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Arata Azuma

Publications and source records attributed to Arata Azuma.

11 recordsLinked to original sources
PubMed2003

Effect of the proteolytic enzyme serrapeptase in patients with chronic airway disease.

OBJECTIVES: The proteolytic enzyme serrapeptase (SER) is widely used in clinical practice in Japan. We investigated the effect of SER on sputum properties and symptoms in patients with chronic airway diseases. METHODS: This study was an open-labelled trial with a non-treatment control group. Patients were randomly assigned to oral treatment with (n = 15) and without (n = 14) SER 30 mg/day for 4 weeks. Patients collected sputum samples for about 4 h in the morning on the day the trial began and 4 weeks later. We measured the amount of sputum by weighing. Part of each sputum sample was weighed and then completely dried and reweighed. The percentage solid component, viscosity and elasticity of the sputum were measured. Mucociliary transportability index was measured using ciliated bovine trachea ex vivo. Sputum smears were also prepared to count sputum neutrophils. Patients' symptoms were assessed by a questionnaire that used a visual analogue scale. RESULTS: After 4 weeks of SER treatment, sputum weight in the morning, percentage solid component, viscosity and elasticity of sputum, sputum neutrophil count, frequency of coughing and frequency of expectoration significantly decreased. The mean mucociliary transportability index increased from 13.3 +/- 1.8 to 24.4 +/- 2.5 (P = 0.0103). CONCLUSIONS: SER may exert a beneficial effect on mucus clearance by reducing neutrophil numbers and altering the viscoelasticity of sputum in patients with chronic airway diseases.

Adult↗
PubMed2003

Diabetes mellitus may increase risk for idiopathic pulmonary fibrosis.

STUDY OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease of unknown etiology. The incidence of IPF increases with age. Aging contributes to lifestyle-related diseases, including diabetes mellitus (DM); therefore, it is possible that lifestyle-related diseases may affect either the initiation or progression of IPF. DESIGN: Case-control study. SETTING: Nippon Medical School and Omiya City Clinic. PATIENTS AND PARTICIPANTS: Sixty-five consecutive patients with IPF who were admitted to Nippon Medical School Hospital from 1995 to 2000, and 184 control subjects selected from 15,798 subjects who were admitted to Omiya City Clinic for routine medical examination between September 1999 and August 2000. MEASUREMENTS: Age, sex, smoking history, and results of physical examinations, blood examinations, and lung function testing were extracted from medical records and were compared with the diagnostic criteria for lifestyle-related diseases. RESULTS: The adjusted odds ratios for cigarette smoking were 5.40 (95% confidence interval [CI], 2.30 to 12.66) and 4.06 (95% CI, 1.80 to 9.15) for diabetes. There were no differences in clinical characteristics of patients with IPF that could be related to the presence of DM. CONCLUSION: DM may be a risk factor for IPF.

Aged↗
PubMed2003

[Macrolide].

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Animals↗
PubMed2003

Familial clustering of dendriform pulmonary ossification.

Dendriform pulmonary ossification is an extremely rare disease, which is usually found and analysed postmortem. Pathogenesis of pulmonary ossification is therefore still unknown. We describe two males in the same family (a 29 year-old patients and his 58 year-old father) with pulmonary ossification. The young male was symptomatic pneumothorax but his father had been asymptomatic since youth. Familial clustering of pulmonary ossifications strongly suggests a genetic predisposition for the pathogenesis. This is the first report of two cases of dendriform pulmonary ossification in the same family.

Adult↗
PubMed2002

Differential secretion of cytokines and adhesion molecules by HUVEC stimulated with low concentrations of bleomycin.

Bleomycin (BLM) is known to induce lung inflammation and subsequent fibrosis. Endothelial cells have been reported to play an important role, producing cytokines and adhesion molecules during the inflammatory process in pulmonary fibrosis. To examine the effects of BLM on endothelial cells, we investigated the expression profiles of various cytokines and adhesion molecules produced by endothelial cells stimulated with BLM. Increased expressions of interleukin-8 and monocyte chemoattractant protein-1 measured as protein as well as mRNA by human umbilical vein endothelial cells (HUVECs) were detected after exposure to BLM. Similarly, increased expressions of E-selectin and intercellular adhesion molecule-3 were detected both at the protein and mRNA levels. Under these conditions, a small but significant decrease of [3H]thymidine uptake was detected. These findings indicate that HUVEC were stimulated to secrete cytokines and express adhesion molecules in the presence of low concentrations of BLM which have a mildly inhibitory effect on cellular proliferation.

Bleomycin↗
PubMed2002

Long-term inhalation of diesel exhaust affects cytokine expression in murine lung tissues: comparison between low- and high-dose diesel exhaust exposure.

The authors investigated the effect of diesel exhaust (DE) on cytokine expression in murine lung tissues. BALB/c mice were exposed to DE for 1 month at different dose levels of DE (low dose: diesel exhaust particles [DEP] 100 micro g/m(3); high dose: 3mg/m(3)). After exposure, the authors examined mRNA expression of cytokines (tumor nocrosis factor alpha [TFN-alpha], Interleukin [IL]-1beta, IL-4, IL-6, IL-10, IL-12p40, and interferon gamma [IFN-gamma] and inducible nitric oxide synthase (iNOS) in the lung, and also measured the secretion of TNF-alpha and IL-10 protein by alveolar macrophages (AM). The mRNA expression levels of inflammatory cytokines (TNF-alpha, IL-1beta, IL-6, IL-12p40, IFN-gamma) and iNOS, which are important for host defense, were suppressed significantly. However, the IL-10 mRNA level was increased by DE exposure. The IL-4 mRNA level was increased by low-dose DE exposure but suppressed by high-dose DE exposure. TNF-alpha and IL-10 secretion by AM paralleled mRNA expression. Chronic inhalation of DE affects cytokine expression in murine lung. These results suggest that DE alters immunological responses in the lung and may increase susceptibility to pathogens, and that increased IL-4 expression by low-dose DE exposure may induce allergic reaction such as asthma.

Administration, Inhalation↗
PubMed2002

[Attenuated mRNA induction of molecules associated with neutrophil migration by 14-membered ring macrolides inhibits bleomycin induced acute lung injury in mice].

BACKGROUND: Although the pathogeneses of interstitial pneumonia are not well understood, it has been reported that inflammatory cells, especially neutrophils, and their injurious substances play important roles in the progression of interstitial pneumonia. Erythromycin and other 14-membered ring macrolides (14-MRMLs) have been reported to inhibit chronic airway inflammation by mechanisms of anti-neutrophil and several other anti-inflammatory activities. The present study was undertaken to investigate the effects and mechanisms of 14-MRMLs (erythromycin: EM; clarithromycin: CAM; roxithromycin: RXM) on an experimental model of bleomycin (BLM) -induced acute lung injury in mice. METHODS: BLM was administered intravenously to ICR mice. For the evaluation of early-phase inflammation, cell populations in broncho-alveolar lavage fluid (BALF) and induction of mRNA of adhesion molecules (E-selectin, P-selectin, ICAM-1, VCAM-1) and TNF-alpha tested by RT-PCR in lung tissues were examined at 0 to 13 days after BLM. These parameters were also compared with those of the control (NS alone), 14-MRMLs-untreated (BLM alone) and-pre-treated (BLM+pre 14-MRMLs) groups. RESULTS: The number of neutrophils, macrophages, and lymphocytes significantly increased in BAL. Neutrophils especially increased with two peaks after BLM administration. 14-MRMLs significantly inhibited both peaks of neutrophil. The increase in number of macrophages in BALF was significantly attenuated by EM and RXM, and slightly attenuated by CAM. Number of lymphocytes in BALF was significantly attenuated by EM and CAM, and slightly attenuated by RXM. Changes in mRNA expression of E-selectin, P-selectin, ICAM-1, VCAM-1, and TNF-alpha were associated with the number of neutrophils migrating into the airspace. 14-MRMLs clearly inhibited the induction of VCAM-1 mRNA, and tended to attenuate the induction of ICAM-1 and TNF-alpha mRNA, but did not inhibit the induction of E-selectin and P-selectin mRNA. DISCUSSION: These findings show that 14-MRMLs clearly attenuated the expression of VCAM-1mRNA, and tended to attenuate the induction of ICAM-1 and TNF-alpha mRNA, and subsequently inhibited leucocyte, especially neutrophil migration into the airspace during the early phase of BLM-induced lung injury and finally inhibited lung fibrosis. This might be one potent mechanism of the anti-inflammatory effects of 14-MRMLs in BLM-induced acute lung injury. The findings suggest that prophylactic administration of 14-MRMLs may be clinically efficacious in preventing acute exacerbation of interstitial pneumonia and acute lung injury.

Animals↗
PubMed2002

Fourteen-membered ring macrolides inhibit vascular cell adhesion molecule 1 messenger RNA induction and leukocyte migration: role in preventing lung injury and fibrosis in bleomycin-challenged mice.

BACKGROUND AND OBJECTIVE: Although the pathogenesis of interstitial pneumonia and pulmonary fibrosis are not well understood, it has been reported that inflammatory cells, especially neutrophils, and the injurious substances produced by them play important roles in the progression of interstitial pneumonia and subsequent fibrosis. Erythromycin and other 14-membered ring macrolides (14-MRMLs) have been reported to improve the survival of patients with diffuse panbronchiolitis by antineutrophil and several other anti-inflammatory mechanisms. The present study was undertaken to investigate the effects of 14-MRMLs on an experimental model of bleomycin-induced acute lung injury and subsequent fibrosis in mice. METHODS: Bleomycin was administered IV to ICR mice. At 28 days after bleomycin injection, fibrotic foci were histologically observed in left lung tissues, and hydroxyproline content in right lung tissues was chemically analyzed. The inhibitory effects of 14-MRMLs were assessed by overall comparison between control (normal saline solution [NS] alone), untreated (bleomycin alone), and treated (bleomycin plus 14-MRMLs) groups. For evaluation of early-phase inflammation, cell populations in BAL fluid and induction of messenger RNA (mRNA) of adhesion molecules (E-selectin, P-selectin, intercellular adhesion molecule 1 [ICAM-1], and vascular cell adhesion molecule 1 [VCAM-1]) in lung tissues were examined at 0 to 13 days after bleomycin treatment. These parameters were also compared with those for the control (NS alone), 14-MRML untreated (bleomycin alone), and 14-MRML pretreated (bleomycin plus 14-MRML pretreated) groups. RESULTS: Bleomycin-induced pulmonary fibrosis was inhibited by erythromycin and other 14-MRMLs on day 28 after bleomycin injection in ICR mice, especially those pretreated with 14-MRMLs. Hydroxyproline content in lung tissues was also decreased in the 14-MRML-pretreated groups. The number of neutrophils in BAL fluid significantly increased, with two peaks at 1 day and 9 days (from 6 to 11 days) after bleomycin administration. 14-MRMLs significantly inhibited both peaks of neutrophil infiltration into the airspace. Changes in mRNA expression of adhesion molecules (E-selectin, P-selectin, ICAM-1, VCAM-1) were associated with leukocyte migration into the airspace. 14-MRMLs clearly inhibited the induction of VCAM-1 mRNA, and tended to attenuate that of ICAM-1 mRNA, but inhibited the induction of neither E-selectin mRNA nor P-selectin mRNA. CONCLUSION: These findings indicate that attenuation of inflammatory cell migration into the airspace by 14-MRMLs, especially of neutrophils and macrophages, resulted in inhibition of lung injury and subsequent fibrosis. 14-MRMLs clearly attenuated the expression of VCAM-1 mRNA during the early phase of bleomycin-induced lung injury, and this might be one mechanism of inhibition of neutrophil and macrophage migration into the airspace by 14-MRMLs. This may be one mechanism of the anti-inflammatory and antifibrotic effects of 14-MRMLs. These findings suggest that prophylactic administration of 14-MRMLs may be clinically efficacious in preventing acute exacerbation of interstitial pneumonia and acute lung injury.

Animals↗
PubMed2002

[Clinicopathological analysis of patients with idiopathic pulmonary fibrosis which became acutely exacerbated after video-assisted thoracoscopic surgical lung biopsy].

Nine patients undergoing video-assisted thoracoscopic surgical (VATS) lung biopsy over a five-year period from 1997 to 2001 with the ultimate diagnosis of usual interstitial pneumonia without underlying connective tissue disease were identified. In two of nine patients, acute exacerbation occurred six days after VATS lung biopsy. We reviewed the clinical records and pathology of all nine cases, and found that the two cases of exacerbation had higher peripheral white blood cell counts and KL-6, lower PaO2, VC and FEV 1, and a longer inhalation of FIO 2 = 1.0 during VATS, and needed a longer period of chest drainage after VATS. Abundant inflammatory cell infiltration and fibroblastic foci were observed in the exacerbation cases. Thus, patients with usual interstitial pneumonia of the idiopathic type, who have high disease activity and low pulmonary function, may be at high risk of acute exacerbation following VATS lung surgery.

Biopsy↗
PubMedDate not supplied

Effects of diesel exhaust on murine alveolar macrophages and a macrophage cell line.

To investigate the effects of diesel exhaust particles (DEP) and mycobacterial infection on macrophages, we examined protein and mRNA expression levels of various cytokines, including tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-12, and IL-18 in BALB/c mouse alveolar macrophages (AM) and a macrophage cell line (RAW264.7) after in vitro stimulation with diesel exhaust (DE), with and without Mycobacterium bovis bacillus Calmette-Guérin (BCG). The cells were exposed to DE freshly generated in an in vitro system. When AM were exposed to DE (mean DEP exposure level, 300 microg/m3), the levels of TNF-alpha and IL-12 decreased significantly (by 51% to 61% for TNF-alpha and by 69% to 78% for IL-12), whereas those of IL-1beta and IL-18 remained unchanged. When AM were exposed to DE and then treated with BCG, the level of TNF-alpha decreased by 45 % to 71%, whereas the level of IL-1beta increased by 154%, compared with AM treated with BCG alone. Similarly, RAW2264.7 cells were stimulated with DE with and without M. bovis BCG and cytokine mRNA levels examined by reverse transcriptase-polymerase chain reaction (R7-PCR). Longer exposure to DE decreased TNF-alpha and IL-12 mRNA levels in the RAW264.7 cells. When the cells were exposed to DE and subsequently treated with BCG, levels of TNF-alpha, IL-1beta, and IL12 mRNAs decreased compared with those of cells treated with BCG alone. These results show that DE exposure has complex and diverse effects on cytokine production by AM, and that longer exposure (>8 hours) may suppress cytokine production by AM in vitro. Longer exposure of DE may therefore suppress the host defense in the lung and may increase susceptibility to lung infections such as mycobacterial infection.

Air Pollutants↗