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Biomedical subjects

T Takishima

Publications and source records attributed to T Takishima.

At least 163 records · Page 9Linked to original sources

Partitioning of pulmonary responses to inhaled methacholine in subjects with asymptomatic asthma.

To partition the central and peripheral airway resistance, a catheter-tip micromanometer sensing lateral pressure of the airway was wedged into the right lower lobe of a bronchus with a 3 mm inner diameter in 10 patients with asymptomatic asthma. We simultaneously measured mouth flow, transpulmonary pressure (PL) and intra-airway lateral pressure during tidal breathing. Total pulmonary resistance (RL) was calculated from PL and mouth flow, and central airway resistance (RC) was calculated from intra-airway lateral pressure and mouth flow. Peripheral airway resistance (Rp) was obtained by subtraction of RC from RL. Therefore, our measurement of Rp included lung tissue resistance. The technique permitted identification of the site of changes in airway resistance. The baseline values of resistances were 2.3 +/- 0.2 cm H2O/L/s in RL, 1.5 +/- 0.1 cm H2O/L/s in RC, and 0.8 +/- 0.1 cm H2O/L/s in Rp, respectively. To determine the site of airway hyperresponsiveness, dose-response curves of central, peripheral, and total airways to inhaled methacholine were separately constructed. Bronchial responsiveness was evaluated by a log methacholine unit requiring a 35% decrease (PC35) and a 50% decrease (PC50) in pulmonary conductance (a reciprocal of RL). We calculated the increase of resistances in total (delta RL), central (delta RC), and peripheral (delta Rp) airways from the baseline values at either PC35 or PC50.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Human lung mast cells and pulmonary macrophages produce tumor necrosis factor-alpha in sensitized lung tissue after IgE receptor triggering.

Tumor necrosis factor (TNF) is considered to play a key role in the pathogenesis of allergic disorders. We examined TNF production in human lung fragments after IgE receptor triggering at mRNA and protein levels. IgE receptor triggering was performed by sensitizing lung fragments with monoclonal human IgE and then exposing them to anti-human IgE antibody. Cytotoxic activity against L929 cells appeared in the culture supernatant of lung fragments 2 h after IgE receptor triggering and increased for up to 4 h. This cytotoxic activity was completely neutralized by anti-human TNF antibody. Northern blot analysis demonstrated that 1.8-kb TNF mRNA transcripts in sensitized lung fragments were expressed as early as 1 h after IgE receptor triggering and continued up to 4 h. Immunohistochemical analysis revealed TNF localization in tissue mast cells, alveolar macrophages, tissue macrophages, and bronchial epithelial cells. Double staining with anti-TNF antibody and alcian blue clearly identified that lung mast cells are one of the TNF-positive cell types in the pulmonary tissue. With immunoelectron microscopy, TNF immunoreactivity was detected in the rough endoplasmic reticulum and the perinuclear spaces in tissue macrophages, and in the cytosol and the perinuclear spaces in bronchial epithelial cells. In addition, IgE was detected on the cell surface of mast cells, tissue macrophages, and alveolar macrophages. These results suggest that TNF is released from mast cells and pulmonary macrophages through IgE receptor triggering and may play a key role in the allergic reaction in human airway.

Animals↗

Aging effects on myocardial hypertrophic response and coronary circulation in pressure-overload.

We examined the effect of age on capacity for myocardial hypertrophy, pressure-generating ability and coronary circulation after imposition of pressure-overload. Marked right ventricular and cellular hypertrophy was observed 1 week after pulmonary artery constriction in the developmental phase of rats (2 months of age) and after 3 weeks in the young-adult rats (7 months). In old rats (18 months) similar increases in peak right ventricular pressure did not produce significant hypertrophy even after 3 weeks. The right ventricular hypertrophy at the organ and cell levels in response to pressure-overload decreased with age. In vivo pressure-generating ability, which was determined by maximum isovolumic pressure during pulmonary artery occlusion, correlated with the degree of myocardial hypertrophy in each age group. During the ascending aortic constriction experiment the age-associated diminution in hypertrophic response was also observed in the left ventricle. Coronary dilator capacity, which was determined after brief ischemia in an isolated, blood-perfused, beating but nonworking heart model, was decreased in the presence of myocardial hypertrophy in young-adult rats (7 months) and in the absence of significant myocardial hypertrophy in old rats (18 months). The age-associated diminution in capacity for myocardial hypertrophy, pressure-generating ability and maladaptation in the coronary circulation may explain the higher incidence of heart failure or increased vulnerability of the myocardium to ischemic episodes during hemodynamic stress in aged patients.

Aging↗

Ventricular contractility evaluated by mechanical perturbation of the myocardium--experimental and clinical approach adopting small amplitude vibration input.

Small amplitude mechanical vibration has been reported to depress the function of the isolated left ventricle in an amplitude dependent manner. We examined, 1) contractility and preload dependency of the magnitude of functional depression (VID) by applying 50 Hz, 2 mm amplitude vibration to the epicardium of the canine left ventricle and 2) whether VID is present in the failing human ventricle. The magnitude of VID was independent of preload in the physiological range of LV volume showing peak LV pressure greater than 75 mmHg, and VID was correlated with Emax at each inotropic state. In the in-situ condition, VID appeared only in the failing condition with a sensitive increase at a mild level of heart failure. In a study during routine cardiac catheterization (n = 27), the presence of VID has been demonstrated in the human ventricle (n = 18). The magnitude of VID was correlated with ejection fraction (EF) as, VID in peak LV pressure (mmHg) = 80.6 - 110 x EF, r = 0.84, p less than 0.01 in patients with EF less than or equal to 0.7 (n = 14). Therefore, we concluded that VID could be a clinical tool for evaluation of mild heart failure.

Animals↗

Marked goblet cell hyperplasia with mucus accumulation in the airways of patients who died of severe acute asthma attack.

To examine the changes in airways in bronchial asthma (BA) during an asthma attack causing death, we performed morphometric analysis of autopsied lungs from three outpatients who died of severe acute asthma attacks (group A) and compared these to five patients who died of non-status asthmaticus (group B). Controls (group NL) were four patients who died of diseases other than respiratory disorders. Area proportions of bronchial glands to bronchial wall (gland [percent]) and of goblet cells to total epithelial layer (goblet [percent]) and the intraluminal amount of mucus in the airways (MOR) were measured in a paraffin section. There were no significant differences in age, sex, smoking history, duration of BA history, and dosage of glucocorticoids received between groups A and B. Although both groups A and B showed significantly larger values of gland (percent) in the central airways and of inflammatory cell numbers in the airway walls than did group NL, no significant differences were observed between groups A and B. In contrast, markedly significant increases in goblet (percent) and in MOR were observed in group A compared to groups B and NL. These increases in group A were more dominant in the peripheral airway: 30-fold and threefold increases of group B in goblet (percent) and MOR, respectively. Furthermore, MOR significantly correlated with goblet (percent) in the peripheral airways (p less than 0.05). These findings suggest that a marked increase in goblet cells of the airways is a feature characteristic of patients with BA who die of a severe acute attack.

Epithelium↗

P wave height during incremental exercise in patients with chronic airway obstruction.

We examined changes in P wave height in lead 2 of an ECG obtained during progressive exercise in 23 patients with COPD, and measured both P wave changes and pulmonary hemodynamics during exercise at a constant workload corresponding to approximately 50 to 60 percent of VO2 max in nine patients. The P wave response to exercise (delta P/delta VO2, %/ml/min), estimated by the relationship between percentage of change in P wave height and VO2, was significantly greater (p less than 0.01) in 15 patients who had a decrease in PaO2 with exercise (group A) than eight patients who did not have a fall in PaO2 with exercise (group B). There was a significant negative correlation between change in PaO2 and change in P wave height from rest to maximal exercise (r = -0.68, p less than 0.001). Oxygen therapy in nine patients in group A reduced the increase in P wave height during exercise. Furthermore, change in P wave height from rest to exercise correlated significantly with that of mean pulmonary artery pressure (r = 0.75, p less than 0.01). These results suggest that increase in P wave height during exercise in COPD patients is related partly to oxygen desaturation during exercise, and continuous measurement of P wave change may be useful for noninvasively predicting the pulmonary vascular pressure response to exercise.

Aged↗

Role of chronic Pseudomonas aeruginosa infection in the development of bronchiectasis.

To understand the role of Pseudomonas aeruginosa infection in the development of bronchiectasis, we investigated by CT the presence of bronchiectasis in two groups of chronic bronchitis patients and in a control group. There were no differences in clinical or laboratory findings between groups A and B. Three observers without any knowledge of these patients reported bronchiectasis on a scale of 0 to 3 and bronchial wall thickness on a scale of 0 to 3 in each lobe of both lungs. Bronchiectasis and wall thickness scores in group A (chronic bronchitis with P aeruginosa infection) were significantly higher than bronchiectasis scores and wall thickness in group B (chronic bronchitis without P aeruginosa infection). Both scores in group B were higher than those in group C (control group). These findings support the idea that chronic P aeruginosa infection plays a role in the development of bronchiectasis.

Adult↗

Perivascular fibrosis of muscular pulmonary arteries in chronic obstructive pulmonary disease.

We performed a morphometric analysis of peribronchiolar and perivascular fibrosis in lungs obtained at autopsy from six patients with chronic bronchitis, six with pulmonary emphysema, and four normal control subjects. The areas of fibrosis outside the smooth muscle layer of bronchioles and outside the external elastic lamina of muscular pulmonary arteries were measured and their thickness was then calculated by assuming a round airway or artery. Patients with chronic bronchitis had significantly thicker peribronchiolar fibrosis in bronchioles of 1 mm or less in diameter and also thicker perivascular fibrosis of the adjacent muscular pulmonary arteries than the other two groups. The extent of perivascular fibrosis was significantly correlated with peribronchiolar fibrosis only in the muscular pulmonary arteries adjacent to the bronchioles but not in those away from the bronchioles. These findings suggest direct extension of chronic inflammation from bronchioles to the adjacent muscular pulmonary arteries in chronic bronchitis but not in pulmonary emphysema. Such perivascular fibrosis might lead to sustained pulmonary hypertension.

Aged↗

Bilateral Bochdalek hernias in an elderly patient diagnosed by magnetic resonance imaging.

An elderly patient with asymptomatic bilateral Bochdalek hernias is reported. The chest roentgenogram showed dome-shaped supradiaphragmatic masses about 6 cm in diameter in the posteromedial regions of both sides of the lungs. Computed tomography showed a discontinuity of the lines of diaphragmatic musculature in the left thorax, and a mass with a homogenous low density area indicative of fatty tissues in the right thorax. The magnetic resonance imaging, coronal and sagittal T1-weighted images revealed interruptions of the diaphragmatic musculature adjacent to the masses and protrusion of retroperitoneal fat into the thoracic cavity. The lesions were therefore diagnosed as bilateral Bochdalek hernias of the diaphragm.

Adipose Tissue↗

[Bronchial asthma].

In the first study, to clarify whether increased vagal afferent activity contributes to the increase in ventilatory response to CO2 in patients with asthma, we examined the effects of prostaglandin E2 (PGE2) inhalation on the respiratory response to CO2 in seven normal subjects. After PGE2 inhalation, the ventilatory and occlusion pressure responses to CO2 increased significantly compared with those after saline inhalation, with no increase in respiratory resistance. These results suggest that increase in vagal afferent activity may play a role in the increased hypercapnic response during acute exacerbations of asthma. In the second study, to clarify the reduced respiratory chemosensitivity associated with asthma-related deaths, we examined the hypercapnic and hypoxic ventilatory responses in five patients with near-fatal asthma who were given artificial ventilation and/or became unconsciousness during an acute exacerbation of asthma. Hypoxic ventilatory response was significantly lower in these subjects than in patients with uncomplicated asthma and normal subjects, suggesting that lowered hypoxic ventilatory response may be related to death from asthma.

Asthma↗

[Home oxygen therapy using liquid oxygen system].

Home oxygen therapy (HOT) for patients with chronic respiratory failure has been believed to increase the quality of life and to improve the prognosis of such patients. In Japan, HOT for chronic respiratory failure has been supported by health insurance since March 1985. Since then, patients with HOT have increased progressively, and it has been reported that there are now over 20,000 patients with HOT. The oxygen concentrator which extracts oxygen from atmospheric air has been commonly used as the oxygen delivery system. Recently the liquid oxygen system has provided an attractive, convenient source of oxygen. Since April 1990, HOT using liquid oxygen system has been supported by health insurance, and its use will become widespread in Japan. A major characteristic of this system is that oxygen condensed into a liquid form allows storage of a larger supply. This system consists of two parts: stationary type which stores the liquid oxygen, and a portable type which can easily be refilled with oxygen a larger source. In the present study, we examined the efficacy of portable liquid oxygen in 50 patients with chronic pulmonary diseases including patients with chronic respiratory failure who had PaO2 < 55 mmHg during air breathing. We measured changes of ten minutes walking distance (10 MD) and blood gas analysis with and without portable liquid oxygen. We also performed on estimation of efficacy of liquid oxygen by questionnaires in patients receiving liquid oxygen for HOT. We did not find a significant improvement of 10 MD with portable liquid oxygen, but found a significant improvement of arterial oxygen tension at the end of walking.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbon Dioxide↗

[Three-dimensional display of 99mTc-MIBI myocardial scintigraphy].

One of 99mTc-hexakis, 99mTc-methoxyisobutyl isonitrile (MIBI), has been demonstrated to have a myocardial uptake proportional to regional coronary blood flow. In this study, 99mTc-MIBI myocardial scintigraphy were performed for 16 patients with ischemic heart disease. After injection of 740 MBq of 99mTc-MIBI, 64 projection images were collected during a 360-degree rotation. Three-dimensional (3D) display of the left ventricle was reconstructed with depth-shading method from 99mTc-MIBI SPECT images, which were reconstructed by filtered back projection method. In 9 of the patients, left ventricular cineangiography were performed as diagnostic gold standard. Four physicians blinded to patients' clinical informations interpreted 3D images and SPECT images on separate occasions. Diagnosis of hypoperfusion by 3D displays agreed with those of SPECT in 92.9% (104/112 segments), and disagreed in 7.1% (8 segments). Sensitivity and specificity of 3D images were 87.0 and 93.9%, which were not statistically different (p less than 0.05) from that of SPECT images (91.3, 97.0%). Receiver operating characteristic (ROC) analysis revealed nearly identical curves for the two. Although 3D display had nearly identical diagnostic ability with SPECT, observers reported that 3D images were easier to diagnose than SPECT images. An advantage of the 3D display is that the display gives a more realistic impression of the left ventricle to an observer than tomography or planar imaging. Another advantage is that 3D display can reduce the amount of data storage compared with that of SPECT. In conclusion, 3D images may be useful for diagnosis of hypoperfusion of left ventricle.

Adult↗

Pre- and postjunctional muscarinic receptor subtypes in dog airways.

To examine muscarinic receptor subtypes involved in cholinergically mediated contractions of the airway, we studied the effects of the M1-selective antagonist, pirenzepine, the M2-selective antagonist, AF-DX 116, the M3-selective antagonist, 4-diphenyl-acetoxy-N-methylpiperidine (4-DAMP) methiodide, and the non-selective antagonist, atropine, on acetylcholine (ACh)- and electrically induced contractions in dog bronchi and bronchioles. The relative potencies of the antagonists based on IC50 values of each antagonist for contractions induced by the two concentrations of ACh that produced 50% of the maximum (ED50) and the maximum (EDmax) contractions and the pA2 values were atropine greater than or equal to 4-DAMP methiodide greater than pirenzepine = AF-DX 116 in both the bronchi and bronchioles. The IC50 and pA2 values of each antagonist did not differ significantly between the bronchi and bronchioles. 4-DAMP methiodide significantly inhibited the contractile response to electrical field stimulation (EFS) at 5 Hz at concentrations that did not alter the contractile responses to exogenous ACh in both the bronchi and bronchioles, whereas pirenzepine, AF-DX 116 and atropine inhibited the EFS-induced contraction only at the concentrations that reduced the contraction induced by exogenous ACh. The present results suggest that the cholinergic contraction is mediated via the postsynaptic receptor M3, based on functional potencies of muscarinic antagonists and presynaptic receptor auto-facilitatory M3, based on the suppression of the contractile response to EFS by 4-DAMP methiodide in central and peripheral airways.

Acetylcholine↗