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Biomedical subjects

S Motojima

Publications and source records attributed to S Motojima.

At least 55 records · Page 3Linked to original sources
PubMed1991

[Fundamental studies on measurement of the eosinophil cationic protein in sputum from patients with bronchial asthma].

One of the characteristics of patients with bronchial asthma is activation of eosinophils in the bronchi, which can be evaluated by measuring concentrations of the cationic granule proteins. Sputum seems to be the best material to evaluate the activation of eosinophils in the bronchi because it can be collected easily from the same patient every day even if he (she) has an asthmatic attack. Recently it has become possible to measure the concentration of the eosinophil cationic protein (ECP) thanks to the availability of the ECP RIA kit. However no fundamental studies have been carried out on the handling of sputum samples, and whether only ECP released into sputum is measured. We prepared supernatants of sputum samples according to the method of Gleich and others by adding the same volume of physiological saline, mixing it for one minute by a vortex mixer and centrifuging at 40000 Xg, 4 C, for 30 minutes. We found that the measurement of ECP is not inhibited by materials in sputum supernatants through a dilution test and a recovery test. We also found that the followings did not influence the measurement of ECP; the times of dilution, the duration from collection to handing of sputum, the solution added to sputum, and the gravity of centrifugation. In addition, it was suggested that only ECP released into sputum is measurable from the results of an electron microscopic study and the measurement of ECP after centrifugation following the addition of white blood cells to sputum.

Asthma↗
PubMed1990

[Creola bodies and the eosinophil cationic protein in sputum in acute asthmatic attacks with respect to their clinical significance].

Creola bodies (CrB) are characteristically present in sputa from patients with asthma. We studied the relationship among the numbers of CrB, the course of asthmatic attacks and the concentration of sputum eosinophil cationic protein (ECP). Twenty-two asthmatic attacks in 17 patients were studied. Sputum collections pulmonary function tests were made before or during treatment in patients who came to the outpatient clinic or emergency room. Smears of 100 microliters of sputum were made on glass slides and CrB were studied over the whole area of glass slide stained with Papanicolaou's stain. CrB scores were determined from the number and the size of CrB on each slide. In hospitalized patients the CrB scores, the concentrations of sputum ECP and the severity scores of asthmatic attacks were highest on the day of admission, decreasing in association with each other and returning to the baseline level in approximately 5 days. There were significant correlations among the CrB score, the concentration of sputum ECP and %FEV1.0 (p less than 0.001). The CrB score on the day of clinical appraisal significantly correlated with the number 6f days of treatment needed for remission. These results are in keeping with the hypothesis that eosinophils cause desquamation of respiratory epithelial cells resulting in prolongation of asthmatic attacks. Observation of CrB seemed to be useful as a marker of duration of asthmatic attacks.

Acute Disease↗
PubMed1990

[The participation of epithelial desquamation in the increase of bronchial hyperresponsiveness after antigen challenge in patients with bronchial asthma].

Bronchial hyperresponsiveness (BHR) was evaluated before and after antigen challenge in 12 patients with bronchial asthma as allergic reaction to house dust mites. Six out of the 12 showed an increase in BHR 48 hours after antigen challenge. Although there was no difference in the decrease of FEV1.0 in IAR and LAR between patients with (group A) and without (group B) the increase of BHR after antigen challenge, patients in group A expectorated a significantly larger number of clumps of respiratory epithelial cells (Creola bodies, CrB) in their sputum in both IAR and LAR. In addition, the degree of the increase of BHR significantly correlated with the CrB score, which was determined from the number and the size of CrB. These results suggest that epithelial desquamation participates in the increase of BHR after antigen challenge. The concentration of the eosinophil cationic protein (ECP) in their sputum did not change significantly in IAR and LAR compared with that before antigen challenge. There was no difference in the concentration of ECP in their sputum between the two groups either. One antigen challenge seemed to be too mild to induce an elevation of the concentration of ECP in their sputum. Judging from the fact that CrB could be observed not only at LAR but also IAR, epithelial desquamation seemed to be dependent on the degree of damage before antigen challenge rather than on the activation of eosinophils after antigen challenge.

Adult↗
PubMed1990

[Antigen-induced biphasic eosinophil infiltration in the airways of actively sensitized guinea pigs and its inhibition by PAF antagonist and cyclosporin A].

Bronchial eosinophilia is a characteristic of asthma. To elucidate the mechanisms of eosinophil accumulation in the airways, the time course of eosinophil infiltration in the airway mucosa after antigen inhalation was examined in actively sensitized and passively sensitized guinea pig models of asthma. The lungs and tracheae were removed at intervals after antigen challenge, fixed and stained. The eosinophil infiltration was quantitated in the tracheal walls by counting the number of cells per square millimeter. Guinea pigs sensitized by intraperitoneal injection of ovalbumin (OA) responded to a single exposure to aerosolized OA with biphasic infiltration of eosinophils in the tracheal walls; a striking early-phase which peaked at 6 hr and a delayed-phase which peaked at 24 hr and persisted for as long as 5 days. These kinetics were different from those observed with passively sensitized animals which showed only early-phase infiltration. Administration of CV-6209, a specific PAF antagonist, before and 12 hrs after antigen challenge significantly (p less than 0.01) inhibited the early-phase but not the delayed-phase eosinophil infiltration in actively sensitized animals. In contrast, when guinea pigs were treated with Cyclosporin A, a T lymphocyte-selective immunosuppressive agent, throughout the immunization period, the delayed-phase but not the early-phase infiltration was significantly (p less than 0.01) inhibited. These results suggest that PAF may contribute to early-phase and T cell factor(s) may contribute to delayed-phase eosinophil infiltration of the airways.

Animals↗
PubMed1990

[The role of eosinophils, neutrophils and lymphocytes for the development of bronchial hyperresponsiveness in a guinea pig model of asthma].

To elucidate the role of eosinophils, neutrophils and lymphocytes for the development of bronchial hyperresponsiveness (BHR) following antigen exposure, we have developed a guinea pig model of BHR. Guinea pigs immunized by repeated exposure to aerosolized ovalbumin (OA) were intravenously given metopirone, a cortisol synthesis inhibitor, 24 hrs before and 30 min before antigen challenge, and to prevent death from immediate severe bronchoconstriction, chlorpheniramine maleate was also injected. After antigen challenge with high dose of OA, LAR occurred in twelve of fifteen animals (80%) and the bronchial responsiveness to acetylcholine (Ach) was significantly increased. Histologic examination at 72 h showed a significant increase in the number of eosinophils but not neutrophils within the tracheal walls. However, there was no significant correlation between the change in bronchial responsiveness to Ach at 24 h and the number of eosinophil in the tracheal wall at 72 h. When guinea pigs were treated with Cyclosporin A or FK506, T-lymphocyte selective immunosuppressive agents, from the beginning of immunization period, both eosinophil infiltration and an increase in bronchial responsiveness were inhibited. These results suggest that eosinophils and T-lymphocytes may play an important role in the development of bronchial hyperresponsiveness.

Acetylcholine↗
PubMed1990

[Relationship between bronchial reactivity to inhaled acetylcholine, eosinophil infiltration and a widening of the intercellular space in patients with asthma].

The hypothesis that epithelial damage is related to the development of bronchial hyperreactivity has been supported by many studies. Therefore, we further examined whether or not subjects with bronchial epithelium damage showed increased bronchial responsiveness. We took biopsy specimens of the airway mucosa from 20 asthmatic patients with various degrees of disease severity and bronchial hyperreactivity by using a bronchofiber scope. The morphology of the biopsy specimens was studied by electron microscopy. Bronchoscopy was carried out after local anesthesia. Specimens of bronchial mucosa were obtained from 20 asthmatic patients (14 males, 6 females) in remission. The electronmicroscopic studies showed widening of the intercellular space between the epithelial cells and openings of the tight junctions, as well as infiltrations of eosinophils and their granules beneath and between epithelial cells. The tight junction refers to the space between epithelial cells exposed to the airway surface, leading down to the intercellular space. The intercellular space refers to the space between epithelial cells, below the tight junction. Interestingly, eosinophils and their granules were found mainly in the widened intercellular space. The incidence of a widening of the intercellular space was higher in specimens showing eosinophil infiltration than in those not showing eosinophil infiltration. A significant correlation was found between the respiratory threshold to acetylcholine and the percentage of opened tight junctions (r = -0.47, p less than 0.05) and/or the widening of the space between epithelial cells (r = -0.65, p less than 0.01). These results suggest that widening of the intercellular space may be caused by infiltrations of eosinophils and that this widening increases bronchial reactivity.

Acetylcholine↗
PubMed1990

[Relationship between presence of Creola bodies and airway hyperresponsiveness in patients with bronchial asthma].

It has recently been suggested that epithelial damage participates in the development of bronchial hyperresponsiveness. In this study we investigated the relationship between the presence of clusters of desquamated respiratory epithelial cells (Creola body. CrB) in sputum and airway responsiveness. Sputa were collected from asthmatic patients and acetylcholine inhalation tests were performed to assess airway responsiveness. Smears of 100 microliters of sputum were spread in pairs of two glass slides. One slide was stained with Papanicolaou's stain, the other with Giemsa stain. CrBs were detected on the whole glass slide stained with Papanicolaou's stain and the CrB score was determined by summing up the points given to each CrB on a glass slide according to the number of epithelial cells composing one CrB. The CrB score was significantly higher in patients with CrBs than in patients without CrBs. The patients with higher CrB score (CrB score greater than or equal to 6) had significantly greater number of eosinophils in sputa than the patients without CrBs. These results suggest the participation of damage to the respiratory epithelium in the development of airway hyperresponsiveness in bronchial asthma. The detection of CrBs is easy and we consider it clinically useful in the estimation of airway hyperresponsiveness.

Acetylcholine↗
PubMed1989

Changes in airway responsiveness and beta- and alpha-1-adrenergic receptors in the lungs of guinea pigs with experimental asthma.

The effects of inhaled allergen on airway responsiveness and on beta- and alpha-1-adrenergic receptors on lung membrane were investigated in guinea pigs. After measuring the respiratory threshold to histamine (RT-HIS), one group of guinea pigs passively sensitized for ovalbumin was challenged by allergen inhalation (challenged group). Measurement of the RT-HIS 24 h following challenge revealed a significant decrease from 687 micrograms/ml (mean, n = 16) to 407 micrograms/ml (P less than 0.05). In addition the RT-HIS 24 h after challenge was also significantly lower in the challenged group than in controls (n = 9, P less than 0.05). The density of beta-adrenergic receptors on the lung membrane of the challenged group was 594 +/- 32 (mean +/- SE) fmol/mg protein (n = 11) compared with 712 +/- 24 fmol/mg protein (n = 9) in the controls, a statistically significant difference (P less than 0.05). A significant correlation was found between the RT-HIS and density of beta-adrenergic receptors. From these results, we concluded that the exaggerated airway responsiveness 24 h after allergen challenge is in part due to a decrease in the density of beta-adrenergic receptors. There was no difference in the density of alpha-1-adrenergic receptors nor a significant correlation between the RT-HIS and the number of alpha-1-adrenergic receptors in the challenged vs. the control groups.

Anaphylaxis↗
PubMed1989

Toxicity of eosinophil cationic proteins for guinea pig tracheal epithelium in vitro.

We tested the effects of four eosinophil granule cationic proteins: major basic protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and eosinophil-derived neurotoxin (EDN), on guinea pig tracheal epithelium in vitro. Examination by inverted microscopy revealed that MBP, both the form stabilized by alkylation of sulfhydryl groups as well as the native form of the molecule, ECP, EPO by itself, as well as EPO + H2O2 + halide, but not EDN, cause dose-related damage to the tracheal epithelium. The lowest concentrations of MBP and ECP causing damage were 10 and 100 micrograms/ml, respectively. In contrast, EDN, although biochemically similar to ECP, did not damage the tracheal epithelium in concentrations of up to 200 micrograms/ml. MBP caused exfoliation, as well as bleb formation and ciliostasis. EPO in the presence of the H2O2-producing enzyme glucose oxidase (GO), Cl-, 0.11 M, and iodide caused ciliostasis, bleb formation, and exfoliation of epithelial cells at concentrations as low as 1 U/ml (3.9 micrograms/ml). EPO + GO in the presence of Cl-, 0.11 M, alone or with Cl- and l-, 10(-4) M, or Cl- and Br-, 5 x 10(-5) M, were all toxic to epithelium. Surprisingly, EPO by itself caused partial ciliostasis, bleb formation, and exfoliation of epithelial cells in a dose-related manner at concentrations as low as 10 to 30 U/ml (39 to 121 micrograms/ml). These results confirm prior observations showing the toxicity of MBP to tracheal epithelium and indicate that ECP and EPO alone, as well as EPO + GO + halide, cause damage. Thus, several eosinophil granule proteins are able to damage respiratory epithelium.

Alkylation↗
PubMed1989

[Three cases of food-dependent exercise-induced anaphylaxis].

A variety of systemic reactions associated with exercise are recognized. This article describes three cases of anaphylaxis induced by exercise within 2 hours after the ingestion of causative foods. Their symptoms were urticaria, angioedema, bronchial asthma, fall in blood pressure and syncope. Cases #1 and #3 showed exercise-induced anaphylaxis after ingestion of wheat. However, case #1 reacted only to toasted wheat. In case #2 the most likely responsible food was also wheat, although we could not definitely confirm this. Two subjects exhibited an elevation in plasma histamine level when symptoms developed. In addition, we observed inhibition of these symptoms by pretreatment with anti-allergic drugs. These observations suggest that type I allergic reaction is involved in the development of these symptoms. However, why exercise combined with ingestion of food is needed for this type of anaphylaxis still remains unknown.

Adult↗
PubMed1989

[Effects of sulbactam/cefoperazone in patients with respiratory infections in aged and/or with underlying respiratory diseases].

Sulbactam/cefoperazone (SBT/CPZ), a new antibacterial drug, was administered to 14 cases with respiratory infections for a duration of 5 approximately 13 days at a daily dose of 4 g. Diagnoses of these patients were 7 respiratory tract infections, and 7 bronchopneumonias. The underlying diseases were chronic pulmonary emphysema in 6 cases, bronchial asthma in 2 cases, and one each of bronchiectasis, diffuse panbronchiolitis and lung cancer with bronchoesophageal fistula. All patients had underlying respiratory diseases and/or were more than 70 years old. The rate of clinical efficacy was 78.6%. The incidence of penicillinase production by isolated bacteria was 18.2% and that of cephalosporinase was 63.6%. SBT/CPZ was expected to be more effective than CPZ alone in 3 cases judging from the susceptibility of the bacterial strains concerned, to antibiotics. No side effects were observed. We conclude that SBT/CPZ is useful in the treatment of respiratory infections of patients of advanced age and/or with underlying respiratory diseases.

Aged↗
PubMed1988

Changes in bronchial response after Sendai virus infection in guinea pigs.

Enhanced bronchial reactivity to inhaled histamine was observed in guinea pigs infected with Sendai virus with concomitant decrease of beta-adrenergic receptor density in the pulmonary parenchyma 2 to 3 weeks after the inoculation. Histologic examination of the bronchi showed shedding of epithelial cells with a marked infiltration of mononuclear cells. These observations suggest that damage of the bronchial epithelium and decreased density of beta-adrenergic receptor may be the causes of observed bronchial reactivity.

Administration, Inhalation↗
PubMed1987

The eosinophilic leukocyte and the pathology of fatal bronchial asthma: evidence for pathologic heterogeneity.

Classically, bronchial asthma is associated with peripheral blood eosinophilia and striking eosinophilia of bronchial tissues and sputum. Evidence exists that eosinophil degranulation commonly occurs during bronchial asthma and eosinophil granule proteins are discharged onto damaged bronchial epithelium. Analyses of 10 patients with fatal asthma showed striking eosinophil participation in eight, whereas two patients showed marked epithelial desquamation in the virtual absence of eosinophils. These results point to the possibility that a pathologic heterogeneity exists in fatal bronchial asthma, with most, but not all, patients showing evidence of eosinophil participation.

Animals↗
PubMed1986

[Effects of cefoperazone on respiratory infections of patients of advanced age and/or with underlying respiratory diseases].

Respiratory infections of 19 subjects of advanced age and/or with underlying respiratory disease were treated with cefoperazone (CPZ) and its clinical effects were studied. Sixteen subjects suffered from respiratory tract infection and 3 subjects had pneumonia. The age of the subjects ranged from 39 to 77 years with the mean of 63.8, 7 of them being more than 70 years of age. The underlying respiratory diseases included chronic pulmonary emphysema in 6 subjects, diffuse panbronchiolitis in 3, bronchiectasis in 3, silicosis in 2 and one each of chronic bronchitis, pulmonary fibrosis, lung cancer and old pulmonary tuberculosis. One case, 75 years of age, had renal insufficiency. The daily dose of CPZ was 4 grams in 18 of the 19 subjects and the duration of administration ranged 5 to 22 days. The remaining 1 subject received 2 g of CPZ daily for 6 days. Clinical effects were judged from the changes in fever, cough, amount of sputum, dyspnea, rales, cyanosis, chest X-ray, white blood cell counts, CRP, erythrocyte sedimentation rates and results of sputum culture. Clinical effects were good in 16 subjects, fair in 1, and poor in 2. Bacteriological follow-up was carried out in 13 subjects. Infecting bacteria were eliminated from 5 subjects, reduced in 2 and, in 4 subjects, they were replaced by other bacteria. In 1 subject, P. aeruginosa was isolated from sputum even after the treatment with CPZ, and in another subject H. influenzae relapsed immediately after the cessation of the CPZ treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗