Acute gastric lesions were experimentally induced by local hyperthermic treatment (42°C, 40 min). Thiobarbituric acid (TBA) reactants in the gastric mucosa were significantly increased 40 min after the hyperthermia. There were no changes in gastric mucosal blood flow and gastric acid secretion. The total area of gastric erosions and TBA reactant in gastric mucosa of rats deficient in vitamin E were significantly increased compared with those of rats supplemented with vitamin E. The increase in the total area of gastric erosions and TBA reactants in gastric mucosa were significantly inhibited by the treatment of bovine Cu, Zn-SOD and bovine catalase, and by the depletion of polymorphonuclear leukocytes (PMN). Allopurinol did not show any influence on these pathological changes induced by hyperthermia. These results suggest that lipid peroxidation and PMN-derived oxygen radicals may play an important role in the pathogenesis of gastric lesions induced by hyperthermic treatment.
This study was done to test effects of indomethacin (IND) on cell damage and prostaglandin (PG) synthesis in mucosal epithelial cells isolated from rat stomach in vitro. IND caused the cell damage in a dose-related way at concentrations over 5×10-4M. This damage was inhibited by 16, 16-dimethyl PGE2 (10-6M). IND abolished the synthesis of PGE2, PGI2, and TXA2 at the concentration of 10-4M at which IND alone did not cause cell damage. The cells treated with 10-4M IND were significantly susceptible to damage caused by 15% ethanol compared to the cells not trated with IND. 16, 16-Dimethyl PGE2 also inhibited the damage caused by IND+ethanol. These results suggest that the IND-induced susceptibility of the cells to damage is related to PG deficiency.
We extracted immunoreactive CCKs from rat duodenum and brain. We fractionated these samples by gel-filtration and analyzed with immunoreactivity and bioactivity of each fraction. 1) Elution profile of CCKs in duodenum and brain was well corresponding to that of bioactive CCKs. 2) Contents of CCKs determined by both RIA and Bioassay in each fraction were well colelated with each other. 3) Apparent molecular weights of CCKs of duodenum caribrated in column chromatography were approximately 2200, 1000 and 800. 4) Apparent molecular weight of CCK of brain seemed to be 1000.
The absolute number of T cell subsets and the rate of T cell DR antigen expression in the peripheral blood and the intestinal mucosa in IBD patients were compared with those in healthy normalc controls by two color analysis. The methods used here were flow cytometry for the peripheral blood and immunohistological fluorescent staining for the intestinal mucosa. In peripheral blood lymphocyte (PBL), helper (CD4+Leu8-) T cells increased in ulcerative colitis (UC), whereas suppressor (CD8+ CD11+) T cells decreased in Crohn's disease (CRD). In lamina propria lymphocyte (LPL) of intestinal mucosa, there were no changes in the proportion of T cell subsets in UC, whereas suppressor (CD8+ CD11+) T cells increased in inflamed mucosa of CRD. DR antigen positive T cells did not increase in PBL, but they increased in LPL of both UC and CRD. In conclusion, there are some differences in distribution of T cell subsets and DR antigen positive T cells between the peripheral blood and the intestinal mucosa in IBD patients. Moreover, the heterogeneity of the distribution of T cell subsets is observed between UC and CRD.
Natural Killer cell activity and lymphocyte subset in peripheral blood were studied in 16 patients with Crohn's disease. The effect of interferon administration was evaluated in 4 patients with Crohn's disease. In the patients with acitve Crohn's disease, natural killer cell activity was significantly lower in level compared to that in normal controls. Those without increase of natural killer cell activity in non-active stage, had trend of early relapsing. Peripheral lymphocyte subpopulations of OKT4, OKT8, OKIa1, OKT4/8 and Leu7 by flowcytometry showed no significant differences between the patients and the normal controls. Clinical remission was maintained in 2 out of 4 patients for the period from 7 to 21 months after the interferon administration. Benefit of interferon administration was suggested in patients with Crohn's disease.
An immunohistochemical method (peroxidase antiperoxidase method) was carried out to examine the distribution of endogenous estradiol (E2) and testosterone (Te). One hundred and twenty four (48.2%) of 257 colo-rectal cancer cases, and 36.7% of male cases and 58.4% of female cases revealed E2-immunostain. This immunohistochemical reaction for E2 was found more frequently in female patients than in male patients, while Te-immunostain was found in 15 (17.6%) of 85 colo-rectal cancer cases. E2 and Te were demonstrated mainly in the cytoplasms and occasionally in the nuclei of cancer cells. Since E2 or Te-positive cancer cells were mainly distributed in the deeper or invasive portion of tissue sections, it might deserve further investigation to elucidate a certain relationship between cancer growth and endogenous sex-hormones.
Regional distribution, age, sex, type of disease and history of surgery of the biliary tract were examined in 134 patients with hepatolithiasis in the Kamigoto district. The ratio of patient to populatin was 1:126 in the region showing the highest incidence. When classified by age at establishment of the diagnosis, patient in their sixties comprised the largest portion in both sexes. The ratio of men to women was 1:1.2. When classified in accordance with the draft by Resarch Group for the Study of Hepatolithiasis, 103 cases (76.9%) were of the intrahepatic type, and 31 cases (23.1%) were of the intra-extrahepatic type. The stones were found in the right lobe in 58 patients (43.3%), the left lobe in 59 patients (44.0%) and the both lobes in 17 patients (12.7%). Fortyfour patients (32.8%) had a history of surgery of the biliary tract. Ultrasonographic examinaiton of the abdomen in junior high school students revealed hepatolithiasis in one. As a result, the intrahepatic type and the right lobe type are high frequency in this district, and epidemiological survey of the family history and the food habit in this district is necessary.
The esophageal variceal pressure was determined by endoscopic pneumatic pressure sensor method in patients with liver cirrhosis, complicating esophageal varices. The variceal pressure by this method was significantly correlated with percutaneous transhepatic portal venous pressure. The variceal pressure was related with endoscopic findings of varices, especially of red-color sign, form and location. The variceal pressure below 200mmH2O showed negligible risk of variceal bleeding, and the pressure over 350mmH2O was associated with high risk of variceal bleeding. These results indicate that esophageal variceal pressure by this method may provide useful informations in natural history of esophageal varices.
Recently, hepatic microcirculation has been focused on as an important pathogenic factor in progression of alcoholic liver disease (ALD). Therefore, blood levels of several prostaglandins, which are associated with organ microcirculation, were determined in various liver diseases, including ALD. Blood thromboxane B2 (TXB2) level was significantly increased in ALD, when compared to other types of liver diseases, whereas both 6-keto prostablandin F1α (6-keto PGF1α) and prostaglandin E were not changed. These consequences resulted in the imbalance of 6-keto PGF1α to TXB2, which might promote platelet aggregation and blood vessel contraction. Indeed, the increase of β-thromboglobulin and platelet factor 4 in boood was observed in ALD. Furthermore, in ALD, the rate of arachidonate-induced platelet aggregation was prominently enhanced, and malondialdehyde production in platelet, which was well correlated with blood TXB2 levels, significantly increased. Thus, the present study may indicate that, in ALD, hyper-aggregability of platelet is produced, because of the derangement of prostaglandin metabolism and platelet dysfunction.
In order to investigate the production of PGE2 and its' function in human hepatocellular carcinoma, the effects of indomethacin and PGE2 on tumor growth were examined using in vivo and in vitro techniques. HH2-6 cells produced PGE2 in the culture media, and the inverse relationship was observed in between the cell proliferation and the culture supernatant PGE2 levels. While in vivo, plasma and tumor tissue PGE2 levels of tumor bearing nude mice were significantly increased for 1 or 2 weeks after tumor inoculation. In the case of which indomethacin was injected daily into the abdominal cavity (4mg/kg body weight), the elevation of plasma and tissue PGE2 levels was remarkably suppressed, and the latent time of tumor growth was also prolonged. On the other hand, another case of which PGE2 was injected (10μg or 0.1μg i.p.) at first 10 days revealed shortened latent time. These results indicate the intimate relation between PGE2 and latent time on tumor growth. Furthermore, histological findings suggest that tumor derived PGE2 might play an important role in tumor angiogenesis.
After the transhepatic arterial therapy, irradiated 11 patients with hepatocellular carcinoma were investigated clinically and pathologically. As the effect to the main tumors except for 3 cases who dropped out because of the side effect of irradiation, partial response (PR) was found in 1 case, minor response (MR) was in 2. There was no change (NC) in 4 and 1 had progressive disease (PD), so the rate of effectiveness was 12.5%. Irradiation to the tumor thrombosis of the portal vein were done for seven cases, 2 of them (28.6%) showed the decrease of the thrombosis or improvement of the blood stream in the portal vein on angiography or histology. AFP decreased in four of seven measurable cases within one month after the irradiation. Side effects were jaundice, fever, appetiteloss and so on, which were seen especially in cases of Child's B or C. Liver dysfunction and bone marrow suppression were also observed though not so severe. For the cases received lipiodol injection before radiation, lipiodol collection to the tumor was beneficial for the determination of the irradiated field.
The effectiveness and significance of the various therapeutic methods of extracorporeal circulation were assessed in an experimental model of septic endotoxin shock. After sepsis was produced in 30 puppies by intravenously injecting 5×109CFU/ml/kg of E. coli, on-line plasma exchange, conventional plasma exchange, charcoal plasma perfusion, hemofiltration, and sham perfusion were performed for 2hr. As a result, 4 of the 5 puppies in the on-line plasma exchange group and one of the 5 in the conventional plasma exchange group survived; the others all died. In the on-line plasma exchange group, the number of E. coli decreased to 2.5×10CFU/ml at the end of the treatment, while it was 1.3×103CFU/ml in the sham perfusion group. The endotoxin concentration was also reduced significantly, while plasma opsonin activity was remarkably elevated. These results suggest the significance of achieving the elimination of endotoxin in blood and an increase in plasma opsonin activity simultaneously in the treatment of septic endotoxin shock.