Search PubMed⌕ Search

Biomedical subjects

H Nakaya

Publications and source records attributed to H Nakaya.

At least 37 records · Page 2Linked to original sources
PubMed1999

Histamine H1-receptor-mediated modulation of the delayed rectifier K+ current in guinea-pig atrial cells: opposite effects on IKs and IKr.

1. Histamine receptor-mediated modulation of the rapid and slow components of the delayed rectifier K+ current (IK) was investigated in enzymatically-dissociated atrial cells of guinea-pigs using the whole cell configuration of the patch clamp technique. 2. Histamine at a concentration of 10 microM enhanced IK recorded during strong depolarization to potentials ranging from +20 to +40 mV and inhibited IK recorded during mild depolarization to potentials ranging from -20 to -10 mV. The increase of IK was more prominent with longer depolarizing pulses, whereas the inhibition of IK was more marked with shorter depolarizing pulses, suggesting that histamine enhances IKs (the slow component of IK) and inhibits IKr (the rapid component of IK). 3. The histamine-induced enhancement of IKs and inhibition of IKr were abolished by 3 microM chlorpheniramine but not by 10 microM cimetidine, suggesting that these opposite effects of histamine on IKr and IKs are mediated by H1-receptors. 4. In the presence of 5 microM E-4031, an IKr blocker, histamine hardly affected IK during mild depolarization although it enhanced IK during strong depolarization in a concentration-dependent manner. Histamine increased IKs with EC50 value of 0.7 microM. In the presence of 300 microM indapamide, an IKs blocker, histamine hardly affected IKs but inhibited IKr in a concentration-dependent manner. Histamine decreased IKr with IC50 value of 0.3 microM. 5. Pretreatment with 100 nM calphostin C or 30 nM staurosporine, protein kinase C inhibitors, abolished the histamine-induced enhancement of IKs, but failed to affect the histamine-induced inhibition of IKr. 6. We conclude that in guinea-pig atrial cells H1-receptor stimulation enhances IKs and inhibits IKr through different intracellular mechanisms.

Animals↗
PubMed1999

Effects of AH-1058, a new antiarrhythmic drug, on experimental arrhythmias and cardiac membrane currents.

AH-1058 is a newly synthesized antiarrhythmic agent. We investigated the antiarrhythmic and electrophysiological effects of AH-1058 in experimental arrhythmia models and isolated cardiomyocytes. In the ouabain-induced arrhythmia model of the guinea pig, pretreatment with AH-1058 (0.1-0.3 mg/kg, i.v.) delayed the appearance of premature ventricular complex (PVC) and ventricular fibrillation (VF) induced by intravenous infusion of ouabain. However, disopyramide (10 mg/kg, i.v.) delayed only that of PVC, and verapamil (1 mg/kg, i.v.) failed to affect the ouabain-induced ventricular arrhythmias. In the reperfusion-induced arrhythmia model of the rat, in which 5-min coronary occlusion and 10-min reperfusion were produced, AH-1058 (0.1-0.3 mg/kg, i.v.) inhibited the incidence of both ventricular tachycardia (VT) and VF, whereas disopyramide (5 mg/kg, i.v.) inhibited only reperfusion-induced VF. On the other hand, a higher dose of AH-1058 (1 mg/kg, i.v.) did not affect the aconitine-induced arrhythmias in rats, which were inhibited by disopyramide (5 mg/kg, i.v.). We also confirmed oral activity of AH-1058 in the reperfusion-induced arrhythmia model of the rat. AH-1058, at doses of 2-4 mg/kg, dose-dependently inhibited VT and VF. Electrophysiological experiments with patch-clamp techniques revealed that AH-1058 potently suppressed the L-type Ca2+ currents in isolated cardiomyocytes of the guinea pig. These results suggest that AH-1058 is a potent antiarrhythmic drug having a Ca2+ channel-blocking action. The antiarrhythmic profile of AH-1058 is different from that of disopyramide and verapamil.

Aconitine↗
PubMed1999

An investigation of the disabled elderly in a geriatric health services facility in an urban area of Japan and attitudes of their family caregiver.

We investigated characteristics of 72 clients in a geriatric health services facility (hereafter called GHSF), conditions of their family caregivers, and the factors associated with the caregivers choice of discharge destination. Most of the clients were elderly females with a low degree of independence, and dementia was observed in about 60% of them. The clients had children, but many of them lived alone before admission to the GHSF. The rate of admission from hospitals was high (54%), and that of discharge to hospitals was also high (50%). Sixty-seven percent of the clients stayed in for a period of over six months. Most of the family caregivers were daughters or daughters-in-law, and considered themselves to be healthy. Sixty-three percent of them had jobs, and most of the caregivers had no sub-caregiver to assist them. The family caregivers desired the client's home (19.4%), hospital or another GHSF (54.2%), or nursing home (26.4%) as the discharge destination from the GHSF. According to Hayashi's quantification theory type II, the factors related to the home as the discharge destination desired by client's family caregivers are as follows; caregivers used formal home public health nursing visit service before entering the GHSF, the job of the caregiver was a part-time job, the client did not show dementia, the period of care experience was shorter than one year.

Aged↗
PubMed1999

Inhibitory effects of the antihistamines epinastine, terfenadine, and ebastine on potassium currents in rat ventricular myocytes.

We examined and compared the inhibitory effects of three non-sedating antihistamines, terfenadine, ebastine, and epinastine, on delayed rectifier potassium current (IK) and transient outward potassium current (Ito) of rat isolated ventricular myocytes, using a patch clamp technique. Terfenadine, ebastine and epinastine were found to inhibit IK with IC50 values of 5.96, 15.3 and 145 microM, respectively. Ito was suppressed by epinastine with an IC50 value of 69.5 microM. The order of arrhythmogenicity, assessed by the inhibition of IK, was ranked as terfenadine > ebastine > epinastine, consistent with that of the potencies of each drug for QT prolongation reported in rats.

Animals↗
PubMed1999

Effects of angiotensin inhibitors on renal injury and angiotensin receptor expression in early hypertensive nephrosclerosis.

Angiotensin converting enzyme inhibitors (ACEI) are known to inhibit the progression of established renal failure. The aim of this study was to compare the efficacy of an ACEI and an AT1 receptor antagonist (AT1R-Ant) in preventing the development of renal disease, at an early stage of hypertensive nephrosclerosis. SHRSP/Izm rats (n = 61) were treated from 10 wk until 22 wk with the ACEI delapril (40 mg/kg/d) or the AT1R-Ant candesartan cilexetil (1 mg/kg/d). Proteinuria, and structural/ultrastructural changes were assessed at 14 and 22 wk. Treatment with either agent resulted in reductions in blood pressure and cardiovascular hypertrophy. Neither proteinuria nor major renal histological changes were evident at 14 wk. At 22 wk, however, proteinuria accompanied by nephrosclerotic changes was seen in the untreated SHRSP/Izm. Treatment with either ACEI or AT1R-Ant resulted in similar reductions in proteinuria (untreated, 32.2 +/- 7.4; delapril-treated, 5.5 +/- 1.2; candesartan-treated, 3.9 +/- 0.3 mg/100 g/d). Prominent sclerosis of small-to-medium sized renal arteries was seen in the untreated SHRSP/Izm at 22 wk, but was similarly attenuated by the ACEI and AT1R-Ant. The glomerular ultrastructure was comparable between the two groups. No significant changes in renal AT1a or AT1b receptor subtype mRNA expression were seen throughout the course of the study. In contrast, a decrease in AT2 receptor mRNA was seen in the drug-treated groups at 14 wk but not at 22 wk. These results suggest that both ACEI and AT1R-Ant have similar efficacy in attenuating the onset of renal injury in early hypertensive nephrosclerosis, and that treatment with either agent is associated with a transient decrease in AT2 receptor mRNA expression.

Angiotensin Receptor Antagonists↗
PubMed1998

Effects of ACTH on adrenal angiotensin II receptor subtype expression in vivo.

Control of adrenal aldosterone secretion is an important endocrine mechanism mediated by angiotensin II (Ang. II). Recently three subtypes of angiotensin receptors have been demonstrated in the rat adrenal. Our aim was to examine if these receptors are affected by hormone treatment in vivo. Treatment of rats with ACTH resulted in a decrease in AT2 receptor binding from 766 +/- 95 to 310 +/- 51 fmol/mg protein (P < 0.05), without significant changes in AT1 receptors. AT2 receptor mRNA was also decreased (18 +/- 2%, of control, P < 0.05; 25+/-7% of control, P < 0.05) after both 2 and 7 day treatment with ACTH. Changes in AT1a receptor mRNA or total AT1 mRNA did not reach statistical significance. Moreover, treatment with dexamethasone or aldosterone did not affect AT1a, AT1b, or AT2 mRNA. These results demonstrate that ACTH treatment results in subtype-specific changes in adrenal AT receptor gene expression in vivo.

Adrenal Glands↗
PubMed1998

Adrenal angiotensin II type 1 and type 2 receptors in Cushing's and Conn's syndromes.

Cushing's and Conn's syndromes are well recognised endocrine diseases, but the pathobiology of the tumors causing these disorders is unclear. In this study we examined AT1 and AT2 gene expression in adrenal adenomas of Cushing's and Conn's syndromes. AT1 and AT2 receptor mRNA, as well as alternatively spliced AT1 transcripts, were detected by RT-PCR using adjacent adrenal cortex tissue as controls. Whereas no consistent differences in AT1 mRNA were seen compared to control adrenal cortex, AT2 mRNA levels were significantly decreased in the adenomas of Cushing's and Conn's syndromes. No changes in alternative splicing of AT1 mRNA were observed in the adrenal tumors. The fact that no consistent changes were seen in AT1 mRNA or its splicing, whereas AT2 mRNA were reduced in both forms of hormone producing adrenal tumor suggests that the AT2 receptor, rather than the AT1 subtype, may be correlated with adrenal tumorigenesis.

Adrenal Cortex↗
PubMed1998

Inhibitory effects of class I and IV antiarrhythmic drugs on the Na+-activated K+ channel current in guinea pig ventricular cells.

Recently we have reported that class III antiarrhythmic drugs including amiodarone inhibit the Na+-activated K+ (KNa) channels in isolated cardiac cells. In this study effects of antiarrhythmic drugs having class I and/or IV properties on the single KNa channel current were examined in inside-out membrane patches of guinea pig ventricular cells by using patch clamp techniques. The KNa channel current, which was activated by increasing [Na+]i from 0 mM to 100 mM in the presence of 150 mM [K+]o, showed a large slope conductance (212 pS) and inward-going rectification. Quinidine (100 microM), mexiletine (100 microM) and flecainide (10 microM) were selected as representative of class Ia, Ib and Ic drugs, respectively. These drugs at relatively high concentrations incompletely inhibited the KNa channel by decreasing the open time (flickering block). The class IV drug verapamil inhibited the KNa channel current mainly by decreasing the open probability although the IC50 value of verapamil (3.36 microM) was higher than the therapeutic concentrations. Bepridil and SD-3212, antiarrhythmic drugs having both class I and IV properties, potently inhibited the KNa channel current by decreasing the open probability. The IC50 values of bepridil and SD-3212 for inhibiting the KNa channel current was 0.51 microM and 0.53 microM, respectively, both of which are within the therapeutic range. Most antiarrhythmic drugs inhibit cardiac KNa channels by different modes and at different concentrations. The KNa channel blocking action of bepridil and SD-3212 may partly contribute to the prolongation of the action potential duration by these drugs at rapid stimulation rates.

Animals↗
PubMed1998

Selective impairment of HCO3(-)-dependent pHi regulation by lysophosphatidylcholine in guinea pig ventricular myocardium.

OBJECTIVE: The aim was to examine the effects of lysophosphatidylcholine (LPC), an amphiphilic lipid metabolite in ischemic myocardium, on intracellular pH (pH(i)) regulatory systems in guinea pig papillary muscles. METHODS: In CO2/HCO(3-)-buffered Tyrode solution, pH(i), intracellular Na+ activity (aNai) and membrane potential of isolated guinea pig papillary muscles were measured using ion-selective microelectrode and conventional microelectrode. Standard ammonium prepulsing with 20 mM NH4Cl was used to produce an intracellular acid load, and effects of LPC on the pH(i) recovery from acidosis were evaluated in the absence and presence of a transport inhibitor. RESULTS: LPC acidified the resting pH(i) by 0.03 +/- 0.01 pH units (n = 15, p < 0.01) concomitantly with a slight decrease in resting membrane potential and an increase in aNai in quiescent preparations. The pH(i) recovery rate from an intracellular acid load was decreased to 83 +/- 4% of the control value by 30 microM LPC (n = 8, P < 0.05) but not by 30 microM phosphatidylcholine (PC). In the presence of 10 microM 5-(N,N-hexamethylene) amiloride (HMA), a Na(+)-H+ exchange inhibitor, LPC still slowed pH(i) recovery from an intracellular acid load to 77 +/- 4% of the control (n = 5, P < 0.05). However, LPC failed to alter the pH(i) recovery rate in the presence of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS, 0.5 mM), a Na(+)-HCO3- symport inhibitor. CONCLUSION: LPC impairs Na(+)-HCO3- symport but not Na(+)-H+ exchange, and LPC may potentiate its arrhythmogenic action by intensifying the intracellular acidosis in ischemic myocardium.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1998

Preferential inhibition of Ikr by MCI-154, a putative cardiotonic Ca2+ sensitizer, in guinea pig atrial cells.

OBJECTIVE: To define the electrophysiologic mechanism(s) by which MCI-154, a putative Ca2+ sensitizer, produces a positive inotropic response without a positive chronotropic response, we examined effects of MCI-154 on the action potential of atrial preparations and the membrane currents of atrial myocytes. METHODS: The action potentias were recorded from left atrial and sinoatrial node preparations of guinea pigs by the use of standard microelectrode techniques. The whole-cell membrane currents were recorded from enzymatically-dissociated guinea pig atrial myocytes using conventional patch clamp techniques. RESULTS: In isolated left atria, MCI-154 increased the developed tension in a concentration-dependent manner. MCI-154 at concentrations of 10 and 100 microM increased the action potential duration (APD) in left atria stimulated at 0.5 Hz. In sinoatrial node preparations MCI-154 at a concentration of 100 microM produced a negative chronotropic response and prolonged APD. In single right atrial myocytes, MCI-154 at concentrations of 10 and 100 microM failed to increase the inward L-type Ca2+ current, but decreased the delayed rectifier K+ current (IK) in a concentration-dependent manner. MCI-154 decreased IK elicited by short depolarizing pulses more markedly than that induced by long depolarizing pulses. In addition, MCI-154 produced only a little inhibition of IK in the presence of E-4031, a specific blocker of rapidly activating component of IK (IKr). CONCLUSIONS: MCI-154 preferentially blocks IKr and the inhibitory action on IKr may be partly involved in the negative chronotropic and positive inotropic responses in atrial preparations.

Action Potentials↗
PubMed1998

Bradykinin B2-receptor-mediated modulation of membrane currents in guinea-pig cardiomyocytes.

1. In order to define the electrophysiological mechanism(s) responsible for bradykinin (BK)-induced positive inotropic and chronotropic responses in isolated guinea-pig atria, effects of BK on the membrane currents were examined in isolated atrial cells using patch clamp techniques. 2. BK (0.1-1000 nM) increased the L-type Ca2+ current (I(Ca)), which was recorded from enzymatically-dissociated atrial myocytes by the nystatin-perforated patch method, in a concentration-dependent fashion, and the calculated EC50 value for increasing I(Ca) was 5.2 nM. In conventional ruptured patch experiments, BK inhibited the muscarinic acetylcholine receptor-operated K+ current (I(K.ACh)) that was activated by the muscarinic agonist carbachol (1 microM) with an EC50 value of 0.57 nM. Both the increase in I(Ca) and the decrease in I(K.ACh) were blocked by HOE140, a selective bradykinin B2 receptor antagonist. 3. The BK-induced inhibition of I(K.ACh) was significantly attenuated by staurosporine and calphostin C, protein kinase C inhibitors. In addition, the I(K.ACh) inhibition by BK was also attenuated by the tyrosine kinase inhibitor genistein or tyrphostin but not by daidzein, an inactive analogue of genistein. However, neither protein kinase C inhibitor nor tyrosine kinase inhibitor affected the BK-induced increase in I(Ca). 4. In the presence and absence of muscarinic stimulation, BK prolonged the action potential recorded from the atrial cells in the current clamp mode. 5. We conclude that BK increases I(Ca) and decreases I(K.ACh) in atrial cells, resulting in positive inotropic and chronotropic responses in atrial preparations. Protein kinase C activation, and possibly tyrosine kinase activation, may be involved in the B2-receptor-mediated I(K.ACh) inhibition.

Action Potentials↗
PubMed1998

Pure red cell aplasia and myasthenia gravis with thymoma: a case report and review of the literature.

A case of pure red cell aplasia (PRCA), myasthenia gravis (MG) and thymoma is reported. A 70-year-old woman presented with severe anemia. She had been diagnosed as having MG 8 years earlier and her symptoms were adequately controlled with ambenonium chloride. When she visited our hospital, her hematocrit was 13.7% with a hemoglobin concentration of 4.7 g/dl and her reticulocyte counts were persistently abnormal at 0.1%. Although both direct and indirect Coombs' tests were positive, there was no evidence of hemolysis. Routine screening tests for other etiologies of anemia were negative. Serological tests for anti-DNA and anti-acetylcholine receptor antibodies gave positive results. A bone marrow examination revealed severe erythroid hypoplasia. PRCA was diagnosed and the patient was treated with periodic transfusions. A lateral view chest roentgenogram and a computed tomography scan of the thorax showed the presence of an anterior mediastinal mass which was suspected to be thymoma. The patient underwent thymothymectomy and the tumor was diagnosed as a thymoma. Although the patient received no treatment for MG and PRCA after surgery, her hematological test results rapidly improved and she was discharged from the hospital on the 29th postoperative day. At that time, her hematocrit was 33.2%, her hemoglobin concentration was 10.0 g/dl, her peripheral reticulocyte level was 1.8% and her left partial ptosis had improved. She is doing well, 9 months after surgery. For a patient to remain in remission without treatment for PRCA and MG after thymothymectomy is extremely rare.

Aged↗
PubMed1998

Tonic block of the sodium and calcium currents by ketamine in isolated guinea pig ventricular myocytes.

Effects of ketamine on the sodium (INa) and L-type calcium currents (ICa) were examined by using whole-cell patch clamp techniques in guinea pig single ventricular myocytes. The mode of action of ketamine was compared with those of quinidine, a sodium channel blocker, and verapamil, a calcium channel blocker. Ketamine (30-300 microM) inhibited both INa and ICa in a concentration-dependent manner. Quinidine (30 microM) and verapamil (0.1 microM) produced use-dependent depression of INa and ICa, respectively. The amplitude of INa elicited by the first depolarizing pulse after a long quiescent period was slightly decreased by quinidine. During a train of depolarizing pulse the current amplitude decreased gradually, and reached a steady state level in the quinidine-treated cell (use-dependent block, UDB). Verapamil produced a similar mode of inhibition of ICa, i.e., UDB. In contrast, ketamine produced significant decrease in INa and ICa elicited by the first depolarizing pulses and the decreases of both currents were not augmented during a train of depolarizing pulses. From these results, it can be concluded that ketamine produces tonic block of the cardiac sodium and calcium channels and the mode of inhibition is clearly different from UDB by quinidine and verapamil.

Animals↗
PubMed1997

Pirmenol inhibits muscarinic acetylcholine receptor-operated K+ current in the guinea pig heart.

We examined the effects of pirmenol and disopyramide on the muscarinic acetylcholine receptor-operated K+ current (I[K.ACh]) in atrial cells and on experimental atrial fibrillation in isolated guinea-pig hearts. In isolated atrial myocytes, both pirmenol and disopyramide concentration-dependently inhibited the I(K.ACh) induced by carbachol or intracellular loading of GTPgammaS. Their inhibitory effects on the carbachol-induced current were more potent than those on GTPgammaS-induced current, suggesting that these drugs inhibit I(K.ACh) mainly by blocking muscarinic receptors. In Langendorff-perfused hearts these drugs reversed the carbachol-induced decreases in effective refractory periods and atrial fibrillation threshold. These drugs may be useful for the prevention of vagally induced atrial fibrillation.

Action Potentials↗
PubMed1997

The first skull of Australopithecus boisei.

Australopithecus boisei was first described from a cranium recovered in 1959 from Olduvai Gorge, Tanzania. This and subsequent finds, mostly from Kenya's Turkana basin, resulted in its characterization as a specialized Australopithecus species with a hyper-robust masticatory apparatus. A distinct A. boisei facial morphology has been emphasized to differentiate robust Australopithecus lineages from East and South Africa. A preference for closed and/or wet habitats has been hypothesized. Here we report some new A. boisei specimens, including the taxon's first cranium and associated mandible, from Konso, Ethiopia. These fossils extend the known geographical range of A. boisei. They provide clear evidence for the coexistence of A. boisei and Homo erectus within a predominantly dry grassland environment. The A. boisei specimens from Konso demonstrate considerable morphological variation within the species. The unexpected combination of cranial and facial features of this skull cautions against the excessive taxonomic splitting of early hominids based on morphological detail documented in small and/or geographically restricted samples.

Animals↗
PubMed1997

Dual effects of extracellular ATP on the muscarinic acetylcholine receptor-operated K+ current in guinea-pig atrial cells.

Adenosine 5'-triphosphate (ATP) is stored in sympathetic and parasympathetic nerve terminals and co-released with norepinephrine and acetylcholine during nerve stimulation. In the heart in situ parasympathetic nerve is tonically stimulated and the activated muscarinic acetylcholine-receptor-operated K+ current (I(K,ACh)) plays an important role in the repolarization of the atrial action potential, the sinoatrial node automaticity and the atrioventricular conduction. In the present study, effects of extracellular ATP on the I(K,ACh) activated by carbachol or adenosine were examined in isolated guinea-pig atrial cells by use of the patch-clamp technique. ATP (10 microM) per se produced a transient activation of I(K,ACh) in atrial cells held at -40 mV. When I(K,ACh) was preactivated by 1 microM carbachol or 10 microM adenosine, ATP (1-100 microM) produced a transient increase followed by a sustained decrease of the current. These ATP-induced biphasic changes of I(K,ACh) were abolished by suramin (100 microM) or reactive blue-2 (30 microM), but not by theophylline (500 microM), indicating the involvement of P2 purinoceptors. ATP also enhanced and then partially reversed the action potential shortening induced by carbachol or adenosine in current-clamped atrial cells. Extracellular ATP did not increase but decreased the openings of the single K(ACh) channel that were recorded by use of a pipette solution containing 1 microM carbachol in the cell-attached mode. Thus, P2 purinoceptor stimulation produces dual effects of ATP on the pre-activated I(K,ACh) and may modulate the chronotropic and inotropic responses during autonomic nerve stimulation.

Adenosine Triphosphate↗
PubMed1997

Effect of monochlorohydrins of linoleic acid on guinea-pig cardiac papillary muscles.

The hydrogen peroxide (H2O2)-myeloperoxidase system can convert linoleic acid (LA) to monochlorohydrins. LA monochlorohydrins can also be produced when LA monoepoxides are subjected to low pH solutions. We chemically synthesized and purified LA monochlorohydrins and examined their effect on the developed tension of guinea-pig papillary muscles in vitro in terms of both concentration and the duration of exposure. A decrease in muscular tension was observed immediately after addition of LA monochlorohydrins at concentrations of 30, 100, and 300 microM. We also compared the effect of LA monochlorohydrins on muscle tension with those of LA monoepoxides.

Animals↗