Natural killer (NK) activities of peripheral blood lymphocytes (PBL) in 50 patients with non-alcoholic liver cirrhosis (LC) were prospectively studied in order to clarify the relation between the ...development of hepatocellular carcinoma (HCC) and impaired NK activities. Patients were divided into two groups according to their NK activities at the beginning of the study, namely, Group A with normal NK activity (n = 21) and Group B with decreased NK activity (n = 29). NK activities were serially determined in each patient for up to 40 months. During the observation period, the occurrence of HCC was identified in 12 patients (four to 36 months). Of the patients who developed HCCs, two belonged to Group A (9.5%) and 10 belonged to Group B (34.5%). These results suggest decreased NK activity in LC patients to be one of the critical factors increasing their risk of developing HCC, and serial determinations of NK activities to be important in predicting the occurrence of HCCs in following the clinical course of LC patients.
A rat hepatoma cell line was established from primary culture using RPMI 1640 without supplements. Hepatomas were induced in rats by 0.06% 3'-methyl-4-dimethylaminoazobenzene. An established cell ...line, FF101, has been maintained as a monolayer for longer than 34 months and subcultured for 42 passages. The population-doubling time was 78 h. The modal chromosome number was 66. FF101 was transplantable, and morphological examination of the transplanted tumors revealed a mixed type of hepatocellular and cholangiocellular carcinoma. FF101 retained the ability to express tyrosine aminotransferase and glucose-6-phosphatase. Also, FF101 synthesized alpha-fetoprotein. FF101-conditioned medium stimulated DNA synthesis and proliferation of several cell lines such as AH66, K562, and BALB/c3T3. The growth-promoting activity of FF101-conditioned medium was abolished by protease, dithiothreitol, acidic treatment, and heating. Gel filtration of conditioned medium on Sephacryl S-200 disclosed the growth-promoting activity at the molecular size of approximately 60,000 Da, and the isoelectric point (pI) was between 5.5 and 6.5. These results suggest that FF101 synthesizes a novel growth factor which has little specificity in both species and organs.
The level of a bile canalicular membrane antigen in serum during extrahepatic cholestasis was serially analyzed using HAM.4, a monoclonal antibody against a bile canalicular membrane glycoprotein of ...normal rat hepatocytes. After bile duct ligation, the level of HAM.4 antigen in serum promptly increased within 1 hr, reached a maximum at 3 hr, and declined somewhat until 48 hr, where it plateaued. Elevated levels of HAM.4 antigen in serum preceded those of well-known biliary marker enzymes activities. Immunohistochemical studies showed that the expression of HAM.4 antigen in hepatocytes and bile duct cells was not altered appreciably after bile duct ligation even when HAM.4 antigen in serum reached a maximal level. The serum and hepatic HAM.4 antigen had a molecular weight of 110 kDa. These results suggest that HAM.4 antigen may be regarded as a potential marker of the early stage of cholestasis, with release occurring before apparent histological changes.
The effect of BCG, an immunopotentiator, on the hepatocarcinogenesis of the rat induced by 3'-methyl-4-(dimethylamino) azobenzene (3'-Me-DAB) was investigated. After administration of 3'-Me-DAB for 6 ...weeks, BCG was injected to the rats at 2-week intervals for 50 weeks and the serial determinations of serum α-fetoprotein and morphological examination of the liver were made. In the control group, the second rise of serum α-fetoprotein, which reflected the occurrence of hepatoma, was seen at about 12 weeks after discontinuance of 3'-Me-DAB. On the other hand, the second rise of serum α-fetoprotein in the group treated with BCG was delayed about 10 weeks compared to control group, although there was no significant difference in the final incidence of hepatomas between these two groups. Infiltration of the lymphocytes was observed in the liver of rats treated with BCG without hepatoma. BCG seems to have an inhibitory effect on 3'-Me-DAB carcinogenesis of the rat, possibly by stimulating the cell-mediated immunity, although it is not strong enough to prevent the occurrence of hepatoma completely.
The concentration of benzyl alcohol (BA) in the blood of the patients after the intravariceal injection of ethanolamine oleate (EO) with meglumine amidotrizoate (EO-MA) for endoscopic sclerotherapy ...of esophageal varices was determined by GLC method. BA appeared in the peripheral blood immediately after the interavariceal injection of EO-MA, therefore it was found that the leak of BA from the varix occurred very early. But BA disappeared rapidly from the blood (t1/2= 10 minutes). The hemolysis after the intravariceal injection had no relation to the concentration of BA in the blood. The actions of BA and EO on erythrocytes were examined in vitro, and the hemolyzing effect of EO was much stronger than that of BA. From these results, it is thought that the effect of BA on the hemolysis after the intravariceal injection of EO-MA is only a little and the hemolysis probably results from EO.
Changes in the expression of a cell membrane antigen during hepatocarcinogenesis and in the developing liver were analyzed by HAM.4, a monoclonal antibody (MAb) against a membrane glycoprotein of ...normal rat hepatocyte. Of the precancerous lesions observed during hepatocarcinogenesis induced by diethylnitrosamine, 2-acetylaminofluorene and partial hepatectomy, early neoplastic foci were uniformly stained by HAM.4. In contrast, some cells in the neoplastic nodules at the late stage did not express HAM.4 antigen on the cell surface. Of the cancer tissues, well-differentiated hepatocellular carcinomas were stained by HAM.4 whereas poorly differentiated carcinomas did not bind HAM.4 In developing rat liver, HAM.4 antigen was first expressed on fetal hepatocytes at the 18th day of gestation. It gradually increased until 4 weeks after birth when the intensity of the stain was almost the same as in adult rat liver. These results suggest that the expression of a membrane antigen defined by HAM.4 is closely associated with the differentiation of bile canalicular face and that HAM.4 might be useful in characterizing differentiation of cells during malignant transformation of hepatocytes.
Disappearance of proteinuria was observed in a patient with hepatitis B-associated chronic glomerulonephritis after treatment with leukocyte interferon. The decrease of proteinuria was preceded by ...the disappearance of both deoxyribonucleic acid polymerase activity and hepatitis B e antigen from the patient's sera.
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