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)

An immunologic profile may be useful to predict the development of Acquired Immune Deficiency Syndrome (AIDS) in both high risk patient groups including homosexuals, hemophiliacs, Haitians, and users of illicit intravenous narcotics as well as the general population. We evaluated 76 consecutive, apparently healthy, adults with congenital bleeding disorders for serum beta-2 microglobulin concentration by competitive enzyme immunoassay, T-lymphocyte subpopulations with monoclonal antibodies and serum interferon by inhibition of vesicular stomatitis virus plaque forming units. Findings on physical examination were remarkable with 24% of the group having longstanding splenomegaly and 24% lymphadenopathy. beta-2 microglobulin levels were 3232 +/- 220 micrograms/l (mean +/- SEM) with normal controls 2134 +/- 119 micrograms/l. The ratio of Leu3a (helper/inducer) positive to Leu2a (suppressor/cytotoxic) positive T-lymphocytes was 1.33 +/- 0.1 (mean +/- SEM, median = 1.18). Normal control ratios were all greater than 1.35 with a mean +/- s.d. = 1.96 +/- 0.28. Abnormal ratios of T-lymphocyte subpopulations appeared to persist over time. Increases in beta-2 microglobulin correlated with an inverted helper/suppressor T-lymphocyte ratio, the presence of lymphadenopathy, and elevations in aspartate aminotransferase. Interferon was detected in 18% of patient sera. More frequently transfused and more severely affected patients had a higher frequency of immunologic abnormalities although abnormalities also occurred in some rarely and never transfused less severely affected patients. These studies document a high incidence of immunologic abnormalities in patients with inherited coagulation defects.
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PMID:Immunologic profiles of adults with congenital bleeding disorders. 608 22

A two-stage surgical occlusion of the portal vein was employed to produce hyperammonaemia in the rat. The procedure resulted in a significant rise of arterial blood ammonia level from 70 . 5 +/- 6 . 5 mumol/l (mean +/- SEM, n = 10) to 214 . 0 +/- 37 . 7 mumol/l and in a rise of venous blood ammonia from 65 . 0 +/- 9 . 4 mumol/l to 122 . 2 +/- 7 . 4 mumol/l during the first day following the complete vein occlusion. A marked increase of the arteriovenous difference of ammonia concentration from virtually zero in sham-operated controls to 72 +/- 9 (n = 8) mumol/l in rats 1 day after the surgical manipulation suggested uptake of ammonia by skeletal muscle. Rat muscle glutamine synthetase activity increased from 0 . 46 +/- 0 . 06 u/mg (n = 7) in controls to 2 . 7 +/- 0 . 3 u/mg (n = 7) on the fourth day following portal vein ligation, and muscle branched chain amino acids aminotransferase increased from 0 . 2 +/- 0 . 05 u/mg in controls to 0 . 96 +/- 0 . 1 u/mg (n = 7) during the first day of ligation. Glutamine dehydrogenase and aspartate aminotransferase activities were not affected by the surgical procedure. These observations suggest that ammonia trapping in skeletal muscle is coupled to glutamine formation via amination of glutamic acid. This conclusion was further supported by the finding that ammonia uptake correlated (r = 0 . 92) with enhanced release of glutamine from muscle and that treatment with methionine sulfoximine, a potent inhibitor of glutamine synthetase, changed the arteriovenous difference of glutamine from -0 . 92 +/- 0 . 01 mmol/l in ligated animals (net release) to +0 . 12 +/- 0 . 01 mmol/l (net uptake) in ligated and inhibitor-treated animals. Similarly, the inhibitor also abolished the arterio-venous difference of ammonia. Thus, the animal model of hyperammonaemia and the muscle enzyme assays reveal that skeletal muscle is involved in the regulation of blood ammonia level by conversion of ammonia, via glutamic acid, to glutamine.
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PMID:Ammonia uptake by skeletal muscle in the hyperammonaemic rat. 612 77

The clinical significance of serum aspartate aminotransferase (GOT) isozymes was studied in 18 patients with polymyositis. Abnormally high levels of mitochondrial GOT (mGOT) (6.2 +/- 1.2 IU/L, mean +/- SEM; normal, less than 2.0 IU/L) and cytosol GOT (sGOT) (95 +/- 21.6 IU/L; normal, less than 25 IU/L) were observed in sera. In polymyositic muscles, the sGOT level was significantly decreased but mGOT was not. The levels of serum sGOT and mGOT and the ratio of mGOT/tGOT before corticosteroid therapy correlated well with the severity of muscle weakness. Serial determination of CPK, sGOT, and mGOT during corticosteroid therapy revealed that mGOT most rapidly returned to normal. Exercise did not increase serum mGOT in polymyositis.
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PMID:Serum mitochondrial aspartate aminotransferase in patients with polymyositis. 683 Jan 52

Plasma glucagon and growth hormone concentrations were measured fasting and after oral glucose in 19 patients with portal vein block with extensive portal-systemic shunting but minimal liver cell damage, 11 cirrhotic patients and 12 matched control subjects. Portal vein block patients and controls had similar fasting glucose and glucagon levels (glucose 3.8 +/- 0.1 mmol/l VS control 3.4 +/- 0.1 mmol/l (mean +/- SEM); glucagon 57.5 +/- 9.1 pg/ml VS control 51.3 +/- 7.8 pg/ml). Cirrhotic patients were hyperglycaemic (cirrhosis 4.3 +/- 0.2 mmol/l VS control 3.4 +/- 0.1 mmol/l, p < 0.01) with significantly elevated glucagon levels (167.3 +/- 61.1 pg/ml VS control 51.3 +/- 7.8 pg/ml, p < 0.05), which suppressed towards control values after oral glucose. There was no correlation between fasting plasma glucagon levels and the degree of portal-systemic shunting in cirrhotic patients. There was a strong correlation between fasting plasma glucagon concentrations and aspartate transaminase levels (r = 0.68; p < 0.01) in cirrhotic and portal vein block patients. Significant elevations of growth hormone were seen only in cirrhotic patients. It is concluded that hyperglucagonaemia is a feature of hepatocellular damage rather than portal-systemic shunting but the relationship between elevated glucagon and growth hormone concentrations and carbohydrate intolerance in cirrhosis remains unclear.
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PMID:Hyperglucagonaemia in cirrhosis. Relationship to hepatocellular damage. 741 64

We examined the effects of temperature on the activity and steady-state kinetics of aspartate aminotransferase (EC 2.6.1.1), using purified human soluble (s-AspAT) and mitochondrial (m-AspAT) isoenzymes, human serum, and porcine s-AspAT. All enzymes obeyed similar linear Arrhenius relationships over the range 20-40 degrees C. Apparent energies of activation (52.3 kJ.mol-1) and ratios of activity between 30 and 37 degrees C (0.626) were identical for the human s- and m-AspAT. This ratio was 0.623 (SEM 0.004) for human sera; deviation from the predicted ratio by individual sera was within analytical error. Similar activity/temperature relationships were observed for porcine s-AspAT. The use of factors to convert AspAT activities at 30 and 37 degrees C influenced neither precision of measurement of frequency distributions of results. The apparent Michaelis constants for the human isoenzymes increased with temperature. The least-influenced Km was for 2-oxoglutarate and s-AspAT: K2-oxoglutarate was 0.24 mmol.L-1 at 25 degrees C and 0.29 mmol.L-1 at 37 degrees C; apparent enthalpy change for substrate binding (delta HS) was 12.1 kJ.mol-1. The largest variation was for 2-oxoglutarate and m-AspAT: K2-oxoglutarate was 0.46 mmol.L-1 at 25 degrees C and 1.02 mmol.L-1 at 37 degrees C; delta HS was 50.8 kJ.mol-1. Incubation of the human isoenzymes with substrate mixture (without 2-oxoglutarate) at 23 and 37 degrees C did not affect activity during 60 min if tris(hydroxymethyl)aminomethane buffer was used. When the isoenzymes were diluted to 10 nmol-L-1 (about 200 U.L-1) in buffer alone and incubated at 50 degrees C, m-AspAT activity was decreased by 20% after 120 min; the cytoplasmic enzyme was unaffected.
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PMID:Effects of temperature on the steady-state kinetics and measurement of aspartate aminotransferases. 746 Feb 69

The mechanism by which FK506 (FK) prevents hepatic injury induced by ischemia/reperfusion was studied. Adult Sprague-Dawley rats were subjected to 60-min normothermic liver ischemia. Animals were divided into two groups: group I, controls, saline vehicle treatment; group II, FK treatment. FK (1 mg/kg/day, p.o.) was given for 4 consecutive days prior to inducing ischemia. In addition to a survival study, plasma levels of endotoxin and serum activities of tumor necrosis factor-alpha (TNF) and aspartate aminotransferase (AST) were assessed in the blood collected from suprahepatic vena cava. Results showed: (1) FK therapy significantly improved 7-day survival (80.0%) compared with nontreated animals (50.0%, p < 0.05); (2) both TNF and endotoxin were elevated following reperfusion, reaching maximum values at 3 h after reperfusion (217.0 +/- 40.6 and 280.5 +/- 31.4 pg/ml, respectively, in the control; mean +/- SEM), and (3) serum activities of TNF and AST following reperfusion were substantially suppressed with FK treatment, whereas FK did not reduce the rise in endotoxin. These findings suggest that suppression of TNF production in response to endotoxemia might account at least in part for the protective effect of FK against ischemia-induced hepatic injury.
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PMID:Evidence that FK506 alleviates ischemia/reperfusion injury to the rat liver: in vivo demonstration for suppression of TNF-a production in response to endotoxemia. 751 91

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

It has been shown previously that erythropoietin expression in vitro by hepatoma cells increases in response to hypoxia. To verify whether hypoxia of the tumor might result in hepatic release of erythropoietin in vivo, serum erythropoietin concentrations were measured immunoenzymatically in 12 patients (5 women, 7 men) who underwent transarterial chemoembolization for hepatocellular carcinoma. Peripheral blood samples were collected at baseline, and after 6 hours and 1, 2, 3, and 7 days after the procedure. In a second set of experiments, performed in three male patients also undergoing chemoembolization for hepatocellular carcinoma, paired blood samples were collected after catheterization of the hepatic veins and of the right antecubital vein. None of the patients had erythrocytosis. In comparison with a baseline mean value +/- SEM of 100.6 +/- 12.6 micrograms/L, serum erythropoietin concentrations were the following; +6 hours, 55.4 +/- 18.0 (P < .001); +1 day, 102.4 +/- 24.7 (P = NS), +2 days, 183.0 +/- 31.1 (P < .05); +3 days, 155.0 +/- 26.0 (P < .05); +7 days, 153.3 +/- 27.4 (P < .05) (matched Student's t-test). The ratio of hepatic vein/antecubital vein serum erythropoietin concentrations increased from 0.85 at baseline to 1.30 at +2 days, paralleling the increase of aspartate transaminase (r = .914, P < .005). After chemoembolization, no correlation was found between serum erythropoietin and alpha-1-fetoprotein concentrations. The concentration of the latter, stable initially, decreased 7 days after the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hepatic release of erythropoietin induced by transarterial chemoembolization in patients with hepatocellular carcinoma. 760 7

The objective was to assess the association of fetal liver function tests in various (noninfectious) abnormal fetal conditions. Liver function tests and complete blood counts were evaluated in 72 consecutive fetal blood specimens obtained by cordocentesis. The indications for cordocentesis included: fetal malformation (24), red blood cell alloimmunization (23), possible fetal infection (17), oligohydramnios (5), and immunologic thrombocytopenic purpura (3). Statistical analysis included analysis of variance and linear regression analysis. Liver function tests including total protein, albumin, total bilirubin, alanine and aspartate aminotransferase were all within the range of previously published normal values. However, fetal gamma-glutamyltransferase levels (mean +/- SEM) were 157.1 +/- 15.1 IU/l (norm: 24.4 +/- 1.2 IU/l; p < 0.001). There were no statistically significant differences in the gamma-glutamyltransferase levels between the various groups of fetal abnormalities. Mean fetal gamma-glutamyltransferase levels in 8 normal fetuses were 106.2 +/- 17.5 IU/l. In conclusion, fetal gamma-glutamyltransferase levels are significantly elevated in several abnormal fetal conditions.
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PMID:Fetal liver function tests: umbilical cord gamma-glutamyltransferase as a marker for fetal abnormality. 791 28

Cholestasis is the predominant complication in patients with total parenteral nutrition-related liver disease. Ursodeoxycholic acid has been reported to be beneficial for patients with various chronic cholestatic liver diseases. The aim of this prospective study was to determine the effects of short-term administration of ursodeoxycholic acid in nine patients (mean age 54 years) treated with home total parenteral nutrition (31 +/- 2 (mean +/- SEM) kcal/kg per day) for 13.9 +/- 5.2 months for short bowel syndrome; all presented biological evidence of hepatic cholestasis (mean alkaline phosphatase activity 5.2 times the upper limit of the normal) which appeared during nutrition; there was no cause of hepatic dysfunction other than total parenteral nutrition. Patients received 11.2 +/- 0.8 mg/kg per day of ursodeoxycholic acid orally for 1 (n = 9) or 2 (n = 5) 2-month periods, each of which was followed by a 2-month wash-out period. Liver function tests were performed before and at the end of each period. Compared with non-treatment periods, the two periods of ursodeoxycholic acid administration induced a significant reduction in gamma-glutamyl transpeptidase (27.1% and 20.4% respectively; p = 0.001) and alanine aminotransferase serum activities (7.0% and 34.8% respectively; p = 0.01) from baseline values. Alkaline phosphatase activity (p = 0.09), aspartate aminotransferase (p = 0.11) and bilirubin (p = 0.75) serum activities underwent no significant change during the study. These preliminary results strongly suggest that short-term ursodeoxycholic acid administration leads to biochemical improvement in liver function tests in patients with total parenteral nutrition-related liver disease.
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PMID:Is ursodeoxycholic acid an effective therapy for total parenteral nutrition-related liver disease? 800 5


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