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Biomedical subjects

H Kitagawa

Publications and source records attributed to H Kitagawa.

At least 469 records · Page 26Linked to original sources
PubMed1986

A simple method for estimation of gastric mucus and effects of antiulcerogenic agents on the decrease in mucus during water-immersion stress in rats.

In the present study Corne's technique that has been commonly used to quantify the gastric mucus in situ using the dye, Alcian blue, has been improved. Furthermore, the effects of antiulcerogenic agents on the decrease in gastric mucus gel during water-immersion stress were also studied. In order to increase the extraction of dye-recovery, we used 30% dioctyl sodium sulfosuccinate (docusate sodium, DSS) instead of 0.5 mol/l MgCl2 used in Corne's technique. The control values of the dye-recovery extracted with DSS were about 5 times higher than those with MgCl2. Indomethacin (20 mg/kg s.c.) failed to influence dye-recovery with DSS and MgCl2, while reserpine (5 mg/kg i.p.) significantly decreased the dye-recovery in both extractions. Water-immersion stress for 2 h decreased the dye-recovery with DSS but the dye-recovery with MgCl2 decreased only 15 min after water-immersion. These results suggest that extraction with DSS reflects the mucus gel secretion, and that dye-recovery with DSS is more sensitive to alteration of mucus gel than that with MgCl2. Bombesin (10 micrograms/kg), secretin (100 U/kg) and mild irritants increased the dye-recovery with DSS. Cimetidine remarkably reduced the mucus secretion and failed to improve the decrease in mucus during water-immersion stress. Pirenzepine and atropine dose-dependently prevented the decrease in the dye-recovery during water-immersion stress.

Alcian Blue↗
PubMed1986

Monoclonal antibodies with fine specificities distinguishing alpha-fetoproteins of hepatoma and yolk sac tumor origin.

Monoclonal antibodies with fine specificities distinguishing alpha-fetoproteins of hepatoma (HEP-AFP) and yolk sac tumor (YST-AFP) origin have been obtained. These murine antibodies were produced by hybridomas made by fusion of X63-Ag8.653 myeloma cells with BALB/c spleen cells immunized with either HEP-AFP or YST-AFP and selected for their differential association with these antigens on the basis of Scatchard plot analysis. Three monoclonals (MA120, MA132 and MA136) selectively reacted with HEP-AFP. Their reactivity with YST-AFP was low. One monoclonal (MA122) reacted strongly with YST-AFP, whereas the reaction with HEP-AFP was significantly less strong. The difference in the association constants of these antibodies for the two AFPs appeared to be due to their specificity for the carbohydrate portions of the AFPs, which are different, at least in part. Indirect immunoperoxidase staining confirmed that MA122 was able to stain sections of an infantile embryonal carcinoma, but not of hepatoma.

Animals↗
PubMed1986

Effects of co-administration of monomethylaminoantipyrine with diethylaminoethyl 2,2-diphenylvalerate (SKF 525-A) on gamma-glutamyltranspeptidase, glutathione S-transferase and hepatic drug metabolizing enzyme activities in rats.

4-Monomethylaminoantipyrine (MAA)-induced increase of hepatic drug metabolizing enzymes was suppressed by SKF 525-A. This may be due to the partial binding of SKF 525-A to a portion of cytochrome P-450. On the other hand, glutathione S-transferase and gamma-glutamyltranspeptidase (gamma-GTP) activities of rat liver were both induced by repeated administration of MAA in combination with SKF 525-A. In addition, under the same condition, glutathione level in rat liver was significantly decreased.

Aminopyrine↗
PubMed1986

Gastric mucosal erosion due to a mucosal ischemia produced by thromboxane A2-like substance in rats under water-immersion stress.

The involvement of a thromboxane (TX) A2-like substance in the decrease of mucosal blood flow (MBF) and occurrence of gastric erosions in rats under water-immersion stress was examined. MBF was estimated by aminopyrine clearance. Stress increased acid output without a parallel increase in MBF and caused erosions. OKY-046, an inhibitor of TXA2 synthesis, and ONO-11120, an antagonist of TXA2 receptors, increased MBF during stress in parallel with an increase in acid output, and erosions did not form. In another experiment, the effects of a TXA2-like substance on MBF during vagal stimulation were examined. Although vagal stimulation alone increased acid output, there were no erosions in the stomach, probably because MBF was increased in parallel with acid output. Intra-arterial administration of a TXA2-like substance formed by the metabolism of arachidonic acid in the blood reduced MBF during vagal stimulation. Intra-arterial administration of ONO-11113, an agonist of TXA2 receptors, also reduced MBF during vagal stimulation. Neither agent affected the elevated level of acid output during vagal stimulation, and erosions formed in the glandular part of the stomach. These results suggested that the gastric mucosal erosions induced by water-immersion stress in rats were due to mucosal ischemia produced by the presumed formation of a TXA2-like substance and to the increased secretion of acid.

Animals↗
PubMed1986

Dissociation between acid secretion and mucosal blood flow after treatment of rats with reserpine.

The correlation between acid secretion and mucosal blood flow in the gastric mucosa after administration of reserpine to rats was determined in an attempt to define the etiology of reserpine-induced gastric erosions. Although gastric acid output was increased gradually by administration of reserpine, mucosal blood flow was not significantly affected. The increase in acid output induced by reserpine was completely prevented by pretreatment with atropine. Reserpine-induced increase in acid secretion may have been mediated by the vagus nerves, probably as a result of central and/or peripheral diminution in noradrenergic inhibitory mechanisms. The dissociation between mucosal blood flow and acid secretion, resulting in a relative ischemic state in the gastric mucosa, may have occurred in part from reduced cardiac function after treatment with reserpine. Vagal stimulation induced a parallel increase in both acid secretion and mucosal blood flow in control rats. 6-Hydroxydopamine-induced sympathectomy did not increase mucosal blood flow to a degree corresponding to the increase in acid output by vagal stimulation. In animals treated with 6-hydroxydopamine, gastric erosions occurred. We conclude that reserpine increases acid output but without a parallel increase in the mucosal blood flow and that the erosions which occur are probably due to the relative ischemic state of the gastric mucosa.

Animals↗
PubMed1986

Effects of brotizolam on cardiovascular functions and autonomic nervous system.

The effects of brotizolam (2-bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno(3,2-fl-1,2,4-triazolo [4,3-a]-1,4-diazepine, We 941, Lendormin), a new thieno-triazolo-diazepine, on the heart, hemodynamic functions and the autonomic nervous system were investigated in rats, guinea pigs, rabbits, cats and dogs: In pentobarbital anesthetized dogs, 1 or 5 mg/kg brotizolam administered intravenously, decreased heart rate, with a frequency-dependent prolongation of the intervals and heightening of the T-waves in the electrocardiogram, depressed respiration, whereas the blood pressure was unaffected. In urethane anesthetized rabbits, 5 or 10 mg/kg brotizolam intravenously had almost no distinct effect on blood pressure and heart rate, though it slightly decreased respiratory rate at 10 mg/kg. In nonanesthetized rabbits, brotizolam exerted similar actions on respiration, blood pressure and heart rate. In isolated guinea pig atria, 1-10 mg/l brotizolam did not show noticeable effects on contractile force but decreased slightly the pulse rate. In pentobarbital anesthetized dogs, vertebral and carotid blood flow remained almost unchanged after 0.05 mg/kg brotizolam intravenously, but were increased following 0.5 mg/kg. Cardiac output and coronary flow were not changed by 0.5 mg/kg brotizolam but slightly decreased accompanied by a decrease in blood pressure and heart rate by 1 mg/kg. Femoral flow was not affected by 0.5 or 1 mg/kg. After 5 mg/kg brotizolam given intravenously in dogs, the pressor effect of epinephrine was significantly enhanced and the positive chronotropic effect increased to a certain degree. Both effects of norepinephrine also tended to be enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Effects of brotizolam on smooth muscle and other organs.

Effects of brotizolam (2-bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f]-1,2,4-triazolo [4,3-a]-1,4-diazepine, We 941, Lendormin) on smooth muscle and other biological systems were examined. In isolated intestinal preparations, brotizolam in higher concentrations shifted the concentration-contractile response curve after addition of acetylcholine down to the right. However, brotizolam did not affect the intestinal transport. Therefore, even if brotizolam possesses a non-specific inhibitory action on smooth muscle, it would be quite weak. Brotizolam, nitrazepam and estazolam in high doses showed a miotic action. Brotizolam had no effect on the digestive system, that is, gastric secretion, bile secretion and intestinal propulsive activity were not influenced. A depression of salivary secretion, which may be due to an additive action of Eidelberg's mixture, was observed. Brotizolam, nitrazepam and estazolam enhanced the sleeping time induced by ethanol and increased locomotor activity induced by methamphetamine, but did not affect the chewing behavior. There was no indication that continuous administration of brotizolam affected significantly the levels of lipids and sugar in the blood serum.

Animals↗
PubMed1986

Comparison of glutathione S-transferases in mouse, guinea pig, rabbit and hamster liver cytosol to those in rat liver.

The glutathione S-transferases (GSTs) of hepatic cytosol of rats, mice, guinea pigs, rabbits and hamsters were simultaneously investigated with respect to substrate specificity, subunit composition and elution profile of GSTs. The activity towards 1-chloro-2,4-dinitrobenzene was the highest in hamsters, followed by rabbits, guinea pigs, mice and rats. On the analysis of SDS-PAGE, Ya subunit band of GST was detected in only rats, not others. There was also seen a marked species difference in elution profile of GST activity on S-sepharose column. The elution patterns from rats, mice and rabbits were quite different from hamsters and guinea pigs.

Animals↗
PubMed1985

Age-associated alterations in hepatic glutathione-S-transferase activities.

Age-associated alterations of hepatic cytosolic glutathione-S-transferase (GST) activities towards sulfobromophthalein sodium tetrahydrate (BSP), styrene oxide (STOX), trans-4-phenyl-3-butene-2-one (PBO), 1,2-dichloro-4-nitrobenzene (DCNB), and 1-chloro-2,4-dinitrobenzene (CDNB) were investigated in Fischer-344 rats of both sexes with ages ranging from 1.5 to 28 months. The GST activities towards PBO and DCNB in male rats increased with age till 6-12 months when maximum values were attained, and then gradually decreased till 28 months when the values became the lowest. The GST activities towards STOX and BSP did not show any significant increase after 1.5 months and stayed at this level till 12 months, followed by a gradual decrease till 28 months when the values were the lowest. In contrast, the GST activity towards CDNB in male rats did not show much of an age-associated alteration. Age-associated alterations in GST activities in females were much smaller than those observed in males. Sex differences in GST activities (significantly higher male values than female values) were observed with all the substrates examined at least at some time of the animal life. The kinetic studies of GST activities indicated that alterations in the relative abundance as well as the total quantity of GST isozymes caused the substrate selective alterations of GST activities with age.

Age Factors↗
PubMed1985

Monoclonal antibody to glycoprotein Ib inhibits both thrombin- and ristocetin-induced platelet aggregations.

A monoclonal antibody named TM60, which inhibited both thrombin- and ristocetin-induced platelet aggregations, was obtained by hybridoma technique. TM60 inhibited binding of von Willebrand factor to platelets under the presence of ristocetin. The subclass of TM60 was IgG2a. TM60 did not inhibit ADP-, collagen-A-23187-, arachidonic acid- and PAF-induced platelet aggregations, but inhibited polylysine-, polybrene- and cationized ferritin-induced platelet aggregations. ATP-release from platelets induced by thrombin was also inhibited by TM60. Immunoprecipitation and SDS-PAGE experiments demonstrated that TM60 recognized an epitope on GPIb whose molecular weight was 165,000 under non-reduced and 145,000 under reduced conditions.

Adenosine Triphosphate↗
PubMed1985

Effect of hypoxic cell radiosensitizers on glutathione level and related enzyme activities in isolated rat hepatocytes.

A comparative study of the effect of misonidazole and novel radiosensitizers on glutathione (GSH) levels and related enzyme activities in isolated rat hepatocytes was performed. Incubation of hepatocytes with 5 mM radiosensitizers led to a decrease in the intracellular GSH level. The most pronounced decrease in cellular GSH was evoked by 2,4-dinitroimidazole-1-ethanol (DNIE); after incubation for only 15 min, GSH was hardly detected. DNIE-mediated GSH loss was dependent upon its concentration. DNIE reacted with GSH nonenzymatically as well as with diethylmaleate, while misonidazole and 1-methyl-2-methyl-sulfinyl-5-methoxycarbonylimidazole (KIH-3) did not. Addition of partially purified glutathione S-transferase (GST) did not enhance DNIE-mediated GSH loss in a cell-free system. DNIE inhibited glutathione peroxidase (GSH-Px), GST, and glutathione reductase (GSSG-R) activities in hepatocytes, while misonidazole and KIH-3 did not. GSH-Px activity assayed with H2O2 as substrate was the most inhibited. Inhibition of GSH-Px activity assayed with cumene hydroperoxide as substrate and GST was less than that of GSH-Px assayed with H2O2 as substrate. GSSG-R activity was decreased by DNIE, but not significantly. Incubation of purified GSH-Px with DNIE resulted in a little change in the activity when assayed with H2O2 as substrate.

Animals↗
PubMed1985

Structural organization of the human kininogen gene and a model for its evolution.

The entire human kininogen gene has been isolated as a set of overlapping genomic DNA fragments, and the 11 exons encompassing approximately 27 kilobase pairs have been mapped by restriction enzyme analysis and nucleotide sequence determination. The nine 5'-terminal exons encode the 5'-untranslated region and the protein-coding region for the signal peptide and the heavy chain, which are common for high molecular weight (HMW) and low molecular weight (LMW) prekininogen mRNAs. Exon 10 consists of the common sequence for bradykinin and the immediately following unique sequence for HMW prekininogen mRNA. Exon 11 is then located following a 90-nucleotide sequence downstream from exon 10 and precisely specifies the sequence unique to LMW prekininogen mRNA. This, together with the hybridization analysis of total human cellular DNA, leads us to conclude that human HMW and LMW prekininogen mRNAs are produced from a single gene as a consequence of alternative RNA processing events. The structural analysis of the kininogen gene also shows that each of the nine 5'-terminal exons discretely specifies the nine protein domains observed in the amino-terminal portion of the kininogens. Furthermore, these nine genetic domains can be characterized by a thrice repeated pattern of three genetic segments, and two sets of these three domains, encompassing exons 3-5 and exons 6-8, are most closely related to each other. Therefore, we have proposed two successive duplication mechanisms as a model for the generation of the structure of the kininogen gene.

Base Sequence↗