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Biomedical subjects

T Takishima

Publications and source records attributed to T Takishima.

At least 271 records · Page 15Linked to original sources

Effect of hypercapnia on ventilatory response to intravenous nicotine administration in anesthetized dogs.

We studied the effects of hypercapnia on the ventilatory response to nicotine in thirty anesthetized mongrel dogs. Ventilatory (VE) and occlusion pressure (P0.2) changes were assessed before and after intravenous injection of nicotine at concentrations of 1, 4, 16 and 64 micrograms/kg in four different groups of five dogs each. An end-tidal CO2 (PETCO2) was set at 40 mm Hg or 60 mm Hg by inspiration of 7% CO2 in oxygen through a non-rebreathing valve. With PETCO2 maintained at 40 mm Hg, P0.2 had increased 1 min after nicotine injection from 1 to 16 micrograms/kg in a dose-dependent manner, and a subsequent decrease in P0.2 below the initial value was observed at around 4 min. Injection of 64 micrograms/kg of nicotine produced a marked increase in P0.2 and subsequent apnea. With PETCO2 at 60 mm Hg, the time course of P0.2 was qualitatively similar to that observed with PETCO2 at 40 mm Hg, except that the change in P0.2 was larger in the former case than in the latter, for a given nicotine dose. The ratio of the difference in maximal P0.2 observed with PETCO2 of 40 mm Hg and that at 60 mm Hg to the difference between PETCO2 values (delta PO2/delta PETCO2) increased with nicotine dose from 1 to 4 micrograms/kg and, with a further increase in nicotine dose, the maximal delta P0.2/delta PETCO2 plateaued, while delta P0.2/delta PETCO2 obtained from the minimal PO2 values decreased in a nicotine dose-dependent fashion. These results suggest that hypercapnia enhances both stimulative and subsequent depressive ventilatory responses to nicotine.

Animals↗

Direct write-out of particle size distribution of inhaled aerosol deposition using a laser scattering method.

We developed a device to measure inhaled aerosol deposition in the lung from the difference in particle size distribution of the aerosol during inspiration and expiration. To measure quantity and size distribution of nebulized aerosol particles directly at the subject's mouth we used a He-Ne gas laser scattering technique. To test the reliability of the instrument, we measured particle size distributions of saline aerosols generated by four kinds of nebulizer and compared the results with those from a Malvern 2600D particle sizer as a standard of comparison. Measured mass median diameters (MMDs) were almost identical by both methods. Aerosol deposition in five normal subjects showed that the deposition fraction of the particles increased the larger the particle sizes inhaled. The data suggest that the newly developed aerosol spectrometer can directly analyze aerosol particle size distribution at the mouth during tidal breathing, and that the instrument is useful for quantitative analysis of aerosol inhaled and of inhaled aerosol deposition.

Aerosols↗

Scintigraphic and CT findings of Tietze's syndrome: report of a case and review of the literature.

A case of Tietze's syndrome is reported. A 43-year-old woman, who had experienced right anterior chest pain and tender swelling of the right first costosternal junction for seven months, showed increased accumulation of the right first, the right fourth, and the left first costochondral junction on bone imaging. Ga-67 imaging showed increased accumulation at the right first costosternal junction. CT showed sclerosis of the sternal manubrium, partial calcification of costal cartilage, and soft tissue swelling. Biopsy of the right first costal cartilage showed chronic inflammation with fibrosis and ossification. Increased uptake of bone gallium imaging is consistent with Tietze's syndrome.

Adult↗

Laryngeal resistance immediately after panting in asthmatic subjects.

The panting manoeuvre may be used during the assessment of airway resistance and in asthmatic patients during bronchial provocation testing or spontaneous asthma. To study whether panting opens the larynx in patients with asthma, laryngeal resistance was examined in six patients with stable asthma before and after methacholine induced bronchoconstriction and in another six patients with spontaneous asthma. Subjects were asked to pant and then to hold their breath immediately afterwards. Laryngeal resistance after panting was compared to that during quiet tidal breathing. Change in laryngeal resistance was estimated by a method using low frequency sound and respiratory resistance by forced oscillation at 10 Hz. Mean baseline respiratory resistance during inspiration was 0.245 and 0.470 kPa/l.s before and after methacholine in the patients with stable asthma and 0.480 kPa/l.s in the patients with spontaneous asthma. In the patients with stable asthma mean laryngeal resistance was lower after panting than during the preceding quiet tidal breathing, both before and after methacholine induced bronchoconstriction (by 0.08 before and by 0.065 kPa/l.s after). In contrast, the patients with spontaneous asthma showed an increase in laryngeal resistance after panting of 0.089 kPa/l.s. The magnitude of change in laryngeal resistance after panting was similar to the change in respiratory resistance in the patients with spontaneous asthma and in the patients with stable asthma after methacholine, but was greater than the change in respiratory resistance in the patients with stable asthma before methacholine. These results suggest that panting may cause different effects on the laryngeal aperture in patients with stable and spontaneous asthma.

Adult↗

Modulation of human basophil growth in vitro by xiao-qing-long-tang (syo-seiryu-to), chai-pu-tang (saiboku-to), qing-fei-tang (seihai-to), baicalein and ketotifen.

Our previous study showed the inhibitory effect of Qing-Fei-Tang (Q.F.T.) and baicalein on the leukotriene (LT)B4 synthesis of human alveolar macrophages. It has recently been demonstrated that LTs support various cell growth, and basophil and its precursor numbers increase in atopic patients. Therefore, we examined the effect of anti-allergic drugs, including Q.F.T., Xiao-Qing-Long-Tang (X.Q.L.T.), Chai-Pu-Tang (C.P.T.), baicalein and ketotifen which have been used for treatment of bronchial asthma, on human basophil growth in vitro using cord blood mononuclear cells as a basophil precursor source and conditioned medium of T cell leukemia cell line Mo as a growth factor. Two-week cultured basophil numbers identified by alcian blue-safranin staining and those histamine contents assayed fluorometrically were inhibited by Q.F.T. (1.0 mg/ml), X.Q.L.T. (0.01-1.0 mg/ml), C.P.T. (0.01-1.0 mg/ml), baicalein (1-100 microM) or ketotifen (1-100 microM) in a dose-dependent manner while low dose (0.01-0.1 mg/ml) of Q.F.T. showed an enhancing effect on the basophil growth and the histamine content. However, LTB4 or LTC4 failed in restoring the basophil growth reduced by 1 mg/ml of C.P.T. or 100 microM of ketotifen. These results suggest that anti-allergic drugs may modulate basophil growth and differentiation in vitro and/or in vivo and therefore be useful and reasonable for controlling allergic diseases including bronchial asthma.

Basophils↗

Platelet-activating factor increases platelet-dependent glycoconjugate secretion from tracheal submucosal gland.

Using isolated glands from feline trachea, we examined the effect of platelet-activating factor (PAF) on radiolabeled glycoconjugate release and glandular contraction by measuring induced tension in the absence or presence of platelets. PAF alone did not produce any significant glandular contraction nor any significant change in glycoconjugate release from isolated glands. In the presence of purified platelets containing no plasma, PAF (10(-8) to 10(-5) M) produced significant glycoconjugate secretion in a dose-dependent fashion, but it produced no significant glandular contraction. PAF-evoked glycoconjugate secretion was time dependent, reaching a peak response of 277% of control 15-30 min after the exposure of isolated glands to 10(-5) M PAF in the presence of platelets and returning to 135% of controls at 2 h. Platelets alone did not produce any significant stimulation in glycoconjugate release. CV-3988, a known PAF antagonist, inhibited the secretory response to PAF. Methysergide, a known antagonist to receptors for 5-hydroxytryptamine, did not alter PAF-evoked glycoconjugate secretion. Both indomethacin and SQ 29,548, a thromboxane receptor antagonist, abolished the PAF-evoked glycoconjugate secretion from isolated submucosal glands. Epithiomethanothromboxane A2, a stable thromboxane A2 analogue, produced a significant increase in glycoconjugate secretion in a dose-dependent fashion. These findings indicate that PAF increases glycoconjugate release in the presence of platelets and that the increase is dependent on some aspect of platelet function, namely thromboxane generation.

Animals↗

Effect of epithelium on mucus secretion from feline tracheal submucosal glands.

We studied the effect of airway epithelium on mucus secretion by use of an isolated tracheal submucosal gland preparation reported previously (J. Appl. Physiol. 60: 1237-1247, 1986). Mucus glycoconjugate release from submucosal glands of feline trachea was examined using [3H]glucosamine as a mucus precursor. Isolated glands showed significantly higher secretory responses to cholinergic, alpha-, and beta-adrenergic agonists and dibutyryladenosine 3',5'-cyclic monophosphate (average 400% of control) than the conventional tracheal mucosal explants, which contained epithelium and submucosal tissues in addition to submucosal glands (average 160% of control). The addition of isolated epithelium depressed the secretory response of isolated glands to the same level as that of tracheal explants. However, the supernatant from isolated epithelium failed to inhibit secretory responses to methacholine in isolated glands, suggesting that the epithelium-derived inhibitory factor to secretion may be short-lived. Leukotriene D4 antagonist (FPL 55712), cyclooxygenase and/or lipoxygenase inhibitors (indomethacin or BW 755C) caused no significant change in the inhibitory action of epithelium, suggesting that the inhibition is not due to arachidonic acid metabolites. The newly found secretory inhibitory action of epithelium is of particular interest in the pathogenesis of hypersecretion associated with epithelial damage.

Animals↗

Acute effect of cigarette smoke on cytoplasmic motility of alveolar macrophages in dogs.

To study effects of cigarette smoke on the cytoplasmic motility (CM) of alveolar macrophages (AM), we measured remanent field strength (RFS) in dogs in vivo. Four days after instillation of ferrimagnetic particles (Fe3O4, 3 mg/kg) into the right lower lobe bronchus, RFS was measured at the body surface immediately after magnetization of the Fe3O4 particles by an externally applied magnetic field. RFS decreased with time due to particle rotation (relaxation), which is thought to be inversely related to CM of AM (J. Appl. Physiol. 55: 1196-1202, 1983). The initial relaxation curve was fitted to an exponential function. The relaxation rate (lambda 0) increased during cigarette smoke inhalation and returned to base-line values within 15 min. With the inhalation of the smoke of up to five cigarettes, peak lambda 0 was increased; with a further increase in the number of cigarettes, the effect of cigarette smoke decreased or disappeared. Nicotine injection and acetylcholine inhalation increased respiratory resistance to a degree similar to that observed with cigarette smoke but did not change lambda 0. However, either substance P (SP) or capsaicin injection increased lambda 0 in a fashion similar to that noted with cigarette smoke inhalation. Repeated administration of SP produced a significant tachyphylaxis of the effect, and capsaicin did not increase lambda 0 after the cigarette smoke-induced tachyphylaxis of the effect. Colchicine inhibited the cigarette smoke-induced increase in lambda 0. These results suggest that cigarette smoke increases CM of AM, probably through the release of tachykinins including SP from sensory nerves in the lung.

Acetylcholine↗

Step response of lung surface-to-volume ratio by light-scattering stereology.

By means of backscattered light from a pointlike source on the pleural surface, we investigated the dynamic behavior of the surface-to-volume ratio (S/V) in excised dog lobes subjected to small volume steps both in and out on both the inflation and deflation limb of standard pressure-volume maneuvers. The technique utilizes the established correlation of the pattern of backscattered light with morphometric mean linear intercept and is suitable for dynamic studies. We hypothesized that 1) there would be a difference in the timing of stress relaxation or recovery between alveolar septa and the fibromuscular tissue in the alveolar duct that would reveal itself as a temporally changing S/V after a step-volume change and 2) that geometric hysteresis (looping of S/V with volume), as seen with large volume excursion histories, would be similarly present in small tidal volume loops. Our experimental results contradicted both hypotheses. In particular, we found virtually no change in S/V after a step-volume change, even in the presence of substantial stress adaptation. In addition, when geometric hysteresis of small loops was present, it was always in the sense opposite to the geometric hysteresis of large loops. We conclude that 1) there is a functional "matching" of the stress-adaptive timing between alveolar septa and ductal mouths and 2) during small volume looping, the stress hysteresis (looping of stress with volume) in the ductal tissue may be larger than that of the septa, including surface tension.

Animals↗

Pharmacological effect of KC-404 on leukotriene release from human leukocytes induced by ionophore A23187.

Release of leukotriene (LT) B4, LTC4 and histamine from human peripheral mixed leukocytes stimulated with calcium ionophore A23187 was evaluated. The amounts of LTB4 and LTC4 in supernatants were analyzed by high performance liquid chromatography and histamine was measured by an automated fluorometric technique. A time-course study demonstrated the characteristic patterns of the release of these mediators. LTB4 and LTC4 were more slowly released than histamine and the release of these LTs was inhibited by KC-404, a novel anti-asthmatic drug which has no effect on histamine release.

Calcimycin↗

Leukotriene C4 and B4 in bronchoalveolar lavage fluid during biphasic allergic bronchoconstriction in sheep.

To study the contribution of leukotriene C4 (LTC4), leukotriene D4 (LTD4), leukotriene B4 (LTB4), and inflammation to the antigen-induced late bronchial response, these leukotrienes, histamine, and cell differentials were evaluated in bronchoalveolar lavage fluid (BALF). Immediate and late responses were induced by Ascaris suum antigen inhalation in 11 conscious sheep. Bronchoalveolar lavage was performed on 3 separate test days, before challenge (control), during the immediate response, and during the late response. Leukotrienes were measured by radioimmunoassay after purification by reverse-phase high-performance liquid chromatography. LTB4 and LTC4 were detected in control BALF, but LTD4 was not. LTC4 and LTB4 were increased in the late response (p less than 0.05 compared with each control). The percent neutrophils recovered by bronchoalveolar lavage was increased during the late response, and this was significantly correlated with pulmonary resistance (p less than 0.01). Histamine levels in BALF were elevated during the immediate response but not during the late response. Our results suggest that histamine and LTC4 may contribute to the contraction of bronchial smooth muscle in the immediate and the late response, respectively. The increase in LTB4, a neutrophil chemotactic factor, during the late response may be responsible for the increase in the percent neutrophils.

Administration, Inhalation↗

Sensory receptors and reflex pathways of nonadrenergic inhibitory nervous system in feline airways.

The sensory receptors and reflex pathways of the nonadrenergic inhibitory nervous system (NAINS) were examined, using separately ventilated left and right lungs in cats. During bronchoconstriction induced by 5-hydroxytryptamine (5-HT) (50 to 250 micrograms/kg/min, i.v.) infusion after atropine (3 mg/kg, i.v.) and propranolol (2 mg/kg, i.v.), one lung was challenged with (1) citric acid aerosol or (2) capsaicin aerosol or (3) lung volume change (lung inflation). Citric acid or capsaicin inhalation to one lung produced significant bronchodilatation in not only the stimulated lung (SL) but also in the opposite lung (OL). The 5-HT-induced change in pulmonary resistance (RL) was reduced 66.5 +/- 3.3% (mean +/- 1 SE) (SL) and 53.0 +/- 8.1% (OL) by citric acid (20%) and 40.5 +/- 8.9% (SL) and 44.0 +/- 9.9% (OL) by capsaicin (0.1%) inhalation, respectively. These bronchodilatations were abolished by bilateral vagotomy. Inflation of one side of the lung did not reduce the 5-HT-induced change in RL in the OL. These findings indicate that (1) C-fiber and irritant receptors are the possible sensory receptors of the NAINS reflex pathway, and (2) afferent nerve stimulation of NAINS in one lung can produce reflex bronchodilatation in both lungs.

Animals↗

Morphometric analysis of intraluminal mucus in airways in chronic obstructive pulmonary disease.

Mucus volume in both central and peripheral airways was assessed in 13 patients, six with chronic bronchitis (CB) and seven with chronic pulmonary emphysema (CPE), by morphologic quantitative measurement in autopsied lungs, and the results were compared with those from four control lungs (NL). The patients with CB and CPE had severe obstructive impairment that did not differ significantly between the two groups (FEV1%, mean 45% in CB and mean 49% in CPE). Mucous hypersecretion during clinical remission differed significantly between the CB and CPE groups (mean 80 ml/day in CB and mean 8 ml/day in CPE). The length of the airway basement membrane and the area of mucus were measured with a digitizing computer. The volume ratio of mucus to airway lumen, which was defined as the volume ratio of mucus to airway lumen calculated as a cylinder by the length of basement membrane, was regarded as the mucus occupying ratio (MOR). MOR was significantly higher in CB lungs (4.1 +/- 1.0% in central airways and 19.6 +/- 3.8% in peripheral airways, mean +/- SE) than in NL (0.3 +/- 0.1% in central airways and 0.6 +/- 0.3% in peripheral airways, respectively) in both central and peripheral airways (p less than 0.05 and p less than 0.01, respectively), whereas no significant increase in MOR was found in CPE lungs, compared with NL. Furthermore, peripheral airway MOR was significantly higher than that of central airways in CB lungs (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Effects of electrical stimulation of the genioglossus on upper airway resistance in anesthetized dogs.

We examined the relationship between the frequency of stimulation of the genioglossus and upper airway resistance in six anesthetized dogs in the supine position. The upper airway was isolated from the lower airway by transecting the cervical trachea, and the pressure flow relationship of the upper airway was obtained by applying constant negative pressure (5, 10, and 20 cm H2O) to the proximal cut end of the trachea. Electrical stimulation of the genioglossus was performed at a constant voltage (10 to 20 V) and at various frequencies (as high as 100 Hz). Upper airway resistance (Rua) during both inspiration and expiration increased with an increase in tracheal negative pressure, and at each tracheal negative pressure Rua was significantly reduced by stimulation of the genioglossus. The effects of genioglossal muscle stimulation were nonlinearly dependent on the stimulating frequency. Below 50 Hz, Rua decreased markedly as the stimulating frequency was increased, but above 50 Hz, Rua plateaued at a minimum value. These findings suggest that at a stimulating frequency of more than 50 Hz, upper airway patency is stably maintained in anesthetized dogs.

Airway Resistance↗

Effects of submental electrical stimulation during sleep on upper airway patency in patients with obstructive sleep apnea.

We examined the effects of percutaneous electrical stimulation of the genioglossus in six patients with obstructive sleep apnea syndrome (OSAS) during sleep and investigated the possible applicability of this procedure as a treatment of OSAS. Six patients with OSAS were polysomnographically studied in the supine position during all-night sessions with and without electrical stimulation of the genioglossus. Using an apnea demand-type stimulator that we developed, electrical pulses of 0.5 ms (repetition rate, 50 Hz) and 15 to 40 V were delivered through bipolar electrodes (10 mm in diameter) attached to the skin of the submental region when apnea lasted more than 5 s, and was stopped immediately after breathing resumed or after 10 s at the longest. With submental stimulation, the apnea index, apnea time/total sleep time, longest apnea duration, and the number of times per hour that oxygen saturation dropped below 85% decreased significantly compared with those on control nights. The lowest arterial oxygen saturation and the duration of sleep stages III and IV increased significantly. The stimulation employed did not cause arousal, and it did not affect blood pressure or heart rate significantly. These findings show that submental stimulation decreases the incidence of apnea episodes and promotes deeper sleep without accompanying serious side effects, suggesting that the apnea demand-type stimulator may be a noninvasive and effective treatment for OSAS.

Electric Stimulation↗

Increase in luminal mast cell and epithelial damage may account for increased airway responsiveness after viral infection in dogs.

To elucidate the mechanisms of airway hyperresponsiveness induced by viral infection, we examined histologically and analyzed bronchoalveolar lavage (BAL) fluid using dogs infected with influenza C and noninfected control dogs. Airway responsiveness was assessed as inhaled acetylcholine concentration required to increase pulmonary resistance by 5 cm H2O/L/s (ACh PC). Airway responsiveness was determined before and 2 wk after virus or vehicle inoculation in infected and control dogs, and BAL and histologic studies were performed after the final challenge. Differential cell numbers and histamine concentration were determined in the BAL fluids of both groups. The ACh PC of control dogs did not change with the vehicle inoculation. However, that of infected dogs decreased two to five times as much as their initial value with viral infection. Histologic studies revealed diffuse epithelial damage in the central airways of infected dogs, but infiltrated cell counts within the airway tissue of both groups were not significantly different. From BAL analysis, mast cell number and the histamine concentration of infected dogs increased significantly compared with those of control dogs (3.1 +/- 0.4 x 10(5) versus 0.9 +/- 0.3 x 10(5) cells/ml and 7.3 +/- 1.7 versus 1.9 +/- 0.5 ng/ml, respectively). Luminal mast cell number and epithelial damage score in each dog was correlated with the increase in airway responsiveness. These findings indicate that airway inflammation in virus-induced hyperreactive dogs is characterized by epithelial damage and luminal increase in mast cells and related mediators, and these changes may be related to the appearance of virus-induced airway hyperreactivity.

Acetylcholine↗

Complete reversibility of physiological coronary vascular abnormalities in hypertrophied hearts produced by pressure overload in the rat.

Using an experimental model of ascending aortic banding in the rat, we examined whether coronary circulation abnormalities in hypertrophied hearts are reversible after debanding. 4-wk banding produced significant increases in in vivo left ventricular (LV) pressure (194 +/- 13 vs. 114 +/- 9 mmHg in shamoperated controls) and LV dry wt/body wt (48 +/- 5% above controls). In isolated hearts perfused with Krebs-Henseleit buffer, coronary flow rate (CFR) was estimated under nonworking conditions. During maximal vasodilation after 1 min-ischemia, CFR at a coronary perfusion pressure (CPP) of 100 mmHg and CFR/myocardidial mass at CPPs of 100 and 150 mmHg decreased significantly (72 +/- 5%; 53 +/- 4 and 61 +/- 4% of controls). 1 or 4 wk after debanding, LV systolic pressures were similar to control values, and the degree of myocardial hypertrophy decreased to levels 23 +/- 6 (P less than 0.01) and 11 +/- 6% (P less than 0.01) above their control values, respectively. At 1 wk there was no significant increase in CFR/myocardial mass, compared to values in the banded group (67 +/- 8 vs. 53 +/- 4% of controls at 100 mmHg and 67 +/- 9 vs. 61 +/- 4% at 150 mmHg of CPP). At 4 wk, CFR and the ratio had increased toward normal. Thus, decreased coronary perfusion in hypertrophied hearts is completely reversible.

Animals↗

Left ventricular pump function in right ventricular overload.

To clarify how left ventricular pumping action is altered in cor pulmonale, an experimental study was performed using canine heart preparations in which the effects on left ventricular performance of right ventricular overload, with and without depressed systolic function, were investigated. For this purpose, two methods using excised perfused hearts (n = 16) and in vivo hearts (n = 6) were employed, and in the latter condition, pulmonary artery constriction (n = 7), femoral arterial-venous (A-V) shunt (n = 3) and right coronary artery occlusion (n = 6) were induced. Left ventricular systolic function was assessed by the relationship between left ventricular isovolumic developed pressure and left ventricular volume in excised heart, and by ejection fraction with 2 dimensional echocardiogram in the vivo condition, taking into account preload and afterload changes. From the excised heart preparation, it was shown that left ventricular developed pressure significantly decreases when right and left ventricular diastolic pressure increases greatly. On the other hand, in vivo right ventricular overload due to pulmonary constriction and A-V shunt, the left ventricular ejection fraction increased following afterload reduction. When we compare the left ventricular ejection fraction in pulmonary constriction with that in right coronary occlusion, in which reduction of left ventricular diastolic area from the control was similar, the latter was significantly decreased despite afterload reduction. These results suggest that right ventricular overload does not necessarily induce left ventricular systolic dysfunction unless left ventricular end-diastolic pressure, as well as that of the right ventricle, increases definitely and simultaneously.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗