Since it was suggested that intracellular glutathione may play a significant role in protein synthesis, the authors attempt to study the inhibitory effect of diamide and oxidized glutathione on protein synthesis in isolated hepatocyte culture. Diamide is diazenedicarboxylic acid bis (N, N-dimethylamide) and has been shown to be an active agent which causes the selective conversion of intracellular reduced glutathione to oxisidized glutathione. The authors also investigated the effect of reduced glutathione, N-mercaptopropionyl glycine (tiopronin) and pantethine on the inhibited protein synthesis induced by diamide or oxisidized glutathione.
The results obtained were following.
1) The synthesis of both secretory and non-secretory proteins in the isolated hepatocytes was remarkably inhibited by addition of either diamide or oxisidized glutathione to the cell culture. A significant inhibition of protein synthesis was also observed by administration of the relatively higher dose of tiopronin.
2) The inhibition of protein synthesis induced or oxisidized glutathione was significantly reduced by addition of reduced glutathione or tiopronin.
3) Pantethine, a kind of non-SH compound, was also reduce the inhibition of protein synthesis induced by diamide or oxisidized glutathione. It is likely that pantethine is reduced at least partially in hepatocytes to pantethine or other SH-derivatives and they act on the protein synthesizing apparatus in a similar way as reduced glutathione.

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Attentions have been recently focused on the characteristics of the stellate cells (fat-storing cells) from the standpoint of the liver fibrosis; therefore, the present investigations were performed by means of von Kupffer's gold impregnation method on the tissues collected from 30 cases of liver biopsy specimens.
Staining of the stellate cells was less satisfactory when the original method (von Kupffer) was used. We therefore modified this method to a new one in which the specimen was immersed in chromic acid solution for only 3-5 minutes, and vitamin A was administered intramuscularly five days before the liver biopsy.
By means of the above described modified method, following findings were clarified: (1) Vitamin A lipid droplets in the stellate cells were variable in number and size in each liver of chronic hepatitis. (2) Stellate cells in the parenchyma around fibers bundle showed a strong gold chloride reaction, whereas the cells in fibers bundle were not stained.
Thus, our modified method was considered to be useful not only to detect the distribution change of stellate cells, but also to examine the relation between liver fibrogenesis and the stellate cells.

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The clinical and epidemiological studies of sporadic type A hepatitis were reported. Fifteen cases were diagnosed as hepatitis A by radioimmunoassay (HAVAB), immune adherence hemagglutination and immune electron microscopy. Eleven cases were taken sporadically between January and April, and two patients were infected by secondary spread in the family. Two other patients developed after travel in Southeast Asia. However, sources of the infection were not proved in these sporadic cases. Signs, symptoms and laboratory data of hepatitis A were compared with sporadic hepatitis B and non-A non-B hepatitis. Patients with hepatitis A often had various preicteric symptoms as fever, general fatigue and anorexia. Of laboratory data, both thymol turbidity and immunoglobulin. M were elevated in hepatitis A. The histology of liver biopsies obtained from 3 cases of them in the recovery stage showed the convalescent stage of acute hepatitis, but were not significantly different from that of hepatitis B.

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Liver specimens obtained from 11 cases of acute hepatitis A (aged 25 to 48 yrs; sex ratio 1:1) were morphologically examined. These percutaneous liver biopsies were performed between 4 to 37 days after onset of jaundice. In more earlier 4 cases (4, 6, 7 and 8 days later from jaundice) showed histological findings described below; portal tracts were enlarged by mononuclear cell infiltration, and focal necrosis of hepatocytes distributed diffusely not only periportal area but centrizonal area and especially it manifested by hydropic degeneration and coagulation necrosis. Regeneration of hepatocytes have already recognized.
On the other hand, in more later cases showed minimal cell infiltration in portal tracts without enlargement. The hepatocytic alteration in centrizonal area, however, still showed hydropic degeneration and spotty necrosis. Electronmicroscopic manifestation of liver were proliferation and dilatation of endoplasmic reticulum, and swelling and degeneration of mitochondria. HAV can be detected in the hepatocyte and sinusoidal lining cells by electronmicroscopically and the method of immunoperoxidase in one case whose HAV was still shedded in a stool.

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To study the prognosis of asymptomatic HBsAg carrier, 63 HBsAg positive blood donors were followed for more than 4 years, and their sera were examined for HBeAg, anti-HBe, and liver function tests. Only one of 10 HBeAg positive donors under 25 years old at the entry showed abnormal GPT, and 3 of them developed abnormal GPT within 4 years of follow up. Six of 12 HBeAg positive donors over 25 years old showed abnormal GPT at the entry and 10 of them developed abnormal GPT within 4 years. Especially in 6 cases of them, high elevated GPT were noted, later HBeAg disappeared, and hepatic biopsy specimens revealed chronic aggressive hepatitis. Frequency of abnormal GPT within 4 years was higher in HBeAg positive donors over 25 years old than in those under 25 years of age. (P<0.05)
On the other hand, none of 4 anti-HBe positive donors under 25 years of age showed abnormal GPT for 4 years. Seven of 14 anti-HBe positive donors over 25 years old developed abnormal GPT for 4 years, but GPT levels were less than 200 I.U..
It is concluded that anti-HBe positive carriers and HBeAg positive carriers under 25 years of age may have a better prognosis than HBeAg positive carriers over 25 years old who may progress to chronic active hepatitis.

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The course and prognosis of 64 asymptomatic HBsAg carriers were studied. All of them confirmed histologically to have normal or minimal changes on initial biopsy with informed consents. They were consisted of 26 HBeAg positive cases and 38 anti-HBe positive cases. The average follow-up period was 30.4 months in HBeAg positive cases and 27.8 months in anti-HBe positive cases. Seventeen of 26 HBeAg positive cases showed the abnormal transaminase during the follow-up period. The peak of their transaminase level were over 100 units in 13 of them. The liver biopsy was performed sequently twice to fourth times in 11 of those 13 cases. Their final histologic findings were liver cirrhosis in 2, chronic active hepatitis in 5, chronic inactive hepatitis in 2 and acute viral hepatitis in 2 cases. On the other hand, in 38 anti-HBe positive cases, 10 showed abnormal transaminase, but the peaks were below 100 units in all cases. Four cases of them were biopsied twice. Their histologic findings revealed normal or minimal changes as initial biopsies.
All 64 cases had HBsAg persistently. Five cases showed seroconversion from HBeAg to anti-HBe. Those 5 cases showed elevation of transaminase temporaly before seroconversion.
These data suggest that the presence of HBeAg is closely to the occurence of hepatitis in asymptomatic HBsAg carriers. As the other factors cocerned with the prognosis of them, sex, age and family clustering of liver disease were considered.

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HBsAg and HBcAg in liver tissue were studied in formalin fixed paraffin sections of 806 liver biopsy materials. HBsAg in liver tissue was negative in 429 specimens without HBsAg in serum and in 39 cases (45 specimens) with acute hepatitis type B (AH-B). The positive rate of HBsAg in liver tissue with AH-B is supposed to be influenced mainly by the interval from the onset of AH-B to the time liver biopsy was done. HBsAg in liver tissue was detected in 249 (89.9%) out of 277 specimens with HBsAg carriers, in that HBsAg in serum was persistently positive more than three months. Detection of HBsAg in liver tissue is very useful to differentiate acute exacerbation in HBsAg carriers from AH-B.
Inclusion (I), cytoplasmic (C) and membranous (M) types were recognized with regard to the shape of HBsAg in hepatocytes. M type was distributed focally in pericentral area of the lobule. In cases with M type, a lot of C type were also found in the same section and HBsAg-titer in serum was high significantly. It is thought that both I and C types exist in the liver of HBsAg carriers with variation of quantity and distribution of those and the variation influences the positive rate of HBsAg in paraffin sections. According as the disease progressed to liver cirrhosis, I type was distributed focally or diffusely in the lobule and irregularly among the lobules. The positive rate of HBsAg in liver tissue was lower and it of HBcAg higher in "active" group of chronic liver diseases (CLD) as compared with in "inactive" group of CLD.
It was suggested that HBs & cAg were produced almost simultaneously in Rappaport's Zone 1, therefore hepatitis B virus multiplied in this area. That seems to be one of the most important factors which cause acute exacerbation in CLD. Changes of HBs & cAg in liver tissue in the course of acute exacerbation resembled those in the course of AH-B, except that HBs & cAg continued to exist after recovery from acute exacerbation in CLD. Distribution patterns of HBs & cAg in liver tissue did not suggest prognosis of the disease, nor progression from chronic hepatitis to liver cirrhosis.

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Acute effect of ethanol ingestion on hemoperfusion, rate of oxygen consumption and redox level of mitochondrial cytochrome c(+c1) in the liver in situ of anesthetized rats were measured by reflectance spectrophotometry. It was shown in fed rats that the ethanolstimulated O2 uptake in the liver by 30%. This increased O2 uptake initially caused a decrease in spectrophotometrically measured O2 saturation of hemoglobin and an increase in the redox level of cytochrome c(+c1) in the respiratory chain in the liver in situ, which was followed by an increase in blood supply to the liver. The redox change of cytochrome c(+c1) corresponds well with the change of the rate of O2 uptake. The ethanol-stimulated O2 uptake in the liver is discussed with respect to the pathogenesis of ethanol-induced liver damage.

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In this study, the analysis of the mechanism of alpha-naphthylisothiocyanate (ANIT) induced cholestasis was attempted by the examination of cytochrome P-450 (P-450) levels in liver microsome and nucleus using phenobarbital and cycloheximide. From the result of this examination, following hypothesis might be proposed. ANIT might be metabolized and turned to a hepatotoxic compound in the liver microsome, these chemically active ANIT might disturbe the bile canalicular portion and bile epithelium. Pretreatment of phenobarbital enhances P-450 production in the microsome. Therefore, the large amount of P-450 metabolizes a correspondingly large amount of ANIT to chemically active materials which resulted in progressive cholestasis. On the other hand, cycloheximide inhibits the production of microsomal P-450 which is closely related to the appearance of cholestasis with ANIT.
This study clarified in part the mechanism of ANIT induced cholestasis and the relationship, such as a precursor-product, between nuclear P-450 and microsomal P-450 was suspected.

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The phenotypic similarities of hyperplastic liver nodules and hepatomas have been well recognized. However, there are two kinds of hyperplastic nodules having reversible or irreversible character which may be closely linked to the induction of hepatoma. Therefore, we tried to analyze these characters in regard to cell growth. In conclusions, it might be difficult to understand reversibility and irreversibility of the nodules from the incidence of DNA synthesizing cells, although of course it seems that the nodules indicating low incidence of S-phase cells could be nongrowing.
On the other hand, a study of ploidity by means of cytophotometry showed that the huge nodules over 10mm in diameter could be "quiet" nodules which might be free from carcinogenesis.

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A 58 year-old male with alcoholic liver cirrhosis had been associated with persistent hemolytic anemia and died of acute DIC. On microscopic and scanning electron microscopic studies, approximately 80% of erythrocytes were of spur cell in shape. Biochemical studies revealed decreased serum level of lecithin cholesterol acyltransferase, and elevated cholesterol/phospholipid ratio in serum and erythrocyte membrane. Lipoprotein pattern by the polyacrylamide gel Disc Electrophoresis showed a midband between VLDL and LDL band, and also an abnormal HDL band. The levels of total bile acid and chenodeoxycholic acid increased in serum. Spur formation of erythrocytes was assumed to be caused by abnormalities in lipid and bile acids. Acute DIC was suggested to be induced by persistent hemolysis and severe impairment of hepatic reticuloendothelial system.

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The patient was a 48-year-old woman, whose earliest symptoms were generalized pruritus and skin pigmentation, and was admitted to our university hospital in November, 1971. The results of liver function tests on admission showed a cholestasis with markedly elevated alkaline phosphatase and cholesterol levels and with strongly positive antimitochondrial antibody. Histological examination of a surgically biopsied specimen of the liver revealed findings of chronic non-suppurative destructive cholangitis. Various kinds of therapy were tried without beneficial effects except for plasmapheresis, which was aimed at the relief of the xanthomatous neuropathy of the hands with a resultant improvement of symptoms, decreased serum cholesterol level and reduction of xanthoma.
In autopsy, about 6 years after the onset, the liver was cirrhotic and 850g in weight, and the result of histological examination was compatible with the diagnosis of primary biliary cirrhosis.

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A case (76 year-old female) of liver cell adenoma in the left lobe was reported. She had not used oral contraceptives. ⁶⁷Ga-citrate liver scintigram revealed positive tracer localization in the tumor. The resection of the left lateral segment with the tumor and cholecystectomy was done without incident. The tumor measured 6.5×7×6cm and was similarly grossly encapsulated. The histological findings showed well-differentiated liver cell trabeculus, Kupffer cells, no bile duct, no glisson's sheath and no nodularity.

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A 51-year-old woman with a cavernous hemangioma of the liver and hypofibrinogenemia was presented. Measurements of the plasma coagulation factor revealed a decreased fibrinogen concentration and an increase of fibrinogen degradation products. Platelet count and prothrombin time were within normal limit. Fibrinogen concentration and FDP were improved slightly by the heparinization. ¹³¹I-Fibrinogen was accumulated at the site of the tumor on the liver scintigram, this accumulation corresponded with defect of the liver scintigram with ⁹⁹mTc-phytate. A consumption of fibrinogen in the hemangioma was considered.
The resected tumor by extended right lobectomy of the liver was 2500g. in weight and 17×15×16cm in size. Fibrin was histopathologically proved in the section of the tumor by phosphotangstic acid hematoxylin staining. Fibrinogen concentration and FDP was normalized respectively after the surgery.

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A liver cell adenoma occuring in 18-year-old school girl with no history of drug use was reported.
She admitted for postprandial abdominal pain of several years' duration. Physical examination revealed no abnormalities except for a right-upper-quadrant mass.
Laboratory datas were normal, including CBC, liver function tests, urinalysis and stool. Liver scintigram and ultrasonogram revealed a tumor protruding from the right hepatic lobe. Peritoneoscopic examination demonstrated a grape-fruit sizcd rounded mass pedunculated from the infero-lateral margin of the right hepatic lobe.
Angiographic findings were compatible with liver cell adenoma.
The surgical specimen mesured 10.5×10.5×4.5cm and weighed 360g.
The tumor consisted of cords and sheets of well differentiated hepatocytes which did not exhibit lobular differentiation and formation of bile ducts or portal triads.

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