Tadayoshi Takemoto

Morphologic studies of the liver cell dysplasia.

Light and electron microscopic changes in human liver cells which were considered to be precancerous lesions, were studied. In our micrometrical examination, dysplastic liver cells were classified into two types: large and small dysplastic cell. Each type had nuclear pleomorphism and multinucleation; however, the nucleocytoplasmic ratio of the large dysplastic cell remained normal. Electron microscopically, the large dysplastic cell had some features of regenerative cells. The nucleocytoplasmic ratio of the small dysplastic cell was between that of normal hepatocytes and liver cancer cells. The difference in the incidence of the small and large dysplastic cells in normal livers and cirrhotic livers having hepatocellular carcinoma was statistically significant. In addition, the small dysplastic cell had more of a tendency to produce a small round focus. It was morphologically suggested that the more important candidate for the precancerous cell in the liver was the small dysplastic cell.

Human serum immuno-reactive copper, zinc-superoxide dismutase assayed with an enzyme monoclonal immunosorbent in patients with digestive cancer.

Two types of monoclonal antibodies, N4 and N6, were raised against human copper, zinc-superoxide dismutase (Cu,Zn-SOD). An enzyme-linked immunosorbent assay for Cu,Zn-SOD was developed in sandwich method using these monoclonal antibodies. The measurable assay range was 1.0-100 micrograms/l and the coefficient of variation within and between series were 7.5% and 8.1%. Sera of 154 healthy control subjects displayed a low level (14 micrograms/l) of immunoreactive Cu,Zn-SOD with a logarithmic normal distribution. On the other hand, serum Cu,Zn-SOD levels were significantly elevated in patients with various digestive cancers.

Clinical evaluation of teprenone, a mucosal protective agent, in the treatment of patients with gastric ulcers : a nationwide, multicenter clinical study

The recurrence rate of gastric ulcers healing to a white scar is low, whereas that of ulcers healing to a red scar is high. Teprenone is a mucosal protective agent that can promote epithelial regeneration by increasing the mucosal hexosamine content. It promotes white scar formation when administered as maintenance therapy for ulcers. A nationwide, multicenter study was performed to determine whether white scar formation was also promoted when teprenone was used during initial therapy. Analysis of the data from 1249 patients showed that teprenone significantly promoted white scar formation. The presence of severe ulcers (large size and active stage), ulcer location at the gastric angulus, and smoking retarded white scar formation irrespective of the use of teprenone.

Gastric mucosal protection and superoxide dismutase.

Diethyldithiocarbamate (DDC), an inhibitor of Cu,Zn-su-peroxide dismutase (SOD), at a dose of 500 mg/kg or aminotriazole (AT), an inhibitor of catalase, at a dose of 2,000 mg/kg reduced slightly gastric mucosal SOD activity, did not change gastric mucosal blood flow (GMBF), and did not cause gastric ulcers. However, when both DDC and AT were administered together, gastric mucosal SOD activity and GMBF remarkably decreased, and gastric ulcers appeared. Moreover, the administration of SOD attenuated gastric ulcer induced by DDC plus AT. These results suggested that SOD may play an important role in the gastric mucosal defense mechanisms against active oxygen species.

Role of active oxygen species in diethyldithiocarbamate-induced gastric ulcer in the rat.

Diethyldithiocarbamate, an inhibitor of Cu,Zn-superoxide dismutase, was recently found to be ulcerogenic in the rat stomach, and active oxygen species were found to be responsible for its ulcerogenicity. To clarify which active oxygen species play a role in ulcerogenesis, the effects of various scavengers and iron-chelators were studied. As superoxide dismutase and catalase reduced the ulcerogenesis induced by diethyldithiocarbamate, the superoxide radical and hydrogen peroxide were considered to play a pathogenic role in this ulcer model.

Clinical use of glucagon and insulin in therapy of fulminant hepatic failure

SummaryWe have reported 5 cases of fulminant hepatic failure who were treated with a combination of glucagon and insulin. Marked improvement of hepatic coma was characteristically noted in all cases.

Early lesions and development of primary hepatocellular carcinoma in man--association with hepatitis B viral infection.

SummaryIt is well known that primary hepatocellular carcinoma could be derived from chronic hepatitis and liver cirrhosis in epidemiologic studies. However, it is still not clear what kinds of hepatocyte are premalignant cells. Recently we have focused on liver cell dysplasia as a possible premalignant cell, and showed localization of α-fetoprotein in the cytoplasma of these cells. Although the dysplastic cells were often seen in the liver of chronic active hepatitis, hepatitis B virus associated DNA polymerase activity was also significantly high in the sera from the patients with chronic active hepatitis. In this paper, we discuss the possible role of hepatitis B virus through hepatocarcinogenesis in human.

An immunohistochemical study of copper, zinc-containing superoxide dismutase detected by a monoclonal antibody in gastric mucosa and gastric cancer

The immunohistochemical localization of copper, zinc‐superoxide dismutase (Cu, Zn‐SOD) in human gastric mucosa and gastric cancer was studied using a monoclonal antibody. In gastric mucosa, parietal cells, pyloric glandular cells and foci of intestinal metaplasia showed positive staining in the cytoplasm and/or nucleus. The wide distribution of Cu, Zn‐SOD in the gastric mucosa suggests cell function may be vulnerable to active oxygen species. In gastric cancer, 34 of 70 cases showed a positive reaction for Cu, Zn‐SOD. There was a relationship between the grade of Cu, Zn‐SOD immunoreactivity and the histological type of gastric cancer, well‐differentiated types of gastric cancer being more frequently positive. The positive cases of poorly‐differentiated adenocarcinoma were characterized by a pattern of diffusely infiltrative invasion. These results suggest that some types of gastric cancer are resistant to active oxygen species.

Electronic endoscopy: Its present and future

As its image sensor, the electronic endoscope incorporates the so‐called charge‐coupled device (CCD) at its tip. The device was developed by the high technology of microelectronics, and it has a quite new construction, different from fibre‐optics. Two years after the electronic endoscope was produced first by Welch‐Allyn from the USA, the first Japanese electronic endoscope model was developed in 1985, and now an upper gastrointestinal model, a duodenoscope model, and a colonoscope model are available commercially from four companies worldwide.

Clinical evaluation of glucagon and insulin in therapy of fulminant hepatitis

SummaryForty five patients were examined in order to evaluate the usefulness of glucagon and insulin as a therapy of fulminant hepatitis. Thirty patients were treated with simultaneous infusion of glucagon and insulin, whereas prednisolone was given at a daily dose of 60 to 90 mg in 15 cases. In the former group, 1 mg of glucagon and 10 units of regular insulin were infused over a period of 2 to 6 hours. Two such treatments were given per day in the early critical period of fulminant hepatitis. The therapeutic effect of glucagon and insulin was evaluated in comparison with that of prednisolone, and additionally, with a combination therapy of either blood exchange or plasmapheresis in both groups. The survival rate was superior in the group treated with glucagon and insulin (46%) and in the one with combined infusion of these hormones plus plasmapheresis (33%).