Gastric fundic mucosal content of 5 prostanoids and gastric submucosal blood flow rates in rats were measured under HCl-induced adaptive cytoprotection with a 1 hour interval between oral administration of mild and strong irritants. PGE2 and PGF2α increased transiently after mild irritation (MI) and increased even more after subsequent strong irritation (SI). TXB2 increased after SI, but pretreatment with MI partially suppressed this increase. 6-keto-PGF1α and PGD2 increased only after a single SI. Pretreatment with indomethacin decreased all prostanoids below the control levels. Gastric submucosal blood flow rates increased transiently after MI or SI. Pretreatment with indomethacin prolonged the transient increase of gastric submucosal blood flow after MI. HCl-induced adaptive cytoprotection appeared to be related to the transient increases of PGE2 and PGF2α, which were believed to be unrelated to the blood flow increases after MI.
In our previous reports, low dose acid secretagogues caused increase in corpus mucus glycoprotein content in rats. This increase was not due to the direct action of protons. The present study was conduced to determine whether this increase has a mucosal function or not. Rats were given histamine (0.8mg/kg) intraperitoneally or tetragastrin (12μg/kg) subcutaneously. One hour following the acid secretagogues administration, the animals were given 1ml of 30, 40 or 50% ethanol orally and then sacrificed after one hour. Gastric mucus glycoproteins were isolated from the corpus region of stomach. The following results were obtained: 1) Histamine prevented the gastric mucosal damage and the decrease of corpus mucus glycoprotein content induced by 40% ethanol ingestion. 2) Tetragastrin prevented the gastric mucosal damage induced by 30-50% ethanol ingestion and the decrease of corpus mucus glycoprotein content induced by 40-50% ethanol ingestion. Based on these results, the increase of corpus mucus glycoprotein content induced by acid secretagogues has a mucosal function. Moreover, tetragastrin strengthened the mucosal defence together with acid secretion.
Using SDS-PAGE and Immuno-blotting assay, we analysed antigens defined by anti-Anisakis Larvae antibodies of IgE and IgG type in the sera of patients with acute gastrointestinal anisakiasis. 1) Humoral IgE response to 76, 64 and 60 kDa molecular weight proteins of Anisakis Larvae and IgG response to 91, 76, 64 and 60 kDa molecular weight proteins were demonstrated in the sera of patients with acute gastric anisakiasis. Those humoral antibody responses were also demonstrated in the sera of two patients with intestinal anisakiasis. 2) Those antibodies to 76, 64 and 60 kDa proteins may be Anisakis-specific antibodies, because anti-Anisakis Larvae antibodies of IgE and IgG type did not react with the similar MW proteins of Ascaris suum homogenates. 3) Also anti-Anisakis Larvae antibodies reacted with Anisakis Excretory and Secretory (E.S.) protein which included specific 76 and 60 kDa proteins, but they did not react with purified Anisakis hemoglobin.
Fecal intestinal flora in patients with colon adenoma showed significant decrease of Bifidobacterium. A tendency of decrease of Bifidobacterium and increase of Clostridium-other was shown in adenomas with higher degree atypia, but no definite tendency could be found concerning its size. Compared with the control group, patients with colon cancer showed significant increase of Clostridium-other and decrease tendency of Bifidobacterium which was not relevant to its percentage of total circum ference involved by the cancer. From the above findings, it is suggested that tumor growth or malignant transformation has relation to Bifidobacterium and Clostridium-other.
When trinitrophenylated (TNP) hepatocytes and lipopolysaccharide (LPS) are intravenously injected into TNP-liver protein sensitized guinea pigs, massive hepatic cell necrosis was induced in most of mice. using this experimental acute hepatic failure model, the tryptophan metabolism in the liver, brain, kidney and serum was studied. As a result, the tryptophan level was remarkably high in all three organs and serum, and the metabolism of both the tryptamine pathway and serotonin pathway was induced. Also, in the brain, the tryptamine metabolism was more induced compared to the serotonin. These results suggest that the metabolites of tryptophan may be involved in this acute hepatic failure model.
To clarify the effects on blood coagulation-fibrinolytic system after transcatheter hepatic arterial therapy for cases of hepatocellular carcinoma (HCC), plasma levels of Plasmin-α2PI complex (PIC), Ddimer and Thrombin-ATIII (TAT) before and after therapy were measured by EIA, in addition to other conventional coagulofibrinolytic parameters. In the group (9 cases) treated with intra-arterial injection of adriamycin, there were no significant changes of coagulofibrinolytic parameters except for Ddimer (P<0.05) which was elevated 1-2 days after therapy. However, only two cases in whom plasma PIC, Ddimer and TAT levels were clearly elevated before therapy, showed further marked elevation of those parameters after therapy. In the group (29 cases) treated with intra-arterial injection of adriamycin-lipiodol suspension, whether or not embolized with gelfoam, plasma PIC, Ddimer and TAT levels were significantly elevated (P<0.01) after therapy, as well as other conventional coagulofibrinolytic parameters. These results indicate that hypercoagulable and hyperfibrinolytic states were induced by treatment. Moreover, the secondary hyperfibrinolytic state tended to persist longer than the hypercoagulable state. The 14 cases embolized with gelfoam seemed to have more apparent effects on blood coagulation-fibrinolytic system than cases not treated with gelfoam. Therefore, we conclude that caution and prophylaxis for the occurrence of disseminated intravascular coagulation are necessary for transcatheter arterial therapy for cases of HCC.
Serial changes of total bile acid concentrations (TBA) in the peripheral and portal blood after partial hepatectomy were examined on rats with both normal and impaired liver which was induced by CCl4. Changes of TBA in the peripheral blood, clearance index and intrahepatic shunt index were marked in proportion to the volume of resectin and in the damaged liver. No significant changes of TBA in the portal blood were seen. TBA in the peripheral blood were significantly correlated with TBA in the portal blood, clearance index and intrahepatic shunt index. Clearance index was also significantly conrrelated with the rate of regeneration. Therefore, it is concluded that decrease of hepatic extraction of bile acid and increase of intrahepatic shunts between portal vein and hepatic vein elevated TBA in the peripheral blood. It seems useful for evaluation of postoperative hepatic regeneration to measure TBA in the peripheral and portal blood and to calculate clearance index after partial hepatectomy.
Ras genes are converted to active oncogenes by point mutations occuring in either codon 12, 13 or 61. We used ploymerase chain reaction and direct sequence method for the analysis of these mutations. We examined 13 hepatocellular carcinomas, 8 cholangiocarcinomas, 2 hepatoblastomas and 1 biliary cystadenocarcinoma. Of these tumors, ras gene mutations were detected soley in cholangiocarcinomas. Cholangiocarcinoma showed a high incidence of K-ras gene mutation. Among 8 patients with cholangiocarcinoma, the mutation was detected at colon 12 in 4 and at colon 61 in 1. The incidence of K-ras gene mutation was especially high in the hilar type of cholangiocarcinoma as compared with the peripheral type.
Portosystemic shunt index was estimated in 7 patients without liver disease and 95 patients with various liver diseases by portal scintigraphy with transrectally administered 123I-iodoamphetamine (IMP). The shunt index was 0% in patients without liver diseases, 5.3% in acute hepatitis, 5.9% inchronic inactive hepatitis, 11.4% in chronic active hepatitis, 56.6% in compensated livercirrhosis and 88.1% in decompensated liver cirrhosis. The shunt index was significantly higher in liver cirrhosis, especially decompensated stage. In 5 of 9 patients with acute hepatitis, shunt index was 0%. In 3 of remaining 4 patients with elevated shunt index, shunt index became 0% within 1-2 months. Significant relatioship was observed between the shunt index and hepatic function tests such as ChE, albumin, γ-globulin and ICG-R15. These results suggest that the sunt index is independent of hepatic cell necrosis and reveals the shunted blood flow exactly. Therefore, this technique is useful for evaluating the portosystemic shunt in various liver diseases.
The effect of ethanol on pancreatic exocrine secretion and intraduodenal pH was inverstigated in 3 dogs, after making pancreatic, gastric, and jejunal fistula. After intragastric and intrajej unal administration of ethanol the intraduodenal pH went doun and pancreatic juice, pancreatic bicarbonate output was increased. The integrated value of pancreatic juice, pancreatic bicarbonate and pancreatic portein output was greater in case of intrajejunal administration rather than intragastric administration of the ethanol. After intragastric and intrajejunal administration of the ethanol the plasma concentration of CCK was unchanged. The decrease of intraduodenal pH and increase of pancreatic exocrine secretion was though be mainly due to the secondary action of gastric acid secretion stimulated by ethanol.
Pancreatico-biliary diversion (PBD) by jejunal transposition in rats caused pronounced hyperplasia of pancreas. The increase of pancreatic trypsinogen contents exceeded the pancreatic growth, while pancreatic lipase and amylase contents relatively reduced. The high level of plasma CCK at the early period of PBD gradually decreased. The plasma secretin levels remained unchanged for 14 days after PBD. The plasma CCK levels were not elevated in fasting, but increased after intrajejunal infusion of 0.1N HCl or Clinimeal®. In acini prepared from PBD rats, the responsiveness to CCK8 was decreased when amylase release was expressed relative to DNA. The dose-response curve for CCK8 was shifted 3 fold toward higher concentrations of CCK8 4 days after PBD, but on 7 and 14 days after PBD returned to the same curve as the transected rats (control).
Thirty four murine monoclonal antibodies were produced against mucin which was isolated from nude mouse xenografts of the SW1990 pancreatic adenocarcinoma cell line. Twelve of them reacted with formalin-fixed SW1990 cells. The antigenic determinants of these antibodies were composed of carbohydrates and their immunoreactivities were predominant at CsCl fraction #6. The remaining 22 antibodies did not react with formalin-fixed cells, 5 epitope specificities of which antibodies are present in the polypeptide part or the part of linkage between oligosaccharide and polypeptide and the immunoreactivities were predominant at CsCl fraction #5. Immunohistochemical study showed that the incidence of epitope expression of the latter 22 antibodies were higher in pancreatic cancer tissues and lower in normal pancreatic tissues than that of the former 12 antibodies. The incidence of Nd2 (one of the 22 antibodies) expression was highest in pancreatic cancer tissues and lowest in normal tissues. ELISA showed that Nd2 antigen was non-secreting type. In vivo tumor distribution studies showed that Nd2 antibody tended to accumulate in cancer tissues. These results seem to support the clinical availability of Nd2.