The mechanism by which PGE2 directly protects individual gastric cells from ethanol-induced injury was studied by using isolated gastric chief cells from guinea pig. Ethanol dose-dependently caused chief cell injury which was estimated by the release of lactate dehydrogenase (LDH) from chief cells. Pretreatment of chief cells with PGE2 reduced the cell damage caused by ethanol in time- and dose-dependent manner. The pretreatment at 37°C and pH 7.4 with PGE2 maximally reduced the cell damage. This protective effect was reduced when the pretreatment was performed at either acid or alkaline pH or at reduced temperature. PGE2 did not stimulate any increase in cytosolic free Ca2+ concentration and initial Ca2+ influx rate. On the other hand, PGE2 stimulated an increase of cAMP accumulation in chief cells. However, pretreatment of chief cells with secretion, VIP, dbcAMP or forskolin failed to reduce subsequent injury caused by ethanol. These results suggest that PGE2 may protect chief cells against ethanol-caused injury probably via PGE type receptors coupled to as yet unidentified signal in gastric chief cells.
The immunoreactivity and affinity of seven kinds of monoclonal antibody raised against human gastric cancer (MKN-45) secreted carcinoembryonic antigen (CEA) were determined with the method of cell binding assay in vitro. Tumor localization and biodistribution of radiolabeled antibodies were performed in athymic mice implanted MKN-45 xenografts. Results obtained were as follows: 1) The affinity constant of CEA-specific three antibodies (1A4, 1B2, 4H11) was the same approximately, whereas the immunoreactivity found to be quite different among them. While CEA-nonspecific four antibodies (7D1, 6C7, 2C3, 5H7) showed the much higher affinity constant than that of the former. 2) In an animal model on tumor localization and biodistribution studies, CEA-specific antibodies obtained more highly tumor targeting and cleared more rapidly from the blood and non-tumor organs than CEA-nonspecific antibodies did, so that tumor to nontumor ratios was increased. 3) In this model system it is the immunoreactivity preparation of antibodies that improved tumor targeting and tumor activity retention, on the other side, the affinity constant of antibodies were associated with rapid clearance from the blood and non tumor sites. In conclusion, this studies would also be beneficial for practical use and clinical application of radiolabeled monoclonal antibodies.
In order to clarify the usefulness of EUS in the diagnosis of gastrointestinal carcinoid tumor, we examined 15 patients, who had carcinoid tumors of gastrointestinal tract (stomach: 5, duodenum: 2, rectum: 8), on the diagnosis in quality and depth by comparing endoscopical ultrasonography (EUS) with resected specimen. Carcinoid tumors of gastrointestinal tract were detected as homogenous hypoechoic tumors with sharp border in all site by EUS. Especially, it was characteristic that 14 of the 17 lesions (82%) which invaded into submucosa were mainly located in the third layer, and the second layer covered the tumor at the foot, and near the top, it touched the tumor and got indistinct. We decided the depth of invasion by comparing the hypoechoic tumor with normal structure of 5 layers. The accuracy rate was 88%. In conclusion, EUS was thought to be useful in the diagnosis and choice for treatment of carcinoid tumors of gastrointestinal tract.
Two hundred and three patients with Crohn's disease seen at our clinics and affiliated centers from April 1973 to August 1988 were followed for 4.4±3.2 years (mean±SD), in order to evaluate the prognosis of Crohn's disease in Japan. These 203 patients (142 males and 61 females) fulfilled the following criteria; 1) they have been followed at the outpatients clinic for more than six months or 2) they have been admitted to us for more than a month. Of these, 83 (40.9%) had ileitis, 60 (29.6%) ileocolitis, 25(12.3%) colitis, 15(7.5%) miscellaneous types and the remaining 20(9.9%) had undergone bowel resection. Cumulative survival rate and cumulative probability of surgery were calculated by life table method. Cumulative survival rate in these patients was compared with expected survival rate of sex and age matched general population. Cumulative survival rates five and ten years after diagnosis were 98.9% and 98.9%, respectively. There were no significant differences in the survival rates between two groups. Cumulative probability of surgery five and ten years after onset of symptoms were 16.2% and 39.1%, respectively. Cumulative probability of surgery five and ten years after diagnosis were 25.9% and 46.9%, respectively. From these results, the prognosis of Japanese patients with Crohn's disease appears to superior to that in European and American literatures.
The relationship between ulcerative colitis (UC) and pregnancy was studied in 83 cases (124 deliveries). The results were as follows: 1) In women with UC, there was no significant difference in fertility compared with the general population. 2) The existance of UC and treatment of UC during pregnant period had no significant adverse effects for the course of pregnancy. 3) In the 17 out of 36 pregnancies with inactive UC at the onset of pregnancy suffered relapses. Relapse rate in same patients in the pregnant period was significant higher than that in the non-pregnant period. 4) First attack of UC developing in 12 cases during pregnancies or the puerperium, the onset being commonly in the first trimester. UC developing during pregnancy was especially severe in other patients. We concluded that the relapse rate of UC is high during pregnant period, however, the course of pregnancy is not affected with UC.
The Second Department of Internal Medicine, Toho University School of Medicine The aim of the study was to know influences of estrogen and testosterone on carbon tetrachloride-induced liver damage in male Wistar rats. One hundred and two rats were divided into following six groups on the basis of the treatment: olive oil as control (O), carbon tetrachloride (0.1ml/100g, C), estradiol benzoate (0.1mg/100g, E), testosterone propionate (5mg/100g, T), C+E and C+T, in which each drug was intraperitoneally injected twice per week for consecutive 12 weeks. In the C+E group, decreases in serum albumin level at the 4th week and total cholesterol level at the 8th week seemed to be suppressed. And fibrotic change and fatty change were weak on the histological observation. However, hepatocellular hyperplasia was observed in 40% cases after the 8th week. On the flow cytometry analysis of the liver at the 4th week, an enhancement of hepatocellular proliferation was shown. Survival rate of the C+E group rats was lower than C group rats. On the other hand, in the C+T group, liver injury occurred in the same grade as C group, and the survival rate was worst among all six groups. These results suggest that simultaneous administration of estrogen with carbon tetrachloride could reduce hepatic injury, though it might cause hepatocellular hyperplasia.
In order to evaluate the role of a expression of HBV-associated, we investigated histological and cytological distribution of HBeAga, HBeAgb, and HBcAg by immunoperoxidase procedure using monochronal antibodies. Materials submitted for this study were needle biopsied specimens obtained from 41 chronic carriers and serial paraffin sections were used for the immunohistological study. The localization of HBeAga/b antigens was limitted in hepatocellular nuclei, and hepatocellular cytoplasm was HBeAg negative, HBeAg was detected in 11 cases (33%) of 33 cases with chronic active hepatitis (CAH) and in 5 cases (63%) of 8 cases with chronic inactive hepatitis (CIH). Among the HBeAg positive 16 cases, HBeAgb was demonstrated in 15 cases, however, HBeAga was revealed only each one case of CAH and CIH, respectively. Most of HBeAg positive cells were distributed in the peripheral zone of the hepatic lobules while the positive cells were found in central to midzonal zones of 3 cases CAH and one case of CIH. All in histopathologically HBeAga/b positive cases were also HBeAg positive serologically. On the other hand, in HBeAg sero-positive patients, histological positive rate of HBeAga/b was in 33% in CAH and 50% in CIH.
In order to clarify the angioarchitecture of the palisade zone in the lower esophagus for portal hypertensive cases, we examined the thirty untreated autopsy cases of portal hypertension. At autopsy, barium added gelatin was injected from gastric cornary vein of the gastric wall and we observed them histologically and histometrically. 1) In portal hypertension, the palisade zone has increasing veins running in the submucosa, which veins belonged originally to the lamina propria. 2) A difference in angioarchitecture is present between the palisade and truncal zones. 3) The palisade zone in esophageal varices was classified into two types of angioarchitecture by Hashizume. Our 30 cases were composed of 22 cases with palisading type and of 8 those with bar type. The later showed well developed varises than the formar.
In a prospective, randomized controlled trial, 43 patients with cirrhosis and variceal hemorrhage were allocated after control of the bleeding to treat by elective sclerotherapy alone (n=23) or by oral propranolol after elective sclerotherapy (n=20). The dose of oral propranolol was based on a reduction of the resting pulse rate by 25%. The end points of the study were rebleeding or death. Both treatment groups were comparable with respect to origin and severity of liver disease, size of esophageal varices and portal pressure at entry. The mean follow up was 27±19 months for all patients. Patients treated sclerotherapy alone had more rebleeding (n=11) did than those in the sclerotherapy plus propranolol (n=3). The cumulative percentages of patients free of rebleeding 1 and 2 years after inclusion were 77 and 66% in sclerotherapy alone, and 100 and 85% in sclerotherapy plus propranolol; the difference between the two groups was significant. No statistically significant effect on mortality was seen. These data support that oral propranolol after sclerotherapy reduces the risk of recurrent bleeding in cirrhotics treated elective sclerotherapy.