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Biomedical subjects

K Saigenji

Publications and source records attributed to K Saigenji.

At least 91 records · Page 5Linked to original sources
PubMed1994

Effects of the new histamine H2 receptor antagonist, FRG-8813, on gastric mucin in rats with or without acidified ethanol-induced gastric damage.

It is not presently well understood whether the histamine H2 receptor antagonist has a function other than the inhibition of gastric acid secretion, such as the effect on the gastric mucosal defence mechanism. In this paper, we report the effect of FRG-8813 (N-[4-[4-(piperidinylmethyl)pyridyl-2-oxy]-(Z)-2-butenyl]-2- (furfurylsulfinyl) acetamide), a new histamine H2 receptor antagonist, on the rat gastric mucin content with or without 0.15N HCl-ethanol (60 %)-induced gastric damage. The prior administration of FRG-8813 significantly inhibited the occurrence of macroscopically observable hemorrhagic lesions induced by the acidified ethanol treatment. Using a newly developed biochemical method, the mucin content of the deep corpus and antral mucosa of the acidified ethanol-treated animals was significantly reduced to 50% and 32% of the control, respectively. These reductions were inhibited by the pretreatment with FRG-8813. Total mucin content in the entire stomach recovered to about 80% of the control value after pretreatment with FRG-8813. A single oral administration of FRG-8813 (30 mg/kg) caused no significant change in the total mucin content, but mucin in the adherent mucus gel layer selectively and significantly increased to 250% of the control. These results suggest that FRG-8813 not only inhibits acid secretion but may also affect the gastric mucosal defensive mechanism as well.

Acetamides↗
PubMed1994

Suppressive effects on cancer cell proliferation of the enhancement of superoxide dismutase (SOD) activity associated with the protein-bound polysaccharide of Coriolus versicolor QUEL.

The protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) expresses superoxide dismutase (SOD) mimicking activity. Examination was made of the suppressive effects of PS-K on cancer cell lines cultured in vitro. SOD activity of incorporated PS-K was 5.88 u/mg in LLC-WRC-256 (Walker 256 fibrosarcoma) cells and 4.73 u/mg in NRK-49F (rat normal kidney fibroblast) cells. SOD activity in both cell types was enhanced about 7-8 times that of the original PS-K. PS-K was not incorporated into H4-11-E or H4-11-E-C3 (rat hepatoma) cells. SOD activity of 1 mg/ml PS-K incubated with cell homogenates of LLC-WRC-256 cells for 6 hours increased from 0.68 u/mg to 1.35 u/mg. SOD activity of PS-K 1 mg/ml in 0.05 M phosphate buffer incubated with 50 microM NADPH increased from 0.68 u/mg. The consumption of NADPH at the same concentration was confirmed spectrophotometically by incubation with PS-K. The mechanism for the enhancement of SOD activity associated with PS-K is considered to be collaboration with NADPH as an electron donor in the cytoplasm of cancer cells whose SOD and coupling enzyme activities are significantly lower than in normal cells.

Animals↗
PubMed1994

Enhancement of anti-cancer activity of cisdiaminedichloroplatinum by the protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) in vitro.

The protein-bound polysaccharide of Coriolus versicolor QUEL (PS_K) expresses superoxide dismutase (SOD) mimicking activity. Examination was made of the effects of PS-K on cancer cell lines following administration of the anti-cancer drug cisdiaminedichloroplatinum (cisplatin). Cell proliferation of each cell line was inhibited markedly by cisplatin from 0.5 to 5 micrograms/0.5 ml per well. Fifty percent of the inhibitory concentration (IC50) was 0.33 micrograms/0.5 ml per well in NRK-49F and human ovarian cancer cells, and 1.5 micrograms/0.5 ml per well in H4-II-E. PS-K 50 micrograms/0.5 ml per well prevented cytotoxicity due to cisplatin toward NRK-49F, but enhanced the cytotoxicity on H4-II-E and human ovarian cancer cells. Increase in lipid peroxide and decrease in SOD activity were observed following an IC50 dose of cisplatin. With PS-K 50 micrograms/0.5 ml per well, all the above were augmented in H4-II-E and ovarian cancer cells, but diminished in NRK-49F cell line. PS-K may have effect on cancer patients through its combining with cisplatin.

Animals↗
PubMed1994

Oxidative stress relief for cancer-bearing hosts by the protein-bound polysaccharide of Coriolus versicolor QUEL with SOD mimicking activity.

The protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) expresses the mimetic activity of superoxide dismutase (SOD). Human cancer patients usually suffer from oxidative stress (OS). Examination was made to determine the capacity of this drug with SOD mimetic activity for relieving OS. Rats transplanted with Walker 256 fibrosarcoma showed OS on day 12. After confirming high levels of OS on day 13, PS-K50 mg/kg was intraperitoneally administered, and prompt decrease in O2-release from RBC was noted. The drug ceased to have any effect 24 hours following the first inoculation. Average OS in human cancer patients was found twice that in healthy persons. In human cancer patients perorally administered PS-K3.0 g/day, OS decreased to the normal level one day after the initial administration. Plasma lipid peroxide (LPO) in cancer patients treated with PS-K for 28 days increased and withdrawal of the drug led to decreased LPO.

Administration, Oral↗
PubMed1994

Suppression of cancer cell growth in vitro by the protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) with SOD mimicking activity.

The protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) expresses the mimicking activity of superoxide dismutase (SOD). Examination was made of the suppressive effects of PS-K on cancer cell lines cultured in vitro. The SOD activity of LLC-WRC-256 (Walker 256 fibrosarcoma) cell lines was less than that of NRK-49F (rat normal kidney fibroblast), H4-II-E (rat hepatoma) and H4-II-E-C3 (rat hepatoma) cell lines. This activity in Walker 256 fibrosarcoma cells increased by 3.6 times and H2O2 concentration, by 2.56 times by PS-K 500 micrograms/ml. Cell proliferation was consequently suppressed and living cells decreased to less than 50% of the cells cultured without PS-K. Catalase and glutathione peroxidase activity changed little by PS-K. The sensitivity of cancer cells to PS-K can be predetermined based on SOD activity in tumor tissue.

Animals↗
PubMed1994

Effects of Z-300, a new histamine H2-receptor antagonist, on mucin biosynthesis in rat gastric mucosa.

We examined the effects of Z-300 (N-[3-[3- (piperidinomethyl)phenoxy]propyl]-2-(2-hydroxy-ethyl-1-thio)acetam ido.2- (4-hydroxy benzoyl)benzoate), a newly-synthesized selective histamine H2-receptor antagonist, on mucin in rat gastric mucosa. Deep corpus mucin content increased significantly to 127% of the control after the administration of 30 mg/kg of Z-300, whereas that in the antral mucosa did not increase. The addition of Z-300 significantly increased [3H]-labeled mucin in the corpus region. In the antrum, biosynthetic activity showed no significant change by 10(-8)-10(-5) M of Z-300. These results suggest that Z-300 not only inhibits acid secretion but may also promote gastric mucus metabolism in the corpus region.

Acetamides↗
PubMed1994

Intragastric pH in postlaparotomy patients--effects of cimetidine.

Intragastric pH was continuously monitored in 21 patients who underwent colorectal surgery. Monitoring was started before surgery, and was continued for two days after surgery. Intragastric pH tended to increase during surgery, compared with measurements obtained before and after surgery, but was not affected by the duration of anesthesia or of the surgical procedure, or surgical position. After surgery, patients were divided into two groups: the cimetidine group (10 patients) received intravenous cimetidine 200 mg 4 times a day, while the control group (11 patients) received no treatment. Postoperative intragastric pH was higher than 3.0 throughout the study in the cimetidine group, but was approximately 1.3 in the control group. Upper gastrointestinal bleeding occurred in 2 patients in the control group, with intragastric pH falling abruptly during the bleeding episode. To prevent post-operative upper gastrointestinal bleeding, in addition to the administration of H2-blockers or antacids, appropriate treatments in response to changes in intragastric pH are necessary. Continuous monitoring of intragastric pH in surgical patients is considered to be of clinical importance.

Aged↗
PubMed1994

Immunohistochemical study of hepatocellular carcinoma-specific aldehyde dehydrogenase.

Tumor-associated aldehyde dehydrogenase (ALDH) was reported in cases of human hepatocellular carcinoma and animal hepatoma models. This ALDH isozyme is similar to ALDH3 which exists in the stomach and lung; however, the biochemical and clinical significance of this unique ALDH isozyme have not been established. Human tumor-associated ALDH was purified, and polyclonal antibodies prepared. Using these antibodies, specific development of tumor-associated ALDH was confirmed by immunohistochemical techniques. It was found that about 50% of hepatocellular carcinomas reacted with the antibody. This unique ALDH isozyme may be a novel tumor marker of hepatocellular carcinoma.

Aldehyde Dehydrogenase↗
PubMed1993

Stimulation of mucus glycoprotein biosynthesis in rat gastric mucosa by gastrin.

We examined the effects of the gastrin family of peptides on gastric mucus glycoprotein (mucin) biosynthesis in rat gastric mucosa using an organ culture technique. Radiolabeled mucin was obtained from the tissue and culture medium of the corpus and antrum of rat stomach incubated for 5 hr with [3H]glucosamine (GlcN), [14C]threonine (Thr), and [35S]sulfate in vitro. With the addition of 10(-8) and 10(-7) M tetragastrin to the culture medium, [3H]GlcN labeled mucin in the corpus tissue increased to 120-135% that of the control (P < 0.01). The biosynthetic responses to cholecystokinin (CCK)-8 and the 17-peptide gastrin were essentially the same as that to tetragastrin. Tetragastrin 10(-8) M also increased the incorporation of [35S]sulfate into the corpus mucin but failed to change [14C]Thr incorporation. In the antrum, biosynthetic activity showed no significant change with 10(-9) approximately 10(-5) M tetragastrin. Ranitidine, diphenhydramine and omeprazole at 10(-5) M did not suppress the tetragastrin-induced increase in [3H]GlcN incorporation into mucin, but L-365,260 at a concentration of 10(-6) M completely blocked this effect. These results suggest that gastrin stimulates mucin production via CCK-B/gastrin receptors in the oxyntic region of rat gastric mucosa.

Animals↗
PubMed1993

An immunohistochemical study of c-erbB-2 protein in gastric carcinomas and lymph-node metastases: is the c-erbB-2 protein really a prognostic indicator?

An immunohistochemical study of the c-erbB-2 protein was conducted on formalin-fixed paraffin-embedded tissue sections from 136 primary gastric carcinomas and 50 metastatic lymph-node tumors obtained at gastrectomy. Expression of the protein was detected in 35 of 136 primary gastric carcinomas (25.7%) and 22 of 50 metastatic lymph nodes (44%). The staining pattern of tumor cells was classified as membranous or cytoplasmic. An immunohistochemical study using serially diluted antibody demonstrated that 82.6% of positive cases in metastatic lymph nodes showed c-erbB-2 immunoreactivity stronger than that in the primary tumors. Membranous staining was stronger than cytoplasmic staining. c-erbB-2 protein of the cytoplasmic as well as membranous types was confirmed to be a 185-kDa whole molecule by immunoblotting. Correlation between the expression of c-erbB-2 protein and clinical and histological parameters was investigated. No significant correlation between 5-year survival rate of patients and expression of c-erbB-2 protein was found. In the poorly differentiated carcinoma group possessing c-erbB-2 protein, overall survival was significantly shorter than in cases without protein expression (p < 0.01). We conclude that c-erbB-2 protein is not a useful prognostic indicator in gastric carcinomas.

Female↗
PubMed1993

Immunoglobulin-complexed aspartate aminotransferase.

We report a case of increased aspartate aminotransferase (AST, EC 2.6.1.1; GOT) in a 17-year-old girl which persisted for 3 years. The patient was healthy, but a high level of serum AST was detected during a school health check. Further examination revealed that AST was increased to as high as 259 IU/l while alanine aminotransferase (ALT) was normal. Immunoelectrosyneresis and immunoprecipitation methods revealed that this atypical AST combined with IgG--kappa, lambda globulin and formed macromolecular complexes. Including the present case, 26 cases of IgG-complexed AST have been reported. It is important to be aware of this syndrome, and thereby avoid unnecessary examinations and therapies.

Adolescent↗
PubMed1993

Effects of the muscarinic receptor agonist carbachol and/or antagonist pirenzepine on gastric mucus secretion in rats.

The effects of the muscarinic agonist carbachol on the secretion and accumulation of gastric mucus glycoprotein (mucin) were examined. Gastric mucin obtained from the soluble mucus, adherent mucus gel, and surface mucosal and deep mucosal layer was isolated and quantified. One hour after the subcutaneous administration of carbachol (0.08-80 micrograms/kg body weight) the deep corpus mucin content had decreased significantly (75% of control), corresponding to an increase (120% of control) in the soluble mucin content with 0.8 microgram/kg of carbachol treatment. These changes were counteracted by 10 mg/kg of pirenzepine (selective M1 antagonist) pretreatment. On a single administration of 10 mg/kg of pirenzepine, deep corpus mucin tended to increase, and soluble mucin decreased significantly (49% of the control). These two drugs failed to cause any significant change in the mucin content of the surface and antral deep mucosa or the adherent mucus gel. The muscarinic agonist and the M1 antagonist are thus shown to accelerate the secretion and accumulation, respectively, of mucin in the deep corpus mucosa. Thus intrinsic M1 receptor may possibly be involved in the secretion of mucin in the gastric deep corpus mucosa.

Animals↗
PubMed1993

[The effect of prostaglandin E1 and prostaglandin F2 alpha in the ischemic small intestine of dogs].

The effect of PGE1 and PGF2 alpha in the ischemic intestinal tract were examined. In 40 mongrel dogs, we studied ischemic models of small intestine. PGE1 or PGF2 alpha was injected into the anterior mesenteric artery after reperfusion according to each occlusion time, and the tissue blood flow was measured on both mucosal and serous sides of small intestinal loop by laser flowmeter to examine the relation to the extent of tissue damage. Tissue blood flow of the ischemic intestine after the injection of PGE1 increased by 148-208% in the 3-5 hr occlusion group and by 86-110% in the 7-10 hr occlusion group. Tissue blood flow after the injection of PGF2 alpha decreased by 39-59% in the 3-5 hr occlusion group and by 1-15% in the 7-10 hr occlusion group. These results indicate that the effect of PGE1 and PGF2 alpha in the ischemic intestine would be available up to 3-5 hr of ischemia. Histological examination revealed that viability of the remaining crypt was high in the PGE1 injection group but low in the PGF2 alpha injection group. These findings suggest that PGE1, if try at the early stage, would be effective for the treatment of ischemic lesion.

Alprostadil↗
PubMed1992

[The biphasic response of hepatic arterial blood flow caused by vasoactive substances--an experimental study in dogs].

In ten male mongrel dogs, blood flow was measured in the common hepatic artery (CHA), portal vein (PV) and liver tissue before and after the injection of vasoactive substances: angiotensin II (1.0 micrograms/kg), prostaglandin F2 alpha (1.0 micrograms/kg) and vasopressin (0.1 Unit/kg), under observation of the systemic circulation. Each injection caused a biphasic response in CHA blood flow, an initial decrease followed by a marked increase, while PV blood flow decreased. Liver tissue blood flow was reduced just after injection, but soon returned to a normal level. The duration of action was the shortest with prostaglandin F2 alpha and the longest with vasopressin. In using vasoactive substances in pharmaco-angiography, it is important to consider the biphasic response in CHA blood flow as well as the duration of action of these substances.

Angiotensin II↗
PubMed1992

Suppression of myoelectrical activity of gastric smooth muscle by endogenous gastric prostaglandin E2.

The myoelectrical activity of the gastric smooth muscle, recorded by a bipolar electrode placed at the gastric antrum in rats, could be recorded when the stomach was distended with 5 ml of physiological saline. This activity may be induced by a mucosal reflex and was inhibited both by atropine and by pirenzepine. Replacement of physiological saline with solutions of NaCl suppressed this myoelectrical activity. This suppression was dependent on the concentrations of NaCl in the solutions, from 0.3 to 1.0 M. Pretreatment with indomethacin (10 mg/kg, intravenous) completely prevented this suppression induced by different concentrations of NaCl solutions. Intragastric administration of 1.0 M NaCl in solution caused an increase in the levels of PGE2 in the gastric lumen. Intragastric administration of OU-1308, a synthetic derivative of PGE1, also suppressed the myoelectrical activity in a dose-dependent manner. It is concluded that the suppression of gastric myoelectrical activity by hyperosmolar NaCl may be attributable to the generation of endogenous PGE2 in the stomach.

Alprostadil↗
PubMed1992

Effects of tetragastrin on mucus glycoprotein in rat gastric mucosal protection.

The effects of tetragastrin on mucus glycoprotein (mucin) metabolism and mucosal protection in rat gastric mucosa were investigated. Rats were administered with various doses of tetragastrin (12, 120, or 400 micrograms/kg body weight; s.c.), followed by 50% ethanol-induced gastric injury. Tetragastrin caused a significant increase in mucin content in the corpus mucosa and prevented 50% ethanol-induced gastric mucosal damage in a dose-dependent manner. For assessment of the effects of tetragastrin on the metabolism of gastric mucin in detail, changes in mucin distribution in the three different layers of rat gastric mucosa were examined one hour after single administration of tetragastrin. A significant increase in the mucin content was noted in the mucus gel and surface mucosal layer. Mucin content in the deep mucosa corresponding mainly to the mucus neck cell mucin underwent virtually no change by this treatment. An increase in mucin in the mucus gel and surface mucosa would thus appear due to the administration of tetragastrin and may possibly be related to the protective action of the gastric mucosa against injury. The data demonstrate a possibility that gastrin may have potential for enhancing gastric mucosal protection associated with mucus secretion and/or mucus synthesis on the surface mucosa of rat gastric mucosa.

Animals↗