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Biomedical subjects

Masaki Fujimura

Publications and source records attributed to Masaki Fujimura.

At least 19 recordsLinked to original sources

Prostaglandin I2 enhances cough reflex sensitivity to capsaicin in the asthmatic airway.

Inflammatory mediators are involved in the pathogenesis of airway inflammation, but the role of prostaglandin I2 (PGI2) remains obscure. This study was designed to investigate the role of PGI2 in cough reflex sensitivity of the asthmatic airway, which is characterized by chronic eosinophilic airway inflammation. The effect of beraprost, a chemically and biologically stable analogue of PGI2, on cough response to inhaled capsaicin was examined in 21 patients with stable asthma in a randomized, placebo-controlled cross over study. Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough reflex sensitivity. The cough threshold was significantly (p < 0.05) decreased after two weeks of treatment with beraprost [17.8 (GSEM 1.20) microM] compared with placebo [30.3 (GSEM 1.21) microM]. PGI2 increases cough reflex sensitivity of the asthmatic airway, suggesting that inhibition of PGI2 may be a novel therapeutic option for patients with asthma, especially cough predominant asthma.

Journal Article↗

Eosinophilic inflammation, remodeling of lower airway, bronchial responsiveness and cough reflex sensitivity in non-asthmatic subjects with nasal allergy.

BACKGROUND: It has been reported that nasal allergy influences the lower airway inflammation and functions. We elucidated whether nasal allergy would contribute to lower airway inflammation and functions. METHODS: 266 subjects aged 21-39 years were interviewed with special emphasis on history of asthma and nasal allergies (perennial allergic rhinitis (PAR) and seasonal allergic rhinitis (Japanese cedar pollinosis; PO)). Symptomatic subject was defined when nasal symptoms were present during a 3-week study period. Pulmonary function, provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 s (PC20), capsaicin cough threshold defined as capsaicin concentration eliciting 5 or more coughs (C5) and eosinophil percentage in hypertonic saline-induced sputum were measured. RESULTS: Based on the interview, 232 subjects without asthma were divided into symptomatic (n = 25) and asymptomatic (n = 22) PAR, PO on-season (n = 15) and off-season (n = 36), and non-nasal allergy subjects (control) (n = 134). Sputum eosinophils were significantly greater in symptomatic PAR than another four groups (p < 0.01). FEV1/FVC ratio was significantly lower in PAR than control (p < 0.05). Maximum mean expiratory flow was lower in PAR than control (asymptomatic: p < 0.05, symptomatic: p = 0.06). C5 was not different among groups. PAR tended to have a lower PC20 compared to control (symptomatic: p = 0.078; asymptomatic: p = 0.086). CONCLUSIONS: These results suggest that eosinophilic inflammation occurred in symptomatic period of PAR may contribute to development of lower airway remodeling and bronchial hyperresponsiveness. Reversely, PO may not be associated with lower airway eosinophilic inflammation or abnormal bronchial functions. Nasal allergy dose not influence the cough reflex sensitivity.

Adult↗

Selective inhibitors for phosphodiesterase 3 and 4 in antigen-induced increase of cough reflex sensitivity in guinea pigs.

Effects of the selective phosphodiesterase 3 (PDE3) inhibitor olprinone and the selective PDE4 inhibitor SB207499 were investigated on antigen-induced increase of cough reflex sensitivity and normal cough response to capsaicin in guinea pigs. Number of coughs elicited by inhalation of capsaicin (10(-8), 10(-6) and 10(-4)M) was counted 24h after an antigen challenge in actively sensitized guinea pigs, and then bronchoalveolar lavage (BAL) was performed. Olprinone (1 or 10mg/kg) or SB207499 (1 or 10mg/kg) was given twice intraperitoneally: One hour after the antigen challenge and 1h before the capsaicin provocation. SB207499, but not olprinone, significantly reduced both antigen-induced increase of cough response to inhaled capsaicin in sensitized animals and normal cough response in non-sensitized animals. SB207499, but not olprinone, also reduced the antigen-induced BAL eosinophilia. PDE4 inhibitors may be useful in treating cough associated with airway allergy via inhibiting both allergic airway inflammation and the common pathway of cough reflex.

Allergens↗

Pulmonary sarcoidosis with usual interstitial pneumonia distributed predominantly in the lower lung fields.

Nodular and reticular opacities were detected in both lower lung fields of a 75-year-old man in 2000. Bronchoscopy revealed pulmonary sarcoidosis. In 2002, nodular and reticular opacities were shown in the right upper lobe, and video-assisted thoracoscopic surgery was performed. The histological findings revealed usual interstitial pneumonia (UIP)-like lesions, whereas non-caseous granulomas were not detected. In the present case of pulmonary sarcoidosis, nodular and reticular opacities were predominantly distributed in both lower lung fields, and the histological findings obtained by video-assisted thoracoscopic surgery showed UIP-like lesions. These findings may enlighten the assist in understanding of the process of development of pulmonary sarcoidosis.

Aged↗

Bronchial asthma showing reduction in FEV1 after inhalation of Qvar.

The administration of Qvar (a hydrofluoroalkane-134a beclomethasone dipropionate; HFA-BDP) is highly useful for the treatment of patients with asthma. However, we found in a case of bronchial asthma that replacing the prior inhaled corticosteroids with Qvar resulted in temporary dyspnea and reduction in forced expiratory volume in 1 second (FEV1). Qvar contains beclomethasone dipropionate combined with absolute ethanol and an alternative to fluorocarbon. The patient had complicated alcohol-induced asthma. FEV1 decreased markedly and immediately after Qvar inhalation. The Qvar placebo is free of beclomethasone but contains other ingredients (ethanol and fluorocarbon). FEV1 did not decrease after the Qvar placebo, Aldecin inhalation, and Qvar inhalation orally treated with atropine before inhalation of Qvar. It seems unlikely that the components of Qvar (except beclomethasone) are responsible for the reduction in FEV1 observed immediately after inhalation of Qvar. These findings would be noteworthy when using Qvar for Japanese patients with asthma known to have a relatively high frequency of the complication of alcohol-induced asthma.

Administration, Inhalation↗

A case of acute hypersensitivity pneumonitis associated with an oil fan heater.

We report here a case of acute hypersensitivity pneumonitis induced by an oil fan heater. A 57-year-old man was admitted to our hospital because of fever, nonproductive cough, and dyspnea. Paeccilomyces variotii and Paeccilomyces nivea were identified from an oil fan heater in his house. The result of an environmental challenge test was positive. Intradermal reaction and precipitin results to sugar antigen of those fungi were positive only in the patient. This is the first described case of acute hypersensitivity pneumonitis caused by an oil fan heater.

Alveolitis, Extrinsic Allergic↗

Evaluation of pulmonary function using breathing chest radiography with a dynamic flat panel detector: primary results in pulmonary diseases.

OBJECTIVES: Dynamic flat panel detectors (FPD) permit acquisition of distortion-free radiographs with a large field of view and high image quality. The present study was performed to evaluate pulmonary function using breathing chest radiography with a dynamic FPD. We report primary results of a clinical study and computer algorithm for quantifying and visualizing relative local pulmonary airflow. MATERIALS AND METHODS: Dynamic chest radiographs of 18 subjects (1 emphysema, 2 asthma, 4 interstitial pneumonia, 1 pulmonary nodule, and 10 normal controls) were obtained during respiration using an FPD system. We measured respiratory changes in distance from the lung apex to the diaphragm (DLD) and pixel values in each lung area. Subsequently, the interframe differences (D-frame) and difference values between maximum inspiratory and expiratory phases (D-max) were calculated. D-max in each lung represents relative vital capacity (VC) and regional D-frames represent pulmonary airflow in each local area. D-frames were superimposed on dynamic chest radiographs in the form of color display (fusion images). The results obtained using our methods were compared with findings on computed tomography (CT) images and pulmonary functional test (PFT), which were examined before inclusion in the study. RESULTS: In normal subjects, the D-frames were distributed symmetrically in both lungs throughout all respiratory phases. However, subjects with pulmonary diseases showed D-frame distribution patterns that differed from the normal pattern. In subjects with air trapping, there were some areas with D-frames near zero indicated as colorless areas on fusion images. These areas also corresponded to the areas showing air trapping on computed tomography images. In asthma, obstructive abnormality was indicated by areas continuously showing D-frame near zero in the upper lung. Patients with interstitial pneumonia commonly showed fusion images with an uneven color distribution accompanied by increased D-frames in the area identified as normal on computed tomography images. Furthermore, measurement of DLD was very effective for evaluating diaphragmatic kinetics. CONCLUSIONS: This is a rapid and simple method for evaluation of respiratory kinetics for pulmonary diseases, which can reveal abnormalities in diaphragmatic kinetics and regional lung ventilation. Furthermore, quantification and visualization of respiratory kinetics is useful as an aid in interpreting dynamic chest radiographs.

Adult↗

Asthma severity is associated with an increase in both blood CXCR3+ and CCR4+ T cells.

OBJECTIVES: A predominance of type 2 helper T cells (Th2) in the bronchoalveolar space and peripheral blood is a well-accepted feature of bronchial asthma. However, the relationship between peripheral blood Th2 cells and asthma severity has not been thoroughly investigated. METHODS: As Th1 cells predominantly express the chemokine receptor CXCR3 and Th2 cells express CCR4, we assessed the distribution of peripheral blood CXCR3+ and CCR4+ lymphocytes using flow cytometry in 186 patients with asthma and 75 normal subjects. RESULTS: The proportion of CXCR3+/CD45RO+ cells in CD4+ T cells increased as the severity of asthma increased. The percentage of CCR4+/CD45RO+ cells in CD4+ T cells were elevated in mild to severe asthma patients compared with controls. However, there was no significant difference in CCR4+/CD45RO+ cells between the mild to severe asthma patients. There was no relationship between the patient's age and the numbers of CXCR3+ or CCR4+ T cells. The percentage of CCR4+ cells in CD45RO+/CD4+ T cells correlated with the levels of total serum IgE (r = 0.630, P < 0.0001). CONCLUSIONS: The proportion of CCR4+ cells in blood memory helper T cells may be increased in patients with asthma and is associated with the level of serum IgE, but severity of asthma is also associated with the increase of blood CXCR3+ cells in memory helper T cells.

Adult↗

[A case of small-cell lung cancer responding remarkably to CPT-11 and CDDP combination chemotherapy].

A 73-year-old man was admitted to our hospital complaining of general malaise, loss of appetite and body weight loss. Chest X-ray film showed left-sided pleural effusion. Computed tomographic (CT) scan of the chest also demonstrated left-sided pleural effusion with lung tumor and lymphnode swelling. Repeated treatment with 60 mg/m(2) of cisplatin on day 1 followed by 80 mg/m(2) of irinotecan on days 1 and 8 were effective in this patient.

Aged↗

[Fungal culture from pharyngeal swab and seasonal influence in patients with chronic non-productive cough].

It has been suggested that Basidiomycetes is an important fungal aeroallergen. We have reported that Basidiomycetes may be important for allergic airway disorders such as atopic cough, cough variant asthma and bronchial asthma. In this study, 141 patients with chronic nonproductive cough underwent pharyngeal swab culture for fungi, and 18.4% of all patients were positive for Candida (10.6%) and Basidiomycetes (6.4%). Positive results for Basidiomycetes culture were relatively frequent in August and September. It is suggested that Basidiomycetes is important as a fungus colonizing in the pharynx, and that of causative and/or exacerbating for allergic airway disorders presenting with chronic non-productive cough.

Adult↗

[Longitudinal decline of forced expiratory volume in one second in non-smoking Japanese women].

We prospectively studied 1,696 clinically healthy non-smoking women to assess the influence of aging on longitudinal decline in forced expiratory volume in one second (FEV10). All the subjects took an annually medical examination involving a pulmonary function test from 1995 to 2001. The mean value of annual decrease in FEV10 (slope) was 19.6 mL/year. Multiple regression analysis revealed that initial age, height, and FEV10 were significant parameters determining the slope. This study clearly showed the aging-related longitudinal decline in pulmonary function in non-smoking Japanese women.

Adult↗

[A case of primary choriocarcinoma of the mediastinum in a Japanese woman].

A 32-year-old Japanese woman was referred to our hospital complaining of non-productive cough and dyspnea when in a dorsal position. Physical examination revealed left cervical lymph node swelling. Laboratory data showed HCG 17,700mIU/ml, betaHCG 130ng/ml, CYFRA 104ng/ml, AFP<2.0ng/ml, and LDH 802IU/l. A chest radiograph showed a giant mass shadow in the left hilum and many round mass shadows in both lung fields. Chest CT showed a mass shadow in the anterior mediastinum and many round mass shadows in both lung fields. There was no abnormality on abdominal and pelvic CT. A CT-guided transcutaneous lung biopsy specimen obtained from a mass in the left lower lobe revealed necrotized portions and atypical cells which were positive for HCG. We diagnosed primary choriocarcinoma of the mediastinum. The patient received 4 courses of the standard BEP regimen, resulting in partial response. This is the first reported case of primary choriocarcinoma of the mediastinum in a Japanese woman.

Adult↗

[A case of malignant mesothelioma presenting with recurrent pneumothorax].

A 71-year-old man was found to have right hydropneumothorax by chest X-ray film on a regular checkup. Thoracic drainage and bullectomy by thoracoscopy did not improve the pneumothorax, so pleurodesis with OK-432 was done. Pneumothorax recurred twice, requiring thoracic drainage and pleurodesis. Although pneumothorax was treated successfully, increased pleural effusion, pleural thickening and subcutaneal tumor at the thoracic drainage suture site developed. The concentration of hyaluronic acid in the pleural fluid was very high. The histological examination of the biopsied subcutaneous tumor showed mixed type malignant pleural mesothelioma. Chemotherapy with gemcitabine and vinorelbine could not control the progression.

Aged↗

[Prognostic factors of vaginal cancer].

Vaginal cancer is a rare disease entity in the gynecologic oncology field. Prognostic factors of the disease, however, are not established to date. Possible prognostic factors such as tumor location in vagina, tumor size, age,staging and histopathological grading are discussed following a literature review. Because the case number of the report from a single institute is really limited, accumulation and analysis of the case of multi-institutional registration are mandatory.

Aged↗

Phosphodiesterase 3 inhibition and cough in elderly asthmatics.

AIMS: Cough is a common symptom of bronchial asthma, a chronic inflammatory airway disease. Recently, the therapeutic effects of selective phosphodiesterase (PDE) inhibitors have been focused on bronchial asthma. This study was designed to investigate the clinical effect of PDE 3 inhibition on cough reflex sensitivity in elderly patients with bronchial asthma. METHODS: Effects of cilostazol, a PDE 3 inhibitor, on cough response to inhaled capsaicin were examined in 11 patients over 70 years with stable asthma in a randomized, placebo-controlled cross over study. Capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough reflex sensitivity. RESULTS: The cough threshold was significantly (p < 0.05) increased after two-week treatment with cilostazol (100 mg twice a day orally) compared with placebo [48.8 (GSEM 1.4) vs. 29.2 (GSEM 1.3) muM]. CONCLUSION: These findings indicate that PDE 3 inhibition may be a novel therapeutic option for elderly patients with asthma, especially for their cough symptoms.

Journal Article↗

Inhaled lysophosphatidylcholine provokes bronchoconstriction in guinea pigs in vivo.

Lysophosphatidylcholine is increased in the airway of bronchial asthma, but its role is not clear. We investigated the role of lysophosphatidylcholine in asthma in anaesthetized, mechanically ventilated guinea pigs. Pressure at the airway opening was measured as an index of bronchial response. Increasing doses of lysophosphatidylcholine (1--10 mg/ml) were inhaled and then bronchoalveolar lavage was carried out. 100 and 200 microg/ml methacholine were inhaled 10 min after inhalation of 2.5 mg/ml lysophosphatidylcholine, 10 mg/ml dipalmitoyl phosphatidylcholine and 10 mg/ml glycerophosphocholine, all of which per se did not change the pressure at the airway opening. Effect of 1.0 microg/kg salbutamol, or 60 mg/kg diphenhydramine on the lysophosphatidylcholine-induced increase in the pressure at the airway opening was investigated. Inhalation of lysophosphatidylcholine dose-dependently increased the pressure at the airway opening and increased bronchial responsiveness to methacholine. On the other hand, inhalation of dipalmitoyl phosphatidylcholine decreased the pressure at the airway opening and decreased bronchial responsiveness to methacholine. Intravenously administered salbutamol, but not diphenhydramine, prevented the lysophosphatidylcholine-induced increase in the pressure at the airway opening. The percentage of leukocytes in bronchoalveolar lavage fluid did not change significantly at least within 20 min after the lysophosphatidylcholine inhalation. Lysophosphatidylcholine causes bronchoconstriction and enhances bronchial responsiveness without inducing leukocyte infiltration in the airway, suggesting that lysophosphatidylcholine may be a new bronchoconstrictor mediator in bronchial asthma.

1,2-Dipalmitoylphosphatidylcholine↗

Comparison of cough reflex sensitivity after an inhaled antigen challenge between actively and passively sensitized guinea pigs.

BACKGROUND: Late asthmatic response is observed following antigen challenge in actively, but not passively, sensitized guinea pigs. Although cough reflex sensitivity is increased after antigen challenge in actively sensitized guinea pigs, it is unknown whether the antigen-induced increase in cough reflex sensitivity develops in passively sensitized animals. The aim of this study was to compare the cough reflex sensitivity to inhaled capsaicin after an inhaled antigen challenge between actively and passively sensitized guinea pigs. METHODS: Measurement of number of coughs elicited by increasing concentrations of capsaicin (10(-6) and 10(-4) M) and bronchial responsiveness to ascending concentrations of methacholine, and analysis of bronchoalveolar lavage fluid (BALF) were separately performed 24 h after an antigen challenge in actively and passively sensitized guinea pigs. RESULTS: Percentage of eosinophils in BALF and bronchial responsiveness to methacholine were increased 24 h after the antigen challenge in both actively and passively sensitized animals compared with saline-challenged actively and passively sensitized animals, respectively. Absolute number of eosinophils in BALF from actively sensitized and antigen-challenged guinea pigs was significantly greater than that from passively sensitized and antigen-challenged animals. Cough response to capsaicin and concentration of substance P in BALF were increased 24 h after the antigen challenge in actively sensitized guinea pigs, but not in passively sensitized guinea pigs. Bronchial responsiveness, cough reflex sensitivity and substance P concentration and total cells in BALF were increased in actively sensitized and saline challenged guinea pigs compared with passively sensitized and saline challenged animals. CONCLUSION: The results suggest that active sensitization per se increases cough reflex sensitivity accompanied by increased inflammatory cells and substance P level in BALF, and antigen challenge further increases them, while simple IgE- and/or IgG-mediated allergic reaction per se or the low intensity of eosinophil infiltration in the airway itself may not affect cough reflex sensitivity in guinea pigs.

Journal Article↗