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:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum glycocholic acid (SGC) was measured by radioimmunoassay in 277 samples from 122 children with hepatobiliary disorders and from 23 healthy age-matched controls. In patients with hepatobiliary disease the SGC was more frequently abnormal (83%) than values for serum albumin (7%), prothrombin time (17%), bilirubin (22%), alkaline phosphatase (45%), aspartate transaminase (57%) and gammaglutamyl transpeptidase (63%). The cumulative frequency of abnormality of these six tests was equal to that of SGC alone. Serum glycocholic acid concentrations were raised in 13 patients in whom all other tests of liver function were normal. Two of these had clinical and histological evidence of liver disease, while four had biopsy-proven hepatic fibrosis or cirrhosis, and two of three with chronic active hepatitis in remission subsequently relapsed. Four patients have as yet, no other clinical or biochemical evidence of continuing liver disease. Serum glycocholic acid was normal in seven children with abnormal aspartate transaminase or gammaglutamyl transpeptidase in whom there is strong suspicion of significant hepatic disease. A wide range of values of SGC was found with marked overlap between the values found in the different disease entities studied. The SGC value was related to the serum concentration of aspartate transaminase and gammaglutamyl transpeptidase but not to other tests of liver function. Serum glycocholic acid concentration was considered in relation to the severity of histological abnormality in 25 percutaneous liver biopsies. The extent of the rise in SGC was related to the presence or degree of histological severity of oedema in the portal tracts, disruption of the limiting plate, parenchymal fibrosis and hepatocellular necrosis but not to other histological features. The very high incidence of abnormal SGC values found in this study does suggest that in an ordinary inpatient and outpatient service SGC determination is a practical and sensitive indicator of the presence of significant liver disease but for its comprehensive identification aspartate transaminase and gammaglutamyl transpeptidase must also be determined.
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PMID:Radioimmunoassay of serum glycocholic acid, standard laboratory tests of liver function and liver biopsy findings: comparative study of children with liver disease. 711 20

Renal and hepatic function was investigated in groups of 7 rats for 14 days after a single i.p. injection of 125 mg/kg purified kappa (kappa), lambda (lambda) or iota (iota) carrageenan. Kappa carrageenan was clearly nephrotoxic, as evidenced by a progressive, marked increase in serum creatinine and urea levels and in urinary N-acetyl-beta-D-glucosaminidase (NAG) activity. It also caused significant elevation in serum aspartate aminotransferase (AAT) activity from Day 2 to Day 7, and a progressive decrease in circulating albumin concentrations. Lambda carrageenan had no significant effect on serum creatinine or urea levels and caused only a transient increase in urinary NAG which was maximal on Day 2. Serum AAT levels were also significantly raised on Day 2. Iota carrageenan injection resulted in the deaths of 2/7 animals. Significant increases in serum creatinine levels were observed on Day 4: in 2 rats these increase were very pronounced as were those in urea levels, but no significant alterations in serum urea or urinary NAG levels were observed. No significant elevation in serum AAT was found, except for minor changes on Days 7 and 14. Whereas lambda carrageenan decreased serum albumin throughout the 14-day course of the experiment, albumin levels in lambda carrageenan-injected rats, whilst depressed during the first week, returned to normal by Day 14.
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PMID:A comparative study of renal and hepatic function in Sprague-Dawley rats following systemic injection of purified carrageenans (kappa, lambda and iota). 723 1

In primary biliary cirrhosis (PBC) liver copper retention occurs as a complication of cholestasis. By analogy with Wilson's disease, it has been suggested that copper retention is hepatotoxic in PBC, and this has been the rationale for the use of D-penicillamine in this disease. The hypothesis that copper is hepatotoxic in PBC has not been tested and in this study we have evaluated the role of liver copper retention in the pathogenesis of PBC. Sixty-four patients with PBC have been studied. Fifty-four had increased liver copper concentrations. Liver cell synthetic function was well preserved. All the patients had normal prothrombin times, and only two had subnormal serum albumin concentrations. There was no correlation between liver copper concentrations and the degree of liver cell damage assessed biochemically (aspartate transaminase), and histologically. Electron microscopy was performed on liver biopsies from five patients with markedly increased liver copper concentrations. The liver cell ultrastructure was compatible with cholestasis. Liver cells contained electron dense lysosomes, which were shown to contain copper and sulphur by x-ray probe microanalysis. The characteristic organelle changes associated with copper toxicity in Wilson's disease were not observed. The biochemical, histological, and histochemical differences between PBC complicated by liver copper retention, and Wilson's disease, indicates that there are differences in the handling of copper in these disease. In this study we could find no evidence to suggest that copper plays an important role in the pathogenesis of liver dysfunction in PBC.
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PMID:Is copper hepatotoxic in primary biliary cirrhosis? 730 88

Administration of a single high dose of styrene (878 mg/kg ip in corn oil) to young male rats produced significant elevations in the activities of serum transaminases: 230, 209, and 71% increases in the activity of serum glutamic-oxaloacetic transaminase (SGOT) and 163, 437, and 227% in that of serum glutamic-pyruvic transaminase (SGPT) at 2, 6, and 24 h, respectively, after the dose. These results demonstrated that styrene could produce acute hepatic injury in young rats. Urinary nonprotein sulfhydryl contents and mandelic, phenylglyoxylic, and hippuric acids were all increased. Pretreatment of rats with phenobarbital and 3-methylcholanthrene did not further enhance the activities of SGOT and SGPT after styrene, but produced changes in other biochemical parameters, for example, an increase in liver weight, decrease in serum albumin and globulin concentrations, increase in serum alkaline phosphatase activity at 2 and 6 h, and increase in urinary urobilinogen concentrations. In addition, such pretreatments further increased the nonprotein sulfhydryl contents at 2 and 6 h after styrene injection. Pretreatment of rats with the microsomal enzyme inhibitor SKF 525-A failed to prevent the hepatotoxicity induced by styrene and did not modify the overall urinary excretion profiles of styrene metabolites. This study suggests that the mechanism of the activation/deactivation process leading to the metabolism and hepatotoxicity of styrene is complex and that alternative pathways not dependent on cytochrome P-450 might also be involved.
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PMID:Effects of microsomal induction and inhibition on styrene-induced acute hepatotoxicity in rats. 733 32

The liver is thought to be the major source of circulating insulin-like growth factor (IGF-I) and IGF-binding protein-1 (IGFBP-1), whereas the primary production site of circulating IGFBP-3 remains unknown. As other tissues may contribute to the circulating pool of IGF-I and IGFBP, the aim of the present study was to assess the hepatic and renal arterio-venous difference and production rates of IGF-I, IGFBP-1, IGFBP-3, and GH in cirrhotic patients (n = 22) and matched control subjects (n = 27). IGFBP-1 and -3, IGF-I, and GH levels were measured by RIA in hepatic, renal, and peripheral veins and in the femoral artery. Levels of IGFBP-1 to -4 were additionally determined by Western ligand blotting. Hepatic venous IGFBP-1 was significantly increased in the cirrhotic patients (mean +/- SEM, 33.6 +/- 9.1 vs. 10.4 +/- 1.9 micrograms/L; P < 0.001), and arterio-renal-venous extraction was significant in both patients (6 +/- 2%; P < 0.01) and controls (11 +/- 1%; P < 0.001). Conversely, IGFBP-3 was decreased in the cirrhotic patients (1265 +/- 149 vs. 2712 +/- 137 micrograms/L; P < 0.001). IGFBP-3 correlated significantly with the wedged hepatic venous pressure (r = -0.49; P < 0.05), serum aspartate aminotransferase (r = -0.66; P < 0.01), serum bilirubin (r = -0.65; P < 0.01), serum albumin (r = 0.64; P < 0.01), and the Child score (r = -0.57; P < 0.01). IGF-I was significantly lower in the cirrhotics (57 +/- 10 vs. 143 +/- 11 micrograms/L; P < 0.001). No significant IGFBP-3 proteolysis was demonstrated in cirrhotics or controls. No significant differences were found in the values obtained simultaneously from hepatic, renal, and brachial veins or femoral artery, which suggests that no major net production or release of IGFBP-3 or IGF-I occurs in these tissues. No differences in IGFBP-2 or IGFBP-4 determined by Western ligan blot were found between patients and controls. The IGF-I concentrations correlated significantly with parameters of biochemical liver function. Basal GH concentrations were significantly higher in the cirrhotics (1.19 +/- 0.13 vs. 0.58 +/- 0.08 micrograms/L; P < 0.001). A significant hepatic disposal of GH was found in the patients (P < 0.05) and controls (P < 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Concentrations, release, and disposal of insulin-like growth factor (IGF)-binding proteins (IGFBP), IGF-I, and growth hormone in different vascular beds in patients with cirrhosis. 753

To explore the relationship between mitochondrial aspartate aminotransferase (mAspAT; EC 2.6.1.1) and plasma membrane fatty acid-binding protein (FABPpm) and their role in cellular fatty acid uptake, 3T3 fibroblasts were cotransfected with plasmid pMAAT2, containing a full-length mAspAT cDNA downstream of a Zn(2+)-inducible metallothionein promoter, and pFR400, which conveys methotrexate resistance. Transfectants were selected in methotrexate, cloned, and exposed to increasing methotrexate concentrations to induce gene amplification. Stably transfected clones were characterized by Southern blotting; those with highest copy numbers of pFR400 alone (pFR400) or pFR400 and pMAAT2 (pFR400/pMAAT2) were expanded for further study. [3H]Oleate uptake was measured in medium containing 500 microM bovine serum albumin and 125-1000 microM total oleate (unbound oleate, 18-420 nM) and consisted of saturable and nonsaturable components. pFR400/pMAAT2 cells exhibited no increase in the rate constant for nonsaturable oleate uptake or in the uptake rate of [14C]octanoate under any conditions. By contrast, Vmax (fmol/sec per 50,000 cells) of the saturable oleate uptake component increased 3.5-fold in pFR400/pMAAT2 cells compared to pFR400, with a further 3.2-fold increase in the presence of Zn2+. Zn2+ had no effect in pFR400 controls (P > 0.5). The overall increase in Vmax between pFR400 and pFR400/pMAAT2 in the presence of Zn2+ was 10.4-fold (P < 0.01) and was highly correlated (r = 0.99) with expression of FABPpm in plasma membranes as determined by Western blotting. Neither untransfected 3T3 nor pFR400 cells expressed cell surface FABPpm detectable by immunofluorescence. By contrast, plasma membrane immunofluorescence was detected in pFR400/pMAAT2 cells, especially if cultured in 100 microM Zn2+. The data support the dual hypotheses that mAspAT and FABPpm are identical and mediate saturable long-chain free fatty acid uptake.
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PMID:3T3 fibroblasts transfected with a cDNA for mitochondrial aspartate aminotransferase express plasma membrane fatty acid-binding protein and saturable fatty acid uptake. 756 34

Adult female mink (Mustela vison) were fed a diet that contained Fusarium moniliforme culture material that provided dietary concentrations of 89 ppm fumonisin B1, 21 ppm fumonisin B2, and 8 ppm fumonisin B3 for 87 days. During the trial, there was mild lethargy in the mink fed fumonisins, but no other clinical signs or differences in feed consumption (measured during the first two weeks), body weights, or survivability were observed between the fumonisin-treated and control mink. Several hematologic parameters (mean corpuscular hemoglobin concentration, plasma total solids, and lymphocyte concentration) and serum chemical concentrations (globulin, phosphorus, potassium, blood urea nitrogen, creatinine, bilirubin, and cholesterol) and activities (alkaline phosphatase, alanine aminotransferase, amylase, and aspartate aminotransferase) were greater in the mink fed fumonisins than in the controls. Serum albumin/globulin and sodium/potassium ratios and chloride concentrations were lower in the fumonisin-fed mink than in the controls. The concentrations of free sphinganine and the ratio of free sphinganine to free sphingosine in the liver and kidneys of the fumonisin-treated mink were greater than in the control mink. No histopathologic alterations were associated with fumonisin treatment. These results indicate that long-term dietary exposure to F. moniliforme culture material containing 118 ppm total fumonisins is not lethal to adult mink, but can produce adverse physiological effects in the animals.
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PMID:Chronic toxicity of fumonisins from Fusarium moniliforme culture material (M-1325) to mink. 757 84

PD 138142-15 is a substituted urea hypolipidemic and potential anti-atherosclerotic agent. To determine the toxicity of PD 138142-15, beagle dogs were given oral doses of 1, 10, 30, and 100 mg/kg daily for 13 weeks. Two animals at 100 mg/kg were euthanized during Week 5 due to poor condition. Clinical findings included decreased serum albumin at > or = 30 mg/kg, and increased ALP (up to 30-fold) and 5'-nucleotidase activities (up to 9-fold) at doses > or = 10 mg/kg. ALT and AST activities were elevated only at 100 mg/kg. There was a two- to threefold increase in cytochrome P450 content of hepatic microsomes from all treated animals and increases in liver weights at 10 mg/kg and above. Hepatic changes included hepatocellular hypertrophy and increased cytoplasmic eosinophilia at > or = 10 mg/kg; single cell necrosis of hepatocytes was noted in moribund animals. ACTH-stimulated cortisol levels were decreased at 30 and 100 mg/kg. Adrenal cholesterol esters were decreased at 10 mg/kg and above, while total adrenal cholesterol was decreased at > or = 30 mg/kg. These changes correlated with adrenal cortical zonal atrophy, principally of the zona fasciculata and zona reticularis, present at 30 and 100 mg/kg. Plasma concentrations of PD 131842-15 increased with increasing dose; plasma levels were significantly lower during Week 12 than those on Day 1, possibly due to autoinduction. Overt hepatotoxicity occurred at 100 mg/kg, whereas hepatic changes at 10 and 30 mg/kg were consistent with cytochrome P450 induction. The hepatic lesions were reversible within 4 weeks, while adrenal lesions were still evident after 4 weeks without treatment.
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PMID:Hepatic and adrenal toxicity of a novel lipid regulator in beagle dogs. 758 16

Morbid obesity has been associated with hepatic steatosis and occasional cirrhosis. Despite producing weight loss, intestinal bypass procedures formerly performed to correct morbid obesity, often worsened steatosis and fibrosis, and occasionally resulted in hepatic failure. Current surgical procedures of choice for morbid obesity involve gastric bypass with gastrojejunostomy. Ninety-one liver biopsies taken at the time of gastric bypass for morbid obesity (mean body weight 125.8 kg), and 106 biopsies taken from the same patients from 2 to 61 months later (mean body weight 89.4 kg) were studied. Steatosis and perisinusoidal fibrosis were assessed in histologic sections. Serum albumin, alkaline phosphatase, aspartate aminotransferase (AST), and total bilirubin levels were measured before most biopsies were taken. Both pre- and post-gastric bypass hepatic steatosis varied directly with body weight (r = .5231, P < .001). Steatosis varied inversely with length of time after gastric bypass (r = .4590, P < .001). Of the original biopsies, 37% had lipid vacuoles in at least 26% of hepatocytes. After gastric bypass, 65 patients had reduced steatosis, 18 patients with no steatosis, and 5 patients with minimal steatosis had no change, and 3 patients had increased steatosis. Pre-gastric bypass biopsies from 13 patients had perisinusoidal fibrosis (PSF) that was marked with bridging in three patients, was moderate in one patient, and slight in nine patients. Following gastric bypass, PSF was eliminated in 10 patients, reduced in one patient, and the same in two patients. One patient developed PSF after gastric bypass. Of the three patients who had undergone previous intestinal bypass procedures, two had slight PSF in the biopsies taken at the time of gastric bypass, and one of these had slight PSF in the follow-up biopsy. Serum biochemical abnormalities tended to be slight. Before gastric bypass, serum albumin was low in 11% of cases, alkaline phosphatase was high in 14% of cases, AST was high in 11% of cases, and total bilirubin was high in 1% of cases. After gastric bypass, there was a small reduction in mean serum albumin from 43 g/L before to 41 g/L afterward (P < .05), and a slight rise in mean total bilirubin from 7.0 mumol/L before to 9.6 mu mol/L afterward (P < .01). Most hepatic fatty change and probably some PSF occurring in morbidly obese persons is reduced or eliminated with weight loss following gastric bypass surgery.
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PMID:Regression of hepatic steatosis in morbidly obese persons after gastric bypass. 761 Nov 76

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.
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PMID:The prognostic significance of caffeine half-life in saliva in children with chronic liver disease. 771 86


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