Changes of serum gastrin levels and immunoreactive gastrin (IRG) concentrations of antral and upper intestinal mucosa in the course of growing rats were examined. The results obtained were as follows; 1) Serum gastrin levels were already detectable in rats at one week after birth, and thereafterincreased to 199pg/ml temporarily at two weeks after birth. 2) Intra-tissue IRG and G cells were only of a trace amount even in the antral mucosa during the fetal period. However, there was a definite increase of them in the antral mucosa both at the commencement of suckling as well as at the commencement of weaning and feeding. 3) In the duodenum, jejunum and corpus of the stomach, the value of IRG showed a temporary increase also at two weeks after birth when serum gastrin levels increased rapidly. 4) The molecular form in the antral IRG was mainly the so-called little gastrin (LG, G-17)throughout the fetal and adult ages. However, the molecular form in duodenal and jejunal IRG were mainly LG in the fetal period and thereafter it became big gastrin (BG, G-34) which increased gradually in parallel with aging. From these observations, it was suggested that feeding played an important physiological role not only in the production but also in release of gastrin with special regards to its influence on the metabolism of gastrin.
Changes of serum gastrin levels and immunoreactive gastrin (IRG) concentrations in the antral mucosa of rats following low protein feeding and in condition of starvation were examined. The results obtained were as follows; 1) Low protein feeding showed few influence on serum gastrin levels, whereas the antral IRG concentrations showed decrease in group with low protein feeding compared to group with ordinary food feeding. 2) Significant decreases of serum gastrin levels and the antral IRG concentrations were seen in group kept in starved conditions (p<0.05). 3) Control group which was kept in freely food intake condition showed significant increases of both serum gastrin levels and antral IRG concentrations (p<0.05, p<0.41) compared with those of groups in starved conditions. Summarizing the results, it was clarified that the feeding as well as the protein contents of food played an important physiological role in the production, storage and release mechanism of gastrin.
Atropine and scopolamine have been widely used as an anticholinergic agent in clinic, however, the lack of organ selectivity of these natural belladonna alkaloids has led to intensive efforts to find antimuscarinic drugs with more selective effects. The major development made in this field was to have a quaternary ammonium structure and a typical compound now clinically used is scopolamine butylbromide. Another undesireable effect of these quaternary ammonium compounds is a delay in transport-time of gastrointestinal contents, which could not be overcome. In the present study we investigated the effect of etomidoline, a newly developed antispasmodic drug with an isoindoline ring and a tertiary amine, on gastrointestinal motor activity in conscious dogs. In our system, dogs were chronically implanted with force transducers in the gastric antrum and the upper jejunum and gastrointestinal contractile activity was continuously recorded for long period of time. Etomidoline, dissolved in 0.9% saline, was continuously infused intravenously in a dose of 0.3mg/kg-30min. It was found that gastric and jejunal contractile activity was strongly inhibited for 96.3±0.05min and pentagastin (0.1μg/kg-hr)-stimulated gastric motor activity was also suppressed for 78.5±4.44min during the digestive state. Oral administration of this drug in a dose of 0.6 and 0.4mg/kg of body weight for 30min before each meal resulted in shortening of time for digestion and absorption for 0.9 and 2.2hr, respectively, though contractile force in the gastric antrum was significantly lowered when compared with the control. Its mechanism is not clearly known at present, however, it is noteworthy that time required for digestion and absorption of food was not prolonged by this antimuscarinic agent.
In order to study the ability to excrete bilirubin phosphate into the bile in the rat, bilirubin phosphate, one of the direct bilirubin, was prepared from patients' jaundiced urine by siliconized kieselguhl column chromatography, and further fractionated with cellulose cloumn chromatography. Bilirubin phosphate fraction showed positive phosphate ester reaction. The mean molar ratio of phosphorus to bilirubin was 1.94±0.19 S.D.. After intravenous injection of bilirubin phosphate into heterozygous Gunn rat and Wistar strain rat, the biliary excretion rate of bilirubin phosphate as well as other bilirubin fractions was studied. The following results were obtained. 1) The excretion ratio up to eight hours after intravenous loading of 760mcg of bilirubin phosphate was calcurated to be 59.2±11.4% in the Gunn rat and 70.1±14.8% in the Wistar strain rat. There was no significant difference in the excretion ratio between the Gunn rat and Wistar strain rat. This finding supports the concept that bilirubin phosphate is easily excreted in the bile without modification. 2) A significantly increased excretion of bilirubin phosphate in the bile was observed in the first two hours after its loading whereas there was on alteration of the amount of the other bilirubin fractions. The bilirubin phosphate fraction consisted 92.5±1.8% and 91.5±3.3% of the bilirubin excreted in the first two hours in the Gunn rat and Wistar strain rat respectively. 3) No statistically significant difference between the excretion ratio of the bilirubin phosphate and that of bilirubin glucuronide was determined after their loading. 4) The concentrations of indirect bilirubin and salt-form bilirubin in the bile in the preceeding two hours before loading and in the every two hours up to eight hours after loading of bilirubin phosphate did not show significant change.
The cytotoxic activity of peripheral blood lymphocytes was investigated in cases of chronic hepatitis, liver cirrhosis and hepatoma by microcytotoxicity assay. The cytotoxicity against HeLa cell was significantly decreased in cases of chronic hepatitis and liver cirrhosis but not significant in patients with hepatoma. The cytotoxicity against hepatoma cell line (LiC-1 Ohtsuka) was decreased in cases of liver cirrhosis and hepatoma but not significant. Non T cell fraction showed cytotoxicity against HeLa cell and hepatoma cell line either. Scanning electron microscopy revealed numerous microvilli on cell suface of the lymphocytes which were in process of destroying target hepatoma cell in vitro. It was considered that"spontaneous lymphocyte mediated cytotoxicity"by non T cell was detected in microcytotoxicity assay. For the T cell fraction of lymphocytes from the patients with hepatoma didn't show the cytotoxicity against hepatoma cell line, it could be concluded that cytotoxic T lymphocytes might not be induced in patients with hepatoma.
Correlation between hepatocellular deposition of orcein positive granular substances and biochemically increased concentration of liver-copper in many livers of various liver diseases and normal livers was examined. Orcein positive granular substances and the excess liver-copper were frequently associated in livers of infant, Wilson disease and long standing cholestatic liver diseases including primary biliary cirrhosis, congenital biliary atresia and hepatic sarcoidosis. This intimate association of both materials was further supported by the fact that orcein positive materials were seen histochemically to contain copper. It seems, therefore, likely that an excess liver-copper was stored in an form of orcein positive granular substance, probably metallothionein, in hepatocytes of many cases of above mentioned liver diseases.
Concentration and composition of lipid and bile acid in bile were studied in 33 patients with gallstone before and after 1 to 18 months of oral therapy with ursodeoxycholic acid (UDCA, 450mg per day). A molar percentage ratio of bile acids plus lecithin to cholesterol was remarkable elevated after the administration of UDCA. This change was associated with a reduction off cholesterol excretion in bile and an increase of biliary bile acid concentration. UDCA was detected in bile of all cases with an average of 28.8% of total biliary bile acids after the treatment. In this study, the administration of UDCA did not significantly increase the concentration of lithocholic acid in bile. The data suggest that UDCA lowers lithogenicity of bile and UDCA seems to be effective and safe for the treatment of gallstone.
The purpose of this study is to clarify the correlation between cholangiographic and histological features of the intrapancreatic segment of the common bile duct. Studies were made using 100 specimens obtained either by surgery or autopsy. There were many variances in the anatomical relationship between the common bile duct and the pancreatic head. They usually did not influence cholangiographic features. However, cholangiographic features of the common duct were influenced by fibrosis and cancer infiltration into the periductal area as well as the pancreas. Featues of the stenosis of the bile duct primarily caused by compression from a pancreatic lesionwere almost always modified to varying degrees by changes in the intramural or periductal areas of the duct itself. The type of stenosis, localized or tubular, was essentially determined by the interaction of two factors; the extent of the infiltration of the lesion and the anatomical relationships between the bile duct and the pancreas. Stenosis caused by pancreatic lesion tends to be limited to the left side of the bile duct in its earlier stages. On the contrary, bile duct carcinoma tends to cause a stenosis on the right side of the duct because bile duct carcinoma preferentially grows dextroposteriorly towards the duodenal wall where the bile duct is usually devoid of coverings by pancreatic tissue. The secondary dilatation of the adjacent segment proximal to the stenosis is often the cause of contradiction between the radiological and histological findings.
In order to clarify the effect of gallbladder mucosa upon gallstone formation, gallstones were experimentally induced in Syrian golden hamsters. Stones were formed by the crystallization of cholesterol and the combining and further growth of these crystals. Gallbladder mucosal tissue samples were taken at regular intervals and prepared for light and scanning electron microscope study. PAS, alcian blue positive substances (i.e. mucus) were found on the surface of the epithelial cells before crystallization and increased markedly at the onset of crystallization and stone formation. Corresponding with this histochemical change, scanning electron microscopy showed a series of degenerative changes in the epithelial cells; beginning with isolated cells of varying sizes and the enlargement and adhesion of microvilli to each other, progressing to indentation of the cellular surface and coagulation of mucus and ending in hyaline-like degenration. The increased secretion of mucus and the changes in the gallbladder surface seem to suggest that gallbladder mucosa offers a preferred site for the crystallization of cholesterol and the combining and growth of these crystals.
Stones of the gallbladder from 174 patients obtained on surgery were divided into three principal groups of the radiated, lamellar and amorphous stones from gross findings of their cross section. A close relationship was found among their gross findings, chemical composition and cholangiographic features. Based on these results, the nature of gallstones is assessed with accuracy by the cholangiographic featue without inspecting the cross section or analysing the chemical composition. Various patient's position in cholangiographic procedure such as prone, supine or upright one were indispensable to demonstrate clearly the nature of the stone. Especially, compression upon the gallbladder area in upright position was essential for the study of fine calcification. Indication for dissolution therapy of gallstones was studied based on the cholangiographic features of 63 patients with cholesterol stones out of the 174 patients and of 29 patients in whom stones disappeared after chenodeoxycholic acid therapy. Floating stones and non-floating, round or oval, small or middle sized stones as well as similarly figured large stones in small numbers are indicated for the dissolution therapy.
Annular pancreas in the adult is a rare anatomic anomaly which is detected by symptoms based on chronic partial obstruction of the duodenum. Four patients with annular pancreas were treated at our clinic during the past 5 years. Of them, 3 patients were male and one was female. The age range was 40 to 44 years. The annulus was found to be a complete ring in one patient, while in the remaining patients only a partial one was present. In all patients, the annulus was situated in the region of the second part of the duodenum. These patients had complications such as peptic ulceration, cholelithiasis, and others. Therefore, the symptoms of our series were influenced by the ones that were seen in the complications. The diagnosis was dependent exclusively on the findings of upper gastrointestinal barium x-ray studies, especially hypotonic duodenography. Surgical treatment of these patients consisted of a partial gastrectomy (Billroth II), a partial resection of the annulus, and others. These patients had a good prognosis after operation. It is concluded that hypotonic duodenography is a beneficial way for the diagnosis of annular pancreas, and that the operative treatment should consist of relief of any obstruction to the duodenum by a procedure suitable to each patient.
Computed tomograms (CT) were studied in 59 control subjects, 38 patients with chronic pancreatitis, 10 patients with pancreatic tumor and 2 patients with pancreatic cyst, a total of 109 patients. The ratio of the largest width of the pancreas to the width of th vertabral body (P/V) was 0.60± 0.10 in the head, 0.55±0.08 in the body and 0.54±0.09 in the tail of the normal pancreas (mean±SD), which appeared as a rod-like organ with homogenous density. The diameter of the pancreatic tumor permitting confirmation by P/V>0.80 appears to be above 3.0cm. In small or diffuse pancreatic cancer, P/V is normal, and unbalanced shape of the pancreas and inhomogenous density of the tumor represent important findings. In cancer of the head of the pancreas, cholestatic findings such as the dilated gallbladder should be emphasied. In malignant pancreatic cyst, unlkie the benign cyst, the inside of the cyst is irregularand the internal density is inhomoggenous. In chronic pancreatitis, CT is useful for detecting pancreatic calcification. CT is capable ofconfirming stones in the pancreas and permits a clearer demonstration of the shape and distribution of the stone than simple X-ray film of the abdomen.
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 symptoms, duration of symptoms and laboratory findings have been analysed. Initial symptoms were usually vague and the average duration of symptoms from their first appearance until the time of hospitalization was 6.8 months in carcinoma of the head, 5.2 months in carcinoma of the body and tail and 3 months in carcinoma of the entire pancreas. The commonest chief complaints were abdominal pain, anorexia, and abdominal discomfortableness. The most frequent symptom at the time of admission was weight loss. In the greater number of the cases total billirubin, alkaline phosphatase and glucose level were abnormally high during the course of the disease. Cholangiography showed abnormal findings in 63.3%, pancreatic exocrine function test, in 71.5%, abdominal angiography, in 81.3%, pancreatic scanning, in 95.0%, and percutaneous transhepatic cholangiography, in 100% of the cases examined.
Intrapancreatically administered heat-killed E. coli complexed with Freund's incomplete adjuvant (FIA) induced chronic pancreatic injuries in dogs similarly observed with Freund's complete adjuvant treatment in previous paper. E. coli with FIA demonstrated chronic pancreatic injuries, but not E. coli alone in this experimental study. In the former, the degree and incidence of injuries were depend upon the dosage of administered E. coli. Specific antigens of E. coli were retained in pancreatic tissue for at least 7 weeks. In this process, circulating pancreatic antibodies were detected and gave a specific precipitin line to microsomal fraction of pancreas. The persistence of E. coli as well as its direct action in the pancreatic tissue may implicate to correlate with the evolution of chronic pancreatic injuries.