Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activities of glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT) and glutamate dehydrogenase (GLD) were determined in liver biopsy specimens and sera of patients with various liver diseases. Mitochondrial and cytosol isozymes of GOT were also separated for their assay. The activity ratio of GOT/GPT in serum was found to reflect the ratio in liver cytosol. The increased ratio in advanced or severe liver diseases, such as liver cirrhosis, was due to the greater decrease in liver cytosol GPT activity, this being pronounced in primary hepatoma. The activity of GLD decreased similarly but less markedly. The relatively greater decrease in GPT compared with GOT in advanced liver diseases was not mainly due to leakage of the enzyme from the liver, but to a specific mechanism associated with hepatic injury or its progression. Other pathological conditions of the liver such as those in obstructive jaundice and alcoholic liver injury also appeared to result in reduced liver GPT activity, which was reflected in the serum as an increased GOT/GPT ratio.
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PMID:The mechanism of release of hepatic enzymes in various liver diseases. II. Altered activity ratios of GOT to GPT in serum and liver of patients with liver diseases. 16 Jan 82

In order to establish whether a complete obstructive jaundice can abolish the accumulation of diethyl-HIDA (EHIDA) in the liver parenchyma, the common bile duct was ligated in 14 mongrel dogs. Before as well as at regular intervals after ligature of the common bile duct, a sequence scintigraphy was performed with 2 mCi 99mTc-EHIDA. For evaluation, time-activity curves (Tmax, T1/2), and analogue scintigrams as well as laboratory parameters were used for assessment. Up to seven weeks after ligation of the common bile duct, there was a marked accumulation of EHIDA in the liver parenchyma. The relative liver uptake (liver/background ratio) fell from 8.9 to 2.7, whereas conversely the cholestasis indicators aP and bilirubine rose markedly. Tmax did not show any significant alterations, whereas T1/2 was prolonged from about one week after ligation. Because of the duct ligation, there was no excretion of activity into the intestines. Immediately after ligation of the common bile duct, the gallbladder was shown up as a "hot" area in which the majority of the applied activity appeared from about one hour p.i. Begining with the fifth to the seventh day after ligation, the gallbladder was seen as a "cold" area in the liver paraenchyma. Bilirubine and aP were raised by about 50 times the initial value. With longer lasting cholestasis, the scintigram no longer altered whereas bilirubine and aP rose further. Histological examination after ligation for more than five weeks showed slight alterations as a whole. Gamma-GT and in particular GPT were likewise slightly raised compared to bilirubine and aP. The conclusion was drawn from this that the good accumulation of EHIDA in the liver parenchyma which is to be observed without exception even in cholestasis lasting for several weeks could be explained by a relatively slight hepatocellular damage. Only when there is a consecutive parenchymal damage in extrahepatic jaundice, accumulation of EHIDA in the liver can be abolished.
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PMID:[Animal experiments with 99mTc-diethyl-HIDA in acute complete bile duct occlusion (author's transl)]. 53 Aug 50

Changes in serum amino acid levels and time course of hepatic function derangements were studied in mongrel dogs with choledochus ligature and subsequent biliarly reconstruction through cholecysto-duodenostomy. In the second week after choledochus ligature, serum ammonium level increased along with intensification of jaundice. After four weeks, GPT activity was higher than GOT and plasma albumin level markedly decreased with similar reduction in serum amino acid levels. Biliary reconstruction, when performed during three or four weeks after the ligature, restored the hepatic function as well as serum amino acid levels toward normal. When it was performed in the fifth or sixth week after the ligation, the liver function did not restore and serum levels of total amino acids, essential and non-essential amino acids increased even 4 weeks lapse after reconstruction. Among the changes observed, His., Val., Ser., Arg., Leu., Ileu, Phe, and Lys. were increased, whereas Pro. and Cys. disappeared from the serum. These results suggest that recovery from metabolic changes of amino acids due to choledochus ligature depends upon the duration of obstructive jaundice, i.e., it appears necessary to perform the biliary reconstruction within four weeks after the initiation of obstruction.
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PMID:[Experimental study on changes in serum amino acid levels following choledochus ligature and subsequent biliary reconstruction (author's transl)]. 82 88

To find the feasibility of treatment for congenital bile duct atresia, we studied the usefullness of extracorporeal hemoperfusion over activated charcoal in canine obstructive jaundice. One, three and five weeks after ligation and disection of common bile duct in 5 dogs we performed the hemoperfusion over activated charcoal extracorporeally (group 3). In this animals we examined hematological and blood coagulation studies, serum electrolyte levels, kidney function tests and liver chemistries. As control in 5 animals we carried out after sham operation the perfusion without common bile duct ligation (group 2) and in 5 animals only common bile duct ligation without perfusion (group 1). In the liver chemistries we found 2 weeks after 2nd and 3rd perfusion (5 and 7 weeks after bile duct ligation) lower levels of serum bilirubin, GOT, GPT and SDH in treated group than in non-treated jaundiced animals. It suggest the effectiveness of hemoperfusion with activated charcoal in the treatment of occlusive jaundice. There were no alteration in the hematological studies, serum electrolyte levels and kidney function tests. PT and PTT was prolonged in the jaundiced animals there were no significant differences with and without hemoperfusion.
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PMID:Treatment of extrahepatic occlusive jaundice with activated charcoal hemoperfusion in dogs. 97 83

Role of platelet-activating factor (PAF) as a potential mediator of hepatic pathophysiology was investigated using a rat model of obstructive jaundice. Over a 1-wk course of bile duct ligation, a sixfold increase in tissue levels of PAF (1.57 +/- 0.43 ng/g vs. control 0.24 +/- 0.08 ng/g) occurred in the liver, whereas no change was observed in PAF levels in plasma. Concomitantly, endotoxin was detected in portal blood drawn from jaundiced rats, and antagonism of the putative effect of endotoxin by neomycin plus polymyxin B reduced local PAF concentrations in livers from jaundiced animals. Induction of neutropenia failed to alter the elevated hepatic PAF concentrations. Moreover, a large quantity of PAF was released spontaneously from Kupffer cells isolated from livers derived from jaundiced rats but not from endothelial cells or hepatocytes from the same animals. An in vitro study using cultured Kupffer cells from normal rats indicated that Kupffer cells secreted a significant amount of PAF in response to lipopolysaccharide challenge; pretreatment of cells with polymyxin B prevented this stimulated PAF release. Treatment of animals with either of two PAF receptor antagonists (BN 52021 and WEB 2170) partially prevented the increase in tissue levels of eicosanoids and O2-derived free radicals and partially alleviated liver injury as judged by the appearance of glutamate-pyruvate transaminase in the plasma of jaundiced rats. The present study indicates 1) that endogenous PAF may be an important signaling mediator for the hepatic inflammatory alterations associated with short-term bile duct ligation and 2) that the interaction of Kupffer cells with portal endotoxin is the mechanism by which PAF is produced locally.
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PMID:Role of platelet-activating factor in hepatic responses after bile duct ligation in rats. 144 33

Carcinoma of the hepatic duct bifurcation was diagnosed in a 67-year-old women with obstructive jaundice. As metastatic spread could not be demonstrated the carcinoma was removed with a view of achieving a cure (hemihepatectomy, resection of the hepatic duct and the bifurcation, cholecystectomy and hepatojejunostomy). Histological examination indicated adenocarcinoma of the biliary tract. Seven months postoperatively the patient was found to be cachectic and cough up greenish liquid sputum. Bilirubin concentration in sputum was 500 mumol/l. There was no jaundice and total bilirubin concentration was 33 mumol/l. Alkaline phosphatase was 508 U/l, but GOT and GPT were normal (23 U/l and 21 U/l). Computed tomography confirmed the clinical diagnosis of a biliobronchial fistula. The patient died 9 days after renewed hospitalization of tumour cachexia. The biliobronchial fistula was found at necropsy.
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PMID:[Bronchobiliary fistula in carcinoma of the hepatic duct bifurcation]. 145 22

Serum Mn-superoxide dismutase (Mn-SOD) was determined in patients with various liver diseases including 31 patients with primary biliary cirrhosis (PBC), 46 with hepatocellular carcinoma (HCC), 17 with liver cirrhosis (LC), 23 with chronic hepatitis (CH) and 12 patients with obstructive jaundice with an enzyme-linked immunosorbent assay using a specific monoclonal antibody. The serum level in patients with PBC (407 +/- 35 ng/ml, mean +/- SEM; n = 31) was significantly increased (p less than 0.01) compared with those of other liver diseases. Mn-SOD level did not correlate with total bilirubin level, gamma-glutamyl transpeptidase activity, alkaline phosphatase activity, alanine aminotransferase activity, IgM, or with ceruloplasmin level in the sera of the patients. When the patients with PBC were histologically subdivided into four groups according to Scheuer's classification (Scheuer PJ. Primary biliary cirrhosis. In: Scheuer PJ, ed. Liver biopsy interpretation. 3rd ed. London: Bailliere Tindall, 1980:47-56), a high level of serum Mn-SOD was noticed in the early stage as well as in the advanced stage of the disease. Immunoblot analysis confirmed the reactivity and specificity of the monoclonal antibody to the enzyme protein in the patients' sera. Immunostaining of a liver biopsy specimen from the patients with PBC revealed increased expression of the enzyme protein in damaged epithelial cells of interlobular bile ducts, bile ductules, and degenerated hepatocytes. These data suggested that free radicals including superoxide anion are possibly involved in the pathogenesis of the disease and Mn-SOD may play some role in a protection against the superoxide anion.
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PMID:Elevated level of serum Mn-superoxide dismutase in patients with primary biliary cirrhosis: possible involvement of free radicals in the pathogenesis in primary biliary cirrhosis. 168 6

The usefulness of the serum aspartate aminotransferase (AST): serum alanine aminotransferase (ALT) ratio as a guide to the presence of alcoholism was evaluated in four groups of patients. In alcoholics with elevated transaminases the mean AST:ALT ratio was found to be 1.50 (95% confidence interval (CI): 1.49-1.51), in hepatitis B infection 0.51 (95% CI: 0.50-0.52), in liver cancer 1.25 (95% CI: 1.20-1.29), and in nonmalignant obstructive jaundice 0.59 (95% CI: 0.57-0.61). In alcoholics with normal transaminases the AST:ALT ratio was 1.64 (95% CI: 1.61-1.67). The combination of an AST:ALT ratio of greater than 1.00 with an erythrocyte mean cell volume (MCV) above 90.0 fL resulted in a sensitivity of 97.3% and a specificity of 88.9% for detecting alcoholism in these four groups of patients.
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PMID:A combination of raised serum AST:ALT ratio and erythrocyte mean cell volume level detects excessive alcohol consumption. 238 15

The purpose of this investigation was to elucidate the influence of interruption of the hepatic blood flow on survival and on prolonged jaundice after biliary decompression in dogs with obstructive jaundice. There were three experimental groups. Two or three weeks after inducing obstructive jaundice by ligation of the common bile duct with cholecystectomy, the hepatic artery (group A), portal vein (group B) or both (group C) were interrupted for various intervals, with antibiotics administration. Biliary decompression was simultaneously performed with choledochoduodenostomy. The one week survival rate after the interruption of hepatic blood flow was more than 60% at 2 and 1 hours in group A, 20 and 10 minutes in group B, 10 and 5 minutes in group C at two and three weeks after biliary obstruction, respectively. Necrosis more than 50% of the liver was observed in early death cases. Edema and stasis in the bile canaliculi were markedly observed histologically in survivors in groups A and C, accompanied with significant elevations of serum T. Bil and GPT. The changes were greater in cases with longer periods of jaundice. In obstructive jaundice, hepatic artery occlusion causes hepatic necrosis, in spite of antibiotics administration, and may induce prolonged jaundice after biliary decompression. As an indicator of the prognosis, the serum total bile acid value was useful.
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PMID:[Experimental study on the interruption of hepatic blood flow in obstructive jaundice, with special reference to the causes of death and prolonged jaundice after biliary decompression]. 261 33

Serum bile acid (SBA) concentration was determined weekly for 4 weeks in dogs with experimentally induced hyperbilirubinemic liver disease. Obstructive jaundice was created in 6 dogs by surgical ligation of the common bile duct, and hepatocellular jaundice was created in 6 sham-operated dogs by administration of dimethylnitrosamine; 6 other sham-operated dogs served as controls. Serum bile acid concentration increased rapidly after bile duct ligation (from 0.6 +/- 0.1 to 69.2 +/- 15.3 mumol/L at 3 days), peaked at 14 days (247.8 +/- 54.1 mumol/L), and then gradually decreased (179.9 +/- 27.1 mumol/L at 28 days). Serum bile acid concentration in dimethylnitrosamine-treated dogs increased more gradually to 38.9 +/- 10.7 mumol/L at 28 days, at which time the serum bilirubin concentration was comparable with that of bile duct-ligated dogs. Mean total SBA values in bile duct-ligated dogs were significantly (P less than 0.01) higher than those in control and dimethylnitrosamine-treated dogs at days 3 through 28, with no overlap of individual values. Serum bile acid concentration at day 28 correlated positively (P less than 0.01) with cholestasis and bile duct proliferation observed in liver biopsy specimens, but did not correlate with necrosis or inflammation. Serum bile acid concentration also correlated positively (P less than 0.01) with serum bilirubin and cholesterol concentrations and with serum alkaline phosphatase and alanine transaminase activities. Results of the study reported here indicated a relationship between SBA concentration and cholestasis in dogs; extrahepatic bile duct obstruction resulted in the highest SBA values.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum bile acid analysis in dogs with experimentally induced cholestatic jaundice. 335 42


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