Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aspartate aminotransferase in the sera of normal subjects and of patients with hepatic diseases has been immunologically separated into two isoenzymes, cytosolic aspartate aminotransferase and mitochondrial aspartate aminotransferase. The activity of the isoenzymes was measured in three different buffer solutions with or without pyridoxal 5'-phosphate. To attain maximal activation, the apoenzyme of mitochondrial fraction must be preincubated with pyridoxal 5'-phosphate longer than that of the cytosolic fraction in either of the three reaction mixtures. In most sera the activity of both isoenzymes increased substantially in the presence of pyridoxal 5'-phosphate regardless of the type of buffer solutions. Both the apoenzymatic activity and the ratio of apo- to holo-enzymatic activity of each of the isoenzymes varied among samples from the patients with hepatic diseases. However, significantly high ratios of apo- to holo-enzymatic activity of both isoenzymes were observed in the patients with hepatoma in contrast with those with other hepatic diseases. These findings suggest that the simultaneous measurement of both apo- and holo-enzyme activities of aspartate aminotransferase isoenzymes may be useful in the clinical assessment of hepatic diseases.
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PMID:Apoenzyme of aspartate aminotransferase isozymes in serum and its diagnostic usefullness for hepatic diseases. 22 64

Response to hepatitis B virus (HBV) infection [HBV surface antigen (HBsAg) and antibody to HBsAg (anti-HBs)], serum iron, total iron-binding capacity, hematological status (erythrocytes, Hb, and hematocrit), and evidence of liver damage (serum glutamic pyruvic transaminase; aspartate aminotransferase, L-aspartate:2-oxoglutarate aminotransferase, EC 2.6.1.1) were determined for 201 patients on chronic renal dialysis. Four factors-serum iron level, transminase level, sex, and HBV response [i.e., infected-HBsAg(+) (HBsAg positive), anti-HBs(+) (anti-HBs positive), or no response]-were analyzed simultaneously to test the hypothesis that serum iron is higher in those with HBsAg in their serum than in those without HBsAg, independent of the transaminase level. Four independent, statistically significant two-factor interactions were identified. (i) Serum iron is higher in those HBsAg(+). (ii) Serum iron is higher in those with increased transaminase. (iii) Transaminase is higher in those HBsAg(+). (iv) Males are more likely to be HbsAg(+) and females are more likely to be anti-HBs(+). Also, those who are HBsAg(+) have significantly higher percent iron saturation (serum iron/total iron-binding capacity). That is, the hypothesis was supported by the findings. Several additional biological hypotheses are suggested, including a possible role of increased iron levels in susceptibility and response to HBV infection and the possible relationship between higher iron levels and the likelihood of HBV infection progressing to primary hepatocellular carcinoma. In addition, further tests of the initial hypothesis in nonhospitalized populations with endemic HBV infection are proposed.
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PMID:Serum iron levels and response to hepatitis B virus. 28 82

Six patients with hepatitis B surface antigen-positive (HBsAg-pos) chronic liver disease have been treated with transfer factor (TF) prepared from leucocytes of normal blood donors with no history of hepatitis, and with TF from subjects recently recovered from type B hepatitis. In three patients there were transient elevations of aspartate transaminase (AsT) after 'specific' TF, representing damage or destruction of hepatocytes, and in two of these patients there was coincidental complement consumption, suggesting that TF had stimulated production of antibody. In one other patient there was an increase in E-rosetting lymphocyte (ERL) concentration representing a change in T-lymphocyte reactivity. One of the two patients who had no measured response to TF had a primary liver cell carcinoma and was receiving prednisolone therapy. TF prepared from subjects who have recently recovered from type B hepatitis may have temporarily altered the immunological status of patients with HBsAg-pos chronic liver disease, but it did not have a beneficial therapeutic effect.
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PMID:Transfer factor in the attempted treatment of patients with HBsAg-positive chronic liver disease. 60 32

Increased concentrations of neopterin have been found in conditions causing a stimulation of cellular immunity, including various malignancies. In liver diseases, serum or urinary neopterin levels have been studied in acute viral hepatitis, chronic hepatitis, fatty liver and liver cirrhosis. In the present study neopterin serum levels have been measured in 16 patients with hepatocellular carcinoma (HCC), in 32 patients with liver cirrhosis, and in 28 healthy subjects as controls. Mean values of serum neopterin were significantly increased (p < 0.01) in patients with HCC (15.89 +/- 6.34 nmol/l) when compared with those of normal subjects (4.74 +/- 2.13 nmol/l), but no difference was observed between patients with HCC (associated or not with liver cirrhosis) and patients with liver cirrhosis. Neopterin concentrations are not affected by liver cirrhosis aetiology, nor by its clinical severity, and are not correlated to the values of serum alpha-fetoprotein, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl-transferase, and gamma-globulin. The results show that there is a consistent overlap of values in patients with HCC and liver cirrhosis; macrophage activation seems to be a feature of chronic liver diseases, irrespective of HCC development.
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PMID:Serum neopterin levels in patients with hepatocellular carcinoma. 128 21

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 Cu concentration was about 40 and 60 times higher in the liver in Long-Evans with a cinnamon-like coat color (LEC) rats aged 80 days (without hepatitis) and 130 days (with hepatitis), respectively than in the liver in Fischer rats. Most hepatic Cu was recovered in the cytosol fraction. Furthermore, about 96% and 84% of the cytosolic Cu was found in the metallothionein region on a Sephadex G-75 column in LEC rats aged 80 and 130 days, respectively. The hepatic metallothionein concentration was about 130 to 140 times higher in LEC rats than in Fischer rats when the concentration was expressed as metallothionein-bound Cu. Three forms of Cu-metallothionein were isolated by DEAE-cartridge. Although the concentration of hepatic Cu-metallothionein and its composition of polymorphic form were not changed greatly in hepatitis phase (in the 130-day-old LEC rats), activities of serum enzymes, aspartate aminotransferase (GOT) and alanine aminotransferase (GPT) were increased significantly. The LEC rat showed a significantly low concentration of biliary Cu and markedly low activity of ceruloplasmin (as ferroxidase). Serum Cu showed a low concentration in the 80-day-old LEC rats, but recovered to the control level in the 130-day-old LEC rats. The abnormal accumulation of Cu may be due to the inherent reduction of excretion of Cu into the bile and blood. Such deposition may be a trigger for the onset of the spontaneous hepatitis occurring at 90-120 days after birth and for the onset of hepatoma later.
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PMID:Excessive accumulation of hepatic copper in LEC rats aged 80 days without hepatitis and 130 days with hepatitis. 144 42

The activities of serum malate dehydrogenase (MDH) and its mitochondrial isoenzyme (MDHm) were studied in sera of patients with liver disease. They proved to be more useful than those of aspartate aminotransferase (AST) and its mitochondrial isoenzyme for detection of hepatocellular carcinoma and acute circulatory failure, and for estimation of the severity of acute hepatitis. The N/T value measuring system, which is adaptable for autoanalysis and allows simultaneous determination of activities depending on NAD and thionicotinamide adenine dinucleotide (thio-NAD), yields both the total activity of MDH and the N/T value which was correlated significantly with MDHm/MDH (r = 0.748). Assay of MDH and its mitochondrial isoenzyme in association with the N/T value measuring system seems to be more useful and less time consuming for estimation of the severity of liver diseases than that of AST and its mitochondrial isoenzyme.
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PMID:Clinical usefulness of malate dehydrogenase and its mitochondrial isoenzyme in comparison with aspartate aminotransferase and its mitochondrial isoenzyme in sera of patients with liver disease. 217 15

The aim of our work was to assess the performance of tissue polypeptide antigen in detecting hepatocellular carcinoma in cirrhotic patients, while also checking for any influence of liver dysfunction on the serum level of the marker. One hundred and twenty-five consecutive cirrhotic patients, 35 with and 90 without, hepatocellular carcinoma were studied. Tissue polypeptide antigen had a different distribution in the two groups and the best diagnostic accuracy with 48.6% sensitivity and 85.6% specificity was found at the cut-off value of 240 UL-1. In cirrhotic patients significant linear correlations were found between tissue polypeptide antigen and alanine-transaminase, aspartate-transaminase, G-glutamyl-transpeptidase and alkaline phosphatase; there was no correlation with bilirubin or pseudo-cholinesterase. In patients with hepatocellular carcinoma a significant linear correlation was found only with alanine and aspartate transaminase and G-glutamyl-transpeptidase. The analysis of covariance still showed a significant difference between mean tissue polypeptide antigen levels in the two groups also accounting for covariates. These results suggest that: a) the liver dysfunction may be involved in increasing tissue polypeptide antigen values; b) tissue polypeptide antigen has a different distribution in cirrhotic patients with and without hepatocellular carcinoma also accounting for covariates; these findings further support the specificity of tissue polypeptide antigen.
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PMID:The serum tissue polypeptide antigen in the detection of hepatocellular carcinoma in cirrhotic patients. 217 22

The inner mitochondrial membranes from bovine heart, rat liver, and Morris hepatoma 7777 all bound the mitochondrial isozymes of aspartate aminotransferase and malate dehydrogenase with comparable affinities and binding ratios (mg of enzyme bound per mg of membrane protein). A low molecular weight fraction separated from a detergent extract of the heart membrane by chromatography on Sephacryl S-300 contained most of the binding activity of the extract for the aminotransferase and had a dissociation constant for the aminotransferase of 0.2 microM. The protein component of the membrane binding sites for the aminotransferase was apparently present in this fraction because binding activity was largely eliminated by proteolysis with trypsin. When this fraction was chromatographed on an aminotransferase affinity column, only the portion that was bound and eluted by 0.25 M KCl associated with added aminotransferase. Unlike the membrane, which was markedly inhibited by the non-ionic detergent Genapol but was inhibited only 20% by trypsin, the binding activity of this subfraction was completely inhibited by trypsin but not by Genapol. This suggests, on the membrane, that the aminotransferase binds to the binding protein and is then transferred to lipids specifically associated with the binding protein. These putative lipids are presumably removed on the affinity column. Although the yield of the binding protein was low, there is probably ample binding protein in mitochondria to accommodate the aminotransferase. In every case, binding of the aminotransferase to the membrane inactivated the malate dehydrogenase binding site whereas malate dehydrogenase had little effect on the binding of the aminotransferase and only associated with the higher molecular weight fractions from the Sephacryl column that contained Complex I activity. Inactivation of the malate dehydrogenase site by the aminotransferase, but not vice versa, could result from aminotransferase associating with the binding protein and malate dehydrogenase with Complex I followed by association of the enzymes with lipids located in the same region of the membrane. However, since aminotransferase is more cationic, it is not displaced readily from the lipids by malate dehydrogenase. The relevance of these interactions to the organization of the enzymes is discussed.
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PMID:Interactions among mitochondrial aspartate aminotransferase, malate dehydrogenase, and the inner mitochondrial membrane from heart, hepatoma, and liver. 224 39

The promoter of the gene coding for the rat cytosolic aspartate aminotransferase was cloned from a Charon 4A genomic library. We have sequenced a 1.1-kilobase PstI-PstI fragment which contains the first exon of the gene, the beginning of the first intron and 682 base pairs of the 5' regulatory region (+1 being the A of the first ATG codon), which exhibits promoter activity. The promoter region is G + C rich, does not include any TATA-like element, but has 4 putative Sp1-binding sites and 6 regularly spaced CCAAT boxes. The promoter activity of the 5' regulatory region, as well as its sensitivity to glucocorticoids, were assessed by transient gene expression assays after fusion to the chloramphenicol acetyltransferase gene in the hepatoma cell lines HepG2 and Fao. Multiple transcription start sites were found on the gene over a short distance (55 base pairs), but they were differentially regulated by glucocorticoids as determined by both primer extension analysis and S1 mapping. In particular, transcription from 2 start sites was increased 15- to 18-fold, whereas transcription from the 3 other ones was increased 3-fold. In addition, three new start sites, below the detection limit in control cells, were highly induced. Therefore, a hormonal regulatory element can discriminate among closely related transcription start sites.
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PMID:Hormonal discrimination among transcription start sites of aspartate aminotransferase. 230 72


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