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Biomedical subjects

M Inada

Publications and source records attributed to M Inada.

At least 109 records · Page 6Linked to original sources

Enhanced expression of group II phospholipase A2 in human hepatocellular carcinoma.

Enzyme activity, protein contents, and mRNA contents of group II phospholipase A2 (PLA2) in hepatocellular carcinoma (HCC) surgically obtained from 8 patients were compared with those in either its neighboring liver tissues or control liver tissues. The PLA2 specific activity towards the mixed micelles of 1-palmitoyl-2-oleoyl-phosphatidylglycerol and cholate was significantly greater in the tumor tissues (6.62 +/- 1.46 nmol/min/mg) than those in the surrounding liver tissues (1.33 +/- 0.22 nmol/min/mg) and controls (0.43 +/- 0.04 nmol/min/mg). The results of immunoblot analysis using a specific anti-human group II PLA2 antibody and of Northern blot analysis using a human group II PLA2 cDNA as a probe demonstrated that group II PLA2 was responsible for the increased enzyme activity. The contents of immunoreactive group II PLA2 in the tumor tissues (8.81 +/- 1.24 ng/mg) were significantly higher than those in the surrounding liver tissues (1.74 +/- 0.27 ng/mg); those in the control tissues were below the analytical range of the method used. The group II PLA2 mRNA was also significantly increased in the tumor tissues, compared with that in the surrounding liver tissues, whereas it was not detectable in the controls. This indicates that group II PLA2 in HCC is induced at the pretranslational level.

Carcinoma, Hepatocellular

Clinical significance of pericardial effusion in Q-wave inferior wall acute myocardial infarction.

To assess the clinical significance of pericardial effusion in Q-wave inferior wall acute myocardial infarction, 185 consecutive patients were examined by means of electrocardiogram, echocardiogram and hemodynamic monitoring. A pericardial effusion was present in 44 patients and was absent in 141 patients. Electrocardiographic right ventricular infarction (> or = 1 mm of ST-segment elevation and Q wave in V4R) was detected in 54 patients, with 20 patients having pericardial effusion. Patients with pericardial effusion had significantly more left ventricular segments with advanced asynergy, lower cardiac output, higher pulmonary artery wedge pressure and higher incidence of right ventricular infarction than those without pericardial effusion. There were 17 in-hospital deaths. Although there was no significant difference in the mortality rate between patients with and without right ventricular infarction, a significantly higher hospital mortality rate was observed in patients with pericardial effusion compared to those without it (23 vs 5%). Pericardial effusion was selected with age and pulmonary artery wedge pressure as important variables associated with hospital mortality by the discriminant analysis. Patients who developed pericardial effusion, regardless of right ventricular infarction, had more extensive myocardial damage, and hence, pericardial effusion was one of the predictors of increased hospital mortality.

Acute Disease

Clinical significance of PQ segment depression in acute Q wave anterior wall myocardial infarction.

OBJECTIVES: This study was designed to evaluate the clinical significance of PQ segment depression and to examine the frequency of PQ segment depression in infarction-associated pericarditis. BACKGROUND: PQ segment deviation is almost as characteristic as the classic ST segment deviation and is detected in most patients with pericarditis. However, the incidence and clinical characteristics of PQ segment depression in acute myocardial infarction are not defined. METHODS: Three hundred four consecutive patients with acute Q wave anterior wall myocardial infarction were examined carefully by auscultation, electrocardiogram, echocardiogram and chest roentgenogram. The diagnosis of pericarditis was made on the basis of pericardial rub detected by more than two observers during the 1st 3 days after hospital admission. At least 0.5 mm of PQ segment depression from the TP segment observed for > 24 h in both limb and precordial leads was considered diagnostic of PQ segment depression. RESULTS: A pericardial rub was present in 65 patients (21%) and absent in 239 patients. PQ segment depression was detected in both limb and precordial leads in 30 patients (10%): 18 patients with pericardial rub and 12 patients without pericardial rub. On the basis of five clinical variables, multivariate analysis was performed to determine the important variables related to the occurrence of PQ segment depression. Pericardial rub was selected with left ventricular segments with advanced asynergy as a significant factor related to PQ segment depression. There were 31 in-hospital deaths, and a significantly higher hospital mortality rate was observed in patients with PQ segment depression (23% vs. 9%). CONCLUSIONS: Although PQ segment depression was observed in a minority of patients with infarction-associated pericarditis, it was one of the clinical signs of larger infarct size and increased hospital deaths.

Echocardiography, Doppler

Difference between women and men in left ventricular pump function during predischarge exercise test after acute myocardial infarction.

To evaluate the difference in left ventricular (LV) pump function during predischarge exercise testing between postmenopausal women and age-matched men with myocardial infarction, global and regional ejection fraction, LV end-diastolic volume, and the ratio of systolic blood pressure to LV end-systolic volume were investigated using radionuclide angiography in 25 postmenopausal women and 37 age-matched men. There were no significant differences in the resting radionuclide angiographic indexes between women and men. Global and regional ejection fraction of noninfarcted area, and the ratio of systolic blood pressure to LV end-systolic volume decreased at peak exercise in women, but these indexes increased in men. Although there was no significant difference in the amount of change in LV end-diastolic volume during exercise between the 2 groups, the amount of increase in LV end-systolic volume was significantly larger in women than in men. The ratio of systolic blood pressure to LV end-systolic volume had a curvilinear relation with LV end-diastolic volume at rest and peak exercise, but the ratio of systolic blood pressure to LV end-systolic volume was larger at any LV end-diastolic volume in men than in women during exercise. Thus, lower global ejection fraction and the ratio of systolic blood pressure to LV end-systolic volume during exercise in postmenopausal women compared with age-matched men indicate that gender may have played an important role in the LV remodeling process.

Aged

Quantification of infarct size by thallium-201 single-photon emission computed tomography using the unfolded map method. Comparison with QRS score and angiographic infarct size at 4 weeks after infarction.

A new technique of data processing, the unfolded map method, was used with thallium-201 single-photon emission computed tomography to quantify infarct size in 35 patients with single-vessel disease at 4 weeks after their first myocardial infarction (24 anterior and 11 inferior infarcts), and the results were compared with those obtained by electrocardiography and contrast left ventriculography. The myocardial borders and the infarcted region were defined using the threshold technique and a cutoff value of 55%. Count profile data for each short-axis slice were unfolded zonally into single planes with the same ratio, and their areas were calculated from the slice thickness and radius. Thus, the size of the unfolded map represented the actual left ventricular myocardial area Infarct size was quantitated from the ratio of pixels in the infarcted region to those in the whole map, and the ratio itself was used as the percent infarct size. Although a defect 1 cm in diameter (0.8 cm2) could not be detected in a phantom study, defects > or = 2 cm in diameter (> or = 3.1 cm2) could be measured satisfactorily. The infarct size and percent infarct size determined by the unfolded map method correlated well with the QRS score (r = 0.841 and r = 0.838), the percentage of abnormally contracting segments on left ventriculography (r = 0.835 and r = 0.877), and the ejection fraction (r = -0.835 and r = 0.856). These data indicate that the unfolded map method provides adequate quantification of infarct size, even in the chronic phase, without complicated data processing.

Adult

The effect of successful angioplasty on variables of signal-averaged electrocardiogram and ventricular wall motion in patients with a first myocardial infarction.

The correlation among three variables of late potentials (LPs) obtained by signal-averaged electrocardiography (SAECG) and improvement of ventricular wall motion estimated by echocardiography were studied in 66 patients with a first acute myocardial infarction (MI). Patients with bundle-branch block, intraventricular conduction delay, multi-vessel disease, previous MI, repeat percutaneous transluminal coronary angioplasty (PTCA), or evidence of reinfarction during a 6-month follow-up were excluded. A total of 66 patients was divided into two groups, with (Group 1: n = 27, age 56 +/- 11) or without (Group 2: n = 39, age 61 +/- 10) improvement of ventricular wall motion. Three variables of LPs and ventricular wall motion index (WMI) estimated and scored by echocardiography at admission (WMI 1) and at 6 months after MI (WMI 2) were compared in each group. In Group 1 (WMI 1 vs. WMI 2, p < 0.002), 20 of 27 patients underwent successful angioplasty; in Group 2 (WMI 1 vs. WMI 2, p = NS), 7 of 39 patients had successful emergency angioplasty. There were significant differences in three variables of LPs between the time of admission and at 6 months after MI in Group 1 but not in Group 2. Higher incidence of LPs and greater frequency of successful emergency PTCA were found in Group 1 compared with Group 2. These results suggest that because myocardial ischemia is reversed by successful angioplasty, ventricular wall motion is improved and the arrhythmogenic substrate that generates LPs is stabilized electrically. Stunned or hibernating myocardium may be the arrhythmogenic substrate that generates LPs.

Adult

Alteration of glycosaminoglycans induced by cadmium in cultured vascular smooth muscle cells.

Alteration of glycosaminoglycans (GAGs) in cultured bovine aortic smooth muscle cells after exposure to cadmium was investigated. It was revealed that cadmium increased the accumulation of GAGs metabolically labeled with [3H]glucosamine but decreased that with [35S]sulfate in the cell fraction, the cell surface fraction and the medium fraction. This suggested that cadmium stimulated the biosynthesis of GAGs but inhibited their sulfation in the cells. A similar alteration was observed in cadmium-treated human aortic smooth muscle cell layer. Of tested cations including cadmium, bismuth, cobalt, copper, lead, manganese, nickel and zinc, only cadmium stimulated [3H]glucosamine incorporation, with a strong inhibition of the [35S]sulfate incorporation in the bovine cells. Characterization of bovine smooth muscle GAGs showed that the cadmium-induced increase in the [3H]glucosamine incorporation was mainly observed in heparan sulfate; the inhibition of the [35S]sulfate incorporation occurred non-selectively. Cadmium accumulated in bovine vascular smooth muscle cells in a dose-dependent manner with an increase in the leakage of lactate dehydrogenase into the medium. The present data suggest that vascular smooth muscle cells respond to the cytotoxicity of cadmium and promote the GAG synthesis with a reduction of their sulfation. It is postulated that this response may be a defensive one to the damage of the vascular tissue caused by cadmium but would be a component of the metal-induced atherosclerosis.

Animals

Right ventricular ejection fraction during exercise in patients with recent myocardial infarction: effect of the interventricular septum.

To investigate the effect of interventricular septum (IVS) on right ventricular function during exercise, radionuclide angiocardiography was performed in 50 patients with recent myocardial infarction. Twenty-five patients had involvement of IVS according to thallium uptake in IVS (group I), and 25 patients were free of IVS involvement (group II). Although there was no statistical difference between the two groups in right ventricular ejection fraction (EF) at rest (45% +/- 10% vs 48% +/- 8%), patients in group I had significantly lower left ventricular (LV) EF (40% +/- 11% vs 53% +/- 11%, p < 0.01) and larger LV end-diastolic volume (129 +/- 46 vs 106 +/- 31 ml, p < 0.05) than those in group II. All parameters increased significantly during exercise in both groups, but patients in group I had significantly lower exercise right ventricular EF (50% +/- 10% vs 56% +/- 9%, p < 0.05), LVEF (44% +/- 11% vs 56% +/- 13%, p < 0.01), and larger LV end-diastolic volume (155 +/- 44 vs 129 +/- 37 ml, p < 0.05) than those of group II. Significant correlations were observed between right ventricular EF and LV end-diastolic volume at rest and during exercise (r = -0.48, p < 0.05, and r = -0.68, p < 0.01, respectively) in group I, but right ventricular EF correlated with LVEF only at peak exercise (r = 0.65, p < 0.01). In contrast, right ventricular EF did not correlate with any variables at rest or during exercise in group II.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The factor dominating the determination of left ventricular filling varies during the first five days after acute myocardial infarction.

BACKGROUND: Left ventricular diastolic dysfunction may occur after the onset of acute myocardial infarction. Left ventricular diastolic filling dynamics are related to many factors. To evaluate the influence of left ventricular filling pressure on Doppler-derived left ventricular diastolic flow profiles in patients with acute myocardial infarction, we studied serial changes in filling during the first 5 days after the onset of uncomplicated acute myocardial infarction. METHODS: The study population consisted of 14 patients with acute myocardial infarction and 15 normal subjects: Doppler echocardiographic studies (left ventricular transmitral inflow and outflow velocity patterns) were performed on admission, and on the third and fifth days after infarction. Hemodynamic parameters were measured simultaneously using Doppler echocardiography. RESULTS: The E wave was lower, the A wave and A:E ratio were higher, deceleration half time and isometric relaxation time were prolonged, and peak left ventricular ejection flow velocity was lower in myocardial infarction patients than in normal subjects. The E wave and pulmonary capillary wedge pressure were positively correlated on the first and the third day (r = 0.77, P < 0.001, and r = 0.67, P < 0.01, respectively), but not on the fifth day. The E wave and isometric relaxation time were negatively correlated on the fifth day (r = -0.72, P < 0.01), but not on the first and third day. CONCLUSION: Left ventricular filling pressure (preload) was an important mechanism for maintaining left ventricular filling during the first 3 days, but the relaxation of the ventricle began to play a dominant role on the fifth day.

Aged

Residual left ventricular pump function following acute myocardial infarction in postmenopausal diabetic women.

BACKGROUND: The Framingham Study indicated that women with diabetes mellitus developed cardiac failure four times more often than those without diabetes mellitus after acute myocardial infarction. However, there is little information on residual left ventricular pump function after myocardial infarction in female diabetic patients. METHODS: To evaluate the difference between postmenopausal women and age-matched men in the impact of diabetes mellitus on left ventricular pump function during the first year after myocardial infarction, radionuclide angiography was performed during the third week after acute myocardial infarction and again 1 year later in 50 patients (21 women, 29 men) with diabetes mellitus and 62 patients (25 women, 37 men) without diabetes mellitus. RESULTS: Although the radionuclide angiographic indices did not change during the first year after myocardial infarction in non-diabetic patients, left ventricular end-diastolic volume increased, and the left ventricular ejection fraction, the regional ejection fraction of the non-infarcted area, and the ratio of arterial systolic blood pressure to left ventricular end-systolic volume (pressure:volume ratio) decreased in the diabetic patients. Furthermore, the degree of change in the left ventricular end-diastolic volume, the left ventricular ejection fraction, the regional ejection fraction of the non-infarcted area, and the pressure:volume ratio in diabetic women was larger than that in diabetic men. CONCLUSION: The increase in the left ventricular end-diastolic volume and the decrease in the regional ejection fraction of the non-infarcted area during the first year after myocardial infarction in postmenopausal women with diabetes mellitus indicate that female sex associated with diabetes mellitus may be important factors in left ventricular remodeling in postmenopausal women.

Aged

Late potentials during left ventricular healing of acute myocardial infarction.

BACKGROUND: Late potentials and left ventricular remodeling are important factors in the prognosis of acute myocardial infarction. However, the relationship between late potentials and ventricular remodelling has not been fully evaluated. METHODS: We evaluated clinical characteristics, coronary angiographic findings and radionuclide angiographic measures about 1 month after an acute myocardial infarction in patients with and without late potentials. RESULTS: Although the left ventricular ejection fraction of patients with late potentials was not different from that of patients without late potentials, the left ventricular end-diastolic volume of patients with late potentials was larger than that of patients without late potentials (P < 0.05). There was a significant positive correlation between the left ventricular end-diastolic volume and the filtered QRS duration (r = 0.53, P < 0.001). The root mean square of the voltage in the terminal 40 ms and the low-amplitude signal duration of < 40 microV in the terminal QRS sequence were also correlated with the left ventricular end-diastolic volume (r = 0.40, P < 0.02, and r = 0.39, P < 0.02, respectively). Patency of the infarct-related vessel in the late phase of an acute myocardial infarction was an important factor associated with the occurrence of late potentials (P < 0.01). CONCLUSION: A larger left ventricular end-diastolic volume in patients with late potentials might be associated with left ventricular remodeling during the first month after an acute myocardial infarction.

Coronary Angiography

The effect of platelet-activating-factor antagonist TCV-309 on arrhythmias and functional recovery during myocardial reperfusion.

BACKGROUND: We investigated the effects of a platelet-activating-factor antagonist TCV-309, an antagonist of metabolites of ischemia, on arrhythmias and functional recovery during in-situ reperfusion in dogs. METHODS: Open-chest anesthetized dogs were subjected to ligation of the left anterior coronary artery. Ischemia was maintained for 20 min after which reperfusion was allowed. A cardiac surface ECG was recorded continuously with the II limb lead. Monophasic action potential, left ventricular segment shortening measured by sonomicrometer, and left ventricular pressure were recorded simultaneously under atrial pacing (group A, n = 14). In a second group of dogs, TCV-309 (1 mg/kg) was administered before coronary artery occlusion (group B, n = 12). The hearts were constantly paced through the right atrium at 120 beats/min throughout all experiments. Measurements were continuously obtained from before drug administration to 30 min after reperfusion. RESULTS: The 90% repolarization time of monophasic action potentials in group B revealed significant recovery compared with group A until the fifth minute after reperfusion (P < 0.02). Reduction of severe ventricular arrhythmias was observed during reperfusion in group B (P < 0.05). The percentage segment shortening and left ventricular pressure did not differ significantly between the groups. CONCLUSION: The platelet-activating-factor antagonist had beneficial effects on arrhythmias but not on functional recovery during reperfusion after brief coronary artery occlusion in situ in dogs.

Action Potentials

Clinical significance of right ventricular dilatation in patients with right ventricular infarction.

BACKGROUND: Right ventricular infarction can be accurately diagnosed by ST-segment elevation in the right precordial leads. However, the clinical outcome of right ventricular infarction encompasses a wide spectrum, ranging from no hemodynamic compromise to cardiogenic shock. The present study examined the clinical significance of echocardiographic right ventricular dilatation in patients with right ventricular infarction. METHODS: We studied 60 consecutive patients with ECG evidence of right ventricular infarction (at least 1 mm ST-segment elevation and QS or QR in V4R) after their first acute Q-wave inferior infarction. They had been admitted to the coronary care unit within 24 h of the onset of chest pain. The presence of right ventricular dilatation was diagnosed when the end-diastolic ratio between right and left ventricle was more than 0.5 on two-dimensional echocardiogram. RESULTS: Of the 60 patients with ECG evidence of right ventricular infarction, 29 had right ventricular dilatation (group 1) and 31 did not (group 2). We used four clinical variables in multivariate analysis to determine the significant factors related to right ventricular infarction. Mean right atrial pressure and number of left ventricular segments with advanced asynergy were found to be the important factors. Furthermore, a significantly higher incidence of major complications (cardiogenic shock and need for temporary pacing) was observed in group 1 than in group 2. Right ventricular dilatation was found to be the significant factor related to major complications. CONCLUSION: Echocardiographic right ventricular dilatation is an important non-invasive sign obtained on admission in patients with right ventricular infarction, because it is associated with larger left ventricular infarct size and increased risk of major complications.

Aged

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

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