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Biomedical subjects

K Miyatake

Publications and source records attributed to K Miyatake.

At least 19 recordsLinked to original sources

Direct secretion from left atrium and pulmonary extraction of human atrial natriuretic peptide.

To evaluate direct secretion from the left atrium and pulmonary extraction of human atrial natriuretic peptide (hANP), we measured plasma hANP levels in the pulmonary artery, pulmonary vein, and left atrium in patients with either mitral stenosis or atrial septal defect. Left atrial pressure in patients with mitral stenosis was significantly higher than that in patients with atrial septal defect (7.5 +/- 1.0 mm Hg vs 3.1 +/- 0.5 mm Hg, p less than 0.01). The significant increase in the hANP level in the left atrium was recognized only in patients with mitral stenosis (149 +/- 33 pg/ml in the left atrium vs 130 +/- 28 pg/ml in the pulmonary vein, p less than 0.05). The plasma hANP level in the pulmonary vein was significantly lower than that in the pulmonary artery in both patients with mitral stenosis and those with atrial septal defect, which suggests that hANP is extracted in the lung. We conclude that hANP is secreted not only through the coronary sinus but also directly from the left atrium, stimulated by high left atrial pressure, and that circulating hANP is partially extracted in the pulmonary circulation.

Adult

Clinical application of transpulmonary contrast-enhanced Doppler technique in the assessment of severity of aortic stenosis.

OBJECTIVE: The aim of this study was to demonstrate the clinical usefulness of the transpulmonary contrast-enhanced Doppler technique by using it to assess the severity of aortic stenosis. BACKGROUND: Sonicated albumin microbubbles can pass through the pulmonary circulation after peripheral venous injection and have been reported to enhance Doppler signals from the left side of the heart. Therefore, their use to determine aortic flow velocity would facilitate the assessment of the severity of aortic stenosis. METHODS: Twenty-two patients with aortic stenosis and seven normal volunteers were examined. Aortic flow velocity was recorded with continuous wave Doppler technique from an apical window before and after injection of 2 ml of sonicated albumin. RESULTS: In 10 patients with aortic stenosis, the aortic velocity envelope was too indistinct to determine the peak velocity before sonicated albumin was injected. After injection, the aortic flow Doppler signal was enhanced in 9 of the 10 patients and the velocity envelope became clear enough to measure the peak velocity, enabling calculation of the transaortic pressure gradient. In the remaining 12 patients with aortic stenosis and in all 7 normal volunteers, the velocity envelope was clear before injection and became much clearer after injection. The calculated transaortic pressure gradient showed a good agreement with catheterization measurements (y = 1.1x-6.5, r = 0.88, p less than 0.001, SEE = 16 mm Hg, n = 13). Duration of Doppler signal enhancement was measured as the time during which the envelope was clearer than before injection throughout the ejection period. The duration was significantly shorter in patients with aortic stenosis than in normal volunteers (16 +/- 5 vs. 52 +/- 32 s, p less than 0.01). There was a significant correlation between left ventricular systolic pressure measured by catheterization and the duration of signal enhancement (r = -0.69), suggesting that albumin microbubbles were fragile at high pressure. CONCLUSIONS: The transpulmonary contrast-enhanced Doppler technique using sonicated albumin is useful for assessing the severity of aortic stenosis even in patients with poor Doppler recordings, although the duration of signal enhancement might be affected by left ventricular systolic pressure.

Aortic Valve Stenosis

Left ventricular function and the relationship between left atrial pressure and peak early diastolic filling velocity in dog.

OBJECTIVE: The aim was to clarify the roles of left atrial pressure and ventricular function in the determination of early diastolic filling. METHODS: Various grades of ventricular dysfunction were made in 12 mongrel dogs by coronary microembolization under pentobarbitone anaesthesia. Left atrial pressure was altered by volume loading. Peak early diastolic filling velocity was measured using pulsed Doppler echocardiography. Ventricular fractional shortening was measured using M mode echocardiography. RESULTS: Peak early filling velocity increased as left atrial pressure increased. There was a direct relationship between mean left atrial pressure and the velocity before and after induction of ventricular dysfunction. The slope of the regression line between mean left atrial pressure and peak early filling velocity decreased as the grade of the dysfunction increased. There was a significant correlation between the slope of the regression line and mean left ventricular fractional shortening (r = 0.65, n = 31, p less than 0.01). CONCLUSIONS: Early diastolic filling was affected by both left atrial pressure and left ventricular function. These facts are useful in interpreting the various transmitral flow patterns observed clinically.

Animals

Quantitative assessment of coronary artery stenosis by intravascular Doppler catheter technique. Application of the continuity equation.

BACKGROUND: Quantitative assessment of coronary artery stenoses plays a central role in clinical decision making. According to the continuity equation, the ratio of the time-velocity integral of prestenotic to stenotic flow velocities represents the ratio of the cross-sectional area of the stenotic to prestenotic segments. However, no data exist regarding the application of this method to clinical assessment of human coronary artery diseases. Therefore, we attempted to determine the severity of coronary artery stenoses by applying the continuity equation to the coronary circulation. METHODS AND RESULTS: Nineteen patients with a stenosis of the proximal left anterior descending coronary artery (LAD) and one patient with a stenosis in an aortocoronary bypass graft to the LAD were studied. Coronary flow velocities at the prestenotic and stenotic segments were measured with an end-mounted Doppler catheter (3F, 20 MHz), and the time-velocity integral ratio was calculated. Percent area stenosis was calculated as (1-time-velocity integral ratio) x 100. In three patients with severe stenosis (greater than 90% in area stenosis), velocity at the stenosis could not be determined because of aliasing of Doppler signals, and in four, Doppler signals at the stenosis were not measurable because of technical difficulties. The stenotic flow velocity was successfully recorded in 13 patients (65%) with mild to moderate stenosis. The diastolic peak flow velocity at the stenosis was 90 +/- 36 cm/sec (mean +/- SD), and was significantly greater than the velocity at the prestenotic segment, 48 +/- 18 cm/sec (p less than 0.01). Percent area stenosis determined by Doppler continuity equation correlated closely with that by biplane coronary angiography (r = 0.83, y = 0.92x-0.45, p less than 0.01). CONCLUSIONS: Application of the continuity equation to Doppler catheter measurement of coronary flow velocity can be used to successfully compute the severity of coronary stenoses. This may be a useful alternative method to estimate functional severity of coronary artery disease, although further technical developments will be necessary to improve the sensitivity.

Aged

The gap between mitral leaflets as a cause of mitral regurgitation: relationship to mitral valve prolapse.

The gap between the tips of the anterior and posterior mitral leaflets was studied to assess the significance of this gap in the diagnosis of mitral valve prolapse. The subjects were 39 patients in whom the gap was seen and the mitral valve did not exceed the mitral annular line in systole on two-dimensional echocardiography. Forty eight healthy subjects, in whom phonocardiography disclosed no abnormalities, served as controls. The site of the gap as well as the site and severity of mitral regurgitation were assessed with two-dimensional echocardiography and Doppler flow imaging. The incidence of mitral regurgitation was 82%, which was comparable to that in the controls (67%). The site of the gap was consistent with that of regurgitation. The gap was also seen in a low percentage of healthy subjects, but clinically significant mitral regurgitation did not accompany the gap in healthy subjects including the gap-carrying controls. On the other hand, many of the gap-carrying patients showed clinically significant mitral regurgitation. Also the fact that a gap between the tip of the anterior and posterior mitral leaflets was found to be frequently accompanied by phonocardiographical features corresponding to mitral valve prolapse indicates that the presence of a gap is a significant finding.

Adolescent

[Serum neuron specific enolase (NSE) levels in patients with non small cell lung cancer].

Serum NSE levels were measured in 126 patients with previously untreated NSCLC. The NSE level was greater than 10 ng/ml in 29 patients (23.0%) and this was considered to be positive. Elevation of serum NSE levels correlated closely with clinical stage except stage I and II. The effect of chemotherapy was evaluated in 74 cases included 22 NSE-positive cases. The response rate was 50% in positive cases and 34.6% in negative cases. However, the median duration of response in positive cases (2.2 months) was significantly shorter than that in negative cases (6.6 months). The median survival time of 6.0 months in positive cases was brief compared with 9.6 months in negative cases. These results indicate that elevation of serum NSE level in patients with NSCLC may be a marker of poor prognosis.

Adenocarcinoma

Serial changes of mitral flow pattern after percutaneous transvenous mitral commissurotomy--assessment of Doppler and two-dimensional echocardiography.

To evaluate the acute change in the mitral flow pattern, especially pressure half-time after percutaneous transvenous mitral commissurotomy (PTMC) and to investigate the factors influencing the mitral flow pattern, Doppler and two-dimensional echocardiographic studies were performed in 15 patients before and two, six, 10 and 24 hours and seven days after PTMC. Mitral valve area increased and the mean mitral pressure gradient decreased after PTMC (1.0 +/- 0.4 cm2 to 1.8 +/- 0.4 cm2; 11 +/- 6 mmHg, to 3 +/- 2 mmHg, p < 0.01). Pressure half-time also decreased two hours after surgery, from 292 +/- 70 msec to 176 +/- 48 msec (p < 0.01) and then gradually decreased to 140 +/- 47 msec within seven days of the procedure without remarkable changes in mitral valve area and the mean transmitral pressure gradient. Left atrial dimensions decreased and left ventricular end-diastolic dimensions gradually increased after PTMC (51 +/- 6 mm to 46 +/- 5 mm; 47 +/- 4 mm to 50 +/- 3 mm). The time course of this was similar to that of the pressure half-time. Further study, in which the changes in pressure half-time were evaluated within 30 minutes of PTMC in 17 patients, indicated that pressure half-time significantly decreased from 248 +/- 69 msec to 139 +/- 28 msec five minutes after balloon inflation, slightly increasing again after 30 minutes to 153 +/- 31 msec.(ABSTRACT TRUNCATED AT 250 WORDS)

Catheterization

[High incidence of left ventricular thrombosis and systemic embolism in patients with left ventricular assist system].

The purpose of this study was to determine the incidence of left ventricular (LV) thrombosis and systemic embolism in 14 patients with LV assist systems. Echocardiography was used to detect LV wall motion abnormalities, intracavitary smoke-like echoes and thrombosis, and the effect of anticoagulant therapy was serially examined. During full assist of the circulation, the aortic valve did not open in any patient. Smoke-like echoes were observed in 9 patients (64%) and thrombi in 8 (57%). The thrombus developed within the first 3 assist days. Systemic anticoagulant therapy decreased the thrombus size in only 3 patients, but there was a possibility of intracranial or mediastinal bleeding in other 3 patients. Systemic embolism was noted in 7 of 11 autopsy patients (64%). The characteristic finding was that there were multiple embolized organs, such as the brain, kidneys, spleen and liver, in all patients. Development of a thrombus is a serious complication in all patients with LV assist systems. However, the problem does not lie in the assist system but in the left ventricle of the patient's own heart. It is also noteworthy that systemic anticoagulation is not effective for an LV thrombus. A new method of assisting the failing heart, or a new anticoagulant delivery technique for the LV cavity to prevent LV thrombus development is needed.

Adult

[Immunohistochemical detection of carcinoembryonic antigen and P-glycoprotein in small cell lung cancer at diagnosis and relapse, with special reference to the tissue expression of CEA and response to chemotherapy].

Small cell lung cancer (SCLC) is one of the most sensitive tumors to drug therapy; however, the majority of patients eventually relapse within a few years. Emergence of drug resistance is thought to play a major role in the dismal course of this disease. However, the mechanism of drug resistance in SCLC still remains obscure. Based on the clinical observation that a significant proportion of patients with relapsing tumor show an elevated serum carcinoembryonic antigen (CEA) concentration while serum neuron-specific enolase (NSE) concentration remains normal, we attempted to determine whether the tissue of CEA is indicative of a clonal change in SCLC, in contrast with the tissue expression of NSE and P-glycoprotein (P-gp). We examined 22 SCLC patients with tumor specimens available both at diagnosis and at relapse. Of the 22 patients, two had CEA expression at diagnosis, and a further three patients showed CEA expression at relapse. It is of note that there were two patients whose tumors expressed NSE alone at diagnosis but expressed CEA alone at relapse. Serum CEA concentration was concordant with the tissue expression of CEA; however, serum NSE concentration was not concordant with the tissue expression of NSE. Tumors with CEA expression at relapse were generally resistant to salvage chemotherapy, while there was no close relationship between the tissue expression of P-gp and refractoriness to drugs at relapse. These findings indicate that the tissue expression of CEA in SCLC is a marker of a clonal change during chemotherapy, and such a clonal change would play a role in the emergence of drug resistance in SCLC.

ATP Binding Cassette Transporter, Subfamily B, Mem

Validity of catheter-tip Doppler technique in assessment of coronary flow velocity and application of spectrum analysis method.

Measurement of coronary flow velocity in clinical cases contributes to understanding the pathophysiology of coronary circulation. To determine absolute coronary flow velocity, coronary blood flow was assessed with an end-mounted Doppler catheter (3Fr, 20 MHz), which was combined with a custom-designed fast-Fourier transformation analysis system. In vitro study using model circuit, actual flow velocity (8 to 96 cm/s) was well correlated with that determined by this catheter system (y = 1.01 X +1.5, r = 0.988). In a clinical study of 12 patients with normal coronary arteriograms, the Doppler catheter was positioned at the proximal left anterior descending artery. Clear flow velocity patterns, which consisted of predominant diastolic components and preceding small systolic components, were obtained in all cases. The peak flow velocity was 17 +/- 8 cm/s (mean +/- standard deviation) during systole and 44 +/- 12 cm/s during diastole in this portion. In 5 patients, the great cardiac vein flow, which reflects the left anterior descending artery flow, was simultaneously measured during rapid atrial pacing. During pacing, percent increases in flow velocity were well correlated with those in great cardiac vein flow (y = 0.90 x +6.4, r = 0.935). These results indicate that catheter-tip Doppler technique with fast-Fourier transformation analysis may be useful in quantitatively determining coronary flow velocity in clinical cases.

Aged

Effects of percutaneous transvenous mitral commissurotomy on levels of plasma atrial natriuretic peptide during exercise.

To clarify the factors that influenced the secretion of human atrial natriuretic peptide (ANP) during exercise, we studied the relations between the changes in ANP, transmitral pressure gradient, heart rate and blood pressure at exercise in 16 patients with mitral stenosis before and after percutaneous transvenous mitral commissurotomy (PTMC). Before PTMC, ANP levels increased from 107 +/- 70 to 183 +/- 96 pg/ml during exercise testing (p less than 0.01), concomitant with the increment in mean transmitral pressure gradient, heart rate and systolic blood pressure. After PTMC, ANP levels also increased from 78 +/- 43 to 117 +/- 64 pg/ml, concomitant with the increment of those parameters. However, increments of ANP, mean transmitral pressure gradient and heart rate after PTMC were lower than those before PTMC. Because the most important factor influencing the secretion of ANP was unclear, the differences between these parameters were calculated at submaximal exercise before and after PTMC. There was a significant relation only between the change in ANP and mean transmitral pressure gradient (r = 0.70, p less than 0.01). These results suggest that the most important factor influencing the secretion of ANP during exercise is the change in transmitral pressure gradient in patients with mitral stenosis.

Atrial Natriuretic Factor

Balloon diameter of the Inoue balloon catheter during percutaneous transvenous mitral commissurotomy: clinical and experimental study.

To determine adequate and effective balloon diameters of the Inoue balloon catheter, we reviewed clinical results and characteristics of the Inoue balloon catheter, especially the relationship between the intra-balloon pressure and the balloon diameter, experimentally and clinically, in 46 patients with mitral stenosis undergoing percutaneous transvenous mitral commissurotomy (PTMC). Mitral valve area increased from 1.1 +/- 0.3 to 2.1 +/- 0.3 cm2 in all patients after PTMC. Based on balloon diameter settings, mitral valve area increased from 1.3 +/- 0.4 to 2.3 +/- 0.5 cm2 in patients treated with a balloon setting greater than 26 mm in diameter, from 1.1 +/- 0.3 to 2.0 +/- 0.5 cm2 in patients with a balloon setting at 26 mm in diameter, and from 1.1 +/- 0.4 to 1.7 +/- 0.4 cm2 in those treated with a balloon setting less than 26 mm in diameter, with an increase in mitral valve area of 1.0 +/- 0.6, 0.9 +/- 0.4, and 0.7 +/- 0.2 cm2, respectively. There was a significant difference between the increase in mitral valve area at a setting of 26 mm in diameter and that observed at a setting less than 26 mm in diameter. We next investigated differences between balloon diameter settings and actual balloon diameters measured from cineangiograms at maximum balloon inflation. The ratio of actual balloon diameter to a setting diameter of less than 26 mm was smaller than that of 26 mm. To evaluate the reason for the difference, we investigated the relationship between intra-balloon pressure and balloon diameter. In the prototype Inoue balloon catheter, intra-balloon pressure increases from 1.0 kg/cm2 at 20 mm in diameter to 2.2 kg/cm2 at 30 mm in diameter at atmospheric pressure. In conclusion, the increase in mitral valve area was inadequate when the balloon was less than 26 mm in diameter because of inadequate intra-balloon pressure. We, therefore, recommend a balloon size set above 26 mm to obtain adequate intra-balloon pressure when using the Inoue balloon catheter.

Catheterization

Acute reduction of mitral valve area after percutaneous balloon mitral valvuloplasty: assessment with Doppler continuity equation method.

Mitral valve areas before and after balloon mitral valvuloplasty were serially determined by the Doppler continuity equation method in 16 patients. Ultrasound examinations were performed before and immediately after balloon inflation and 24 hours, 1 week, and 1 month after valvuloplasty. Mitral valve area determined by the Doppler continuity equation method correlated well with that determined at catheterization by the Gorlin formula, not only before but also immediately after balloon inflation (y = 0.87 x + 0.05, standard error of estimate = 0.22 cm2, r = 0.90). Serial calculation of mitral valve area by the Doppler continuity equation method showed a slight but significant decrease in the valve area at 24 hours after balloon mitral valvuloplasty but no change after that. We conclude that the Doppler continuity equation method provides an accurate estimation of mitral valve area before and even after balloon valvuloplasty. Mitral valve area dilated by balloon inflation is decreased slightly within 24 hours after the procedure, which corroborates valve stretch as one mechanism for increasing mitral valve area with balloon valvuloplasty. Estimation of mitral valve area immediately after balloon mitral valvuloplasty may overestimate the long-term efficacy of the procedure.

Cardiac Catheterization

Pyruvate:NADP+ oxidoreductase from Euglena gracilis: limited proteolysis of the enzyme with trypsin.

Pyruvate:NADP+ oxidoreductase from Euglena gracilis, a homodimeric protein with a molecular weight of 309 kDa, is an iron-sulfur flavoenzyme that contains thiamin pyrophosphate (TPP). The functional structure of the enzyme was studied by a limited proteolysis experiment using trypsin. The evidence obtained shows that the enzyme consists of two functional domains, one of which contains an iron-sulfur cluster, which can be isolated as a homodimeric fragment of approximately 220 kDa by proteolysis. The other domain that contains FAD is released as a monomeric fragment of approximately 55 kDa. The pyruvate dehydrogenase reaction is still catalyzed by the large fragment when NADP+ is substituted by methyl viologen, while the small fragment retains a diaphorase-like electron-transfer activity from NADPH to MV. It is thus shown that pyruvate is oxidized in a CoA-dependent reaction to form CO2 and acetyl-CoA in the iron-sulfur domain, and that the two electrons formed are transferred to the FAD domain in which NADP+ is reduced. TPP is considered to be associated in the iron-sulfur domain. The NH2-terminal sequences of the enzyme and its proteolytic fragments reveal that the iron-sulfur domain occurs in the NH2-terminal side of the enzyme. For elucidation of the O2 instability of the enzyme, limited proteolysis was attempted in air. The tryptic fragment derived from the iron-sulfur domain, similar to the native enzyme, appears to be inactivated by direct contact with O2. In contrast, the FAD domain, when separated from the other domain, is quite stable in air, although the diaphorase activity decays when the native enzyme is exposed to O2.

Amino Acid Sequence