An aetiological relationship between Crohn's disease (CD) and Mycobacteria has been suggested. Recently Chiodini et al. isolated Mycobacterium (M.) sp. closely related to M. paratuberculosis, namely M. linda, from tissues of patients with CD and they reported greater seroactivity to M. paratuberculosis in patients with CD. In the present study, human intestinl tissue proteins of patients with CD, ulcerative colitis (UC), control and bovine paratuberculosis tissue proteins were analyzed for immune recognition, using transblot experiments, with anti-M. paratuberculosis antibody. Although bovine paratuberculosis tissue contains some 40-50 kilodalton proteins derived from M. paratuberculosis, CD, UC and control tissues did not contain any protein recognizable by anti-M. paratuberculosis antibody. M. paratuberculosis protoplasmic antigen was analyzed for immune recognition, using transblot experiments, with the sera of CD and control. However, there was no protein recognized specifically by sera from CD. Serum antibody titer to M. linda whole cell antigen was also evaluated using ELISA. There was no significant difference in CD, UC and control. Patients with tuberculosis had a significant increase in antibody titer (p<0.01) to M. linda compared with three other groups. No correlations were observed between antibody titer of patients with CD and activity of the disease process. The results showed no evidence for the hypothesis that M. paratuberculosis or its related species might be an aetiological agent in CD.
Stimulation with COOH-terminal octapeptide of cholecystokinin (CCK8) or carbachol resulted in a rapid increase in Quin-2 fluorescence of isolated guinea pig gastric chief cells, whereas histamine, vasoactive intestinal peptide, secretin and forskolin had no effect. The minimum effective dose of CCK8 or carbachol to elicit the rise in Quin-2 fluoresecence was very close to that for pepsinogen secretion. Removal of Ca++ from extracellular medium or Ca++ channel blockers did not affect CCK8- or carbachol-induced increase in Quin-2 fluorescence. Moreover, following the addition of CCK8, carbachol was unable to stimulate a second increase in Quin-2 fluorescence. These results suggest that CCK8 and carbachol share common Ca++ pools and an increase in free cytosolic Ca++ concentration may mediate CCK8- or carbachol-induced pepsinogen secretion from gastric cheif cells.
We monitored 24-hour intragastric pH using ambulatory pH monitor to compare the effects of histamine H2-receptor antagonist and proton pump inhibitor in 10 normal subjects. Histamine H2-receptor antagonist, famotidine (FAM) 40mg b.i, d., significantly increased nocturnal intragastric pH, but the drug scarecely affected intragastric pH pattern in the day time when compared with basal study. Proton pump inhibitor, omeprazole (OPZ) 20mg hs, increased not only nocturnal intragastric pH but also diurnal intragastric pH in the day time, and the effect lasted over 24 hours. The differance of the effect of the two drugs suggests the existence of differant mechanism of acid secretion in the day time and the night time.
In rats, the authors studied the effect of dopamine (DA) treatment (10μg/kg/min) to increase gastric mucosal blood flow and tried to elucidate the mechanisms of these effects. In vivo, pretreatment with a beta-blocker suppressed the action of DA to increase blood flow in the gastric mucosa, whereas the same action was not suppressed by pretreatment with an alpha-blocker. In addition, blood flow was elevated by treatment with DA1 or DA2 agonist in vivo. In an experiment in vitro which involved perfusion of the isolated gastric blood vessels, treatment with DA1, DA2 receptors were also present in the gastric vascular system. These results indicate that the increase in gastric mucosal blood flow observed following DA treatment is attributable to stimulation of beta-receptors and to vasodilation induced by stimulation of DA1 and DA2 receptors in the gastric vascular system.
We studied the quantitative changes of gastric mucus glycoproteins in rats after treatment with acid secretagogues (histamine and gastrin) or HCl in order to clarify whether the changes in gastric mucus glycoprotein contents were caused by the direct action of HCl. Rats were given histamine 0.08-80mg/kg body weight intraperitoneally, tetragastrin 0.4-120μg/kg subcutaneously, or 1ml of 0.001-0.6N HCl orally. The animals were killed one hour after administration of these reagents. The results were as follows; 1) Low dose histamine (0.8mg/kg) and tetragastrin (12μg/kg) tended to increase corpus mucus glycoproteins, but HCl did not exhibit this tendency. 2) Low pH (<3) on gastric mucosal surface decreased gastric mucus glycoprotein contents. 3) Macroscopical mucosal damage was produced by histamine (8-80mg/kg) or HCl (0.35-0.6N), but no lesion was induced by tetragastrin. These results suggested that low dose acid secretagogues increased corpus mucus glycoproteins and this phenomenon was not caused by direct action of HCl, and also suggested that an excess luminal H+ induced the decrease of mucosal mucus glycoprotein contents and then made the mucosal defence weak. However, gastrin strengthened the mucosal defence together with acid secretion.
Sequential appearance of duck hepatitis B virus (DHBV DNA), messenger RNA, and viral antigen (DHBsAg) in the liver was studied in the eraly phase of infection. After the appearance of DHBV DNA and mRNA, DHBsAg became detectable in a diffuse fashion on day 3. This coincided with the appearance of viral DNA in serum. The amount of DHBsAg in hepatocytes became markedly increased after the 4th week. In the 5th week, DHBsAg became detectable in the bile duct epithelium. The viral antigen tended to be localized in the liver in the late phase of infection. The study of three parameters in this model may give more insight into the study of pathogenesis of liver disease in hepatitis B virus infection.
The altertion of plasma amino acid concentration were studied in 55 cases with alcoholic iver disease and 23 cases with non-alcoholic, HBsAg positive chronic liver disease. The concentration of Tyrosine (Tyr) was significantly decreased and molar ratio (MR) was elevated in alcoholics on admission. The level of Tyr was rapidly increased after abstinence and intake of food. MR was also decreased. On admission, the ratio of Tyrosine/Phenylalanine (Tyr/Phe ratio) was markedly decreased, and increased after recovery. It was considered that these phenomenon wer coused by dministration of alcohol and decrease of food intake. It was useful for diagnosis of alcoholic liver diseases that the low level of Tyr. The elevation of MR and the reduce of Tyr/Phe ratio.
Normal peripheral blood mononuclear cells which were cultured with a lymphokine, recombinant interleukin 2 (IL2), for 72 hours developed lytic activity for natural killer-resistant Daudi cells. Lymphokine-activated killer (LAK) cells were thought to produce some cytolytic substance, because the culture supernatant from IL2-mediated mononuclear cells which were coclutured with Duadi cells caused on injury of Daudi cells as well as isolated hepatocytes. The active factor contained in the culture supernatant was found to be a protein having a molecular weight of 10 to 40K daltons. The activity was diminished by trypsin digestion but not by RNase, DNase or neuraminidase treatment. The active factor was rather stable to heat treatment.