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Biomedical subjects

T Takishima

Publications and source records attributed to T Takishima.

At least 199 records · Page 11Linked to original sources

Effect of age on coronary circulation after imposition of pressure-overload in rats.

We examined the effects of pressure overload on coronary circulation in young adult (7 months old) and old rats (18 months old). Four weeks after the ascending aorta was banded, in vivo left ventricular pressure was measured to estimate the degree of pressure load. In the two age groups, similar increases in peak left ventricular pressure were observed (113 +/- 7 mm Hg in sham-operated rats versus 160 +/- 11 mm Hg in banded rats of the young adult group; 103 +/- 7 mm Hg in sham-operated rats versus 156 +/- 11 mm Hg in banded rats of the old group). After isolating the hearts, they were perfused with Tyrode's solution containing bovine red blood cells and albumin. Resting coronary perfusion pressure-flow relations and reactive hyperemic response after a 40-second ischemia were obtained under beating but nonworking conditions. In young adult banded rats, significant myocardial hypertrophy was observed at the organ level (124% of controls in left ventricular dry weight/body weight ratio; 119% in left ventricular dry weight/tibial length ratio) and at the cell level. Minimal coronary vascular resistance obtained by the perfusion pressure-peak flow relation during reactive hyperemia increased to 150% of controls, and coronary flow reserve decreased significantly. In contrast, myocardial hypertrophy was not observed at the organ or cell level in old banded rats. However, minimal coronary vascular resistance increased, and flow reserve decreased significantly. Thus, pressure overload with coronary arterial hypertension caused abnormalities of the coronary circulation in old subjects even in the absence of myocardial hypertrophy.

Aging↗

Prognosis of idiopathic pulmonary fibrosis in patients with mucous hypersecretion.

In order to determine the prognosis of patients with chronic idiopathic pulmonary fibrosis (IPF), we evaluated clinical, laboratory, and bronchoalveolar lavage (BAL) data at the onset of IPF in 25 patients who survived beyond 1 yr (nine women and 16 men, 59 +/- 3 yr of age, mean +/- SE). When the patients were divided into two groups according to whether they had or did not have mucous hypersecretion, 11 patients with hypersecretion (Group A) had a poorer survival rate (6 yr) than did 14 patients without hypersecretion (Group B) (10 yr) (p less than 0.01). Further, there was a significant negative correlation between sputum volume and the duration of survival in 25 patients (r = -0.55, p less than 0.01). Before glucocorticoid treatment, we also found significantly larger numbers of neutrophils (17%) and eosinophils (5%) in differential cell counts of bronchoalveolar lavage fluid (BALF) in Group A than in Group B (neutrophils, 1%; eosinophils, 0.6%) (p less than 0.05 each). Chest radiographic findings and other laboratory data including pulmonary function tests did not correlate with the survival rate. These findings suggest that mucous hypersecretion as well as neutrophils and eosinophils in BALF are among the determinants of prognosis in patients with chronic IPF.

Aged↗

Role of hypoxic drive in regulation of postapneic ventilation during sleep in patients with obstructive sleep apnea.

To elucidate the role of chemoresponsiveness in determining postapneic ventilation in sleep-disordered periodic breathing, we measured ventilatory response associated with apnea-induced arterial oxygen desaturation during sleep and compared it with the awake hypoxic ventilatory response (HVR) in 12 male patients with obstructive sleep apnea (OSA). Awake HVR was measured at a slight hypocapnic level (end-tidal PCO2 = 37 +/- 1 mm Hg, mean +/- SEM), and separately at a PCO2 of 45 mm Hg. During non-REM sleep both the ventilatory rate (VE) and the average respiratory frequency (f) in the ventilatory phase between apneic episodes were inversely correlated with the nadir of arterial oxygen saturation (nSaO2) produced by the preceding apneic phase in all patients (VE versus nSaO2; r = -0.74 +/- 0.03, mean +/- SEM; f versus nSaO2, r = -0.56 +/- 0.04). The average tidal volume (VT) also was correlated with nSaO2 in 10 of the patients (r = -0.56 +/- 0.05). During REM sleep VE was correlated with nSaO2 in 11 patients (r = -0.75 +/- 0.03, p less than 0.02). The response of VE to nSaO2 (delta VE/delta nSaO2) varied widely among the patients (non-REM, 0.52 to 2.16; REM, 0.29 to 1.44 L/min/%) and was significantly lower during REM than non-REM sleep (p less than 0.01). The value of delta VE/delta nSaO2 during both non-REM and REM sleep was correlated with awake HVR at an end-tidal PCO2 of 45 mm Hg (non-REM, r = 0.83, p less than 0.02; REM, r = 0.76, p less than 0.05) but not with that at the hypocapnic level.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Neuropeptides and airway submucosal gland secretion.

Our study using feline tracheal isolated submucosal gland preparation has revealed that substance P (SP) produces an increase in submucosal gland secretion through the actions of both mucus ejection by glandular contraction and macromolecule secretion from secretory cells, and that the two actions are both mediated by a peripheral cholinergic action. In contrast, SP has no significant effect on macromolecule secretion from secretory cells in tracheal explants, probably because of epithelial suppression. Our study using an isolated gland preparation has also indicated that VIP potentiates mucous glycoprotein secretion induced by cholinergic stimulation through an interaction between muscarinic and VIP receptors in secretory cells. However, VIP failed to induce any significant glandular contraction or relaxation, indicating a lack of VIP receptors or a difference in the subtypes of muscarinic receptors in myoepithelial cells in submucosa glands.

Animals↗

Discrete phase of calcium excess in the process of deterioration in an individual rat myocyte.

While there have been many reports of the significant role of cytoplasmic free calcium ion in myocardial injury, these have been carried out in multicellular preparations. Since cell injury may occur inhomogeneously, it is necessary to observe the 'history' of an individual myocyte in order to investigate the detailed role of the calcium ion in the process of myocardial injury. We have observed the natural history of individual myocytes isolated from the left ventricle of rats with respect to changes in shape and cytoplasmic free calcium concentration ([Ca2+]i) measured with fura-2. We can discriminate four phases in the time course of cell deterioration. In the first phase (phase O), the myocyte is rod shaped, quiescent and responsive to electrical stimulation. The [Ca2+]i is stable. In the next phase (Phase 1), once initiated, the myocyte exhibits an asynchronous wavy contraction and gradually decreases in length. The [Ca2+]i gradually increases with some fluctuation. Phase 2 is characterized by rapid development of contracture with a marked increase in [Ca2+]i. In the period following establishment of contracture (Phase 3), changes in [Ca2+]i vary from cell to cell, possibly because of leakage of the dye caused by loss of cell membrane integrity. Our results indicate that, during naturally occurring cell deterioration, loss of [Ca2+]i control at the membrane of the sarcoplasmic reticulum precedes contracture and catastrophic increase in [Ca2+]i.

Animals↗

Role of chronic Pseudomonas aeruginosa infection in airway mucosal permeability.

The role of Pseudomonas aeruginosa infection in airway mucosal permeability was studied in 16 patients with chronic bronchitis by measuring the amounts of radiolabeled albumin in sputum. One group (A) consisted of six patients (two female, four male, 53 +/- 6 years, SEM) with chronic P aeruginosa infection for 5 +/- 0.9 years. Another group (B) consisted of ten patients (five female, five male, 67 +/- 4 years) without P aeruginosa infection for at least two years. No significant differences between groups A and B were found in the volume of sputum (63 +/- 21 ml/day in group A and 45 +/- 8 ml/day in group B, p = 0.44), the obstructive changes (FEV1 of 57 +/- 6 percent in group A and 51 +/- 4 percent in group B), or the duration of disease (19 +/- 4 years in group A and 14 +/- 4 years in group B). Saliva, sputum, and serum samples were collected at intervals of 2 h over an 8-h period, and at 24 h after intravenous administration of 131I-labeled human albumin. For counting, free 131I was removed by dialysis. Radiocounts (cpm) of saliva were significantly smaller than those of sputum or serum. The cpm from each sputum sample was divided by serum cpm at the time of each sampling. Group A showed significantly higher values in the ratio of sputum- to serum-cpm than did group B at all sampling times. Furthermore, the ratios at 2 and 4 h after 131I-albumin injection significantly correlated with sputum volume per day, whereas they did not correlate with any other factors (age, obstructive impairment, and duration of disease). These findings suggest that chronic P aeruginosa infection produces an increase in airway mucosal permeability to albumin.

Adult↗

Bradykinin-induced cough reflex markedly increases in patients with cough associated with captopril and enalapril.

We studied the effects of angiotensin converting enzyme (ACE) inhibitors on cough responses to bradykinin (BK), substance P (SP) and citric acid in a double blind, random study on 10 hypertensive patients receiving ACE inhibitors. Of these patients, five had reported cough with ACE inhibitors. Cough responses to citric acid were similar between patients with and without cough, and SP up to 10(-5) M did not cause cough in any of the subjects. BK caused cough at 13.4 +/- 1.2 (-log M) in 5 patients with cough associated with ACE inhibitors, but it did not cause cough at concentrations up to 10(-5) M in other 5 patients. One month after the withdrawal of ACE inhibitors, 5 patients were free from cough symptoms, and BK did not cause cough up to 10(-5) M in these patients, except for one who coughed at 10(-9) M, without changes in responses to citric acid. BK caused cough at 14.3 +/- 0.7 (-log M) although BK1-7, a major metabolite of BK by ACE, caused cough at 5.7 +/- 0.7 (-log M) in another 3 patients with cough associated with ACE inhibitor. These results suggest that impaired metabolism of BK induced by ACE inhibitors may relate to the manifestation of cough in hypertensive patients receiving ACE inhibitors.

Adult↗

Vibration analysis of the human left ventricular posterobasal wall at the moment of the first heart sound emission.

We examined whether human left ventricular (LV) wall vibration at the first heart sound emission (LVvibr) could be a potential source of information about the left ventricular physical properties, as has been demonstrated by experimental forced vibration studies. LV posterobasal wall vibration in 51 subjects characterized by functional murmur (n = 13), mitral stenosis (n = 8), hypertrophic cardiomyopathy (HCM, n = 8), ischemic heart disease with old myocardial infarction (n = 12) and without prior infarction (n = 10), was detected with a miniature intraesophageal vibration sensor. Peak frequency, sharpness and peak power of LVvibr in patients with functional murmur and mitral stenosis were linearly related to the Q-vibration interval. HCM patients showed a higher peak frequency and sharper configuration in the power spectrum. However, differing from previous reports, we found no characteristic difference in configuration of power spectrum in patients with ischemic heart disease. These results suggest that human LVvibr possibly includes information demonstrated by experimental forced vibration analysis.

Adolescent↗

Effects of elastic loading and exercise on pulmonary gas exchange in dogs.

We assessed the effects of negative intrathoracic pressure induced by inspiratory elastic loading on pulmonary, gas exchange with and without electrically induced hindlimb exercise in 8 normal, anesthetized dogs. Two elastic loads (EL) were used; one of 81 and one of 140 cmH2O/liter. These are equivalent to doubling and tripling the normal elastance of the dog's respiratory system, respectively. Elastic loading decreased ventilation and caused hypoxemia and hypercapnia, but it did not affect systemic arterial pressure or heart rate. During exercise, increase in ventilation was limited, whereas increase in cardiac output was not affected by elastic loading. Alveolar-arterial O2 tension difference (A-aDO2) was not changed significantly by exercise alone. However, elastic loading accompanied by exercise increased A-aDO2. Although comparable end-inspiratory pleural pressure was achieved with large EL (-29 +/- 2 cmH2O, mean +/- SE) and small EL with exercise (-30 +/- 2 cmH2O), the latter increased A-aDO2 whereas the former did not. Large negative intrapleural pressure combined with increased cardiac output may have caused transient interstitial edema.

Animals↗

Effect of pericardium on regional myocardial systolic function in acute ischemia.

To know whether or not the pericardium affects regional myocardial systolic function in acute ischemia, we measured ischemic and non-ischemic segment lengths of the left ventricle using ultrasonic crystals in 10 open-chest dogs with the pericardium preserved. When the left ventricular pressure and segment lengths were stable after left circumflex coronary occlusion, we opened the pericardium widely. After coronary occlusion, end-diastolic length (EDL) in ischemic and non-ischemic segments increased, and the ischemic segment showed paradoxical systolic expansion while the non-ischemic segment increased its active shortening. After pericardiectomy, heart rate, left ventricular systolic pressure, and peak positive and negative dP/dt did not change. EDL in ischemic and non-ischemic segments further increased from 12.02 +/- 0.18 to 12.50 +/- 0.16 mm (mean +/- S.E., p less than 0.01) and from 11.12 +/- 0.20 to 11.45 +/- 0.18 mm (p less than 0.05), respectively, despite the concomitant fall in left ventricular end-diastolic pressure (LVEDP) from 12.4 +/- 0.6 to 10.6 +/- 0.8 mmHg (p less than 0.01). End-systolic length in ischemic and non-ischemic segments also increased from 12.37 +/- 0.25 to 12.70 +/- 0.20 mm (p less than 0.05) and from 8.50 +/- 0.13 to 8.74 +/- 0.13 mm (p less than 0.01), respectively, although the left ventricular end-systolic pressure did not change. Maximum expanded systolic length of the ischemic segment also increased from 12.99 +/- 0.20 to 13.42 +/- 0.16 mm (p less than 0.01). These results indicate that, in acute ischemia, the pericardium inhibits paradoxical systolic expansion of the ischemic region and increase in end-systolic length of non-ischemic segment. Thus, it is concluded that the pericardium modifies the regional myocardial systolic function in acute ischemia, perhaps through the mechanical restraint of the pericardium.

Animals↗

Treatment of status asthmaticus with intravenous magnesium sulfate.

The bronchodilating effect of magnesium sulfate (MgSO4) was studied in two patients with status asthmaticus, who were intubated and mechanically ventilated by a respirator. Airway resistance was continuously monitored by the respiration-controlled interruption technique. After administration of 0.5 mmol/min MgSO4 intravenously, airway resistance decreased from 17 to 9, and from 13 to 8 mmHg/L/s in the two patients, respectively, and piping rales diminished or disappeared. We conclude that while corticosteroid therapy requires several hours to demonstrate significant effects in status asthmaticus, MgSO4 is of great benefit in the rapid improvement of airflow obstruction.

Adolescent↗

[The group study of diagnostic efficacy of cerebro-vascular disease by I-123 IMP SPECT images obtained with ring type SPECT scanner--the ROC analysis on the diagnosis of perfusion defect and redistribution].

We performed two image reading experiments in order to investigate the diagnostic capability of I-123 IMP SPECT obtained by the ring type SPECT scanner in cerebro-vascular disease. Fourteen physicians diagnosed SPECT images of 55 cases with reference to clinical neurological informations, first without brain XCT images and second with XCT images. Each physician detected perfusion defects and redistributions of I-123 IMP and assigned a confidence level of abnormality for these SPECT findings by means of five rating method. From results obtained by ROC analysis, we concluded as follows: (1) Generally, I-123 IMP SPECT is a stable diagnostic modality in the diagnosis of cerebro-vascular disease and the image reading of XCT had no effects on the diagnosis of SPECT on the whole of physician, (2) However, there were unnegligible differences among individuals in the detectability of findings and the effect of XCT image reading, (3) Detectability of redistribution of I-123 IMP was lower than that of perfusion defect and inter-observer variation in the diagnostic performance for redistribution was larger than that of perfusion defect. The results suggest that it is necessary to standardize diagnostic criteria among physicians for redistribution of I-123 IMP.

Amphetamines↗

[The effect of an oral gold compound, auranofin, on bronchial responsiveness to inhaled methacholine in well-controlled bronchial asthma].

Recently, in Japan, auranofin (6 mg/day) has been demonstrated to be a useful treatment for patients with moderate to severe asthma in a double-blind clinical trial. Therefore, to investigate the mechanism of auranofin on bronchial asthma, we examined pulmonary functions and bronchial responsiveness to inhaled methacholine in well-controlled asthmatics after 12 wks of treatment with auranofin, in a double-blind, placebo-controlled fashion. Twenty-five adult patients with asthma received orally 3 mg of auranofin or inactive placebo twice daily for 12 weeks. Bronchial responsiveness, pulmonary function tests and concentrations of gold in the blood were measured before and 6 and 12 wks after the therapy. Bronchial responsiveness (PD35-Grs) was significantly decreased after 12 wks of treatment with auranofin, compared with that 12 wks after treatment with inactive placebo. We suggest that inhibition of bronchial hyperresponsiveness by auranofin is one of the mechanisms by which auranofin is effective against bronchial asthma.

Adult↗

[New method for estimating left ventricular myocardial elasticity by vibration analysis].

We solved numerical solutions of Advani-Lee's equation, which treats free vibrations of fluid-filled spherical shells, and forms the basis for non-invasive estimation of left ventricular myocardial elasticity. Numerical results showed that elasticity is approximated by E = 86.5.a2.f2 (E: elasticity (dyn/cm2), a: internal radius (cm), f: eigen-frequency (Hz)). To examine the accuracy of this theoretical equation in estimating elasticity, we made 7 spherical shells of silicone rubber, and compared the estimated elasticity by this equation with that by a standard stretch test. The elasticity calculated by Advani-Lee's equation and by stretch test proved to be nearly identical. Therefore, we concluded that we can estimate the elasticity of a spherical shell using this equation. We calculated the myocardial elasticity at the first heart sound emission in 25 normal persons with a simplified (approximated form of) Advani-Lee's equation. The mean elasticity in normal subjects was (7.04 +/- 2.46) x 10(5) dyn/cm2.

Elasticity↗