A significant correlation has been found between serum PG 1 and gastric secretory function such as basal acid output (BAO), maximal acid output (MAO), basal pepsin output (BPO) and stimulated pepsin output (SPO) in patients of peptic ulcer. The various feeding tests in healthy volunteers revealed no significant response of serum PG 1 level to the stimuli used, although the tendency of increase was found. Neither protein meal nor fatty meal showed any certain effect on serum PG 1 level. In sham-feeding test, serum PG 1 was increased five minutes after stimulation but rather depressed by pretreated with atropine (1mg) without statistical significance. It was concluded that serum PG 1 can be used as a good marker of gastric secretory function although the releasing mechanism of serum PG 1 into blood circulation remained uncertain.
The purpose of this study was to examine the morphological changes and endocrine profile (gastrin, somatostatin) in the gastric mucosa of mice with atrophic gastritis induced by neonatal thymectomy. The mice were killed on 2 months after thymectomy which was done on 3 days after birth in BALB/c (+/?) mice. Of the thymectomized mice, 27.4% had marked reduction of parietal and chief cells as well as inflammatory cell infiltration especially lymphocytes, plasma cells and eosinophilic cells, 64.1% of which had positive parietal cell antibody. Hypergastrinemia, antral G cell hyperplasia and increase of mucosal concentration of antral gastrin was observed in mice with this type of atrophic gastritis. On the other hand, mucosal concentration of somatostatin and the number of D cells in the body mucosa in mice with gastritis were decreased when compared to those in the control, but in the antrum the concentration and the number of D cells were almost the same as those in the control.
We investigated the effect of senna, one of the laxatives, on the levels of prostaglandins (PG) in the rat gastric mucosa. Intragastric (i.g.) instillation of senna (3mg/kg) increased PGE2 by 3.6 times (p<0.025), PGI2 by 3.7 times (p<0.01), TXA2 by 2.8 times (p<0.01), in the fundic mucosa; PGE2 by 2.9 times (p<0.01), PGI2 by 3.4 times (P<0.025), TXA2 by 1.5 times (N.S.) in the antral mucosa. High dose of senna (300mg/kg, i.g.) also increased PG levels dose-independently. I.g. instillation of senna (300mg/kg) inhibited the gastric lesions induced by the necrotizing agent (0.6N HCl)-the ulcer index, 10.0±8.3; significantly different at p<0.05 from controls indicating the ulcer index at 49.2± 12.1-. These results suggest that the cytoprotective effect of senna is mediated by the endogenous PG in the gastric mucosa.
In order to investigate the participation of gastric mucosal connective tissue catabolism in the ulcer formation, Wistar strain rats were administered with 1ml of 0.25N HCl and 2ml of 0.6N HCl solution per Os, injected with pentagastrin (25μg/ml body weight), and restricted by means of a plastic bandage for six hours. The gastric mucosa of each rat was scraped off from the stomach, washed with saline, weighed and homogenized for the estimation of collagen-bound hydroxyproline (HOP) content, hexosamine content, uronic acid content and coliagenase activity. These treatments increased collagen catabolism in gastric mucosa, that is, decreased HOP content and increased collagenase activity. Gastrin injection decreased HOP content compared with that of control rats (814±71μg/g tissue (n=5) vs. 1, 476±166 (n=5); p<0.02) and increased collagenase activity (0.54±0.04μg collagen degraded/hr/mg protein (n=5) vs. 0.32±0.03 (n=5); p<0.05). Restraint stress increased collagenase activity up to 206%. On the other hand, administration of cimetidine, proglumide and pirenzepine effected the collagenase activity restraint stress and made the activity 208%, 181% and 81%, respectively. These data suggested the presence of the close correlation between connective tissue metabolism ingastric mucosa and the secretion of acid and gastrin.
This study was designed to clarify the mechanism of glucose intolerance in patients with total gastrectomy. 1) Oral glucose tolerance tests (OGTT) to pre and post totally gastrectomized patients and intraduodenal administration of glucose (IDGTT) to patients before operation were performed. Blood gulcose levels following 50g oral glucose ingestion changed from normal to diabetic pattern after the operation. In patients with total gastrectomy, plasma insulin response to oral glucose tended to be higher than those in preoperative subjects, while plasma glucagon rose after the operation and significantly higher than the response to IDGTT. 2) 10 dogs were subjected to one of the four conditions as follows; a) OGTT to nonoperated dogs, b) IDGTT before truncal vagotomy, c) IDGTT after truncal vagotomy and d) OGTT after total gastrectomy: OGTT to nonoperated dogs showed a slight increase of glucagon, whereas IDGTT caused moderate rises of glucagon, and totally gastrectomized dogs showed marked glucagon responses to OGTT. Meanwhile, IDGTT revealed no significant difference in glucagon levels either before and after truncal vagotomy. These results suggest that elevated glucagon after oral glucose may contribute to the glucose intolerance in patients with total gastrectomy and that not only the rapid inflow of glucose to the intestine but also removal of the stomach itself may be responsible for the excessive glucagon responses to an oral glucose administration in the subjects with total gastrectomy.
The depth of cancer invasion, classified into 4 groups (1; m.sm, 2; pm, 3; ss.se, 4; sei) was evaluated by selective angiography of celiac, left gastric, common hepatic and superior mesenteric arteries on 137 gastric cancer patients before surgery. The rate of correct angiographyic diagnosis was found 88.3% by examining the surgical specimen in reference to the depth of invasion. The pm cancer, of which the depth of invasion is difficult to estimate by X-ray or endoscopy, was correctly evaluated in 76.5%. The angiography found 84.6% of the early simulating advanced cancer as advanced, of which the depth of invasion was correctly diagnosed by angiography in 69.2%. It is believed that the angiographic study would lead to more correct diagnosis as to the depth of cancer invasion, is found helpful for establishing appropriate surgical plan.
We have studied the effect of a novel H2-receptor antagonist, Famotidine (YM-11170), on a gastric acidity, plasma secretin and gastrin in 5 patients with duodenal ulcer. 24-hour intragastric pH was monitored continuously by wired glass electrode in each case, administrating of Famotidine (40mg/day, twice orally, after breakfast and at bedtime) and of placebo in the following week, who was on a standard diet. Without administration of Famotidine, basic intragastric pH varied from 1.0 to 1.5 with transient increases at prandial time and midnight time. Famotidine was effective to regulate intragastric pH values in the nighttime (pH 5-7). Mean intragastric H+ activity, which was converted from pH measurements, was significantly suppressed by Famotidine in the daytime (% suppression, 47.0%), nighttime (81.2%) and 24-hour (56.8%). Thus, it was revealed that oral administration of Famotidine 40mg/day would be valuable for the inhibitory effect on gastric acidity in duodenal ulcer patients. With administration of placebo, significant increase in plasma secretin concentrations occurred after a meal. However, with Famotidine, postprandial secretin elevation did not occur significantly. On the other hand, postprandial gastrin concentrations increased more significantly in comparison with placebo.
Fifty male Wistar rats were divided into five groups of each 10 rats and operated in order to examine the effects of intraluminal pressure and devascularization in pathogenesis of ischemic colitis. In group 1, marginal arteries of the left colon were ligated in two points at intervals of 2cm. In group 2, rectum was completely obstructed by ligation. In group 3, were operated with combination of both precedures. In group 4, 30mg sodium picosulfate (laxoberon) was administered orally for 2 days after ligation of marginal artery. In group 5, the same laxative was only administered orally for 2 days without operation. The animals were sacrificed 72 hours after the surgery and were examined on morphological changes of the colon macroscopically and histologically. The activities of serum GPT, LDH and Al-pase were also examined in each group. The experiments gave the following results -2 rats of group 1 (20%), one rat of group 2(10%), 8 rats of group 3(80%) and 2 rats of group 4(20%) showed ischemic lesions on the left colonic mucosa. Histologically, the observed ischemic changes consisted of necroses in several degrees from mucosa to muscularis propria, erosions or ulcerations. The incidence of ischemic lesion in group 3 was significantly higher than in other groups. It may be concluded that increasing intraluminal pressure additional to devascularization of colonic wall, is considered to play an important part in pathogenesis of ischemic colitis.
Human liver microsomal epoxide hydroloase (EH), which was a single polypeptide band with 50, 000 molecular weight and 361 unit/mg protein enzyme activity, was purified from an autopsied normal liver tissue by means of Lus' method. It was immunized with a rabbit to get a specific anti-human EH serum. The localization of EH, γ-glutamyl transpeptidase (γ-GTP) and α-fetoprotien (AFP) were simultaneously studied on the tissue sections with primary hepatocellular carcinoma by the immunoand /or histochemical staining method. The intensity of EH in tumor tissues increased in 4 cases (16%), showed the equal level in 12 cases (48%) and decreased in 9 cases (36%), as compared with the surrounding non-tumor tissues. The intensity of γ-GTP or AFP in tumor tissue increased in 12 cases (48%), 19 cases (76%) respectively. There was no definite relation among their intensities in tumor tissues. These results suggest that EH is an important protein to identify a precancerous lesion of human hepatocellular carcinoma.
Hepatic hemodynamics in patients with alcoholic liver injuries has been studied by organ-reflectance spectrophotometry and hydrogen clearance method during peritoneoscopy. The regional hepatic blood volume (ΔEr569-650) assessed by organ-reflectance spectrophotometry was correlated positively with the regional liver blood flow measured by hydrogen electrode. Both the regional hepatic blood volume and the saturation level of hepatic blood hemoglobin decreased with progress of liver fibrosis to liver cirrhosis. On the other hand, the regional hepatic blood volume decreased with fatty metamorphosis, but the saturation level of hepatic blood hemoglobin didn't. The regional hepatic blood volume was correlated positively with prothrombin time and negatively with γ-globulin. It is concluded that the liver blood flow decreases with the progress of fibrosis and fatty metamorphosis in patients with alcoholic liver injuries.
Hyperamylasemia is frequently observed in cirrhotic patients. To clarify the mechanisms of the elevated enzyme activity, we investigated the importance of renal excretion of amylase in these patients. Upon separation of serum isoamylases with inhibitor method, the amylase levels of pancreatic and salivary type were both elevated in cirrhotic patients as compared with those of nomal controls. However, the ratio of the P/S isozyme were similar in both the cirrhotic patients and the control group. The clearance studies indicated that Cam, Cpam, Csam, Cam/Ccr, Cpam/Ccr and Csam/Ccr were all decreased in cirrhotic patients, and simultaneously the total amount of urinary excretion of these amylases were reduced. Using polyacrylamidegel electrophoresis of serum amylase, the "slower moving peak" which is distinct from P and S type was detected in the serum of 5 of 29 patients with cirrhosis of the liver. This peak was also present in one of 23 normal sera, however, the amount of "slower moving peak" amylase were small and seemed to be not the major determinant of amylase clearance. We concluded that hyperamylasemia and low Cam/Ccr ratio in cirrhotic patients were mainly on the basis of reduced renal excretion of the enzyme.
To elucidate the lowering mechanism of serum γ-glutamyl transpeptidase (γ-GTP) activities in patients with acute intrahepatic cholestasis (AIHC), liver γ-GTP activities were determined. In patients with AIHC, in spite of low activities of serum γ-GTP, the liver enzyme levels were significantly higher than those in healthy subjects and in patients with chronic liver disease (p<0.02). Liver γ-GTP activities in all subjects significantly correlated with the liver alkaline phosphatase (ALP) levels (p<0.001). On the other hand, liver ALP activities in AIHC patients also increased, and the ALP levels in all subjects significantly correlated with serum ALP levels (p<0.001). An electrophoretic study of liver γ-GTP showed similar mobility among normal, liver cirrhosis and AIHC. Moreover, no inhibitors of γ-GTP were detected in sera of patients with AIHC. These results suggest that low γ-GTP activities in sera of AIHC are due to the release obstacle of the enzyme from the liver.
In order to study on abnormality of fat absorption from intestine in patients with hepatobiliary diseases, fecal bile acid, serum bile acid and fecal fat were determined in 13 normal subjects and 19 patients (liver cirrhosis, primary biliary cirrhosis (PBC) and cholestasis). The results were as follows: 1. The mean values of daily fecal excretion in cirrhosis, PBC, and cholestasis were 157, 343 and 124gm respectively. These data were not significantly different from controls (149gm). 2. In all patient groups a significant increase of fecal fat, a remarkable decrease of fecal bile acid and elevation of serum bile acid were detected. Then, there was a significantly negative correlation between fecal fat and fecal bile acid excretion. When excretion of fecal bile acid was decreased below 30mg per day (one-tenth of that in controls), chemical steatorrhea in hepatobiliary diseases was always noted. Therefore, we concluded that chemical steatorrhea in hepatobiliary diseases could be induced due to the reduced amonuts of bile acid in intestine.
The ability of carboxyl-terminal tetra-(CCK4) and octapeptide (CCK8) of cholecystokinin (CCK) to increase pancreatic exocrine and endocrine secretion was examined in the isolated perfused rat pancreas. CCK8 had a biphasic dose-response curves for stimulating pancreatic juice and amylase secretion in that, as the concentration of CCK8 increased, fluid and amylase secretion increased, became maximal at 100pM, and then decreased with supramaximal concentration. The minimal effective concentration of CCK8 (10pM) tested for pancreatic exocrine secretions was the same as that for insulin release. In contrast to exocrine pancreatic secretions, supramaximal concentrations of CCK8 for stimulating pancreatic juice and amylase output did not cause submaximal stimulation of insulin release. The dose-response curves for exocrine and endocrine secretion to CCK4 were shifted 100, 000 fold to the right compared with those to CCK8. The concentration dependence of CCK4-stimulated pancreatic exocrine secretions and insulin release was similar with the threshold concentration being 1μM.