Department of Surgery and Pathology Division of Central Laboratory, Shinshu University School of Medicine, Matsumoto 390 Processes in the development of intestinal metaplasia of the stomach were investigated from the morphological and histochemical approaches using light and electron microscopic techniques. The specimens taken from 38 gastric carcinomas and 15 gastric and/or duodenal ulcers were subjected to this study. Morphological appearances of the intestinal metaplasia observed in routine examination with hematoxylin and eosin staining was able to be divided into complete and incomplete metaplasia by the light and electron microscopic histochemical stainings of the mucosubstances. The columnar cells at the area of the incomplete metaplasia had both the properities of the intestinal and the gastric foveolar epithelia. The incomplete metaplasia as well as the complete metaplasia arose from the generative cells at the isthmus of the gland. The generative cells, however, sometimes gradually transformed to produce the complete metaplastic cells. The two processes of the development of the intestinal metaplasia were proposed and discussed.
Gastrin cell (G cell) population in gastroduodenal mucosa was studied quantitatively by immunoflorescence in 10 patients with gastric ulcer and 12 patients with duodenal ulcer. In both groups of patients G cells were mostly populated in the pyloric antrum and they were much less in the intermediate zone and the proximal duodenum. Distribution of G cells in the pyloric antrum was greater in density at the greater curvature than at the lesser curvature. This could be explained through greater thickness of the mucosa and less frequent incidence of intestinal metaplasia of the gland at the greater curvature. The number of G cells per unit mucosal surface area in each block of the pyloric antrum was statistically greater in the duodenal ulcer group than in the gastric ulcer group. The estimated total number of G cells in the whole pyloric antrum including the intermadiate zone in the duodenal ulcer group was (1.806±0.307 S.E.M.)×107, the value being significantly greater (P<0.05) than that of (0.807±0.207)×107in the gastric ulcer group. This difference was chiefly brought about by less frequent incidence of intestinal metaplasia of the antral mucosa in the duodenal ulcer group. The estimated total number of G cells showed a significant negative correlation not only with the age of the patients but with the degree of intestinal metaplasia of the antral mucosa in both the groups.
The relationship between jejunal bacterial overgrowth and urobilinogen excretion in the urine was studied in 9 patients with jejuno-or ileotransversostomy and 3 healthy volunteers. Jejunal juice was obtained by intubation, and the total urobilinogen excretion in 24 hours was estimated by I2-H2O method by Watson. In 5 cases whose jejunal juice contained many bacterium such as E. coli and Streptococcus faecalis, 4 showed abnormally high urobilinogen excretion in the urine. In two of the cases with jejunal bacterial overgrowth, antibiotics (AB-PC, 1g daily) was administered, and the results was the marked decrease in urine urobilinogen excretion to the normal level, with negative bacterial growth in the jejunal juice. On the other hand, in 4 cases whose jejunal juice showed less growth (less than 105 colonies/ml) in culture, all excreted normal value of urobilinogen. It is suggested that the abnormally high urobilinogen excretion in the urine of such cases with anastomoses between small intestine and colon, is due to the overgrowth of bacterium in the jejunum.
The role of tissue fibrinolysis and lysosomal enzymes on the hemorrhagic necrosis of digestive mucosa was investigated in an experimental model of DIC (disseminated intravascular coagulation), produced by intravenous administration of bacterial lipopolysaccharide (endotoxin) in dogs. The fibrinolytic activity in the biopsied digestive mucosa revealed marked elevation following the administration of endotoxin, to which the changes of the lysosomal enzymes such as acid phosphatase and beta-glucuronidase were found to be correlated. Pretreatment of the intestinal mucosa of dogs by trans-AMCHA, or by Trasylol, prevented the intestinal mucosa from hemorrhagic necrosis in DIC. The lysosomal enzymes were markedly reduced at the mucosa pretreated by these chemicals, suggesting the possibility that the release of lysosomal enzymes from the mucosal cells were inhibited, or the activity of lysosomal enzymes released were inhibited by either trans-AMCHA or Trasylol. These data led us to conclude that the lysosomal enzymes, including plasminogen activator, play an important role in the pathogenesis of hemorrhagic necrosis associated with DIC.
Biliary excretion of BSP or ICG and the influence of synthetic ATP thereupon were examined on the ATP deficient rat through an intraperitoneal injection of d-frunctose (20mmole/Kg b.w.). the following results were obtained. 1) Content of ATP in the whole liver homogenate was increased through either intraperitoneal or oral administration of synthetic ATP, although it was less and slow through the latter. 2) The hepatic content of ATP was decreased through an intraperitoneal injection of dfructose. 3) An intraperitoneal administration of d-fructose decreased the hepatic content of Y and Z proteins, but the activity of hepatic microsomal cytochrome P-450 and the hepatic uptake of 3H-bilirubin were unchanged. On electron microscopy no distinct abnormality was noticed in the hepatocyte and bile ductule. 4) The decrease of hepatic content of ATP through an intraperitoneal injection of d-fructose was inhibited by either an oral or intraperitoneal administration of synthetic ATP. 5) Bile output and biliary excretion of BSP or ICG were decreased through an intraperitoneal injection of d-fructose. In general, the decrease of biliary excretion of dyes was based on thediminished bile output. 6) The decrease of bile output and biliary excretion of BSP through d-fructose were inhibited by an administration of synthetic ATP, but the inhibition was not clear in the case of ICG excretion. It was concluded that hepatic ATP is indispensable to the mechanism of bile excretion and that either oral or intraperitoneal administration of synthetic ATP can increase the hepatic content of ATP and participate in the mechanism of biliary excretion of dyes.
Antibody-dependent cell-mediated cytotoxicity was studied in patients with chronic active hepatitis (CAH) and healthy controls (N) using a nonimmune normal non E-rosette forming cells (non E-RFC), tested sera and cultured rat liver cells (Coon cells) with a ratio of target cell to non E-RFC of 1:300. Non E-RFC alone showed a mild cytotoxicity to Coon cells in the absence of human sera (21.5±1.5%) and in the N-sera treatment of Coon cells (26.0±5.1%). After preincubation of Coon cells with CAH sera, % cytotoxicity of normal non E-RFC was increased to 49.4±8.7%. This augmentation of cytotoxicity by CHA sera was blocked by aggregated IgG, antihuman-IgG and -IgG/Fc. CAH sera, absorbed with Coon cells or rat hepatocyte-surface membranes, did not show any augmentation of cytotoxicity to Coon cells. In the absence of normal non E-RFC the control and test sera alone did not induce cytotoxicity to Coon cells. In 7 of 10 sera from patients with CAH, membrane-fixed IgG on Coon cells was detected and showed a fine granular pattern. There was no difference of staining pattern between sera with and without HBsAg. Neither IgA nor IgM membrane-bound immunoglobulin was detected in CAH sera. It would appear that the IgG-antibody-dependent cell-mediated cytotoxicity may play a role in pathogenesis of CAH.
Male Wister rats (200g weigt) were strenuously exercised in a rotating cage for 2 hours. Immediately after the exercise, there were significant elevations of serum glutamic oxalacetic transaminase, serum glutamic pyruvic transaminase, serum lactic dehydrogenase and plasma free fatty acids, and decreases of serum alkaline phosphatase, serum glucose and serum triglyceride. Pathologic studies revealed an acidophilic degeneration of the hepatocyte, an appearance of fat droplets and depletion of glycogen contents in the hepatocyte. Under electron microscopy, in addition to occational occurrence of coagulation necrosis of the hepatocyte, changes of the mitochondria, increased smooth surfaced endoplasmic reticulum and fat droplet, and decreased amount of glycogen particle were noted in the hepatocyte. Those changes were also proved by morphometric analysis on those organellar changes in the hepatocyte. It seemed likely that those morphological changes of the liver are closely related with biochemical changes of the serum.
The mode of expansion of bile duct carcinoma in the longitudinal direction was investigated in 24 surgical or autopsy specimens with special reference to the problem of epithelial invasion. In 5(21%) of these 24 cases the epithelial invasion was more extensive than the longitudinal nonepithelial invasion within the duct wall, the maximal discrepancy being no less than 26.2mm. In some of these cases, the main focus of the carcinoma was so-called"early cancer", the extent of the lesion being confined within the duct wall. These findings seem to be of great clinical significance in relation to the problem of residual cancer cells and the recurrence of carcinoma after surgical resection of bile duct carcinoma.
This study covers a period of 13 years (1963-1975) and is based on the records of 80 cases of primary malignant tumor of the pancreas. Various aspects such as diagnosis, prognosis and causes of death have been analysed. Diagnostic accuracy of clinical diagnosis of the cases was 71.3%. Incorrectly diagnosed cases clude primary multiple cancer including pancreas cancer, cases which were unnable to undertake necessary examinations, cases of which metastatic lesions were predominant and mistaken for primary sites. Primary multiple cancer including pancreas cancer was detected in 9 out of 80 cases (11.3%). Duration of disease was less than 6 months in 39.4%, between 6 and 12 months in 33.8%, between 12 and 24 months in 21.1% and more than 24 months in 5.6%. The commonest causes of death of patients with pancreas malignancy were respiratory complications, tumor death, prulent peritonitis, gastrointestinal bleeding, and hepatic complications.
Pancreatic carcinoma in 49 of 52 (94%) golden hamsters was induced by a weekly subcutaneous injection (500mg/kg b.w.), for a period of 20 to 30 weeks, of 2, 2'-dihydroxy-di-N-propylnitrosamine (DHPN). Both light and trasmission electron microscopy indicated that the neoplasms originated from the ductal epithelium, thereby paralleling the pancreatic adenocarcinoma most often seen in humans. Ductal hyperplasia and adenomatous alteration were also observed in all 52 animals, and some were thought to be precarcinomatous alterations. In order to elucidate the changes in the ducts and their relation to carcinoma, pancreatography was performed by injection of gelatin-barium sulfate. The pancreatographic alterations were classified into the following 4 types: obstructed, stenosed, displaced and diffused. There was unambiguous parity between the pancreatograms and the histological findings concerning the early alterations of the pancreatic ducts and the development of pancreatic neoplasms. The use of DHPN in the investigation of the morphological aspects of pancreatic carcinoma has proven to be most promising.
Operation of fistula of the stomach and the pancreas was made in four mongrel dogs according to the method of Thomas. The dogs were used for the present study under non-anesthesized condition. The dogs were infused through the duodenal cannula for 5 minutes with acid solution (50ml of 0.1 N HCL), with butter emulsion (2g/kg/40ml water) or with acidified emulsive butter (2g/kg/0.1 N HCL 40ml). Pancreatic juice was collected every 10 minutes through the fistula of the pancreas. Blood samples were obtained from the cubital vein. Plasma immunoreactive secretin (IRS) measured by the method of double antibody system significantly increased 3 or 5 minutes after the start of the infusion of acid solution or acidified emulsive butter. The duodenal infusion of the latter evoked an increase in the protein output and the volume of the pancreatc juice more than the former infusion. On the contrary, by the duodenal infusion of the emulsive butter, IRS did not increase but the protein output and the volume of the pancreatic juice tended to increase. The present study shows that endogenous secretin induced by the duodenal infusion of the acid solution or the acidified emulsive butter directly stimulates the exocrine pancreas. It is thought that the other intestinal factors than secretin may stimulate the exocrine pancreas by the duodenal infusion of the emulsive butter.