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Biomedical subjects

I Kimura

Publications and source records attributed to I Kimura.

At least 19 recordsLinked to original sources
PubMed1992

Retinoic acid ambivalently regulates the expression of MyoD1 in the myogenic cells in the limb buds of the early developmental stages.

The expression of MyoD1 in myogenic cells located in the muscle prospective region of the limb bud at stage 20-22 was highly sensitive to retinoic acid. Unlike RAR-beta, the expression of MyoD1 mRNA in the muscle precursor cells was significantly increased by retinoic acid at lower concentrations (0.1-10 nM), but inhibited by it at higher concentrations (0.1-1 microM). The ambivalent modulation of MyoD1 expression suggested that MyoD1 expression is regulated by not only the retinoic acid receptor and its response element, but also by other factors. Retinoic acid may be involved in the differentiation of the myogenic cells during early development.

Animals↗
PubMed1992

Hyperglucagonemia induced in mice by tryptamine: involvement of the peripheral 5-HT2 receptors.

The effects of an indoleamine, tryptamine, on plasma glucagon levels were investigated in mice. Tryptamine induced dose-related increases in plasma glucagon levels. The hyperglucagonemia effects of tryptamine were completely antagonized by methysergide and ketanserin which have a high affinity to 5-HT2 receptors. In addition, the peripheral 5-HT2 receptor antagonist, xylamidine, also strongly inhibited tryptamine-induced hyperglucagonemia. Our results indicate that the peripheral 5-HT2 receptors mediate the increase in plasma glucagon levels induced by tryptamine and that these receptors may have a role in the control of glucagon secretion.

Animals↗
PubMed1992

Blocking action of succinylcholine with beta-eudesmol on acetylcholine-activated channel activity at endplates of single muscle cells of adult mice.

The neuromuscular blockade produced by succinylcholine (SuCh) is potentiated by beta-eudesmol, a sesquiterpenoid alcohol isolated from Atractylodes lancea. beta-Eudesmol blocks the nicotinic acetylcholine receptor (nAChR) channel in both open and closed conformations. To clarify the mechanism of potentiation, we investigated the blocking effect of SuCh (0.1-10 microM) with beta-eudesmol on nAChR channel activity using the cell-attached patch clamp technique. Pretreatment with beta-eudesmol (20 microM) affected neither resting membrane potential nor ACh-activated channel activities. beta-Eudesmol produced the following changes in ACh-activated channel currents modulated by SuCh: reduction of SuCh (above 0.3 microM)-induced prolongation of channel open time and decrease in the frequency of channel opening in the presence of SuCh (above 3 microM). These results suggest that the potentiating effect of beta-eudesmol is postsynaptically due to accelerated desensitization of the nAChR, presumably resulting from preferential blocking action during the closed state of the receptor channel.

Acetylcholine↗
PubMed1992

Actions and cross-reactivity of antiallergic agents and a calcium channel antagonist on rat peritoneal mast cells. Difference in the action mechanisms and cross-reactivity among the agents.

The actions of the antiallergic agents, disodium chromoglycate (DSCG), tranilast and ketotifen, and of a calcium channel antagonist, nicardipine, and cross-reactivity among the agents were examined by observing the inhibition of 45Ca uptake and histamine release in rat mast cells stimulated by antigen and compound 48/80 (comp. 48/80). 1) All agents inhibited 45Ca uptake and histamine release in mast cells stimulated by antigen. The inhibition of 45Ca uptake by the antiallergic agents paralleled the inhibition of histamine release, while nicardipine inhibition of 45Ca uptake was stronger than its inhibition of histamine release. 2) The action of DSCG on 45Ca uptake and histamine release was significantly decreased in cells stimulated with antigen and phosphatidylserine (PS), while tranilast inhibition of histamine release was not affected by the addition of PS despite a significant decrease in the inhibition of 45Ca uptake. 3) The inhibitory effect of DSCG and tranilast was significantly lower in mast cells stimulated by comp. 48/80 than in the cells stimulated by antigen. 4) Tachyphylaxis was observed in cells re-exposed to DSCG and tranilast following previous exposure to the agents. 5) Cross-reactivity was found between DSCG and tranilast.

Animals↗
PubMed1992

Purification of human blood basophils using negative selection by flow cytometry.

Basophils were purified from peripheral blood of normal donors using Percoll discontinuous gradients and negative selection by flow cytometry. The mean purity of basophils obtained was 84.7 +/- 4.1 (s.d.)% (range 77.3-90.0%, n = 13). The overall yield of these procedures was 16.0 +/- 2.6% (range 11.0-19.9%, n = 13), and cell viability of purified basophils exceeded 90%. Properties of highly purified basophils obtained by flow cytometry did not differ from those of partially enriched basophil preparations from Percoll discontinuous gradients in respect of: (i) intracellular histamine content; (ii) percentage of spontaneous histamine release in buffer; and (iii) percentage of histamine release triggered by ionophore A 23187 or anti-IgE. Moreover, purified basophils responded chemotactically to complement C5a in a dose-dependent manner. These findings suggest that our procedure for purification of human basophils does not affect the functions of basophils and may be useful for in vitro studies on the role of basophils in hypersensitivity reactions such as bronchial asthma.

Basophils↗
PubMed1992

Effects of cytokines on human basophil chemotaxis.

Basophil chemotactic activity (BCA) of eight recombinant human (rh) cytokines was examined. Highly purified basophils were obtained by Percoll discontinuous gradients, followed by negative selection using flow cytometry. Then BCA was measured by means of modified Boyden chamber method. Both interleukin (IL)-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) had much more potent BCA than complement C5a, leukotriene B4 and platelet activating factor, well known as granulocyte chemotactic factors. Chemotaxis rather than chemokinesis was shown in chequerboard analysis of basophil migration induced by IL-3 and GM-CSF. Relatively high concentrations of IL-5 also induced basophil migration, although predominantly chemokinetic. IL-8 had apparent BCA, which was not so high as that of C5a. In contrast, IL-2, IL-4, interferon(IFN)-gamma and granulocyte colony-stimulating factor (G-CSF) had no significant BCA. These findings suggest that IL-3, IL-5, GM-CSF and, perhaps, IL-8 have an effect on basophil migration as well as modulation of basophil mediator release and may provide some insight into the basophil accumulation observed in late-phase allergic responses.

Basophils↗
PubMed1992

Indirect inhibitory effect of succinylcholine on acetylcholine-activated channel activities and its modulation by external Ca2+ in mouse skeletal muscles.

1. The effect of extracellular calcium on single acetylcholine (ACh)-activated channel activities when desensitizing concentrations of succinylcholine (SuCh) were applied to the surrounding endplate membrane was investigated by the cell-attached patch-clamp technique at endplates of single skeletal muscle (flexor digitorum brevis) fibres of adult mice. 2. Bath-applied SuCh (0.1-3 microM, in 2.5 mM Ca2+) increased in a concentration-dependent manner the mean open time of ACh-activated channel currents recorded at membrane potentials which cancelled the SuCh-induced depolarizations. 3. In the presence of 0.5 and 2.5 mM external Ca2+, SuCh (3 microM) applied outside the patch pipette prolonged the mean open time of ACh-activated channel currents in a time-dependent manner (by 45% and 52%, respectively), and simultaneously significantly decreased the single channel conductance (by 14% and 10%, respectively). These SuCh-induced effects did not occur in a nominally Ca(2+)-free extracellular medium. 4. Under the same conditions, SuCh (3 microM) augmented the time-dependent decline in the opening frequency of ACh-activated channel currents obtained in nominally Ca(2+)-free medium. 5. These results suggest that external calcium ions act to modulate nicotinic ACh receptor channel activity, and accelerate desensitization of the receptor.

Acetylcholine↗
PubMed1992

Quantitative assessment of digitized portal images: effect of sampling frequency on observer performance.

To investigate spatial resolution requirements for digitized portal images in radiation therapy, observer performance tests were performed. One hundred twenty portal images were digitized with sampling frequencies of 0.700, 0.350, and 0.175 mm for observation. Receiver operating characteristic analysis was used to determine the acceptable sampling frequency for clinical portal images. The detectability of setup errors was significantly better on the original images than on the digitized images with sampling frequencies of 0.700 mm (P = .005) and 0.350 (P = .046). Some clinical disadvantages might accrue with the use of a sampling frequency of 0.350 mm or larger.

Humans↗
PubMed1992

Diabetic state-induced modification of insulin-stimulated, glucose uptake into and kinase activity in, the diaphragm muscle of genetically diabetic KK-CAy mice.

The effect of insulin on glucose and 2-deoxyglucose uptake into isolated diaphragm was investigated in genetically diabetic KK-CAy mice, and in part in alloxan-treated mice. Concentration-response curves of insulin for glucose uptake (8.3 mM in vitro) for 1 h were shifted to the left in two kinds of diabetic model mice. Insulin-stimulated glucose uptake was biphasic; it was high 1 week, and returned to the normal level 4 weeks, after alloxan injection despite high blood glucose levels. Insulin-stimulated glucose uptake was the same at higher glucose levels (25 mM) as at 8.3 mM glucose for 1 h, despite an increase in basal glucose uptake (without insulin) in KK-CAy mice. Insulin-receptor kinase activity in diabetic KK-CAy mouse diaphragm also changed biphasically as the glucose concentration increased: an increase at 8.3 mM, but no increase at 16.7 mM or 25.0 mM glucose for 3 h-pretreatment including 1 h-insulin treatment. These results suggest that although the initial state of diabetes enhances insulin action, the prolonged hyperglycemia rather suppressed the insulin action in vivo.

Animals↗
PubMed1992

Suppression by high glucose concentration of insulin receptor up-regulation in diaphragm and flexor digitorum brevis muscles from diabetic KK-CAy and streptozotocin-diabetic mice.

The specific binding of insulin to diaphragm and flexor digitorum brevis (FDB) muscles isolated from diabetic KK-CAy and streptozotocin (STZ)-diabetic ddY mice was investigated under high glucose concentration in vitro. For high-affinity insulin receptor under 2.8 mM glucose, amounts of the receptor and values of dissociation constant (Kd) were greater in both diabetic muscles than in the corresponding normal control muscles, respectively. High glucose concentration up to 16.7 mM reduced both the up-regulation of the receptor and the decrease in the affinity by the diabetic state. These studies strongly suggest that high glucose level in the diabetic state in vivo may suppress the up-regulation of high-affinity insulin receptor in both models of diabetic mice.

Animals↗
PubMed1992

Platelet-derived growth factor (PDGF) accelerates induction of competence, and heparin does not inhibit PDGF-induced competence in primary cultured smooth muscle cells of rat aorta.

The time-dependent effect of platelet-derived growth factor (PDGF) on cell proliferation was investigated to clarify whether PDGF accelerates the rate of proliferation or its start in primary cultured smooth muscle cells (SMC) of rat aorta. In synchronized SMC at the G0 phase, 1, 10 and 100 ng/ml PDGF started DNA synthesis at 24, 15-18 and 12 hr, respectively, after stimulation by 3% fetal bovine serum (FBS) or hypophysectomized rat plasma (deficient in insulin-like growth factor-I (IGF-I)). Heparin (1, 10 or 100 micrograms/ml) decreased only the rate of DNA synthesis stimulated by PDGF in synchronized SMC. DNA synthesis in non-synchronized cells stimulated by PDGF with FBS was determined up to 10 days in culture. The stimulation with 1% FBS plus 30 ng/ml PDGF potentiated the DNA synthesis which was saturated with stimulation by 10% FBS alone, suggesting that prolonged treatment of PDGF transforms SMC. These results demonstrated that PDGF concentration-dependently accelerated the induction of competence independently of IGF-I, and heparin did not inhibit PDGF-induced competence but inhibited progression in primary cultured SMC of rat aorta.

Animals↗
PubMed1992

The effects of the serotonin1A receptor agonist buspirone on the blood glucose and pancreatic hormones in rats.

The effects of the serotonin1A (5-HT1A) receptor agonist buspirone on the plasma glucose and pancreatic hormones insulin and glucagon were investigated in rats. Buspirone elicited significant hyperglycemia and hyperglucagonemia, although it did not affect the insulin levels. Adrenodemedullation inhibited both the increase in blood glucose and glucagon levels. These results indicate that buspirone-induced hyperglycemia and hyperglucagonemia are mediated by adrenaline release from the adrenal gland.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

Different modes of potentiation by beta-eudesmol, a main compound from Atractylodes lancea, depending on neuromuscular blocking actions of p-phenylene-polymethylene bis-ammonium derivatives in isolated phrenic nerve-diaphragm muscles of normal and alloxan-diabetic mice.

The essential moieties in p-phenylene-polymethylene bis-ammonium (PMBA) derivatives, C6H4[X(CH2)nN+R3]2, on the potentiating effects by beta-eudesmol, a main component of Atractylodes lancea, of their neuromuscular blockades were investigated in isolated phrenic nerve-diaphragm muscle preparations of normal and alloxan-diabetic mice. PMBA derivatives were separated into the following three groups based on the patterns of the potentiating effects: group I: PMBA-23 (n = 6, R = Me) and PMBA-24 (n = 6, R = Et); group II: PMBA-1 (n = 4, R = Me), PMBA-21 (n = 4, R = Et) and PMBA-2 (X = O, n = 3, R = Me); and group III: PMBA-31 (X = S, n = 3, R = Me), PMBA-3 (X = CO, n = 3, R = Me) and PMBA-4 (X = CHOH, n = 3, R = Me). The pretreatment with 80 microM beta-eudesmol for 60 min did not affect group I-induced neuromuscular blocking action, and it potentiated group II- and group III-induced ones. The potentiating effect of beta-eudesmol on group III was greater in diabetic muscles than in normal one and that on group II was to the same extent in both muscles. These results suggest that the four-methylene length of the side chains in normal muscles and the hydrophilic moieties adjacent to a phenylene ring in diabetic muscles are related to the potentiating effect by beta-eudesmol on PMBA derivatives.

Animals↗
PubMed1992

Heparin inhibits the progression phase of subcultured endothelial cell proliferation in rat aorta.

The anti-proliferative effects of heparin on subcultured endothelial cells (EC) of rat aorta were investigated to determine whether heparin inhibits the competence phase or the progression phase in the cell cycle using the starting time and the rate of proliferation. Fetal bovine serum (FBS)-stimulated EC proliferation increased to 1.5-times in cell number, but decreased to 0.5-times in 3H-thymidine incorporation, compared with the proliferation of rat primary cultured smooth muscle cells (SMC). The FBS-effects on EC proliferation were attributed to the progression phase rather than the competence phase. Heparin (1, 10 or 100 micrograms/ml) significantly inhibited the proliferation of FBS (5%)-stimulated EC, and the extent of inhibition was the same in both cell number and 3H-thymidine incorporation. In the 3H-thymidine incorporation every 3 hr, heparin reduced the rate of incorporation into G0-arrested EC, but did not affect the starting time of DNA synthesis. When the index of competence phase, starting time, was plotted against that of progression phase, rate of proliferation, the inhibition of heparin was attributed to the progression phase. These results demonstrate that heparin selectively inhibits the progression phase in subcultured EC of rat aorta.

Animals↗
PubMed1992

Antiproliferative effects of the traditional Chinese medicine shimotsu-to, its component cnidium rhizome and derived compounds on primary cultures of mouse aorta smooth muscle cells.

Antiproliferative effects of the Japanese-Sino medicine Shimotsu-to (a combined prescription of cnidium rhizome, angelica root, peony root and rehmannia root) were investigated in the primary culture of smooth muscle cells (SMC) of mouse aorta. Fetal bovine serum (10%)-induced proliferation of primary cultured SMC was inhibited by Shimotsu-to at 4, 20, 100 or 500 micrograms/ml. The inhibitory effect was selective on SMC and due to cnidium rhizome or angelica root. The IC50 values of senkyunolide H, senkyunolide A, ligustilide and butylidenephthalide derived from cnidium were below 0.1, 1.52, 1.68 and 3.25 micrograms/ml, respectively. These results indicate that the antiproliferative effect of Shimotsu-to may depend on these cnidium-derived phthalides.

Animals↗
PubMed1992

Inhibitory effects of magnoshinin and magnosalin, compounds from "Shin-i" (Flos magnoliae), on the competence and progression phases in proliferation of subcultured rat aortic endothelial cells.

Anti-proliferative effects of magnoshinin and magnosalin derived from "Shin-i" (Flos magnoliae) were investigated using subcultured endothelial cells (EC) of rat aorta. The inhibitory effects of magnoshinin were 2-fold greater at 10 micrograms/ml than that of magnosalin on the increase in cell number when EC were stimulated by 5% fetal bovine serum. In the 3H-thymidine incorporation monitored at 3 hr-intervals, magnoshinin (0.1-3 micrograms/ml) prolonged the starting time of DNA synthesis and reduced the rate of incorporation into EC. Magnosalin (0.3-3 micrograms/ml) reduced only the incorporation rate. These results suggest that magnoshinin inhibits both the competence phase and progression phase, but magnosalin preferentially inhibits the progression phase in EC proliferation.

Animals↗
PubMed1992

Comparison of antitumor activity of new anthracycline analogues, ME2303, KRN8602, and SM5887 using human lung cancer cell lines.

In an attempt to predict the clinical activity of newly developed anthracycline analogues, ME2303, KRN8602, and SM5887 in the treatment of lung cancer, we compared antitumor activity of these drugs with that of adriamycin, using six human lung cancer cell lines and two drug-resistant human lung cancer sublines. Taking the pharmacokinetic data into consideration, we evaluated the relative antitumor activity: the ratio of area under the concentration-time curve of each drug to the 50% inhibitory concentration of the drug. Regarding this ratio, ME2303 was more potent than adriamycin, SM5887, and KRN8602. Cross-resistance of the new analogues to adriamycin was investigated using an adriamycin-resistant small cell lung cancer subline, SBC-3/ADM100 and an etoposide-resistant subline, SBC-3/ETP. SBC-3/ADM100 being 106-fold more resistant to adriamycin than the parent SBC-3 showed less resistance to the analogues: 1.80-fold to KRN8602, 3.80-fold to SM5887, and 8.60-fold to ME2303. SBC-3/ETP which was 52.1-fold more resistant to etoposide and 39.5-fold more resistant to adriamycin were also less resistant to the new analogues: 3.27-fold to KRN8602, 9.07-fold to SM5887, and 17.3-fold to ME2303. In conclusion, ME2303 was found to be the most potent agent among drugs tested for the treatment of lung cancer, and KRN8602 can be expected to be beneficial for the treatment of drug-resistant small cell lung cancer.

Anthracyclines↗