Role of tissue fibrinolysis in the pathogenesis of protein-losing gastropathy was further investigated in an experimental model of dogs using Dithiothreitol (DTT). Perfusion of the dog stomach revealed increased protein loss from the gastric mucosa in association with the elevation of either fibrinolytic activity or β-glucuronidase activity in the biopsied gastric mucosa. Beta-glucuronidase activity was also found to increase in the gastric perfusate in the presence of DTT. Antifibrinolytic agent, trans-AMCHA, revealed suppressive effect on protein loss into the gastric cavity induced by DTT, while failed to reduce β-glucoronidase activity in the gastric mucosa. It was concluded that tissue fibrinolytic activity in the gastric mucosa was increased by the use of DTT, and to which lysosomal labilization seemen to play a part. Trans-AMCHA acted as an inhibitor of fibrinolytic system, and probably not as a stabilizer of lysosomal enzyme, and exerted the preventing effect on the protein loss through the gastric mucosa.
Gastric acid secretion induced by intravenous infusion of tetragastrin, histamine, 2 deoxy-D-glucose, insulin and acetylcholine was markedly inhibited by additional infusion of PGE1 in Schild's rat. Intravenous infusion of PGE1 or PGE2 (0.04μg/kg-min) inhibited basal acid secretion, but did not inhibit pepsin secretion in man. In rat, tetragastrin-stimulated acid secretion was accompanied with the increase of intragastric excretion of methyleneblue dye, but the dye excretion was not always inhibited by PGE1. Intravenous infusion of PGE1 increased basal serum gastrin, but inhibited histamineinduced serum gastrin in rat. From these results, it is considered that E type of prostaglandin, produced inhibition of gastric acid secretion, may act directly on the parietal cell of the stomach.
The carcinoembryonic antigens in the cancerous and noncancerous tissue of the stomach and colon as well in the plasma of patients with cancer of the digestive tract were quantitatively estimated by means of a kit of radioimmunoassay. Several factors influencing plasma level of CEA were analysed by histological studies of the cancerous tissues. Major factors hich influence plasma CEA level of patients were found to be the CEA concentration in tumorous tissue and the CEA content in the whole tumorous tissue along with depth of cancerous invasion and metastasis. The CEA content of the tumorous tissue of gastrointestinal cancer varied depending on the organs from which the cancer grew and on their histological types. In the cases with colonic cancer, there is a correlation between them was noted in the patients with the gastric cancer. Cases with gastric and colonic cancer in which severe cancerous infiltration or heavy interstitial fibrosis were noted showed low levels of plasma CEA. Patients with colonic cancer in which invasion of lymphvessel or vein were noted showed high levels of plasma CEA. CEA was also detected in the non-cancerous mucosa of the stomach and colon, though the amount was small, and an order of CEA amounts of in them was colonic, pyloric gland and fundic gland mucosa.
Colonic mucosal and enterobacterial antigen-induced cytotoxicity of lymphocytes in patients with ulcerative colitis on non-specific target L cells was studied using 51Cr release assay. PHA-induced cytotoxic effect of lymphocytes was also studied. The following results were obtained. 1. There was no statistically significant difference between PHA-induced cytotoxicity of lymphocytes from patients with ulcerative colitis and from healthy controls on L cells. 2. The cytotoxic effect of lymphocytes from patients with ulcerative colitis on L cells was obviously low in quiscent stage compared with that in other stages. 3. The lymphocyte-mediated cytotoxicity by colonic mucosal and enterobacterial antigens was respectively found in 13% and 29% of patients with ulcerative colitis which was clinically diagnosed as active stage. 4. In healthy controls, significant cytotoxicity of lymphocytes to both antigen was not detected.
Carcinomas and adenomas were induced in Wistar rats by 1, 2-Dimethylhydrazine subcutaneous administration. In this experimental model we have found that colonic tumors developed frequently on the paticular site of the ascending colon, where the lymphoid follicle is normally present under the obliquely running folds. Four different modes of morphogenesis of colon cancer at this site was noticed from our observation. 1. Signet ring cell carcinoma evolving from the bottom of the tubules covering the lymphoid follicle. 2. Well-differentiated adenocarcinoma arising from the covering mucosa of the lymphoid follicle. 3. Adenocarcinoma presumably arising from misplaced epithelium in the lymphoid follicle. 4. Multicentric occurrence of adenocarcinomas in the covering mucosa of the lymphoid follicle.
Characteristic pharmacodynamic in 1-(2-tetrahydrofuryl)-5-fluorouracil (FT-207) metabolisms and its clinical efficacy in 10 patients with primary hepatoma were studied by comparing those in 14 cases with gastrointestinal and lung cancers as control. The clearance rates (K) of FT-207 from the circulating blood in patients with hepatoma were significantly smaller as compared to those in control patients with normal liver functions. The unresponsiveness of the K values to pretreatment with indomethacin and tocopheryl nicotinate, which decreased and increased the K values in control patients, respectively, was observed in primary hepatoma. Only a case with hepatoma had a positive clinical response to FT- 207 chemotherapy, much better responses being obtained in patients with gastrointestinal cancers. Time courses of FT-207 concentrations in the blood during the continuous oral administration indicated higher levels in hepatoma patients than in control patients. However, the levels of FT-207 in the blood and the K values were not directly correlated with its clinical efficacy and the occurrence of side effects in those patients.
The effects of obesity, hyperlipidemia and impaired glucose tolerance on the liver function tests (total protein, A/G ratio, ZTT, TTT, ALP, GOT, GPT and LDH) were studied in the subjects who were examined generally in our hospital. In males the liver function tests were more closely associated with obesity than with hyperlipidemia and impaired glucose tolerance. Abnormal liver function tests in the obese subjects were characterized by mild elevations of serum transaminase with a greater rise in SGPT than in SGOT. In females the liver function tests were hardly influenced by obesity, hyperlipidemia and impaired glucose tolerance, and the majority of females had normal results in the liver function tests.
This study was designed to determine AFP producing cells during restitution of acute rat hepatitis induced by galactosamine administration. When galactosamine was given to animals intraperitoneally, liver restitution was first seen after 3 days. AFP positive hepatocytes were detected in an area where regeneration of the damaged liver cells occurred. By concurrent application of immunoperoxidase and autoradiographic methods, it was shown that the AFP positive hepatocytes tended to appear with a little delay from the appearance of the DNA synthesizing hepatocytes. In immunoperoxidase electron microscopy, AFP was demonstratedd in close association with polyribosomes. The present study suggests that AFP in acute galactosamine hepatitis was produced by the regenerating hepatocytes.
Bile acid and lipid composition of bile was estimated in 39 patients with gallstones and 8 controls. Twenty four patients with pigment stones in the biliary ducts and/or the gallbladder showed normal lipid composition of bile. In their bile acid composition, relative proportion of cholic acid significantly decreased, chenodeoxycholic acid increased and among many of them, ursodeoxycholic acid was detected. Many of them, including 4 old patients showed markedly elevated glycine/taurine-conjugated bile acid ratio, perhaps by proliferation of bacterial floras in the intestine. Meanwhile, 15 patients with cholesterol stones in the gallbladder showed significantly low bile acid/cholesterol ratio of bile, indicating supersaturation of bile with cholesterol. In their bile acid composition, relative proportion of cholic acid and deoxycholic acid elevated and chenodeoxycholic acid significantly decreased. Considering the relationship of biliary lipid composition to glycine/taurine-conjugated bile acid ratio, decrease of bile acid synthesis was suspected. In 6 patients with acute obstructive jaundice, proportion of cholic acid markedly elevated.
Eight patients with congenital cystic dilatation of the common bile duct (choledochal cyst) had been diagnosed by the ultrasonographical examination as a screening test for diseases of the hepato-biliary system at Tenri Hospital from 1970 to 1978. Final diagnoses of these patients were confirmed at operation. Only one of these involved male and the others females. The youngest was 2 month-old boy and the oldest 57 year-old female with arising of papillary adenocarcinoma in the cyst. On the ultrasonographical findings of these patients simple cystic pattern was revealed in 5 cases and mixed pattern in 3 cases. Differential diagnosis from the other cystic lesions in the right upper abdominal cavity and retroperitoneal space is a difficult problem on the ultrasonographical examination for this disease. Ultrasonographical examination, we think, is now more effective for this disease than other radiological diagnostic methods.
130 cases of Transduodenal Papilloplasty (TDP) were performed in the Institute of Gastroenterology, Tokyo Women's Medical College since 1969. This operation was mainly indicated to the benign papillary stenosis c/s gall stones. Our preference in this procedure is to excise the upper part of the papillary area and to make sutures between the duodenal mucosa and the common bile duct. 50 patients were followed up to see any postoperative changes along biliary system mainly from the view point of clinical aspects and ERCP. Results are following: 1. The results of this operation was not satisfactory in 8 patients among 50 (16%). 2. There is a statisticaly significant correlation between the diameter of the biliary orifice and the length of papillary excision. 3. Above results indicated that the length of excision should be over 25mm. 4. There was no recurrent or remnant stones. 5. Well-indicated, well-excised TDP may lead to the good results.
In order to clartify abnormalities of lipid metabolism in patients with cholestasis, plasma lipids and lipoproteins were analyzed by various methods such as electrophoresis, gel filtration, electron microscopic examinations, and analytical ultracentrifugation. Lipid analysis revealed enhancements of phospholipid, free cholesterol and triglyceride, whereas cholesterol ester ratio and phospholipid/free cholesterol ratio were decreased. Lipoprotein analysis showed the presence of a distinct lipoprotein in plasma. Immunological and ultracentrifugal studies disclosed that the special lipoprotein was identical with Lp-X, isolated by Seidel's method. Most of the changes observed in both lipids and lipoproteins in plasma of patients with cholestasis can be explained by the presence of abnormal Lp-X. On the other hand, several other changes of plasma lipoproteins and lipids, such as reduction (or absence) of either α-or pre-β lipoprotein, as well as elevation of triglyceride, are not due to the consequences of elevated Lp-X. In cholestatic plasma, major portion of triglyceride was found to be in LDL fraction rather than in VLDL fraction, indicating the abnormality in LDL fraction, the Sf coefficient of which was significantly higher than that of plasma LDL in normal subjects. Fatty acid analysis of lecithin and cholesterol ester of isolated Lp-X showed that both lipids were originated from the bile, since their fatty acid compositions were similar to those of bile lipids, but neither to those of normal plasma nor chylomicron.
This study was carried out to find a difference of clinical pictures of 112 patients with chronic pancreatitis, who were divided into 4 groups according to its etiologies, seen in Hokuriku district during the past 8 years. The patients were divided into idiopathic group (44 cases), alcoholic group (42 cases), bile tract group (17 cases) and other origin group (9 cases). Chronic pancreatitis was diagnosed by the following criteria: calcification of pancreas on X-ray, positive P-S test or histological proofs of chronic pancreatitis. The idiopathic group showed no difference in sex and a less frequency of abdominal pain and pancreatic calcification than other groups. The alcoholic group, of which 97.6% were male, showed the highest percentage of pancreatic calcification, had a low pancreatic function in many of them and showed a poorer prognosis than other groups. The bile tract group was seen in older age than other groups, and clinical findings concerning diseases of the bile tract were observed. The other origin group was seen in younger age, and had a low pancreatic function in many of them and showed more resistence to therapy. Accordingly, it is recognized that there was a difference of clinical pictures among each groups.
We classified 36 cases of pancreatolithiasis into six types by pancreatogram, excluding the cases not confirmed by pancreatogram and those with the translucent pancreatolithiasis associated with congenital choledochal cyst. Six types are as follows: I: large calculi exist in branches, II: large calculi exist in main duct, III: large calculi exist in main duct & minute calculi, in branches, IV: minute calculi exist in branches, V: minute calculi exist in both main duct & branches, VI: translucent pancreatolithiasis. The patients with large calculi rarely have the history of the alcoholic ingestion and the complication of diabetes mellitus. All women have large calculi. But half of patients with minute calculi have the history of alcholic ingestion and complication of diabetes mellitus. As all the patients with translucent pancreatolithiasis have the history of alcoholic ingestion and half of them were complicated with diabetes mellitus, those cases may be dealt with pancreatolithiasis. Pancreatic stones located only in the branches of pancreas head appears to be a special subgroup.