In order to clarify mechanisms of the exocrine pancreatic secretion, the auther carried out quantitative study on the exocrine secretion by using the perfusion procedure of in vivo dog pancreas, especially on H+ and HCO3- transport. The pH of venous blood which perfused the pancreas was measured by a pH electrode of perfusion type and it was 7.20±0.1. However, the pH of arterial blood was 7.32±05. This difference (4pH) was about 0.1 pH. The venous pH became lower with the stimulation of secretin; the average of decrement was 0.075±0.022 pH (S.D., n=14). The rate of H+ release into the blood during secretion was calculated as (ΔpH)×(buffer value of the blood)×(flow rate). The rate of HCO3- secretion into the pancreatic juice was calculated as (flow rate)×(HCO3- concentration). It was demonstrated that the rate of H+ release was larger in quantity than the rate of HCO3- secretion into the duct. Discussion was made on the view that metabolic CO2 in cells or CO2 in the blood would be hydrated, being hydrolysed into H+ and HCO3- by carbonic anhydrase in cells, then it would be utilized in the transport processes: H+ was transported to the blood and HCO3- was secreted into the pancreatic juice.
In order to clarify the mechanism of the pancreatic exocrine secretion, transport processes of Na+, K+, and CI- were studied on the perfused dog pancreas. First, the relation between the flow rate of perfusion and perfusion pressure was studied. Judging from the result of measured values of perfusion flow rate and perfusion pressure, a temporary decrease of perfusion pressure was observed after slimulation of secretin. The change was considered to be due to a vascular dilatation. Second, in an attempt to analyse Na+, K+, and CI- transport induced by secretin, the perfusion with normal Ringer solution was carried out, and the ionic concentration of arterial and venous perfusates and pancreatic juice was measured. The temporary efflux of K+ from the cell to the perfusate and the prominent influx of Na+ and CI- from the perfusate to the cell were observed. These ionic changes occured faster than the secretion of pancreatic juice. In the perfusion with isotonic containing low Na (as replaced with sucrose) Ringer solution, Na+ in the pancreatic juice showed higher concentration than in the perfusate, though they were isosmolal. In fact, as described above, it was verified that an active transport of Na+ exists in the secretory process of pancreas.
In order to determine gastrin release into blood following an appropriate stimulation and clarify pathophysiological features in gastroduodenal diseases, bouillon test (B test) wasexamined. Fasting serum gastrin levels of normal control subjects were 102±14.1 pg/ml and the levels increased up to 178±60.0 pg/ml (p<0.05) at five minutesafter the B test.The B test was carried out on various gastroduodenal diseases and the response in increaseof serum gastrin level was classified into three types of “high”, “normal” and “low” reactions. Of 30 patients with gastroduodenal diseases, 16.7%, 20.0% and 63.3%of cases belonged to high, normal and low reaction types, respectively. These findings suggested that moreor less different mechanisms in the gastrinrelease from the normal control subjects should be involved in relation to the disease states. There were, however, highly significant correlations between fasting serum gastrinlevels or the peak gastrin levels in the B test and gastrin-like immunoreactivities of thehuman antral mucosae, showing r=0.65 (p<0.01) and r=0.72 (p<0.001), respectively. Summarizing the results, serum gastrin response in the B test seems to be parallel to the functional G cell mass in the antral mucosae, and clinical availability of the B test was discussed.
Several immunological studies in ulcerative colitis were carried out in comparison with these in control subjects. The obtained results were as follows: 1) The average number of IgA-containing cells in the rectal mucosa significantly increased in patients with ulcerative colitis than in control subjects. Between these two groups, however, no significant difference could be found in the incidence of IgG-and IgM-containing cells of the rectum. 2) T-cell proportion of lymphocytes in peripheral blood was apparently going down in patients with ulcerative colitis than in control subjects. 3) There was no significant difference in the lymphocyte responce to PHA between both groups. 4) Patients with ulcerative colitis were in lower incidence in positive Mantoux reaction and PHA skin test than control subjects. From these results, it was assumed that patients with ulcerative colitishad some abnormalities in their cellular immune systems, compared with control subjects.
In order to evaluate the factors influencing a healing process of peptic ulcer, relationships between a period of time required for the healing and each of 26 factors seemingly affecting the healing process were studied in 253 patients with gastric ulcer. The degree of correlation between the parameters was tested by means of Hayashi's quantification type II, principal component analysis and multiple regression analysis. The factors such as “treatment enviroment” i. e. out-patient or in-patient, age, location and depth of the ulcer, were revealed to have a close relation with the healing process. Among endoscopic findings, degree of the marginal elevation and hemorrhage in surroundings were found to be moreimportant than the others. The age, the location of ulcer and accompanying gastritis were important factors for the healing process in in-patients, whereas the location and the depth of ulcer and the hemorrhage in surroundings were influential in out-patients. These facts suggest that there is a difference in the healing process of ulcer between these groups of patients.
The analysis of gastric juice were carried out on about 80 patients who were admitted to Karasawa Hospital under the diagnosis of hemorrhagic erosion from Nov. 1973 to May 1974. During the endoscopic examination, the gastric juice was aspirated through the fiberscope and was titrated by the method of Toöpfer-Michaelis. On the patients with normal findings in the stomach and the duodenum, the free acid output and the fbee acid concentration of gastric juice were determined as 0.35±0.32mEq.(mean±S.D.) and 14.7±10.9 cl.u. respectively. As for the patients of hemorrhagic erosion, the average free acid output and free acid concentration on the first day of hospitalization showed hyperacidity as 7.8±2.4 mEq. and 54.0±17.7 cl. u. They, however, gradually decreasedto normal acidity within a week. By histalog test, M. A. O. revealed more than 20mEq/hr on the day of onset and it also decreased gradually to normal level within a week. During the period of hyperacidity, the medical vagotomy achieved remarkable decrease of gastric acid output and the mean reduction rate of acidity was 75%. The reduction rate also gradually decreased in a short time. The result of medical vagotomy suggest that the cause of hemorrhagic erosion will much depend on the neural pathway of hypothalamovagal route.
Sera from patients with primary hepatoma markedly suppressed normal lymphocyte response to PHA when compared with normal sera. Fractionations of normal and hepatoma sera wre carried out by DEAE cellulose column chromatography using a continuous concave gradient. The elution patterns of both sera were quite similar and separated into nine fractions. Protein analysis by immunoelectrophoresis and immunodiffusion showed that any differences between subfractions obtained from normal and hepatoma sera, could not be detected. However inhibitory activities of hepatoma sera on PHA response of normal lymphocytes existed in alpha-, beta-globulin and albumin fractions. On the other hand, in the fractions from normal sera, alpha-and beta-globulin fractions disclosed similar degree of inhibition to PHA response of normal lymphocytes, but albumin fraction dismissed the inhibitory activity. Further investigations of these inhibitory fractions of hepatoma sera on Sephadex G-200 gel filtration showed that alpha-globulin fbaction with the highest degree of inhibitory activity, contained the carcinoembryonic protein (alpha-fetoprotein and ferritin) and IRA protein. The albumin fraction with moderate degree of inhibitory activity, contained alpha-2 macroglobuline.The carcinoembryonic proteins and alpha-2 macroglobulin obtained from patients withhepatoma revealed the remarkable suppression to PHA responses of normal lymphocytes. The electrofocusing pattern of alpha-2 macroglobulin fractions obtained from normal and hepatoma sera showed the definite difference of protein composition. These results indicated that function of lymphocytes in patients with primary hepatoma may be regulated by a variety of humoral factors.
Modified Anson's method and radial difiusion assay for the measurement of peptic activity on protein substrate were studied. 1) The products soluble in trichloroacetic acid were estimated by spectrophotometric measurement at 280 nm (UV method) or by the Folin's phenol reagent (phenol method). 2) The results obtained by UV method appeared to be in agreement with the results obtained by the latter method. 3) The reproducibility of both methods were prominent. 4) UV measurement was much more easier and simpler than phenol method. 5) Radial diffusion assay was superior to the Anson's method with the simplicity, speed, and convenience for clinical utility, but not accuracy.
We have attempted endoscopic retrograde cholangiography (ERC) in 484 patients with gallstone disease, and in this paper referred to some problems about the characteristics of the shadows and differential diagnosis. In all those patients with gallstone, ERC was succeeded in 85.3%(415 out of 484 cases). Opacified areas in 414 patients without a history of cholecystectomy were as follows, all biliary system distinctly in 49.3%, novisualization of the gallbladder and cystic duct in 11.1%, obstruction of the cystic duct in 18.6%, obstruction of the bile duct in 5.1% and the failure of the ERC in 15.9%. The frequency of visualization of the gallbladder with stones in the cystic duct or gallbladder was 57.7% atmost. It was impossible to distinguish from malignant diseases in some patients whose choledochograms showed saw or convex like obstruction or stricture with irregular surface of the bile duct. Misdiagnosed cases which were proven by the operation have been experienced in 22 cases: disappearance of gallstone, cholecystitis, mucus or blood, aplasia of the gallbladder, foreign body in bile duct and so forth.
Using column chromatography containing Sephadex G-200 and preparative ultracentrifugalflotation method, we found the fact that ICG bound to VLDL, LDL and HDL2in lower concentration, further in higher concentration it bound to all lipoproteins and 4S proteins in vitro. In control group we obtained three distinct peaks on the ICG curve, and thesethree peaks corresponded 19S (VLDL, LDL and HDL2), 7S (HDL3) and 4S protein peaks. In acute hepatitis 2nd ICG peak disappeared during acute phase, followed inrecovery phase 2nd ICG peak appeared and then returned to normal binding pattern. In chronic hepatitis, liver cirrhosis and Wilson's disease, ralative increase in 2nd ICG peak and transference of it to heavier protein were observed. ICG·Eserum protein binding pattern using 8 M-urea as coeffluent was equal to that using 0.033M phosphate buffer (pH 7.4). On analytical ultracentrifugation HDL1was not obtained in liver disease, and in liver cirrhosis separation of HDL2and HDL3was not clear. Whreas agarose agar gel electrophoresis of each lipoprotein fraction revealed not remarkable abnormality. Transfer rate of 2nd ICG peak (HDL3) to heavier protein correlated with plasma ICG retention (r=0.792, p<0.001). Furthermore Kavg. of HDL3 in Sephadex G-200 obtained from ICG·Eserum protein binding pattern correlated with plasma ICG retention (r=-0.751, p<0.001). From these facts it suggested that HDL3in liver disease was increased in molecular weight or in capacity. Stillmore it suggested that plasma ICG retention in liver disease was affected from these plasma lipoprotein (HDL3) abnormalities.