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Biomedical subjects

H Yamamura

Publications and source records attributed to H Yamamura.

At least 289 records · Page 16Linked to original sources
PubMed1988

Effect of cimetidine on inhibition by tetragastrin of carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effects of combined administration of cimetidine and tetragastrin on gastric acid secretion, the labeling index of the gastric mucosa, and the incidence of gastric adenocarcinomas induced by N-methyl-N'-nitro-N-nitrosoguanidine were investigated in inbred Wistar rats. Prolonged administration of tetragastrin in depot form after treatment with N-methyl-N'-nitro-N-nitrosoguanidine resulted in a significant increase in gastric acid secretion, a significant decrease in the labeling index of the antral mucosa, and a significant decrease in the incidence of adenocarcinomas of the glandular stomach. Administration of cimetidine at 20 mg, but not 10 mg, per kg body weight with tetragastrin significantly reduced the gastric acid secretion induced by tetragastrin alone but did not influence the labeling index of the antral mucosa or the inhibitory effect of tetragastrin on gastric carcinogenesis. These findings indicate that gastric acid secretion has no influence on the development of gastric adenocarcinomas and that the inhibitory effect of tetragastrin on gastric carcinogenesis may be related to its effect in decreasing proliferation of cells in the antral mucosa.

Adenocarcinoma↗
PubMed1988

Protein phosphorylation and activation of human platelets by sodium fluoride.

The ability of sodium fluoride (NaF) and thrombin to stimulate aggregation and protein phosphorylation in intact human platelets was measured and compared. When platelets were stimulated by NaF, phosphorylation of the 20 KDa protein was transient and after 5-10 min returned to the same level as that of unstimulated cells. On the other hand, 47 KDa protein was slowly phosphorylated without obvious dephosphorylation. The slow activation of the 47 KDa protein phosphorylation correlated well with the time required for the aggregation and secretion. Phosphoamino acid analysis showed that the phosphorylated amino acids of the 47 KDa protein from platelets activated by NaF and thrombin were slightly different. These results suggest that different stimuli may lead to the same protein phosphorylation by different biochemical mechanisms of action.

Amino Acids↗
PubMed1988

Inhibition by tetragastrin of experimental carcinogenesis in rat colon: effect of wheat bran consumption.

The effect of dietary wheat bran consumption on the anticarcinogenic action of tetragastrin upon colon carcinogenesis induced by azoxymethane was investigated in 122 inbred Wistar rats. Rats were given a control fiber-free diet or the same basal diet plus 20% wheat bran. From week 5, they were given 250 micrograms per kg body weight of tetragastrin in depot form every other day until the end of the experiment at week 45. Prolonged administration of tetragastrin resulted in a significant reduction of the incidence and number of colonic tumors per rat in the group given the fiber-free diet. The adenocarcinomas that did develop in this group had high mucin-producing activity, unlike the cancers produced in controls without tetragastrin. However, administration of tetragastrin had little or no influence on the incidence, number or histology of colonic tumors in the group given basal diet plus wheat bran. Dietary supplementation with wheat bran alone had little or no effect on the development or histology of colonic tumors. Before and during the administration of carcinogens, addition of fiber to the diet resulted in a significant fall in the colonic pH and a significant increase in the crypt column length, but administration of tetragastrin did not have an additive effect on the crypt column length in rats fed diet supplemented with fiber.

Adenocarcinoma↗
PubMed1988

Insulin-stimulated serine kinase in Xenopus oocyte plasma membrane.

Insulin-stimulated protein kinase activities detected in Xenopus oocyte membrane were examined. The plasma membrane proteins solubilized in a buffer containing Triton X-100 were immunoprecipitated with anti-phosphotyrosine antibodies and adsorbed materials were eluted with a buffer containing p-nitrophenyl phosphate. The eluate contained protein serine kinase activity toward H1 histone which was increased 2-3 fold by insulin. Protein tyrosine kinase activity was also exhibited in Xenopus oocyte membrane and the close parallel to serine kinase activity was observed in response to insulin. These results suggest that insulin-stimulated serine kinase is activated through the phosphorylation by protein tyrosine kinase.

Animals↗
PubMed1988

Lack of involvement of leukotriene and platelet activating factor in passive cutaneous anaphylaxis in rats.

Possible chemical mediators contributing to 48 hour passive cutaneous anaphylaxis (PCA) in rats were investigated. Forty-eight hour PCA was inhibited considerably by mepyramine and methysergide given intravenously, a finding suggestive of a major role for histamine and serotonin in the reaction. AA-861, a selective 5-lipoxygenase inhibitor did not inhibit the PCA, and leukotriene (LT)D4 or LTE4 and the combination with prostaglandin (PG)E2 had no significant skin reaction. In addition, only small amounts of slow reacting substance of anaphylaxis (SRS-A) were detected in skin fragments, in vitro. Although CV-3988, a selective platelet activating factor (PAF) antagonist, dose-dependently inhibited the PAF-induced skin reaction, the PCA was not affected by treatment with this compound. Indomethacin also had no inhibitory activity on PCA. Thus, sulfidopeptide LTs, PAF and arachidonate cyclooxygenase metabolites probably do not contribute to PCA, at least in rats.

Animals↗
PubMed1988

The acute and chronic toxicities of nivalenol in mice.

In an attempt to ascertain precisely the toxic effects of nivalenol (NIV), we conducted the determination of LD50 values, and interim kills during the carcinogenic study in mice. LD50 values (mg/kg) of NIV in 6-week-old male ddY mice were determined as 38.9 (po), 7.4 (ip), 7.2 (sc), and 7.3 (iv). Seven-week-old female C57BL/6CrSlc SPF mice were fed diets containing 0, 6, 12, and 30 ppm (mg/kg) NIV over 1 year, and were assessed for effects on body weight gain, feed efficiency, terminal organ weights, hematology, and histopathology. The rates of body weight gain and feed efficiency showed a good dose-dependent correlation in all experimental periods. Gross and histopathological evaluation of the liver, thymus, spleen, kidneys, stomach, adrenal glands, pituitary gland, ovaries, sternum, bone marrow, lymph node, brain, and small intestines with or without Peyer's patch portion from control and all NIV-exposed mice revealed that these tissues were normal in appearance and in histopathological structure. Also, no changes were observed in the ultrastructural studies on the bone marrow. Dietary NIV did, however, cause dose-dependent decreases of absolute organ weights (mg) and increases of relative organ weights (mg/g body weight) in the terminal organ weights recorded. A significant leukopenia was observed in the 30 ppm group at 6 months and in all NIV-treated groups at 1 year. No marked changes were observed in the other hematological parameters. These results indicated that 6 ppm or more of dietary NIV for 1 year showed a characteristic toxic effect of trichothecene mycotoxins in mice.

Animals↗
PubMed1988

Ionic strength-dependent proteolytic activation of protein kinase C by trypsin-like protease.

Protein kinase C, reversibly bound to rat liver plasma membrane through Ca2+, was activated by endogenous trypsin-like protease in an ionic strength-dependent manner. In an attempt to understand the reaction mechanism, the EGTA-extracted protein kinase C and the trypsin-like protease (Tanaka, K. et al. (1986) J. Biol. Chem. 261, 2610-2615) were separately purified from plasma membrane. In the reaction system using these purified enzymes, increasing the ionic strength with NaCl (140-210 mM) effectively enhanced the proteolytic activation of the protein kinase C in the presence of Ca2+ and phospholipid. These results suggest that ionic strength is an important factor for the proteolytic activation of membrane-bound rat liver protein kinase C.

Animals↗
PubMed1988

Value of gastric juice carcinoembryonic antigen in identifying high-risk patients for gastric cancer.

The relationship of the level of carcinoembryonic antigen (CEA) in the gastric juice to the extent of intestinal metaplasia and gastric cancer, and clinical values of gastric CEA for identifying high-risk patients for gastric cancer were examined. A significant correlation was found between the levels of gastric CEA and the distribution of intestinal metaplasia. Studies were made by the endoscopic Congo red-methylene blue test developed at our hospital. Gastric CEA levels were significantly higher in patients with localized and diffuse intestinal metaplasia than in those with no intestinal metaplasia. The mean levels of gastric CEA in patients with well-differentiated adenocarcinomas were significantly higher than in those with diffuse intestinal metaplasia. They were also significantly higher in patients with poorly differentiated adenocarcinomas than in patients with no intestinal metaplasia, but not significantly higher than in those with diffuse intestinal metaplasia. Endoscopic follow-up examinations show that gastric cancer was detected in only 1 patient with a gastric CEA level of 10 ng/ml or more, but in none of those with gastric CEA of less than 10 ng/ml, during the average observation period of 4.3 years. These results indicate that gastric CEA is produced both by intestinal metaplasia and well- and poorly differentiated adenocarcinomas, and that gastric CEA is useful in identifying high-risk patients for gastric cancer.

Carcinoembryonic Antigen↗
PubMed1988

Comparison of photodynamic inactivation of experimental stomach tumors sensitized by acridine orange or hematoporphyrin derivatives.

The photodynamic inactivations of Walker carcinosarcoma 256 stomach tumors by the concomitant use of acridine orange (AO) and argon laser, and by the combined use of hematoporphyrin derivatives (HPD) and dye laser were compared. Wistar rats bearing stomach tumors of 4-6 mm in diameter 5-10 days after their implantation were injected intraperitoneally with 40 mg/kg body weight of AO or HPD, and 24 h later their stomach tumors were exposed to argon laser at 488 nm or dye laser at 630 nm, respectively, at an intensity of 15 mW/cm2 for 20 min. Temperature rise was less than 3 degrees C during irradiation. Seven days after irradiation, complete or partial necrosis with sparing of the surrounding mucosa was seen histologically in all rats treated by the two therapy methods. Phase contrast and electron microscopy showed nuclear pyknosis and damage to the inner layer of the nuclear envelope in tumor cells treated with AO and argon laser, while cytotoxicity involved damage to the outer layer of the nuclear envelope and intracytoplasmic organelles in tumor cells treated with HPD and dye laser. This difference between AO and HPD is considered to be a difference in their intracellular localization in tumor cells.

Acridine Orange↗
PubMed1988

[Antiallergic effects of mequitazine. 1. In vitro experiments].

The antiallergic effects of 10-(3-quinuclidinylmethyl)phenothiazine (mequitazine) were investigated in vitro. The results obtained were as follows: 1) In the isolated trachea and lung parenchyma of guinea pigs, mequitazine showed a fairly potent antagonistic action against contractions induced by both histamine (Hi) and acetylcholine (ACh). Mequitazine was much less potent in antihistaminic action and slightly more potent in anticholinergic action than ketotifen. The contractions of the preparation by leukotriene (LT) D4 were antagonized by mequitazine, although the potency was moderate, showing an IC50 value of 2.3 x 10(-5) g/ml in the trachea and 5.1 x 10(-5)g/ml in the lung parenchyma. Mequitazine had no effect on the contraction of the trachea by PGF2 alpha, but inhibited that of the lung parenchyma with pA2 = 7.0. 2) Mequitazine (10(-6) g/ml) slightly inhibited the Schultz-Dale reaction of the isolated guinea pig trachea, while ketotifen at the same concentration did not show any effect. 3) The contraction of the isolated guinea pig trachea by Ca2+ influx was slightly inhibited by mequitazine (10(-5) g/ml). 4) Mequitazine competitively inhibited the cyclic AMP-dependent phosphodiesterase activity from the rat lung with a potency of 10 times and 5 times more than those of ketotifen and theophylline, respectively. 5) Mequitazine (10(-6) to 10(-5) M) suppressed both the anaphylactic and phospholipase A2-induced histamine release from the peritoneal cells of rats. 6) Mequitazine (10(-5) g/ml) also inhibited the anaphylactic and Ca ionophore-induced histamine release from the leukocytes of the atopic patients and normal subjects. 7) The anaphylactic releases of histamine, LTB4 and peptide LT from the human lung fragments were dose-dependently inhibited by mequitazine (10(-7) approximately 10(-5) g/ml).

Acetylcholine↗
PubMed1988

[Antiallergic effects of mequitazine. 2. In vivo experiments].

Antiallergic effects of mequitazine were investigated in vivo and compared with those of ketotifen and disodium cromoglycate (DSCG). The results obtained were as follows: 1) Mequitazine in doses of 2 and 5 mg/kg given, p.o., 1 hr prior to antigen challenge inhibited dose-dependently the 48-hr passive cutaneous anaphylaxis in rats. Five mg/kg of mequitazine showed almost the same extent of inhibitory activity as that of 1 mg/kg of ketotifen. An i.v. administration of 1 mg/kg DSCG 1 min before antigen challenge also showed a marked inhibition. 2) The experimental asthma induced by challenge with an i.v. injection of antigen in passively sensitized guinea pigs was fairly inhibited by the pretreatment with 5 mg/kg of mequitazine administered p.o., although 2 mg/kg of this drug showed only a slight inhibition. 3) The experimental asthma induced by aerosolized antigen was also fairly inhibited by the pretreatment with 5 mg/kg of mequitazine given p.o.

Administration, Oral↗
PubMed1988

Effect of AA-861, a selective 5-lipoxygenase inhibitor, on models of allergy in several species.

The effects of 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone (AA-861), a selective 5-lipoxygenase inhibitor, on immunological or non-immunological release of slow reacting substance of anaphylaxis (SRS-A) and histamine and its effects on experimental asthma were investigated. AA-861 showed a dose-dependent inhibition of SRS-A release, with no effect on histamine release from passively sensitized guinea pig, monkey (M. irus) and human lung fragments. An analysis of the anaphylactic diffusate from the human lung fragments, using the combined technique of high performance liquid chromatography and radioimmunoassay, revealed that AA-861 markedly suppresses biosynthesis of the leukotrienes. However, this drug inhibits the release of histamine as well as SRS-A from lung fragments of anaphylactic monkey (M. mulatta) and in the Ca ionophore-stimulated rat peritoneal cavity. AA-861 suppressed the anaphylactically-induced airway resistance in mepyramine- and cimetidine-treated guinea pigs. These results suggest that AA-861 may be clinically effective for treating allergy-related asthma by modulating the 5-lipoxygenase pathway and that an inhibitory mechanism of histamine release by AA-861 may be present in some species.

Animals↗
PubMed1988

Effects of rokitamycin on young rats with hyperbilirubinemia--determination of unbound and brain bilirubin levels and examination for localized yellow discoloration of brain tissue.

The effects of rokitamycin (RKM), a macrolide antibiotic, on young rats with hyperbilirubinemia were investigated. RKM at a dose of 1,000 mg/kg was orally administered to 14-day-old rats with hereditary, non-hemolytic hyperbilirubinemia (homozygous Gunn rats, total plasma bilirubin concentration: about 7 mg/dl). Animals given 10 ml/kg of 0.5% carboxymethyl cellulose (CMC) were used as control. Plasma total bilirubin concentration, plasma unbound bilirubin concentration and cerebellar bilirubin level did not significantly change during 1, 3, 6 and 24 hours after administration of RKM or CMC. There was no significant difference in plasma total bilirubin concentration, plasma unbound bilirubin concentration and cerebellar bilirubin level between RKM-treated and control animals at 1, 3, 6 and 24 hours after the administration. No localized yellow discoloration of the brain tissue (non-cerebellar parts) was noted at 1, 3, 6 and 24 hours after administration of either RKM or CMC.

Animals↗
PubMed1988

Comparison of phosphorylation sites in protamines between protein kinase C and cAMP-dependent protein kinase.

Phosphorylation sites of protamines by protein kinase C and cAMP-dependent protein kinase (protein kinase A) were studied. Using clupeine Y1 as a substrate, protein kinase C phosphorylates both Ser and Thr residues, whereas protein kinase A phosphorylates only Ser residue(s). Protein kinase C phosphorylates all Ser and Thr residues of clupeine Y2 and Z, however protein kinase A phosphorylates mainly Ser9 and slightly Thr5 in clupeine Y2 and Ser6 and Ser10 in clupeine Z. These results suggest that protein kinase C recognizes more sites than those of protein kinase A and may participate in protamine phosphorylation in vivo.

Amino Acid Sequence↗
PubMed1988

Enhancement by vagotomy of experimental induction of intestinal metaplasia and atypical glandular hyperplasia in Wistar rats.

The effect of truncal vagotomy on the induction of intestinal metaplasia and atypical glandular hyperplasia by intragastric instillation of 5% NaOH solution was investigated in Wistar rats. Truncal vagotomy resulted in significant increases in the incidences and numbers of intestinal metaplasia and atypical glandular hyperplasias in experimental week 52. Histological examinations show that unlike goblet cell metaplasia and mild atypical glandular hyperplasia in the sham-operated rats, intestinal metaplasia without Paneth cells and moderate atypical glandular hyperplasia were more frequent in rats treated with NaOH solution and vagotomy. These findings indicate that the promoting effect of truncal vagotomy on gastric carcinogenesis may be related to its enhanced effect on induction of intestinal metaplasia and atypical glandular hyperplasia.

Animals↗