Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intercellular adhesion molecule-1, an immunoglobulin supergene family member, is known to account for important steps in cell activation and the immune response. By a non-isotopic slot-dot immunoblotting assay, we measured circulating levels of intercellular adhesion molecule-1 in 26 patients with hepatitis C virus-associated chronic active liver disease before and after beta-interferon therapy, in 6 patients with non-A, non-B acute self-limiting hepatitis and in 13 healthy subjects. Circulating intercellular adhesion molecule-1 was found in 10 of 13 (77%) normal controls at low concentrations which were not statistically different from those measured in patients with hepatitis C virus-associated chronic active liver disease responsive to beta-interferon, whereas significantly higher levels were found in unresponsive patients. Higher serum intercellular adhesion molecule-1 levels were found in 4 of 10 (40%) beta-interferon-responsive patients compared with 13 of 16 (18%) unresponsive patients. Intercellular adhesion molecule-1 levels persisted after discontinuation of beta-interferon treatment and did not correlate with hepatocytolysis (as indicated by alanine aminotransferase serum activity) either in chronic active liver disease or acute hepatitis. However, a good correlation was found between intercellular adhesion molecule-1 and its expression on liver cells, thus emphasizing that induced circulating levels may reflect the state of activation at the sites of the inflammatory process. These data strongly support the view that intercellular adhesion molecule-1 plays an important role in liver cell damage in hepatitis C virus-associated acute and chronic liver disease, and that its circulating levels may be a good prognostic parameter of responsiveness to beta-interferon therapy.
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PMID:Circulating levels and liver tissue distribution of intercellular adhesion molecule-1 during beta-interferon therapy of hepatitis C virus-associated chronic active liver disease. 135 8

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.
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PMID:Soluble intercellular adhesion molecule-1 in serum in chronic hepatitis B and C. 795 56

The aim of this study was to assess the hypothesis that hepatic failure after extensive hepatectomy in patients with obstructive jaundice (OJ) may be mediated by polymorphonuclear neutrophils (PMN). In the OJ group, rats underwent a partial hepatectomy of 78% after 2 weeks of cholestasis and subsequent external biliary drainage for 5 days. In the sham-operated control group, rats were partially hepatectomized 19 days after the sham surgery. The concentration of the serum cytokine-induced neutrophil chemoattractant (CINC), which is homologous with the growth-related oncogene (gro) product, a member of the human interleukin (IL)-8 family, and a major neutrophil chemotactic factor in rats, increased concomitantly with accumulation of PMNs in the hepatic sinusoids during cholestasis and subsequent external drainage. However, changes in the serum purine nucleoside phosphorylase (PNP)/alanine transaminase (ALT) ratio as a marker of sinusoidal endothelial cell (SEC) injury showed no significant differences between the two groups. Intercellular adhesion molecule-1 (ICAM-1) expression on SECs was not affected by cholestasis and external drainage. After partial hepatectomy, the serum CINC concentration immediately elevated more prominently in the OJ group than in the sham-operated control group, and accumulation of PMNs in the sinusoids was more obvious and prolonged in the former. ICAM-1 expression was enhanced in both groups with a peak between 24 and 48 hours after partial hepatectomy. At this peak period, a significantly higher PNP/ALT ratio was observed in the OJ group. These results suggest that accumulation of PMNs in the sinusoidal space and ICAM-1 expression on SECs might be closely associated with the development of SEC injury after extensive hepatectomy in cholestasis.
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PMID:Neutrophil-mediated sinusoidal endothelial cell injury after extensive hepatectomy in cholestatic rats. 904 11

Soluble intercellular adhesion molecule-1(ICAM-1) is probably released from a variety of cells, including leukocytes and endothelial cells at sites of inflammation or in the circulation, and serum levels may therefore be used to give an indication of immune activation and inflammatory processes. In the present study, an ELISA was used to measure serum ICAM-1 levels in forty patients with endemic chronic liver diseases and these were correlated with histological changes in the liver and with liver functions. Serum ICAM-1 levels were significantly higher in patients with chronic active liver diseases than in normal subjects and correlated positively with the grade of histological activity. Furthermore, serum levels of ICAM-1 were substantially greater in patients with cirrhosis than in those without cirrhosis. There was also a significant positive correlation between serum levels of ICAM-1 and serum alanine aminotransferase activities. It is concluded that, in chronic liver disease, intercellular adhesion molecule-1 serum concentration seems to represent hepatocellular damage. The authors suggest that serum ICAM-1 may prove worthy in the investigation, diagnosis and therapeutic monitoring of various inflammatory conditions of the liver.
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PMID:Circulating intercellular adhesion molecule-1 in endemic chronic liver diseases. 909 39

The intercellular adhesion molecule 1 (ICAM-1, CD54) and the lymphocyte associated antigen 3 (LFA-3, CD58) have been found in soluble form (sCD54 and sCD58) in human sera. Data concerning their role in chronic liver disease and their usefulness in disease monitoring are contradictory. We addressed the question whether elevated sCD54/sCD58 correlated either with disease activity or with decreased elimination secondary to reduced liver function in chronic hepatitis B. We studied 31 patients with chronic hepatitis B undergoing interferon alpha therapy in a longitudinal fashion. Serum concentrations of sCD54 and sCD58 were measured at four weeks interval by specific Sandwich ELISA during a follow-up period of ten months. The maximal difference in concentration of each biochemical parameter, e.g., delta AST, delta gGt, delta bilirubin, was determined for each patient during the whole follow-up period. These differences were correlated with the variation in sCD54 (delta sCD54) and sCD58 (delta sCD58) at the respective time points. Using this method, we were able to eliminate interindividual differences in serum concentrations for sCD54 and sCD58 and to avoid bias due to preselection of patients. We found that delta sCD54 correlated with delta AST (p = 0.001) and delta ALT (p = 0.002), whereas there was no such correlation for delta sCD58. Interferon therapy did not affect sCD54 or sCD58 levels. Neither hepatitis B viremia nor the immune response to hepatitis B during the time of seroconversion to anti-HBe did significantly increase sCD54 or sCD58 levels. However, delta sCD54 was associated with delta gamma GT (p = 0.005) and delta sCD58 correlated with delta bilirubin (p = 0.037); a negative correlation was found for delta sCD54 with delta cholinesterase (p = 0.007). Our findings imply that sCD54 and sCD58 may be associated with a decrease in liver function that accompanies hepatic disease activity. sCD54 and sCD58 did not prove useful to monitor disease activity or response to interferon therapy in chronic hepatitis B. From our data we conclude, that decreased elimination of soluble adhesion molecules sCD54 and sCD58 in advanced liver disease may be responsible for increased serum concentrations detected.
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PMID:Circulating ICAM-1 (sCD54) and LFA-3 (sCD58) in chronic hepatitis B--a longitudinal study in patients treated with interferon-alpha. 923 90

The subchronic toxicity of ISIS 2302 and ISIS 3082, phosphorothioate oligonucleotides with antisense activity against human and murine ICAM-1 mRNA, respectively, was investigated in CD-1 mice. ISIS 2302 is currently in clinical trials as an anti-inflammatory agent. Because of the differences in mRNA sequence targets between humans and mice, ISIS 2302 has no pharmacologic activity in mice. ISIS 3082 was specifically designed to inhibit murine ICAM-1 and was included in this study to evaluate the effects of prolonged ICAM-1 inhibition. The oligonucleotides were administered by bolus i.v. injection (via tail vein) every other day for 27 days (14 doses) at dose levels of 0, 0.8, 4, 20, and 100 mg/kg per injection ISIS 2302 or 20 mg/kg per injection ISIS 3082. The basic group size consisted of 10 male and 10 female mice, which were sacrificed 2 days after the last dose and an additional 5 mice per sex in vehicle control and 100 mg/kg ISIS 2302 dose groups, which remained on study for a 28-day treatment-free period. No treatment-related deaths occurred during this study, and there were no effects of either oligonucleotide on body weight gain or food consumption. The most common changes observed in this study included a mixed mononuclear cell infiltrate seen in a number of organs or tissues, splenomegaly, and lymphoid hyperplasia at dose levels of > or = 20 mg/kg ISIS 2302. In the group that received the highest dose level of ISIS 2302 (100 mg/kg), there were alterations in serum chemistry parameters that appeared to be related to perturbations in the liver, including 3- to 4-fold increases in aspartate and alanine aminotransferase and smaller changes in bilirubin, alkaline phosphatase, cholesterol, triglycerides, and albumin levels. Treatment-related effects on hematologic parameters were limited to the 100 mg/kg ISIS 2302 dose group and included slight monocytosis and thrombocytopenia. None of the effects observed appeared to be life threatening. Complete or partial reversal of all effects was evident in the remaining high-dose ISIS 2302 animals at the end of the 4-week recovery period. Comparison of the effects produced by the same dose level (20 mg/kg) of ISIS 2302 and ISIS 3082 did not reveal any differences that could be attributed to exaggerated pharmacology. In conclusion, treatment-related alterations were observed primarily at the 100 mg/kg dose level, including immune stimulation and hepatic alterations, which were partially reversed following a 4-week treatment-free period.
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PMID:Evaluation of the toxicity of ISIS 2302, a phosphorothioate oligonucleotide, in a 4-week study in CD-1 mice. 936 6

In the present study, intrahepatic CD8+ lymphocyte infiltrates as well as HLA class I and CD54 (ICAM-1) antigen expression at both tissue and serum levels were evaluated in 54 untreated patients with chronic hepatitis C stratified on the basis of histological diagnosis (Chronic Persistent Hepatitis/Chronic Lobular Hepatitis -CPH/CLH- and Chronic Active Hepatitis -CAH-: 22 and 32 subjects, respectively). The relationships between soluble HLA-I (sHLA-I) and ICAM-1 (sICAM-1) serum levels and their membrane-bound counterparts, CD8+ liver infiltration and serum alanine aminotransferase (ALT) were also studied. A strong HLA-I and CD54 tissue expression, associated to the presence of CD8+ cell infiltrates in necro-inflammatory areas, and elevated sHLA-I and sICAM-1 serum amounts were observed in all patients. At the same time, no difference was found at tissue level between the two groups of patients with respect to the mean scores of HLA-I and CD54 expression, while CAH subjects displayed a significantly higher CD8 periportal and lobular reactivity in comparison to the other subset. Serological assays outlined higher values of circulating HLA-I molecules in CPH/CLH patients and higher sICAM-1 levels in the CAH group. Finally, a negative correlation was found between sHLA-I and ALT in CAH subjects while, in all patients, sICAM-1 positively correlated with both CD8 tissue infiltration and ALT. Our findings confirm the occurrence of an immune activation status during chronic hepatitis C and suggest that sHLA-I molecules might play a down-modulating role on immunoresponsiveness of these patients.
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PMID:Immunoresponsiveness in chronic hepatitis C patients: correlation between tissue and serum findings. 973 40

To test the hypothesis that leukocyte infiltration mediated by intercellular adhesion molecule (ICAM)-1 is involved in early alcohol-induced liver injury, male wild-type or ICAM-1 knockout mice were fed a high-fat liquid diet with either ethanol or isocaloric maltose-dextrin for 4 wk. There were no differences in mean urine alcohol concentrations between the groups fed ethanol. Alcohol administration significantly increased liver size and serum alanine aminotransferase levels in wild-type mice over high-fat controls, effects that were blunted significantly in ICAM-1 knockout mice. Dietary ethanol caused severe steatosis, mild inflammation, and focal necrosis in livers from wild-type mice. Furthermore, livers from wild-type mice fed ethanol showed significant increases in the number of infiltrating leukocytes, which were predominantly lymphocytes. These pathological changes were blunted significantly in ICAM-1 knockout mice. Tumor necrosis factor (TNF)-alpha mRNA expression was increased in wild-type mice fed ethanol but not in ICAM-1 knockout mice. These data demonstrate that ICAM-1 and infiltrating leukocytes play important roles in early alcohol-induced liver injury, most likely by mechanisms involving TNF-alpha.
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PMID:ICAM-1 is involved in the mechanism of alcohol-induced liver injury: studies with knockout mice. 1135 23

Neutrophil adhesion and recruitment represents one of the early cellular events that occur during hepatic ischemia/reperfusion (IR) injury and plays a critical role in determining the extent of tissue damage. The adhesion molecules, such as selectins and intercellular adhesion molecules (ICAM), are important in mediating neutrophil-endothelial cell interactions and neutrophil emigration. The goal of this study was to evaluate the role of P-selectin and ICAM-1 in hepatic IR injury. Male wild-type and P-selectin/ICAM-1-deficient (P/I null) mice underwent 90 minutes of partial hepatic ischemia followed by reperfusion at various time points (0, 1.5, 3, and 6 hours). Reperfusion caused a time-dependent hepatocellular injury in both wild-type and P/I null mice as judged by plasma alanine aminotransferase (ALT) levels and liver histopathology examination. Although ALT levels were slightly lower in the P/I null mice compared with the wild-type mice the differences were not statistically significant. Neutrophil infiltration to the ischemic liver was observed in both mouse groups after 6 hours of reperfusion; however, the infiltration to the midzonal region of the ischemic liver was more pronounced in the wild-type group. This study suggests that hepatocellular injury induced after hepatic IR was independent of P-selectin and ICAM-1 in this model of acute inflammatory tissue injury.
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PMID:Hepatic ischemia/reperfusion injury in P-selectin and intercellular adhesion molecule-1 double-mutant mice. 1151 May 73

Intercellular adhesion molecule-1 (ICAM-1) has been implicated in the hepatic microvascular dysfunction elicited by gut ischemia-reperfusion (I/R). Although the effects of chronic ethanol (EtOH) consumption on the liver are well known, it remains unclear whether this condition renders the hepatic microcirculation more vulnerable to the deleterious effects of gut and/or hepatic I/R. The objectives of this study were to determine whether chronic EtOH consumption alters the severity of gut I/R-induced hepatic microvascular dysfunction and hepatocellular injury and to determine whether ICAM-1 contributes to this response. Male Wistar rats, pair fed for 6 wk a liquid diet containing EtOH or an isocaloric control diet, were exposed to gut I/R. Intravital video microscopy was used to monitor leukocyte recruitment in the hepatic microcirculation, the number of nonperfused sinusoids (NPS), and plasma concentrations of endotoxin and tumor necrosis factor-alpha. Plasma alanine aminotransferase (ALT) levels were measured 6 h after the onset of reperfusion. In control rats, gut I/R elicited increases in the number of stationary leukocytes, NPS, and plasma endotoxin, tumor necrosis factor-alpha, and ALT. In EtOH-fed rats, the gut I/R-induced increases in NPS and leukostasis were blunted in the midzonal region, while exaggerated leukostasis was noted in the pericentral region and terminal hepatic venules. Chronic EtOH consumption also enhanced the gut I/R-induced increase in plasma endotoxin and ALT. The exaggerated responses to gut I/R normally seen in EtOH-fed rats were largely prevented by pretreatment with a blocking anti-ICAM-1 monoclonal antibody. In conclusion, these results suggest that chronic EtOH consumption enhances gut I/R-induced hepatic microvascular dysfunction and hepatocellular injury in the pericentral region and terminal hepatic venules via an enhanced hepatic expression of ICAM-1.
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PMID:Role of ICAM-1 in chronic ethanol consumption-enhanced liver injury after gut ischemia-reperfusion in rats. 1218 Nov 65


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