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Biomedical subjects

K Koike

Publications and source records attributed to K Koike.

At least 703 records · Page 39Linked to original sources
PubMed1986

Protein kinase C activators and calcium-mobilizing agents synergistically increase GH, LH, and TSH secretion from anterior pituitary cells.

A series of studies was designed to determine the effects of protein kinase C activators on TSH, LH, and GH release from anterior pituitary cells. A 15-min incubation of cultured pituitary cells with synthetic diacylglycerol or phorbol myristate acetate, stimulators of protein kinase C, increased GH, LH, and TSH release. Similarly phospholipase C, which liberates endogenous diacylglycerol, stimulated GH, LH, and TSH secretion. The potentiation of the effects of protein kinase C activators is achieved by calcium mobilization in various cell types. The results of the present studies show that calcium ionophore A23187 or calcium channel activator maitotoxin potentiate diacylglycerol-, phorbol ester-, or phospholipase C-induced GH, LH, or TSH release. These findings suggest that activation of protein kinase C by diacylglycerol and mobilization of calcium may be synergistically involved in the regulation of GH, LH, and TSH release.

Animals↗
PubMed1986

Maitotoxin, a calcium channel activator, increases prolactin release from rat pituitary tumor 7315a cells by a mechanism that may involve leukotriene production.

Arachidonate and its metabolites may play an important role in the release of prolactin. In the present study, the effect of maitotoxin, a calcium channel activator, was measured on the release of arachidonate and its metabolites from the prolactin-secreting 7315a tumor. Maitotoxin increased the release of prolactin, arachidonate, prostaglandins E2 and F2 alpha (PGE2, PGF2 alpha) and leukotriene C4 (LTC4) from 7315a cells prelabeled with [3H]arachidonate. The magnitude of the increase of prolactin and arachidonate release was decreased in low-calcium medium. The release of arachidonate from cellular phospholipids is necessary for the effect of maitotoxin on prolactin release because quinacrine, an inhibitor of arachidonate hydrolysis from phospholipids, blocked the maitotoxin-induced release of prolactin. The ability of maitotoxin to induce prolactin release appears to require metabolic transformation of arachidonate to its metabolites because BW755c, an inhibitor of the conversion of arachidonate, blocked the maitotoxin-induced prolactin release. In particular, LTC4 may be an important component of the prolactin release process because nordihydroguaiaretic acid and nafazatrom, which block the production of leukotrienes and other lipoxygenase-generated products, decreased LTC4 and prolactin release without affecting arachidonate, PGE2 or PGF2 alpha production. In contrast, indomethacin, a prostaglandin synthesis inhibitor, decreased PGE2 and PGF2 alpha production without affecting LTC4 or prolactin release. These data indicate that release of LTC4 and prolactin are closely linked events in 7315a tumor cells.

Animals↗
PubMed1986

Dopaminergic inhibition of anterior pituitary adenylate cyclase activity and prolactin release: the effects of perturbing calcium on catalytic adenylate cyclase activity.

The dopaminergic inhibition of anterior pituitary adenylate cyclase activity, cAMP accumulation, and prolactin release was studied in the presence of the Ca2+ channel activator, maitotoxin. In isobutylmethylxanthine (IBMX)-treated cells, maitotoxin stimulated prolactin secretion within 30 s and cAMP accumulation within 1 min. Although dopamine reduced cAMP accumulation and prolactin release, the effectiveness of the catecholamine was reduced in the presence of maitotoxin. When hemipituitary glands were exposed for 10 min to 100 ng maitotoxin/ml, their membranes showed increased adenylate cyclase activity. The hypothesis that maitotoxin stimulates adenylate cyclase activity by increasing Ca2+ availability was supported by the observation that, at concentrations up to 100 microM, Ca2+-stimulated anterior pituitary adenylate cyclase activity. Although dopamine decreased basal and maitotoxin-stimulated pituitary cAMP accumulation, via changes in adenylate cyclase activity, the decrement in cyclic nucleotide production, but not prolactin release, can be ascribed to the effect of the catecholamine on the basal activities of these parameters. These data provide additional evidence that an increased Ca2+ flux is stimulating to cAMP generation and prolactin release, whereas dopamine is inhibitory to these processes.

Adenylyl Cyclases↗
PubMed1986

Declining sensitivity to interleukin 3 of murine multipotential hemopoietic progenitors during their development. Application to a culture system that favors blast cell colony formation.

When spleen cells of 5-fluorouracil (5-FU)-treated mice were cultured in the presence of interleukin 3 (IL-3), most colonies revealed IL-3 concentration-dependent colony formation except for mast cell colonies and blast cell colonies. While most colonies were smaller in lower concentrations of IL-3, the size of the blast cell colonies were similar between high and low IL-3 groups. These data suggested that blast cell colony development requires less IL-3 than the development of multilineage colonies from blast cell colonies. This notion was supported by experiments in which IL-3 was added twice to cultures of spleen cells of 5-FU-treated mice. When low concentrations of IL-3 were added on day 7, there was a reduction in the number of multilineage colonies formed without an effect on the number of blast cell colonies. Using this information, we developed a culture system that favors blast cell colony formation by cells of normal mice. When low (20 U/ml) concentrations of IL-3 were added to cultures of spleen cells of normal mice on day 7 of incubation in media containing 2-5% fetal calf serum, blast cell colonies were the predominant colony type. The blast cell colonies revealed high but variable secondary replating efficiencies. These data suggest that multipotential progenitors may become less sensitive to IL-3 as they differentiate in culture.

Animals↗
PubMed1986

A difference in alpha-adrenoceptor mechanisms in vasa deferentia isolated from young and old rats.

A difference in alpha-adrenoceptor mechanisms in vasa deferentia isolated from 3 weeks old and 40 weeks old rats were studied by analysis of the concentration-response curve of norepinephrine and Scatchard plot of specific [3H]-prazosin binding to microsomal fractions. The efficacy of norepinephrine and capacity of the maximum binding sites of [3H]-prazosin estimated in 40 weeks old rats were larger than those in the 3 weeks old rats, while there was no difference in the affinity of norepinephrine estimated in the 3 weeks old rats and in the 40 weeks old rats. The increase of efficacy for norepinephrine in the vas deferens from the 40 weeks old rats is due to the increase in the total concentration of alpha-adrenoceptors.

Aging↗
PubMed1986

A beta-adrenergic partial agonist (befunolol) discriminates two different affinity sites.

Interactions of beta-adrenergic partial agonists with the beta-adrenoceptor were studied in isolated guinea-pig taenia caecum. The competitive inhibition curve for specific binding of a high concentration (50 nM) of [3H]-befunolol by befunolol showed a biphasic shape, although the curve for specific binding of a low concentration (1 nM) was monophasic. All the competitive inhibition curves for specific binding of [3H]-befunolol (1 nM and 50 nM) by isoprenaline and propranolol showed monophasic shapes. These results suggest that befunolol may be able to discriminate two different binding sites of the beta-adrenoceptor: the high affinity site and the low affinity site.

Adrenergic beta-Agonists↗
PubMed1986

Branching architecture of canine pulmonary arteries: a quantitative cast study.

The purpose of this investigation is to analyze the branching pattern of pulmonary artery. The excised right lower lobes of six mongrel dogs were fixed by perfusion with 1.2% glutaraldehyde solution. Pressure of the pulmonary artery, vein and airway were controlled during perfusion. After fixation, resin was injected manually into the artery. When resin was completely polymerized, the lung was placed in 15 N NaOH solution to remove lung tissue. The diameters and lengths of branches were measured by stereomicroscopy. The results obtained were as follows: The basically dichotomous pulmonary arteries showed not only fairly regular dichotomies but monopodies, in the latter of which the diameter of parent branch was almost the same as that of its larger daughter branch. The diameter of monopodial branch was less than 500 microns, even when the parent branch was a large central segment. In arteries of over 1,000 microns in diameter, 75% or more of branchings were monopodies, whereas in small arteries of 200-300 microns in diameter, half the bifurcations were monopodies. At a bifurcation, the average daughter-to-parent diameter ratio was 0.8-0.9 for the larger daughter branch and 0.5 for the smaller one. The average length of branches was in proportion to their average diameter.

Animals↗
PubMed1986

Rapid and simple isolation procedure for three component enzymes of pig heart 2-oxoglutarate dehydrogenase complex.

A novel procedure was developed for rapid separation of the three component enzymes of pig heart 2-oxoglutarate dehydrogenase complex by high performance liquid chromatography on a gel filtration column. The complex was dissociated and separated into two fractions of the first dihydrolipoamide succinyltransferase and a second yellow fraction within 1 h by chromatography on a preparative TSK-GEL G4000SW column equilibrated with 0.05 M potassium phosphate buffer (pH 7.0) containing 0.7 M guanidine hydrochloride, 0.05% Triton X-100 and 2 mM dithiothreitol at 10 degrees C. The dihydrolipoamide succinyltransferase fraction was further purified by incubation with 0.5% sodium deoxycholate and subsequent ammonium sulfate fractionation. The other two component enzymes, 2-oxoglutarate dehydrogenase and lipoamide dehydrogenase were separated from the second yellow fraction by chromatography on a calcium phosphate gel-cellulose column. The TSK-GEL column permitted very rapid dissociation and separation of the three component enzymes accompanied by good preservation of their activities and high overall yields.

Acyltransferases↗
PubMed1986

Macrophage colony formation supported by purified CSF-1 and/or interleukin 3 in serum-free culture: evidence for hierarchical difference in macrophage colony-forming cells.

Using a serum-free culture system, we examined murine macrophage colony formation from bone marrow cells cultured in the presence of purified CSF-1, interleukin 3 (IL 3) or a combination of the two factors. CSF-1 supported macrophage and neutrophil-macrophage colony formation, whereas IL-3 supported the formation of various types of single lineage and multilineage colonies. CSF-1 supported more macrophage colonies from bone marrow cells of normal mice than IL 3, whereas in cultures of bone marrow cells of 5-fluorouracil-treated mice, IL 3 supported more macrophage colonies. A combination of CSF-1 and IL 3 resulted in granulocyte-macrophage (GM) colony formation that was equal to or greater than the sum of GM colony formation supported by the factors individually. The combination of CSF-1 and IL 3 resulted in significant increases in the size of both macrophage and neutrophil-macrophage colonies. Similar increases in colony size were observed when CSF-1 was added to cultures five days after incubation of marrow cells with IL 3. These data support the concept that some of the macrophage colony-forming cells that respond to IL 3 are more primitive than those that are sensitive to CSF-1.

Animals↗
PubMed1986

Hemopoietic colony formation by mouse spleen cells in serum-free culture supported by purified erythropoietin and/or interleukin-3.

We examined colony formation by mouse spleen cells in a serum-free culture system containing purified erythropoietin (Ep), interleukin-3 (IL-3) or a combination of the two factors. Purified Ep supported erythroid colony and burst formation but did not support formation of other types of colonies. IL-3 alone did not support erythroid burst formation in culture. However, IL-3 significantly increased the number and size of erythroid bursts. IL-3 but not Ep supported megakaryocyte colony formation. Ep did not enhance megakaryocyte colony formation or megakaryocyte populations in multilineage colonies supported by IL-3.

Animals↗
PubMed1986

[Pharmacokinetic and clinical studies of imipenem/cilastatin sodium in the field of obstetrics and gynecology].

Imipenem/cilastatin sodium (MK-0787/MK-0791) was studied for its penetration into the adnexa uteri and uterine tissue, as well as for its clinical efficacy in the treatment of patients with obstetric and gynecologic infections. The following results were obtained. When 500 mg/500 mg of MK-0787/MK-0791 was administered by an intravenous drip infusion, peak levels of MK-0787 in tissues of adnexa uteri and uterus ranged from 14.6 micrograms/g to 25.8 micrograms/g, Tmax ranged from 0.55 hour to 0.98 hour, and the AUC ranged from 25.6 micrograms X hr/g to 45.2 micrograms X hr/g. Thus, the penetration of the drug into these tissues was good. Clinical efficacy of MK-0787 was evaluated in 30 patients in the field of obstetrics and gynecology. The clinical efficacy was excellent or good in all patients. Bacteriological effects of MK-0787/MK-0791 were very good, and 90% of the organisms detected before the treatment were eradicated. The antimicrobial activity of MK-0787 was tested against pathogens isolated before, during and after the treatment. Mean MIC80 values of MK-0787 were 0.39-0.78 micrograms/ml against all Gram-positive bacteria, 0.20-0.39 micrograms/ml against all Gram-negative bacteria, and less than or equal to 0.10-0.20 micrograms/ml against all anaerobic bacteria. The antimicrobial activity of MK-0787 appeared very good. No side effects or abnormal laboratory findings were observed except a slight elevation of S-GPT in 1 patient.

Adult↗
PubMed1986

Time dependent effects of selenium on cadmium-induced acute mouse testicular damage.

Twenty-four hr after a single subcutaneous injection of Cd (0.024 mmol/kg), the testis showed severe and widespread degeneration. The damage was accompanied by an increase of lipoperoxide and a decrease of glutathione in the testis. Se (0.048 mmol/kg) injections 2 hr before, at the same time, and 1 hr after the Cd injection, decreased the damage. In these groups, the level of glutathione and lipoperoxides was restored to the control level. With a Se injection 6 hr after the Cd injection, the preventive effect of Se was no longer found. In the testis in which Se injection alleviated the damage caused by Cd, the changes in Ca, Mg and Zn were also restored to the control level. Uptake of Cd into the testis was stimulated by the Se injection. However, the uptake still remained at a low level in the testis in which the Se preventive effect was not found. These results suggest that the preventive effect of Se against testicular Cd toxicity is dependent on the interval between Cd and Se injections.

Acute Disease↗
PubMed1985

Calcium mobilization potentiates prolactin release induced by protein kinase C activators.

The in vitro effect of synthetic diacylglycerol (DG) and phorbol myristate acetate (PMA), potent stimulators of protein kinase C, was studied on prolactin release. These substances increased, in a concentration-dependent manner, prolactin release from primary cultures of anterior pituitary cells. Similarly, exposure of pituitary cells to phospholipase C, which liberates endogenous DG from various substrates, also enhanced prolactin release. The effect of Ca2+ mobilization on PMA-, synthetic DG- or phospholipase C-induced prolactin release was examined. A23187 at 400 nM or 2 ng/ml maitotoxin, a Ca2+ channel activator, did not affect prolactin release by themselves, but enhanced the release of prolactin induced by DG, PMA or phospholipase C. The stimulatory effects of DG, PMA and phospholipase C on prolactin release were reduced by co-incubation with dopamine. These results suggest that the presumed activation of protein kinase C by DG and mobilization of Ca2+ may be synergistically involved in the regulation of prolactin release. Dopamine appears to inhibit prolactin release at a point distal to the DG-enhanced stimulation of the process.

Animals↗
PubMed1985

A beta-adrenoceptor blocking agent, befunolol as a partial agonist in isolated organs.

A beta-adrenoceptor blocking agent, befunolol, which is clinically used in the treatment of glaucoma in Japan, was found to have intrinsic sympathomimetic activities in isolated right atria, trachea and taenia caecum of guinea pig (intrinsic activities are 0.22-0.28). The pD2-values of befunolol estimated in the isolated organs were significantly different from its pA2-values against isoprenaline. A possible explanation of our findings would to be as follows: befunolol interacts with the beta-adrenoceptor where there may be two different sites: one site for agonistic action and the other for competitive antagonistic action. Both sites are supposed to be mutually exclusive through unknown mechanisms. The intrinsic activity of befunolol may be equal to its selectivity for both the sites.

Adrenergic beta-Agonists↗