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)

A novel, simple, clinically useful quantitative liver function test, called the galactose single point (GSP) method, was developed by measurement of galactose blood concentration 1 h after galactose was administered (0.5 g/kg). It was quickly infused intravenously in 55 normal healthy volunteers, 73 patients with chronic hepatitis (CH), 36 with cirrhosis and 41 with hepatocellular carcinoma (HCC). Patients with CH diagnosis were assessed by liver biopsy. Cirrhosis was diagnosed by histological examination or a chronic hepatitis history with esophageal varices or ascites, whereas HCC was diagnosed either histologically, or cytologically proved, or as implied in the 'one imagine study' being positive with AFP > 300 ng/dl. Highly significant galactose blood levels were observed between normal healthy volunteers and patients 50, 60 and 70 min after galactose was administered. Galactose elimination capacity (GEC), modified GEC (MGEC) and consecutive GSP tests were performed in 6 healthy volunteers for 2 days. 0.64-16.87% variation was observed for each subject. The significant differences (p < 0.001) in average GSP values were 247 +/- 18.1, 422 +/- 27.3, 629 +/- 42.8 and 579 +/- 43.6 micrograms/ml for normal healthy volunteers, CH, cirrhosis and HCC patients, respectively. Highly significant correlations (p < 0.001) were obtained among GSP, GEC and MGEC for all patients. Positive correlations were observed between GSP, GEC, MGEC and AST (serum aspartate aminotransferase), ALT (serum alanine aminotransferase), serum bilirubin, albumin, prothrombin time and r-globulin. According to results obtained from 202 normal healthy volunteers and patients, the GSP method may be a simple, clinically useful quantitative measurement of liver function for the determination of a patient's residual liver function, the prognosis of liver function for patients with cirrhosis, postoperational follow-up and, finally, the timing of a liver transplant.
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PMID:Assessment of liver function using a novel galactose single point method. 133 11

The abilities of potential chemoprotectants to inhibit cytotoxicity of ricin have been determined in vitro, using the macrophage cell line J744A.1. Six compounds were tested: alpha- and beta-galactopyranosylamine; N-bromoacetyl-alpha-D-galactopyranosylamine; N-bromoacetyl-beta-D-galactopyranosylamine; N-bromoacetylglucopyranosylamine; and N-bromoacetylmannopyranosylamine. Of the six compounds which were tested, only N-bromoacetyl-alpha-D-galactopyranosylamine and N-bromoacetyl-beta-D-galactopyranosylamine exhibited significant activity against ricin toxicity, as indicated by the release of lactate dehydrogenase (LDH) and aspartate aminotransferase (AST). The alpha-isomer provided greater protection against ricin toxicity and also exhibited less inherent cytotoxicity in the absence of ricin, as compared to the beta-isomer. Neither the alpha- and beta-galactopyranosylamines nor the glucose and mannose analogs were promising as potential chemoprotectants.
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PMID:An assessment of potential chemoprotectant activity against ricin toxicity by mechanism based glycosidase inhibitors in macrophage J744A.1 cell cultures. 148 63

We studied the effect on the progression of glomerular sclerosis of two different experimental maneuvers, peritoneal dialysis and oral adsorbent, which remove circulating substances in different fashions. Munich-Wistar rats with established glomerular sclerosis, verified by renal biopsy analysis at seven weeks after subtotal nephrectomy, were treated for four weeks with either peritoneal dialysis (PD) or oral charcoal adsorbent (AST-120). Treatment was initiated at eight weeks. Rats were paired in treatment and control groups according to the similarity in the degree of sclerosis determined at biopsy with a minimum of 50 glomeruli analyzed. Systolic blood pressure and BUN and creatinine clearance, measured at seven to eight weeks, were not different among groups. In Group 2 rats, PD was performed with 1.5% dextrose for eight one-hour cycles, six days per week, while Group 1 control rats had zero indwelling time of the dialysate. Group 4 rats received AST-120, an oral adsorbent charcoal, mixed 5% by weight with standard rat chow and given ad libitum from 8 to 12 weeks after subtotal nephrectomy, while control Group 3 rats received only rat chow. Whole kidney GFR at 12 weeks was significantly higher in Group 2 PD versus Group 1 control (0.50 +/- 0.08 vs. 0.30 +/- 0.05 ml/min, P less than 0.05). There was no statistical difference for BUN and whole kidney creatinine or inulin clearance in Group 4 AST-120 treated versus Group 3 control rats. Light microscopic studies in autopsy specimens revealed that both PD and AST-120 attenuated progression of glomerular sclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role for "uremic toxin" in the progressive loss of intact nephrons in chronic renal failure. 178 46

The effect of parenteral amino acid administration on nutritional state, liver function and mortality was assessed in patients with severe alcoholic hepatitis. Twenty-eight patients received 2 l/day of a solution of dextrose (65 gm/L) and amino acids (25.8 gm/L) for 1 mo, whereas 26 received only the dextrose solution. All patients were allowed to eat a standard hospital diet. During the month in the hospital, there were six deaths in the treatment group and five deaths in the control group. Nitrogen balance improved in the treated group, but not in the control group. Creatinine-height index, triceps skin fold measurement and levels of serum albumin and prealbumin increased similarly in both groups. Serum retinol binding protein increased more in the treatment group than it did in the control group, and transferrin was increased only in the treatment group. Serum bilirubin, type III amino-terminal procollagen peptide and aminopyrine clearance improved more in the treatment group than in the control group, whereas serum AST and prothrombin time improved in the treatment group but not in the control group. Cumulative 2-yr survival rates from the day of entry into the study were 42% and 38% in the treatment and control groups, respectively. Patients who survived 2 yr and patients in the treatment group who died during the 2-yr follow-up had continued improvement in serum retinol binding protein, transferrin, bilirubin and prothrombin time. These parameters were unchanged in patients in the control group who died during follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of parenteral amino acid supplementation on short-term and long-term outcomes in severe alcoholic hepatitis: a randomized controlled trial. 195 59

A Pacific white-sided dolphin (Lagenorhynchus obliquidens) developed clinical signs, serum biochemical values, and serologic viral markers consistent with chronic persistent hepatitis caused by a hepatitis B-like virus. The hepatitis had a sporadic cyclical pattern of lethargy, inappetance, and icterus, with leukocytosis and increased serum activities of alanine transaminase, aspartate transaminase, and gamma-glutamyltransferase. The serum from this dolphin contained hepatitis B virus core antibodies, hepatitis B surface antibodies, and hepatitis B viral DNA. Supportive treatment consisted of administration of antibiotics, cimetidine, menadiol sodium diphosphate, and vitamin/dextrose supplementation. A clinically normal killer whale (Orcinus orca) housed in the same pool had serum hepatitis B surface antibodies, suggesting immunologic responsiveness and that this disease was not species-specific.
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PMID:Hepatitis B-like infection in a Pacific white-sided dolphin (Lagenorhynchus obliquidens). 229 47

In an open, exploratory study, the safety of ursodeoxycholic acid (UDCA) in the treatment of primary biliary cirrhosis (PBC) was investigated. Seven patients in stages I to III and two patients in stage IV were treated for 1 year with 1 g/day of UDCA. Clinical symptoms, and alkaline phosphatase, gamma-glutamyltransferase, alanine aminotransferase (GOT) and aspartate aminotransferase (GTP) levels improved significantly within three months and remained at the lower levels for the period of observation. Results of the galactose elimination capacity (4.7 +/- S.D. 1.4 mg/min per kg) and the aminopyrine breath test (0.60 +/- 0.33% dose/kg per mmol CO2) remained unchanged for 1 year. In all patients total serum bile acids increased and quantitatively UDCA became the most important bile acid. In patients in stages I to III this increase, however, was modest, whereas in patients in stage IV, total serum bile acids reached levels of 140 and 157 mumol/l and UDCA, levels of 90 and 103 mumol/l, respectively. It is concluded that UDCA appears to be safe only in stages I to III and that prognostic stratification based on bile acid levels or on the histological stage of the disease should be an important aspect of controlled clinical trials.
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PMID:Ursodeoxycholic acid in primary biliary cirrhosis: no evidence for toxicity in the stages I to III. 236 81

A previously healthy 35-year-old woman was seen at 37 weeks' gestation with a 10-day history of fever, vomiting, diarrhea and malaise. Serum laboratory findings included elevation of serum bilirubin and AST, prolongation of serum prothrombin time and a positive monospot. A tentative diagnosis of acute fatty liver of pregnancy was made, and a healthy male infant was delivered by emergency cesarean section because of fetal distress. Over the subsequent 3 days, acute progressive oliguric renal failure, disseminated intravascular coagulation, hypoglycemia requiring intravenous dextrose infusion and pancreatitis developed; her mental status progressed to stage III encephalopathy. Quantitative computed tomography estimated the liver volume to be 770 cm3. The decision to proceed with orthotopic liver transplantation was made on the basis of progressive clinical deterioration despite aggressive support and because of her small liver size. After transplant, the patient's multisystem failure rapidly reversed. Histopathological examination of the native liver demonstrated predominantly zone 3 microvesicular steatosis with characteristic ultrastructural changes consistent with acute fatty liver of pregnancy. Southern blot analysis for Epstein-Barr virus DNA was negative. We conclude that orthotopic liver transplantation should be considered for the small group of patients with fulminant hepatic failure associated with acute fatty liver of pregnancy who manifest signs of irreversible liver failure despite delivery of the fetus and aggresive supportive care.
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PMID:Fulminant hepatic failure caused by acute fatty liver of pregnancy treated by orthotopic liver transplantation. 240 63

We recently described a preferential reduction of the secretory response to nutrient secretagogues (glucose; leucine plus glutamine) in islets maintained in culture after in vitro exposure to streptozotocin (SZ). The present study is an attempt to further clarify the biochemical mechanisms behind this defective insulin response. Mouse pancreatic islets were collagenase isolated and, after 4-5 days in culture, exposed during 30 min at 37 C to 1.8 mM SZ or vehicle alone (controls). The islets were subsequently cultured for 7 days in medium RPMI 1640 plus 10% calf serum, before the enzymatic and metabolic studies were performed. The activities of the glycolytic enzymes, hexokinase, glucokinase, and glyceraldehyde 3-phosphate dehydrogenase, were similar in the control and SZ-exposed islets. The relative amount of cytosolic and mitochondria-bound hexokinase was also unaffected by SZ. However, there was a 30-40% decrease in the activity of NAD+- and NADP+-dependent glutamate dehydrogenase and glutamate-aspartate transaminase in the SZ-treated islets. This coincided with a 40% decrease in L-[U-14C]glutamine oxidation in the SZ-treated islets. The D-glucose catabolism was further examined in the presence of D-[5-3H] and D-[6-14C] glucose. There was no difference between control and SZ islets in terms of glucose utilization at either 1.7 or 16.7 mM glucose. The oxidation of D-[6-14C]glucose was nevertheless decreased by more than 50% in SZ islets incubated at 16.7 mM (but not 1.7 mM) glucose. Altogether, these converging observations suggest a perturbation of distal regulatory processes, apparently at the mitochondrial level, in the D-glucose and L-glutamine catabolism of SZ-exposed islets. Whether this reflects a primary action of SZ on the islet mitochondria, or an inhibitory effect of SZ on the synthesis of mitochondrial enzymes, as a result of nuclear DNA damage, remains to be elucidated.
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PMID:Defective catabolism of D-glucose and L-glutamine in mouse pancreatic islets maintained in culture after streptozotocin exposure. 296 23

Hepatic function can be monitored using exogenous (e.g., sulfobromophthalein, indocyanine green, antipyrine, aminopyrine, galactose) and endogenous substances (e.g., bile acids, PT/PTT, albumin, ammonia, bilirubin). Test of hepatic necrosis include aspartate aminotransferase, and alanine aminotransferase. The hepatobiliary system can be assessed using alkaline phosphatase, 5'-nucleotidase, gamma-glutamyl transpeptidase, ultrasound, and iminodiacetic acid scans.
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PMID:Monitoring hepatic function. 306 53

Twenty-eight patients with biopsy or clinical acute alcoholic hepatitis were prospectively randomized to 21 days of conventional therapy (14 control patients) or, in addition, to 2 L/day of a peripheral iv infusion of a 900 mosmol amino acid-glucose solution (14 patients). Cirrhosis was present in 64% of controls and in 54% of infused patients. There were three deaths in controls and one in the infused group. There were no significant intergroup differences in mortality, clinical findings, liver tests, or functional mass by the galactose elimination capacity either at entry or after completion of the study. In controls, there was intragroup improvement in serum bilirubin (p = 0.033) and AST (p = 0.008) but not in other "liver tests" or in functional hepatic mass by galactose elimination capacity. In infused patients there was improvement in bilirubin (p = 0.001), AST (p = 0.008), and serum albumin (p = 0.016). Improvement in functional mass by galactose elimination capacity was significant at the p = 0.052 level. Hyaline was initially present in six of eight pairs of biopsies in both groups. After treatment, five of six pairs in controls but only one of six pairs in the infused group still had hyaline (p = 0.03). This latter finding, if confirmed in larger groups, may be of considerable clinical importance. It is suggested that 3- to 4-wk trials of such protocols may require a longer duration of follow-up in greater numbers of patients to detect important advantages of amino acid-glucose infusions which are only implicit in these findings.
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PMID:A prospective randomized clinical trial of peripheral amino acid-glucose supplementation in acute alcoholic hepatitis. 330 90


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