both chronic alcoholics without evidence of active liver disease (AWLD), and alcoholics admitted for acute alcoholic liver disease (ALD). Mean B cell numbers were normal in AWLD, but significantly reduced in ALD. Analysis of B cells by three-colour flow cytometry in 20 patients and 29 controls revealed a sharp decrease in the percentage of alcoholics’ B cells which were CD5⁺, 37·6% versus 16·3%, P<0·00001; absolute CD5⁺ B cell numbers were similarly reduced (58·9 cells/μl versus 20·9; P =0·0012). In addition to the loss of CD5⁺ B cells, there was a reduction in the percentage of B cells which are CD5⁻CD45RA^hi, leaving many patients with a B cell profile which was predominantly CD19⁺CD5⁻CD45RA^lo. This subset appears phenotypically similar to the IgM-producing CD5⁻CD45RA^lo subset described by others, and may be enriched for autoantibody-producing cells. One outlier patient was an ALD with 61% of B cells which were CD5⁺, which also is a profile consistent with increased autoantibody production.     

Characterization of a soluble form of CD58 in synovial fluid of patients with rheumatoid arthritis (RA)

Reduced levels of a soluble form of the adhesion receptor and CD2 ligand CD58 (sCD58) were previously described in RA patients. In order to understand the biological significance of this finding we biochemically characterized sCD58 in RA and asked how well sCD58 binds to CD2. sCD58 concentrations were measured in serum and synovial fluid (SF) samples of RA patients by two ELISAs, one detecting domain 1 of CD58 (CD58-D1), and the other one the complete molecule (CD58-D1 + D2). Small amounts of split sCD58-D1 were found in most RA sera, but not SF. In addition, split sCD58-D2 was detected in SF by affinity chromatography, SDS–PAGE, and Western blotting. Gel filtration gave similar peaks at 95–125 kD for RA sera, SF, and normal serum. Binding of SF-sCD58 to the CD2⁺ Jurkat variant JBB1 or recombinant CD2 was stronger than urinary sCD58 and reached binding of oligomeric recombinant CD58 at low concentrations. In conclusion, sCD58-split products were found in RA sera and SF. At concentrations as they occur in vivo, SF-sCD58 binds to CD2 much more strongly than urinary sCD58. It is conceivable that locally released sCD58 blocks the CD2/CD58 interaction under physiological conditions. Insufficient release of sCD58, e.g. in synovitis, might result in T cell accumulation and perpetuation of inflammation.     

Loss of cell polarity causes severe brain dysplasia in Lgl1 knockout mice

Disruption of cell polarity is seen in many cancers; however, it is generally considered a late event in tumor progression. Lethal giant larvae (Lgl) has been implicated in maintenance of cell polarity in Drosophila and cultured mammalian cells. We now show that loss of Lgl1 in mice results in formation of neuroepithelial rosette-like structures, similar to the neuroblastic rosettes in human primitive neuroectodermal tumors. The newborn Lgl1(-/-) pups develop severe hydrocephalus and die neonatally. A large proportion of Lgl1(-/-) neural progenitor cells fail to exit the cell cycle and differentiate, and, instead, continue to proliferate and die by apoptosis. Dividing Lgl1(-/-) cells are unable to asymmetrically localize the Notch inhibitor Numb, and the resulting failure of asymmetric cell divisions may be responsible for the hyperproliferation and the lack of differentiation. These results reveal a critical role for mammalian Lgl1 in regulating of proliferation, differentiation, and tissue organization and demonstrate a potential causative role of disruption of cell polarity in neoplastic transformation of neuroepithelial cells.     

中枢神经系统感染患者血清NSE和sICAM-1的改变

目的 :探讨中枢神经系统感染患者血清中NSE和sICAM 1水平的改变。方法 :采用ELISA法检测了 30例CNS感染的患者和 2 0例正常健康人血清中的NSE和sICAM 1水平。结果 :在CNS感染患者血清中NSE( 12 5 .6 8± 14 .38μg/L)和sICAM 1( 4 48.94± 96 .70μg/L)显著高于正常对照组的NSE( 6 .6 6± 1.2 5 μg/L)和sICAM 1( 2 91.78± 39.18μg/L) ,P <0 .0 1。在CNS感染各组中病毒性脑炎患者的NSE亦显著高于其他各组 ;sICAM 1在CNS感染各组间无显著性差异 ,P >0 .0 5。结论 :提示NSE和ICAM 1可作为CNS损害和感染的监测指标