In order to study interaction between human fibroblasts and gastric cancer cells in vitro, biological behavior of fibroblasts (cell line WI-38) was investigated under the co-culture with the established gastic cancer cells (cell line KATO-III derived from a signet-ring cell carcinoma and cell line MKN-28 derived from a well differentiated adenocarcinoma). 1) Fibroblasts were co-cultured with two kinds of the cancer cells. The growth of WI-38 cells seemed to be inhibited by the proliferation of KATO-III cells. However, when co-cultured with MKN-28 cells, WI-38 cells proliferated vigorously. A mass of MKN-28 cells was surrounded by WI-38 cells, the scattered cancer cells resembling paving stones. PAS-positive material was observed in the interface between WI-38 and MKN-28 cells. 2) Effect of conditioned medium and cell debris of cancer cells on DNA- and glycosaminoglycans (GAG)-synthesis of fibroblasts were investigated by the incorporation of 3H-thymidine and 3H-glucosamine. DNA-synthesis of fibroblasts was stimulated by the conditioned medium of KATO-III, but GAG-synthesis was unaffected in any cases. GAG-synthesis of fibroblasts was enhanced by cell debris of KATO-III cells, and by cellulose acetate membrane electrophoresis, it was found that dermatan sulfate-synthesis was much more.
Among approximately 220 cases of ulcerative colitis accumulated in our Department during the period from 1954 to 1980; patients who were not operated on were investigated regarding their prognosis. The 106 cases were investigated by questionaires, and interviews were carried out in 66 cases. From these investigations, the following results were obtained. 1) Sixty nine percent of patients who underwent only medical treatment had complete remissions. In 21% of patients with proctitis, extension to the proximal colon developed during the observation period. 2) Surgical intervention was necessary in 39% of total colitis cases and 13% of left-sided colitis cases. Most of the operations were carried out within 2 years after the onset of symptoms. 3) In 1979, a relapse rate of 60% per year was observed and the relapse rate per month was about 40%. The relapse rates were constant and not related to the extent of the lesion or the length of the follow up period. Approximately 30% of patients of either sex experienced some inconvenience in daily life. 4) The relapse rate of patients during either pregnancy or puerperium was not higher than nonpregnant patients. However, relapses during both pregnancy and puerperium seemed to be more severe. 5) Seven patients died from causes related to ulcerative colitis in our University; 5 of them died within one year after the onset of symptoms.
The cholestatic factor showing a potent intrahepatic cholestatic activity was produced from the activated lymphocytes of tuberculine-snsitized guinea pigs by stimulation with PPD. The activity was observed in two fractions obtained by gel filtration on Sephadex G-75 followed by DEAE-cellulose column chromatography. When these two fractions were analyzed by means of an isoelectric focussing electrophoresis, it was shown that they contained different electric charges; one with an isoelectric point at 3.0-3.5 and the other at pH 7.8-8.0.
The change of flow volume and composition of hepatic bile following intravenous glucagon injection of 1mg was studied in 11 patients with obstructive jaundice. The examination was carried out 5 to 14 days after PTC-drainage. Glucagon produced 46.1% increase of bile flow volume and small increase of bilirubin concentration. Cholesterol, lecithin and bile acid concentration were slightly decreased. After glucagon injection, the output of bilirubin was significantly increased, however that of cholestrol and bile acid was slightly increased. Glucagon failed to increase the lecithin output. This choleretic effect of glucagon indicates that glucagon treatment is useful for additional reduction of the hyperbilirubinemia after biliary drainage in obstructive jaundice.
The kinetics of bile acids was investigated in patients with cholesterol gallstones. The bile was saturated with cholesterol, but the concentration ratio of each bile acid and the glycine/taurine ratio of bile acids were similar to those of normal subjects. The bile acids pool size was determined by isotope dilution method with deuterium labeled chenodeoxycholic acid which was administered intraduodenally. The pool size was decreased (0.47g, approximately one half of normal). The synthetic rate (190.8mg/day) was approximately one and half times greater and the turnover rate (39.8%) was about 2 times greater than the values obtained in the controls, while the half life of the labeled bile acid (1.67 day) was about one third of that in normal subjects. The rate of bile acid synthesis was also determined in 9 patients with cholesterol gallstones by measuring the activity of cholesterol-7α-hydroxylase which was considered to be the rate limiting enzyme for bile acid synthesis. The enzyme activity (8.77pmol/mg protein/min.) was reduced. It was considered that the relatively reduced bile acids synthesis, the lithogenic bile formation and diminished bile acids pool size were the essential features in patients with cholesterol gallstones.
The curreut investigation was designed to developed a radioimmunoassay method of pancreatic elastase in rats and to study the elastase levels. The presence of serum elastase inhibitors did not have an effect of the radioimmunoassay with the active sitespecific reagent Di-iso-propylfluorophosphate. The molecular size distribution of 125I-elastase or DFP- 125I-elastase after incubation with normal rat serum by Sephadex G-200 filtration suggested that 125I-elastase was bound to α2-macroglobulin and α1-antitrypsin, however DFP- 125I-elastase did not. Radioimmunoassayable elastase in serum was elastase-α1-antitrypsin complexes, following gel filtration of pooled serum with added exogenous elastase. There were no cross-react between human elastase I, procine elastase and bovine trypsin. A mean of 127ng/ml in normal rat serum have been determined and the minimal detectable amount was 4.7ng/ml. These results suggested that the radioimmunoassay for rat elastase which has been developed in this experiment is a specific and highly sensitive method for pancreatic elastase in rats.