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Biomedical subjects

S Motojima

Publications and source records attributed to S Motojima.

At least 37 records · Page 2Linked to original sources

[Measurement of serum and sputum eosinophil cationic protein concentrations in asthma].

Concentrations of eosinophil cationic protein (ECP) were measured in serum from patients with asthma, patients with chronic obstructive pulmonary disease (COPD), and healthy subjects. The relationships between serum ECP concentration and percent of predicted FEV1 (%FEV1), and between serum and sputum ECP concentrations were also examined in patients with asthma. Serum ECP concentration in asthma was significantly higher than those in COPD patients and healthy subjects. There was a significant inverse correlation between serum ECP concentration and %FEV1 when analysis was restricted to data from asthma patients less than 60 years old. ECP concentration in serum and in sputum were significantly correlated. These results suggest that in asthma patients, eosinophils are activated in serum, and that the degree of eosinophil activation in the airway can be estimated by measuring serum ECP to some extent. Because it does not require bronchial biopsy or bronchoalveolar lavage, measurement of serum ECP may be useful as a minimally invasive monitoring of asthma.

Adult↗

Detection of interleukin-5 messenger RNA and interleukin-5 protein in bronchial biopsies from asthma by nonradioactive in situ hybridization and immunohistochemistry.

Recently direct evidence for the role of interleukin-5 (IL-5) in eosinophilic inflammation in the airways of persons with asthma has been provided by an in situ hybridization study that used radioisotope-labeled IL-5 complementary RNA probes. Radioisotope-labeled probes, although sensitive, require autoradiographic detection, which is time-consuming. In the most recent study we attempted to detect IL-5 messenger RNA in the bronchial biopsy specimens from patients with asthma using nonradioactive in situ hybridization, which gives rapid results. Bronchial biopsy specimens were obtained from eight patients with asthma and seven diseased control subjects. IL-5 complementary DNA probes were labeled with digoxigenin-deoxyuridine triphosphate and hybridized to permeabilized sections. Hybridization signals were visualized by an immunohistochemistry technique. Positive hybridization signals were observed in six of the eight biopsy specimens from patients with asthma. Pretreatment with ribonuclease or hybridization with an unrelated probe produced negative results. Immunohistochemical staining of serial sections with a monoclonal antibody to IL-5 revealed that a few cells within the mucosa positively stained, suggesting active synthesis of IL-5. Biopsy results from the seven diseased control subjects did not show any hybridization signal. These results confirm and extend previous observations of IL-5 messenger RNA expression in the airways of patients with asthma, and suggest that digoxigenin-labeled IL-5 complementary DNA probes would be a powerful research tool.

Adult↗

[Role of eosinophils and lymphocytes in the pathogenesis of bronchial asthma].

Lymphocytes and eosinophils are the two major inflammatory cells in the airways of patients with asthma. We studied the phenotypic composition and activation status of eosinophils and lymphocytes in bronchial biopsies obtained from asymptomatic and symptomatic asthmatics and nonasthmatic controls. The number of EG2-positive cells (activated eosinophils), CD3- and CD4-positive cells, and CD25-positive cells (activated lymphocytes) were significantly increased in the symptomatic asthmatics. In addition, significant correlations were noted between the density of CD4- and CD25-positive cells and the degree of eosinophil infiltration and activation. These data suggest that activated eosinophils and lymphocytes are involved in the pathogenesis of asthma and that activated helper T-lymphocytes play a central role in eosinophil infiltration and activation in the airways of asthmatics. Recently, eosinophil infiltration has been though to induce airway hyperresponsiveness by damaging airway epithelium through eosinophil granule proteins. To test this hypothesis, we investigated whether the number of clusters of desquamated respiratory epithelial cells in sputum is related to the eosinophil granule proteins in sputum and whether the ultrastructural changes in the bronchial epithelium are related to the presence of eosinophils in the bronchial mucosa. The results of both studies supported the hypothesis.

Asthma↗

[Multicenter study of the effects of sulbactam/cefoperazone on bacterial infections in the fields of internal medicine focused mainly on respiratory infections in Tochigi Prefecture].

Clinical effects of sulbactam/cefoperazone (SBT/CPZ) was studied on variety of bacterial infections in the fields of internal medicine focused mainly on respiratory infections. The total 135 infections were consisted of 103 respiratory infections, 15 urinary tract infections, 4 sepsis, 7 biliary tract infections, and 6 other infections, of which 86 patients had underlying diseases. The daily doses of SBT/CPZ were 2 to 6 g divided into 2 to 3 times i.v. or d.i.v., and the duration of administration was from 3 to 35 days. The clinical effects were judged by the attending doctors based on the changes in fever, cough, rales, chest rentogenograms, white blood cell counts, CRP values, ESR, etc. The total efficacy rate was 76.9%, and 69.0% of the isolated organism was eradicated by SBT/CPZ. The side effect was noted in 1 case, and the abnormal laboratory findings were noted in 1 case, however it was difficult to determine whether they were due to SBT/CPZ. These results suggest that the clinical usefulness of SBT/CPZ for the infections in the fields of internal medicine.

Adult↗

High serum soluble interleukin-2 receptor concentrations in elderly individuals and smokers.

The effects of sex, age, and smoking on the serum concentrations of soluble interleukin-2 receptor (sIL-2R) were investigated in 83 healthy subjects. No sex-related difference was found. The correlation between age and the serum sIL-2R concentration was weak, but significant, in the nonsmokers (r = 0.30, n = 50, p < 0.05). The serum sIL-2R concentration was significantly higher in smokers than in nonsmokers (41.0 +/- 2.8 pM (mean +/- SEM), n = 33, vs. 31.9 +/- 1.0, n = 50, p < 0.005). These results suggest that age and smoking habits should be taken into consideration when interpreting the serum sIL-2R concentration, although the mechanism by which sIL-2R concentrations are altered remains unknown at present.

Adult↗

Soluble interleukin-2 receptor in sputum from patients with bronchial asthma.

To evaluate the activation of T-lymphocytes in the airways of patients with asthma, we attempted to measure the concentration of soluble interleukin-2 receptor (sIL-2R) in sputum extracts from asthma patients with acute attacks or in remission. The large amount of alkaline phosphatase in the sputum extracts excluded the use of an ELISA kit. Measurement was attempted by radiolabeling the second antibody in the ELISA kit. sIL-2R was detectable in 10/23 (43%) of the sputum extracts from patients with acute asthma attacks, but not in those from patients in remission (n = 12, p < 0.02). These observations suggest that T-lymphocyte activation takes place in the airways of patients with acute asthma attacks.

Acute Disease↗

Effect of eosinophil peroxidase on beta-adrenergic receptor density on guinea pig lung membrane.

We studied whether eosinophil peroxidase (EPO), an eosinophil granule basic protein, can alter beta-adrenergic receptor (BAR) density on the guinea pig lung membrane. Lung membrane was first preincubated with 1-10 U/ml EPO and then incubated with 10(-4) M NaI and 10(-4) or 10(-6) M H2O2 for 2 hours. BAR density was determined using (-)125I-cyanopindolol. EPO combined with 10(-4) M H2O2 and I decreased the BAR density in a concentration-dependent manner. When only 10(-4) M H2O2 was used, the decrease in BAR density was small but significant. When compared to I, bromide was less effective and chloride alone was not effective. These results suggest that EPO is one of the factors responsible for beta-adrenergic blockade in asthma.

Animals↗

Airway hyperresponsiveness, increased intracellular spaces of bronchial epithelium, and increased infiltration of eosinophils and lymphocytes in bronchial mucosa in asthma.

Inflammation of the airway wall and airway hyperresponsiveness are consistent features of chronic asthma. We investigated how damage of the bronchial epithelium is related to airway hyperresponsiveness and how bronchial infiltration of eosinophils and lymphocytes is related to bronchial epithelial damage. We examined the biopsy specimens of bronchial mucosa taken from 19 patients with chronic asthma by electron microscopy. We also measured the incidence of opening of epithelial tight junctions, the widening of intercellular spaces in the epithelium, and the density of infiltrated eosinophils and lymphocytes in bronchial mucosa. Airway responsiveness was accessed by measuring PC20-acetylcholine (PC20-ACh). The inflammatory cells in the airway mucosa were counted by electron microscopy. Lymphocytes were most abundant, being 54.5% of the cells counted; eosinophils were 22.1%, neutrophils were 4.9%, and mast cells were 4.6%. A significant correlation was noted between the density of eosinophils and that of lymphocytes infiltrated in the airway mucosa (r = 0.80, p less than 0.01), suggesting that T cells may potentiate eosinophil infiltration. With increased density of eosinophils infiltrated in bronchial mucosa, both the incidence of opening of tight junctions of epithelial ciliary cells and the degree of widening of intercellular spaces in epithelium increased significantly (r = 0.51, p less than 0.05; r = 0.52, p less than 0.05), suggesting that eosinophils are related to damage of the bronchial epithelium. No correlation was observed between the density of lymphocyte infiltration and the degree of epithelial damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

[Effect of eosinophil peroxidase on beta-adrenergic receptor-adenylate cyclase system].

We studied the effect of eosinophil peroxidase (EPO) on beta-adrenergic receptor (BAR)-adenylate cyclase system based on the hypothesis that eosinophils may participate in the pathogenesis of beta-blockade in acute asthma. The effect of EPO on BAR density on guinea pig lung membrane was studied first. The BAR density was decreased significantly by 10(-4) M H2O2 alone. EPO combined with 10(-4) M H2O2 and iodide caused additional decrease in BAR density, and the decrease was EPO concentration-dependent (1-10 U/ml). The effect of EPO on cyclic AMP (CAMP) accumulation in S49 cells was studied next. The CAMP accumulation with 10(-4) M isoproterenol was significantly inhibited with combination of EPO and H2O2, and the decrease was again EPO concentration-dependent (0.1-1 U/ml) without any changes in BAR density on the cells. Thus, EPO was demonstrated to have an influence on the BAR-adenylate cyclase system.

Adenylyl Cyclases↗

[The role of bronchial responsiveness to leukotrienes in antigen-induced immediate and late asthmatic response].

In order to clarify the role of leukotriene in the antigen-induced asthmatic response, we carried out mite-antigen, leukotriene D4 (LTD4) and histamine inhalation tests in 21 mite-sensitive atopic asthma patients, and investigated the relationship between the bronchial responsiveness to mite (PD20-Mite) and that to LTD4 and histamine (PD20-LTD4, PD20-Hist). We then compared PD20-LTD4 and PD20-Hist between the groups with and without late asthmatic response (LAR), and investigated the relationship between the peak percentage fall of FEV1.0 in LAR (magnitude of LAR) and PD20-LTD4 and PD20-Hist. There were significant correlations between PD20-LTD4 and PD20-Mite (r = 0.590, p < 0.01), and between PD20-Hist and PD20-Mite (r = 0.669, p < 0.001). The bronchial responsiveness to LTD4 and histamine was significantly higher in the group with LAR. In addition, PD20-LTD4 showed a significant negative correlation with the magnitude of LAR (r = 0.724, p < 0.001). Furthermore we analyzed the relationship between PD20-LTD and the ratio of the magnitude of LAR to that of IAR (immediate asthmatic response), because there was a significant correlation between the magnitude of IAR and that of LAR (r = 0.842, p < 0.001) in 16 asthmatic patients with dual asthmatic response, and found that the correlation coefficient was also very high (r = -0.836, p < 0.001). These results suggest an important role of leukotriene in the antigen-induced asthmatic response.

Adolescent↗

Inhibition of antigen-induced late asthmatic response and bronchial hyperresponsiveness by cyclosporin and FK 506.

Using a guinea pig model of asthma, we have shown that the administration of cyclosporin, a T-lymphocyte-selective immunosuppressive agent, from the beginning of the immunization period inhibits the development of the late asthmatic response and bronchial hyperresponsiveness after antigen challenge. Similar results were obtained with FK 506, a new potent immunosuppressive agent. Since these compounds have been shown to suppress the activation of guinea pig T lymphocytes, the present data suggest that T lymphocytes may be important for the elicitation of the late asthmatic response and bronchial hyperresponsiveness.

Animals↗

[Eosinophil activation in acute asthma attacks evaluated by electronmicroscopic findings of eosinophils and the concentration of eosinophil cationic protein in sputum].

We evaluated the activation of eosinophils in the airways of patients with acute asthma attacks by measuring the concentration of sputum eosinophil cationic protein (ECP) and changes in the electron densities of the eosinophil specific granules in sputum. In six hospitalized patients with asthmatic attacks, sputum samples were collected for seven consecutive days after admission and were used for the evaluation of eosinophil activation. The concentration of sputum ECP, the incidence of changes in the electron densities of eosinophil specific granules and the severity of asthma attacks were highest on the day of admission and decreased in association with each other after treatment. A significant correlation was found between the concentration of sputum ECP and the incidence of changes in the electron densities of eosinophil specific granules. These findings suggest that the eosinophils in the airways are markedly activated and degranulated in asthma attacks.

Adult↗

[Clinical and physiological features of chronic pulmonary emphysema with paroxysmal dyspnea attacks masquerading as bronchial asthma--improvement of respiratory function after combination therapy of intravenous aminophylline and subcutaneous epinephrine following daily oral administration of prednisolone].

Cases of chronic pulmonary emphysema accompanied with paroxysmal dyspnea attacks are often misdiagnosed as bronchial asthma. These patients repeatedly fall into a state of life-threatening respiratory failure. We must make an accurate diagnosis of emphysema to provide care of them. To clarify the possibility of doing this, we investigated the clinical and physiological features (primarily respiratory function) of emphysema. We observed twenty-five patients with chronic pulmonary emphysema and with chronic bronchial asthma, previously confirmed by selective alveolo-bronchogram (SAB); this technique reliably diagnoses emphysema, but often induces dyspnea attacks due to the stimulation resulting from intratracheal and intrabronchial procedures. In eight patients, chronic pulmonary emphysema was accompanied by an attack of paroxysmal wheezing and dyspnea; chronic pulmonary emphysema with wheezing (WPE). In eight other patients, chronic pulmonary emphysema was present without such attacks; usual pulmonary emphysema (UPE). In the final nine patients, chronic bronchial asthma (CBA) was present, while emphysema was ruled out by means of SAB. In all patients, we measured respiratory function before and after the combination therapy of intravenous aminophylline and subcutaneous epinephrine, which followed daily oral administration of prednisolone (PAE-treatment). In the WPE group, significant increases in measurement of various respiratory functions, including VC, RV, RV/TLC%, FVC, FEV1.0, PFR and V75 (p less than .05 excluded in FEV1.0 and PFR were p less than .01), were found after the PAE-treatment, compared with the values revealed before the treatment. In the UPE group, there were few changes PAE-treatment, compared with the values revealed before the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

The eosinophilic injury to the mucosa of the airways in the pathogenesis of bronchial asthma.

Eosinophilic bronchitis and desquamation of the bronchial mucosa are the salient features of the pathology of both allergic (extrinsic) and nonallergic (intrinsic) asthma. Because of this association, the possibility of the eosinophil being the cause of the injury to the bronchial mucosa has been investigated during the last decade. In vitro, eosinophil granule major basic protein (MBP) concentrations as low as 10 micrograms.ml-1 cause desquamation and destruction of the epithelium of the airways which mimic the morphology of damage to the mucosa of the bronchi in asthma. Concentrations of MBP in the cytotoxic range for the bronchial mucosa in vitro have been measured in sputum of asthmatics (up to 92 micrograms.ml-1) and decline with treatment. Deposits of MBP have been detected by immunofluorescence within ulcerated areas of bronchial mucosa and necrotic portions of the bronchial wall in patients who had died of asthma. Most recently, the eosinophil peroxidase (EPO) and the eosinophil cationic protein (ECP) have also been found to be toxic for the epithelium of the airways in vitro, thus increasing the cytotoxic capability of the eosinophil against the bronchial mucosa in asthma. These latest research data continue to support the "eosinophil hypothesis" in the pathogenesis of this disease. According to this hypothesis, in the formidably complex network of cells and mediators responsible for the bronchial obstruction, the destruction of the mucociliary apparatus and the characteristic hyperresponsiveness of the airways in asthma; the eosinophil is the principal effector cell. In bronchial asthma a T cell modulated eosinophilic bronchitis is the primary abnormality while bronchospasm and hyperreactivity of the airways are secondary phenomena.

Animals↗