Studies of liver phosphorylase in hepatic injuries. I. Alteration in enzyme activity

Phosphorylase activities (total and a form) were determined in the livers of experimental hepatic injuries with carbon tetrachloride or galactosamine and the livers of patients with liver diseases. Experimental liver injuries caused a slight decrease in total activity in later stages and a marked increase in a form activity in earlier stages. In human livers, low values of total activity were found in acute hepatitis and cirrhosis of the liver with no consistent alteration in a activity. Phosphorylase activities in hepatocellular carcinomas were also low. The importance of the altered phosphorylase activities in hepatic injuries is discussed in relation to the disorder in glycogen metabolism in the injured liver.</p

Studies of liver phosphorylase in hepatic injuries II. Alteration in isozyme pattern

Enzyme deviations in injured livers were studied by analyzing isozyme patterns of phosphorylase using a newly developed electrophoretic method, which separates six molecular species of this enzyme, i.e. M,FM,F,L,L', and FL'. In hepatic injuries caused by CCl4 and galactosamine intoxications of rats, F appeared in early stages and L' (and FL') in later stages of the injuries with a concurrent decrease or loss of L, which is a sole isozyme component of adult liver. In injured livers of patients with hepatitis and cirrhosis of the liver, increases in FL' activity were also found. Appearance of F was found only in hepatocellular carcinoma. The results obtained with phosphorylase isozyme analysis support the idea that an undifferentiated gene expression takes place in the injured livers of non-malignant hepatic disorders.</p

Elevation of Collagenase Activity in Fatty Liver

Liver collagenase activity increased without liver cell necrosis in non-alcoholic and alcoholic fatty liver induced by feeding rats a choline-deficient diet or alcohol-liquid diet, respectively. The liver hydroxyproline content did not increase during a marked rise in collagenase activity in non-alcoholic fatty liver, but the content gradually increased after collagenase activity diminished. However, the hydroxyproline content increased slowly with a slight concomitant increase in collagenase activity in alcoholic fatty liver. The regulatory mechanism of fibrogenesis in fatty liver is discussed

Experimental and Numerical Investigations of Annular Freejets

The structure of an axisymmetric freejet issuing from an annular orifice is described for the stagnation chamber to ambient pressure ratio of 13. The flowfield is numerically calculated. In the calculations, the physical plane is transformed to the computational one because of taking more grid points in the vicinity of the orifice. For two-dimensional calculations, the operator splitting method is used, and also the two-step Lax-Wendroff scheme is applied to each operator. To verify the computational data, laser interferometry is employed to determine the density in the freejet. The radially resolved densities are determined by means of the Abel inversion. The experimental results show a fairly good agreement with the computational results

Anti-Carcinogenic Effects of a Serine Protease Inhibitor (FOY-305) through the Suppression of Neutral Serine Protease Activity During Chemical Hepatocarcinogenesis in Rats

Anti-carcinogenic effect of a serine protease inhibitor, [N, N-dimethylcarbamoylmethyl 4-(4-guanidinobenzoyloxy)-phenylacetate] methanesulfate (FOY-305), was studied in rats with neutral serine protease during hepatocarcinogenesis induced by a single intraperitoneal administration of diethylnitrosamine (DEN) and following feeding of a diet containing 2-N-fluorenylacetamide (FAA) for 32 weeks. Oral administration of FOY-305 significantly suppressed development of -γ-glutamyl transpeptidase (γ-GTP)positive hyperplastic nodules, preneoplastic lesion, at the 8th week of DEN injection, and that of hepatocellular carcinoma (HCC) formation at the 32nd week. Neutral protease activity increased in the preneoplastic and neoplastic livers. The activities in the preneoplastic and tumor-bearing livers were much lower in FOY-305-treated group compared with those in control group. Neutral protease partially purified from neoplastic liver at the 32nd week was inhibited by FOY-305 in vitro. The data suggest that neutral protease plays a crucial role in the process of chemical hepatocarcinogenesis

Liver Injury Following Long-Term Administration of Large Doses of Sake to Rats

The hepatotoxic effect on rats of long-term (55 weeks) administration of sake (a rice wine, 17% ethanol by volume) at large doses (average 12.6 g ethanol/kg body weight/day) was investigated in order to gain an insight into the reasons for the high incidence of liver fibrosis in Japanese alcoholics. Rats grew favorably under the experimental conditions, and daily variations in blood ethanol and acetaldehyde levels ranged from 3.8 to 21.1 mM and from O to 3.5 μM, respectively. Fatty and fibrotic liver was shown histologically and biochemically in sake-administered rats

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Potential and Support for e-learning at Correspondence High Schools

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Serum type IV collagen-degrading enzyme in hepatocellular carcinoma with metastasis.

The activity of serum type IV collagen-degrading enzyme was measured in 18 patients with hepatocellular carcinoma (HCC). The enzyme activity was significantly higher, in HCC patients with a tumor thrombus in the portal vein than in healthy controls, liver cirrhosis patients and HCC patients without a tumor thrombus. Moreover, the activity in HCC patients with lung metastasis tended to be higher than that in HCC patients without lung metastasis. The activity of serum type IV collagen-degrading enzyme did not correlate with tumor size, serum alpha-fetoprotein level, or macroscopic classification of tumor growth. These results suggest that the activity of serum type IV collagen-degrading enzyme represents the metastatic potential or the ongoing metastatic activity of HCC. The enzyme is a useful serum marker of metastasis from HCC.</p