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Biomedical subjects

M Inada

Publications and source records attributed to M Inada.

At least 181 records · Page 10Linked to original sources
PubMed1993

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↗
PubMed1993

Mononuclear cell infiltration and its relation to the expression of major histocompatibility complex antigens and adhesion molecules in pancreas biopsy specimens from newly diagnosed insulin-dependent diabetes mellitus patients.

We examined pancreas biopsy specimens from 18 newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients to elucidate the mechanism underlying beta cell destruction. Pancreas islets were seen in all patients and insulitis in eight patients. Infiltrating mononuclear cells consisted of CD4+T, CD8+T, B lymphocytes, and macrophages. Among them, CD8+T lymphocytes were predominant and macrophages followed. The expression of MHC class I antigens was increased in islet and endothelial cells in nine patients. MHC class II expression was increased in endothelial cells of the same patients. The expression of intercellular adhesion molecule-1 was increased in endothelial cells in two of the nine patients with MHC hyperexpression; in one of them, lymphocyte function-associated antigen-3 expression was also increased. Out of the eight patients with insulitis, seven showed MHC class I hyper-expression, whereas 2 of the 10 patients without insulitis showed the phenomenon (P < 0.05). The relation between insulitis and the hyperexpression of adhesion molecules was not evident. In conclusion, we revealed the close relation between CD8+T lymphocyte-predominant insulitis and MHC class I hyperexpression in islet cells. This suggests that infiltrating CD8+T lymphocytes recognize islet autoantigens in association with increased MHC class I molecules and act as major effector cells in autoimmune response against islet cells in IDDM pancreases. The role of adhesion molecules in the pathogenesis of IDDM still remains to be elucidated.

Adolescent↗
PubMed1993

Effect of the leukotriene receptor antagonist ONO-1078 on extravascular lung water after coronary ligation in dogs.

To determine whether or not leukotrienes are associated with pulmonary edema after coronary ligation in dogs, we studied the effects of a specific leukotriene C4/D4 antagonist, ONO-1078, on extravascular lung water, as measured by the thermal-dye double indicator dilution method (Extravascular thermal volume, ETV). Six dogs served as a sham control (group 1). The proximal left anterior descending coronary artery was ligated for 45 min in 6 dogs (group 2), and in 6 others the coronary artery was ligated after pretreatment with ONO-1078 (1 mu/kg/min) (group 3). ETV and pulmonary arterial pressure were measured at control and 45 min after coronary ligation. In group 1, no significant change was found in ETV. Although there was no significant increase in pulmonary arterial pressure after coronary ligation, ETV significantly increased in groups 2 and 3. ETV increased more in groups 2 and 3 than in group 1, but there was no significant difference between groups 2 and 3. Thus, ONO-1078 did not effectively prevent the accumulation of extravascular lung water after coronary ligation, indicating that leukotrienes are not important mediators of pulmonary edema after myocardial ischemia.

Animals↗
PubMed1993

Overshoot in mixed venous oxygen saturation during recovery from supine bicycle exercise in patients with recent myocardial infarction.

During recovery from dynamic exercise, systemic oxygen extraction rapidly decreases below the resting level in patients with heart failure, which leads to a subsequent increase in mixed venous oxygen saturation (SvO2) above its resting value (postexercise SvO2 overshoot). To evaluate the pathophysiologic basis of this phenomenon, postexercise SvO2 overshoot was evaluated in relation to hemodynamic, metabolic, and neurohumoral responses during recovery from maximal supine bicycle exercise in 22 patients with recent myocardial infarction. Postexercise SvO2 overshoot closely correlated with increased systemic vascular resistance (r = 0.79, p < 0.001) and reduced cardiac output (r = -0.74, p < 0.001), suggesting that SvO2 overshoot is primarily due to increased peripheral arteriovenous shunting caused by an enhanced peripheral vasoconstriction in the setting of reduced cardiac output. Postexercise SvO2 overshoot and systemic vascular resistance were significantly higher and cardiac output was significantly lower in New York Heart Association functional class 3 and 4 (8 patients) compared with class 1 and 2 (14 patients), whereas systemic arterial blood pressure was maintained at normal levels in both groups. Thus, postexercise SvO2 overshoot and, hence, decreased systemic oxygen extraction during recovery represent a compensatory response of an enhanced peripheral vascular tone that maintains systemic arterial blood pressure in the setting of reduced cardiac output by linking central and peripheral blood flow.

Adult↗
PubMed1993

Natural history of left ventricular function in patients with uncomplicated acute myocardial infarction.

To investigate the serial changes of the infarcted and the noninfarcted areas, first-pass radionuclide angiocardiography was performed in 16 patients with uncomplicated anterior myocardial infarction (MI) at four weeks, one year, and two years after the onset of MI. Global ejection fraction (EF) and regional EF of the infarcted area improved significantly from four weeks to one year after MI (from 39 +/- 16 to 44 +/- 16 percent, 23 +/- 3 to 29 +/- 5 percent, both p < 0.01), but did not change from one year to two years after MI. Regional EF of the noninfarcted area and left ventricular end-diastolic and end-systolic volume did not change during the study period. There was a significant relation in the direction of the changes of global EF and regional EF of the infarcted area during the first year after MI, whereas no relation was observed between the changes of global EF and regional EF of the noninfarcted area. A greater improvement in regional EF of the infarcted area was observed in seven patients who had spontaneous recanalization compared with nine patients with totally occluded coronary arteries. Thus, a significant improvement in cardiac function, mainly due to the increase in regional EF of the infarcted area, was observed during the first year after MI, which was related to patency of coronary artery.

Adult↗
PubMed1993

Pulmonary edema after anteroseptal acute myocardial infarction.

To evaluate the clinical characteristics of patients with anteroseptal myocardial infarction (MI) initially presenting with pulmonary edema, we analyzed 58 patients with anteroseptal MI who underwent emergency coronary arteriography that revealed single-vessel disease of the left anterior descending coronary artery. Of the 58 patients, pulmonary edema was observed in 24 patients (group A) and was absent in 34 patients (group B). Pulmonary capillary wedge pressure was significantly higher, and cardiac output was significantly lower in group A. The site of coronary stenosis, maximum serum creatinine kinase value, and wall motion point score did not differ between the two groups. However, the incidence of previous hypertension and posterior wall thickness > or = 11 mm was significantly higher in group A than in group B (p < 0.001 and p < 0.05, respectively). Thus, impaired left ventricular diastolic filling in the non-MI segments due to higher incidence of hypertension and left ventricular hypertrophy was considered to be the possible cause of pulmonary edema.

Cardiac Output↗
PubMed1993

Effect of infarct site on diastolic time during exercise.

To assess the difference in left ventricular performance during exercise between anterior (11 patients) and inferior (10 patients) myocardial infarction (MI) of equivalent size, patients performed a supine bicycle exercise 6 to 8 weeks after the first acute MI. All patients had negative exercise test results and despite no significant differences in HR, blood pressure and stroke volume index at peak exercise, pulmonary artery wedge pressure was significantly higher in anterior (35 +/- 7 mm Hg) than in inferior MI (27 +/- 9 mm Hg). Although there were no significant differences in electromechanical systole (QS2) and diastolic time (DT) at rest, a significant prolongation of QS2 with consequent shortening of DT (p < 0.01) was observed at peak exercise in anterior MI. In addition to decreased subendocardial coronary blood flow from increased left ventricular end-diastolic pressure, a disproportionate shortening of DT in anterior MI may initiate subendocardial ischemia in the noninfarcted segments, which may further impede subendocardial blood flow.

Blood Pressure↗
PubMed1993

Clinical significance of pericardial effusion associated with pericarditis in acute Q-wave anterior myocardial infarction.

To elucidate the incidence and clinical factors related to the occurrence of pericardial effusion in infarction-associated pericarditis, 303 consecutive patients with their first Q-wave anterior myocardial infarction were examined carefully by means of auscultation, echocardiography, chest radiography, and hemodynamic monitoring. During the first 3 days, a pericardial rub was detected in 65 patients and was absent in 238 patients. Among the 65 patients with pericardial rub, pericardial effusion was present in 27 patients (group 1) and was absent in 38 patients (group 2). Although there were no significant differences in cardiac output, pulmonary artery wedge pressure and right atrial pressure between the two groups, patients in group 1 had significantly more left ventricular segments with advanced asynergy and higher radiographic scores (diffuse interstitial infiltrate or alveolar infiltrate) compared with those in group 2. Thus, pericardial effusion and increased extravascular lung water in infarction-associated pericarditis were not caused by left ventricular failure but by other mechanisms reflecting a larger infarct.

Electrocardiography↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

[Gadolinium-DTPA magnetic resonance imaging in the diagnosis of left atrial myxoma in the elderly].

A 85-year-old woman consulted our hospital with general fatigue, palpitation and chest discomfort changing with different postures. Her electrocardiogram showed sinus tachycardia, atrial premature beats and left atrial overload. 53% cardiothoracic ratio, slightly protruding third arch of the cardiac silhouette and dilated pulmonary artery were seen on the chest X-ray. Two dimensional echocardiography revealed a mass in the left atrium although the quality of echocardiography was suboptimal due to her thoracic deformity. There was no uptake of T1-201 or Ga-67 by the mass. The four-chamber view of Tc-99m ECG-gated SPECT radionuclide angiocardiography showed a filling defect in the left atrium. The T1 weighted magnetic resonance imaging revealed a left atrial mass with relatively low signal intensity. After intravenous injection of Gadolinium-DTPA the signal intensity of the mass increased significantly and the contrast of the mass was improved. The size of the mass was 4 x 4 x 3 cm with a stalk connecting to the interatrial septum. These findings were compatible with left atrial myxoma. Gadolinium-DTPA magnetic resonance imaging is useful in diagnosing left atrial myxoma because it provides information on the size, anatomical location, relationship with other cardiovascular structures and even the characteristics of the mass.

Aged↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

Changes in lipid composition of erythrocyte membranes with administration of S-adenosyl-L-methionine in chronic liver disease.

This study was undertaken to determine whether S-adenosyl-L-methionine (SAMe) changes the lipid composition and fluidity of erythrocyte membranes in chronic liver disease. SAMe was administered intravenously at a daily dose of 600 mg for 2 weeks to 10 patients; 6 patients with cirrhosis and four with primary biliary cirrhosis. The elevated free cholesterol to phospholipid molar (C/PL) ratio of the erythrocyte membranes of the patients (0.857 +/- 0.018) significantly decreased after the administration of SAMe (1 week, 0.823 +/- 0.021; 2 weeks, 0.823 +/- 0.013). In all of the four patients whose erythrocyte membrane fluidity was measured, fluidity improved with the administration of SAMe and correlated with the C/PL ratio of the membranes. These results suggest that SAMe decreases the C/PL ratio of erythrocyte membranes and thus improves membrane fluidity in chronic liver disease.

Adult↗