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)

Human alpha-L-fucosidase, a lysosomal enzyme, hydrolyzes alpha-L-fucose from glycolipids and glycoproteins. Its activity is deficient in human fucosidosis an autosomal recessive disease. In order to understand the molecular basis of this lysosomal storage disorder we have cloned several cDNAs coding for human alpha-L-fucosidase from a human hepatoma and a human liver cDNA library constructed in lambda gt11. Compiling the cDNA sequences of these clones we have identified 1,829 base pairs (bp) encoding human alpha-L-fucosidase. This includes an open reading frame of 1,172 bp, a consensus polyadenylation signal AAT AAA and a poly(A)+ tail. The sequence is incomplete at the 5'-end, and clones encoding the amino terminus of the native protein, the propeptide and leader signal have not yet been isolated. The open reading frame encodes for 390 amino acids with a calculated Mr of 45,557. This represents 78-95% of the mature processed alpha-L-fucosidase. The availability of these cDNA clones has enabled us to map the structural gene for alpha-L-fucosidase to chromosome 1p34.1-1p36.1 by Southern blot analysis of DNA from human-rodent somatic cell hybrids and by in situ hybridization. Furthermore, a Pvu II restriction fragment length polymorphism (RFLP) has been identified at the human alpha-L-fucosidase gene locus. Analysis of mRNA by Northern blotting gives a major species of 2.25 kb. In 4 patients with fucosidosis no mRNA signal was detected and Western blots gave no immunoreactive enzyme. Southern blotting after Eco RI digestion in two fucosidosis families revealed a banding abnormality (extra 6-kb band).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular biology of the alpha-L-fucosidase gene and fucosidosis. 289 6

In vitro supplementation with the active form of vitamin B6, pyridoxal-phosphate (PLP), increases measurements of both serum aminotransferase enzymes, L-aspartate: 2-oxoglutarate amino transferase, EC 2.6.1.1 (AST) and L-alanine: 2-oxoglutarate aminotransferase, EC 2.6.1.2 (ALT). The plasma PLP level in normal individuals clearly relates inversely to the degree of stimulation of serum AST and ALT. PLP added in vitro increases the reference values but does not decrease the biological variability of AST measurements in healthy individuals. Since B6 deficiency is observed in alcoholics, in some significant percentage of hospitalized patients and in apparently healthy people over age 64, these individuals will show PLP stimulation of their serum amino-transferase enzymes. Patients with liver disease show lesser activation with PLP of AST activity but not ALT activity than patients with heart disease (myocardial infarction). AST isoenzyme measurements in the form of a mitochondrial AST/total AST ratio may discriminate alcoholic hepatitis from all other hepatic diseases. In renal dialysis patients including transplant patients, it may be desirable to measure the aminotransferases with added PLP in order to reflect better the cytolytic state of the liver. While unconfirmed studies suggest the combination of PLP activation and AST isoenzyme measurements may aid in the diagnosis of hepatoma, PLP activation per se does not provide clear cut improved diagnostic value of AST and ALT in liver diseases. However, in view of PLP incorporation into the IFCC reference methods for AST and ALT, and the National Reference System for the Clinical Laboratory, it is recommended that PLP be included in all AST and ALT measurements.
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PMID:Review of pyridoxal phosphate and the transaminases in liver disease. 300 34

We measured the activity of carnosinase, a prominent hepatic peptidase, in sera from 69 patients with liver disorders. Mean values (and SDs) for those with liver cirrhosis (17 cases) and hepatoma (seven cases) were 0.51 (0.28) and 0.68 (0.21) mumol/mL per hour, respectively--clearly less than for normal adults: 4.19 (0.95) mumol/mL per hour. Samples from 17 cases of chronic hepatitis also showed moderately decreased activity, 1.41 (0.97) mumol/mL per hour. In contrast, 14 cases of acute hepatitis generally showed values falling within the normal limits: 3.41 (1.97) mumol/mL per hour. Our results for carnosinase correlated with those for cholinesterase (r = 0.70) and with the concentration of albumin in serum (r = 0.59), but not with the activity of either creatine kinase, aspartate aminotransferase, or alanine aminotransferase in serum. Carnosinase values differed more among groups of disorders than did the values for cholinesterase or albumin. Measurement of serum carnosinase activity may be of clinical value in assessing the severity of chronic liver-cell damage, but not in differentiating liver disease from nutritional, muscle, or endocrine disorders.
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PMID:Decreased activity of carnosinase in serum of patients with chronic liver disorders. 373 53

The tightness of DNA-protein binding in the nuclei of mouse spleen T- and B-lymphocytes was assessed, using nucleoprotein celite chromatography, and changes in the number of T- and B-suppressors in the course of o-AAT-induced chemical hepatocarcinogenesis were studied. Attenuation of DNA-protein bonds in T-lymphocytes at the early stages (up to 3 months) was observed, and by the time of hepatoma formation (8 months) about 50% of T-lymphocyte DNA was loosely bound to proteins, which is a typical feature of quiescent cells. In B-lymphocytes attenuation of DNA-protein interaction was only observed by the 8th month of carcinogenesis. By the time of hepatoma formation the number of T-suppressors in mouse spleen increased 2.8-fold, while the number of B-suppressors in lymph nodes remained unchanged.
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PMID:[Change in the strength of DNA-protein binding in T- and B-lymphocytes of the spleen of C3HA mice during chemical hepatocarcinogenesis]. 387 31

A human hepatocellular carcinoma cell line (FOCUS--Friendship of China and United States) was derived from a patient with primary hepatocellular carcinoma. This cell line has been in continuous culture over an 18-mo period. The morphological and ultrastructural features of FOCUS are consistent with its neoplastic hepatocellular origin. FOCUS cells contain aspartate aminotransferase and glucose-6-phosphatase activity. In addition, alpha 1-antitrypsin, fibrinogen, alpha fetoprotein, and carcinoembryonic antigens were detectable in the cytoplasm of the cultured cells by immunochemical staining techniques. The karyotype of the FOCUS cell is human in origin and its contains human DNA sequences as detected by molecular hybridization analysis. The FOCUS cells do not show evidence of density-dependent inhibition of growth under confluent conditions. Repeated growth curves over an 18-mo period were identical, revealing a doubling time of 42 to 48 h. The malignant potential of FOCUS cells was further demonstrated by their ability to lead to gross tumor formation after subcutaneous injection into nude mice. From one of the solid tumors grown in nude mice, recultured cell lines have been established and found to have properties identical to the original FOCUS cell line. This FOCUS cell line represents an additional model for further investigation of tumor specific antigens and the relationship between hepatitis B virus (HBV) and hepatocellular carcinoma. Preliminary molecular characterization has indicated the existence of integrated HBV sequences within the FOCUS genome.
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PMID:Establishment and characterization of a new human hepatocellular carcinoma cell line. 608 98

The clinical effectiveness of conservative therapeutic modalities for hepatocellular carcinoma (HCC) was evaluated in terms of extension of survival. The therapeutic methods included one-shot therapy (OST) using Mitomycin C (MMC), Adriamycin (ADM), simultaneous ADM & MMC, with or without transcatheter arterial embolization (TAE). Prior to estimating the effectiveness, the subjects were graded into three stages according to the pretreatment severity of their residual liver function, based on total bilirubin, aspartate aminotransferase/alanine aminotransferase ratio, and ascites as constituent factors. OST with or without TAE significantly prolonged the mean survival time in stage I cases in good condition and in stage II cases in fair condition, but not in stage III cases in poor condition. Concerning OST without TAE, the results of ADM were slightly better than MMC in terms of extension of survival. OST combined with TAE was far more effective than OST without TAE. Extension of survival by simultaneous ADM & MMC is now under observation, but the toxicity of the modality has so far not proved serious. The long-term influence of repeated TAE on liver function was revealed to be mild within an average observation period of approximately one year. This study confirmed the validity of the present staging system in evaluating the efficacy of OST and TAE in terms of extension of survival.
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PMID:Evaluation of conservative therapeutic modalities for hepatocellular carcinoma--analysis of 206 cases. 609 97

A physician's personal series of 10 women treated from 1970-1979 for oral contraceptive-associated liver tumors is presented. Of the 10 women treated, 7 had hepatocellular carcinoma and 3 had benign adenomas. Symptomatology is described. Problems with diagnosis of liver dysfunctions included misleading biopsies and liver scans. The erythrocyte sedimentation rate was raised in all but 1 woman, and it was above 70 mm/h in 7. Changes in liver function tests were consistent with an intrahepatic tumor, with a striking increase in alkaline phosphatase in 9 (1170 IU/ml), and with only a slight rise in serum aspartate transaminase (mean 55 IU/ml). None of the patients had alpha fetoprotein levels above the upper limit of normal, and all patients were negative for hepatitis B surface antigen and antibody and anticore antibody. The carcinoma characteristics were similar in 7 patients (irregular trabecular arrangement with basophilic and dysplastic cells with nuclear pleomorphism and increased mitotic figures). When these oral contraceptive users were compared with 7 women diagnosed with hepatocellular tumors who had never used oral contraceptives, several striking differences were found. None of the poll users with carcinoma had raised alpha fetoproteins, whereas 4/7 nonpill users did. By arteriography, tumors in nonusers were much less vascular and less well defined. Survival rates also differed, with a 50% survival time of 1-8 years in nonusers compared with 4-8 years in pill users. The striking feature of this series is the delay in reaching a diagnosis in most of the 10 cases treated.
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PMID:Oral-contraceptive-associated liver tumours: occurrence of malignancy and difficulties in diagnosis. 610 35

In 1964 a 42-year-old woman was hospitalized with clinical and laboratory signs of posttransfusion hepatitis five weeks after administration of six whole blood transfusions. During the following 17 years anicteric chronic liver disease was repeatedly documented by elevations of serum aspartate aminotransferase (SGOT) and alkaline phosphatase enzymes. In 1981 hepatomegaly, progressive jaundice, and a serum alphafetoprotein level of 516,000 ng/ml were observed. Percutaneous liver biopsy showed a primary hepatocellular carcinoma (PHC). Serologic examinations failed to reveal markers for hepatitis B virus including HBsAg, anti-HBs, and anti-HBc by radioimmunoassay; antibody to hepatitis A virus was also absent. This sequence of events demonstrates a presumptive association of PHC and the agent(s) of non-A, non-B viral hepatitis.
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PMID:Primary hepatocellular carcinoma following non-A, non-B posttransfusion hepatitis. 619 33

Alpha 1-antitrypsin has been examined in formalin-fixed, paraffin-embedded liver specimens from Greek patients with cirrhosis (35 cases) and hepatoma (55 cases) by peroxidase-antiperoxidase (PAP) method. Ring-like AAT globules were found in the non-neoplastic cells in 12% of the cases of hepatoma and in 11% of the cases of cirrhosis. Atypical globules were seen in neoplastic cells in 5.4% of the cases of hepatoma and in 17% of the cases of liver cirrhosis. A diffuse fine granular pattern of AAT distribution was present in 31% of the cases of hepatoma in the neoplastic cells and in 27% of those in the non-neoplastic cells. The relatively high incidence of ring-like AAT-globules, and of atypical globules in cases of hepatoma and cirrhosis is not in agreement with the extremely low gene frequency of Z allele in a Greek population of patients with cirrhosis and hepatoma. Thus, there is some doubt whether AAT-globules in the liver represent a histopathologic marker of genetically determined AAT deficiency. A relationship between AAT deposits and the degree of differentiation of hepatoma was noted in this series. AAT-positive cells were found in 55% of moderately differentiated, in 29% of highly differentiated and in 20% of poorly differentiated hepatomas.
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PMID:Demonstration of alpha 1-antitrypsin in paraffin sections of hepatoma and cirrhosis. 629 75

We measured serum guanase (EC 3.5.4.3) activity in patients with various diseases and in healthy controls, and evaluated the clinical usefulness of this enzyme in liver diseases. The reference range, which showed no significant difference between sexes and ages over the range studied, was 0 to 1.8 U/L. The mean guanase activities for patients with various liver diseases, including acute hepatitis, chronic hepatitis, liver cirrhosis, hepatoma and metastatic carcinoma, were above the upper limit of the reference range. In acute hepatitis and metastatic carcinoma of the liver, the activities were especially high. Validity (sensitivity + specificity) of guanase, which in all tests was above 1.66, was compared to that of AST and ALT in liver diseases. With guanase, the highest validity (1.98) was found in acute hepatitis and metastatic carcinoma. Specificity of guanase was 0.98, whereas sensitivity of AST was 1.00 in all diseases. Sensitivity and specificity of ALT were 0.85 to 0.97 in all diseases. As guanase was specific, including this enzyme with other liver function tests, such as AST and ALT, may decrease false-positive results and may be effective for prediction of liver disease.
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PMID:Clinical evaluation of serum guanase activity in liver diseases. 649 63


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