Sukeo Yamamoto

Primary biliary cirrhosis in japan: National survey by the subcommittee on autoimmune hepatitis

SummaryA total of 280 cases of primary bijiary cirrhosis were reported from 86 institutes in Japan, of whom 208 were middle aged women. Four clinical stages (asymptomatic, pruritus, icteric and terminal stage) were set up for analysing clinical and histopathological features based on the natural course of the disease. The clinical and histopathological findings were similar to the study reported from the United States and European countries. Out of 270 cases examined, 245 (90.7%), had mitochondrial antibodies. Concerning the prognosis 37 of 120 asymptomatic patients developed symptoms and the average symptom-free period in these patients was 28.7 months. Fifty-eight cases were fatal and causes of death were hepatic failure in 27, gastrointestinal bleeding in 20 and others in 11 cases. Patients were subdivided into three groups to elucidate the survival rate in patients with different symptoms. Asymptomatic patients showed almost the same survival rate as the patients with pruritus alone, showing about 50% survival 8 years after the diagnosis, in contrast to jaundiced cases with only 13.6% surviving 8 years after the onset of this symptom.

Effect of water-immersion stress on prostaglandin E2 in rat gastric mucosa

SummaryWe investigated the effect of stress on the prostaglandin E2 levels in rat gastric mucosa. In untreated controls, prostaglandin E2 levels were higher in the antral than the fundic mucosa. Stress experiments showed that 3O-min stress induced no gastric lesions but effected a significant (p<0.05) increase in antrai prostaglandin E2; after 7-hr stress exposure, hemorrhagic lesions and prostaglandin E2 levels significantly (p<0.05) below normal control values were noted. The formation of HCl-induced gastric mucosal lesions was markedly inhibited if 30-min stress preceded HCl-administration. The infusion of 5 μg/kg 16, 16-dimethyl prostaglandin E2 prior to 7-hr stress exposure inhibited ulcer formation markedly. Our results suggested that stress-induced decrease in intramucosal prostaglandin E2 plays an important role in the pathogenesis of stress ulcer formation.

Autoimmune hepatitis: The present status in Japan

SummaryA nationwide survey using questionnaires was carried out concerning lupoid hepatitis and related diseases (518 cases) during the 8-year period from January, 1975 to December, 1982. The following results were obtained.1.A total of 253 cases of autoimmune hepatitis, consisting of 97 lupoid hepatitis and 156 lupoid type CAH, were reported.2.Autoimmune hepatitis was overwhelmingly predominant in females, while male cases of B type CAH with a γ-globulin level of more than 2 g/dl significantly outnumbered female CAH cases of the same type.3.The liver function tests at the first examination demonstrated that transaminases, total bilirubin, ICG (R15) and γ-globulin were increased, and ChE was decreased in lupoid hepatitis. Lupoid type CAH showed a close similarity with lupoid hepatitis rather than to the nLnB type or B type with regard to liver function.4.Of the 289 patients who could be followed up, 280 cases (97%) received steroid hormones, and 247 (85%) received no another drug. Immunosuppressive treatment was also performed in 40% of the HBs antigen-positive cases of B type CAH.5.The efficacy was about 90% in the lupoid hepatitis group as well as in the lupoid type CAH group. It was no greater than approximately 70% in any other group.6.Analysis of survival revealed the following: 1) The cumulative survival rates of autoimmune hepatitis was lowest among the different types of CAH. 2) Patients who had a high serum level of total bilirubin tended to die sooner than those who had a low level. There was no correlation between the cumulative survival rate and serum γ-globulin concentration or antinuclear antibody titer. 3) The duration of steroid hormone therapy and the total dosage of immunosuppressants were thought to be important factors affecting the prognosis of autoimmune hepatitis.

A comparison of transcatheter arterial embolization with one shot therapy for the patients with hepatic cell carcinoma

SummaryIt has been confirmed gradually that transcatheter arterial embolization is the most effective, conservative therapy for the treatment of unresectable hepatic cell carcinoma (hepatoma). Embolization or one shot therapy was carried out in a clinical trial involving 41 patients with unresectable hepatoma visiting our department. Embolization group (emboli G): 19 cases. 1 to 6 embolizations in each case. One shot group (one shot G): 22 cases. Medications: Mitomycin C 10–40 mg and others.Disappearance rate of icterus after treatment was 50% (emboli G) and 25% (one shot G). Decrease in size of hepatomegaly or tumor was seen in 84% (emboli G) and 32% (one shot G) which was statistically significant (< 1 %). Serum AFP titer after embolization decreased in all cases but in only 5 of 12 cases (ca 41 %) after one shot (< 1 %). Effective cases measured by Karnofsky’s method were 18 out of 19 cases (95%) in emboli G, but in one shot G only 10 out of 22 cases (ca 45%)(< 0.1%). Survival rate after each therapy was 67% (emboli G) and 38% (one shot G) after 6 months, and 59% (emboli G) and 19% (one shot G) at 1 year respectively.One study showed that transcatheter arterial embolization therapy was much more effective than one shot therapy.

Inhibition by interferon (α + β) of mouse liver regeneration and its reversal by putrescine

Mouse interferon (α + β) given to mice by intraperitoneal injection suppressed both the accumulation of putrescine and stimulation of DNA synthesis in liver caused by partial hepatectomy. The suppression of DNA synthesis was completely reversed by exogenous putrescine. The same results were obtained when core 2,5‐oligoadenylate instead of interferon was given to partially hepatectomized mice. These results suggest that interferon inhibits putrescine formation through elevating the 2,5‐oligoadenylate level and thus inhibits DNA synthesis in the regenerating liver.

Changes in leukotrienes and prostaglandins in the liver tissue of rats in the experimental massive hepatic cell necrosis model

When heat-killed Propionibacterium acnes is intravenously injected into rats followed by an intravenous injection of a small amount of Gram-negative lipopolysaccharide (LPS) 7 days later, massive hepatic cell necrosis is induced and most of the rats die within 24 hours of LPS injection. Using this experimental model, we studied the changes in the levels of leukotrienes (LTs) and prostaglandins (PGs) in the liver tissue and bile of rats with experimentally-induced massive hepatic cell necrosis. Both the levels of LTs and PGs in the liver tissue and LTs in the bile increased before the microscopic appearance of hepatic cell necrosis. These results suggest that arachidonic acid metabolites may play an important role in the induction of liver cell injury.

Release of leukotriene B4 from rat Kupffer cells

In order to examine the production of leukotriene B4 (LTB4) from Kupffer cells, Kupffer cells isolated from the normal rat liver were incubated with calcium ionophore A23187, opsonized zymosan, or platelet activating factor (PAF), and the amount of LTB4 in the culture supernatant was determined by the combined technique of reverse-phase high-performance liquid chromatography and radioimmunoassay. As a result, when activated in vitro with calcium ionophore A23187, Kupffer cells generated LTB4. When Kupffer cells were stimulated with calcium ionophore after 10-min preincubation with AA861, a selective 5-lipoxygenase inhibitor, the release of LTB4 from Kupffer cells was markedly suppressed. PAF, which is a phospholipid mediator having a wide spectrum of biological activities, significantly enhanced the release of LTB4 from Kupffer cells stimulated with calcium ionophore or opsonized zymosan. Even when the Kupffer cell were not stimulated with calcium ionophore or opsonized zymosan, LTB4 production was significantly increased by PAF. Thus, our studies indicate that Kupffer cells could generate LTB4 as well as polymorphonuclear leukocytes and macrophages. In addition, it is suggested that Kupffer cells may be able to modify inflammatory and immunological events in the liver tissue by the release of LTB4.

Detection of hypersensitivity to drugs by lymphocyte cultures in drug-induced allergic hepatitis

SummaryFifty-three out of 70 patients with drug-induced liver injury showed an immunological response to the drug using either the lymphocyte transformation test or the macrophage migration inhibitory test (MI test) or both. Both the separated lymphocyte culture and the microvolume whole blood culture technique are available as assay methods. The latter method is simpler and the results of both methods are comparable. The administration of a synthetic copolymer of polyadenylic and polyuridylic acid (poly A: U) to the culture medium enhances the lymphocyte response to antigen and is therefore very useful to detect weak responses.

Comparison of results for Phase I studies with recombinant and plasma-derived hepatitis B vaccines, and controlled study comparing intramuscular and subcutaneous injections of recombinant hepatitis B vaccine

A comparison was made of the results obtained in separate Phase I studies conducted in Japan on a recombinant hepatitis B vaccine (HBX-R) and a plasma-derived hepatitis B vaccine (H-B-VAX). Recombinant hepatitis B vaccine was administered intramuscularly (IM) to 40 subjects in a dose of 10 micrograms, while H-B-VAX was administered IM to 35 subjects in a dose of 20 micrograms. Each subject received three doses of the vaccine at times zero, 1 month and 6 months. In both trials, at the end of 7 months from the first vaccination all vaccinees had become seropositive for anti-HBs antibody. During the 1-6 month period after the first dose, the seroconversion rate was always higher in the H-B-VAX subjects than in the HBX-R subjects. The anti-HBs antibody titre was also always higher in the H-B-VAX group during that same 6-month period, but there was no longer any difference at the 7th month (H-B-VAX: HBX-R = 1064: 1164 IU/L). In an additional study on the effect of the administration route on the efficacy of HBX-R, 124 subjects were randomly allotted to an IM group and a subcutaneous (sc) group. In each group, HBX-R was administered in 3 doses of 10 micrograms, again at time zero, 1 month and 6 months. At the end of the 7th month, the anti-HBs seroconversion rates were 98% (55/56) in the IM group and 97% (57/59) in the sc group.(ABSTRACT TRUNCATED AT 250 WORDS)

Synthesis of eicosanoids by Propionibacterium acnes-elicited liver adherent cells and their effect on production of interleukin 1 and tumor necrosis factor.

When heat-killed Propionibacterium acnes (P. acnes) is intravenously injected into rats or mice, liver adherent cells including macrophages and Kupffer cells increase in number and they synthesize various kinds of biologically-active materials. We studied the production of eicosanoids and the cytokines, interleukin 1 (IL-1) and tumor necrosis factor (TNF), by P. acnes-elicited liver adherent cells and the regulatory mechanisms of eicosanoids in the synthesis of cytokines. As a result, P. acnes-elicited liver adherent cells synthesized not only prostaglandin (PG) E2, 6-keto-PGF1 alpha, thromboxane B2 and leukotriene B4, but also IL-1 and TNF. In addition, PGE2 and PGI2 suppressed the production of these cytokines. These results suggested that there are auto-regulatory mechanisms in production of cytokines in the liver.