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Biomedical subjects

M Inada

Publications and source records attributed to M Inada.

At least 91 records · Page 5Linked to original sources
PubMed1994

Effect of FK-506 on xenografted human Graves' thyroid tissue is severe combined immunodeficient mice.

OBJECTIVE: We studied the macrolide antibiotic FK-506, an immunosuppressive agent, in an attempt to ameliorate the lesion of autoimmune thyroid disease in human thyroid tissue xenografted into severe combined immunodeficient (SCID) mice. It was not felt appropriate to employ this agent directly in patients with autoimmune thyroid disease because adequate therapeutic modalities are available and the introduction of new, experimental agents could not be justified. Moreover, the study of the tissue before and after treatment could not have been undertaken directly in patients. DESIGN: Human thyroid xenografts from four patients with Graves' disease and two normal persons were xenografted into SCID mice. Two weeks after xenografting, human immunoglobulin G (IgG) was detectable in all SCID mice xenografted with Graves' thyroid tissue. Mice were divided into two groups with human IgG levels similar to each other. Mice in the first group were treated with FK-506 daily for 6 weeks; mice in the second (similar) group were given phosphate-buffered saline (PBS) only (control group). MEASUREMENTS: Blood samples were taken every 2 weeks from the tail veins for human IgG, thyroid stimulating antibody, thyroperoxidase antibodies, thyroglobulin antibodies, and interferon-gamma (IFN-gamma). After 8 weeks treatment, animals were sacrificed; thyroid tissue was examined histologically and for thyrocyte HLA-DR expression. FK-506 was also added to thyrocytes in in-vitro tissue culture conditions. RESULTS: After 4-6 weeks of FK-506 therapy, human IgG, all thyroid antibodies and IFN-gamma were suppressed, while the levels remained elevated in the control group. Lymphocytic infiltration virtually disappeared in the human thyroid tissue of the FK-506-treated mice and thyrocyte HLA-DR expression markedly declined; in the control mice, lymphocytic infiltration remained heavy and HLA-DR expression remained high. On the other hand, FK-506 added directly to thyrocytes in vitro (without lymphocytes) did not reduce thyrocyte HLA-DR expression. CONCLUSIONS: FK-506 appears to suppress the activation of intrathyroidal lymphocytes, but not thyrocytes. From these observations, it is concluded that this agent, by its action on intrathyroidal lymphocytes, is able to ameliorate the immunologically mediated histological and serological disturbance in human autoimmune thyroid disease, at least under these circumstances.

Animals↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
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↗