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Biomedical subjects

S Shimura

Publications and source records attributed to S Shimura.

At least 37 records · Page 2Linked to original sources
PubMed1999

Cholinomimetic action of macrolide antibiotics on airway gland electrolyte secretion.

We investigated the acute effects of erythromycin (EM) and its derivatives on ionic currents in airway glands from feline tracheae. Therapeutic concentrations of EM or clarithromycin (CAM) attenuated the whole cell currents evoked by ACh in a competitive manner. The maximally stimulated inward Cl- currents were reduced to 54 and 83% and the outward K+ currents to 55 and 84% of control values by EM and CAM, respectively, whereas the responses induced by phenylephrine, norepinephrine, caffeine, or ionomycin were unaffected by EM, CAM, or EM523, a synthetic derivative of EM. K+ channels in excised outside-out patches were not influenced by macrolides. Although therapeutic concentrations of macrolides showed no effect on the baseline currents, high concentrations of macrolides alone evoked currents mimicking the ACh response, which were abolished completely by atropine. We concluded that macrolides act as a partial agonist on cholinergic receptors, resulting in a reduction of Cl- secretion at pharmacological doses of the agents, which may exhibit a pronounced effectiveness on hypertrophied and/or cholinergically sensitized submucosal glands in pathological airways.

Acetylcholine↗
PubMed1999

Morphometric analysis of bronchial cartilage in chronic obstructive pulmonary disease and bronchial asthma.

To clarify the changes in bronchial cartilage in diseased airways, we performed morphometric analysis of airways in autopsied lungs of 16 patients with chronic bronchitis (Group CB), pulmonary emphysema (Group PE), and bronchial asthma (Group BA), and in control patients without respiratory diseases (Group CN). Although degeneration of bronchial cartilage was clearly observed in airways from all groups except Group CN, the most extreme change was seen in Group CB. Increased perichondrial fibrosis was observed in both Groups CB and BA, and the more extreme change was seen in Group BA. Both the area proportions of degenerated cartilage (Deg%) and perichondrial fibrosis (Fib%) to total cartilage in bronchi (3 to 8 mm in diameter), cut vertically in the cross-section profile, were measured with a digitizing tablet coupled to a computer. No significant differences in the area proportion of cartilage to bronchial wall were observed among the four study groups. The Deg% values of Groups CB (mean: 15.4%), BA (mean: 12.9%), and PE (mean: 9.6%) were significantly higher than those of Group CN (mean: 1.0%) (p < 0.01 in each case). The Deg% values correlated significantly with the number of neutrophils in the bronchial walls (r = 0.63, p < 0. 01). Both Group CB (mean: 28.5%) and Group BA (mean: 33.6%) showed significantly higher values of Fib% than did Group CN (mean: 18.5%) (p < 0.01, each), and the value for Group PE (mean: 21.8%) was slightly increased (p < 0.05). The values of Fib% correlated significantly with the number of eosinophils in the bronchial walls (r = 0.51, p < 0.05), thickness of basement membrane (r = 0.77, p < 0.0002), bronchial gland area (r = 0.56, p < 0.02), and goblet-cell area (r = 0.55, p < 0.02). Further, the values of Deg% correlated significantly with those of Fib% (r = 0.64, p < 0.01). These findings indicate that airways in chronic obstructive pulmonary disease and bronchial asthma have both degenerative changes in the cartilage (chondrocytes) and increased perichondrial fibrosis, and that these alterations in bronchial cartilage may differ in chronic bronchitis and bronchial asthma.

Aged↗
PubMed1999

Age-dependent increase of IgE-binding and FcepsilonRI expression on circulating basophils in children.

Peripheral blood basophils are sparse in the circulation, but they express high-affinity receptors for IgE (FCepsilonRI) and bind IgE efficiently. The present study was performed to elucidate the role of IgE bound on the basophil surface in the development of allergic responses during infancy and early childhood. IgE-binding and FcepsilonRI expression on basophils were evaluated by two-color flow cytometry. Basophil-bound IgE increased rapidly and reached adult levels during infancy in atopic patients, while it gradually increased with advancing age in parallel with serum IgE in normal controls. IgE-binding and FcepsilonRI expression in atopic children were higher than in normal controls among various age groups. They correlated with serum IgE levels but reached a plateau when serum IgE exceeded 300 ng/mL. A low, but significant level of FcepsilonRI expression was observed on cord blood basophils, although IgE-binding was usually undetectable. Incubation of cord blood with IgE rapidly saturated the preexisting IgE receptors and basophil-bound IgE levels increased. When neonatal basophils were cultured for 48 h with IgE, FcepsilonRI expression was upregulated dose-dependently and IgE-binding increased further. The up-regulation of FcepsilonRI was completely inhibited by cycloheximide, indicating that it was dependent on de novo protein synthesis. These results suggest that IgE-binding on basophils serves as a sensitive indicator of allergic sensitization, and that IgE functions as a positive regulator of FcepsilonRI expression in vivo.

Adolescent↗
PubMed1999

[Clinical study of grade 3, superficial transitional cell carcinoma of the urinary bladder].

PURPOSE: To evaluate the treatment of grade 3 superficial (stage pTa and pT 1) transitional cell carcinoma (T.C.C.) of the urinary bladder, retrospective analysis was performed with special reference to tumor prognostic factors. MATERIALS AND METHODS: From July 1971 to september 1995, 51 cases with grade 3 superficial T.C.C. of the urinary bladder were treated. The survival rates and prognostic factors of these patient were analyzed. RESULTS: Five year survival rate of grade 3, superficial tumors was 92.3% and showed significantly better prognosis compared to patients with pT 2 and pT 3 tumors of grade 3 (p < 0.001). As a initial treatments, transurethral resection (TUR) was conducted in 45 patients (88%). Intravesical recurrence was observed in 20 of 45 patients (44%) and 12 of 20 patients (60%) were recurred within 1 year. Non-recurrent rates of the patients treated with TUR were 69.6% at 1 year, 58.8% at 3 year, 49.7% at 5 year, respectively. No significant differences were noted regarding factors of tumor size, figures and a number of tumor. Of the 51 patients, 10 (19.6%) progressed beyond stage T 2 and 6 died with the disease. Survival rates at 10 years follow up in patients with non-papillary and papillary tumor were 57.1% and 97.8%, respectively. CONCLUSION: These results suggested that TUR should be performed as a initial treatment for the patients with grade 3 superficial T.C.C. of the urinary bladder. However, non-papillary tumors should be considered of more intensive treatment like as radical cystectomy, adjuvant chemotherapy or irradiation.

Adult↗
PubMed1999

[Bronchoalveolar lavage in diagnosis of chronic obstructive pulmonary disease].

In addition to understanding the pathophysiology, bronchoalveolar lavage (BAL) and bronchial lavage (BL) are used for the diagnosis of chronic obstructive pulmonary disease (COPD). Abundant neutrophils and mononuclear cells (lymphocytes) with a few of eosinophils are observed in BAL or BL fluids from chronic bronchitis patients, while abundant neutrophils and macrophages are seen in BAL fluids from emphysema patients. COPD patients combined with bronchial asthma show an increase in eosinophil number in BAL or BL fluid. In BAL fluids from diffuse panbronchiolitis (DPB) patients, increased neutrophils alone are observed without any increases in eosinophils or mononuclear cells.

Asthma↗
PubMed1998

Laminin inhibits Cl- -secretion across canine tracheal epithelium.

We examined the effect of laminin (a major component of the basement membrane) on potential difference (PD) and short circuit current (SCC) in both posterior epithelial membranes (native tissue) and cultured epithelial cell layers from canine trachea using an Ussing chamber. Although laminin itself did not alter the baseline values of SCC or PD, it significantly inhibited in a dose-dependent manner the isoproterenol induced SCC and PD rises of the epithelial membrane. In the cultured epithelial layer treated with amiloride, laminin did not alter the baseline values of SCC, PD or resistance (R) but it significantly inhibited the isoproterenol induced SCC rises. However, laminin did not significantly inhibit the bradykinin induced SCC rise in the cultured epithelial layer treated with amiloride. These findings indicate that laminin is a determinant in ion transport (mainly Cl- secretion) across canine tracheal epithelium, inhibiting the beta-agonist induced Cl- transport.

Adrenergic beta-Agonists↗
PubMed1998

Dexamethasone suppresses gene expression and production of IL-13 by human mast cell line and lung mast cells.

BACKGROUND: IL-13 has been shown to induce IgE production in B cells by promoting class switching to IgE. Mast cells are known to play an important role in the pathogenesis of allergic diseases. We evaluated the ability of human mast cells to produce IL-13 using human mast cell line HMC-1 and freshly isolated lung mast cells and then examined the effect of dexamethasone on the gene expression and production of IL-13 by these cells. METHODS: HMC-1 cells and lung mast cells were cultured with 10 ng/ml phorbol 12-myristate 13-acetate (PMA) and 1 micromol/L ionomycin and with 5 microg/ml phytohemagglutinin (PHA) and 10 ng/ml PMA, respectively, in the presence of dexamethasone. The gene expression of IL-13 at 3 hours (HMC-1 cells) or 12 hours (human lung mast cells) after stimulation was assessed semiquantitatively by sequential reverse transcription-polymerase chain reaction and Southern blot analysis. IL-13 production at 12 hours after stimulation was assayed by ELISA. RESULTS: The gene expression of IL-13 by HMC-1 cells and human lung mast cells, which was detected at a low level in an unstimulated condition, was increased by PMA/ionomycin and suppressed by dexamethasone. The supernatant of HMC-1 cells and human lung mast cells showed a low level of IL-13, which was increased by the stimulation and suppressed by dexamethasone. CONCLUSION: These findings indicate that HMC-1 cells and human lung mast cells produce IL-13 and that dexamethasone suppresses the production of IL-13 by these cells through an inhibitory action on the gene expression.

Cell Line↗
PubMed1998

Evaluation of left ventricular volume using automatic border detection in children: a comparison with conventional off-line echocardiographic quantification.

BACKGROUND: Evaluation of the clinical usefulness of the one-line automatic border detection system for determination of left ventricular volume in children in comparison to the conventional off-line method. METHODS: Eighty consecutive patients in whom clear images were obtained by two-dimensional echocardiography were studied. Using the Hewlett-Packard Sonos 2500 with a 3.5 or 5.5 Mhz phased array transducer, all patients were studied in the apical four-chamber imaging plane for automatic border detection and apical four-chamber and two-chamber imaging planes for manual tracing. Left ventricular end-diastolic and end-systolic volumes were measured and compared using the bi-plane Simpson method. RESULTS: Left ventricular end-diastolic volumes obtained by automatic border detection correlated well but were slightly underestimated compared to those obtained by manual tracing (r = 0.98). Left ventricular end-systolic volumes obtained by automatic border detection also correlated well with those obtained by manual tracing (r = 0.96). Left ventricular ejection fractions compared favorably. However, left ventricular volumes obtained using the classical Pombo M-mode echocardiography showed poorer correlation with those obtained by manual tracing methods. CONCLUSIONS: Automatic border detection is a promising method for real-time estimation of left ventricular volume. In patients with good endocardial tracking, automatic border detection can be used for routine studies of cardiovascular disease, even in children.

Adolescent↗
PubMed1998

Pulmonary function and regional distribution of emphysema as determined by high-resolution computed tomography.

In patients with pulmonary emphysema, emphysematous changes are not uniform and vary from minimum alveolar destruction to advanced bullous formation, depending on the lobe or site in the lungs. However, we have little knowledge on whether or how this nonuniformity or localization affects pulmonary function in PE patients. Therefore, we measured the computed tomography (CT) density of divided sites in lungs with high-resolution CT images from 25 PE patients (FEV1.0%, mean +/- SD 36 +/- 9%, %DLCO 48 +/- 16%, all men, 68 +/- 4 years) and compared them to various parameters of pulmonary function. The mean CT density of whole lungs correlated with 12 pulmonary function parameters including FEV1.0 and diffusion capacity. When both lung fields were divided into peripheral, intermediate and central portions, the CT density of the central portion correlated with all pulmonary function parameters with which CT density of whole lungs correlated. In contrast, the CT density of the peripheral portion significantly correlated with only 7 parameters with smaller correlation coefficient values than those of the central portion. When divided into upper, middle and lower portions, the CT densities of upper, middle and lower portions correlated with 6, 8 and 10 of the 12 pulmonary function parameters which correlated with the density of whole lungs, respectively. The delta value of CT densities between the upper and lower portions or between the lateral and medial portions correlated with obstructive impairment (FEV1.0 and FEV1.0%). These findings suggest that (1) central rather than peripheral emphysematous changes affect pulmonary function, and (2) uniformity of emphysematous change correlates with the severity of airway obstruction in PE patients.

Adult↗
PubMed1998

Methacholine bronchial hyperresponsiveness in chronic sinusitis.

The coexistence of chronic sinusitis (CS) may deteriorate the clinical condition of lower airway diseases such as bronchial asthma (BA) or chronic bronchitis (CB). However, the bronchial hyperresponsiveness (BH) in CS without any apparent lower airway disease is not fully understood nor are the effects of treatment. We examined lower airway hyperresponsiveness to methacholine (MCh) in 42 subjects with CS but without allergic rhinitis (AR) who had normal lung functions without any pulmonary symptoms, comparing it with that of 50 subjects with stable BA, 50 subjects with simple CB and 40 subjects with AR, and further examined the effect of endoscopic sinus surgery in 7 CS subjects with BH. The BH to MCh was measured in terms of the minimum dose (Dmin), defined as the cumulative dose at the point where respiratory conductance began to decrease. A Dmin <50 units was defined as BH. Seventy-one percent of CS subjects showed BH without relation to the severity or duration of CS, or atopic status. BH in CS subjects, which was less than that in BA subjects, was similar to that in simple CB or AR in both its prevalence and degree. After the surgical treatment of CS, BH significantly decreased (p < 0.01) with improvements in both nasal symptoms and sinus lesions. These findings suggest that CS itself induces BH to a degree similar to simple CB and AR without any relationship to the clinical background, and that adequate treatment of CS reduces BH.

Adolescent↗
PubMed1998

Surfactant protein A2 gene expression by human airway submucosal gland cells.

To determine whether human airway submucosal glands produce and secrete surfactant proteins, we examined their protein and gene expression in submucosal glands from trachea and bronchi obtained from operated and autopsied lungs within 4 h of death. Using a monoclonal antibody (PE-10) against surfactant protein A (SP-A), a positive immunoperoxidase stain was observed over serous cells of submucosal glands in histologic sections of airway walls. Measurement of SP-A in culture medium samples using single-step enzyme-linked immunosorbent assay showed a significant secretion of SP-A by isolated submucosal glands (1.2 +/- 0.08 ng/ml/h, SEM, n = 40). In gene expression experiments by reverse transciption-polymerase chain reaction, the SP-A complementary DNA (cDNA) segment was amplified from isolated submucosal glands, indicating the presence of SP-A messenger RNA (mRNA) in airway submucosal glands. Bronchial superficial epithelial cells failed to show the presence of SP-A mRNA. No cDNA segment of SP-B, SP-C, or SP-D cDNA was amplified from isolated submucosal glands or superficial epithelial cells, whereas all were amplified from alveolar tissue. Furthermore, in contrast to the control alveolar tissue, which expressed both SP-A1 and SP-A2 genes, SP-A2 gene transcript alone was detected in isolated submucosal glands by Southern analysis that included the digestion of the amplified SP-A cDNA fragment with the restriction enzyme Apa I. These findings indicate that human airway submucosal gland cells can transcribe the SP-A2 gene and produce SP-A protein in a manner different from peripheral airways and alveoli, playing a role in the airway defense mechanism.

Adult↗
PubMed1998

Effects of histamine and endothelin-1 on membrane potentials and ion currents in bovine tracheal smooth-muscle cells.

We tested the effects of tetraethylammonium (TEA), acetylcholine (ACh), histamine, and endothelin-1 on single airway smooth-muscle cells from bovine trachea, using the patch-clamp technique. Resting membrane potential was -48 +/- 1 mV (n = 47). Both TEA and ACh significantly depolarized the membrane, by +28 +/- 4 mV (P < 0.001, n = 12) and +21 +/- 2 mV (P < 0.01, n = 7), respectively, in the whole-cell configuration. In contrast, both histamine and endothelin-1 hyperpolarized the membrane, by -21 +/- 6 mV (P < 0.01, n = 8) and -15 +/- 2 mV (P < 0.01, n = 8), respectively. Calcium-dependent large-conductance K+-channels (127 pS) and small-conductance K+ channels (21 pS) were identified in excised patches. The small-conductance K+ channel was inhibited by 4-aminopyridine and activated by both histamine and endothelin-1. Furthermore, TEA did not alter the membrane hyperpolarization by these agonists, suggesting that the small-conductance K+ channel or delayed-rectifier K+ channel was involved in the membrane hyperpolarization. Membrane hyperpolarization by histamine and endothelin-1 suggests that activation of voltage-dependent calcium channels (VDCCs) or of calcium influx does not contribute substantially to the contractile response of airway smooth-muscle contraction to these agonists.

Acetylcholine↗
PubMed1998

Anomer-selective glucosylation of l-menthol by yeast alpha-glucosidase.

l-Menthol was glucosylated by the alpha-glucosidase (EC 3.2.1.20) of Saccharomyces cerevisiae using maltose as the glucosyl donor. When 50 mg of l-menthol and 1.6 M maltose in 10 mM citrate-phosphate buffer (pH 5.5) were incubated at 45 degrees C, l-menthyl alpha-D-glucopyranoside (alpha-MenG) was alpha-anomer-selectively formed as a product. The specificity of the alpha-linkage was confirmed by 13C-NMR analysis. In the reaction mixture after 2 h, alpha-MenG was mainly accumulated in a crystalline form and the concentration of dissolved alpha-MenG was constant at 1.4 mM. The molar conversion yield of alpha-MenG produced based on the supplied l-menthol was maximally 30.7% at 48 h of reaction.

Catalysis↗
PubMed1998

Suppression of gene expression and production of interleukin 13 by dexamethasone in human peripheral blood mononuclear cells.

We examined the effect of dexamethasone on the gene expression and production of interleukin (IL)-13 by human peripheral blood mononuclear cells from healthy controls. The gene expression was assessed semiquantitatively by sequential transcription polymerase chain reaction and Southern blot analysis, and the production of this cytokine was assessed by enzyme-linked immunosorbent assay (ELISA). Dexamethasone suppressed IL-13 gene expression induced by stimulation with phytohemagglutinin and phorbol 12-myristate 13-acetate in a dose-dependent manner, with 96% suppression at 10(-6) M, and also suppressed the increased production of IL-13. This is suggested to be one of the mechanisms by which glucocorticoids suppress allergic inflammation.

Anti-Inflammatory Agents↗
PubMed1997

Role of cyclic ADP-ribose in ATP-activated potassium currents in alveolar macrophages.

There is growing evidence that extracellular ATP causes a dramatic change in the membrane conductance of a variety of inflammatory cells. In the present study, using the nystatin perforated patch recording configuration, we found that ATP (0.3-30 microM) induced a transient outward current in a concentration-dependent manner and that the reversal potential of the ATP-induced outward current was close to the K+ equilibrium potential, indicating that the membrane behaves like a K+ electrode in the presence of ATP. The first application of ATP to alveolar macrophages perfused with Ca2+-free external solution could induce the outward current, but the response to ATP was diminished with successive applications. Intracellular perfusion with a Ca2+ chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N', N'-tetraacetic acid, also diminished the response. When cyclic ADP-ribose (cADPR) was applied to the macrophage cytoplasm, a transient outward current was elicited. Thereafter, the successive outward current was inhibited, suggesting the involvement of cADPR in the response. Intracellular perfusion with inositol 1,4, 5-trisphosphate also induced a transient outward current, but the successive current was not inhibited. The ATP-induced outward current was abolished when 8-amino-cADPR (as a blocker of cADPR, 10(-6)-10(-5) M) was introduced into the cytoplasm. Homogenates of alveolar macrophages showed both ADP-ribosyl cyclase and cADPR hydrolase activities, and CD38 (ADP-ribosyl cyclase/cADPR hydrolase) expression was confirmed by reverse transcriptase-polymerase chain reaction and Western blot analyses. These results indicate that ATP activates K+ currents by releasing Ca2+ from cADPR-sensitive internal Ca2+ stores.

Adenosine Diphosphate Ribose↗
PubMed1997

Signature current of SO2-induced bronchitis in rabbit.

To investigate abnormalities of airway epithelial ion transport underlying chronic inflammatory airway diseases, we performed electrophysiological, histological, and molecular biological experiments using rabbits exposed to SO2 as a model of bronchitis. By comparison with control, the SO2-exposed trachea exhibited decreased short circuit current (Isc) and conductance associated with increased potential difference. In normal trachea, apical ATP induced a transient Isc activation followed by a suppression, whereas the bronchitis model exhibited a prolonged activation without suppression. This pathological ATP response was abolished by diphenylamine 2-carboxylate or Cl--free bath solution. A significant increase in net Cl- flux toward the lumen was observed after ATP in our bronchitis model. Isoproterenol or adenosine evoked a sustained Isc increase in SO2-exposed, but not in normal, tracheas. The Northern blot analysis showed a strong expression of cystic fibrosis transmembrane conductance regulator (CFTR) mRNA in SO2-exposed epithelium. The immunohistochemical study revealed a positive label of CFTR on cells located luminally only in SO2-exposed rabbits. We concluded that the prolonged ATP response in our bronchitis model was of a superimposed normal and adenosine-activated current. The latter current was also activated by isoproterenol and appeared as a signature current for the bronchitis model airway. This was likely mediated by CFTR expressed in the course of chronic inflammation.

Adenosine↗