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)

Interferon alpha is the only available therapy for patients with chronic hepatitis B. With interferon alpha 3-15 MU thrice weekly or 5 MU daily during 3-6 months one-third of the patients achieve seroconversion of HBeAg and HBV-DNA together with normalization of aminotransferases and slight improvement of histology. Loss of HBsAg is reported in a minority of responders during treatment, but increases during follow-up. Patients with baseline alanine aminotransferase of at least twice the upper limit of normal and low HBV-DNA concentration achieve the best response rates. HIV-positive patients with low CD4 counts and Asians are poor responders. As side-effects influenza-like symptoms are experienced by almost all patients. Mild leukopenia, thrombocytopenia and decreased hairgrowth are frequently reported. Severe depression, depersonalization and psychosis are reported in a small number of patients but tend to be poorly recognized in some studies. The decision whether dose reduction is indicated seems strongly related to the opinion of the investigator. Although long-term effects on the occurrence of cirrhosis and the development of hepatocellular carcinoma are not available yet, the achieved results are promising.
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PMID:Current status of interferon alpha in the treatment of chronic hepatitis B. 143 94

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

We determined the molar ratio of branched-chain amino acids to tyrosine (BTR) in plasma and in serum by enzymatic method and compared it with Fischer ratio (the molar ratio of branched-chain amino acids to tyrosine and phenylalanine) in plasma obtained by conventional HPLC method. BTR in plasma and in serum was well correlated with plasma Fischer ratio. The normal range (mean +/- 2SD) of BTR was determined to be 4.41-10.05 in 210 normal subjects. In addition, we investigated the distribution of BTR values in patients with various liver diseases. BTR value decreased according to the severity of liver disease. We evaluated the clinical usefulness of BTR in patients with chronic liver diseases by cumulative distribution analysis (CDA) graph and receiver operating characteristic curve (ROC) analysis. The area under the curve for BTR analyzed by ROC for CH versus LC.HCC group was the highest (86.3%) of any for various concurrently-measured liver function tests, and was significantly higher than AST/ALT, ALT, AST, gamma-GT (each, p less than 0.001) and ALB (p less than 0.05). These diagnostic results showed that BTR is a superior indicator in discriminating between liver cirrhosis and chronic hepatitis.
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PMID:[The clinical usefulness of the molar ratio of branched-chain amino acids to tyrosine (BTR) in discriminating stage of chronic liver diseases]. 151 41

Hepatocellular carcinoma patients were categorized into three grades according to the extent of portal vein invasion by the tumor. Correlations between the extent of portal vein invasion and values of alpha-fetoprotein (AFP), and various biochemical tests were examined. The extent of portal vein invasion by the tumor significantly correlated with the values of glutamic oxaloacetic transaminase (GOT), glutamic oxaloacetic transaminase: glutamic pyrubic transaminase (GOT:GPT), lactic dehydrogenase (LDH), alkaline phosphatase, leucinaminopeptidase (LAP), gamma-glutamic transpeptidase (gamma-GTP) and log10AFP. Results of the multivariate logistic regression analysis showed the values of LAP, LDH, log10AFP and GOT:GPT to be statistically significant independent indicators of portal vein invasion by hepatocellular carcinoma. The calculated probability for portal vein tumor thrombus, which was derived from the results of a step wise multivariate logistic regression procedure, revealed high accuracy and specificity for predictability. To design effective therapy and to predict the prognosis, it would be beneficial to obtain additional information from this calculated probability in patients with hepatocellular carcinoma.
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PMID:Prediction of portal vein invasion by hepatocellular carcinoma: a correlations between portal vein tumor thrombus and biochemical tests. 164 38

N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymers containing doxorubicin (DOX) and galactosamine can be targeted to the hepatocyte galactose receptor for organ-specific chemotherapy of primary and metastatic liver cancer. Here we report the dose-dependent pharmacokinetics of this macromolecular conjugate. Following intravenous administration to mice most efficient liver targeting was seen at low dose (0.05 mg DOX kg-1), with receptor saturation observed using higher bolus doses. Repeated low dose bolus injections did not cause down-regulation of the galactose receptor and targeted drug delivery rates of greater than or equal to 2 micrograms DOX g-1 liver h-1 were achieved. DOX is released from such conjugates intracellularly via action of lysosomal proteinases. It was shown that isolated rat liver lysosomal enzymes (Tritosomes) can release unmodified DOX from the peptidyl side chain Gly-Phe-Leu-Gly at a rate greater than or equal to 3 micrograms DOX g-1 liver h-1 i.e. the hydrolytic capacity is greater than the observed rate of drug delivery to the liver lysosomes in vivo. Although most conjugate would be captured by normal hepatocytes following intravenous administration, it was shown that the human hepatoma cell line HepG2 retains the galactose receptor, accumulating and processing the conjugate efficiently. Potential dose limiting toxicities of such drug conjugates could include cardio- or hepatotoxicity. Administration of conjugate reduced the 15 min heart level of DOX approximately 100-fold compared with that observed for an equivalent dose of free drug. Preliminary experiments showed that plasma levels of alkaline phosphatase, alanine transaminase and asparate transaminase did not change following administration of HPMA copolymer-daunorubicin (DNR) (10 mg DNR kg-1) indicating no significant heptatoxicity.
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PMID:N-(2-hydroxypropyl)methacrylamide copolymers targeted to the hepatocyte galactose-receptor: pharmacokinetics in DBA2 mice. 164 46

The prevalence of antibodies to hepatitis C virus (anti-HCV) was investigated among different populations in Taiwan, where anti-HCV was detected in 0.8% (24/2,994) of adult volunteer blood donors, 0.1% (1/1,305) of youngsters and children, 12.5% (8/64) of adult volunteer blood donors with elevated alanine aminotransferase (ALT), 36.5% (23/63) of hemodialysis patients, 4.1% (13/318) of male homosexuals, 25.4% (16/63) of cases positive for antibodies to human immunodeficiency virus (anti-HIV), 82.2% (578/703) of intravenous drug users (IVDUs), and 10.3% (23/223) of female prostitutes (FPs). Among patients with chronic liver diseases including chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC), the overall prevalence rate for anti-HCV was 34.1% (42/123), and a higher prevalence was noted in hepatitis B surface antigen (HBsAg)-negative cases than in HBsAg-positive cases. The prevalence of anti-HCV in volunteer blood donors and high prevalence found in IVDUs, hemodialysis patients, anti-HIV positive cases, and FPs are consistent with those results from other countries. These findings suggest that hepatitis C virus (HCV) infection is transmitted by both blood-borne and sexual contact routes. Among flavivirus infections, anti-HCV was detected in 0.3% (1/289) and 1.3% (4/310) of Japanese encephalitis and dengue fever patients, respectively. In conclusion, in Taiwan, an area with high endemicity of hepatitis B virus (HBV) infection, the epidemiological status of HCV infection is similar to that observed in other countries, and no serum cross-reactivity was noticed between HCV and flavivirus infections.
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PMID:Prevalence of antibodies to hepatitis C virus (anti-HCV) in different populations in Taiwan. 165 45

The hemodynamics during hemodilution occurred after hepatectomy for hepatocellular carcinoma with liver cirrhosis and its influences on the liver functions were studied. The hematocrit value gradually decreased about 10% until the 4th postoperative day owing to hemodilution after hepatectomy. While anemia progressed, cardiac index inversely increased. Under such a condition, oxygen consumption was maintained so that acidosis did not develop. Arterial blood ketone body ratio was also kept within a normal range except for a case whose hematocrit value decreased to 17.1%. Although the escaped hepatic enzymes such as GOT and GPT increased in the serum after hepatectomy, hemodilution was not responsible for their increase. While total bilirubin increased in the severe hemodiluted group, the increase was not due to hemodilution but caused by blood transfusion. The protein synthesis of the liver measured by rapid turnover protein levels in plasma was depressed after surgery, and this depression prolonged to the 14th postoperative day in the group whose hematocrit value decreased below 20%. These results suggest that it is better to keep hemodynamics without blood transfusion unless the hematocrit value decrease below 20%, and also better to maintain the hematocrit above 20% for liver regeneration after hepatectomy.
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PMID:[The hemodynamics during hemodilution and its influence on the liver functions after hepatectomy for hepatocellular carcinoma with liver cirrhosis]. 165 85

The aim of this study was to elucidate the positive rate of serum anti-HCV in alcoholic (with negative HBsAg and without blood transfusion history) and non-alcoholic (type-B and type-NANB) patients with chronic liver diseases. The clinico-pathological difference between anti-HCV positive and negative alcoholic patients was also investigated. Anti-HCV (Chiron C-100-3) was assayed with Ortho EIA kit in 196 patients. Liver function tests and the histological findings were evaluated in 111 cases of chronic hepatitis (CH) and 39 of liver cirrhosis (LC). Following results were obtained. [1] Positive rate of serum anti-HCV in alcoholic patients was 40% in CH, 36% in LC and 100% in hepatocellular carcinoma. In non-alcoholic type-NANB group, it was 75%, 68% and 69%, respectively. [2] Serum GGT/ALT ratio was higher in anti-HCV negative patients than positive patients both in CH and LC alcoholics. In non-alcoholic group, it was higher in type-NANB patients than type-B patients. [3] Among the histological findings in CH alcoholics, lymph follicles in the portal area were characteristic in anti-HCV positive patients, while these were not seen in negative patients. [4] In LC alcoholics, regenerative nodules were irregular in size in anti-HCV positive patients, while these were even and small in negative patients. [5] Serum HCV-RNA was detected in two out of 14 anti-HCV negative patients. [6] A female alcoholic patient who showed positive serum anti-HCV and negative HCV-RNA was presented. [7] For the evaluation of the influence of HCV in alcoholics, further studies have to be continued with more sensitive HCV markers.
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PMID:[Positive rate of serum anti-HCV in various liver diseases and the clinico-pathological study of chronic liver disease in alcoholics]. 166 37

This study of hepatocellular carcinoma in a homogeneous rural Transkeian population at high risk consisted of: evaluation of liver biopsies of 246 patients with hepatocellular carcinoma using routine histology and immunoperoxidase for HBV stains; collection of reliable data on alcohol consumption, blood HBsAg and ALT status in asymptomatic controls from an adequate population sample; assessment of maize intended for human consumption for contamination by carcinogenic fungi. Tumour histology of rural Blacks did not differ from those described in other studies. Cirrhotic livers were present in 45.1% and iron overload in 68% of cases. Tissue HBsAg was detected in 57% (45% of non-cirrhotic and 59% of cirrhotic livers). Asymptomatic controls showed 9.5% of HBsAg positivity, 3.5% had elevated ALT and 41.3% admitted to alcohol abuse. Maize had insignificant contamination by Aspergillus flavus and very frequent contamination by Fusarium moniloforme. This study suggests a multifactorial aetiology of hepatocellular carcinoma, with viral infection being of the most importance.
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PMID:Hepatocellular carcinoma in a rural population at risk. 166 22

The actual ELISA test for anti-HCV defects an antibody to a non-structural part of the virus. It is present in 0.3 to 1.5% of the blood donors and in about 60% of patients with chronic non-A, non-B hepatitis. Seroconversion occurs 4 to 6 months after the beginning of the disease. The risk of a sporadic transmission is very low but unknown. An ALT elevation occurred only in 7% of the sexual partners of positive chronic liver patients but nobody seroconverted. Vertical, mother to infant, transmission is rare. In all risk groups for HCV infection such as drug abuse, multiple transfusion, haemodialysis, the presence of the antibody is increased between 15 to 80%. There is also evidence that HCV may be an oncogenic factor for hepatocellular carcinoma. It is present in 30 to 60% of the cases.
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PMID:Prevalence and significance of anti-HCV antibodies. 166 70


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