Clinical and experimental studies have been done to elucidate the mechanism of renal excretion of bilirubin, renal involvement by the pigment and behavior of serum bilirubin in disturbance of urinary excretion with human subjects and rats suffering from biliary obstruction. 1) The excretion of bilirubin into urine showed a positive correlation to total and direct serum bilirubin, but negative correlation to reserved binding capacity of serum albumin to bilirubin. This fact might indicate that, on urinary excretion of this pigment, non-albumin bound free direct bilirubin could be excreted into urine. 2) Rats with impairment of urinary excretion by unilateral ligature of ureter and human subjects with renal involvement showed decrease in urinary excretion of bilirubin which induced elevation of serum bilirubin. Therefore, serum bilirubin level was thought to be strongly influenced by renal fruction. 3) With prolonged duration of jaundice, renal impairment was increased and urinary bilirubin excretion was decreased.
In Part I, various factors affecting the prognosis after resection of gastric cancer were reviewed from different viewpoints in relation to clinical and pathohistological indices. In Part II, clinical and pathohistological investgations were done on the mode of vascular invasion after resection of gastric cancer, and the same time, an examination was made on the relationship between these and the survival rates at given number of years. It has been established that male patients showed higher lymphatic vascular invasion, and it stendency increase with age. Even though the the tumors were small, vascular invasion could occur, and in such case, the prognosis was very poor. Moreover, the higher the degree of infiltrative growth and the deeper the extention, the result was a more severe invasion, and especially, the importance of sm (Tela submucosa), as the site of metastasis and infiltration, was confirmed.
Plasma glucagon and insulin responses to intravenous infusion of arginine were studied on 33 patients with chronic pancreatitis, 10 with primary diabetes and 8 healthy controls. Radioimmunoassay of glucagon was carried out using the antiserum 30K which is highly specific for pancreatic glucagon. Responses of plasma glucagon and insulin to arginine decreased in chronic pancreatitis with progression of exocrine pancreatic insufficiency and glucose intolerance. When compared with primary diabetes, pancreatic diabetes suffered from more severe hypofunction of the α and β cells in addition to exocrine insufficiency of the pancreas. These results suggest that the α and β cell function decrease with deterioration of exocrine pancreatic insufficiency in chronic pancreatitis, and that the process and resultant state of the endocrine pancreatic dysfunction are different between pancreatic and primary diabetes.
The author has previously reported that incomplete obstruction of the pancreatic duct and stasis of the pancreatic juice are the most important factors in the mechanism of pancreatic calculus formation. Further studies were carried out to detect the biochemical change of the pancreatic juice in experimental animals with pancreatic duct ligation. The pure pancreatic juice was obtained by Pancreozymin-Secretin stimulation and its volume, bicarbonate concentration, amylase output, and electrolytes were determined. In the incompletely ligated group, the volume of pancreatic secretion was markedly reduced comparing to control, but no significant change in maximum bicarbonate concentration or amylase out-put were observed. In electrolytes, the natrium level decreased and the chloride increased in the ligated group, and the potassium level showed no difference. The calcium level, in contrast, showed remarkable increase in the ligated group. From these results, it is presumed that the elevated calcium concentration in the reduced pancreatic juice accelerates calcium precipitation upon the mucous plugs in the pancreatic duct and forms pancreatic calculi.
Alkaline phosphatase (ALP) isoenzymes in carcinoma tissues of the stomach were investigated on their enzymological and immunological properties. Twenty three specimens of the gastric carcinoma tissues were obtained removed at operation. Their ALPs were extracted with n-butanol by a modification of Morton's method. These were separated into 3 bands of ALP isoenzymes (ALPa, ALPb and ALPc) by polyacrylamide-gel disc electrophoresis. It was•concluded that the enzymological and immunological properties of ALPa was similar to those of hepatic ALP, ALPb similar to placental ALP and ALPc to intestinal ALP. ALPb, which appeared in 8 out of 23 cases (35%) of gastric carcinoma tissues, showed heat-stability at 65°C for 20min. incubation, and seemed to be originated from the cancer cells themselves. ALPc, which appeared in 9 cases (39%), and the other 14 cases (61%) had not intestinal ALP, although various intensities of surrounding intestinal metaplasia were found in 21 cases (91%), and seemed to be originated from surrounding intestinal metaplasia. ALPa detectable in carcinoma tissue extract, which appeared in all cases and its enzymological and immunological properties were similar to normal mesenchymal cells, seemed not to be originated from the cancer cells but from the tissues surrounding cancer cells. There were no relationships between the above 3 isoenzymes and histological findings or Borrmann's macroscopic classifications. But, in well-differentiated type of gastric cancer, the intestinal metaplasia appeared more intensively than in poorly-differentiated type, and we could not deny completely the possibilities of producing the intestinal and hepatic ALPs from the cancer cells.
In order to clarify the mechanism of the secretion of pancreatic juice and bile after the infusion of 1-phenyl-1-hydroxy-n-pentane (PHP) into the duodenum, plasma secretin and gastrin level were measured after PHP administrated orally and infused into duodenum with radioimmunoassay. The following results were obtained. 1) Plasma secretin level was elevated in all the human cases after oral administration of PHP 600mg. 2) Plasma secretin level was elevated in all the human cases after infusion of PHP 600mg into the duodenum. This elevated degree was the same as or higher than the result after infusion of 1/10N-HCl solution. No particular change was observed on the plasma gastrin level. The above results seem to reveal that the secretory effect of PHP on pancreatic juice is performed through the release of secretin.
Using CIS gastrin radioimmunoassay kit, fasting serum gastrin level was measured in 228 various gastroduodenal diseases including one case of Zollinger-Ellison syndrome. Twenty-two normal subjects were examined as the control. The mean fasting serum gastrin level in the control was 54±7pg/ml. The mean fasting serum gastrin level in peptic ulcer and erosive gastritis did not show significant difference from the level of the control. However, the fasting serum gastrin level in gastric cancer, gastric polyp and atrophic gastritis was noticeably high compared to that in the control. The difference was significant in both gastric polyp and atrophic gastritis, but not in gastric cancer. In case of Zollinger-Ellison syndrome, the fasting serum gastrin level after gastrectomy was 405 or 970pg/ml. As the fasting serum gastrin levels were compared in accordance with the location of lesions, the lesions regardless of ulcer or cancer locating in the parietal cell area tended to show a higher gastrin level, while gastric ulcer or gastric cancer locating in the antral area had a lower level of serum gastrin compared to the lesions in other location. The fasting serum gastrin level was found to be slightly inversely proportional to the gastric secretion.
Serum ferritin was quantitated by means of double antibody radioimmunoassay and 2-site immunoradiometric assay using paper disc method and a diagnostic implication of serum ferritin in patients with digestive diseases was evaluated. A double antibody method was initially selected for the radioimmunoassay of serum ferritin. Standard curve showed satisfactory linearity from 10ng/ml to 1000ng/ml. Further sensitivity and reproducibility were obtained by 2-site immunoradiometric assay. The mean value of serum ferritin was diverged according to sex, 95.7ng/ml in the male and 42.8ng/ml in the female. In iron deficiency anemia, the serum ferritin concentration was less than 20ng/ml. In patients with hepatoma and pancreatic carcinoma, high ferritin levels were commonly observed. On the other hand, in patients with carcinomas of the stomach and colon, the serum ferritin concentration was mostly within normal range. In non-malignant diseases, serum ferritin levels showed generally low values except acute hepatitis and acute pancreatitis.
Although lymph follicles which are situated in the mucosa or submucosa of the bowel are not rarely seen in the terminal ileum, their true etiology and clinics are difficult to be assessed due to lack of pathological verification. On the other hand, physiology and pathology of lymph follicles of the large intestine have not been discussed enough yet. The normal lymph follicles in the large intestine are extremely small in size with a range from less than 1 to 3mm and it is difficult to inspect them by usual colonoscope of which focus is fixed. Using dye spraying method of indigocarmine or methylene blue, however, the minute structures of lymph follicles can be observed easily and clearly as slightly elevated and whitish minute granules. Moreover, using a specially designed fiberscope (Olympus CF-MB-M) with which the mucosa can be inspected on close-up, the minute structures of lymph follicles can be also easily visualized. Therefore, using these method, 105 cases of the rectal lymph follicles were classified into four grades by their size and number per unit area on the endoscopical point of views; 21 (20.0%) to grade 0, 57 (54.3%) to grade I, 27 (25.7%) to grade II, but none to grade III. Grades of the rectal lymph follicles correlated to age distribution, but there was no particular correlation between grades of lymph follicles and sex, underlying diseases of the patients and laboratory data such as peripheral lymphocyte count, serum γ-globulin, IgA, C3, C4, PHA skin test, Mantoux's reaction and so on. Therefore, it was suspected that the lymph follicles of the rectum have no specific clinical meanings. In cases of"colitis aphthosa"which is an extremely rare inflammatory colon disease, however, inflammation occurs at lymph follicles. Although its etiology and clinical and/or pathological meanings have been elucidated yet, its inflammatory process is very interesting to discuss the patho-physiological meanings of the rectal lymph follicles.
Immunological aspects of ulserative colitis were studied, especially about humoral immune phenonena. Fifteen sera were obtained from patients with ulcerative colitis verified clinically, rentgenologically and endoscopically. The results of this immunological survey were summalized as follows: 1. Decreased in serum IgG and IgA levels. Serum IgM levels within normal limits. 2. Normal serum C3 levels, as opposed to remarkably increased in serum C4 levels. 3. Decreased in Isohemagglutinin titers. 4. Higher incidence of different antibodies in sera of patients with ulcerative colitis, compared with sera from healthy controls. Rheumatoid factor. 13% (control: 3.3%) Anti-IgG antibodies: 13% (control: 0.4%) Anti-IgA antibodies: 60% (control: 1.3%) Anti-colonic antibodies: 33% (control: 1.3%) Antibodies to cow's milk proteins: 33% (control: 1.3%) 5. No significant difference of salivary IgA levels between patients with ulcerative colitis and healthy control. These abnormalities in humoral immune system were found in patients with ulcerative colitis, but there are no data that firmly link anticolonic antibodies, anti-cow's milk antibodies or immune complexes to the etiopathogenesis of ulcerative colitis.
The preoperative roentgen diagnosis of Meckel's diverticula is seldom made. We found reports of only 2 cases in Japan and we now added 3 additional cases in which the roentgen diagnosis was made. Meckel's diverticula have no specific symptomatology, but periodically recurring symptoms of abdominal pain, rectal bleeding and small bowel obstruction is speiific to diverticula. And dark red or"maroon"stools was characteristic, too. Small bowel examination with frequent fluoroscopy must be performed in the cases which suspected the possibility of Meckel's diverticula by these features.