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Biomedical subjects

M Inada

Publications and source records attributed to M Inada.

At least 55 records · Page 3Linked to original sources

Weight carrying effects on treadmill exercise response in persons without heart disease.

To evaluate the effect of weight carrying on dynamic exercise response, 12 normal subjects were studied during treadmill exercise using ear densitography in two ways: (1) no weight, (2) 10 kg weight in one hand. Although there were no significant differences in diastolic time (DT), tension-time index [TTI: systolic blood pressure x heart rate (HR) x left ventricular ejection time (LVET)] was significantly higher throughout the weight carrying exercise compared to dynamic exercise. The amount of change (delta) in TTI was significantly larger in the initial stage (control to 1 min) of weight carrying exercise compared to dynamic exercise, but there were no significant differences in the later stages (1-3 min and 3-6 min). A prolongation in LVET was observed despite increasing HR during the first minute of exercise in both type of exercise, but LVET was longer at any given HR in weight carrying compared to dynamic exercise. Thus, despite higher TTI throughout the weight carrying exercise, delta TTI was larger only in the initial stage which was caused by prolongation of LVET resulting from disproportionate increase in venous return of early exercise.

Adult

Effect of gender on the left ventricular diastolic performance during isometric handgrip exercise in normal individuals.

To evaluate the effects of gender and isometric handgrip exercise on left ventricular diastolic function in normal individuals, atrial and rapid filling fraction were investigated using M-mode echocardiography in 35 postmenopausal women and 31 age-matched men. There were no significant differences in heart rate, mean blood pressure, atrial filling fraction, and rapid filling fraction at rest between women and men. When the amount of change in hemodynamic variable during exercise was compared, there were no significant differences in heart rate and mean blood pressure between women and men. But the increase in atrial filling fraction and the decrease in rapid filling fraction were significantly larger in women than in men. These data suggest that left ventricular diastolic function is restricted in postmenopausal women, and left atrial booster pump action is mobilized when afterload is increased during isometric handgrip exercise.

Aged

Effect of ventriculoarterial coupling on residual left ventricular pump function in diabetic patients with myocardial infarction.

To study the ventriculoarterial coupling in diabetic patients with myocardial infarction (MI), 26 diabetic and 34 nondiabetic patients were investigated using radionuclide angiography in the 3rd week after acute MI. Effective arterial elastance was nearly one half of left ventricular end-systolic elastance in nondiabetic patients. On the other hand, effective arterial elastance was twice left ventricular end-systolic elastance in diabetic patients. These data suggest that a decrease in left ventricular contractility and an increase in effective arterial elastance lead to increased potential energy and decreased work efficiency in diabetic patients.

Arteries

Differential gene expression and regulation of angiotensin II receptor subtypes in rat cardiac fibroblasts and cardiomyocytes in culture.

Although both rat cardiac nonmyocytes (mostly fibroblasts) and cardiomyocytes have a functional angiotensin II (AngII) receptor, the regulation mechanism of its subtype expression in the rat heart remains unknown. In this study, by using a binding assay and a competitive reverse-transcriptase polymerase chain reaction, we examined the regulation of AngII types 1a and 1b (AT1a-R and AT1b-R) and type 2 receptor (AT2-R) expression in embryonal day 19 (E19) and neonatal (1-d) rat cardiac fibroblasts and cardiomyocytes. The number of AT2-R in E19 fibroblasts was dramatically decreased (from 305 to 41 fmol/mg protein) in 1-d fibroblasts, whereas that of AT1-R and the mRNA levels remained unchanged. The ratio of AT1a-R to AT1b-R mRNA in both E19 and 1-d fibroblasts was 9:1. The number of AT2-R in E19 cardiomyocytes was also significantly decreased (from 178 to 87 fmol/mg protein) in 1-d cardiomyocytes, whereas the magnitude was less prominent compared with that in fibroblasts. AT1-R expression remained unaltered in E19 and 1-d cardiomyocytes. In E19 and 1-d cardiomyocytes, the AT1b-R mRNA level was 1.5-fold higher than that of AT1a-R mRNA. Dexamethasone induced significant increases in AT1a-R mRNA (2.1-fold) and numbers (1.8-fold) without changing the affinity, whereas neither AT1b-R mRNA nor the number of AT2-R was affected by dexamethasone. The AT1a-R gene transcription rate, determined by means of a nuclear run-off assay, was increased (2-fold) by dexamethasone. The half-life of AT1a-R mRNA (18 h) was unchanged by dexamethasone. These data indicate that AngII receptor subtype expression in the rat heart is regulated in a cell- and subtype-specific manner.

Angiotensin II

cAMP responsive element-mediated regulation of the gene transcription of the alpha 1B adrenergic receptor by thyrotropin.

To elucidate the molecular mechanism of the stimulatory effect of thyrotropin on the gene regulation of alpha 1B adrenergic receptor in functioning rat thyroid (FRTL-5) cells, we established a competitive reverse-transcriptase (RT) polymerase chain reaction (PCR) and nuclear run-off assay to quantify changes in mRNA levels and transcription rates. A binding assay showed that FRTL-5 cells predominantly expressed alpha 1B adrenergic receptor and that thyrotropin increased its expression sevenfold. By means of RT-PCR, we found that thyrotropin induced an 11-fold increase in alpha 1B receptor mRNA abundance. The nuclear run-off assay demonstrated that thyrotropin caused a ninefold increase at the gene transcriptional level, which occurred in the presence of the protein synthesis inhibitor cycloheximide. The half-life of the alpha 1B receptor mRNA in cells incubated with thyrotropin for 1 h increased 1.5-fold but returned to the original value after 12 h. Dibutyryl cAMP and forskolin mimicked the stimulatory effects of thyrotropin on the gene transcriptional level. The 5'-flanking region of the rat alpha 1B receptor gene contained a putative cAMP responsive element (CRE) at nucleotide -438 relative to the translation start site. The promoter analysis using the reporter gene indicated that the CRE motif confers the cAMP sensitivity to the transcription of the rat alpha 1B receptor gene. These results demonstrated that a CRE-mediated mechanism is involved in the transcriptional regulation of the alpha 1B receptor gene by thyrotropin without requiring new protein synthesis.

Animals

Cadmium stimulation of glycosaminoglycan synthesis by cultured vascular endothelial cells: comparison of various cell types.

We investigated the effect of cadmium on the synthesis of glycosaminoglycans (GAGs) in confluent cultures of vascular endothelial cells derived from bovine aorta. Cadmium markedly increased the incorporation of [3H]glucosamine into GAGs in both the cell layer and the conditioned medium but decreased [35S]sulfate in the cell layer. This suggested that cadmium induced the GAG synthesis by endothelial cells accompanied by a reduction of the sulfation of cell-associated GAGs. Of the tested heavy metals, the [35S]sulfate incorporation in the cell layer was significantly decreased by lead; zinc slightly but significantly increased the [35S]sulfate incorporation; manganese and copper failed to change the [3H]glucosamine and [35S]sulfate incorporation; and the incorporation of [3H]glucosamine was increased only by cadmium. On the other hand, vascular smooth-muscle cells and fibroblastic Balb/3T3 cells responded to cadmium in a way similar to vascular endothelial cells, while fibroblastic IMR-90 cells, Chang liver cells and epithelial LLC-PK1 cells altered the [3H]glucosamine and [35S]sulfate incorporation after exposure to cadmium in different manners. The alteration of GAGs induced by cadmium may be involved in the pathogenesis of the metal.

Animals

Nucleosides and nucleotides. 131. Synthesis and properties of oligonucleotides containing 5-formyl-2'-deoxyuridine.

Thymidine was converted into 5-formyl-2'-deoxyuridine (1), which was incorporated into oligonucleotides, 5'd(GGAGA1CTCC)3' (I-1) and 5'd(GCTGC1GCGAAAGCTG)3' (II-1). To avoid side-reactions and degradation, protection of the formyl group of 1 using a newly developed protecting group, N,N-di-(3,5-dichlorophenyl)ethylenediamine, was necessary. Compound 1 was unstable under the conditions employed for enzymatic complete digestion of oligonucleotides, so that a peak corresponding to 1 was not detected clearly by HPLC analysis of a nucleoside mixture obtained by complete hydrolysis of I-1. Therefore, the oligonucleotide I-1 was treated with cyanomethylene-triphenylphosphorane to give an oligonucleotide containing (E) and (Z)-5-(2-cyanovinyl)-2'- deoxyuridine, which was then hydrolyzed, and the newly generated nucleosides were detected by HPLC analysis. The Tm of the self-complementary oligonucleotide I-1 (40 degrees C) was higher than that of the parent oligonucleotide, 5'd(GGAGATCTCC)3', (31 degrees C) in a buffer containing 0.01 M sodium phosphate (pH 7.0) and 0.1 M NaCl. DNA replication study on a template-primer system [primer, 5'd(32P-CAGCTTTCGC)3'; template, 3'd(GTCGAAAGCGXCGTCG)5' (X = 1 or T)] showed that dATP was incorporated into the DNA strand at a site opposite to 1 by Klenow DNA polymerase, but with a reduced rate. The formyl group of 1 in the oligonucleotides reacted with amines to give Schiff base derivatives.

Base Sequence

Effect of body characteristics on the variables of signal-averaged electrocardiograms in healthy subjects.

Late potentials have been reported to be affected by body size or left ventricular mass. To our knowledge, however, the effect of subadipose tissue, which is known to influence QRS amplitudes of the surface ECG on the variables of late potentials, has not been evaluated. The relationships between the variables of late potentials and various obesity indices were assessed in 45 men, aged 24 to 38 years, without structural heart disease and bundle branch blocks. QRS duration (DUR), root mean square voltage in the last 40 ms (RMS), and low-amplitude signals < 40 microV (LAS) were obtained by signal-averaged ECG. Left ventricular mass (LV mass) was determined by echocardiography. The DUR and RMS had no correlation with body height, weight, body mass index (BMI), sum of skin folds (triceps and subscapular), or LV mass. Positive linear correlations were found between LAS and weight (r = 0.48, p < 0.002), BMI (r = 0.54, p < 0.002), sum of skin folds (r = 0.57, p < 0.002), and percent BMI (r = 0.54, p < 0.002). Subadipose tissue may shift the onset of the 40-microV point of LAS to the left with a consequent prolongation of LAS by attenuation of the QRS complex. These data suggest that the use of LAS alone or as a combination in an obese population for the definition of positive late potentials is inappropriate.

Adult

Prolonged survival in a patient with a single ventricle without pulmonary stenosis.

Prolonged survival of the patient with a single ventricle is rare. We report the case of a 57-year-old man who has type A3 of Van Praagh's classification of single ventricle with pulmonary hypertension without pulmonary stenosis. Favorable streaming, a large bulboventricular foramen, and intact atrioventricular valves may have contributed to his long-term survival.

Echocardiography, Transesophageal

Effect of sex on left ventricular pump function in patients with anterior wall myocardial infarction treated with primary angioplasty.

BACKGROUND: The prognosis of acute myocardial infarction (AMI) is distinctly worse in postmenopausal women than in age-matched men. Unstable angina before AMI is reported to protect left ventricular pump function during the left ventricular remodeling process in patients who have undergone successful percutaneous transluminal coronary angioplasty (PTCA). We postulate that left ventricular pump function may be different in postmenopausal women and age-matched men with unstable angina before AMI and successful PTCA. METHODS: Twenty-three postmenopausal women (aged 63 +/- 7 years) and 31 age-matched men (aged 65 +/- 6 years) with unstable angina before AMI and successful PTCA were investigated using radionuclide angiography in the late hospital phase. RESULTS: Global ejection fraction (EF), regional EF of the non-infarcted area, and the ratio of systemic arterial systolic blood pressure to left ventricular end-systolic volume (P:V ratio) were lower in women compared with those in men. Global EF, regional EF of the non-infarcted area, and the P:V ratio in women with left ventricular end-diastolic volume (EDV) > or = 140 ml were significantly lower than in those with a left ventricular EDV of less than 140 ml, but no significant differences were noted in these indexes with regard to left ventricular EDV in men. CONCLUSION: Sex may play an important role in the left ventricular remodeling process in postmenopausal women, especially those with a dilated left ventricle.

Aged

Left ventricular diastolic filling properties in diabetic patients during isometric exercise.

Left ventricular diastolic filling properties during isometric handgrip exercise were measured by pulsed Doppler echocardiography in 33 noninsulin-dependent diabetic patients with a normal ejection fraction and 15 control subjects. Diabetic patients were subdivided into two groups according to their resting left ventricular filling pattern (A/E): 18 patients were in group DM-1 (A/E < or = 1.1) and 15 patients were in group DM-2 (A/E > 1.1). At rest, A/E ratio and A wave were higher, and deceleration half-time was longer in group DM-2 than in normal subjects and group DM-1, but there was no significant difference between normal subjects and group DM-1. The A/E ratio increased significantly in all three groups during isometric handgrip exercise. However, the change in A/E from rest to peak exercise in group DM-1 (0.29 +/- 0.20) was significantly greater than in normal subjects (0.09 +/- 0.07). These results suggest that diabetes mellitus patients with normal resting left ventricular (LV) filling pattern (group DM-1) had LV diastolic filling abnormalities with isometric handgrip exercise. Doppler echocardiography with isometric handgrip exercise is useful in identifying underlying left ventricular diastolic dysfunction in diabetic patients.

Diabetes Mellitus, Type 2

Shaker-related potassium channel, Kv1.4, mRNA regulation in cultured rat heart myocytes and differential expression of Kv1.4 and Kv1.5 genes in myocardial development and hypertrophy.

The multiple K+ channels are crucial for repolarization and configuration of the action potential in the neuronal and cardiac cells. In this study, we report the regulatory mechanisms of rapidly inactivating Shaker Kv1.4 channel transcript in the rat heart. Quantitative PCR analysis showed that stimulation with high concentration of KCl, BAY-K 8644, or 12-O-tetradecanoyl phorbol-13-acetate resulted in an immediate and substantial increase (two- to threefold) of Kv1.4 mRNA levels in spontaneously beating myocytes prepared from neonatal rat ventricles. The Kv1.4 mRNA in the ventricle remains at a steady state level after birth and gradually declines with maturation. These results suggest that the Kv1.4 mRNA level is not static and undergoes dynamic modulation by multiple factors that activate intracellular signals. In addition, the expression patterns of Kv1.4 as well as the delayed rectifier Shaker K+ channel Kv1.5 mRNAs were examined in hypertrophied ventricles in which a plateau phase of action potential is remarkably prolonged. The Kv1.5 mRNA level was dramatically repressed while the Kv1.4 mRNA level was remarkably increased. This differential regulation was completely reversed by the normalization of hypertrophy, suggesting that the pathological alterations of K+ channel gene regulation may be involved in the occurrence of ventricular arrhythmias in hypertrophic hearts.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy

Measurement of erythrocyte Na,K-ATPase activity in normal pregnant women.

To investigate the peripheral metabolic status during normal pregnancy, we measured the number of erythrocyte Na,K-ATPase units as well as the cation transport activity of the pump from 32 normal pregnant women and 12 normal controls. The number of pump units determined by maximal ouabain binding to erythrocyte in normal pregnancy was significantly higher than that in normal controls (mean +/- SEM: 0.52 +/- 0.03 vs. 0.39 +/- 0.04 pmol/10(9)RBC, P < 0.05). The total cation transport activity of the pump measured by 86Rb uptake also significantly increased during pregnancy (98.9 +/- 6.4 vs. 73.1 +/- 5.4 nmol/10(9) RBC, P < 0.01). However, the mean cation transport activity per pump unit, which was presumed to be an indicator of the peripheral metabolic status, was unchanged in any of three trimesters when compared with that in normal controls. Serum FT4 levels measured by two different methods were significantly lower in the third trimester than in the first trimester (P < 0.01). In conclusion, erythrocyte Na, K-ATPase activity per pump unit is normal in pregnant women, suggesting that the peripheral metabolic status in pregnancy seems to be normal. Increases in both the number and function of the pump may be influenced by factors other than thyroid function.

Adult

Changes in plasma atrial natriuretic peptide during hemodialysis: mechanism of elevated levels in patients with chronic renal failure.

An elevated plasma atrial natriuretic peptide (ANP) concentration was observed in patients with chronic renal failure, and it was significantly (P < 0.01) decreased by hemodialysis with or without fluid removal. The ANP concentration was decreased by dialysis without fluid removal and the decrease was significantly (P < 0.01) correlated with the pre-dialysis value. The decrease in this peptide during fluid removal without diffusion was significantly (P < 0.05) correlated with the decrease in the circulating plasma volume measured by dye dilution. The decrease in the ANP level was therefore considered to be related to a fall in right atrial pressure caused by the decline in the circulating plasma volume. The circulating plasma volume, osmotic pressure, and blood pressure were not changed by hemodialysis without fluid removal. Moreover, the filtrate concentration of ANP (mean: 5.5 pg/ml) during fluid removal without dialysis was only about 8% of the plasma level, so filtration of ANP from the dialyzer was negligible. The decrease in ANP during hemodialysis without fluid removal may therefore have been caused by the removal of or a change in the level of substances, for example electrolytes, epinephrine, and uremic toxins. In addition to volume expansion, such a substance(s) might influence plasma ANP levels in patients with chronic renal failure.

Adult

Correlation of orbital muscle changes evaluated by magnetic resonance imaging and thyroid-stimulating antibody in patients with Graves' ophthalmopathy.

To evaluate the relationship between eye changes and autoantibody to the thyrotropin receptor in patients with Graves' disease, we evaluated the eye changes using magnetic resonance imaging and the results were correlated with thyroid-stimulating antibody, thyrotropin binding inhibitor immunoglobulin and thyroid growth activity. Subjects were 15 patients with Graves' disease who had Graves' ophthalmopathy, including exophthalmos and other signs and symptoms, and nine patients without ophthalmopathy; all were maintained in a euthyroid state by antithyroid drugs. The thyrotropin-binding inhibitor immunoglobulin was measured by a kit, and thyroid-stimulating antibody and thyroid growth activity were evaluated by cyclic adenosine 3',5'-monophosphate production and [3H]thymidine incorporation, respectively, by cultured functional rat thyroid lined cells. The sum of the swelling ratios (muscle thickness to the diameter of the optic nerve) of the four extraocular muscles correlated well with the degree of exophthalmos. The thyrotropin-binding inhibitor immunoglobulin was positive in nine out of 15 patients with ophthalmopathy; however, no correlation was observed between the activity and exophthalmos or muscle swelling. No significant correlation was observed between muscle changes and thyroid growth activity either. On the other hand, thyroid-stimulating antibody (642 +/- 91%) in Graves' patients with ophthalmopathy was significantly (p < 0.02) higher than that (315 +/- 84%) in patients without ophthalmopathy. Moreover, the level of stimulating activity in Graves' patients with ophthalmopathy showed a significant (p < 0.02) positive correlation with the sum of the swelling ratios of the individual eight eye muscles. These results suggest that thyroid-stimulating antibody has a close relation to Graves' ophthalmopathy.

Adolescent

Preparation of isotopically labeled ribonucleotides for multidimensional NMR spectroscopy of RNA.

A general method for large scale preparation of uniformly isotopically labeled ribonucleotides and RNAs is described. Bacteria are grown on isotopic growth medium, and their nucleic acids are harvested and degraded to mononucleotides. These are enzymatically converted into ribonucleoside triphosphates, which are used in transcription reactions in vitro to prepare RNAs for NMR studies. For 15N-labeling, E.coli is grown on 15N-ammonium sulfate, whereas for 13C-labeling, Methylophilus methylotrophus is grown on 13C-methanol, which is more economical than 13C-glucose. To demonstrate the feasibility and utility of this method, uniformly 13C-labeled ribonucleotides were used to synthesize a 31 nucleotide HIV TAR RNA that was analyzed by 3D-NMR. This method should find widespread use in the structural analysis of RNA by NMR.

Carbon Isotopes

Clinical significance of serum colloid osmotic pressure in relation to pulmonary edema and coronary instability in patients with unstable angina.

Several investigators demonstrated that severe reduction of colloid osmotic pressure (COP) predicts a fatal outcome in patients with cardiopulmonary failure. To evaluate the clinical significance of COP in relation to pulmonary edema, we studied 117 patients with unstable angina admitted in the hospital within 24 h after the chest pain. The mean COP of all 117 patients was 24.8 +/- 3.7 mmHg. COP was significantly lower in patients with pulmonary edema, according to the chest x-ray findings, compared with the patients without it. Among 26 patients with emergency coronary arteriography, a fairly good correlation was observed between coronary jeopardy score and COP (r = -0.57, p less than 0.005). Furthermore, COP in patients who survived 26 months after the hospital discharge was significantly higher than that of the nonsurvivors. Thus, measurement of COP is advised for monitoring patients with unstable angina.

Angina, Unstable