Biomedical subjects

H Kitagawa

Publications and source records attributed to H Kitagawa.

At least 451 records · Page 25Linked to original sources

PubMed1986

Localization of a thrombin-binding site on human platelet membrane glycoprotein Ib determined by a monoclonal antibody.

To determine a thrombin-binding site on GPIb alpha on platelet membrane, we have examined the binding activities of tryptic or chymotryptic fragments of purified GPIb alpha to a monoclonal antibody against GPIb (TM60) and thrombin using (immuno)affinity chromatography. When purified GPIb alpha was digested with trypsin, two fragments (94-kDa, and 43-kDa) were obtained. The 43-kDa fragment was shown to bind to both affinity columns of TM60- and thrombin-Affi-Gel, while the 94-kDa fragment did not bind to either Affi-Gel columns. When trypsin fragments were incubated with TM60 and then applied to the column of thrombin-Affi-Gel, neither fragments were bound to the column. When the same experiment was performed using chymotrypsin, three fragments (94-kDa, 45-kDa and 39-kDa) were observed. On TM60- and thrombin-Affi-Gel columns, the smaller fragments (45-kDa and 39-kDa) were bound to the column. After incubation of these fragments with TM60, neither bound to the thrombin column. These results indicate (i) that the epitope for TM60 is located near, or on the thrombin-binding site of GPIb alpha, and (ii) that the thrombin-binding site is located on the tail portion of GPIb alpha, especially on a chymotrypsin cleavage site.

Antibodies, Monoclonal↗

PubMed1986

Comparison of the in vitro effect of eicosapentaenoic acid (EPA)-derived lipoxygenase metabolites on human platelet function with those of arachidonic acid.

Eicosapentaenoic acid (EPA) has been reported to have a potent anti-aggregatory activity and to be efficiently metabolized by 12-lipoxygenase, not by cyclooxygenase in platelets. In vitro effect of 12-lipoxygenase metabolites of EPA on platelet function was studied and compared with those of arachidonic acid (AA). The 12-lipoxygenase metabolites of AA and EPA; 12-hydroperoxyeicosatetraenoic acid (12-HPETE) and 12-hydroperoxyeicosapentaenoic acid (12-HPEPE), and their hydroxy derivatives, 12-hydroxyeicosatetraenoic acid (12-HETE) and 12-hydroxyeicosapentaenoic acid (12-HEPE) were prepared enzymatically using human platelet lysate. These compounds were purified by high performance liquid chromatography and identified by gas chromatography mass spectrometry. 12-HPETE and 12-HPEPE inhibited dose-dependently washed human platelet aggregation and serotonin (5-HT) release induced by AA and collagen. The potency of 12-HPEPE was almost equal to that of 12-HPETE. Their hydroxy derivatives, 12-HETE and 12-HEPE were less potent. 12-hydroperoxy derivatives of AA and EPA were the most potent in inhibiting platelet aggregation and 5-HT release among 5-, 12- and 15-hydroperoxy isomers of AA and EPA. The inhibitory effects of 12-HPETE and 12-HPEPE on platelet aggregation were additive.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

PubMed1986

Effects of combined administration of diazepam and imipramine hydrochloride in rats.

The effects of daily oral administration of imipramine hydrochloride (5-[3-(dimethylamino)propyl]-10,11-dihydro-5H-dibenz-[b,f]azepine monohydrochloride; 50 mg/kg) and/or diazepam (7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one ; 5 mg/kg) in a 1% aqueous solution of carboxymethylcellulose sodium salt (CMC) on the body weight, organ weights, and activities of various enzymes, including drug metabolizing enzyme systems were investigated in rats during a 15-day period. The plasma concentrations of imipramine and desipramine were also determined. In addition, the effect of a single intravenous administration of imipramine hydrochloride (5 mg/kg) on the plasma concentration-time profiles of imipramine and desipramine was investigated in rats given the same drug treatments. The plasma concentration-time profiles of imipramine and desipramine were analyzed pharmacokinetically. The rats treated with imipramine hydrochloride showed a greater inhibition of body weight gain than those treated with diazepam, and those treated with imipramine hydrochloride and diazepam simultaneously showed a body weight gain similar to those treated with imipramine hydrochloride alone. No significant differences in organ weight (per 100 g of body weight) were found. The imipramine hydrochloride plus diazepam treatment group showed a greater increase in drug-metabolizing enzyme activities than the imipramine hydrochloride treatment group, but the difference was not statistically significant. However, the plasma levels of imipramine and desipramine after oral administration for 15 d suggested that the imipramine hydrochloride plus diazepam treatment group did not show increased imipramine metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Potentiation of the chemotherapeutic action of tegafur against solid adenocarcinoma 755 by combination with L-cystine.

The chemotherapeutic action of tegafur (FT) against adenocarcinoma 755 in mice was markedly potentiated by oral administration of L-cysteine and L-cystine without increasing its toxicity. In particular, the combination of FT at 200 mg/kg per day (maximum dose) and 1000 mg/kg per day of L-cystine markedly inhibited tumor growth. The dose ratio of L-cysteine or L-cystine to FT needs 5 by weight to potentiate the antitumor activity of FT. The antitumor activity of 5-fluorouracil (FU) was slightly, but not significantly, increased by L-cysteine. The total concentration of FT in the plasma and the tumor when it was given in combination with L-cystine was significantly increased when compared with FT alone 1 h after oral administration. The FU level in the plasma after administration of the combination of FT and L-cystine was three times higher than that after FT alone, and the FU level in the tumor after treatment with the combination of FT and L-cystine was also higher (about 20%) than that after FT alone. This significant increase in FT and FU levels in the plasma and the tumor may be related to the potentiation of the antitumor activity of FT by L-cystine.

Adenocarcinoma↗

PubMed1986

Phagocytosis as a defense mechanism against infection with leptospiras.

The role of macrophages in host defense was studied in vivo and in vitro. The intravenous administration of silica, an agent reported to selectively inactivate macrophages, increased the sensitivity to leptospiral infection and inhibited bacterial clearance. Active immunization with killed organisms or with leptospiral lipopolysaccharide (L-LPS), and passive immunization with a monoclonal antibody showed powerful protective effects against infection in mice. The effect of immunization decreased in silica-treated mice. These findings were supported by electron microscopic examination and observation of killing by macrophages in vitro.

Animals↗

PubMed1986

Human interferon-gamma (IFN-gamma) containing cells bear various surface phenotypic markers.

We explored the population of Interferon-gamma (IFN-gamma) containing cells in order to clarify their cell surface phenotypic markers. Here we define gamma-IFN containing cells as gamma-IFN plaque forming cells (PFC). By this method, it was found that IFN-gamma containing cells consist of two cell fractions, i.e., OKT3+, OKT4+, and OKT8- cells and OKM1+ cells. Effective IFN-gamma production seems to require participation of plastic-adherent cells (presumably monocytes), while the addition of cyclosporin A (CyA) almost completely blocked generation of human IFN-gamma. To characterize Con A-stimulated IFN-gamma containing cells, we performed two-color flow cytometry using FACS IV. Most of the IFN-gamma containing cells have surface phenotypic markers for Leu3, Leu8, Leu15, HLA-DR, and IL-2 receptors, but most lack markers for Leu2 and Leu7. Interestingly, most of Leu3+ and IL-2 receptor+ cells belong to the dimly illuminating cell fractions of the IFN-gamma containing cell population. Our results indicate that IFN-gamma containing cells are heterogeneous with respect to surface phenotypic markers but the predominant IFN-gamma containing cell type is the helper T cell (OKT4+). Lastly, OK432, glycyrrhizin, and CCA (lobenzarit disodium) increase the number of IFN-gamma containing cells and are thought to be immunomodulators.

Antibodies, Monoclonal↗

PubMed1986

[Antitussive and expectorant effects of Asada-ame extract].

Asada-ame containing Platycodi Radix, Ginseng Radix, Ephedrae Herba and Ipecacuanhae Radix extracts has been hitherto widely used as an antitussive and expectorant. In the present study, the antitussive effect and tracheo-bronchial secretory activity of Asada-ame extract (AE) were investigated with laboratory animals. Antitussive effect was evaluated with the puncture electrode-induced cough method in conscious guinea pigs. AE showed a significant antitussive effect which lasted more than one hr. 50% Antitussive doses were 76 mg/kg, i.p., and 500 mg/kg, p.o. Airway secretory effect was evaluated with the stopper method in anesthetized dogs. With oral administration of AE, the volume of respiratory tract fluid (RTF) increased, and viscosity of RTF, which was determined using the glass plate method, was decreased in a dose-dependent manner. The effects of AE on secretory activity of canine tracheal secretory cells were investigated in vitro with the histological/histochemical technique. With AE treatment, the thickness of the acini of submucosal glands was decreased, and the ratio of acinar inner diameter of the gland to tracheal wall was increased. Furthermore, the number of acid glycoprotein-containing submucosal glandular cells was decreased by AE, suggesting a mucolytic effect of AE. The above findings indicate that AE has significant antitussive and expectorant effects.

Animals↗

PubMed1986

Effects of cytochrome b5 on aniline hydroxylation catalyzed by a reconstituted system containing acetone or 2,2'-bipyridine.

Cytochrome b5 did not exert any effect on NADPH-dependent aniline hydroxylation in the absence of acetone or 2,2'-bipyridine, whereas cytochrome b5 exhibited a stimulatory effect on the reaction in the presence of acetone or 2,2'-bipyridine. In addition, cytochrome b5 did not have any significant effect on the cumene hydroperoxide-dependent reaction in the presence of acetone or 2,2'-bipyridine.

2,2'-Dipyridyl↗

PubMed1986

Effects of antimuscarinic agents and prostaglandin E2 on the gastric mucosal lesions induced by necrotizing agents and water-immersion stress in rats.

The role of antimuscarinic action in gastric mucosal protection against necrotizing agents and the role of such mucosal protection in antiulcerogenic action were studied in rats with i.v. administered antimuscarinic agents. Pirenzepine, as well as PGE2, prevented the gastric mucosal lesions induced by all necrotizing agents (99.5% ethanol, 0.6 N HCI, 0.15 N NaOH, 0.4 N HCI-50 mM taurocholate), but atropine did not prevent the HCI-induced lesions. Cimetidine inhibited only the ethanol-induced lesions even at the antisecretory dose. Higher doses of pirenzepine (5-fold) and atropine (10-fold) were required to inhibit the gastric secretion in Shay rats than in vagally stimulated rats. There was no difference between the antisecretory doses of cimetidine in Shay rats and vagally stimulated rats. PGE2 (0.03-0.1 mg/kg) did not affect gastric secretion. The protective doses of pirenzepine and atropine against mucosal lesions induced by necrotizing agents were similar to the dose in inhibiting vagally stimulated acid secretion and water-immersion stress-induced lesions. PGE2 (100 micrograms/kg) did not prevent the water-immersion stress induced gastric lesions. These results suggested that antimuscarinic agents protect the gastric mucosa from necrotizing agents via a blocking action on the activation of the intrinsic cholinergic nerve. However, antiulcerogenic action is more deeply concerned with antisecretory action than cytoprotection.

Animals↗

PubMed1986