Biomedical subjects

K Takeyama

Publications and source records attributed to K Takeyama.

At least 91 records · Page 5Linked to original sources

PubMed1995

[A case of status asthmatics relieved by long-term inhalation of isoflurane].

A 58 year old man in status asthmatics refractory to drug therapy, was relieved by long-term isoflurane inhalation. In status asthmatics, it takes long time to recover from airway-damage, and inhalation-time will be prolonged in many cases. It is appropriate to use isoflurane because it is devoid of significant adverse effects compared with halothane and enflurane. Especially, isoflurane did not cause an increase in the serum fluoride revel, and will not lead to renal insufficiency in spite of its inhalation for 120 hours. It seems that isoflurane is suitable for long-term inhalation.

Administration, Inhalation↗

PubMed1994

In vivo isomerization of retinoic acids. Rapid isomer exchange and gene expression.

The in vivo isomerization of all-trans- and 9-cis-retinoic acids (RAs) was evaluated by high performance liquid chromatography after oral administration to rats. All-trans (2 ng/ml)- and 13-cis (1.8 ng/ml)-RAs, but not 9-cis-RA, were detected in the serum of normal rats. When an excess of either all-trans-RA or 9-cis-RA (100 micrograms/rat) was intragastrically administered to the retinoid-depleted rats, a rapid isomer exchange between 9-cis- and all-trans-RAs along with appearance of the administered RA occurred shortly after the dose (30 min). RA rapidly isomerized when an excess of either all-trans- or 9-cis-RA (1 mg/rat) was administered to normal rats. To examine whether the isomerized RAs elicit biological actions in vivo, the induction of target genes-[cellular retinol-binding protein type II (CRBP II) for 9-cis-RA and all-trans-retinoic acid receptor beta (RAR beta) for 9-cis- and all-trans-RAs] was determined. The degree of induction of the two genes did not differ 4 h after administration of either 9-cis-RA or all-trans-RA. However, unlike all-trans-RA, the RAR-specific synthetic retinoids did not induce the CRBP II gene. These results suggested that the apparent actions of 9-cis- and all-trans-RAs on gene expression in vivo may be mediated to some extent by the converted stereoisomer.

Animals↗

PubMed1994

Positive and negative regulation of retinoid X receptor gene expression by thyroid hormone in the rat. Transcriptional and post-transcriptional controls by thyroid hormone.

The 9-cis-retinoic acid receptors (RXRs), belonging to the members of the steroid/thyroid hormone receptor superfamily, act as auxiliary proteins, heterodimerizing with other nuclear receptors such as retinoic acid receptors (RARs), vitamin D receptor, thyroid hormone receptors, and peroxisome-proliferator activated receptor, thereby transactivating target genes in a ligand-dependent manner. We have previously reported that in the rat, thyroid hormone (TH) positively and negatively regulates the hepatic mRNA levels of RXR beta and RXR gamma, respectively. In the present study, we have tried to elucidate the level at which TH regulates the gene expression of RXR beta and RXR gamma in the rat. A RNA synthesis inhibitor (actinomycin D), but not a protein synthesis inhibitor (cycloheximide), blocked the induction of RXR beta mRNA by TH. On the other hand, none of these drugs inhibited the decrease of RXR gamma mRNA levels caused by TH. Nuclear run-on assays showed that the transcription rate of the RXR beta gene was positively regulated by TH, whereas the transcription of RXR gamma gene was not controlled by TH. Taken together, these results indicate that the gene expression of RXR beta is positively regulated by TH at transcriptional level, while the negative regulation of the RXR gamma gene expression by TH may occur at a post-transcriptional level in intact rat. Thus, the RXR-mediated signal transductions may be modulated in part through TH control of the levels of RXR beta and RXR gamma.

Animals↗

PubMed1994

Effects of prostacyclin and beraprost on ciliary motility of rabbit airway epithelium.

The effects of prostacyclin and its stable analog beraprost on ciliary beat frequency (CBF) of rabbit tracheal epithelium were studied by a microphoto-oscillation technique in vitro. Addition of these drugs increased CBF in a dose-dependent fashion: the maximal increase from the baseline value and the drug concentration required to produce a half-maximal effect were 13.3 +/- 2.0% (p < 0.05) and 1.8 +/- 0.4 x 10(-7) mol/l for prostacyclin and 30.8 +/- 3.4% (p < 0.001) and 1.6 +/- 0.5 x 10(-7) mol/l for beraprost. These effects were accompanied by the increase in intracellular cyclic AMP levels. Thus, prostacyclin and beraprost may stimulate ciliary motility and, hence, mucociliary transport through the production of cyclic AMP.

Animals↗

PubMed1994

Interleukin-1 beta inhibits airway smooth muscle contraction via epithelium-dependent mechanism.

To determine whether the cytokine interleukin (IL)-1 beta directly affects airway smooth muscle functions and, if so, what the mechanism of action is, we studied canine isolated bronchial segments under isometric conditions in vitro. Incubation of tissues with human recombinant IL-1 beta (10 ng/ml) for 150 min decreased the contractile responses to acetylcholine, histamine, and KCl. The inhibitory effect of IL-1 beta on the acetylcholine (10(-3) M)-induced contraction was concentration-dependent, the maximal decrease from the baseline contraction being 52 +/- 8% (mean +/- SD, p < 0.001) observed with 10 ng/ml IL-1 beta. Intracellular levels of cyclic AMP and cyclic GMP were not significantly altered by IL-1 beta. The IL-1 beta-induced inhibition of the contractile responses was not affected by pretreatment of tissues with indomethacin or propranolol, but it was greatly attenuated by mechanical removal of epithelium. These results suggest that IL-1 beta may play a protective role against bronchoconstrictor responses via epithelium-dependent mechanism such as the release of epithelium-derived relaxing factor.

Acetylcholine↗

PubMed1994

[Pharmacological study of ebastine, a novel histamine H1-receptor antagonist].

The anti-allergic activity of ebastine, a novel antihistamine, was assessed in comparison with several antihistamines. 1) Orally administered ebastine dose-dependently inhibited 7-day homologous passive cutaneous anaphylaxis (PCA), experimental allergic rhinitis and experimental asthma in guinea pigs or rats (ED50-values were 2.17, 0.29 and 0.35 mg/kg, respectively); and its anti-allergic activity was more potent than those of terfenadine and mequitazine. Moreover, its PCA-inhibitory activity was still observed 24 hr after the administration. 2) Orally administered ebastine also inhibited histamine-induced skin reaction in rats (ED50: 1.10 mg/kg). 3) In isolated guinea pig trachea, ebastine had no effect on histamine-induced contraction, but carebastine, a main metabolite of ebastine, inhibited this contraction (IC50: 0.12 microM). 4) Carebastine (30-100 microM) suppressed the histamine release from rat peritoneal mast cells and human basophils. 5) Ebastine at a high oral dose showed slight inhibition of the specific binding of 3H-mepyramine to the histamine H1-receptor in rat brain. This binding-inhibitory activity of ebastine was little more potent than that of terfenadine, but much less potent than those of mequitazine and ketotifen. These results indicated that ebastine has potent and long acting anti-allergic activity with few side effects based on the antihistaminic activity in the central nervous system. Furthermore, it was suggested that these effects of ebastine are due to the action of a main metabolite, carebastine.

Administration, Oral↗

PubMed1994

A useful method for differential evaluation of anti-inflammatory effects due to cyclooxygenase and 5-lipoxygenase inhibitions in mice.

This study was performed to establish a useful method for monitoring the effects of inhibitors of 5-lipoxygenase (5-LO) and/or cyclooxygenase (CO) and for differential evaluation of these inhibitors. After oral dosing, CO inhibitors such as indomethacin (20-40 mg/kg) and ketoprofen (40-80 mg/kg), zileuton (5-LO inhibitor, 20-80 mg/kg) and MK886 (5-LO-activating-protein inhibitor, 640 mg/kg) potently suppressed arachidonic acid (AA, 0.25 mg)-induced ear edema in mice. Methysergide (serotonin antagonist, 20 mg/kg) showed a slight anti-edematous effect, while mepyramine (160 mg/kg) and bromelain (320 mg/kg) had no effect. The anti-edematous effects of indomethacin and ketoprofen were reduced by concomitant topical application of prostaglandin E2 (PGE2, 1 micrograms/ear), but not by concomitant intradermal application of leukotriene C4 (LTC4, 0.1 micrograms/ear). On the contrary, the anti-edematous effects of zileuton and MK886 were reduced by LTC4, but not by PGE2. Dual (5-LO and CO) inhibitors such as phenidone (80-160 mg/kg) and BW755C (40-80 mg/kg), which inhibited the biosynthesis of LTB4 13-15 times more potently than that of PGE2 in rat peritoneal exudate cells, also showed anti-edematous effects that were reduced by LTC4, but not by PGE2. These results suggest that the AA (0.25 mg)-induced ear edema in mice is mainly mediated by LTs and PGs and is suitable for evaluating inhibitors of 5-LO and/or CO, and that an application of LTC4 or PGE2 with AA is a useful method for differential evaluation of these inhibitors.

Animals↗

PubMed1994

[Modulation of cholinergic neurotransmission by Ca(2+)-activated K channel and Na(+)-K(+)-ATPase in canine airway smooth muscle].

Stimulation of Ca(2+)-activated K+ channel and Na(+)-K(+)-ATPase may play an important role in the relaxant responses of airway smooth muscle to certain bronchodilators. To elucidate whether cholinergic neuroeffector transmission can be modulated by Ca(2+)-activated K+ channel and Na(+)-K(+)-ATPase, we studied canine airway smooth muscle under isometric conditions in vitro. Addition of charybdotoxin (ChTx, 10(-7) M) did not alter the contractile responses to acetylcholine (ACh) but augmented electrical field stimulation (FES)-induced contractions at 1-10 Hz (p < 0.01), whereas apamin and glibenclamide were without effect. This effect was dose-dependent, with the maximal increase being 36.8 +/- 5.3% (p < 0.001). Ouabain at a concentration insufficient to alter the resting tension (10(-7) M) increased contractions induced by both EFS and ACh. The magnitude of the increase in contractile responses to EFS was similar to those to ACh at ouabain concentration of up to 3 x 10(-7) M, but the former was significantly greater at 10(-6) M ouabain (p < 0.05). These results suggest that each Ca(2+)-activated K+ channel and Na(+)-K(+)-ATPase may a modulatory role in the cholinergic neurotransmission by inhibiting the exocytotic ACh release from the vagal nerve terminals.

Acetylcholine↗

PubMed1993

Thyroid hormone affects the gene expression of retinoid X receptors in the adult rat.

Gene expression of three nuclear retinoid X receptors (RXR alpha, beta and gamma) was examined by Northern blot analysis in various rat tissues. The RXR alpha mRNA (5.5 kb) was detected in most tissues and particularly expressed at a high level in the liver. The RXR beta transcripts (2.4 and 3.0 kb) were expressed ubiquitously, and particularly at high levels in the brain and testis. In the liver, heart, kidney and lung, the RXR gamma mRNA (2.0 kb) was specifically detected. Furthermore, we examined the effect of retinoid, vitamin D and thyroid hormone status on the gene expression of RXR alpha, beta and gamma. Though retinoid and vitamin D did not affect the mRNA levels of three RXRs, the mRNA levels of two genes were controlled by thyroid hormone. Namely, positive (RXR beta) and negative (RXR gamma) regulations by thyroid hormone were observed with no effect on the gene expression of RXR alpha. These results suggest that thyroid hormone might affect the signal transduction of retinoid, vitamin D and thyroid hormone by changing RXR levels.

Animals↗

PubMed1993

Long persistent bcr-abl positive transcript detected by polymerase chain reaction after marrow transplant for chronic myelogenous leukemia without clinical relapse: a study of 64 patients.

We report here the results of polymerase chain reaction (PCR) for bcr-abl transcript and clinical details derived from 64 chronic myelogenous leukemia (CML) patients after allogeneic bone marrow transplantation (BMT). A total of 139 samples (2 to 220 weeks after BMT) were analyzed and bcr-abl transcript was detected in 99 samples from 52 patients. Patients were defined as bcr-abl early negative (EN) if they had > or = 1 negative PCR result < or = 1 year post-BMT (n = 13), and bcr-abl late positive (LP) if they had > or = 1 positive PCR result > or = 1 year post-BMT (n = 21). Among LP patients, only two patients had hematologic/cytogenetic (clinical) relapse. Another 19 LP patients remained in clinical remission 7 to 130 weeks after positive analysis for bcr-abl transcript, including 5 patients who had persistent bcr-abl transcript detectable even 2 years after BMT. To estimate the relationship between clinical data and residual bcr-abl transcript, EN patients are compared with LP patients. However, no clinical data studied were significantly associated with the persistent PCR positivity. If only patients in chronic phase are compared, the t-test showed significant correlation between leukocyte count just before BMT and sustained bcr-abl transcript (P < .05). These results suggest that PCR positivity is frequently observed in CML patients who sustain clinical remission after BMT, without being predictive of imminent clinical relapse. Tumor burden at the time of BMT may play an important role in the latency of bcr-abl positivity after BMT.

Adolescent↗

PubMed1993

Relaxation and inhibition of contractile response to electrical field stimulation by Beraprost sodium in canine airway smooth muscle.

To elucidate the effect of Beraprost, a stable prostaglandin (PG) I2 analogue, on airway smooth muscle functions and its mechanism of action, we studied canine bronchial segments under isometric conditions in vitro. Addition of PGI2 and its analogues dose-dependently relaxed bronchial smooth muscle precontracted with acetylcholine, with the rank order of potency being Beraprost (1) > or = Hoprost (0.65) > PGI2 (0.04), accompanied by the corresponding increase in intracellular cyclic AMP levels. The Beraprost- and PGI2-induced muscle relaxations were significantly inhibited by each of the PG antagonist diphloretin phosphate, the adenylate cyclase inhibitor SQ 22,536, and the Na(+)-K(+)-ATPase inhibitor ouabain. Beraprost and PGI2 at concentrations insufficient to cause muscle relaxation reduced the contractile responses to electrical field stimulation, whereas they were without effect on those to exogenous acetylcholine. These results suggest that Beraprost not only potently relaxes airway smooth muscle through cyclic AMP production and the subsequent stimulation of Na(+)-K(+)-ATPase but also reduces neurally mediated contraction by inhibiting the release of acetylcholine from the cholinergic nerve terminals.

Acetylcholine↗

PubMed1993

Antihypertensive effects of AJ-2615, a new calcium antagonist with alpha 1-adrenergic blocking activity in experimental hypertensive animals.

The antihypertensive effect of AJ-2615 [(+/-)-N-(6,11-dihydrodibenzo[b,e]thiepin-11-yl)-4-(4-fluoro phenyl)-1- piperazinebutanamide maleate], a novel calcium (Ca) antagonist having alpha 1-adrenergic blocking activity as well, was compared with that of the existing Ca antagonists (diltiazem, nifedipine, and nicardipine) in various hypertensive models of dogs and rats. When given orally to renal hypertensive dogs (RHDs) and spontaneously hypertensive rats (SHRs), AJ-2615 (RHDs, ED25 mm Hg = 6.0 mg/kg; SHRs, ED25 mm Hg = 24.9 mg/kg) was approximately as effective as diltiazem (RHDs, ED25 mm Hg = 6.3 mg/kg; SHRs, ED25 mm Hg = 54.7 mg/kg) in lowering the blood pressure. This antihypertensive effect was slower in onset and longer in duration (RHDs, > or = 9 h; SHRs, > or = 20 h) compared with any of the other reference drugs. AJ-2615 (10 mg/kg p.o.) given to RHDs once daily for 29 days significantly reduced the blood pressure measured 24 h after each dose and caused a stable antihypertensive effect without major diurnal variations. When given in single oral doses to RHDs and SHRs, AJ-2615 had no large effect on the heart rate while the reference drugs induced a large increase or decrease in heart rate in response to a blood pressure fall. These results suggested that AJ-2615 has potential as a long-acting (once daily dosage regimen) antihypertensive drug without causing a steep blood pressure fall and tachycardia.

Adrenergic alpha-Antagonists↗

PubMed1993

Effect of macrolide antibiotics on ciliary motility in rabbit airway epithelium in-vitro.

We have studied ciliary beat frequency (CBF) of rabbit cultured tracheal epithelium by a photoelectric method in-vitro. Addition of erythromycin and roxithromycin increased CBF in a dose-dependent fashion, whereas clarithromycin was without effect. The rank order potency of macrolide was roxithromycin > erythromycin >> clarithromycin. The roxithromycin-induced increase in CBF was not altered by propranolol, AA-861, or verapamil, but partially attenuated by indomethacin. Roxithromycin increased intracellular cAMP concentrations. These results suggest that certain macrolides can stimulate airway ciliary motility probably via prostaglandin- and cAMP-dependent regulatory pathways, which may affect mucociliary transport function in the respiratory tract.

Animals↗

PubMed1993

Effect of azelastine on sulphur dioxide induced impairment of ciliary motility in airway epithelium.

OBJECTIVE: The effect of azelastine on airway mucociliary transport function was studied by measuring ciliary motility of human bronchial epithelium in vitro with a photoelectric method. METHOD: Bronchial epithelial cells were obtained by fibreoptic bronchoscopy, mounted in a Rose chamber, and perfused with Krebs-Henseleit solution. The preparations were placed on a microscope stage equipped with an illuminator, and the variations of light intensity caused by ciliary beating were detected by a photometer. RESULTS: The addition of azelastine to the perfusate increased ciliary beat frequency (CBF) in a dose dependent manner without ciliary discoordination. The mean (SE) maximal increase from the baseline value and the concentration required to produce a half maximal effect were 27.0 (4.2)% and 9.2 x 10(-6) mol/l, respectively. Exposure of the cells to the perfusate containing 3 ppm sulphur dioxide rapidly decreased CBF by 59.2 (5.0)%, and was accompanied by a reduction in intracellular cyclic AMP levels from 38.1 (4.3) to 10.1 (2.4) pmol/mg protein. This effect was prevented by pretreatment of cells with azelastine in a dose dependent manner. CONCLUSIONS: Azelastine not only stimulates ciliary motility of airway epithelium and hence mucociliary transport function, but may also protect against sulphur dioxide induced ciliary dysfunction, probably by inhibiting intracellular cyclic AMP loss.

Bronchi↗

PubMed1993

Potentiation of beta-adrenergic function by saiboku-to and bakumondo-to in canine bronchial smooth muscle.

To determine the effects of the Kampo drugs Saiboku-to, Bakumondo-to and Orengedoku-to on beta-adrenergic function in airway smooth muscle, we studied isolated canine bronchial segments under isometric conditions in vitro. Incubation of tissues with these drugs did not alter the contractile responses to acetylcholine and histamine. The relaxation of tissues precontracted with acetylcholine induced by isoproterenol was augmented by Saiboku-to and Bakumondo-to, so that the concentration of isoproterenol required to produce a half-maximal effect (IC50) was decreased from 4.6 +/- 0.5 x 10(-8) M to 1.9 +/- 1.0 x 10(-8) M (P < 0.05) and to 1.0 +/- 0.8 x 10(-8) M (P < 0.01), respectively, whereas Orengedoku-to had no effect. These effects were concentration-dependent with the threshold concentrations being 0.3 mg/ml for Saiboku-to and 0.1 mg/ml for Bakumondo-to. Saiboku-to and Bakumondo-to did not affect cyclic AMP levels in airway smooth muscle per se but potentiated the isoproterenol-induced cyclic AMP accumulation. These results suggest that Saiboku-to and Bakumondo-to but not Orengedoku-to potentiate beta-adrenergic function in airway smooth muscle, which may reflect the efficacy of these drugs on airway hyperresponsiveness and asthma.

Adrenergic beta-Agonists↗

PubMed1993

Differences in clinicopathological characteristics and major prognostic factors between B-lymphoma and peripheral T-lymphoma excluding adult T-cell leukemia/lymphoma.

A total of 541 consecutive patients treated between 1975 and 1985, 449 with B-lymphoma and 92 with peripheral T-lymphoma, excluding adult T-cell leukemia/lymphoma (ATL), termed peripheral non-ATL T-lymphoma, were analysed. Clinicopathological features that were predominantly associated with B-lymphoma were low and intermediate grades (defined by the Working Formulation), diffuse large cell type, stage II disease, bulky disease, favourable extranodal sites that are defined as a group of primary tumors such as the eye, Waldeyer's ring, thyroid, and stomach, while other features predominantly associated with peripheral non-ATL T-lymphoma were high grade pathology, diffuse mixed-cell and immunoblastic type, systemic "B" symptoms, poor performance status (PS), generalized lymphadenopathy, involvement of organs such as liver, skin, and nose, leucocytosis, and a high levels of serum alkaline phosphatase. The survival curve for B-lymphoma was better (P < 0.01) than that for peripheral non-ATL T-lymphoma. Multivariate analysis revealed that the major prognostic factors were pathology, stage, and primary site for B-lymphoma, while stage, PS, and total protein levels were important for peripheral non-ATL T-lymphoma. These results indicate that B- and peripheral non-ATL T-lymphomas appear to have different biological characteristics.

Adult↗

PubMed1993

Gene expression of cellular retinol-binding protein I (CRBP I) is affected by dietary proteins in the rat liver.

The effect of dietary proteins and vitamin A status on the gene expression of cellular retinol-binding protein I (CRBP I) was studied in the rat liver. The gene expression was estimated as amounts of transcript (mRNA) by Northern blot analysis using rat CRBP I cDNA. Though vitamin A status is known to positively regulate the gene expression of CRBP I in the extrahepatic tissues, in the present study we observed that the amount of the CRBP I transcript in liver was neither reduced by vitamin A-deficiency, nor affected by replenishment with an excess dose of all-trans retinoic acid. These results indicate that in the liver, different from the extrahepatic tissues, the gene expression of CRBP I may not be controlled by vitamin A. However, when the rats were fed on the diets that differed in dietary proteins, the gene expression of CRBP I in liver was enhanced by higher quality and quantity of dietary proteins, though no effect of dietary proteins was observed upon the hepatic contents of retinol. The concentrations of serum retinol were almost proportional to the mRNA levels of CRBP I. In contrast, the hepatic gene expression of another retinol-binding protein, RBP, and one subtype of retinoic acid receptor, RAR alpha was not influenced in the nutritional condition tested here. Our findings suggest that the gene expression of CRBP I in liver may be under control of the intake of dietary proteins. Thus, it is likely that in the light of the function of CRBP I on cellular transport and metabolism of retinol, dietary proteins may affect the actions of vitamin A in the extrahepatic tissues through changing the amounts of CRBP I in liver.

Animals↗

PubMed1993

[Stimulation of ciliary motility by beta 3-adrenoceptor agonist rabbit tracheal epithelium].

To determine whether atypical beta-adrenoceptor (beta 3-adrenoceptor) agonist, BRL 37344, stimulates airway ciliary motility and, if so, what its mechanism of action is, we studied rabbit tracheal epithelium in vitro. Epithelial cells cultured for 7 days were mounted in the Rose chamber and ciliary beat frequency (CBF) was measured by a photoelectric method. Addition of BRL 37344 rapidly increased CBF from 15.5 +/- 0.6 to 20.3 +/- 1.4 Hz (mean +/- SE, p < 0.01), which remained elevated for at least 20 min. This effect was concentration-dependent, the maximal increase from the baseline value and the EC50 being 27.2 +/- 0.4% (mean +/- SE, p < 0.01) and 1.75 x 10(-7) M, respectively. Other beta-adrenoceptor agonists likewise increased CBF, where the rank order of potency was salbutamol (1) > BRL 37344 (0.57) >> norepinephrine (1.3 x 10(-3)). Preincubation of cells with propranolol inhibited the increase in CBF produced by salbutamol, and BRL 37344 significantly raised intracellular cyclic AMP contents. These results suggest that beta 3-adrenoceptor probably exists in rabbit tracheal epithelium and that stimulation of this type of receptor increases ciliary motility through a cyclic AMP-dependent mechanism, an effect that might be of value in enhancing mucociliary transport function in the airway.

Adrenergic beta-Agonists↗