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Biomedical subjects

S Shimura

Publications and source records attributed to S Shimura.

At least 127 records · Page 7Linked to original sources
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1988

Distribution of alpha-adrenergic bronchoconstriction in feline airways.

We studied the distribution of in vivo alpha-adrenergic bronchoconstriction roentgenographically and histologically as well as functionally, using 13 anesthetised, mechanically ventilated cats. We observed changes in airway diameter by employing tantalum bronchography and studied function by measuring pulmonary resistance (RL), static compliance (Cst), and dynamic compliance (Cdyn). alpha-adrenergic stimulation was produced by intravenous injection of norepinephrine (40 micrograms/kg) after administration of atropine (3 mg/kg, i.v.) and propranolol (2 mg/kg, i.v.). alpha-adrenergic stimulation produced a significant increase in RL (76.2 +/- 4.0 (mean +/- SE)%) and a significant decrease in Cst and Cdyn (23.7 +/- 2.2 and 27.9 +/- 4.2%, respectively). Tantalum bronchograms revealed that alpha-adrenergic stimulation produced a significant decrease in airways with bronchial diameter of 0.5-1.0 mm (9.5 +/- 3.7%). Histological study using a rapid-freezing technique with liquid nitrogen was added to ascertain the site of alpha-adrenergic bronchoconstriction, demonstrating bronchoconstriction in the airways from small bronchi to bronchioli, especially in bronchioli less than 0.5 mm in internal diameter. We conclude that alpha-adrenergic responsiveness can be observed roentgenographically and histologically as well as functionally in vivo, and that the main site of alpha-adrenergic responsiveness is bronchioli less than 1 mm in internal diameter.

Animals↗
PubMed1988

VIP augments cholinergic-induced glycoconjugate secretion in tracheal submucosal glands.

Using isolated submucosal glands from feline trachea, we examined the effect of vasoactive intestinal peptide (VIP) on mucus glycoprotein secretion and glandular contraction by measuring released radiolabeled glycoconjugates and induced tension, respectively. VIP (10(-10) to 10(-6) M) produced a dose-dependent increase in [3H]glycoconjugate release of up to 300% of controls, which was inhibited by VIP antiserum and not inhibited by atropine, propranolol, or phentolamine. VIP at a low concentration (10(-9) M), which did not produce any significant increases over controls, produced a 2.4- to 5-fold augmentation of the glycoconjugate release induced by 10(-9) to 10(-7) M methacholine (MCh). Atropine or VIP antiserum abolished the augmentation. VIP did not produce any alteration in isoproterenol- or phenylephrine-evoked glycoconjugate secretion. VIP (up to 10(-5) M) did not produce any alteration in the tension, even when the gland had contracted with MCh, or any augmentation of contraction induced by MCh (10(-9) to 10(-7) M). These results indicate that VIP induces mucus glycoprotein release from secretory cells and also that it potentiates the secretion induced by cholinergic stimulation.

Animals↗
PubMed1988

Airway mucosal permeability in chronic bronchitics and bronchial asthmatics with hypersecretion.

To determine airway mucosal permeability, radiolabeled albumin in sputum was examined on the basis of a 2-h period of sputum collection for as long as 8h after intravenous administration of 131I-labeled human serum albumin. This technique was applied to 12 patients with bronchial asthma associated with hypersecretion or chronic bronchitis. Group A consisted of 6 asthmatics (2 females and 4 males, 56.0 +/- 6.4 yr of age, mean +/- SEM); Group B consisted of 6 bronchitics (3 females and 3 males, 53.8 +/- 6.5 yr of age). Between Groups A and B, there was no significant difference in sputum volume per day or in obstructive impairment. Radiolabeled albumin concentration (cpm/ml) was obtained from radiocount of each sputum sample and then divided by serum concentration at the time of each sampling (2, 4, 6, and 8 h after administration). Group B showed large values compared with those in Group A. In Group A, the ratios were 2.0 +/- 0.8, 2.5 +/- 0.5, 2.2 +/- 0.2, and 1.5 +/- 0.4% (mean +/- SEM) at 2, 4, 6, and 8 h after the administration, respectively, whereas in Group B, the ratios were 3.0 +/- 0.6, 7.0 +/- 1.8, 7.2 +/- 1.8, and 7.4 +/- 2.4%, respectively. The differences between Groups A and B were statistically significant (two-way analysis of variance). These findings suggest that an increase in airway mucosal permeability is due to mucosal epithelial damage by chronic inflammation in bronchitics and not to the underlying abnormality of asthma.

Asthma↗
PubMed1988

Chemical properties of bronchorrhea sputum in bronchial asthma.

Bronchorrhea, defined as watery sputum of 100 ml or more per day, was seen in 18 of 207 patients (8.7 percent) with bronchial asthma during attack. Fifteen bronchorrhea sputum samples were chemically examined using ten parameters: dry weight, albumin, IgA, pH, Na+, Cl-, K+, prostaglandins E and F and histamine, and compared with eight saliva samples and 17 mucoid sputum samples. Bronchorrhea sputum differed from saliva in its chemical parameters. Bronchorrhea sputum exhibited parameter values intermediate between those of saliva and mucoid sputum, except for the two following parameters. The pH of bronchorrhea sputum was significantly lower than that of mucoid sputum and histamine concentration, expressed as weight per dry weight of sample, was significantly higher in bronchorrhea than in mucoid sputum. Administration of corticosteroid or an histamine H1-blocker to five to nine asthmatic patients with associated bronchorrhea sputum during asthmatic attacks, significantly reduced the volume of bronchorrhea sputum, whereas anticholinergics and H2-blocker did not alter the sputum volume.

Administration, Topical↗
PubMed1988

Viscoelastic properties of bronchorrhoea sputum in bronchial asthmatics.

Dynamic viscoelastic properties of 13 bronchorrhoea sputum samples from asthmatics with bronchorrhoea, defined as the production of watery sputum of 100 ml or more per day during asthmatic attacks, were examined and then compared with 7 saliva and 12 mucoid sputum samples obtained from patients during remission. Dynamic viscosity (eta') and elasticity (G') of bronchorrhoea sputum increased rapidly with time up to 2 hours after collection and slowly thereafter, whereas eta' and G' of saliva and mucoid sputum remained unchanged up to 6 hours after collection. Then, eta' and G' of saliva, bronchorrhoea and mucoid sputum samples were measured between 2 to 4 hours after expectoration. Bronchorrhoea sputum samples showed significantly larger values at frequencies of both 0.1 and 1.0 rad/sec than did saliva samples and also significantly smaller values than did mucoid sputum samples. Thus, bronchorrhoea sputum differed in dynamic viscoelastic properties from saliva, indicating that it does not result from hypersalivation. Based on data of viscoelastic changes with time, it can be assumed that the viscoelasticity of bronchorrhoea sputum in the airways is considerably less than the optimal range reported previously for mucociliary velocity, suggesting the possibility of impaired mucociliary transport.

Adult↗
PubMed1987

Neural control of contraction in isolated submucosal gland from feline trachea.

To determine the autonomic innervation to myoepithelial cells of submucosal gland, we applied electrical field stimulation (FS) to the intrinsic nerves in isolated submucosal glands from feline tracheae. FS induced contraction that was voltage or frequency dependent and abolished by pretreatment with tetrodotoxin. DMPP (1,1-dimethyl-4-phenylpiperazinium iodide) did not produce any significant contraction, and pretreatment with hexamethonium did not alter the response to FS. Atropine inhibited the contractile response to FS and neostigmine augmented the response to FS. Serotonin also augmented the response to FS, whereas the response to methacholine remained unchanged in the presence of serotonin. Phentolamine reduced the response to FS by 15% of control, whereas propranolol induced no significant changes in the response to FS. No significant inhibitory responses were observed by FS. Our findings indicate that the contraction of tracheal submucosal glands is mediated mainly by cholinergic nerves via muscarinic receptors and in small part by adrenergic nerves via alpha-receptors, and serotonin potentiates the contractile response to FS at the postganglionic nerve.

Adrenergic Fibers↗
PubMed1987

Effect of substance P on mucus secretion of isolated submucosal gland from feline trachea.

To elucidate how substance P (SP) produces submucosal gland secretion, we examined the effects of SP on the glandular contractile response and 3H-labeled glycoconjugate release in isolated submucosal glands from feline tracheae. SP (10(-12) to 10(-4) M) produced dose-dependent increases in the contractile response, and the maximal tension induced by SP was approximately 70% of the response to methacholine. SP-induced contraction is blocked completely by atropine and augmented by neostigmine. Pretreatment with hemicholinium 3, an acetylcholine synthesis inhibitor, inhibited the contractile response to SP. Pretreatment with tetrodotoxin did not inhibit the contractile response to SP. Capsaicin induced tension of a magnitude similar to that of SP. SP (10(-7) M) produced a significant increase (74% above control) in radiolabeled glycoconjugate release from isolated glands, whereas SP had no significant effects on glycoconjugate release from tracheal explants, probably because of epithelial suppression. Atropine abolished SP-evoked glycoconjugate release in isolated glands. Our findings indicate that 1) SP induces glandular contraction, which is related to the squeezing of mucus in the ducts and secretory tubules, 2) SP stimulates radiolabeled glycoconjugate release in isolated submucosal gland, probably involving mucus synthesis and/or cellular secretion, and 3) these two actions are mediated by a peripheral cholinergic mechanism.

Animals↗
PubMed1987

Bronchoalveolar lavage and histologic characterization of late asthmatic response in guinea pigs.

To elucidate the mechanisms of late asthmatic response (LAR) observed in asthmatic subjects, we have developed an animal model of LAR using guinea pigs. Fifty guinea pigs were immunized with a mixture of Ascaris suum extract and aluminum hydroxide and then challenged with an inhalation of Ascaris suum extract without anesthesia. Twenty of the 50 guinea pigs showed a dual asthmatic response in which the LAR occurred 3 to 6 h after immediate asthmatic response (IAR). Histologic studies by rapid freezing with liquid nitrogen or bronchoalveolar lavage (BAL) were performed in 14 of these 20 guinea pigs with LAR and compared with those in 10 of 18 guinea pigs with only IAR, 10 control guinea pigs, and 10 nonimmunized but challenged guinea pigs. Both the percentage and the absolute number of neutrophils in the BAL fluid of the guinea pigs with LAR were significantly greater than those of the control guinea pigs (p less than 0.02) and than those of the nonimmunized but challenged guinea pigs (p less than 0.02). However, that of guinea pigs with LAR was not significantly different from that of guinea pigs with only IAR. On the other hand, histologic examination showed that eosinophil infiltration within the airway walls of the guinea pigs with LAR was more prominent than that of the guinea pigs with only IAR, and showed that there was no significant difference in neutrophil infiltration within the airway walls between the guinea pigs with LAR and the animals with only IAR. Contraction of airway (bronchus, bronchiole) smooth muscle, submucosal edema, and mucus in airway lumen were also observed in LAR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Late asthmatic response to Ascaris antigen challenge in dogs treated with metyrapone.

We developed an experimental dog preparation that shows a biphasic bronchoconstriction after allergen exposure. After anesthetization, the dogs were intubated with endotracheal tubes and manually ventilated. Respiratory resistance (Rrs) was measured by the forced oscillation method at 3 Hz. Ascaris suum, diluted from 10(-5) to 10(-2) of the extract, was inhaled during tidal breathing for 5 min. One hour before antigen challenge, 10 dogs received 70 mg/kg of metyrapone (cortisol synthesis inhibitor), and 2 h after antigen challenge 35 mg/kg of metyrapone were injected intravenously. In another 10 dogs, metyrapone was not administered. After the maximal increase in Rrs had been assessed (immediate asthmatic response), Rrs increased again 4 to 6 h after antigen challenge in 8 of the 10 dogs treated with metyrapone (late asthmatic response, 443 +/- 282% mean +/- SD of initial Rrs), which was significantly higher than Rrs 6 h after antigen challenge (124 +/- 41%) in dogs without metyrapone (p less than 0.01). In another 5 dogs, ragweed challenge with metyrapone caused no change in Rrs. Bronchoalveolar lavage at the time of the late response revealed a significant correlation between late asthmatic response and neutrophil accumulation (p less than 0.01) in all dogs. We conclude that cortisol depletion augments the occurrence of the late response. The present dog model may be a useful tool for study of the late response in bronchial asthma.

Airway Resistance↗
PubMed1986

Effects of ageing on the alveolar pores of Kohn and on the cytoplasmic components of alveolar type II cells in monkey lungs.

The effects of ageing on the numbers of alveolar pores of Kohn and on the cytoplasmic components of alveolar type II cells were studied in monkey lungs by scanning and transmission electron microscopy. Lung tissue from 26 female and three male pigtail macaques whose ages ranged from 1 month to 31 years (life span is 35 years) was analysed. From the age of 1 month to 10 years there was a significant increase in the number of alveolar pores (r = 0.85, p less than 0. 001); however, between the ages of 14 years to 31 years there was no significant change. In seven animals ranging in age from 1 month to 4 years (mean 2.4 years) the number of pores was 5.8 +/- 3.9 (mean +/- S.D.), whereas in 10 animals aged 16 to 31 years (mean 20.3 years) the number of pores was 32.7 +/- 17.5 (mean +/- S.D.) per alveolar profile, a significant difference (p less than 0.002). In older animals (15-20 years) there was a significant decrease, both in the number of lamellar bodies per alveolar type II cell (p less than 0.01) and in the volume density of lamellar bodies to cytoplasmic volume (p less than 0.05) compared with young animals (1 month to 4.8 years). In older animals, there was also a significant increase in the volume density of a vacuole-like dilatation of the endoplasmic reticulum in alveolar type II cells (p less than 0.05) compared with young animals. These findings suggest impaired pulmonary surfactant production with aging. Both the increased number of alveolar pores and the postulated decrease of surfactant production could play a role in the pathogenesis of pulmonary emphysema.

Aging↗
PubMed1986

Effect of sublingual isosorbide dinitrate on sputum volume and viscoelasticity in chronic obstructive lung disease.

The effect of isosorbide dinitrate (ISDN) on sputum volume and sputum viscoelasticity in 12 patients with chronic obstructive lung diseases (COLD) was investigated by the double-blind randomized cross-over method with matched placebo. Each patient was given either sublingual ISDN 5 mg or placebo at 9 a.m. and sputum was collected for 3 h before and after 9 a.m. The dynamic viscoelasticity of the sputum was measured using a coaxial cylinder rheometer at an angular frequency of 0.1 rad/s. ISDN significantly increased sputum volume, and it caused a significant decrease in dynamic viscosity and in dynamic elasticity compared to placebo. The findings suggest that ISDN might be useful as an expectorant in the treatment of COLD when abundant and viscous sputum is present.

Adult↗
PubMed1986

Contractility of isolated single submucosal gland from trachea.

We isolated single submucosal glands from canine and feline trachea. Examination by light and electron microscope showed that these isolated glands consist mainly of glandular tissue, and no smooth muscle. Cell components in the glandular tissue were ultrastructurally normal, and myoepithelial cells surrounded acini and secretory tubules. In response to methacholine, the mucus was squeezed from the tip of the collecting ducts in coincidence with the contraction of the glands. The contractile properties of isolated single glands were examined with a force transducer. Cholinergic agents (methacholine and acetylcholine) as well as 40-150 mM K+ showed a dose-response relationship and induced tension up to 12 mg. The length-tension relationship was also observed. The removal of Ca2+ from the medium eliminated contractile response. Caffeine induced approximately 30% of the response to methacholine, and phenylephrine, a tension less than 30% of that with methacholine. These findings suggest that squeezing of mucus due to the contraction of myoepithelial cells has an important effect on secretory response of airway submucosal glands.

Animals↗
PubMed1986

Morphological aspects of the surfactant system in human lungs. A freeze-fracture study.

We examined alveolar type II cells and extracellular surfactant (tubular myelin) of human lungs and compared them with those of experimental animals (mouse, rat and dog) using a freeze-fracture technique for electron microscopy. Lamellar bodies (intracellular surfactant) in alveolar type II cells of human lung showed features different from those of the experimental animal lungs. Namely, multicentric foci of lamellae, an amorphous portion with some degree of lattice-like structure in the mature bodies, unpaired split membranes of lamellae and also our previously reported connection of the lamellar bodies to the endoplasmic reticulum (Am. Rev. resp. Dis. 127: 1983) were found in alveolar type II cells of human lungs but not in type II cells of experimental animal lungs. On the other hand, there were no differences noted in extracellular surfactant between human and experimental animal lungs. These findings indicate the possibility that a mode of surfactant production and/or storage in alveolar type II cells exists in human lung which is different from that in experimental animal lungs.

Aged↗