Detection of hepatitis B surface antigen (HBsAg) containing polypeptide coded by the pre-S region of hepatitis B virus DNA (pre-S antigen) was performed using enzyme immunoassay with monoclonal antibody.
Pre-S antigen was positive in 148 out of 150 (98.7%) serum samples from chronic HBsAg carrier and its titers obtained by quantitative measurement were 29, 303 ± 25, 571 units in hepatitis B e antigen (HBeAg) positive asymptomatic carrier (ASC), 995 ± 1, 085 units in antibody to HBeAg (anti-HBe) positive ASC, 2, 637 ± 3, 538 units in patients with HBeAg positive chronic hepatitis, 1, 414 ± 2, 684 units in anti-HBe positive chronic hepatitis, 1, 385 ± 1, 988 units in HBeAg positive liver cirrhosis, 280 ± 368 units in anti-HBe positive liver cirrhosis and 138 ± 77 units in hepatocellular carcinoma.
There was good correlation between pre-S antigen titer and HBsAg titer by RPHA, r=0.7497 in ASC, r=0.8542 in chronic liver disease.
It remains to confirm the clinical significance of pre-S antigen.

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To evaluate the effect of insulin-like growth factor-I (IGF-I) on liver regeneration, the serum levels of IGF-I in rats after partial hepatectomy were measured by radioimmunoassay. The serum levels of IGF-I were decreased from 2.79 ± 0.28pmol/ml to 1.45 ± 0.12pmol/ml twelve hours after 70% partial hepatectomy. The levels of insulin were significantly decreased and those of glucagon were significantly increased after partial hepatectomy. The serial change of IGF-I levels was similar to that of insulin, and there was a significant correlation between IGF-I and insulin levels. The serum levels of IGF-I, insulin and glucagon were not altered in sham-operated rats.
These findings suggested that IGF-I might stimulate the proliferation of hepatocytes as insulin in liver regeneration after partial hepatectomy.

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A series of T and B cell-specific monoclonal antibodies was used to determine the location and subpopulatiolls of T and B lymphocyte in liver biopsy specimens with lymphoid follicle-like structure (from 12 cases with CAH, 2 cases with LC, 2 cases with AH and 3 cases with PBC) by means of an immunoperoxidase technique.
The majority of cells in the lymphoid follicle-like structure (LFLS) were reactive with T-11 (E-rosette cell) and T-4 (helper/inducer T) antibodies. Increased percentage of the T-4 positive cells in the LFLS was statistically significant compared with that of the other portal areas excluding LFLS and that of the portal areas without LFLS. However, the percentage of T-4 staining cells in this area did not correlate with the levels of serum IgG, γ-glob., TTT and K-ICG respectively.

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Two different monoclonal antibodies (McAb) designated H2 and B2 which were specific for human hepatocytes were developed by fusing P3-NS1 with spleen or lymphnode cells from BALB/c mice sensitized by a fractionated soluble phase of a human liver homogenate. It was demonstrated by immunoperoxidase technique that the reactivities of these McAb were restricted to human hepatocytes. Twenty four other organs, rat, rabbit livers were negative in staining. The cytoplasm of hepatocytes was stained by the both McAb although the cell membrane was also stained by H2 McAb. These results suggest that the antigens defined by these are different from LSP which is known to be species-nonspecific and localized exclusively on cell membrane and other liver-specific antigens already known. It is proposed that the antigen defined by H2 McAb is designated human liver-specific antigen 1 (HLSA1) and that the antigen defined by B2 McAb is designated human liver-specific antigen 2 (HLSA2).

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The stimulating function of peripheral blood monocytes against T cell blastogenesis in patients with chronic liver disease was investigated by measuring its stimulating role on T cell blastogenesis to PHA. Stimulating role of monocytes against T cell blastogenesis in patients with chronic active hepatitis (CAH), chronic hepatitis with sublobular hepatic necrosis (CHcSN) and liver cirrhosis (LC) were decreased, compared with control subjects (p<0.05, p<0.01, p<0.01). In order to eluciate the cause of monocytes hypofunction, the activity of suppressor macrophages was examined. Its activity in patients with CIcSN and LC was markedly enhanced compared with control subjects (p<0.05, p<0.05). It was suggested that suppressor macrophages played a role on monocyte hypofunction. Corticosteroid was proved to suppress the stimulating role of monocytes, but did not suppress suppressor macrophages. It was suggested that monocyte and macrophage participated in dysfunction of cellular immunity in chronic liver diseases.

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We purified the hepatic bile duct antigen from the human bile and confirmed that this antigen showed the antigenic cross reactivity with salivary gland duct, pancreatic duct and renal tubulus, but no cross reactivity with other organs. And we prepared the species specific antibody (bile duct antibody) against the bile antigen in rabbits to detect the bile antibody in circulating immune complex from the patients with PBC by using ELISA. In PBC, 20 of 68 cases showed positive results (29.4%). In contrast, bile antibody was detected in none of 3 cases with lupoid hepatitis, 1 of 4 SLE, 1 of 6 rheumatoid arthritis, 1 of 10 Sjogren's syndrome which is often associated with PBC, and 2 of 36 chronic pancreatitis. The present study showed that bile antibody was contained frequently within circulating immune complex from patients with PBC. These findings support that PBC is likely to be a autoimmune disease.

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There is growing evidence for heterogeneity in antimitochondrial antibodies (AMAs) (M1-M7) and their clinical and pathognomonic significance in AMA positive diseases. In AMA positive liver diseases, it has been reported that M2 antibody (Ab) was detected both in PBC and CAHPBC miXed type, but M4Ab was detected in CAH-PBC mixed type. We investigated the incidence of these two AMAs (M2 and M4Ab) in 26 patients of PBC and in 2 patients of mixed type with complement fixation test (CFT) and also with western immunoblotting (WB) to analyse target antigens. M2Ab was shown to be positive in all 28 cases using both methods, but M4Ab was positive in 4 of 26 cases of PBC with CFT and 7 of 26 cases with PBC with WB M4Ab was detected in all cases with CAH-PBC mixed type by both methods. M2Ab reacted with 8 protein bands: molecular weights of 72, 67, 59, 57, 56, 52, 45, 42 kilodaltons (K.D.), in which each protein band was detected with a different frequency. But protein bands of 72 and/or 67 K.D. were commonly detected in all sera containing M2Ab. M4Ab reacted with a single antigen band of 39 K.D, which was considered to be a newley appearing antigen after trypsinization of submitochondrial particles.

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Cell surface extracts of hepatoma which were prepared for use as antigen to detect the tumor specific immunity of hepatoma patients showed the strong activity to suppress in vitro antigenspecific or nonspecific blastogenesis of peripheral blood lymphocytes. Such activity was also found in surface eXtracts derived from normal liver cells.
In view of recent findings that liver L-arginase can inhibit in vitro cell growth, we examined the correlation between level of arginase activity in extracts and intensity of suppression induced by these extracts, and then the reversibility of suppression by adding arginine to cUlture medium.
Results were as follows;
1) Arginase activity was found in all extracts which were prepared by mild procedure for cell surface extraction. The level of this activity significantly correlated with intensity of suppression by extracts.
2) The suppression could be almost completely reversed by addition of optimal amount of arginine to culture medium.
3) Extracts from normal liver, cirrhotic liver or hepatoma cells showed a distinctive levels of arginase activity, respectively. This seemed to reflect some correlation between synthesis of arginase eXisting presumably on cell surface and pathological state of liver.

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The origin and structue of Mallory body was investigated by light and electron microscopy in the liver of griseofulvin treated mice. Relationship between cytoskeleton and Mallory body formation was also studied in perfusate livers with detergent solution. Cholestasis and protoporphyrin deposition was revealed in early stage. Mallory body was detected after 3 experimental months. Electron microscopy disclosed dilatation of bile canaliculi with loss of microvilli. Increase of pericanalicular microfilament and intermediate filament were also observed. Microtubular change was not clarified. In the early stage, Mallory bodies were appeared as irregularly arranged fibrillar and granular structures, which were surrounded by RER and ribosomes. Intermediate filaments showed reticular pattern in cytoplasm, and they were remarkably increased in number after griseofulvin administration, and they seemed to be contacted with fibrillar component of Mallory body. However, no morphological transition between them was observed. The present study suggest that Mallory body might be formed by a sequel of pathologic keratinization of hepatocyte by griseofulvin.

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Dynamic CT was performed in 14 normal subjects, 11 cases with chronic hepatitis and 43 cases with liver cirrhosis. One ml/kg of 65% meglumine amidotrizoate was injected in 10 seconds via an antecubital vein. Serial scans were undergone at 18sec. as a hepatic arterial phase, 34sec. as an early portal phase, 50sec. as a middle portal phase, 90sec. and 120sec. after the beginning of the injection, on the basis of circulation times of hepatic arterial and portal venous streams determined by 133Xe method as reported previously. Concentration of contrast medium was measured on hepatic parenchyma. The concentration values in liver cirrhosis at 34 and 50sec. were 20.9±5.7 and 27.6±5.7H.U., respectively, and each was significantly (p<0.001) lower than 44.8±5.1 and 40.8±5.5H.U. at each time in normal subject. Those values in chronic hepatitis were indicated to be median between in liver cirrhosis and in normal subjects.
Therefore, it was suggested that dynamic CT based on hepatic hemodynamics was a useful method for diagnosis and evaluaton of hemodynamics in chronic liver diseases.

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We attemped to make an experimental model of IPH by infusing the aggregates of nonpathologenic Escherichia coli (E. coli) and its dog antiserum via the portal vein in the dog from seven to ten times during two weeks.
Blood flow and portal systemic shunting were measured by radioactive microsphere techniques.All IPH dogs model group had portal hypertension (portal venous pressure 15.8±5.4 Vs 7.5±0.9mmHg, in control group; p<0.005), but portal systemic shunting, however, was not abnormally increased in IPH dogs model group (2.1±1.5 Vs 0.8±0.7%, P=NS).
Portal blood flow was increased in IPH dogs model group (27.0±6.5 Vs 18.1±2.5ml/min/kg) (p<0.005). Portal vascular resistence was increased in IPH dogs model group (1.9±0.7 Vs 0.7±0.3dyn·s·cm-³×10³; p<0.005). Splancnic hemodynamics in IPH dogs model group demonstrate that portal hypertension is maintained, at least in part, by a hyperdynamic portal venos inflow and increased portal venous resistance.
Hyperdynamic studies were performed in IPH dogs model group, using nonpathologenic E, coli and its dog antiserum, to define whether the hemodynamic alterations in dog with portal hypertension would conform to flow and vascular resistance dependent form of portal hypertension.

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We studied the effect of vasopressin, infused continually via the superior mesenteric artery, on the hemodynamics of the portal venous system. Superior mesenteric venous blood flow decreased with statistical difference, as did portal venous blood flow and portal venous pressure. However, splenic venous blood flow did not decrease significantly and there were even some cases in which an increase was apparent, despite the decrease in cardiac output, which is considered to be a systemic side effect arising from the use of vasopressin. We suspect there was a increase in the splenic venous flow to compensate for the decrease, caused by the infusion of vasopressin, in the superior mesenteric venous blood flow. The changes in O2 content of the superior mesenteric and splenic veins indicated the same phenomena as indicated by the blood flow measurements.

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We resected 4 cases of multicentric hepatocellular carcinoma (HCC) with cirrhosis. Typical trabecular type HCC were seen in two of cases. At least one of the lesions in all cases has hypovascular tumors by selective hepatic angiography. Accumulation of hepatocytes with high N/C ratio and hyperchromatic nuclei commonly formed in 2 or 3 cell plates, and partially in trabecular pattern. Because of the lack of space, we witnessed hardly any so-called "blood space" in the fields, which leads us to believe that it is hypovascular by angiography. No tumor thrombi were evident. Furthermore, tumor characteristics were different in all cases. Therefore we diagnosed these cases to be multicentric hepatocellular carcinomas.

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Purification of cyt P 450-PB which is induced by the phenobarbital was performed from rat liver microsomes and anti-cyt P 450-PB serum was obtained from rabbit. Localization of cyt P 450-PB was studied by immunofluorescent method using the antiserum in rat with normal liver, hyperplastic nodules and hepatocellular carcinoma, to understand the changes of cell propeties during hepatocarcinogenesis.
Cyt P 450-PB in normal rat localized around the central vein. In hyperplastic nodules and hepatocellular carcinoma, specific fluorescent areas of cyt P450-PB was not observed, although a few cells was positive in hepatocellular carcinoma. Pericentral areas of rat liver carrying hyperplastic nodules and hepatocellular carcinoma are less fluorescent than that of normal rat. To comparison with cyt P 450-PB, localization of epoxide hydrase (EH), which is another drug metabolizing enzyme, was also studied by immunohistochemical method. Hyperplastic nodules are positive areas of EH, but only a few cells are positive in hepatocellular carcinoma.
These changes of localization of cyt P 450-PB and EH were characteristic during experimental hepatocarcinogenesis. Whether these changes are based upon phenotype happened during carcinogenesis or results effected by metabolizing of carcinogens is remained to be explored.

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Cyanosis and clubbed fingers have occasionally been noted in cirrhotic patients. In this report, we present a case who was supposed to have arteriovenous fistulas in the lung by quantitative radionuclide method.
On January 19th 1985, a 60-year-old male was admitted to our hospital because of recurrent esophageal varices and severe hypoxia. Arterial oxygen tension during the breathing of room air was 47mmHg and the traditionally caluculated shunt ratio (Qs/Qt) was 20.1%. Percent right to left shunt estimated by the radionuclide method was as high as 57%. Endoscopic sclerotherapy was performed uneventfully on February 6th and 14th. He was discharged on February 19th and has been followed in the outpatient clinic.

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A 58-year-old male suffered from PBC and PM is reported. He was admitted because of liver dysfunction chanced to be found by screening test asymptomatically. AMA and ANA (both homogeneous and speckled types) were positive. ALP and IgM levels were increased. Laparoscopic and histologic findings proved to be PBC (stage I). Two years after the diagnosis, he was re-admitted on account of muscle weakness and of increased CPK level (1321mU). Muscle biopsy findings were compatible with PM. Oral administration of prednisolone (45 mg/day initially) brought him marked improvement of the symptoms and laboratory data derived from PM. The cases in association with both PBC and PM have been rarely reported. Those literaures are reviewed. Such cases may be present more latently without correct diagnosis. It is important to pay attention to myositic manifestations in PBC patients for early detection of PM association.

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