PubMed HealthSearch

Biomedical subjects

M Yoshimura

Publications and source records attributed to M Yoshimura.

At least 73 records · Page 4Linked to original sources

Capacitative Ca2+ entry regulates Ca(2+)-sensitive adenylyl cyclases.

A number of the currently described adenylyl cyclase species can be regulated by Ca2+ in the submicromolar concentration range in in vitro assays. The regulatory significance of these observations hinges on whether a physiological elevation in intracellular Ca2+ can regulate these cyclase activities in intact cells. However, achieving a physiological elevation in cytosolic Ca2+ is complicated by the fact that hormonal increases in cytosolic Ca2+ can be accompanied by additional effects, such as liberation of beta gamma-subunits of G-proteins and activation of protein kinase C, which can have disparate type-specific effects on cyclase activities. Therefore we have devised a strategy based on capacitative Ca2+ entry to show that, when types I and VI adenylyl cyclase are expressed in human embryonic kidney 293 cells, they are stimulated and inhibited respectively by Ca2+ entry. Blockade of Ca2+ entry by La3+ ions blocks the effects of Ca2+ entry on cyclic AMP synthesis. These studies establish that adenylyl cyclases deemed to be sensitive to Ca2+ in in vitro assays can be regulated by physiological Ca2+ entry, and therefore, such cyclases are poised to respond to changes in intracellular Ca2+ in tissues in which they are expressed.

Adenylyl Cyclases

Treatment of tuberculous empyema with multiple fistulae by reexpansion of the affected lung and restoration of its function: report of a case.

We report herein the case of a patient in whom a calcified tuberculous empyema with multiple fistulae was successfully treated by a new surgical approach. Reexpansion of the affected lung which had calcified over 30 years was achieved by covering the multiple bronchial fistulae using the omentum without obliterating the empyema cavity. Although the patient presented with severe aspiration pneumonia, he made a complete recovery and is now leading a better quality of life than before. This new operative method is less invasive and can therefore be performed much more easily on critically ill patients than conventional methods.

Bronchial Fistula

One hundred and one cases of bronchoplasty for primary lung cancer.

The results of 101 consecutive bronchoplasties performed between 1979 and 1993, including 8 cases of pneumonectomy, 88 cases of lobectomy, 3 cases of segmentectomy, and 2 cases of bronchial resection, are herein reported. Squamous cell carcinoma was the most common disease (59%) followed by adenocarcinoma (30%) and other diseases (11%). Anastomosis was satisfactory in 96 cases. Among the five stenosed cases, local recurrence was found in two cases, and there were three benign strictures. Two of the three benign strictures were treated with bouginage. The pulmonary artery was concomitantly reconstructed in seven cases with satisfactory results. Preoperative chemoradiotherapy was performed in 15 advanced cases and was followed by acceptable surgical results. The 5-year survival rate, according to the postoperative staging of the 86 patients without induction therapy, was 86% in stage I (19 patients), 49% in stage II (21 patients), and 27% in stage IIIA (40 patients). The overall survival rate was 46% at 5 years. There were two indications for this procedure i.e., a positive resection margin in 59 cases and positive hilar nodes in 42 cases. Better survival was noted in patients with squamous cell carcinoma, stage I, and surgery was thus selected for a positive resection margin, and not for a positive node.

Bronchi

Successful surgical treatment of a pseudoaneurysm after composite graft replacement of the aortic valve and ascending aorta: report of two cases.

Composite graft replacement of the ascending aorta and aortic valve has now become a safe surgical procedure; however, early and late complications still frequently occur. Anastomotic dehiscence after a composite graft replacement is one potentially lethal complication. We herein report two cases of a pseudoaneurysm caused by dehiscence of the right coronary anastomosis, and the proximal aortic anastomosis. A follow-up with an echocardiogram and computed tomography scan was found to be very useful and accurate. We thus successfully treated two cases of pseudoaneurysm using either Bentall's or Carbrol's procedures.

Adult

The superiority of exercise testing over spirometry in the evaluation of postoperative lung function for patients with pulmonary disease.

Thoracic surgeons have often been embarrassed by the discrepancy between an improvement in symptoms and the unchanged or even worse results of spirometry in postoperative patients with either bullae or inflammatory lung disease. Forty-four patients with lung diseases, who underwent a total of 47 operations, were categorized as follows: 12 cases of empyema, 16 cases of giant bulla (undergoing surgery a total of 19 times), 4 cases of bronchiectasis, and 12 cases of other miscellaneous diseases. All patients were tested preoperatively and again 4-6 months after surgery on both the spirometer and treadmill exercise tests. The forced vital capacity (FVC) and forced expiratory volume (FEV1.0) results were as follows: the empyema group 1.82 +/- 0.52 liters preoperatively to 1.93 +/- 0.69 liters postoperatively and 1.47 +/- 0.44 liters to 1.56 +/- 0.53 liters, respectively; and the giant bulla group, 3.49 +/- 0.96 liters to 3.35 +/- 0.77 liters and 2.35 +/- 0.96 liters to 2.48 +/- 0.69 liters, respectively. However, the exercise time was prolonged in the empyema group from 6.00 +/- 3.77 min to 8.33 +/- 3.80 min (P < 0.01) and in the giant bulla group from 11.83 +/- 3.71 min to 12.92 +/- 2.84 min (P < 0.05). It was thus concluded that exercise testing should be chosen for the postoperative evaluation of patients with inflammatory pulmonary disease and giant bullae, especially if any discrepancies are seen between spirometry and performance status, because on the basis of our results, it appears that the benefits obtained by surgery are best measured by the dynamic values of exercise testing and not by the static values of spirometry at rest.

Adult

Value of thallium-201 early reinjection for assessment of myocardial viability.

To assess the efficacy of early reinjection for predicting post intervention improvement in thallium-201 (T1) uptake and regional wall motion, we reinjected a small dose of T1 following post-stress imaging and obtained reinjection early images (10 min after early reinjection) and reinjection delayed images (3 hr afterwards) in 40 patients who were referred to us for revascularization (group I). Twenty-nine patients in group I also underwent conventional stress-redistribution T1 scintigraphy (group II). Conventional stress-redistribution T1 scintigraphy was repeated after intervention. Contrast left ventriculography was performed before and after intervention and changes in regional wall motion were assessed in 22 of 40 patients. In group I, the predictive value for improvement and no improvement (the accuracy) of reinjection early images in perfusion was 83%, while that of reinjection delayed images was 91%. Furthermore, the accuracy of reinjection early images in regional wall motion was 80%, while it was 91% for reinjection delayed images. In group II, the accuracy in perfusion was 78% and the value in regional wall motion was 70%. Both accuracy in perfusion and in regional wall motion obtained from reinjection delayed images were significantly higher than the values in group II (p < 0.05). These data suggest that early reinjection is useful for predicting postintervention thallium uptake and regional wall motion.

Aged

A clinical feature of myocardial stunning associated with acute myocardial infarction.

We report a case of myocardial stunning after acute myocardial infarction. In the hyperacute phase of myocardial infarction, the patient's coronary arteries showed normal features on coronary angiography during extensive ST-segment elevation observed on a standard 12-lead electrocardiogram and extensive akinesis observed on a left ventriculogram. Thallium-201 emission computed tomography revealed extensive perfusion abnormality. In the chronic phase, the perfusion abnormality was markedly improved. However, the electrocardiogram demonstrated poor R wave progression, and the left ventriculography revealed slight hypokinesis in the anterolateral wall. The acetylcholine provocation test disclosed coronary vasospasm of the left anterior descending coronary artery. About six months thereafter, left ventricular wall motion became completely normal and no poor R wave progression was observed on the electrocardiogram. The findings in this case indicate that myocardial stunning resulted from brief but sever ischemia due to vasospasm which led to cardiogenic shock, and that the recovery of findings for thallium-201 perfusion might be followed by those of electrocardiography and left ventriculography in the stunned myocardium.

Acetylcholine

Suppression of hyperventilation-induced attacks with infusion of B-type (brain) natriuretic peptide in patients with variant angina.

B-type (brain) natriuretic peptide (BNP) forms a peptide family with A-type (atrial) natriuretic peptide (ANP), which is involved in the regulation of blood pressure and fluid volume. We have demonstrated that BNP is a novel cardiac hormone secreted predominantly from the ventricle and that plasma levels of BNP markedly increase in proportion to the severity of congestive heart failure. Spasm of a major coronary artery (coronary spasm) is the cause of variant angina and can be induced by hyperventilation. We examined whether BNP infusion suppresses coronary spasm in patients with variant angina. The effect of BNP infusion on anginal attacks induced by hyperventilation was studied in 11 patients with variant angina in whom the attacks were reproducibly induced by hyperventilation. This study was performed in the early morning on 3 consecutive days. Fourteen minutes after infusion of BNP was begun (day 2, 0.05 micrograms/kg/min) or saline (days 1 and 3), hyperventilation was started and continued for 6 minutes. Anginal attacks were induced in all 11 patients by hyperventilation on days 1 and 3, respectively. Anginal attacks were not induced in any patient on day 2 (BNP infusion). Fourteen minutes after BNP infusion was begun, plasma BNP levels increased from 23.7 +/- 6.7 pg/ml to peak levels of 2591 +/- 255 pg/ml (p < 0.01) and plasma ANP levels increased from 28.9 +/- 7.5 pg/ml to peak levels of 69.2 +/- 13.2 pg/ml. Five minutes after BNP infusion was finished, plasma levels of cyclic guanosine monophosphate (cGMP) increased from 20.3 +/- 7.4 pg/ml to peak levels of 63.5 +/- 13.7 pg/ml (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Reduced cardiac extraction of norepinephrine and epinephrine in patients with heart failure--correlation with left ventricular function.

To assess whether the impairment of neuronal norepinephrine (NE) uptake is involved in the increased NE release observed in the failing heart, we examined the cardiac extractions of NE and epinephrine (E) and their correlation with left ventricular function in 16 patients with anterior transmural old myocardial infarction (OMI) and 18 patients with dilated cardiomyopathy (DCM). The plasma NE and E levels were both increased in OMI and DCM, particularly in the coronary sinus, as compared with those in 16 control subjects (Control). The cardiac NE and E extractions were significantly reduced in OMI (P < 0.001) and in DCM (P < 0.001) as compared with those in the Control (NE: -38 +/- 36% in OMI, -33 +/- 28% in DCM, and 14 +/- 18% in Control; E: 30 +/- 12% in OMI, 32 +/- 17% in DCM, and 54 +/- 8% in Control). However, there was no reduction in the NE and E extraction in the leg in OMI and DCM. Cardiac NE and E extractions both showed significant correlation with the left ventricular ejection fraction (r = 0.685, P < 0.001 and r = 0.609, P < 0.001, respectively). We conclude that, in patients with heart failure, NE release from the heart is increased partially due to the reduction of the cardiac neuronal uptake of NE which is proportional to the severity of left ventricular dysfunction.

Aged

Infantile progressive spinal muscular atrophy with ophthalmoplegia and pyramidal symptoms.

Two siblings presented with identical features of progressive peripheral paralysis of the lower motor neuron type, pyramidal signs, cranial nerve palsy which included external ocular palsy and deafness, and internal ocular palsy; both died before 1 year of age. Pathologic examination of the central nervous system in both patients revealed degeneration and loss of spinal and cranial nerve motor nuclei, including the oculomotor nucleus. In addition, there was degeneration of the Edinger-Westphal nuclei and demyelination of the corticospinal tract under the midbrain. Although spinal cord lesions were indistinguishable from those of Werdnig-Hoffmann disease, the 2 patients are not considered to have Werdnig-Hoffmann disease from the clinicopathologic findings.

Brain

Centrally induced vasopressor and sympathetic responses to a novel endogenous peptide, adrenomedullin, in anesthetized rats.

Possible central actions of adrenomedullin were explored and compared with the peripheral effects by injecting it into the lateral ventricle, cisterna magna, and femoral vein in urethane-anesthetized rats. Adrenomedullin, 1.0 to 3.0 nmol/kg, injected intravenously (i.v.), caused a transient vasodepression of about 10 to 30 mm Hg, dose dependently, which lasted for < 15 min. On the other hand, intracerebroventricular (ICV) and intracisternal (IC) injections of adrenomedullin elicited sustained elevations of arterial pressure of gradual onset, dose dependently; the arterial pressure started to rise at about 3 min after the injection, and gained peak response after > 20 min. The pressor response lasted for > 2 h. Heart rate was not significantly influenced by these doses of adrenomedullin. The abdominal sympathetic outflow was markedly increased in relation to the blood pressure elevation. The time-course of the responses was quite similar with both ICV and IC injections. Hypotensive effects of i.v. injected adrenomedullin was partially attenuated, and the centrally induced vasopressor responses were abolished by the pretreatment with human calcitonin gene-related peptide (hCGRP)-receptor antagonist, hCGRP(8-37). These findings indicate that the receptors for adrenomedullin exist in the brain, and that the receptor site may be anatomically far from the surface of the brain and the ventricular system because the onset of the pressor response was delayed. Or, CGRP and adrenomedullin may share the same receptors, particularly in the brain.

Adrenomedullin

Modulation of sodium current by lactate in guinea pig ventricular myocytes.

OBJECTIVE: The aim was to elucidate whether or not lactate modifies the fast sodium current (INa) in cardiac cells. METHODS: A tight seal whole cell clamp technique was used to record the action potentials and INa in single ventricular cells from the guinea pig heart. RESULTS: In voltage clamp experiments, superfusion with 20 mM lactate shifted both the normalised conductance (gNa)-voltage relationship and the channel availability curve toward hyperpolarisation by approximately 4 mV, but did not affect the maximum conductance (gNa,max). In the test solution containing only CaCl2 as the main divalent component, 20 mM lactate reduced the ionised calcium concentration from 1.02 to 0.84 mM. When the calcium concentration was kept constant by the addition of CaCl2 into the lactate containing solution the lactate effect was nullified. However, a change in the calcium concentration from 1.0 to 0.84 mM without lactate induced a 4 mV negative shift of the channel availability curve. Current clamp experiments in Tyrode solution showed that 20 mM lactate shifted the threshold for the action potential upstroke by 2.5-3 mV, in accordance with the voltage clamp experiments. CONCLUSIONS: Lactate modifies INa of ventricular myocytes by shifting its kinetics toward hyperpolarisation. This shift seems to be caused exclusively by a decrease in the ionised divalent cation concentrations and a resultant change in the negative surface charge of the sarcolemma.

Action Potentials

Anti-obesity and anti-diabetic effects of carteolol in non-insulin-dependent diabetic mice.

1. When carteolol, a beta-adrenergic blocker, was administered to KK-Ay/Ta Jc1 mice that are obese and develop spontaneously non-insulin dependent diabetes, their increase in bodyweight was arrested from the age of 16 weeks. Since their intake of food and water was not influenced by carteolol treatment, compared with the control KK-Ay/Ta Jc1 mice, abolition of the weight gain might be attributed to increased energy metabolism. 2. Non-fasting serum glucose levels in carteolol-treated mice at the age of 17 weeks were within normal range (118 +/- 4 vs 186 +/- 12 mg/dL). An intraperitoneal glucose-tolerance test revealed that the carteolol treatment markedly restored glucose metabolism; fasting plasma glucose (88 +/- 6 mg/dL) was within normal range, and immunoreactive insulin (IRI; 5.8 +/- 0.8 vs 33.3 +/- 10.5 ng/mL) and plasma glucose levels at 60 min post glucose (361 +/- 44 vs 541 +/- 32 mg/dL) were significantly lower in carteolol-treated mice than those in the control group at the age of 20 weeks. 3. From these findings, carteolol is considered to have little effect on the growth of mice but to correct the obesity that develops after age 16 weeks, when their growth terminates. In addition, the normalization of blood glucose and marked decrease in IRI levels suggests that carteolol improves glucose tolerance by increasing the insulin sensitivity. 4. Since brown adipose tissue (BAT) is closely associated with thermogenesis and energy consumption, we tested whether carteolol may affect BAT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue, Brown

Heterogenous activity of BRL 35135, a beta 3-adrenoceptor agonist, in thermogenesis and increased blood flow in brown adipose tissue in anaesthetized rats.

1. The effects of BRL 35135, a beta 3-adrenergic agonist, on body temperature and regional blood flow in brown adipose tissue (BAT) were simultaneously recorded in anaesthetized rats and compared to isoproterenol. 2. BRL 35135 at doses of 0.1 and 1 micrograms/kg (i.v.) induced dose-dependent increases in BAT temperature with minimal effects on systemic diastolic blood pressure (DBP), heart rate (HR) and BAT blood flow. 3. The thermogenic effect of BRL 35135 at a dose of 10 micrograms/kg (i.v.) was smaller than that at a dose of 1 microgram/kg, and was accompanied by a marked increase in BAT blood flow. 4. Isoproterenol at doses of 0.01-1 microgram/kg (i.v.) dose-dependently increased HR and BAT blood flow and decreased DBP. It did not affect BAT temperature. 5. These findings indicate that unlike isoproterenol, BRL 35135, at the lower doses, selectively causes thermogenesis in BAT which was detectable as changes in BAT temperature, and that the vasodilator effect in BAT is not as sensitive as the thermogenic effect of beta 3-adrenergic agonists.

Adipose Tissue, Brown

Responses of plasma concentrations of A type natriuretic peptide and B type natriuretic peptide to alacepril, an angiotensin-converting enzyme inhibitor, in patients with congestive heart failure.

BACKGROUND: Plasma concentrations of A type or atrial natriuretic peptide (ANP) and B type or brain natriuretic peptide (BNP) are increased in patients with congestive heart failure (CHF). OBJECTIVE: To examine the haemodynamic and hormonal responses, especially of ANP and BNP, to oral administration of an angiotensin-converting enzyme (ACE) inhibitor in patients with CHF and in controls. PATIENTS: 12 patients with CHF and 11 controls. METHODS: Haemodynamic variables and plasma concentrations of ANP, BNP, and other hormones were serially measured for 24 hours after alacepril (37.5 mg) was given by mouth. RESULTS: Pulmonary capillary wedge pressure and systemic vascular resistance decreased significantly in both groups. The cardiac index increased only in the CHF group. In patients with CHF pulmonary capillary wedge pressure, systemic vascular resistance, and cardiac index were significantly changed from 1 to 12 hours after alacepril administration. Plasma ANP and BNP decreased significantly after alacepril was given to the CHF group: neither concentration changed in the control group. In the CHF group plasma ANP was significantly lower between 1 and 6 hours and was highly significantly correlated with pulmonary capillary wedge pressure. Plasma BNP, however, was significantly lower between 6 and 24 hours after alacepril and was not correlated with pulmonary capillary wedge pressure. CONCLUSIONS: The response of plasma BNP after alacepril administration occurred later and lasted longer than the plasma ANP response. This may indicate that the mechanisms of synthesis, secretion, or degradation of the two peptides are different.

Administration, Oral

Growth-factor-like substance in amniotic fluid in the rat: effect on the development of fetal colonic goblet cells.

Extra- and intrauterine fetuses were studied to explore the effect of amniotic fluid on the development of colonic goblet cells. Significant differences in the density of goblet cells in developing colon were observed during fetal days 19-22 between these two groups, suggesting that amniotic fluid affects the development of the colonic goblet cells, especially during the period between days 19 and 21 when rat fetuses began to swallow amniotic fluid, as demonstrated by injecting India ink into the amniotic cavity. By immunological dot blot analysis, the amniotic fluid and gastric juice from intrauterine fetuses were positive for epidermal growth factor (EGF), whereas maternal abdominal serous fluid and gastric juice from extrauterine fetus were negative for EGF. The present results indicate that the amniotic fluid during late gestation greatly affects the development of the colonic goblet cells in rat fetuses and that the trophic factors for the cells seems to be EGF or an EGF-like substance in the amniotic fluid.

Abdomen

Localization and mechanism of secretion of B-type natriuretic peptide in comparison with those of A-type natriuretic peptide in normal subjects and patients with heart failure.

BACKGROUND: B-type or brain natriuretic peptide (BNP) is a novel natriuretic peptide secreted from the heart that forms a peptide family with A-type or atrial natriuretic peptide (ANP), and its plasma level has been shown to be increased in patients with congestive heart failure. This study was designed to examine the sources and mechanisms of the secretion of BNP in comparison with those of ANP in control subjects and in patients with heart failure. METHODS AND RESULTS: We measured the plasma levels of BNP as well as ANP in 16 patients with dilated cardiomyopathy (11 men and 5 women; mean age, 59 years) and 18 control subjects (9 men and 9 women; mean age, 54 years) by sampling blood from the femoral vein, the aortic root, the anterior interventricular vein (AIV), and the coronary sinus using the newly developed immunoradiometric assay systems. In the control subjects, there was no significant difference in the plasma ANP level between the aortic root and the AIV (24.0 +/- 5.2 pg/mL versus 32.2 +/- 17.0 pg/mL), but there was a highly significant step-up of the level between the AIV and the coronary sinus (32.2 +/- 17.0 pg/mL versus 371.4 +/- 111.1 pg/mL, P < .001). In contrast, there was a significant step-up of the plasma BNP level between the aortic root and the AIV (8.6 +/- 6.4 pg/mL versus 19.0 +/- 11.5 pg/mL, P < .01) but not between the AIV and the coronary sinus (19.0 +/- 11.5 pg/mL versus 28.8 +/- 14.0 pg/mL). On the other hand, in patients with dilated cardiomyopathy, there was a significant step-up in the plasma ANP level between the aortic root and the AIV (280.6 +/- 183.7 pg/mL versus 612.3 +/- 431.6 pg/mL, P < .01) and between the AIV and the coronary sinus (612.3 +/- 431.6 pg/mL versus 1229.0 +/- 772.7 pg/mL, P < .01). There was a significant step-up in the plasma BNP level between the aortic root and the AIV (268.4 +/- 293.2 pg/mL versus 511.6 +/- 458.1 pg/mL, P < .01) but not between the AIV and the coronary sinus (511.6 +/- 458.1 pg/mL versus 529.7 +/- 455.3 pg/mL) in patients with dilated cardiomyopathy. The arteriovenous difference at the AIV of the plasma level of BNP had a significant positive correlation with left ventricular end-systolic volume index (r = 0.859, P < .001) and a significant negative correlation with left ventricular ejection fraction (r = -.735, P < .001). CONCLUSIONS: We conclude that (1) BNP is secreted mainly from the left ventricle in normal adult humans as well as in patients with left ventricular dysfunction, whereas ANP is secreted from atria in normal adult humans and also from the left ventricle in patients with left ventricular dysfunction; (2) secretion of BNP as well as ANP from the left ventricle increases in proportion to the severity of the left ventricular dysfunction, suggesting that the secretions of ANP and BNP from the left ventricle are regulated mainly by wall tension of the left ventricle; and (3) the peripheral plasma levels of ANP and BNP reflect the secretion rate of these hormones from the left ventricle and may be used as a marker of the degree of left ventricular dysfunction in patients with left ventricular dysfunction.

Aged