The homogenized stomach of male DONRYU rats was centrifuged. The supernatant fluid was used as the assay sample in our study. Glandular kallikrein in this sample was assayed using the chromogenic substrate L-Prolyl-L-Phenylalanyl-L-Arginine-α-naphthylester (PPA-NE), and expressed in terms of PPA-NE esterolytic activity (BAEE u/ml). The physiological activity of glandular kallikrein was expressed in terms of kallidin concentration (μg/bath) measured according to Magnus' method in the mixture of the assay sample and low molecular weight-kininogen (LMW-Kg) (extracted from human plasma). The PPA-NE esterolytic activity of the assay sample was well correlated with kallidin concentration in the mixture of the assay sample and LMW-Kg (r=0.953). Then, changes with the progress water immersion-induced ulcers in glandular kallikrein activity were investigated using other male rats of the same strain. Glandular kallikrein was 9.32±1.40×10-3 BAEE u/ml before water immersion, and significantly decreased to 4.11±0.65×10-3 BAEE u/ml immediately after the onset of stress ulcers (p<0.001).
Determination of serum PGI has become available recently by RIA, but the correlation between immunoreactive PGI and proteolytic activity remains still uncertain. In the present study, immunoreactive PGI was found to correlate well with proteolytic activity at pH 2.0 both in serum and urine. Proteolytic activity at pH 3.5 was also proportional to that at pH 2.0 in urine, but not in serum. This finding was thought to be highly suggestive of difference in the constitution of zymogens active at pH 3.5 between serum and urine. These data showed that both metods of RIA of PGI and proteolytic assay at pH 2.0 were useful to know the functional state of fundic gland of the stomach. Serum level of immunoreactive PGI was 61.9±30.1ng/ml in healthy controls and was high in peptic ulcer, but was low in pernicious anemia and gastrectomized cases. However the high level of immunoreactive PGI found in patients suffering from uremia suggested the importance of renal function from the diagnostic standpoint.
Radioimmunoassay of serum group I pepsinogens (PG I) and/or group II pepsinogens (PG II) was performed in endoscopically diagnosed 88 cases of gastric ulcer, as previously reported. This time, relationship between the location of gastric ulcer and the PG I (or PG II) levels in serum was evaluated. Results were obtained as follows: 1) The serum levels of both PG I and PG II of the cases with gastric ulcer located in the body area was significantly lower than those of the cases with gastric ulcer located in the angular-antral area, with p<0.05 and p<0.02, respectively. 2) It was suggested that the possibility of using the serum levels of PG I or PG II for the serological screening of the location of gastric ulcer.
Four strain rat, Fischer, Fonryu, Sprague-Dawley and Wistar, were treated with 1, 2-dimethylhydrazine (DMH) 20mg/kg/week, serially five weeks. Donryu rat was most susceptible in induction of colorectal neoplasms, whereas Wistar rat was most resistant among the four strains. Concerning to the distribution of induced tumor, cancer in the Sprague-Dawley rat was induced more often in the distal colon. It can be said that it is better to chose appropriate rat strain according to the purpose of each experiment. One sessile polypoid lesion showed histologically focal severe dysplasia, and this finding seems to suggest that adenoma can be the precursor of colorectal cancer also in experiment.
We have experienced seven cases of toxic megacolon associated with ulcerative colitis, all of the cases being relapsing-remitting type. The laboratory data were characterized by anemia, hypoproteinemia and increased levels of fibrinogen and α2 globulin. Five patients were treated by a one-shot injection of 20-60mg of prednisolone into the mesentric arteries, whereas two patients were given prednisolone intravenously. After these medical therapy, five of seven patients have been recuperated well into the remitting stage for up to seven years without any surgical intervention. From these data, intraarterial injection of prednisolone appears to be very effective means, among other therapy including surgery, in treating toxic megacolon.
Twenty-three patients with cholangiocellular carcinoma were reviewed mainly as for imaging diagnosis. Abnormality of the biliary enzymes was observed in about 90% of the patients. Tumor-like defect was seen in 90.0% of them by liver scintigraphy. By ultrasonography tumor was visulaized in 76.5% of them and dilated intrahepatic bile ducts, obstructed by the tumor, were observed in 41.2%, which was seemed to be characteristic of this disease. Halo was seen only in 15.4% and the echo pattern of the minute tumors under 3cm in diameter was hypoechoic or isoechoic. By CT scan tumors were visualized mostly as low density area except for some cases showing low and high density areas. Many tumors were not enhanced significantly by contrast agent. The margin of the tumor was not so sharp in many cases. By direct cholangiography tapering type obstruction of the intrahepatic bile duct was seen in 66.7% and by the hepatic angiography encasement of the artery was seen in 75.0% respectively.
Progesterone (10-8M-10-6M) reduced 10-6M carbachol induced contractile responses in a dose dependent manner of the guinea-pig gallbladder. And 5×10-7M progesterone reduced the contractile responses evoked by carbachol, histamine, cholecystokinin octapeptide, prostaglandin E2 and prostaglandin F2α. The dose-response curves for these stimulants induced contractions shifted to the right by 5×10-7M progesterone. These results suggested that progesterone had an inhibitory effect directly on the gallbladder smooth miscles. In addition, progesterone had no effects on the contractions evoked by Ca-influx. It was suggested, therefore, that progesterone might inhibit the mechanism of intracellular Ca release.
The abnormal lipoprotein (LP-X) observed in cholestasis was deviled into two subfractions (LP-X1 and LP-X2) by zonal ultracentrifugation. To elucidate the mechanism of the formation, we utilized the common bile duct ligated-rats as an experimental model for extrahepatic cholestasis and those to which α-naphtylisothiocyanate (ANIT, 200mg/kg body weight) was administered as that for intrahepatic cholestasis. LP-X1 appeared in plasma 24hrs after ligation of the common bile duct, whereas LP-X2 also appeared 48hrs after ligation. Seventy-two hours after the ligation, LP-X1 was found to be higher than LP-X2. On the other hand, LP-X2 was exclusively observed in rats treated with ANIT. In percentage composition of protein and lipid, LP-X1 and LP-X2 were composed of mainly phospholipid and free cholesterol; in particular, the cholesterol ester ratio of LP-X2 was extremely low in the ANIT treated group. As to composition of apoproteins, LP-X2 was abundant in Apo E, which was not detectable in LP-X1 fraction. In electron micrographs negatively stained, both LP-X1 and LP-X2 showed to be disc-like in shape. In addition, LP-X1 tended to be larger than LP-X2 in size. In summary, LP-X1 may well be formed by the regurgitation of the bile components into the circulation, while hepatocyte may play a role, at least partly, in the appearance of LP-X2 in plasma, since Apo E is exclusively synthesized in the liver.
For the study of a possible intestinal metaplasia toward absorptive cells in cholelithiasis, the activity of disaccharidases was examined in the mucosal membranes of 70 lithiasic gallbladders by Tes-Tape method and each mucosal area with and/or without the activities was investigated by various morphological methods. Sucrase and/or trehalase was found positive in 41% of the bladders and both activities were located in almost identical areas of their mucosae, showing no definitive correlation with the degree of fibrosis found in the walls. No clear-cut relationships seemed to be present in the bladder mucosae between the disaccharidase activity and the occurrence of intestinal metaplasias other than absorptive cells as well as between the activity and the mucin type of the surface coats. The mucosal epithelial cells in the areas active of the disaccharidases appeared to reveal a formation of spike-like small cytoplasmic protrusions, which were associated with a concentration of microvilli and a slight increase in the thickness of glycocalyces as revealed by both transmission and scanning electron microscopy. There seemed, however, to be no evidence of ultrastructural changes in the epithelial cells within the active areas which would be identifiable as a definitive transformation to intestinal absorptive cells. Consequently, it seemed reasonable to assume that the intestinal metaplasia toward absorptive cells in lithiasic gallbladders would remain incomplete when viewed from morphological aspects though would be substantiated in enzymology.
In order to elucidate the mechanism of pancreatic stone formation, protein-bound γ-carbosyglutamic acid (Gla) in pancreatic juice was examined in 11 cases of chronic pancreatitis, in 6 cases of pancreatic retention cyst, in 16 cases of periampullary cancer and in 9 cases of control. In contrast with control, significant high levels of Gla were obtained in the groups of pancreatolithiasis and pancreatic retention cyst. Besides, Gla content increased with pancreatic ductal dilation, but was reduced by pancreatic ductal drainage. While, Gla content decreased with pancreatic exocrine disorder and showed extremely low level in the cases which pancreatic parenchyma was accounted for less than 19%. As Gla-cantaining proteins have a specific affinity for calcium ion, it is concluded that Gla-containing protein in pancreatic juice, which is secreted from pancreatic exocrine gland, increases as the stagnation of pancreatic juice and is concerned in the formation of pancreatic stone which is chiefly composed calcium carbonate.