Normal gastric mucosae (5 young adults) and the regenerative mucosae over gastric ulcers (45 patients) were biopsied endoscopically and studied under a scanning electron microscope. The regenerative epithelium of the gastric ulcer first appeared as a single layer of flat epithelium gradually spreading over the bottom of the ulcer and gradually assuming a palisade-like structure. A pavement-like structure then appeared through segmentation. Gastric foveolae formation followed, giving the appearance of a pyloric gland-like structure so as to show a transition to the surrounding gastric mucosa. Observation under high magnification revealed numerous processes of various shapes on all cell surfaces, probably representing a form of mucus secretion. Intestinal epithelial metaplasia was found in 37% out of 45 gastric ulcers. Such change appeared separately in each gastric foveola, followed by a gradual spread through fusion. Sharp demarcation was found between the portion with intestinal epithelial metaplasia and that with gastric epithelium, and between the portion with fundic glands and that with pyloric glands.
With regard to the healing process of gastric ulcers, the role and contribution of the mucosa adjacent to the ulcer as well as the granulation tissue in it's basis were assessed in terms of the vasculature and vascular communication with each other as observed under the scanning electron microscope. Plastic models were made of the vasculature of gastric ulcers produced in rats by the topical application of acetic acid. The models were then coated with gold. Subsequently, they were observed under the scanning electron microscope. The regenerating mucosa was observed to keep blood circulation not only with the mucosa adjacent to the ulcer but also with the granulation tissue in the basis of the ulcer. Along with the healing process of ulcers, the capillary vessels in regenerating mucosa were observed to anastomose with the small vessels in the granulation tissue, the latter being supplied from the adjacent submucosa. Formation of meshed vasculature in the regenerating mucosa were delayed in antral ulcers, compared with that in fundic ulcers.
The effects of different intraduodenal pH levels on the release of IRG into the duodenal lumen were studied as the following. Thirty four mongrel dogs were anesthetized with nembutal and underwent whole removal of the G-I tract except the fundic area of the stomach and the duodenum. The duodenal lumen was perfused with distilled water at the designed pH levels, the levels being renged from 1.0 to 9.0. Perfusate and blood were sampled simultaneously every 10 minutes for IRG determination. In order to check the possible leakage of plasma gastrin into the duodenal lumen, 125I-SHG was injected into the femoral vein of the dog identically operated, while perfusing the duodenal lumen with the perfusate of pH 3.0. Perfusate and blood samples were collected every 10 minutes for counting the radioactivity. Results: Perfusing the duodenal lumen with the perfusates of either pH 1.0 or 3.0, we could confirm the release of IRG into the duodenal lumen. All other pH levels of perfusates ranging from 5.5 to 9.0 were inert to elicit IRG release into the duodenal lumen. Intravenous injection of 125I-SHG did not cause any meaningful rise of radioactivity in the duodenal lumen perfused at pH 3.0. Conclusion: IRG was released into the duodenal lumen only when it was perfused at the pH levels of 1.0 and 3.0. Any leakage of plasma 125I-SHG into the duodenal lumen being not observed, the IRG mentioned above was presumed to have been released from G-cells in the duodenal mucosa.
Gastric pepsin and acid secretion, and pepsin acid correlation were studied in three patients with Zollinger-Ellison syndrome (ZES). The results were obtained as follows. In all nocturnal secretion and histamine-, insulin- and gastrin-stimulated secretions, pepsin hypersecretion was not conspicuous as acid hypersecretion, and so pepsin acid correlation showed low level of less than 1.0. Not only before operation but also after vagotomy or gastroectomy, the same results were obtained. These results suggest that both before and after operation ZES should be suspected in the patients with pepsin acid correlation of less than 1.0. in nocturnal secretion or stimulated secretion.
Experimental gastric carcinoma was developed on inbred Wistar strain rats by oral administration of N-methyl-N'-nitro-N-nitrosoguanidine, and resulting tumor was transplanted successfully into subcutane of the same strain rat until 24th generation. Alkaline phosphatase (ALP) isozyme were determined in those transplantable tumor tissues, and their enzymological and immunological charaterizations were analysed. ALP isozymes did not differed significantly until 20th generation, and were similar to those of primary tumors as previously reported (Oncodevelop Biol Med 1: 313, 1980) on out-bred rats. However, after 22nd generation, ALP zymogram from the transplantable carcinoma tissues of rat stomach showed only non-intestinal-type ALP isozyme (A-band). Therefore, it was suggested the possibility that the abnormal gene expression in ALP production, especially intestinal-type ALP isozyme (B-band), had changed during the long transplantation such as over 22nd generation, and did not inherit in transplantable tumor cells.
We employed immunofluorescent staining on formalin-fixed paraffin sections improved by trypsin digestion to exsamine the mucosal expression of secretory component (SC), IgA and CEA in normal and pathologic lesions of the stomach and the colon. This method may be simple as compared with PAP method, and a useful adjuvant to histopathologic study, in which a retrospective immunohistochemical examination may be desireble. By trypsin digestion formalin-fixed paraffin section shows a equivalent staining to ethanol fixed one. Normal colonic mucosa shows strong stainings of SC, IgA, and CEA as compared with normal gastric mucosa. Gastric and colonic carcinomas show decreased stainings of SC and IgA and increased stainings of CEA. In adenomatous polyp of the colon, stainings of SC, IgA and CEA are closely correlated with the grades of cellular and structural atypia. These comparative immunohistochemical study will be able to become one of the useful methods to exsamine either cancer-adenoma sequence in the colon or causal relation between gastric carcinoma and intestinal metaplasia.
Activities of blood coagulation and fibrinolytic systems were investigated. Platelet count was increased in ulcerative colitis, especially in the active stage. Of the coagulation factors, factor VIII was significantly increased in ulcerative colitis as compared with the normal healthy control. Antithrombin III was increased, on the other hand, α1 antitrypsin and alpha;2 macroglobulin significantly diminished. Thromboelastogram showed an increase of Ma value. In fibrinolytic system, euglobulin lysis time was shortened, and plasminogen activity was increased. The present data indicated that the blood coagulation system was activated in ulcerative colitis, particularly in the active stage.
The effects of various drugs on the isolated liver cells were investigated in vitro. When chlorpromazine (CPZ), ajmaline (AJ), cephaloridine (CER), cephalothin (CET) or carbon tetrachloride (CCl4) were added to the isolated liver cell suspension and cell viability was measured by a trypan blue dye exclusion test, the order of cytotoxic effects of these drugs were: CCl4> CPZ>AJ>CER=CET. The order of the capability to induce the lipid peroxide formation in hepatocytes were: CCl4>CER>AJ=CET>CPZ. However, the order of the release of GOT enzyme activity from the hepatocytes were: CCl4>CPZ=AJ>CER=CET. Moreover, surface scanning of the isolated hepatocytes revealed that these drugs produce more or less morphological changes in membrane strcuture.
Although the lymphocyte transformation and lymphokine production have been frequently used for the identification of the causative drug in patients with drug-induced allergic hepatitis, these immunological parameters are not always positive in all patients. This may be reflected on the small population of the sensitized lymphocytes. In order to augment these immunological reactions, we deviced a method which interleukine-2 was added to the lymphocyte culture simultaneously with the antigen (drug and carrier). In four cases which did not show any positive lymphocyte transfromation and lymphokine (cholestatic factor) production by stimulating them with the drug in the presence of the suitable carrier, the addition of interleukine-2 was shown to enhance the immunological responses; lymphocyte transformation with th causative drug was significantly induced. Moreover, long-term culture of the sensitized lymphocytes was shown to be successful by cultivating th activated lymphocytes in the presence of interleukine-2 and lymphocyte transformation and cholestatic factor production were detectable in the culture at least two or three months after the cultivation.
Fifty patients with hepatocellular carcinoma were treated by transcatheter arterial embolization (TAE) alone without combined hepatic artery infusion chemotherapy. The effect and indication of TAE therapy were investigated in comparison with those of the one-shot injection therapy using Mitomycin C through a catheter introduced into the hepatic artery (Chemotherapy). (1) The one year survival rete (34.6%) with TAE therapy was higher than that (18.2%) with Chemotherapy. (2) The response rate (64.0%) with TAE judged from the criteria based on changes of clinical findings after the therapy was higher than that (38.1%) with Chemotherapy. (3) It was concluded that TAE was effective for hepatocellular carcinoma when indication was limited to the cases with a tumor extention smaller than 60%, no portal vein occlusion distal to the 2nd order branches, serum total bilirubin_??_5.0mg/dl, serum GOT_??_200I. U. and no ascites.
Changes of plasma cAMP level and operative mortality after 30% and 70% hepatectomy were evaluated in Wistar stratin rats with obstructive jaundice. The basic plasma cAMP level increased 20 to 60% after bile duct obstruction but did not correlate with the duration of obstruction. The plasma cAMP response to stimulation by glucagon (G-CAMP test) showed a corresponding decrease with the time course, with the response 2 weeks after the obstruction being under 20% that of the preoperative condition. The response just after the release of the bile duct obstruction, increased temoporarily following decrement, but recovered only 70 to 80% even at 8 weeks after the release. The mortality rate of 70% hepatectomy for the rats with jaundice persisted for 2 weeks was increased significantly. The mortality rate was correlated with the plasma G-cAMP response. It is concluded that G-cAMP test is useful as an indicator of the hepatic functional reserve of cases with obstructive jaundice.
Ultrasonic-guided puncture cholecystography was performed in 54 cases with negative cholecystograms by intravenous cholangiography, ERCP or PTC, and the successful results were obtained in 46 cases. The puncture cholecystograms of patients witn gallbladder disease were classified into six types, and the method proved useful with benign/malignant differentiation being easy in 79% of the cases. However, the differentiation was difficult in Type D in which the neck of the gallbladder or the end of the cystic duct showed an obstruction with smooth margin. Cytology of the bile aspirated at gallbladder puncture showed that all benign cases were negative, while positive findings were obtained in 5 out of 8 subjects with carcinoma of the gallbladder. The concurrent use of cholecystography and cytology of the bile made a diagnosis of carcinoma of gallbladder possible in 7 of 8 cases. It is, therefore, considered that the two methods should be used together.
This study was designed to elucidate a relationship between fibrous proliferation and collagenase activity in the pancreas following acute pancreatitis. Necrotizing pancreatitis was produced by a freezing procedure in the splenic segment of the pancreas of male Wistar rats. The freezed areas in the pancreas of these rats were studied at each time on histological changes, hydroxyproline levels determined by KISO method and collagenase activities detected by tissue culture method using neutral soluble collagen as substrate. The fibrous proliferation and hydroxyproline levels in the pancreatic tissue increased gradually after freezing procedure and reached to a peak of them at the 4th week. Following this, the both of them decreased with the lapse of time. The collagenase activities in the pancreatic tissue were found after 2 weeks, and 66.7% of the highest detection rate of the activity and grade 4 of the most intensive activity, exhibiting the lysis of almost all substrate, were recognized at the 5th week. These collagenase activities disappeared after 7 weeks. In examination using polyacrylamide gel disc electrophoresis, the purified collagen used as a substrate revealed 3 basic bands consisted of α, β and γ, and the substrate occurred the lyses by the pancreatic tissue showed further many bands separeted αA, βA and several degraded products. From these findings, it is suggested that there is a close relationship between elevation of collagenase activity and fibrous change in the pancreas following necrotizing pancreatitis, and that collagenase activity plays an important role in dissolution and absorption of proliferated collagen fibers.
The present study was designed to observe the effect of 4-week oral administration of ranitidine, a new histamine H2-receptor antagonist, on pancreatic exocrine secretion in rats. As the result, basal pancreatic flow, basal bicarbonate output, and pancreozymin- and secretin-stimulated pancreatic flow in the ranitidine group were significantly lower than those in the control group. On the other hand, there was no significant difference between the two groups with regard to the output of amylase or protein. These data indicate that long-term administration of ranitidine affects the function of epithelial cells of pancreatic ductules only. However, the pancreas in the ranitidine group was histologically normal, and neither serum secretin level before and after duodenal acidification, nor fasting serum gastrin level in the ranitidine group showed a significant difference from those in the control group. We observed the reduction of pancreatic exocrine secretion after 4-week administration of ranitidine, but the mechanism has not been clarified.