N. Nakamura

Changes in acid mucopolysaccharide in the liver in hepatic fibrosis

Abstract Changes in hepatic acid mucopolysaccharides were examined by testicular hyaluronidase digestion and hexosamine analysis of the acid mucopolysaccharides extracted from rat livers having chronic hepatic damage caused by serial inhalation of carbon tetrachloride. Chronic hepatic damage gave rise to an increase of hyaluronic acid in the early stages of hepatic damage and of chondroitin sulfate B in the advanced stages, the latter being more prominent. The amount of chondroitin sulfate A and/or C was also increased, but the change in its ratio to the total acid mucopolysaccharides was not significant throughout the experiment. Another result was that galactosamine-containing acid mucopolysaccharide was found to exist in the non-sulfated fraction which increased in the early stage. The possibility is suggested that chondroitin sulfate B is related to the progress of hepatic fibrogenesis.

Electrophoretic fractionation of serum γ-glutamyl transpeptidase in human hepatic cancer

Abstract Serum γ-glutamyl transpeptidase from patients with various hepatobiliary diseases was fractionated by polyacrylamide gradient gel slab electrophoresis to study the specific patterns of γ-glutamyl transpeptidase fractions in hepatic cancer. On zymograms of normal serum γ-glutamyl transpeptidase, a total of 10 fractions was observed. Additionally, fractions I′, I″ and II′ were recognized in sera from hepatocellular carcinoma patients. Among these, fraction I′, which migrated slightly, but significantly, slower than fraction I was the most specific; it was found in 55% of the hepatocellular carcinoma patients. Fractions I″ and II′ were also relatively specific, each was observed in about 29% of these patients. Fractions V to IX were observed in few hepatocellular carcinoma cases. Fraction I′ is thought to be a hepatoma-related fraction, highly specific for the serum of hepatocellular carcinoma patients. Fractions I″ and II′ were also thought to be hepatoma-related fractions of 7-glutamyl transpeptidase. We suggest that fractions I′, I″ and II′ may be useful in the diagnosis of hepatocellular carcinoma.

Optimal production planning for a multiproduct, multistage production system

Abstract A mathematical model of production planning for a multiproduct, multistage produetionaystom (production equation, transition equation and objective function) was constructed in order to derive the optimal decision rule to be adapted to demand fluctuation. With this model the optimal solution and the computational algorithm were determined by functional space approach. With use of this algorithm, a numerical example of optimal production planning was solved.

Changes in the cellular glycosaminoglycans of cultured mastocytoma cells induced by sodium butyrate

The effect of sodium butyrate on the cellular glycosaminoglycans of cultured mastocytoma p-815-4 cells was investigated using enzymic digestion, electrophoresis, nitrous acid degradation, and sequential partition fractionation. The average cellular glycosaminoglycan content of mastocytoma p-815-4 cells grown in the presence of 2 mM sodium butyrate was ten times as much as that of the control p-815-4 cells. Approximately 90% of the glycosaminoglycans isolated from the control cells and 70% from the butyrate-treated cells were found to be chondroitin 4-sulfate by enzymic digestion. The remainders were chondroitinase ABC-resistant. Hyaluronic acid and dermatan sulfate were not detected in either control cells or butyrate-treated cells. The chondroitinase ABC-resistant fraction of glycosaminoglycans from butyrate-treated cells showed a molar ratio of sulfate to uronic acid of more than 2.0, and provided some physicochemical properties characteristic to reference bovine lung heparin.

Serum hyaluronidase activity in chronic liver damage

Abstract 1. 1. Hyaluronidase activity in serum of rat with chronic hepatic damage induced by serial carbon tetrachloride inhalation was found to be considerably elevated. In an advanced stage of the hepatic damage, however, the elevation of the activity was not so marked. 2. 2. Elevated serum enzyme activity was seen in patients with chronic hepatitis whereas no significant change was seen in cirrhotic patients. These results seem to show a similar tendency as seen in rats with experimental hepatic damage. 3. 3. The change of the enzyme activity in rat serum was found to be closely related to the activity in liver homogenate. 4. 4. The relationship between the changes in hepatic acid mucopolysaccharides and the serum enzyme activity in chronic hepatic damage is discussed.

Effect of excess vitamin A on acid mucopolysaccharides in rat liver

Abstract Oral administration of excess vitamin A caused a marked decrease of acid mucopolysaccharides in rat liver. This decrease was pronounced in the non-sulfated fraction of acid mucopolysaccharides, but a reduction of chondroitin sulfates A and C was also noticed with prolonged administration. An increase of hepatic hyaluronidase activity in the whole homogenate and the release of the enzyme into the soluble fraction were found with the hypervitaminotic A treatment. The mechanism which causes quantitative and qualitative changes in hepatic acid mucopolysaccharides with hypervitaminosis A is discussed in relation to the changes in hepatic hyaluronidase activity.

Metabolism of sulfated acid mucopolysaccharides in the liver with chronic carbon tetrachloride injury: Estimation of the turn-over rate using35S-sodium sulfate

We reported the characteristic changes in acid mucopolysaccharides in the liver during experimental chronic hepatic damage. A marked increase of sulfated acid mucopolysaccharides, especially dermatan sulfate, was noted in the process of hepatic fibrogenesis. However, the dynamic metabolism of hepatic acid mucopolysaccharides is yet unknown. To study the turn-over rate of sulfated acid mucopolysaccharides in the liver, 35S-sodium sulfate (1 I0 uCi/rat) was injected intraperitoneally to healthy rats, rats with chronic hepatic damage caused by carbon tetrachloride inhalation and rats during convalescent stage from chronic hepatic damage. After 1, 4, 12 and 24 hours, 3-5 animals in each group were sacrificed, and counts of 3~S incorporated into liver acid mucopolysaccharides were measured. At 4 hours after the injection, counts of 3sS in hepatic acid mucopolysaccharides reached maximum and decreased rapidly thereafter. After 24 hours, only 10% of the maximum radioactivity remained in acid mucopolysaccharides fraction in healthy liver and about one-fourth remained in the liver with chronic hepatic damage. The Briggsian logarithms of the ass radioactivities incorporated into liver acid mucopolysaccharides were plotted against the incorporation periods and the biological half-lives were estimated. The half-lives of hepatic sulfated acid mucopolysaccharides were 6 hours in healthy liver, l0 hours in the liver with chronic hepatic damage and 6.5 hours in the liver during convalescent stage. These results indicate that the biological half-life of liver acid mucopolysaccharides is much shorter than that reported on other connective tissues such as cartilage, vessel wall and skin, and that the turn-over rate of sulfated acid mucopolysaccharides is significantly slower in the liver with chronic carbon tetrachloride injury compared with healthy liver.

Focal fibrosis in liver of rat with hepatic injury

Four hundred and fifty cases of cholelithiasis operated in the past 12 years were reviewed. Even in mild cases with no abnormal hepatic functions preoperatively histologic findings of portal inflammation, bile duct proliferation, extension of portal fibrosis: termed biliary portal fibrosis for the convenience to understand histogenesis of this kind, appeared to be more evident, when compared, than those associated with gastric ulcers or carcinomas but not complicated with cholellthiasis. In some of cases with cholelithiasis hepatic injuries became superimposed, as a result, leading to secondary biliary cirrhosis. The cause of death of the majority of fatal cases with cholelithiasis was due to hepatic failure following severe cholestasis and development of an ascending infection via portal system. From the above, to improve therapeutic results, it should be emphasized that early surgical intervention is the treatment of choice tbr the cases with longstanding cholelithiasis.

Studies on hepatic fibrogenesis (XVI) Qualitative changes of hepatic acid mucopolysac-charides in rats with experimental chronic hepatic damage

Materials: 1) Biopsy specimen from a subacute hepatitis case. 2) Human umbilical cord as a test substance. Methods: 1) Fixative: Cetylpyridinium chloride (CPC) containing formalin solution (William & Jackson, 1956). 2) Paraffin sections. 3) Staining solutions: a) Mowry (1960) s Alcian Blue solution, b) Scott & Dorling (1965) s Alcian Blue solution. 4) I;/yaluronidase digestion: 100 mg./ 100ml. solution in 0.1 M, pH 5.0 acetate buffer, 37~ 3h. & 24h. 5) Reagents: Alclan Blue 8GX (Allied Chemical), Bovine testicular hyaluronidase (Sigma, Type-I). Results: 1) Very strong staining was seen in the biopsy specimen with Mowrys solution and it decreased markedly by hyaluronidase digestion. 2) With Scott & Dorlings method, various CECs were detected in the specimen, and it was suggested that chondroitin sulphate (A or C, or both) and hyaluronate were present in the perihepatocellular and portal region of the specimen. 3) Also, small amount of hyaluronidase insensitive AMPS was found. 4) These hyaluronidase sensitive and insensitive AMPs were found in mixed condition in the specimen from the subacute hepatitis case.

N-Acetyl-β-Glucosaminidase activity in the serum in various diseases

In a study of 205 kakke syndrome pat ients in Yokohama Hospital showed 53% positive in the Sawadas reaction. 33 of 115 positive pa t ien ts are examined af te r received I week the activated BI products, TPFD, BTMP, TATD, BTDS, each 75mg ot 150mg per day. I t is found 57% in effectiveness tha t the pat ients who are given BTDS 150mg per day for average 7 days, 45% TPFD 75rag, 33% BTMP 75mg, 20% BTDS 75rag, 20% TATD 75mg. Against expectation, the most improvement group by the activated BI products showed only 57%. Depend upon the upper results it seems to be a few suspicion on the superior of the improvement on glucose metabol ism in man by the act ivated BI products than the old pure BI.