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Biomedical subjects

A Kitabatake

Publications and source records attributed to A Kitabatake.

At least 19 recordsLinked to original sources
PubMed1996

Enhanced expression of beta-adrenergic receptor kinase 1 in the hearts of cardiomyopathic Syrian hamsters, BIO53.58.

We cloned an entire encoding sequence of beta-adrenergic receptor kinase 1 (beta ARK1) cDNA from the hearts of Syrian hamsters through reverse transcription and subsequent polymerase chain reaction. The cloned cDNA contained 2067 nucleotides coding 689 amino acids. The sequence had 95% homology to rat beta ARK1 and 90% homology to human homologue. Cardiomyopathic Syrian hamster, BIO53.58, has been used as a model animal of congestive heart failure. M-mode echocardiography confirmed that left ventricular contractility of 20-week-old BIO53.58 was markedly reduced. The expression of beta ARK1 mRNA in the hearts of BIO53.58 was significantly increased compared to control hamsters, F1b, suggesting that the enhanced beta ARK1 expression is acting as a negative feedback mechanism in order to maintain intracellular homeostasis against accelerated stimulation by catecholamines via phosphorylation of beta-adrenergic receptor.

Aging↗
PubMed1996

A new approach for evaluation of left ventricular diastolic function: spatial and temporal analysis of left ventricular filling flow propagation by color M-mode Doppler echocardiography.

OBJECTIVES: To evaluate left ventricular diastolic function and differentiate the pseudonormalized transmitral flow pattern from the normal pattern, the propagation of left ventricular early filling flow was assessed quantitatively using color M-mode Doppler echocardiography. BACKGROUND: Because the propagation of left ventricular early filling flow is disturbed in the left ventricle with impaired relaxation, quantification of such alterations should provide useful indexes for the evaluation of left ventricular diastolic function. METHODS: Study subjects were classified into three groups according to the ratio of early to late transmitral flow velocity (E/A ratio) and left ventricular ejection fraction: 29 subjects with an ejection fraction > or = 60% (control group); 34 with an ejection fraction < 60% and E/A ratio < 1 (group I); and 25 with ejection fraction < 60% and E/A ratio > or = 1 (group II). The propagation of peak early filling flow was visualized by changing the first aliasing limit of the color Doppler signals. The rate of propagation of peak early filling flow velocity was defined as the distance/time ratio between two sampling points: the point of the maximal velocity around the mitral orifice and the point in the mid-left ventricle at which the velocity decreased to 70% of its initial value. High fidelity manometer-tipped measurement was performed in 40 randomly selected subjects. RESULTS: The rate of propagation decreased in groups I and II compared with that in the control group (33.8 +/- 13.8 [mean +/- SD] and 30.0 +/- 8.6 vs. 74.3 +/- 17.4 cm/s, p < 0.001, respectively) and correlated inversely with the time constant of left ventricular isovolumetric relaxation and the minimal first derivative of left ventricular pressure (peak negative dP/dt) (r = 0.82 and r = 0.72, respectively). CONCLUSIONS: Spatial and temporal analysis of filling flow propagation by color M-mode Doppler echocardiography was free of pseudonormalization and correlated well with the invasive variables of left ventricular relaxation.

Blood Flow Velocity↗
PubMed1995

Purification method for alpha-1-acid glycoprotein with subsequent high-performance liquid chromatographic determination of monosaccharides in plasma of healthy subjects and patients with renal insufficiency.

A simple purification method for human plasma alpha-1-acid glycoprotein (AAG) using an ion-exchange and hydroxyapatite column was developed. The recovery of the method was found to be high. We also improved a determination method for N-acetylneuraminic acid and monosaccharides in the carbohydrate moiety of AAG by using an ion-exchange column and pulse-amperometric detection. By this method, a composition analysis of the carbohydrate moiety of AAG (N-acetylneuraminic acid, fucose, N-acetyl glucosamine, galactose and mannose) was possible with 1.0 ml of plasma. We compared these carbohydrate concentrations in the AAG of patients with renal insufficiency with those of healthy subjects. In the AAG of the patients, the concentrations of N-acetylglucosamine, galactose and mannose were significantly higher than those in the AAG of the healthy subjects.

Acetylglucosamine↗
PubMed1995

Cytosolic localization of beta 3-subunit of heterotrimeric GTP binding protein in rat hearts.

The expression of three different subtypes of GTP binding protein beta-subunits (beta 1, beta 2 and beta 3) was examined in rat hearts at both mRNA and protein levels. Among three subtypes, beta 3 mRNA was more abundant in ventricles while beta 1 and beta 2 mRNAs were expressed ubiquitously among ventricles, atria and aortas. The immunodetectable beta 1- and beta 3-proteins were predominantly found in the cytosolic fraction of rat ventricles. In this study, we demonstrate ventricle-specific expression of beta 3-subunit and localization of G protein beta 3-subunit in the cytosol of rat hearts. This unusual cytosolic localization of G protein beta 3-subunit might indicate subtype-specific function of G protein beta (gamma)-subunits in rat hearts.

Animals↗
PubMed1995

Alpha-1-acid glycoprotein concentration and the protein binding of disopyramide in healthy subjects.

Age- and gender-related changes in serum alpha 1-acid glycoprotein (AAG) concentration and the serum protein binding of disopyramide were examined after intensive medical examination. Based on the clinical chemistry tests over 51 points, 245 subjects were diagnosed as healthy and 71 subjects (22.5%) revealed an abnormal value for at least one item. In the healthy subjects, serum AAG concentration in men was significantly higher than in women (men, 0.78 +/- 0.18 mg/mL, mean +/- SD; women, 0.67 +/- 0.16 mg/mL). In contrast, there were no significant differences in the AAG concentration between age groups for men and women and in the unbound fraction of disopyramide. Gender changes AAG concentration. Age, however, does not change AAG concentration and the protein binding of the basic drug.

Adolescent↗
PubMed1995

Abrupt augmentation of ST segment elevation associated with successful reperfusion: a sign of diminished myocardial salvage.

To investigate the significance of abrupt augmentation of ST segment elevation immediately after reperfusion, 36 patients with an initial acute anterior myocardial infarction successfully treated with thrombolysis were studied. Immediately after reperfusion was performed, 17 (47%) patients showed abrupt augmentation of ST segment elevation of anterior area (E group), and 19 (53%) patients did not (N group). The time to reperfusion was not significantly different between the two groups. In the E group the peak level of creatine kinase MB isozyme was higher (p < 0.05) than in the N group. The left ventricular ejection fraction (EF) did not increase in the E group from acute to chronic phase. However, in the N group EF increased significantly. The difference in EF in the chronic phase was significant between the two groups (p < 0.05). The infarcted regional wall motion (RWM) did not increase in the E group, whereas in the N group it increased markedly (p < 0.05). In addition, the infarcted RWM in the chronic phase was worse in the E group than in the N group (p < 0.05). Abrupt augmentation of ST segment elevation associated with successful reperfusion appears to reflect diminished myocardial salvage.

Aged↗
PubMed1995

Angiotensin-converting enzyme gene polymorphism in Japanese patients with hypertrophic cardiomyopathy.

To examine the contribution of the angiotensin-converting enzyme (ACE) gene to hypertrophic cardiomyopathy (HCM), we determined the ACE insertion/deletion (I/D) polymorphism in 80 patients with HCM and 88 of their unaffected siblings and children. Patients were divided into familial or solitary HCM (FHCM or SHCM) groups with or without affected family members. Genotypes were identified by the polymerase chain reaction (PCR) with oligonucleotide primers flanking the polymorphic region in intron 16 of the ACE gene to amplify template DNA prepared from peripheral leukocytes. D-allele frequencies were 0.38 in all subjects, 0.42 in patients with HCM, and 0.35 in relatives (p < 0.05). The probability ratios were 1.98, 1.46, and 2.97 in patients with HCM, FHCM, and SHCM, respectively. The D allele frequency was higher in SHCM than in FHCM (p < 0.05). The findings suggest that HCM, especially in solitary cases, is partially determined by genetic disposition. Findings imply that the ACE D allele is one of the genetic contributing factors associated with cardiac hypertrophy in HCM.

Aged↗
PubMed1995

Renin-angiotensin system in failing heart.

Extrahepatic synthesis and localization of angiotensinogen have been described in animals, thus establishing the tissue renin-angiotensin system. We examined angiotensinogen messenger RNA synthesis by northern blotting. It was detected not only in the liver, but also in both the atrial and ventricular heart tissues, suggesting that angiotensinogen is synthesized in the human heart. Immunohistochemical studies using a specific antibody to angiotensinogen revealed a stronger reaction in the endocardial layer of the human left ventricle, than in the epicardial layer, and intense immunoreactivity in the conduction system and right atrium. Furthermore, our experiments revealed a widespread immunopositive reaction for angiotensinogen in the left ventricle of diseased hearts. We examined the participation of the collagen in the occurrence and progression of cardiomyopathy. The acetic acid solubility of collagen and reducible crosslink decreased in cardiomyopathic hamsters as the fibrosis progressed, but was unchanged in controls. These findings indicate that in the early phase of cardiomyopathy the extracellular matrix of the myocardium is similar to immature tissues. In the later phase, the matrix resembles that of hard tissues, and is insoluble. Furthermore, we examined the relationship between angiotensin II and collagen synthesis. Basal collagen synthesis in cardiac fibroblasts from spontaneously hypertensive rats was 1.6-fold greater than that in Wistar-Kyoto rats. The responsiveness of collagen production to Ang II was significantly enhanced in SHR. This effect was angiotensin receptor-specific, because it was blocked by the competitive inhibitor. These results indicate angiotensin II may play an important role in collagen accumulation in hypertensive cardiac hypertrophy.

Angiotensin II↗
PubMed1995

Changes in the binding capacity of alpha-1-acid glycoprotein in patients with renal insufficiency.

The elevation of alpha-1-acid glycoprotein (AAG) concentration and the binding characteristics of disopyramide (DP) to AAG in patients with renal insufficiency were investigated. The serum AAG concentration and protein binding of DP in patients were significantly greater than those in healthy subjects. However, in both the serum and the purified AAG, Scatchard analysis showed that the number of binding sites per molecule of AAG in patients was significantly lower than that in healthy subjects, although there was no difference in the dissociation constant (Kd). These results suggest that the AAG induced in renal insufficiency is qualitatively different from normal AAG. Moreover, the change of the unbound DP fraction when DP concentration was increased was larger in the patients than in the healthy controls. Therefore, monitoring of the unbound DP would be important for therapeutic drug monitoring in patients with renal insufficiency.

Adult↗
PubMed1995

Thapsigargin- and cyclopiazonic acid-induced endothelium-dependent hyperpolarization in rat mesenteric artery.

1. The present study was designed to determine whether putative, selective inhibitors of the Ca(2+)-pump ATPase of endoplasmic reticulum, thapsigargin (TSG) and cyclopiazonic acid (CPA), induce endothelium-dependent hyperpolarization in the rat isolated mesenteric artery. The membrane potentials of smooth muscle cells of main superior mesenteric arteries were measured by the microelectrode technique. 2. In tissues with endothelium, TSG (10(-8)-10(-5) M) caused sustained hyperpolarization in a concentration-dependent manner. In tissues without endothelium, TSG did not cause any change in membrane potential. CPA (10(-5) M) also hyperpolarized the smooth muscle membrane, an effect that was endothelium-dependent and long-lasting. 3. The hyperpolarizing responses to these agents were not affected by indomethacin or NG-nitro-L-arginine (L-NOARG). 4. In Ca(2+)-free medium, neither TSG nor CPA elicited hyperpolarization, in contrast to acetylcholine which generated a transient hyperpolarizing response. 5. In rings of mesenteric artery precontracted with phenylephrine, TSG and CPA produced endothelium-dependent relaxations. L-NOARG significantly inhibited the relaxations to these agents, but about 40-60% of the total relaxation was resistant to L-NOARG. The L-NOARG-resistant relaxations were abolished by potassium depolarization. 6. These results indicate that TSG and CPA can cause endothelium-dependent hyperpolarization in rat mesenteric artery possibly by releasing endothelium-derived hyperpolarizing factor and that membrane hyperpolarization can contribute to the endothelium-dependent relaxations to these agents. The mechanism of hyperpolarization may be related to increased Ca2+ influx into endothelial cells triggered by depletion of intracellular Ca2+ stores due to inhibition of endoplasmic reticulum Ca(2+)-pump ATPase activity.

Acetylcholine↗
PubMed1995

Evidence for selective inhibition by lysophosphatidylcholine of acetylcholine-induced endothelium-dependent hyperpolarization and relaxation in rat mesenteric artery.

The effects of lysophosphatidylcholine (LPC) on acetylcholine-induced hyperpolarization and relaxation were examined in rat mesenteric arteries. LPC (3-10 microM) reversibly inhibited endothelium-dependent hyperpolarization by acetylcholine in a concentration-dependent manner. LPC (10 microM) inhibited only partially endothelium-dependent relaxation by acetylcholine. However, acetylcholine-induced relaxation obtained in the presence of 100 microM NG-nitro-L-arginine was almost completely eliminated by 10 microM LPC. These results indicate that LPC inhibits hyperpolarization and relaxation due to endothelium-derived hyperpolarizing factor more specifically than the relaxation due to endothelium-derived nitric oxide.

Acetylcholine↗
PubMed1995

Regression of left ventricular hypertrophy prevents ischemia-induced lethal arrhythmias. Beneficial effect of angiotensin II blockade.

To evaluate the preventive effect of regression of left ventricular hypertrophy (LVH) on sudden cardiac death (SCD), the incidence of ventricular tachycardia or ventricular fibrillation (VT/Vf) after left coronary artery occlusion in Langendorff preparations was studied in the following five groups: (1) spontaneously hypertensive rats (SHR) without treatment (SHR-N), (2) SHR treated with captopril (SHR-C), (3) SHR treated with the angiotensin II receptor antagonist TCV-116 (SHR-A), (4) SHR treated with hydralazine (SHR-H), and (5) Wistar-Kyoto (WKY) rats. Although blood pressure was equally lowered in all treated groups, SHR-C and SHR-A but not SHR-H showed regression of LVH. The incidence of VT/Vf was 5% in WKY rats, 63% in SHR-N (P < .005 versus WKY rats), 0% in SHR-C, 10% in SHR-A, and 45% in SHR-H (P < .05 versus WKY rats). Further evaluation of the effect of TCV-116 revealed that SHR treated with a low dose of TCV-116 (1 mg/kg per day) showed a decrease in left ventricular mass with only a little decrease in blood pressure and that the incidence of VT/Vf was reduced in association with the degree of regression of LVH. Electrophysiological study using microelectrode techniques revealed that in the LVH groups (SHR-N and SHR-H), the action potential duration (APD) of the left ventricular papillary muscle was more prolonged than in WKY rats, whereas APD shortened to a greater extent during superfusion with a hypoxia/no-glucose solution. APD showed no difference in the regression groups (SHR-C and SHR-A) compared with the WKY group.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1995

A case of familial ventricular tachycardia.

Ventricular tachycardia was noted in 4 members of the same family. One showed diffuse hypokinesis of the left ventricle by echocardiography and left ventriculography, 2 showed progressive left ventricular dysfunction and 1 showed regional perfusion defects of the left ventricle shown by thallium scintigraphy. One patient was diagnosed as dilated cardiomyopathy. Although no definitive cause of the left ventricular disturbance was identified in the 3 other patients, they may have all been dilated cardiomyopathy.

Cardiomyopathy, Dilated↗
PubMed1995

Effect of transforming growth factor beta-1 on the intracellular calcium in cardiac fibroblasts.

We attempted to determine the effects of transforming growth factor beta-1 on intracellular Ca2+ concentration changes in the presence of isoproterenol in cardiac fibroblasts. Transforming growth factor beta-1 inhibited the increase of intracellular Ca2+ concentration in the presence of isoproterenol in fibroblasts. It also inhibited the production of cyclic-AMP in fibroblasts in the presence of isoproterenol. Islet-activating protein did not block these reactions of transforming growth factor beta-1. Forskolin did not affect the intracellular calcium concentration change resulting from treatment with transforming growth factor beta-1. Binding of [3H]CGP-12177 was decreased to 47% of control preincubated for 24 hours with transforming growth factor beta-1 in fibroblasts. Scatchard plots suggested a decrease in beta-adrenergic receptor number without specific change in receptor affinity. These results suggested that transforming growth factor beta-1 modulates the signal transduction through beta-adrenergic receptor and intracellular Ca2+ concentration by regulating the number of receptors in fibroblasts.

Animals↗
PubMed1995

[Pathophysiology and treatment of congestive heart failure--recently advanced strategy for heart failure].

The principle functions of the heart are to accept blood from the systemic and the pulmonary circulatory system, pump and deliver it to the whole body tissues and lungs. The term "heart failure" is used to describe the pathophysiological state in which an abnormality of cardiac function is responsible for failure of the heart to pump blood at a rate commensurate with the requirements of the metabolizing tissues, or to do so only from an elevated filling pressure. Thus, for a long period, heart failure has been thought of as a mechanical disorder of the heart and vessels, and its treatment has been based on improving impaired cardiac function and hemodynamic disorder. Recently multi-center, randomized placebo-controlled survival trials revealed that pure inotropic agents such as phosphodiesterase inhibitors succeeded in mechanical improvement, yet not only failed to prolong the patient's life, but also increased mortality. A number of neurohumoral mechanisms, which are activated in heart failure, were thought to be compensatory ones. However, survival trials demonstrated that two types of drug interfering with the renin-angiotensin system and the sympathetic nervous system reduced mortality. Those drugs are angiotensin-converting enzyme (ACE) inhibitors and beta blockers. ACE inhibitors reduce the direct effects of angiotensin II on myocardial cells, which may lead to cell necrosis, imbalanced remodeling through fibrosis, and attenuate the progressive ventricular dilatation. Local tissue renin-angiotensin system may be potentially important in regulating the angiotensin II production in both heart and vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1995

Effects of BQ-485, a selective ETA antagonist, on endothelin-mediated vasomotion in rat coronary vascular beds.

The effects of BQ-485, a selective endothelin (ET)-A receptor antagonist, on the vasomotion induced by a low dose of ET were investigated. In the isolated rat heart perfused with Krebs-Henseleit solution at a constant flow, intracoronary bolus injection of ET-1 or ET-3 (10 pmol) elicited a rapid transient decrease, followed by a slight sustained increase, in the coronary perfusion pressure (CPP). The decrease in CPP induced by ET-1 was similar in magnitude to (approximately 30%) but shorter in duration than that induced by ET-3. Pretreatment of the heart with saponin (30 micrograms/ml) to denude the coronary endothelium abolished the decrease and markedly enhanced the increase in CPP induced by ETs, indicating that the vasorelaxing action of ETs is endothelium-dependent. The selective ETA receptor antagonist BQ-485 (1 microM) significantly prolonged the duration of the ET-1-induced decrease in CPP, made the vasodilatation by ET-1 indistinguishable from that by ET-3, and eliminated the subsequent increase in CPP. In the saponin-treated heart, BQ-485 also eliminated the ET-1-mediated increase in CPP. These findings suggest that, in rat coronary vascular beds, a low dose of ET-1 elicits vasoconstriction and endothelium-dependent vasodilatation through the ETA receptor on the vascular smooth muscle and presumably the ETB receptor on the endothelium, respectively. Furthermore, it is expected that selective ETA receptor antagonists, including BQ-485, may be able to protect the heart against ET-1-induced coronary spasm in situations, such as hyperlipidemia or artherosclerosis, in which the release and/or function of endothelium-derived vasorelaxing substances is impaired.

Animals↗
PubMed1994

Distribution of angiotensinogen in diseased human hearts.

Extrahepatic synthesis and localization of angiotensinogen (ATN) have been described in animals, thus establishing the tissue renin-angiotensin (RA) system. However, there had been no reports of tissue RA systems in human organs, including the heart. In earlier, we have reported the possibility of ATN synthesis in the human heart using ribonuclease protection assay system. ATN mRNA was detected not only in the liver, but also in both the atrial and ventricular heart tissues, suggesting that ATN is synthesized in the human heart. In this report, we looked for the distribution of ATN in diseased human heart. Northern blot hybridization of cDNA with total RNA extracted from human liver, brain, kidney, atrial and ventricular tissues revealed that ATN mRNA exists in cardiac ventricule. Immunohistochemical studies using a specific antibody to ATN revealed a stronger reaction in the endocardial layer of the human left ventricle, than in the epicardial layer, and intense immunoreactivity in the conduction system and right atrium. This distribution pattern was similar to that of human atrial natriuretic peptide (hANP), which functions a smooth muscle relaxant. Double immunostaining of ATN and hANP demonstrated that all myocytes in the right atrium had immunopositive reactions to ATN, hANP or both of ATN and hANP. Double immunoelectron staining enabled us to show more detailed localization of ATN and hANP; hANP only existed in the specific granules and ATN existed in the myofibril, but not in the granule. Furthermore, our experiments provide evidence of ATN in healthy human hearts and also reveal a widespread immunopositive reaction for ATN in the left ventricle of diseased hearts.

Angiotensinogen↗