In an attempt to elucidate the pathophysiology of the digestive diseases, especially the dieases of the stomach, the roles of the mast cell and the histamine in the gastric wall were studied. The tissue histamine was measured by the Shore's method. The mast cell count was expressed as the number in one squre milimeter of the tissue sheet. The results obtained were as follows: 1) The tissue histamine contents of the digestive organs in a man died from other than digestive disease were 1.46μg/g in the cardia and in the corpus of the stomach respectively and 1.0μg/g in the jejunum. In the rabbit, however, the average tissue histamine contents of the digestive organs were 0.48μg/g in the cardia, 0.34μg/g in the duodenum and 0.50μg/g in the jejunum respectively. Those in the guinea pigs were 0.43μg/g in the pylorus, 0.76μg/g in the duodenum, and 0.78μg/g in the jejunum. Those in rats were 0.74μg/g in the stomach, 0.33μg/g in the colon and 0.25μg/g in the small intestine. 2) In the glandular portion of the guinea pigs' stomach a close relationship was found between the tissue histamine content and the mast cell count. 3) In the resected stomachs of the patients with peptic ulcer, the mast cell counts were determined in various non-ulcerated portions. The mast cell counts were more numerous in the pylorus region than in the corpus, and the mast cell counts in the submucosal layer were more evident than in the mucosal layer in both regions. Also the tissue histamine contents in the pylorus region were greater than those in the corpus. 4) In rats, the influences of the administration of the stimulator or the inhibitor for gastric secretion upon the mast cell count and the histamine content as well as pH in gastric juice were studied. The subcutaneous injections of the stimulators such as 0.05mg of histamine hydrochloride, 0.05 of regular insulin, and 0.5 γ or 0.05 γ of gastrinlike substance given individualy brought an increase in numbers of intact-mast cell as well as degranulated mast cells and an increase in content of tissue histamine in the glandular portion of the stomach, and at the sametime these injection caused a decrease in pH of gastric juice. On the contrary, after the subcutaneous injections of 1r.u. of enterogastron, 0.025mg of atropine sulfate, 0.5 μ of secretin or 5 γ of gastrin-like substance the numbers of intact-mast cells as well as degranurated mast cells and the tissue histamine content in the glandular portion of the stomach decreased and at the sametime these injection caused an increase in the pH of gastric juce. 5) The average histamine contents released in the basal gastric juice of the patients with stomach diseases were 139.0μg/l in 7 cases with atrophic gastritis, 95.8μg/l in 5 cases with gastric ulcer and 89.4μg/l in 10 cases with duodenal ulcer respectively, indicating the higher levels than the mean value of 81.3μg/l in 8 healthy persons. From the results mentioned above, the mast cell and the tissue histamine in the glandular portion of the stomach were considered to have a close correlation and to play an important role for the secretion of gastric juice.
Lipid analysis of the biopsy specimen of the human liver was carried out in 6 cases of nonspecific hepatitis, 11 cases of chronic hepatitis, 10 cases of liver cirrhosis, 5 cases of the fatty liver and in 5 cases of mild non-hepatic disease. Biopsy was performed under laparoscopic visual field and the diagnosis was made on the histological findings. Lipids were extracted with chloroform-methanol 2:1, separated on 1D and 2D TLC and estimated by colorimetric assay of phosphorus, ester-linkage and cholesterol. Lipid composition of the control liver in non-hepatic disease showed the total phospholipid 2.95% (±0.29) of the wet weight of the liver, free cholesterol 0.17%, ester cholesterol 0.19%, and triglyceride 0.20-0.80%. In cases of non-specific reactive hepatitis, ester cholesterol was slightly decreased, while. the other components did not show a marked change. In chronic hepatitis and in the early stage of liver cirrhosis, accumulation of triglyceride was observed. Ester cholesterol was also increased in these cases. The liver showing the triglyceride content more than 1% of the wet weight of the tissue was found to have a fatty change on histological observation. Total phospholipid was significantly decreased in most of the cases of chronic hepatitis and liver cirrhosis (2.40±0.22% in chronic hepatitis and 1.4-2.2% in liver cirrhosis). Cholesterol was also decreased. Phosphorus analysis on 2D TLC showed that phosphatidyl ethanolamine was decreased in most of the cases of chronic hepatitis and liver cirrhosis. In cases of hyperlipemia, the decrease of total phospholipid was not so marked as in the early stage of the liver cirrhosis which showed the same extent of the fattt change. In all of the cases of hyperlipemia and in a case of progressive lipodystrophy, an acidic phospholipid tentatively identified as lyso-bis-phosphatidic acid was increased. In a case of hyperlipemia which showed a storage of lipoid substance in the liver, lymphnodes and the bone marrow, this phospholipid encounted 21% of the total phospholipid. Microdetermination of liver lipids in the biopsy specimen seems to be important in the study on fatty liver and hyperlipemia.
Histochemical studies on Leucine Aminopeptidase (LAP) were made on human stomach, surgically resected due to gastric cancer, gastric polyp and gastric ulcer. The results obtained are summarized as follows: 1) Gastric cancer cells of intestine metaplasia origin are LAP negative (with exception of 20-30%) and generally exhibit expansive growth. Above-mentioned exceptional cases show decreased LAP activity with the progression of cell atypism. 2) Gastric cancer cells of gastric mucosa propria origin are LAP positive (with exception of 14%) and show intense infiltrative growth. 3) LAP activity of gastric cancer cell is considered one of the index of malignancy. The function of the activity however, is not connected with proteolysis of surrounding tissues, but with production of intestine mucous, which also prove Alcian blue positive reaction and alkaline phosphatase activity. 4) LAP activity in the stroma of gastric cancer is associated with the fibrous formation, and it does not seem to be reactive changes specific to the neoplasia.
Using the experimental chronic gastric ulcer induced by the clamping cortisone method (c-c ulcer by Umehara & Tabayashi), the micro-vascular changes observed during the course of the ulcer and the influence of drugs on the changes were examined. For observation of the vascular changes, the stomach was infused with India Ink and the stomach preparations were prepared for microscopic study. The results obtained from the c-c ulcers (c-c group), were compared with those of the ulcers induced by clamping alone (the control group), those of the ulcers treated with long term administration of cortisone (the Cr group), those of the ulcers treated with small doses of anabolic steroids (19NAPP) (the D-1 group) and others with large doses (the D-2 groups) The results of the studies are as follows; 1) Regeneration of the vascular phlexuses in the submucosal layer of the c-c ulcer was remarkably inhibited in the early stage of the ulcer and vasclarization directed toward the base on the ulcer was not found in the c-c ulcer at the same stage. 2) In the c-ulcer, the anastomoses of the blood vessels which regenerated from both sides of the ulcer were formed within in 1 week after making the ulcer, but in the c-c ulcer, these horizontal anastomoses were not formed at such an early stage and a vertical vascularization like a palisade began to be built after the first week. This means that the poor development of the holizontal collagen fibers resulted in reterdation of healing of the ulcer. So that, the ulcer deteriorated and a wide base like a plateau was formed. 3) In the Cr-group, development of the vacslsrization and healing of the ulcers were slower compared with those of the c-c group. 4) In the D-1 group, regeneration of the vascular phlexuses in the submucosal layer began in the early stage. The vascularization directed toward the base of the ulcer and contruction of the ulcer became prominent and healed rapidly. On the other hand, the vascular phlexuses in the submucosal layer of the D-2 group regenerated remarkably in the early stages compared with that of D-1 group, but the healing of the ulcer was not promoted in the middle stage. The prolongation of healing in this groups seemed to be due to the wearing off effect of the steroid.