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:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The amphistomes Gigantocotyle explanatum and Gastrothylax crumenifer utilize leucine, alanine, proline and methionine during in vitro incubations. Autoradiography on sections of these flukes reveal a time-dependent differential incorporation of tritium-labelled amino acids in various tissues. The tegument appears to be the primary surface through which amino acids are absorbed. Following absorption, the reappearance of [3H]-leucine and [3H]-alanine on the tegumental surface during late chase periods indicates their possible involvement in tegumental secretion. A combination of diffusion and carrier-mediated uptake, possibly involving gamma-glutamyl transpeptidase, is indicated. The transport loci show differences in carrier-affinity (Kt) and maximum uptake velocities (Vmax) for amino acids under study, which suggest multiple transport molecules. Metabolic studies reveal that aspartate, alanine, ornithine, proline, leucine and methionine undergo transamination through 2-oxoglutarate-linked transaminases, distributed in the cytosolic and mitochondrial fractions of G. explanatum and G. crumenifer. With the exception of alanine transaminase, the enzyme levels in the cytosolic fraction were higher than the mitochondrial fraction of the two amphistomes. Predominantly cytosolic glutamate dehydrogenase which was comparatively higher in G. explanatum, catalyse amination of alpha-ketoglutarate. A high level of cytosolic arginase alone does not indicate a functional urea cycle. A tentative pathway of amino acid metabolism in these amphistomes is proposed.
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PMID:[3H]-amino acid uptake and metabolic studies on Gigantocotyle explanatum and Gastrothylax crumenifer (Digenea: Paramphistomidae). 763 32

The presence of hepatic steatosis was determined in 180 middle-aged male workers by ultrasonography and was found in 39 (22%) of them. Body mass index (BMI), systolic and diastolic blood pressure (BP) and serum levels of asparate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (gamma-GTP) were higher in the subjects with hepatic steatosis. Although the volume of alcohol consumed in a week did not differ between the subjects with and without hepatic steatosis, the hepatic steatosis was thought to relate to both increased body mass and alcohol consumption because the elevations of serum AST and gamma-GTP in the subjects depended largely on alcohol consumption but not on BMI. The results of 75 g oral glucose tolerance test showed a higher blood glucose at 120 minutes and a higher plasma immunoreactive insulin at baseline, 60 and 120 minutes in the subjects with hepatic steatosis, being adjusted for age, BMI and alcohol consumption. The significant association between serum gamma-GTP and BP, which had been often observed in alcohol consumers, was no longer significant after adjustment for plasma insulin levels whereas plasma insulin showed a significant association with BP. These results suggest the possibility that hypertension in alcohol consumers, and also in obese people, relates at least partly to hyperinsulinaemia associated with progression in hepatic steatosis.
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PMID:Association between hepatic steatosis, insulin resistance and hyperinsulinaemia as related to hypertension in alcohol consumers and obese people. 775 70

The use of herbal and other "natural" health products by healthy and ill people is more common than is appreciated by many health care providers. Since most of these substances are not categorized as medicines, they are exempt from U.S. Government approval processes, and are essentially uncontrolled. In this article we describe a patient who developed painless jaundice, fatigue, and pruritus after taking chaparral tablets, 160 mg/day, for approximately 2 months. Serial liver biopsies and serum chemistries documented severe cholestasis and hepatocellular injury, i.e., a severe cholangiolitic hepatitis. Serum enzyme levels were markedly elevated: alk. phos. to four-fold, alanine aminotransferase and aspartate aminotransferase to 25-fold, total bilirubin to 30-fold, and gamma-glutamyl transpeptidase to 35-fold. Endoscopic retrograde cholangiopancreatography showed smooth, but severely narrowed biliary ducts without sclerosing cholangitis, distal obstruction, tumor, or stenosis. The diagnosis remained in doubt until the publication of two cases of chaparral hepatotoxicity. Because of the similarity of our patient's illness to those cases we concluded that chaparral was almost certainly the cause. Chaparral, also known as creosote or greasewood, is used by some practitioners to treat a diverse group of ailments including ethanol withdrawal. This report should heighten the awareness by primary care physicians and gastroenterologists that any chaparral herbal preparation is a potential hepatotoxin that can lead to serious illness.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cholestatic hepatitis after ingestion of chaparral leaf: confirmation by endoscopic retrograde cholangiopancreatography and liver biopsy. 780 38

A total of 107 cancer patients were treated with 148 cycles of subcutaneous (SC) immunotherapy employing interleukin-2 (rIL-2) and/or interferon-alpha (rIFN-alpha). The systemic toxicities of SC cytokine therapy were retrospectively evaluated with regard to hepatic and metabolic adverse effects, and compared to adverse effects previously reported upon high- or intermediate-dose intravenous (IV) rIL-2 therapy. Our study cohorts consisted of 15 patients who received SC rIL-2 at doses of 4.8-14.4 million IU/m2/day on 5 days per week for a total of 8 weeks, 20 patients who received rIFN-alpha 2b at 3.0-6.0 million U/m2/day thrice weekly for a total of 6 weeks, and 72 patients who were given SC rIFN-alpha 2b at 6.0 million U/m2/day thrice weekly plus SC rIL-2 at 14.4-18.0 million IU/m2/day on days 1 and 2, followed by 4.8 million IU/m2/day, 5 days per week for 6 consecutive weeks. These treatment regimens were well tolerated in the outpatient setting; no toxic deaths occurred, and none of the patients developed life-threatening toxicity. Upon SC rIL-2/rIFN-alpha combination therapy, we observed mild decreases in plasma protein and albumin levels (mean nadir +/- standard deviation, 67 +/- 5 g/L and 38.8 +/- 3.9 g/L, respectively), minor albeit significant increases in serum total bilirubin levels (mean peak +/- standard deviation, 7.8 +/- 3.1 mumol/L), serum aspartate aminotransferase (25.9 +/- 9.9 U/L), alanine aminotransferase (42.0 +/- 45.9 U/L), alkaline phosphatase (301 +/- 255 U/L), lactate dehydrogenase (230 +/- 64 U/L), gamma-glutamyl transpeptidase (147 +/- 141 U/L) activities and triacylglyceride (2.6 +/- 0.9 mmol/L) concentrations. Cholinesterase activities (mean nadir +/- standard deviation, 42.6 +/- 13.7 kU/L), and serum cholesterol levels (4.4 +/- 0.9 mmol/L) decreased upon SC rIL-2/rIFN-alpha combination therapy. These mild clinical side effects and laboratory changes were in marked contrast to a multitude of dose-limiting and life-threatening adverse reactions described upon IV rIL-2 therapy. It is concluded that low-to intermediate-dose SC rIL-2/rIFN-alpha combination therapy as used in this study, can be given in the outpatient setting with good practicability and excellent safety.
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PMID:Hepatic and serologic toxicity of systemic interleukin-2 and/or interferon-alpha. Evidence of a risk-benefit advantage of subcutaneous therapy. 791 Jul 16

Liver injury produced by CCl4 depends on its metabolism by the liver cytochrome P450 enzyme system to a highly reactive intermediate (CCl3.). Cimetidine impairs cytochrome P450 and stimulates regenerative processes acting on DNA synthesis. This work was performed to investigate whether cimetidine may prevent CCl4-induced liver cirrhosis. Male Wistar rats were used: animals in group 1 received CCl4 (0.04 g per 100 g, i.p.) three times a week for 8 weeks; group 2 was treated with CCl4 plus cimetidine (120 mg kg-1, p.o.) three times a week for 8 weeks; group 3 received CCl4 for 8 weeks and then cimetidine for 4 weeks. Alkaline phosphatase, gamma-glutamyl transpeptidase (gamma-GTP) and alanine aminotransferase (ALT) activities, as well as protein and bilirubin, were measured in serum; collagen and lipoperoxidation were quantified in liver. Intoxication with CCl4 increased (P < 0.05) serum activities of alkaline phosphatase, gamma-GTP and ALT, and bilirubin concentration; liver collagen and lipoperoxidation were also increased. Cimetidine treatment prevented or reverted the increases in the three enzyme activities and in bilirubin content and the fall in proteins. It is worth noting that cimetidine co-treatment completely prevented both the increase in collagen content and the lipid peroxidation. The protective effect of cimetidine can be attributed to a reduction in cytochrome P450. However, it could also stimulate regenerative processes.
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PMID:Cimetidine prevents and partially reverses CCl4-induced liver cirrhosis. 791 3

HBsAg-positive patients with end-stage renal failure have a high prevalence of asymptomatic chronic hepatitis. In order to determine the usefulness of hepatic cytology in the diagnosis of liver disease, the findings of hepatic needle core biopsy (NCB) and fine needle aspirative biopsy (FNAB) were compared in 15 HBsAg-positive uremic patients. The patients, aged 42 +/- 12 years, 14 males, were on hemodialysis for periods ranging from 13 to 105 months. The NCB was processed by standard histologic and immunohistochemical techniques and FNAB by the conventional technique, using the total corrected increment score (TCI). Plasma samples were collected for evaluation of hepatic function and for viral serologic tests. In 15 patients a diagnosis was made by NCB: normal, 7 cases; chronic persistent hepatitis, 4 cases; and chronic active hepatitis, 4 cases. When the patients were allocated into two groups according to the severity of the liver histologic findings [group I--minor changes (normal+chronic persistent hepatitis), 11 patients; group II--major changes (chronic active hepatitis), 4 patients], statistically higher values were found in the major changes group for alanine aminotransferase (49 +/- 33 vs. 24 +/- 11, p = 0.04), gamma-glutamyl transpeptidase [148 +/- 53 vs. 38 +/- 28, p < (minor) 0.02] and TCI (3.7 +/- 1.2 vs. 2.5 +/- 0.8, p = 0.04). In conclusion, liver FNAB can be useful as a screening procedure for the identification of liver histologic changes (minor or major) in uremic HBsAG-positive patients.
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PMID:Fine needle aspirative biopsy of the liver in HBsAG-positive patients with end-stage renal failure. 793 57

Nine rabbits were fed with Clonorchis sinensis metacercariae (MC) and the blood samples chronologically obtained were analyzed biochemically. Rabbits infected by less than 100 flukes were grouped into Group I, and by 100-250 flukes into Group II. The serum level of alanine aminotransferase (ALT) was increased from 3 weeks after the infection of the metacercariae (AIM) and showed a peak at 8 weeks, and decreased from 12 weeks AIM. The serum level of aspartate aminotransferase (AST) was raised to 92.3 +/- 65.4 U/L at 3 weeks AIM and stayed high until 8 weeks, then lowered thereafter. The serum level of gamma-glutamyl transpeptidase (gamma-GT) was increased rapidly to the highest value (18.9 +/- 14.6 U/L) at 16 weeks AIM, and decreased to the control level after 20 weeks. The serum level of alkaline phosphatase (ALP) was headed down from the early infection to 52 weeks AIM. The serum cholesterol level was increased from 8 weeks and reached at a peak 16 weeks AIM, and decreased thereafter to the control level. It is suggested that serum ALT, AST, ALP and gamma-GT tests be useful to diagnose the early infection of C. sinensis.
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PMID:Liver function in Clonorchis sinensis-infected rabbits. 795 43

Blood alpha-fetoprotein, carcinoembyronic antigen, CA-19-9, alkaline phosphatase, gamma-glutamyltranspeptidase, alanine aminotransferase, aspartate aminotransferase, sorbitol dehydrogenase, glutamate dehydrogenase, hemoglobin and red cell sedimentation rate were measured in patients with stages III and IV gastric carcinoma and patients with benign diseases of the stomach. Alanine aminotransferase, sorbitol dehydrogenase and glutamate dehydrogenase were found diagnostically not informative in gastric carcinoma stages III and IV. A complex of measurements of alpha-fetoprotein, alkaline phosphatase, gamma-glutamyl transpeptidase and aspartate aminotransferase detected gastric carcinoma metastases to the liver in 84.6% of cases as against 61.5% detected by measurements of alpha-fetoprotein alone. A complex of measurements of carcinoembryonic antigen, CA-19-9, alkaline phosphatase, gamma-glutamyl transpeptidase, aspartate aminotransferase helped differentiate between gastric carcinoma stages III and IV. A complex of measurements of carcinoembryonic antigen, CA-19-9, alkaline phosphatase, gamma-glutamyl transpeptidase, aspartate aminotransferase, hemoglobin, and red cell sedimentation rate improved the diagnostic sensitivity in detection of gastric carcinoma stages III and IV to 70.8 and 100%, respectively.
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PMID:[Laboratory tests in the diagnosis of stomach cancer]. 800 Jul 94

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

S-adenosyl-L-methionine (ademethionine) has been recently proposed as a therapeutic agent for the treatment of intrahepatic cholestasis (IHC), a syndrome that overlaps with many different types of liver diseases. To obtain a global assessment of the results of the therapeutic efficacy of this compound, a meta-analysis of 6 controlled clinical trials with ademethionine in the symptomatic treatment of IHC of liver diseases and pregnancy was carried out. The therapeutic response to ademethionine treatment, for 15 to 30 days, proved to be superior to placebo, as assessed by resolution of pruritus, normalisation or 50% improvement in serum total bilirubin, serum conjugated bilirubin, alanine aminotransferase, gamma-glutamyl transpeptidase and alkaline phosphatase. At present, the therapeutic effect of ademethionine should be regarded as symptomatic, but long term studies on the effect of drug administration on the course of the disease and survival are being performed.
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PMID:[A meta-analysis of therapeutic trials with ademetionine in the treatment of intrahepatic cholestasis]. 811 21


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