Marked absorption of collagen fibers has been observed after the discontinuation of noxic stimuli in experimental hepatic fibrosis or pre-cirrhosis induced by chronic carbon tetrachloride intoxication. The authors' enzymo-histochemical and electron microscopical study revealed that the collagen fibers would be degraded mainly in the extracellular process and the degraded fibers would be engulfed by the Kupffer cells and/or macrophages in the perisinusoidal spaces, and lysosomes within these mesenchymal cells would participate in digestion of the degraded collagen fibrils. So it was considered that hepatic collagenase may be present in the extracellular degradation of collagen fibers. However, collagenase has not been completely observed in the liver of animals and human being until authors reported in the Nature (252: 49, 1974). Here is reported that the evidences of the presence of collagenase in rat liver and the changing activity of collagenase in the fibrotic and recovery stage in experimental hepatic fibrosis induced by carbon tetrachloride. 1. Using the culture method by Gross and Lapiere, collagenolytic activity which is active at neutral pH at 37°C and 35°C, employing the native reconstituted collagen fibrils was demonstrated in the fibrotic rat liver induced by chronic carbon tetrachloride intoxication. 2. This collagenolytic activity was identified with mammalian collagenase by disc electrophoretic patterns of reactive products. 3. Collagenase activity was very weak in the non-treated rat liver, but increased in the process of experimental hepatic fibrosis. In the cirrhotic stage, it decreased to the same extent of the non-treated rat liver. 4. In the recovery from experimental hepatic fibrosis, collagenase activity became maximal in 2 days after the discontinuation of carbon tetrachloride for 6 to 8 weeks when the histological findings showed no resorption of collagen fibers yet. And at 7 days after the discontinuation of noxic stimuli when the resorption of collagen fibers was extremely observed, it decreased to the same extent of the non-treated rat liver. Collagenase would be the first attack enzyme on collagen fibers and play an important role in the collagen metabolism in the liver under physiological and pathological conditions.
Three dimentional structures of the villi and the surfaces of epithelial cells of human duodenal mucosa were observed by scanning electron microscope (SEM). The specimens obtained by biopsy were treated with 4% pronase in phosphate buffer and then treated with 4% hyaluronidase in the buffer, thereafter, they were fixed with revised tannin-osmium method of Murakami (1974). After critical point drying the specimens were thin coated by Au-Paradium. The samples were examined with a SEM of Hitachi SSM-2 type. At low magnification, most villi were ridges of moderate length, occasionally leaf shaped villi were observed. On the surface of individual villus there were irregular shallow grooves and numerous pits representing mouths of goblet cells. At higher magnification the epithelial cells became clearly visible. On the surfaces of columnar absorbtive cells numerous microvilli appearing to be rod-shaped structures projected into the lumen. Mouths of goblet cells secreting mucous granules were also observed. On the cut surface of the villi three dimentional structure of thin basement membrane, infiltrating cells and capillaries were observed. The lateral surfaces of epithelial cells were irregular because of projections which could be the remnants of intercellular bridges. On the cut surface of one absorbtive cell there were small holes representing vesicles observed by transmission electron microscope.
A case of cancer complicating tuberculosis of the colon in a 39-year-old man is described. Barium enema showed strictures of coecum, transverse colon, descending colon, sigmoid colon and rectum. The lesion was diagnosed tuberculous on the findings of barium enema and biopsy from the rectal stricture. After the treatment with antituberculotic drugs for a year, passing disturbance of the coecum appeared. Right hemicolectomy was performed and papillary adenocarcinoma was found scattered in the hard scarring tissue of the coecum microscopically.
The investigation was performed on 76 cases with apparent discrepancy between ICG test and BSP test. These cases showed delayed disappearance of ICG and normal disappearance of BSP from plasma. In 37 cases liver function tests were out of normal limits. 10 cases had familial occurrence. 45 cases were considered as a new type of dye excretory disorder of liver, constitutional ICG excretory defect. Plasma disappearance rate (K), retention rate (R), transfer rate constants, step formation on ICG plasma disappearance curve, cholecystography and heredity of these 45 cases were showed as follows: 1) ICG test K: 0.019±0.007, R15: 79.0±12.6%. Three fractional transport rates were determined for the two-pool system: (a) fractional hepatic removal rate: 0.0217± 0.0052, (b) fractional hepatic plasma reflux rate: 0.0230±0.0208, (h) fractional biliary secretory rate: 0.0374±0.0152. 2) BSP test K: 0.092±0.023, R45: 4.5±1.8%, (a): 0.1078, (b): 0.0087, (h): 0.0462. 3) The step formation on ICG plasma disappearance curve during 20 to 25 minutes after injection was observed in 20 cases. 4) The gallbladder was visualized in 18 or 19 cases in which cholecystography was performed. A non-visualized case had cholelithiasis. 5) The delayed plasma disappearance of ICG was showed in 17 members of 10 families. From these results the impaired characteristic hepatic secretory of ICG was suspected to be congenital or constitutional.
The gastric secretory study was done in 8 patients of primary hyperparathyroidim before and after parathyroidectomy. Simultaneously fasting serum gastrin level was assayed by the method of radioimmunoassay. Additionally the upper gastrointestinal tract was examined roentgenologically for peptic ulcer. Gastric secretory study resulted in normal acidity, achlorhydria and hyperacidity in hyperparathyroidism patients. Fasting serum gastrin level was high. Upper gastrointestinal series disclosed I duodenal ulcer patient. Following the correction of abnormal serum calcium, the gastric acid output (both BAO and MAO), peptic output and serum gastrin level was lowered. In 3 cases the gastric secretory study was done again after the patients were discharged. The second postoperative study of gastric secretion revealed higher than the first postoperative examination, however it did not reach the level of preoperative one. The authors learned the calcium had the intimate relationship with the gastric secretion.
Stimulation of lymphocytes, as measured by incorporation of tritiated uridine into the ribonucleic acid of lymphocytes during the culture for 24-hour, were performed in patients with hepatic injury occurring after halothane anesthesia. Fourteen patients showed positive to halothane. Nine patients were injured after a single exposure, four patients after two or three exposure and one was an anesthetist. The interval between halothane exposure and onset of hepatic injury ranged from 8 to 22 days with an average of 14 days in a single exposure, and from 3 to 12 days with an average of 6 days in a multiple exposure group. A transient elevation of fever after exposure was characteristic in these cases. Eosinophilia was observed in 40 percent of blood counts in survived cases and in 14 percent in fatal cases. Liver function tests and histological findings of liver tissur were not able to be distinguished from those of viral hepatitis. The mortality was 50 percent in a multiple exposure group and 11 percent in a single exposure group. It is strongly suggested that the cellular immunity is involved in the role of immune processes in the pathogenesis of halothane induced hepatic injury.