Biomedical subjects
Publications and source records attributed to H Narita.
The cDNA for the rat erythropoietin (EPO) has been cloned and sequenced. The deduced amino acid sequence consists of 166 amino acid residues, which has a 79% and 95% homology with human and mouse EPOs, respectively. Many short stretches, highly conserved in primate and rodent EPOs, are found in the 3'-noncoding region when insertions and deletions are taken into consideration.
We attempted to evaluate left ventricular performance from the shortest distance between the mitral leaflets coaptation and the interventricular septum at end-systole (MVC-IVS distance). The subjects were 37 patients with coronary artery disease (CAD) with prior myocardial infarction (MI), 8 with CAD without prior MI, 22 with atypical chest pain, and 4 with aortic regurgitation. The MVC-IVS distance was measured on a two-dimensional echocardiogram obtained from the parasternal or apical long-axis view and frozen at end-systole. Left ventricular end-systolic volume and end-diastolic volume were obtained by left ventriculography, and the left ventricular ejection fraction was calculated. A significant positive correlation was observed between the MVC-IVS distance and the end-systolic volume (r = 0.83, p less than 0.001); a close correlation was observed between the MVC-IVS distance end-systolic volume and ejection fraction by monoexponential fitting (r = -0.91, p less than 0.001). Thus, a significant negative correlation was observed between the MVC-IVS distance and the left ventricular ejection fraction (LVEF) (r = -0.83, p less than 0.001). An MVC-IVS distance of greater than or equal to 30 mm suggests diagnosis of left ventricular dysfunction (LVEF less than 50%) with high sensitivity (94.4%) and specificity (90.6%), while a value less than 30 mm suggests that the left ventricular performance is likely to be normal. Thus one can easily evaluate the left ventricular performance noninvasively using this new index.
Muir-Torre syndrome is characterized by multiple sebaceous tumors, various internal malignancies and an autosomal dominant inheritance. We herein report a typical case. The patient was a 69-year-old man with sebaceous adenomas, a keratoacanthoma, and actinic keratosis in addition to carcinomas of the prostate, colon, duodenum, and larynx. His family members also suffered from multiple cancers.
1. The pharmacological actions of T-0509, a 3-hydroxy derivative of denopamine, were studied in various guinea-pig tissues; these effects were compared with those of isoprenaline, denopamine and xamoterol. 2. The intrinsic activities of the positive inotropic actions of T-0509, denopamine and xamoterol compared with isoprenaline (= 100%) in the papillary muscle were 99%, 83% and 28%, respectively, while their relative potencies (EC50 agonist EC50 isoprenaline) were 0.23, 33 and 1.4, respectively. The intrinsic activities of T-0509, denopamine and xamoterol as positive chronotropic agents in the right atria were 98%, 69% and 48%, respectively, and their equipotent concentrations (isoprenaline = 1) were 0.24, 50 and 4, respectively. 3. The positive chronotropic actions of T-0509 and denopamine were antagonized by bisoprolol (3 x 10(-8) M), but not by ICI 118,551 (3 x 10(-8) M). 4. The intrinsic activity of T-0509 in histamine-contracted tracheae was similar to that of isoprenaline, but its equipotent concentration was 38; the effects of both agents were antagonized by ICI 118,551 (3 x 10(-8) M), but not by bisoprolol (3 x 10(-8) M). Denopamine and xamoterol did not show any agonist activity on guinea-pig trachea. 5. Denopamine and xamoterol antagonized the positive chronotropic (pA2, denopamine: 6.98, xamoterol: 7.75) and tracheal relaxant (pA2, denopamine: 5.39, xamoterol: 6.25) effects of isoprenaline. 6. Isoprenaline, T-0509 and denopamine, but not xamoterol, contracted the guinea-pig aorta in a decreasing order in the presence of propranolol (10(-6) M).7. Based on the above studies, T-0509 appears to be a highly selective betaI-adrenoceptor agonist with full agonist properties, while denopamine and xamoterol appear to be selective, but partial betaI-adrenoceptor agonists.
The authors investigated the effects of alterations in heart rate, contractility, and loading conditions on a newly defined systolic time interval, the Q-V peak, in 46 anesthetized dogs. The Q-V peak was measured as the time from the beginning of the electrocardiographic Q wave to the moment at which the blood flow rate reached its peak in the ascending aorta as determined with an electromagnetic flowmeter. The Q-V peak did not change significantly as the heart rate was varied by atrial pacing between 70 and 110 beats/minute. The Q-V peak shortened when the contractility was augmented with dobutamine (p = 0.0001) and was prolonged when it was depressed with propranolol (p = 0.0001). However, the Q-V peak did not change significantly when the left ventricular end-diastolic pressure or the mean aortic blood pressure was increased to 130% or decreased to 70% of the baseline values. These findings suggest that one may also evaluate left ventricular performance by measuring the time to systole, which the authors define as the Q-V peak.
The hemodynamic effects of imidapril, a novel nonsulfhydryl angiotensin-converting enzyme inhibitor, were examined in anesthetized dogs by the intravenous injection of its active metabolite 6366A ((4S)-3-((2S)-2-[N-((1S)-1-carboxy-3- phenylpropyl)amino]propionyl)-1-methyl-2-oxoimidazolidine-4-carboxylic acid, CAS 89371-44-8) and were compared to those of enalaprilat. 6366A (1-100 micrograms/kg) reduced the blood pressure and total peripheral resistance in a dose-dependent manner, while causing no marked changes in heart rate, LV dp/dtmax, and pulmonary arterial pressure. The cardiac output and stroke volume were slightly increased. Blood flow in the common carotid artery, the vertebral artery, and the femoral artery was reduced or tended to decrease, while the superior mesenteric arterial blood flow was increased. These effects were similar to those of enalaprilat. 6366A did not inhibit the pressor response of angiotensin II, but markedly inhibited that of angiotensin I, and the effects of 6366A on regional blood flow were opposite to those of angiotensin II. Thus, 6366A appears to produce its hemodynamic effects by angiotensin converting enzyme inhibition, as does enalaprilat. 6366A also tended to decrease myocardial oxygen consumption. These results suggested that the hemodynamic effects of imidapril on the heart and on regional blood flow are similar to those of enalapril.
We tried to differentiate "pseudonormal" from normal transmitral flow velocity waveforms by evaluating isovolumic relaxation times (IRT) in patients with old myocardial infarction. Forty-three healthy volunteers and 54 patients with old myocardial infarction were studied. Transmitral flow velocity waveforms were obtained by pulsed Doppler echocardiography with a phonocardiogram. Early peak filling velocity (E) and late peak filling velocity (A) were measured, and the E/A ratio was calculated. The time from the beginning of the IIA sound to the onset of transmitral flow was defined as IRT. We observed a significantly positive correlation between IRT and age in the healthy volunteers (r = 0.56, p < 0.01). Based on these results, we selected age-matched healthy subjects (control group, n = 23) older than 35 years from the healthy volunteers. We divided the patients into 2 groups; those with a mean pulmonary capillary wedge pressure (mPCWP) of > or = 16 mmHg (H group, n = 9) and those with an mPCWP of < 16 mmHg (L group, n = 45). E, E/A, IRT, mean blood pressure (mBP), and heart rate were compared among the H, L, and control groups. There was no significant difference in mBP or heart rate between these 3 groups. Both E and E/A were significantly lower in the L group than in the control group (p < 0.05), however, no significant difference was observed in E and E/A between the H and control groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Left ventricular performance was evaluated in 51 patients with acute myocardial infarction and angina pectoris using parameters derived from the flow velocity waveform at the ascending aorta. Flow velocity waveforms were obtained from the suprasternal notch by continuous-wave Doppler echocardiography and were recorded on a line-scan recorder at a paper speed of 100 mm/sec with lead II ECG. The peak flow velocity and the systolic time interval from the beginning of ECG Q wave to the peak flow velocity (Q-V peak interval) were measured. Relationships were investigated between these parameters and the left ventricular ejection fraction (LVEF) obtained from multigated equilibrium blood pool imaging with 99mTc-pertechnetate. The peak flow velocity did not correlate with LVEF (r = 0.27). However, a highly significant negative correlation was observed between the systolic time interval Q-V peak and LVEF (r = -0.84, p less than 0.001). The regression equation was LVEF = -0.46 X (Q-V peak) + 142. We conclude that left ventricular performance can be evaluated in patients with coronary artery disease at the bedside using the Q-V peak interval measured from simultaneous recording of the velocity waveform at the ascending aorta and the ECG.
We evaluated relationships between pulsed Doppler echocardiographic (PDE) parameters of flow velocity profiles across the mitral orifice and left ventriculographic (LVG) parameters of left ventricular volume changes. Subjects consisted of 19 patients with coronary artery disease and 12 patients with chest pain syndrome. Peak flow velocities at the rapid filling (E) and atrial contraction (A) were measured by PDE. Time constant of left ventricular relaxation (T), left ventricular minimum pressure (LVPmin), LV end-diastolic pressure (LVEDP) and pulmonary capillary wedge V wave pressure (PCW-V) were measured during cardiac catheterization. From the analysis of LVG, the rapid filling fraction (RFF), and the atrial filling fraction (AFF) were obtained. The left ventricular chamber stiffness (K) was identified by the analysis of the pressure-volume relationship of the left ventricle. We investigated the relationship between A/E and AFF/RFF by univariate linear regression analysis. We then performed stepwise multivariate linear regression analysis to predict E, A, A/E, RFF, AFF and AFF/RFF by the variables of left ventricular filling, i.e., T, LVPmin, LVEDP, PCW-V, K, heart rate (at the examination of PDE or LVG), mean arterial blood pressure (at PDE or LVG) and age. The A/E correlated significantly with AFF/RFF (r = 0.50, p < 0.01). The results of the multivariate linear regression analyses were as follows: [sequence: see text] The correlation of A/E and AFF/RFF were explained by some variables, except the variable T. The results of uni- and multivariate linear regression analyses showed that factors affecting the flow velocity profile across the mitral orifice did not account for the left ventricular volume changes. We also observed that, even in subjects with coronary heart disease, aging is a main factor that influences peak flow velocity at atrial contraction (A).
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We evaluated the pharmacologic action of clentiazem, a new diltiazem derivative, on isolated human coronary artery and right ventricular trabeculae. In addition to its Ca2+ blocking action, clentiazem demonstrated both vasorelaxing and negative inotropic actions, similar to our reference Ca2+ antagonists. The coronary vasorelaxing action of clentiazem on the tonic KCl contraction (EC50 = 2.21 x 10(-7) M) was 3.1 times more potent than diltiazem (EC50 = 6.94 x 10(-7) M) and 28.8 times less potent than nifedipine (EC50 = 7.67 x 10(-9) M). The negative inotropic action of clentiazem (IC50 = 8.78 x 10(-6) M) was similar to diltiazem (IC50 = 7.18 x 10(-6) M) and was 21.1 times less potent than nifedipine (IC50 = 3.98 x 10(-7) M). Selectivity ratios, comparing the effectiveness in cardiac muscle to coronary artery, were nifedipine (51.9) greater than clentiazem (39.7) greater than diltiazem (10.3), when calculated from the EC50 and the IC50, and clentiazem (24.2) greater than nifedipine (15.9) greater than diltiazem (9.3), when calculated from the EC20 and the IC20. In conclusion, clentiazem is a Ca2+ antagonist and demonstrates comparable vasoselectivity to the 1,4-dihydropyridine derivative, nifedipine. Moreover, it has longer lasting action than diltiazem.
We evaluated the pharmacologic action of clentiazem, a newly synthesized diltiazem derivative, on isolated rabbit aorta and myocardium. In addition to its Ca2+ blocking action, clentiazem demonstrated both vasorelaxing and negative inotropic actions similar to diltiazem. The vasorelaxant action of clentiazem on the tonic phase of KCl-induced contraction (EC50 = 6.13 x 10(-8) M) was 4.5 times more potent than diltiazem (EC50 = 2.77 x 10(-7) M). However, the negative inotropic action of clentiazem (IC50 = 4.34 x 10(-5) M) was similar to diltiazem (IC50 = 3.94 x 10(-5) M). Selectivity ratios, comparing the effectiveness in cardiac muscle with aorta, were clentiazem (708) greater than diltiazem (142). In conclusion, clentiazem is a Ca2+ antagonist and demonstrates greater vasoselectivity than diltiazem. It also has a longer lasting action than diltiazem.
Two types of cytosolic phospholipase C specific for phosphoinositides were purified from human platelets. The molecular masses of the purified enzymes were 440 and 290 kDa. These enzymes were concluded to be respectively a trimer and a dimer of homologous 146 kDa polypeptides. The 146 kDa polypeptide may be an immunologically novel isozyme among the 140-150 kDa PLC isozymes. Both enzymes hydrolyzed phosphatidylinositol and phosphatidylinositol 4,5-bisphosphate in a Ca2(+)-dependent manner.
A case of pleomorphic adenoma in the upper lip is reported. A 61-year-old male had a tumor at the left side of the upper lip for 8 years. The tumor was surgically excised without recurrence. Histopathologically, the tumor was a typical pleomorphic adenoma with keratinization and glandular differentiation of tumor cells and fibroblastic, mucinous, hyalinized, and cartilagenous stroma.
Since azido derivatives of 1,5-benzothiazepine Ca antagonist available for photoaffinity labeling are required for further studies of voltage-sensitive Ca channels, we synthesized 3-(p-azidobenzoyloxydeacetyl)- and 3-(4-azidobutyryloxydeacetyl)-diltiazem, and studied their pharmacological properties. Both azido compounds showed similar relaxing actions to diltiazem in K(+)-depolarized dog arteries. They also showed a similar increasing action to diltiazem, but less potent, on the coronary and vertebral blood flow in the anesthetized dog. Moreover, their negative inotropic effects in the guinea pig papillary muscle were similar to or slightly more potent than that of diltiazem under physiological conditions, but were less potent when studied in K+ depolarizing solution. A radioligand binding study in rat skeletal muscle microsomes revealed that the azido derivatives had similar properties to diltiazem, but the nonspecific binding of 3-(p-azidobenzoyloxydeacetyl)-diltiazem was too high to allow estimation of its KD and Bmax values. In conclusion, we synthesized azido derivatives of diltiazem which were considered to share a common binding site on the voltage-dependent Ca channel with diltiazem in skeletal muscle microsomes and in vascular smooth muscle.
Left ventricular function was evaluated using parameters derived from the flow velocity waveforms at the ascending aorta as obtained at the suprasternal notch by continuous-wave Doppler echocardiography in 39 patients; 12 with chest pain but without coronary stenosis, eight with angina pectoris; and 19 with myocardial infarction. Peak flow velocity and the time interval from the beginning of the Q wave of lead II of the ECG to peak flow velocity (Q-V peak) correlated with specific invasive hemodynamic parameters, such as max dp/dt and (max dp/dt)/IP (IP: total left ventricular pressure at the same instant) during isometric contraction of the left ventricle measured with a catheter tip manometer, and left ventricular ejection fraction (LVEF) obtained by bi-plane cineangiography (using the area-length method). There was no correlation between the peak flow velocity and the invasive hemodynamic parameters. However, significant negative correlations were observed between the Q-V peak time and max dp/dt, with r = 0.40 (p less than 0.05), and between the Q-V peak time and (max dp/dt)/IP with r = -0.61 (p less than 0.01). A negative correlation was obtained between the Q-V peak time and LVEF (r = -0.75, p less than 0.01). The regression equation was LVEF = -0.67 x (Q-V peak) + 176. To compare the effectiveness for predicting LVEF between the Q-V peak and the established systolic time intervals as PEP and PEP/ET, these time intervals were measured from flow velocity waveforms invasively obtained with a catheter-type electromagnetic flowmeter inserted into the ascending aorta in 14 patients selected from the original subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Pharmacokinetic and clinical studies on aztreonam (AZT) in pediatric surgery were performed and results obtained are summarized below. 1. Plasma and urinary levels of AZT were measured in 6 neonate patients following drip-infusion for 1 hour of AZT (dose of AZT: 20 mg/kg). Plasma levels reached their peak (42.3-50.4 micrograms/ml) at the end of infusion or in 1 hour thereafter except in case 2. In case 2, plasma level reached its peak (36.6 micrograms/ml) at 2 hours after the end of infusion. Plasma levels of AZT decreased rapidly after reaching their peaks, and plasma half-lives (T 1/2) were 1.85-2.84 hours. Urinary recovery rates were 15.7-65.3%. 2. Bile levels of AZT were determined in 8 patients with biliary atresia following 1 hour drip-infusion of AZT (dose of AZT: 20 mg/kg for 4 patients, 40 mg/kg for the other 4 patients). In the 20 mg/kg group, peak levels of AZT in bile were noted 2 hours after the end of infusion, and they were 3.7-7.1 micrograms/ml. Recovery rates in bile in the first 6 hours after the end of infusion were 0.34-0.9%. In the 40 mg/kg group, peak levels of AZT in bile were found at 2 hours and 2-4 hours after the end of infusion, and they were 4.9-8.8 micrograms/ml. Recovery rates in bile in the first 6 hours after the end of infusion were 0.03-0.33%. 3. AZT and ampicillin were administered to 6 patients as prophylaxis against postoperative infections. Another patient with postoperative cholangitis was given AZT alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Familial odontogenic keratocysts are described in this report. The Case 1 patient, who has 3 sisters, developed odontogenic keratocysts. The 2 younger sisters (Cases 2 and 3) also had odontogenic keratocysts, although the elder sister did not have any odontogenic cysts. The father of the patients had a history of removal of a jaw cyst, and the mother was found later to have malignant ameloblastoma. Besides the odontogenic keratocysts, the Case 1 patient had basal cell nevus, prominent frontal process, and ocular hypertelorism; the Case 2 patient had prominent frontal process; the Case 3 patient had prominent frontal process, ocular hypertelorism, and squint. All 3 sisters are suspected of being patients with the basal cell nevus syndrome. The Japanese dental literature concerning the basal cell nevus syndrome is reviewed.