Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The disposition of total and non-protein-bound etoposide was investigated in 21 cancer patients receiving etoposide and cisplatin combination chemotherapy. Etoposide plasma concentrations were determined using a specific high-performance liquid chromatography (HPLC) method, and etoposide plasma protein binding was determined by equilibrium dialysis. The patients had a wide range of renal function (creatinine clearance, 32 to 159 mL/min/m2) and hepatic function (total bilirubin range, 0.3 to 21.5 mg/dL; aspartate aminotransferase [AST] range, 14 to 415 IU/L; serum albumin range, 2.7 to 4.1 g/dL). The mean etoposide total systemic clearance was not different in 15 patients with total bilirubin less than 1.0 mg/dL versus six patients with total bilirubin 1.1 to 21.5 mg/dL (18.7 +/- 5.9 mL/min/m2 v 26.4 +/- 10.7 mL/min/m2; t-test P = .06), with a trend toward higher total clearance in the patients with abnormal bilirubin values. However, the mean clearance of unbound etoposide was significantly lower in patients with increased total bilirubin (220 +/- 90 mL/min/m2 v 135 +/- 61 mL/min/m2; t-test P = .027). The fraction of etoposide unbound (fu) in plasma was significantly higher in patients with increased bilirubin (9% +/- 3% v 27% +/- 15%; t-test P = .002), explaining the trend toward higher total clearance in these patients. Etoposide clearance (total or unbound) in the 14 patients with measurable hepatic metastases was not different from the clearance in the seven patients without hepatic metastases. This study provides an explanation for why patients with increased bilirubin do not have lower total systemic clearance of etoposide, and indicates that such patients have a higher exposure to unbound etoposide. The results of ongoing pharmacodynamic studies of total and unbound etoposide in patients with increased bilirubin will determine the clinical relevance of altered etoposide protein binding.
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PMID:Changes in the clearance of total and unbound etoposide in patients with liver dysfunction. 223 Aug 75

The optimal conditions for selective proteolytic inactivation of cytosolic aspartate aminotransferase (c-AST) to determine mitochondrial aspartate aminotransferase (m-AST) in serum were studied. Protease 401 was found to be effective over a pH range of 6.0-10.0. A pH of 9.5 with 0.5% albumin in the reagent mixture was determined to be optimal for inactivation of c-AST and preservation of m-AST, lactic dehydrogenase (LDH), and malic dehydrogenase (MDH) in the assay procedure. The presence of serum endogenous protein inhibitors such as alpha 1-antitrypsin and alpha 2-macroglobin did not inhibit protease 401.
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PMID:Optimal conditions for protease use in the assay of serum mitochondrial aspartate aminotransferase. 223 Nov 81

Various aliphatic alcohols potentiate the toxicity of a wide range of xenobiotics including several haloalkanes. The present series of experiments were designed to test: (i) whether a single subtoxic dose of alcohol can potentiate CCl4 and CHCl3 hepatoxicity, and (ii) whether this potentiation leads to greater animal lethality. Selected members of a homologous series of straight chain alcohols were chosen for this study. Methanol, ethanol, isopropanol, t-butanol, pentanol, hexanol, octanol, decanol, and eicosanol at equimolar doses (10 mmol/kg) were tested in the present investigation. Each alcohol was administered orally to male Sprague-Dawley rats (175-250 g) 18 hr prior to a single oral administration of CCl4 or CHCl3. Liver injury was assessed by plasma transaminases (alanine aminotransferase, ALT; aspartate aminotransferase, AST) and histopathological examination of liver sections 24 hr after the halomethane treatment. None of these alcohols alone increased plasma ALT or AST significantly, whereas CCl4 or CHCl3 administration to alcohol-treated animals resulted in significant elevation of plasma transaminases. Eicosanol (20-carbon alcohol) did not potentiate the toxicity of either halomethane. Methanol, ethanol, isopropanol, and decanol in combination with CCl4 caused massive liver damage but failed to augment CCl4 lethality. t-Butanol, pentanol, hexanol, and octanol significantly decreased the LD50 of CCl4. The hepatotoxic effects of CHCl3 were potentiated by all of the alcohols and the LD50s were also decreased significantly. On a comparative basis, alcohol-potentiated CHCl3 toxicity was greater than the toxicity of CCl4. These findings indicate that even though halomethane liver injury might be potentiated by alcohols, the underlying mechanisms differ among alcohols since not all alcohols potentiate the lethal effects of these halomethanes.
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PMID:Potentiation of CCl4 and CHCl3 hepatotoxicity and lethality by various alcohols. 225 8

To assess the utility of the serum aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio in a group of infants with liver disorders, we retrospectively analyzed the charts of 73 infants with chronic liver disorders. Patients were considered as having either a good outcome (n = 40) or a poor outcome (n = 33), based upon the clinical course. AST and ALT in serum were measured simultaneously at the time of initial presentation and at various follow-up visits during the first 13 months after birth. At presentation (mean age 1.65 months), there was no difference in the AST/ALT ratios between the good (1.61 +/- 0.62; mean +/- SD) and poor (1.65 +/- 0.78) outcome groups (P = 0.81). However, over time, the AST/ALT ratio increased in patients in the poor-outcome group and decreased in patients in the good-outcome group. Calculating the AST/ALT ratio appears to be an easy, early, and reliable prognostic indicator for infants with hepatic disease, and may be a useful measure for evaluating liver-disease patients.
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PMID:Aminotransferase as a prognostic index in infants with liver disease. 230 79

The systemic administration of interleukin-2 (IL-2) can lead to significant antitumor responses in some patients with metastatic cancer in whom standard therapy has failed. A limitation of this immunotherapy is the toxicity associated with IL-2 infusion. To assess toxicity, we determined aspartate aminotransferase (AST; EC 2.6.1.1), alanine aminotransferase (ALT; EC 2.6.1.2), gamma-glutamyltransferase (GGT; EC 2.3.2.2), lactate dehydrogenase (LD; EC 1.1.1.27), alkaline phosphatase (ALP; EC 3.1.3.1), creatine kinase (CK; EC 2.7.3.2), total bilirubin (TBI), direct bilirubin (DBI), creatinine, urea nitrogen, and C-reactive protein in serum from 21 patients before and during five consecutive days of IL-2 treatment. Ten patients were followed for an additional five days after the end of IL-2 therapy. The IL-2 infusion caused liver toxicity and prerenal azotemia, as evidenced by significant increases (P less than 0.05) of all analytes except CK by day 1. There was a progressive increase in the results (except CK) for these tests until IL-2 treatment was stopped. Seven tests related to liver function (AST, ALT, GGT, LD, ALP, DBI, and TBI) showed increases, but the test results indicated significant improvement and moved toward the baseline value five days after the end of IL-2 therapy. Concentrations of creatinine and urea nitrogen in serum were normal three days after the cessation of IL-2 therapy.
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PMID:Changes in laboratory results for cancer patients treated with interleukin-2. 231 Dec 9

We describe a new double-antibody ELISA system using avidin-biotin amplication for the mass measurement of mitochondrial aspartate aminotransferase (m-AST) in human serum. The assay is very sensitive and as little as 0.5 ng/ml of m-AST may be detected. The method is linear up to 100 micrograms/l. The within-day and day-to-day coefficients of variation were found to be 8.9% and 11.5% respectively for a low m-AST concentration (2.7 micrograms/l), and 5.9% and 8.0% respectively for a high level of m-AST (30 micrograms/l). The assay requires 100 microliters of serum and can be completed within 5 h. The ELISA procedure and a classical immunoprecipitation technique measuring the catalytic activity of the isoenzyme were applied simultaneously to the sera of 189 subjects. The protein levels determined by ELISA correlated poorly (r = 0.66) with the catalytic activity of m-AST.
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PMID:An avidin-biotin ELISA for the measurement of mitochondrial aspartate aminotransferase in human serum. 232 12

Concentrations of both desialylated transferrin (dTf) and the mitochondrial isoenzyme of aspartate aminotransferase (EC 2.6.1.1, mAST) have been claimed to be increased in sera of alcoholic subjects. To investigate the diagnostic usefulness of these new biochemical markers of alcoholism and to compare them with more conventional markers, we measured dTf and mAST in the sera of controls, alcoholic subjects, and patients with nonalcoholic liver diseases (NALD). Alcoholic subjects had significantly (P less than 0.001) higher ratios of dTf to total transferrin than did either healthy controls or patients with NALD (sensitivity 81%, specificity 97%). The mAST was increased in 92% of alcoholic subjects but also in 48% of patients with NALD. The mAST/total AST ratio differentiated the alcoholic subjects from those with NALD (P less than 0.001) with a sensitivity of 92%, but the specificity was only 70%. In contrast, the conventional markers were less sensitive and less specific. We conclude that the best available single laboratory marker for current heavy alcohol consumption is the ratio dTf/total transferrin.
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PMID:Desialylated transferrin and mitochondrial aspartate aminotransferase compared as laboratory markers of excessive alcohol consumption. 235 19

The medical records of 43 hemodynamically stable children with elevated serum transaminase levels (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) who underwent abdominal computed tomographic (CT) scan for blunt abdominal trauma were reviewed. Nineteen patients (44.2%) had AST levels greater than 450 IU/L and ALT levels greater than 250 IU/L, and 17 of these 19 patients had hepatic injury identified on abdominal CT scan. Of the 43 patients, 25 (58.1%) had AST and ALT levels of less than 450 IU/L and 250 IU/L, respectively, and none of these patients had evidence of hepatic injury on CT scan. Elevated serum transaminase levels (AST greater than 450 IU/L and ALT greater than 250 IU/L) identified all of the patients with hepatic injury visible on abdominal CT scan. The sensitivity and specificity of elevated serum transaminase levels were 100% and 92.3%, respectively, for predicting hepatic injury. It is recommended that hemodynamically stable pediatric patients with blunt abdominal trauma and AST levels greater than 450 IU/L and/or ALT levels greater than 250 IU/L undergo abdominal CT scan to determine the presence and extent of hepatic injury. Children with serum transaminase levels below these values are at decreased risk of liver injury.
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PMID:Elevated liver transaminase levels in children with blunt abdominal trauma: a predictor of liver injury. 235 86

The purpose of this study was to assess the diagnostic value of serum mitochondrial aspartate aminotransferase activity (mAST) and of the mitochondrial aspartate aminotransferase/total aspartate aminotransferase ratio (mAST/t AST) as markers of chronic alcoholism in cirrhotic patients. Sixty-three hospitalized cirrhotic patients (35 drinkers, 28 abstainers) were investigated. Ninety-six per cent of abstainers had normal values of mAST activity, while 89 per cent of drinkers had high levels of mAST activity. Cirrhotic patients were better divided into drinkers and abstainers by mAST activity (92 per cent) than by mean globular corpuscular volume (MCV) (81 per cent, NS) or by gamma-glutamyltransferase activity (GGT) (75 per cent, P less than 0.01). When the hospital costs of these markers were taken into account, MCV had a better "quality/price" ratio (Q/P) defined as diagnostic value/mean hospital cost (Q/P = 2.5) than MCV plus GGT (diagnostic value 61 per cent, Q/P = 1.2). The measurement of mAST activity in patients with high MCV value or with discrepancy between MCV and GGT values increased the diagnostic value of the other laboratory measurement to 89 per cent, but at a higher cost (Q/P = 0.8). Mitochondrial AST activity is a sensitive and specific marker of chronic alcoholism in cirrhotic patients. However, owing to its high cost, it should be proposed as a second marker after MCV and GGT.
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PMID:[Role of the serum level of mitochondrial aspartate aminotransferase as marker of alcoholic intoxication in cirrhotic patients]. 256 11

All cases of liver tumor referred to the King Faisal Specialist Hospital and Research Centre in Saudi Arabia during 2.5 years were reviewed. Hepatocellular carcinoma, 104 cases, was considerably more common than metastatic carcinoma with unknown primary, 15 cases. Lymphoma presenting as liver tumor occurred in three cases and there were no cases of cholangiocarcinoma. There were only two cases of benign tumor, both hemangioma. Hepatocellular carcinoma was characterized by a male predominance of 6:1, positive hepatitis B surface antigen in 60%, presentation with an enlarged, hard liver in over 90%, a systolic-diastolic bruit over the mass in 45%, a single highly echogenic lesion in the right lobe on ultrasound in 80%, and rapid progression. The serum AST (aspartate aminotransferase, serumglutamic oxalacetic transaminase [SGOT]) was abnormal in 97% and was higher than the alanine aminotransferase (ALT) in 93% of cases compared with 17% in 100 consecutive cases of chronic active hepatitis. Sixty-six percent of patients with hepatocellular carcinoma had serum AFP greater than 200 ng/ml. Excluding five cases of germ cell tumor (none involving the liver), and pregnant patients, serum AFP was less than 200 ng/ml in all other patients in whom it was measured between 1979 and 1981. A practical approach to the diagnosis of hepatocellular carcinoma is outlined. Biopsy does not appear to be indicated in many cases of advanced hepatocellular carcinoma.
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PMID:Hepatic tumors in Saudi Arabia. A practical approach to diagnosis. 257 17


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