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M Inada

Publications and source records attributed to M Inada.

At least 163 records · Page 9Linked to original sources
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

Cardioprotective effect of unstable angina prior to acute anterior myocardial infarction.

To evaluate the difference in the process of left ventricular functional recovery after successful percutaneous transluminal coronary angioplasty (PTCA), 25 patients with sudden onset of acute Q wave anterior myocardial infarction (MI [group 1]) and 28 patients with unstable angina prior to MI (group 2) were investigated in the late hospital phase. The circumferential extent of left ventricular dysfunction was significantly larger in group 1 than in group 2. The left ventricular ejection fraction (EF) and the ratio of systemic arterial systolic blood pressure to left ventricular end-systolic volume (P/V ratio) were significantly lower in group 1 compared with group 2. The P/V ratio had nonlinear relationships with left ventricular end-diastolic volume (LVEDV) in both groups and the P/V ratio in group 1 was significantly lower than those in group 2 at any given LVEDV. Thus, in patients with successful PTCA, unstable angina prior to acute MI had better left ventricular pump function in the course of left ventricular remodeling.

Angina, Unstable↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1993

Regulatory elements that mediate expression of the gene for the angiotensin II type 1a receptor for the rat.

To analyze the mechanism of the cell type-specific expression of rat angiotensin II type 1a receptor (AT1a-R) gene, we isolated the 5'-portion of the gene and identified multiple positive and negative regulatory sequences that regulate its transcription. Primer extension and S1 mapping identified a transcriptional initiation site at 33 (position +1) base pairs (bp) downstream of TATA sequence. The transcriptional activities of various 5'-deletion mutants of the AT1a-R gene upstream region, fused to the chloramphenicol acetyltransferase (CAT) gene, were examined using rat vascular smooth muscle cells (A10) and glial cells expressing AT1a-R mRNA predominantly or PC12 cells expressing AT2-R and very small amounts of AT1a-R mRNA. A 980-bp 5'-flanking sequence contained at least three positive elements, P1 (-560 to -489), P2 (-331 to -201), and P3 (-201 to -61). P1 and P3 were active in the tested three cells, and P2 was functional only in glial and PC12 cells. In addition to these positive elements, there was negative element, N1 (-489 to -331), which was active only in PC12 cells. These elements, when cotransfected with the AT1a-CAT fusion gene, had competitive effects against its promoter activity. The present study suggests the presence of multiple trans-acting factors that act on these positive and negative cis-acting elements and regulate the cell type-specific expression of the rat AT1a-R gene.

Animals↗
PubMed1993

Two novel mutations in the vasopressin V2 receptor gene in unrelated Japanese kindreds with nephrogenic diabetes insipidus.

Nephrogenic diabetes insipidus (NDI) is a rare X-linked disorder exhibiting renal resistance to the antidiuretic action of arginine vasopressin (AVP). Recent elucidation of the vasopressin V2 (renal type) receptor gene structure has enabled us to test the hypothesis that the genetic defect in the V2 receptor is the likely molecular basis of NDI. By using the polymerase chain reaction (PCR)-direct sequencing, we identified novel V2 receptor gene mutations in two unrelated Japanese kindreds with NDI. In the male patients of kindred A, a single codon deletion in one of two consecutive GTC triplets (nucleotide 832 to 837) was detected. This base change resulted in the loss of a valine residue in the 6th transmembrane domain. In the affected males of kindred B, a G to C substitution was found at nucleotide 428, altering codon 143 from arginine (CGT) to proline (CCT) in the second cytoplasmic domain. PCR-single strand conformation polymorphism (SSCP) analysis of family members demonstrated that the mutations cosegregated with clinically affected individuals and were absent in normal subjects. Our results suggest that different V2 receptor defects could be responsible for AVP resistance in individual NDI kindreds.

Adult↗
PubMed1993

Disturbance of pulmonary gas exchange in patients with acute myocardial infarction-associated pericardial effusion.

To elucidate the effect of pericardial effusion on pulmonary gas exchange in patients with infarction-associated pericardial effusion, 294 consecutive patients with their first Q-wave anterior wall acute myocardial infarction were examined carefully by echocardiography, chest radiography and hemodynamic monitoring. A pericardial effusion was detected in 77 patients and was absent in 217 (group 1). Of the 77 patients with pericardial effusion, it was mild in 57 (group 2) and moderate in 20 (group 3). Patients with pericardial effusion (groups 2 and 3) had significantly greater pulmonary artery wedge pressure and more left ventricular segments with advanced asynergy than did those in group 1. Although there were no significant differences in pulmonary artery wedge pressure and number of left ventricular segments with advanced asynergy between groups 2 and 3, group 3 had significantly greater right atrial pressure, alveolar arterial oxygen difference and incidence of high radiographic score. Thus, accumulation of pericardial effusion to a moderate amount may contribute to the greater incidence of increase in extravascular lung water, and disturbance of pulmonary gas exchange.

Aged↗
PubMed1993

[Thyroid hormone metabolism].

Most thyroxine (T4) secreted from the thyroid is deiodinated in peripheral tissues. At least three isozymes are known in iodothyronine deiodinase which catalyzes the conversion of T4 to triiodothyronine (T3) or reverse T3. Type I 5'-deiodinase (5'D-I) exists in most tissues including the liver, kidney and thyroid. Type II 5'-deiodinase (5'D-II) which exists mainly in the brain, pituitary, brown fat and placenta plays an important role in the saturation of intracellular T3 receptor. Type III enzyme (D-III) which deiodinases the five positions of T3 is considered to modulate the T3 content by regulating its degradation. The complementary DNA (cDNA) for the rat and human 5'D-I has recently been cloned. 5'D-I contains a rare amino acid selenocysteine, which is essential for normal deiodinative function in humans as well as rats. On the other hand, 5'D-II, whose molecular weight is much heavier than that of 5'D-I, does not contain selenocysteine and its cDNA has not been sequenced. Little is known about the molecular characteristics of D-III. Further studies are needed to clarify the molecular mechanism by which deiodinase proteins are produced in various circumstances and to investigate the meticulous aspects of metabolic pathways other than deiodination.

Adipose Tissue, Brown↗
PubMed1993

Precordial ST segment depression in patients with Q wave inferior myocardial infarction: role of infarction-associated pericarditis.

To examine the diagnostic significance of precordial ST segment depression in Q wave inferior myocardial infarction, 157 consecutive patients were examined carefully by means of auscultation, ECG, and two-dimensional echocardiography. Precordial ST segment depression was transient (lasting < 72 hours from the onset of myocardial infarction) in 63 patients and persistent (> or = 72 hours) in 40. Twenty-eight patients with persistent, 19 patients with transient, and 14 patients without precordial ST segment depression had advanced asynergy (akinesia or dyskinesia) in the posterior segments, whereas 13 patients with persistent, six with transient, and six without precordial ST segment depression had pericardial rub. Patients with persistent precordial ST segment depression had a significantly higher incidence of severe wall motion abnormality (p < 0.01) and inflammation (p < 0.05) of the posterior wall than the other two groups. In 5 of 40 patients with persistent ST segment depression, pericardial rub was detected in the absence of advanced asynergy in the posterior segments. Although not highly sensitive, persistent precordial ST segment depression appeared to be a fairly specific indicator (specificity 92%) of concomitant posterior involvement with severe wall motion abnormality, inflammation, or both.

Aged↗
PubMed1993

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↗
PubMed1993

Effect of subadipose tissue on the variables of signal-averaged electrocardiograms in healthy subjects.

Ventricular late potentials are obtained by signal averaging of surface electrocardiograms. Late potentials have been reported to be affected by body size or left ventricular mass. However, the effect of subadipose tissue, which is known to influence QRS amplitudes of 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 24-38 years, without structural heart disease and bundle branch blocks. QRS duration, root mean square voltage in the last 40 ms and low-amplitude signals < 40 microV were obtained by signal-averaged ECG. Left ventricular mass was determined by echocardiography. QRS duration and root mean square voltage had no correlation with body height, weight, body mass index, sum of skin folds (triceps and subscapular) or left ventricular mass. Positive linear correlations were found between low-amplitude signals and weight (r = 0.48, p < 0.002) body mass index (r = 0.54, p < 0.002), sum of skin folds (r = 0.57, p < 0.002), percent body mass index (r = 0.54, p < 0.002). Subadipose tissue may shift the onset of the 40-microV point of low-amplitude signals to the left with a consequent prolongation of low-amplitude signals by attenuation of the QRS complex. These data suggest that the use of low-amplitude signals alone or as a combination in an obese population for the definition of positive late potentials is inappropriate. The low-amplitude signal has to be used with caution in obese patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1993

Increase in left ventricular ejection rate during recovery from exercise in patients with myocardial infarction.

Changes in left ventricular (LV) ejection rate were evaluated during supine bicycle exercise and recovery in 12 patients with anterior myocardial infarction. Pulmonary artery wedge pressure (34 +/- 9 to 14 +/- 5 mm Hg) and plasma norepinephrine level decreased at 2 min recovery from peak exercise, whereas plasma lactate tended to increase. As a result, LV ejection rate reached the highest value at 2 min of recovery. Thus, both cardiac (optimal filling pressure) and peripheral factors (reduced vascular resistance) caused the increase in LV ejection rate at early recovery.

Acid-Base Equilibrium↗
PubMed1993

Left ventricular function during exercise after aortic valve replacement.

To evaluate the difference in left ventricular function during exercise after successful aortic valve replacement, left ventricular function was investigated using radionuclide angiography in 12 patients with normal resting left ventricular systolic function. Patients were divided into two groups: Group 1 was comprised of 5 patients after aortic valve replacement for aortic stenosis and group 2 was comprised of 7 patients for aortic insufficiency. Left ventricular ejection fraction increased significantly during exercise in both groups. The increase in systolic arterial pressure to left ventricular end-systolic volume was significantly larger in group 1 than group 2, whereas the increase in left ventricular end-diastolic volume was significantly larger in group 2 than group 1. Thus, increase in left ventricular contractility played an important role in regulating increased left ventricular ejection fraction during exercise in patients with aortic prostheses for aortic stenosis, whereas increase in left ventricular end-diastolic volume played an important role in patients with aortic prostheses for aortic insufficiency.

Adult↗
PubMed1993

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

Ventricular late potentials are obtained by signal-averaged surface electrocardiography. Late potentials have been reported to be affected by body characteristics or left ventricular mass. To evaluate late potentials in relation to body characteristics, 52 healthy Japanese young volunteers (21 girls, 31 boys) aged 15-16 years were studied. QRS duration in men was significantly longer than in women. There were no significant differences in low-amplitude signal and root mean square voltage between women and men. When relations between signal-averaged electrocardiographic parameters and body characteristics were examined, QRS duration had positive linear correlations with weight and body mass index. The slope of QRS duration and weight relation, and QRS duration and body mass index relation was significantly steeper in men compared to those in women; a prolongation of QRS duration in men compared to women as weight and body mass index increased. Our results indicated that QRS duration in teenage healthy subjects should be used with caution because it is affected by gender.

Adolescent↗