Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.1 (aspartate aminotransferase)
 21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Liver and kidney injury following acute or chronic exposure to cadmium is well characterized. While hepatocytes and endothelial cells of the sinusoids are thought to be the primary cellular targets in the liver, ultrastructural changes may vary depending upon the exposure regimen and the time following administration. Since acute and chronic liver disease is often associated with the presence of cytokines, we investigated the role of proinflammatory cytokines in cadmium-induced hepatotoxicity. Supernatants from cultured liver slices obtained from acute or subchronic cadmium-exposed rats and mice were collected and cytokine secretion was examined. In addition, mRNA transcripts for IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, MIP-2, IFN-gamma, and ICAM-1 from livers of treated mice were quantitated by reverse transcription-polymerase chain reaction. Modest increases in secretion of TNF-alpha, IL-1 alpha, and IL-6 were observed in response to cadmium which were enhanced in LPS-primed mice. Additionally, cadmium exposure increased IL-1 alpha, IL-1 beta, TNF-alpha, MIP-2, IL-6, and ICAM-1 mRNA transcripts in the liver. Immunohistochemical analysis revealed that TNF-alpha was associated with nonparenchymal cells in livers of cadmium-treated mice. Cadmium exposure produced a marked increase in plasma hepatocellular enzyme levels (i.e., AST, LDH, SDH), acute phase proteins (i.e., serum amyloid A), and foci formation in the liver, while focal inflammation and serum amyloid A (SAA) secretion, but not plasma enzymes, were further increased in cadmium-exposed mice primed with LPS. SAA secretion and focal inflammation were prevented by pretreatment with antibodies to TNF-alpha, indicating that these pathological manifestations are cytokine dependent. These data indicate that TNF-alpha, released from nonparenchymal cells as well as associated cytokines, are responsible for certain manifestations observed with cadmium-induced hepatotoxicity.
 ...
PMID:Role of tumor necrosis factor-alpha in cadmium-induced hepatotoxicity. 753 60

Autoimmune chronic active hepatitis (CAH-A) is a chronic liver disease of unknown etiology that is believed to have an autoimmune pathogenesis. The disease is slowly progressive until hepatic failure and portal hypertension develop and either death or liver transplantation occur. Currently, the only widely recognized therapy is the administration of glucocorticoids, which have both anti-inflammatory and immunosuppressive actions. Many patients cannot tolerate such therapy because of the psychiatric, osteoporotic, and weight-enhancing actions of steroids. Tacrolimus (FK 506) is a new macrolide antibiotic that has an immunosuppressive activity that is estimated to be 10-200 times greater than that of cyclosporine. Because of its greater immunosuppressive activity, we have used it in the treatment of 21 patients with autoimmune chronic active hepatitis. Before each subject was treated, a liver biopsy and a panel of hematological, serological, and biochemical parameters were assessed. The Tacrolimus was administered orally at 12-h intervals, and the dose was controlled by monitoring plasma FK trough levels. After 3 months of therapy at an oral dose of 3 mg twice a day, having achieved a median blood level of 0.5 ng/ml, the serum ALT level was reduced by 80%, and the AST level was reduced by 70%. Modest change in the white blood cell count and platelet count were noted. The median BUN level increased from a level of 12 to 18 mg/dl, and the serum creatinine increased from 0.9 to 1.3 mg/dl. These preliminary data demonstrate that: 1) Tacrolimus can be used to successfully treat CAH-A; 2) the response of CAH-A to Tacrolimus treatment is rapid and sustained; and 3) a minor increase in the serum BUN and creatinine levels occurs as a consequence of Tacrolimus treatment. It is anticipated that with continued treatment for periods of 1-2 yr, the natural history of CAH-A will be changed such that hepatic failure and the requirement for liver transplantation may be averted.
 ...
PMID:Tacrolimus: a potential new treatment for autoimmune chronic active hepatitis: results of an open-label preliminary trial. 753 44

Serum levels of soluble forms of intracellular adhesion molecule-1 (sICAM-1) and lymphocyte function-associated antigen-3 (sLFA-3) in 122 patients with chronic liver disease including hepatocellular carcinoma (HCC) were measured by enzyme-linked immunosorbent assays. Serum levels of sICAM-1 in patients with HCC were significantly higher than those of chronic hepatitis (CH) and cirrhosis. On the other hand, serum levels of sLFA-3 in patients with HCC were almost the same as those of cirrhosis. Western blot analyses showed that molecular sizes of sICAM-1 and sLFA-3 detected in the sera were 90 kd and 50 kd, respectively, indicating that both molecules include whole extracellular domains. In patients with HCC, circulating sICAM-1 levels were significantly (P < .001) correlated with tumor volume (r = .50), total bilirubin (r = .38), serum aspartate aminotransferase levels (r = .51), and gamma-globulin (r = .63). Furthermore, serum sICAM-1 levels were significantly elevated in patients with multiple HCC (tumor number > 3) or HCC with tumor embolus in the first branch or trunk of portal vein. Survival periods were analyzed in relation to serum sICAM-1 levels in patients with HCC who had been treated by transcatheter arterial chemoembolization. The HCC patients with < 1,000 ng/mL of serum ICAM-1 showed significantly (P = .0005) longer survival than those with higher levels of the molecule. The same results were obtained when only patients with moderately differentiated HCC were analyzed (P = .02). Analyses by Cox's proportional hazard model showed that sICAM-1 is a significant (P = .032) prognostic factor for patients with HCC.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Serum concentration of intercellular adhesion molecule-1 in patients with hepatocellular carcinoma is a marker of the disease progression and prognosis. 754 36

To assess the prevalence and long-term impact of HCV on kidney transplant recipients, we assayed 716 pre-transplant sera using a first-generation ELISA. The anti-HCV positive sera were confirmed by a 6-antigen radioimmunoassay (RIA). Patients were followed up for 5 years. Graft survival, function, evidence of chemical hepatitis (AST > 2x normal), patient mortality and cause of death were evaluated. The prevalence of anti-HCV antibody was 10.3%. In the 638 patients who were followed up for 5 years, there were no differences in graft function, graft survival, overall mortality, or death from sepsis or liver disease. Peak AST levels were significantly higher in anti-HCV positive patients compared to anti-HCV negative patients. At 5 years, the AST levels remained significantly higher in the anti-HCV positive group, however, this was only 6 U/1 > normal. Liver biopsies performed 3 to 7 years post-transplant in 80% of anti-HCV positive patients with chemical hepatitis showed 12% CAH, 50% mild hepatitis and 38% normal histology. Six (9.7%) patients seroconverted from anti-HCV positive to anti-HCV negative 2 to 5 years post-transplant. The presence of anti-HCV does not appear to alter long-term patient or graft survival, and histologic evidence of severe chronic liver disease was rare in anti-HCV positive patients with chemical hepatitis. From these results, the presence of anti-HCV antibody should not preclude kidney transplantation.
 ...
PMID:Long-term outcome in kidney transplant patients with hepatitis C (HCV) infection. 759

To evaluate its clinical value, the half-life of caffeine (1,3,7-trimethylxanthine) in saliva (SCT) after 3 mg/kg-1 oral caffeine was measured in 53 children with chronic liver disease (mean age, 4.41 years) and 48 control children (mean age, 6.26 years) in five samples over 24 h and compared with parameters of liver function and outcome. Sensitivity was 60.3% and specificity 97% of SCT for diagnosis of chronic liver disease. The correlation of SCT with serum albumin (ALB) was -0.52 (p < 0.001), total bilirubin (SBR) was 0.585 (p < 0.001), prolonged prothrombin time (PT) was 0.387 (p = 0.004), and aspartate aminotransferase (AST) was 0.538 (p = 0.001). The correlation of SCT with a clinical score of liver dysfunction calculated from the presence of features of hepatic decompensation was 0.627 (p < 0.001) and with Malatack's paediatric prognostic score was 0.505 (p < 0.001). Serial SCT and liver function tests were performed on 53 patients on 127 occasions during a mean follow-up of 361 days (range, 4-709). Of this group, 18 were listed for liver transplantation. Predictive values of outcome by analysis of variance expressed as ratio of mean squares were SBR, 34.1 (p < 0.001); log10 SCT, 20.6 (p < 0.001); ALB, 5.2 (p < 0.05); PT, 1.2 (NS). SCT correlated with clinical and biochemical parameters of severity of liver disease, but SBR was a better predictor of listing for liver transplantation in this group of paediatric patients.
 ...
PMID:The prognostic significance of caffeine half-life in saliva in children with chronic liver disease. 771 86

Chronic hepatitis, cirrhosis, and hepatocellular carcinoma are the accepted sequelae of chronic hepatitis C virus (HCV) infection. However, the real natural history of HCV infection is not still well understood. To approach this problem, we investigated 91 individuals positive for antibodies against HCV (anti-HCV), who have received annual liver function examination in a local town known to have had high carrier rates of hepatitis B virus (HBV) and HCV. Among the 91 anti-HCV-positive individuals, 63 had undertaken the annual examination more than five times in the past 14 years. We analyzed retrospectively the past liver function test results of these 63 subjects and evaluated their present virological status by determining HCV genotypes and estimating quantity of HCV RNA in the sera. Among the 63 subjects, 50 (79.4%) had HCV RNA in the serum and 40 (80%) of the 50 subjects with HCV RNA had abnormal alanine aminotransferase or aspartate aminotransferase level more than once in their records. However, the other 10 (20%) had no abnormal levels during the period examined. Six of 50 (12%) had ultrasonographic findings suggestive of cirrhosis. Thus, HCV-infected individuals in this area did not seem to have progressive liver diseases. Considering the advanced ages of the individuals examined (mean 64 years old), we may have observed a stage in the natural history of HCV infection in which viremia persists in most individuals and the tendency to progress to serious chronic liver disease is mild.
 ...
PMID:A retrospective study of hepatitis C virus carriers in a local endemic town in Japan. A possible presence of asymptomatic carrier. 785 Dec 13

We examined the value of laboratory markers of excessive alcohol (ethanol) intake as predictors of mortality, morbidity, and health-care utilization in a cohort of 330 patients attending an acute ambulatory care service. Among men, all four markers examined--gamma-glutamyltransferase (GGT) and aspartate aminotransferase (AST) activities, high-density lipoprotein cholesterol (HDL-C), and mean corpuscular volume (MCV)--were predictive of medical sequelae and health-care utilization over a 3-year period. In contrast, social problems were more closely related to the amount of alcohol consumption at initial assessment than to any biological marker. Serum GGT and AST activities and MCV were predictive of medical sequelae in women. The predictive value of GGT was an independent risk factor and did not merely reflect recent alcohol intake or the presence of chronic liver disease. We conclude that these readily available laboratory tests provide important prognostic information and should be an integral part of the assessment of persons with hazardous alcohol consumption.
 ...
PMID:Prediction of alcohol-related harm by laboratory test results. 790 Sep 34

The authors measured immunoenzymatically circulating intercellular adhesion molecule-1 (cICAM-1) concentration in 135 patients with liver disease of either viral or toxic etiology: 13 had acute hepatitis; 58 had mild chronic liver disease; and 64 had cirrhosis (superimposed in 30 by hepatocellular carcinoma). Forty patients with extrahepatic diseases (19 with malignancies) and 28 healthy blood donors were tested as controls. One-way analysis of variance demonstrated a significant variability of cICAM-1 concentration among groups (F = 76.67, P < .0001), the highest value being recorded in acute hepatitis (Bonferroni's test for pairwise comparisons, P < .01). Total bilirubin showed a strong correlation with cICAM-1 (R = 0.766, P < .001). By stepwise multiple regression analysis the independent predictors of cICAM-1 concentration were chosen in the following order: total bilirubin; aspartate aminotransferase; cholinesterase; alpha-1-antitrypsin; and immunoglobulins. Thus, in addition to inflammation, cholestasis and decline of functioning hepatic mass may influence cICAM-1 concentration.
 ...
PMID:Circulating intercellular adhesion molecule-1 (cICAM-1) concentration in liver disease. Relationship with cholestasis and functioning hepatic mass. 794 24

Data on the prevalence of chronic liver disease, derived from selected series of hospitalized patients or from mortality registers, underestimate the prevalence of chronic liver disease. The Dionysos Study is a cohort study that investigated for the first time the prevalence of chronic liver disease in a general population. All the citizens of two towns in northern Italy, Campogalliano and Cormons, aged 12 to 65 yr were contacted by letter. From March 1991 through March 1993, 6,917 of a total of 10,150 citizens were enrolled (compliance, 69%). The standardized protocol for each enrollee included (a) a color-illustrated food questionnaire on dietary habits and alcohol intake; (b) a detailed medical history, including questions on risk factors for chronic liver disease; (c) a physical examination; and (d) blood tests for AST, ALT, gamma-glutamyltranspeptidase, mean cell volume, platelet count and hepatitis B virus and hepatitis C virus markers. Signs suggestive of chronic liver disease were seen in 21.3% of the subjects, and who then underwent further liver function tests, upper abdominal ultrasonography and, when necessary, liver biopsy. Persistent signs of chronic liver disease were present in 17.5% of the subjects, including 1.1% with cirrhosis and 0.07% with hepatocellular carcinoma. The prevalence rates of hepatitis B virus and hepatitis C virus positivity (second-generation enzyme-linked immunosorbent assay) were 1.3% and 3.2%, respectively. Alcohol abuse was the etiological agent in 23%.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Prevalence of chronic liver disease in the general population of northern Italy: the Dionysos Study. 798 43

Relationships between liver biochemical test values and reported frequency of consumption of various foods were examined using a principal-component analysis of data from 42 patients with chronic liver disease. The statistical procedure identified relationships among biochemical and dietary variables. One relationship included the variables albumin, bilirubin, and frequency of intake of fruits and vegetables, starch, and meats. A relationship was also found between serum alkaline phosphatase (ALP) levels and fat/oil intake. Data from patients with primary biliary cirrhosis (PBC) and noncholestatic liver disease were compared using a correlational analysis. In patients with PBC, serum ALP levels were positively correlated with frequency of intake of fat/oil (r = 0.59, p < 0.01) and meats (r = 0.46, p < 0.05), whereas serum bilirubin (Bili) and aspartate aminotransferase (AST) levels were significantly correlated with frequency of intake of dairy products (rs = 0.48 and 0.45, ps < 0.05 for Bili and AST, respectively), meats (rs = 0.59 and 0.65, ps < 0.01), and fat/oil (r = 0.54, p < 0.02 and r = 0.48, p < 0.05). In patients with noncholestatic liver disease, Bili levels were correlated with frequency of intake of fat/oil (r = 0.58, p < 0.01), and fruits and vegetables (r = 0.68, p < 0.01). These results suggest that the degree of elevation of some liver biochemical tests in patients with liver disease may be affected by dietary intake.
 ...
PMID:Relationship between liver biochemical tests and dietary intake in patients with liver disease. 807 8


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>