慢性病毒性肝炎与可溶性细胞间粘附分子-1关系的研究

目的　探讨可溶性细胞间粘附分子 - 1(sICAM - 1)与病毒性肝炎的关系。方法　用ELISA法检测 6 1例慢性乙型肝炎及慢性重型肝炎患者的血清sICAM - 1。结果　各组患者的sICAM - 1水平均高于正常人 (P <0 0 1)。而各组患者之间的sICAM水平 ,以慢性重型肝炎患者最高 ,中度慢性肝炎次之 (P <0 0 1) ,轻度慢性肝炎较低 (P <0 0 1)。sICAM水平与血清丙氨酸转氨酶及总胆红素水平呈显著正相关 (P <0 0 1) ,与血清白蛋白水平呈显著负相关 (P <0 0 1) ,与体内乙肝病毒的存在及复制无关。结论　sICAM - 1是一项敏感的、非损伤性的反映肝炎活动性及肝脏损害程度的指标     

Biological implications of circulating soluble intercellular adhesion molecule-1 in colorectal cancer patients

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) is assumed to play a role in cell-cell and cell-extracellular matrix interactions. We evaluated the relationship between local expression of ICAM-1 and the circulating level of sICAM-1, and clarified its biological implications. METHODS: Serum concentrations of sICAM-1 in 94 colorectal cancer patients were determined. Tissue concentrations of sICAM-1 in the tumor, colorectal adenoma, and the normal mucosa were also determined. The expression of ICAM-1 in the tumor was evaluated immunohistochemically. RESULTS: The serum concentration of sICAM-1 in the patients was significantly higher than that in the controls, and the tumor size was the independent pathological factor that was associated with the serum ICAM-1 level. ICAM-1 immunoreactivity was seen intensively in the stromal cells in the tumor. The tissue concentration of sICAM-1 in the normal mucosa was significantly lower than that in the adenoma and the early carcinoma. The tissue concentration of sICAM-1 in the advanced carcinoma significantly decreased in association with the increase in tumor size. This fluctuation of ICAM-1 expression in the tumor was also associated with the metastatic potential even at an early stage of the disease. CONCLUSIONS: The tissue concentration of sICAM-1 increased during tumorigenesis and at an early stage of carcinoma, and decreased in association with progression of the disease. Serum sICAM-1 level reflected the fluctuation of ICAM-1 expression in the tumor. Evaluation of serum concentration of sICAM-1 may be associated with tumor load and can reflect disease progression in colorectal cancer patients.     

Dramatic decline in circulating intercellular adhesion molecule-1 concentration on quitting tobacco smoking

The concentration of soluble ICAM-1 (sICAM-1) is significantly elevated in smokers, but it is unclear if smoking is the direct cause of elevated sICAM-1 levels, if the relationship between smoking and sICAM-1 level is dose-dependent, and if smoking cessation may lead to a decline in sICAM-1. We sought to clarify the relationship between smoking and sICAM-1 in a group of smokers who quit smoking for 1 year (n = 30) and a control group who continued to smoke (n = 30). A dose-dependent relationship between plasma sICAM-1 concentration and daily cigarette consumption (P = 0.02), plasma cotinine level (P = 0.02), and expired CO level (P = 0.007) was observed at baseline (n = 60). The mean change in sICAM-1 concentration after 52 weeks was greater for quitters than for continuing smokers (mean difference = -71.1 ng/ml, P < 0.001). The influence of smoking on sICAM-1 needs to be carefully considered in clinical trials. Soluble ICAM-1 remains bioactive and may contribute to pathogenic processes; therefore, reduction in the concentration of circulating ICAM-1 molecules may directly contribute to the health benefits associated with smoking cessation.     

Serum intercellular adhesion molecule-1 in childhood malignancy

Levels of soluble intercellular adhesion molecule-1 (ICAM-1) were measured in serum samples taken at diagnosis from pediatric patients with Hodgkin's disease (n = 69), acute lymphoblastic leukemia (n = 28), Wilms' tumor (n = 20), osteosarcoma (n = 17), rhabdomyosarcoma (n = 18), or Ewing's sarcoma (n = 15). Median levels of serum ICAM-1 were significantly higher in acute lymphoblastic leukemia and Hodgkin's disease than in controls and other malignancies. Levels were positively correlated with disease stage for patients with Hodgkin's disease, Ewing's sarcoma or Wilms' tumor, and with the frequency of relapse in Hodgkin's disease (P = .016). Serum levels were normal in all of 76 patients tested in remission. It remains to be determined whether increased serum ICAM-1 levels simply reflect a greater tumor burden or whether this molecule contributes directly to the progression of childhood malignancies.     

Soluble intercellular adhesion molecule-1 in serum in chronic hepatitis B and C

Intercellular adhesion molecule-1 (ICAM-1) is expressed on the hepatocyte membrane in patients with chronic hepatitis B and C. We assayed levels of the soluble form of this molecule (sICAM-1) in serum by an enzyme-linked immunosorbent assay method; we then analyzed the results in relation to hepatitis activity. Fifty-one patients with chronic hepatitis (22 with type B and 29 with type C) and 10 normal controls were examined. The serum levels of sICAM-1 in hepatitis B and C were significantly higher (P<0.01) than in normal controls. The serum level of sICAM-1 was correlated with serum glutamic-pyruvic transaminase level (P<0.01), and the level of sICAM-1 in patients in whom exacerbation was seen was significantly higher (P<0.05) than that in patients in a remission. There was no relationship between the serum level of sICAM-1 and the degree of ICAM-1 expression on the hepatocyte membrane. These results suggest that the serum level of sICAM-1 reflects the degree of activity of chronic hepatitis B and C.     

慢性乙型重型肝炎患者血清sICAM-1的检测及临床意义

目的探讨慢性乙型重型肝炎患者血清可溶性细胞间粘附分子-1(sICAM-1)的变化及其临床意义。方法采用双抗体夹心酶联免疫吸附法对50例慢性乙型重型肝炎患者和30例正常人血清sICAM-1水平进行测定。对50例慢性乙型重型肝炎患者用ELISA法检测乙型肝炎病毒血清标志物,荧光定量PCR法检测HBV DNA载量、全自动生化分析仪检测肝功能、全自动血凝分析仪检测凝血酶原活动度(PTA)。结果慢性乙型重型肝炎患者血清sICAM-1水平明显高于健康对照组(P<0.01),存活组血清sICAM-1水平明显高于死亡组(P<0.01);慢性乙型重型肝炎患者血清sI-CAM-1水平与PTA呈显著正相关(r=0.475,P<0.01),与血清总胆红素呈显著负相关(r=-0.395,P<0.01),与丙氨酸氨基转移酶、白蛋白无相关性(r=0.014、-0.214,P>0.05);27例HBV DNA<1×105copies/ml者与23例HBV DNA≥1×105copies/ml者血清sICAM-1水平无显著性差异(P>0.05);7例HBeAg( )/HBeAb(-)者与43例HBeAg(-)/HBeAb( )者血清sICAM-1水平也无显著性差异(P>0.05)。结论慢性乙型重型肝炎患者血清sI-CAM-1水平显著高于健康对照组,存活组血清sICAM-1水平明显高于死亡组。sICAM-1参与了慢性乙型重型肝炎的肝损伤过程,并与患者病情程度有一定的相关性,但与乙型肝炎病毒的复制水平无相关。     

可溶性细胞间粘附分子与肝硬化及其并发症的相关性研究

目的　探讨血清可溶性细胞间粘附分子 1(sICAM 1)与肝硬化及其并发症的关系。方法　采用酶联免疫吸附法测定 61例肝硬化患者及 3 4名正常人血清sICAM水平。结果　肝硬化患者血清sICAM 1水平 [(1183 .5 7±491.83 )ng/ml]明显高于非肝硬化患者 [(3 72 .3 8± 182 .49)ng/ml,P <0 .0 1] ,并与血清白蛋白 (ALB)、谷丙转氨酶(ALT)、总胆红素 (TBiL)及肝功能Child分级之间密切相关 (P <0 .0 5 ,P <0 .0 1)。伴门脉高压性胃病 (PHG)肝硬化患者血清sICAM 1水平 [(13 5 3 .14± 497.45 )ng/ml]较无PHG的肝硬化患者 [(110 6.3 1± 3 92 .0 8)ng/ml]及正常对照组显著增高 (P <0 .0 5 ,P <0 .0 1)。结论　sICAM可能参与了肝硬化病变及其并发症的发生和发展     

Interactions of intercellular adhesion molecule-1 with fibrinogen

The binding of plasma protein fibrinogen (Fg) to intercellular adhesion molecule-1 (ICAM-1) on endothelial cells mediates the attachment of leukocytes and platelets that may result in vascular occlusion. Fg:ICAM-1 interactions elicit an array of effects that could have implications in vascular pathology and inflammation. ICAM-1 expression is regulated during inflammation and upon Fg binding. The mechanistic model presented provides a framework to delineate the consequences of Fg binding to ICAM-1.     

2型糖尿病患者血清可溶性细胞间黏附分子与大血管病变的相关性研究

本研究显示2型糖尿病（T2DM）大血管病变组血清可溶性细胞间黏附分子（sICAM-1）显著高于非大血管病变组和对照组，sICAM-1与hsC—RP、Fib、TG、TC以及LDL—C呈显著正相关，且SBP、hsC—RP和sICAM-1对T2DM大血管病变呈独立正相关影响。     

系统性红斑狼疮患者血清可溶性黏附分子的检测

目的检测系统性红斑狼疮(SLE)患者血清黏附分子中可溶性血管细胞黏附分子-1(sVCAM-1)、可溶性细胞间黏附分子-1(sICAM-1)的水平,并探讨其临床意义。方法采用酶联免疫吸附试验(ELISA)法,检测30名健康人和60例SLE患者血清sVCAM-1、sICAM-1水平,以分析其与SLE活动性变化关系。结果①SLE患者血清sVCAM-1平均水平为2342ng/ml,显著高于正常人对照组1240ng/ml(P<0.001)。②SLE患者中血清sICAM-1平均水平为802ng/ml,显著高于正常人对照组626ng/ml(P<0.001)。③SLE患者中,血清sVCAM-1水平活动期高于稳定期(P<0.05),sICAM-水平活动期高于稳定期(P<0.05)。④SLE组血清sVCAM-1和sICAM-1水平与SLE病情活动指数(SLEDAI)、抗dsDNA抗体水平及尿蛋白的发生呈正相关,与血清补体C3水平呈负相关。结论sVCAM-1,sICAM-1可能参与SLE发病机制。     

Soluble intercellular adhesion molecule-1 in patients with lung cancer and benign lung diseases

Intercellular adhesion molecule-1 (ICAM-1) expression correlates with tumour progression in patients with malignant melanoma or renal cell carcinoma. To assess the value of soluble ICAM-1 (sICAM-1) for lung cancer patients, sICAM-1 was determined by means of an enzyme-linked immunosorbent assay. Sera from 147 patients with lung cancer, from 75 patients with benign lung diseases and from 108 healthy adults were investigated for sICAM-1 expression. Significant differences in sICAM-1 levels were detected in lung cancer patients (387?±?176 ng/ml) and patients with benign lung diseases (365?±?110 ng/ml) compared to the group of healthy adults (310?±?90 ng/ml). There was no difference in sICAM-1 level among the subtypes of lung cancer. Advanced tumour stages and patients with progressive disease tended to be associated with higher sICAM-1 levels, the site of metastasis being relevant for the level attained. Patients with liver metastasis had the highest sICAM-1 levels (547?±?295 ng/ml) compared to patients with cerebral metastasis (317.8?±?92.2 ng/ml). An increase of sICAM-1 expression during the progression of the disease coincided with a poorer survival prognosis for the patients compared to patients with stable or falling sICAM-1 levels.     

Increased intercellular adhesion molecule-1 serum concentration in cholestasis

Background/Aims: Increase of serum levels of the soluble intercellular adhesion molecules in patients with the cholestatic liver diseases primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are known and have been thought to indicate activation of the immune system and the grade of the inflammatory process. In hepatitis and cholestatic diseases, expression of adhesion molecules was found on the surface of bile duct epithelia and hepatocytes.Materials and Methods: Serum levels of sICAM-1 in patients with intrahepatic cholestasis in PBC (n=42) and extrahepatic cholestasis (n=18) due to choledocholithiasis were investigated. sICAM-1 levels and “classical” cholestasis parameters as alkaline phosphatase (ALP), γ-glutamyl-transpeptidase (γ-GTP) and bilirubin levels were compared. Furthermore, sICAM-1 concentrations and “classical” cholestasis parameters were analysed before and after therapy with ursodeoxycholic acid (UDCA). In addition, sICAM-1 was detected in serum and bile fluid of four patients with cholestasis due to choledocholithiasis. Soluble ICAM-1 levels in sera and, if accessible, in bile fluids were determined using a commercially available ELISA system. Statistics were done by Wilcoxon's signed rank exact test and Spearman's rank correlation test. Sensitivity and specificity of cholestasis parameters and sICAM-1 concentrations was analysed by receiver operating characteristic (ROC) curves.Results: Increased sICAM-1 serum concentrations in a similar range were found in patients with PBC (range 251–2620 μg/l; median 966 μg/l) as well as in patients with extrahepatic cholestasis (257–2961 μg/l; median 760 μg/l) compared to healthy controls (n=12; 220–500 gmg/l; median 318 μg/l). sICAM-1 levels correlated significantly to histological stage I to IV (p<0.001), ALP (range 107–1877 U/l; median 545 U/l; r=0.496, p=0.0008), bilirubin (range 0.3–26 mg/dl; median 0.8 mg/dl; r=0.52; p<0.0004) and γ-GTP levels (range 43–705 U/l; median 221 U/l; r=0.36; p=0.02) in PBC patients. In PBC patients a histological stage III or IV (n=21) could be predicted with high sensitivity (95%) and specificity (85%) if sICAM-1 levels were above 840 μg/l. After treatment of PBC patients with UDCA, sICAM-1 levels decreased significantly with decline of other “classical” cholestasis parameters. Increased sICAM-1 levels (range 257–2961, median 745 μg/l) in extrahepatic cholestasis correlated also significantly with serum concentrations of bilirubin (r=0.8; p<0.01; range 0.3–19.7, median 1.6 mg/dl), γ-GTP (r=0.55; p=0.03; range 33–1401, median 179 U/l) and ALP (r=0.61; p=0.1; range 110–1378, median 562 U/l). sICAM-1 2as detectable in bile fluid (264–919 μg/l) of four patients with extrahepatic cholestasis and nose-biliary catheterisation.Conclusions: sICAM-1 concentrations were found to discriminate between histological stage I/II and stage III/IV of PBC with higher sensitivity and specificity than “classical” cholestasis parameters. Increased serum concentrations for sICAM-1 in intra- and in extrahepatic cholestasis and detection of sICAM-1 in the bile may indicate that sICAM-1 is eliminated through the bile. In other words, not only increased synthesis but also decreased elimination may be responsible for increased sICAM-1 serum levels in patients with cholestatic liver diseases.     

冠心病可溶性细胞间黏附分子-1的检测 及其临床意义

目的　检测冠心病患者可溶性细胞间黏附分子-1(sICAM-1)的变化,探讨其在冠心病发病机理、病情监测中的意义。方法　用酶联免疫吸附法检测50例急性心肌梗死(AMI)、50例不稳定性心绞痛(UA)、30例稳定性心绞痛(SA)、30例健康者血浆sICAM-1水平。结果　AMI、UA、SA患者sICAM-1水平均较正常对照组高,且三组间差异有显著性。AMI患者按心功能分组,各组间差异亦有显著性(P均<0.05)。结论　sICAM-1可能参与了冠心病的发病过程,它可作为病情监测的指标。     

胃肿瘤患者循环可溶性细胞间粘附分子-1和血管细胞粘附分子-1

AIM To elucidate the biological and clinical significance of sICAM-1 and sVCAM-1 in patients with gastric cancer.METHODS The serum levels of soluble ICAM-1 and VCAM-1 were measured with sandwith enzyme immunoassay.RESULTS In gastric cancer patients, soluble ICAM-1 and VCAM-1 concentrations were significantly elevated in comparision with those of healthy subjects (289.23μg/L±32.69μg/L vs 190.44μ/L±35.92μg/L,1430.88μg/L±421.71μg/L vs 727.24μg/L±157.68μg/L, respectively, P＜0.01). The increment in serum sICAM-1 and sVCAM-1 concentrations correlated well with the staging of gastric cancer. The serum levels of sICAM-1 and sVCAM-1 in patients of Ⅲ-Ⅳ stages were higher than those of Ⅰ-Ⅱ stages (346.60μg/L±92.10μg/L vs 257.54μg/L±32.77μg/L, 1800.60μg/L±510.76μg/L vs 1262.81μg/L±236.73μg/L). The levels of sICAM-1 and sVCAM-1 were correlated significantly (r=0.49,P＜0.01). The sICAM-1 and sVCAM-1 levels correlated positively with alkaline phophatase (r=0.63,0.71,P＜0.001) and white cell count (r=0.52,0.43, P＜0.01); but correlated negatively with serum albumin (r=-0.41, -0.49, P＜0.01).CONCLUSION The measurement of circulating ICAM-1 and VCAM-1 may bring additional prognostic information for patients with gastric cancer in varying stages.INTRODUCTIONTumor growth and metastasis involves a variety of cell-cell and cell-extracellular matrix interactions mediated by cell adhesion molecules. Currently, a number of cell adhesion molecules, such as intercellular adhesion molecules-1 (ICAM-1), vascular cell adhesion molecules-1 (VCAM-1), etc. have been found.ICAM-1 and VCAM-1 are members of the immunoglobulin supergene family which are cytokine-induced glycoproteins (IL-1, TNFα and IFNγ). Both of them have five or seven extracellular immunoglobulin-like domains, a single transmembranous domain and a short cytoplasmic tail[1,2]. The natural ligand of ICAM-1 or VCAM-1 is LFA-1 (CD11a) and Mac-1 (CD11b) or VLA-4, respectively[3]. ICAM-1 is a widely distributed protein on a variety of tissues, and can be detected in many cells such as macrophage, T- and B-cells, or fibroblasts, endothelial and epithelial cells. VCAM-1 is also a widely distributed protein and is constitutively expressed on tissue macrophage, dentritic cells in lymphoid tissue and skin, as well as on bone marrow fibroblasts and epithelial cells. Expression of VCAM-1 is inducible on vascular endothelial cells under pathological conditions[4].Recently, soluble forms of several adhesion molecules including ICAM-1 and VCAM-1 were found in serum of normal donors[5]. Abnormally high levels of them have been described in some solid malignant tumors, leukemia, autoimmune disease, infectious disease, etc.The present study was carried out to measure the circulating levels of sICAM-1 and sVCAM-1 in gastric cancer before treatment was given and to study their correlation with clinical, histological and routine laboratory parameters.     

不同类型高脂蛋白血症患者血浆可溶性细胞粘附分子变化的探讨

目的 :探讨高脂蛋白血症患者血浆中可溶性细胞粘附分子 1(sICAM 1)与甘油三酯 (TG)、低密度脂蛋白胆固醇 (LDL C)、总胆固醇 (TC)、脂蛋白a(Lp a)、高密度脂蛋白胆固醇 (HDL C)的相互关系及临床意义。方法 :经体检排除心肌梗死、脑卒中、短暂性脑缺血、癌症、严重肝肾疾病的患者 16 0例 ,空腹采血。用ELISA方法测定sICAM 1,全自动生化分析仪测定血脂。结果 :①高脂蛋白血症患者血浆中sICAM I水平与TG(r =0 .15 ,P <0 .0 1)、LDL C(r =0 .16 ,P <0 .0 1)水平呈正相关 ;②高脂蛋白血症患者血浆中sICAM 1水平与HDL C(r =- 0 .15 ,P <0 .0 1)水平呈负相关。结论 :sICAM 1可能是早期动脉粥样硬化性疾病的标志 ,也可能是致病的病因基础     

Quantitative trait locus on Chromosome 19 for circulating levels of intercellular adhesion molecule-1 in Mexican Americans

Circulating soluble intercellular adhesion molecule-1 (sICAM-1) is a biochemical marker of inflammation. We performed variance-components-based quantitative genetic analyses in SOLAR of sICAM-1 in 1170 individuals from Mexican American families in the San Antonio Family Heart Study. The trait is heritable (h(2)=0.50+/-0.06, P<10(-6)). Multipoint linkage analysis using a approximately 10-cM microsatellite map revealed a region on Chromosome 19p near marker D19S586 showing strong evidence of linkage for sICAM-1 (empirically adjusted univariate-equivalent LOD=4.95), coincident with the structural gene ICAM1. This region has been identified previously as a QTL for inflammatory, autoimmune, and metabolic syndrome traits. There is significant evidence (P=0.0023) of locus heterogeneity for sICAM-1 in this sample: a subset of pedigrees contributes most of the linkage signal for sICAM-1 on Chromosome 19, suggesting a logical focus for future genetic dissection of the trait.     

肝硬化患者血清sICAM-1水平变化与肝功能关系探讨

为了解肝硬化（ＬＣ）患者血清可溶性细胞间粘附分子－１（ｓＩＣＡＭ－１）水平的变化及其与患者肝功能损伤的关系。用酶联免疫吸附法（ＥＬＩＳＡ）检测１７例正常人和３３例ＬＣ患者的血清ｓＩＣＡＭ－１。结果显示,ＬＣ患者血清ｓＩＣＡＭ－１水平显著高于对照组（ＨＣ）,且在肝功能分级中,呈现ＣｈｉｌｄＣ〉ＣｈｉｌｄＢ〉ＣｈｉｌｄＡ的规律。相关分析显示,ＬＣ患者血清ｓＩＣＡＭ－１与总胆红素（ＴＢ）及谷丙转氨酶（ＡＬＴ）均呈明显正相关。提示ＬＣ患者血清ｓＩＣＡＭ－１升高与肝细胞损伤有关,可反映ＬＣ的严重程度。     

Phase tissue intercellular adhesion molecule-1 expression in nude mice human liver cancer metastasis model

AIM To study the phase cancer tissue intercellular adhesion molecule-1 (ICAM-1) expression of human cancer metastasis model in nude mice, and to analyze the relationship between ICAM-1 expression and the metastasis and recurrence of hepatocellular cancinoma (HCC).METHODS HCC tissues from liver cancer metastasis model in nude mice (LCI-D20) was orthotopically implanted, and ICAM-1 expression in HCC tissues at different growing time were detected by immunodot blot. Tumor size, intrahepatic and extrahepatic metastasis foci were observed by naked eyes and under light microscope.RESULTS ICAM-1 was positively correlated to the tumor growing time (r=0.88, P＜0.01) and tumor size r=0.5, P＜0.05). It was higher in metastatic HCC than in nonmetastatic HCC (8.24±0.95 vs 3.03±0.51, P＜0.01). ICAM-1 content in cancer tissues increased suddenly after metastasis occurred and then maintained in a high level. ICAM-1 was also higher in multimetastasis group than in monometastasis group (10.05±1.17 vs 5.48±0.49, P＜0.05).CONCLUSION Tissue ICAM-1 could predict not only the metastasis of human liver cancer metastasis model in nude mice early and sensitively, but also the metastasis degree. So tissue ICAM-1 may be a potential index indicating the status of metastasis of HCC patients.