Kiyohisa Sekizawa

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Cigarette smoke, containing reactive oxygen species, is the most important risk factor for chronic pulmonary emphysema (CPE). Heme oxygenase-1 (HO-1) plays a protective role as an antioxidant in the lung. A (GT)n dinucleotide repeat in the 5'-flanking region of human HO-1 gene shows length polymorphism and could modulate the level of gene transcription. To(More)
Activated macrophages express high levels of Nrf2, a transcription factor that positively regulates the gene expression of antioxidant and detoxication enzymes. In this study, we examined how Nrf2 contributes to the anti-inflammatory process. As a model system of acute inflammation, we administered carrageenan to induce pleurisy and found that in(More)
Proteinase/antiproteinase imbalance is the most widely accepted theory for development of chronic obstructive pulmonary disease (COPD). Mutations of tissue inhibitor of metalloproteinases-2 (TIMP-2) that downregulate its activity may increase the activities of matrix metalloproteinases and result in the degradation of the lung matrix. Polymorphisms of the(More)
STUDY OBJECTIVES Interleukin (IL)-4, IL-13, and beta(2)-adrenoceptor (ADRB2) are involved in airway hyperresponsiveness (AHR), and their coding genes are located on chromosome 5q31-q33. AHR is one of the risk factors for COPD. Investigating polymorphisms within these genes may help to pinpoint the genetic susceptibility to COPD. SUBJECTS AND MEASUREMENTS(More)
Exacerbations of asthma are often associated with respiratory infection caused by rhinoviruses. To study the effects of rhinovirus infection on respiratory epithelium, a primary target for respiratory viruses, human rhinovirus (HRV)-2 and HRV-14 were infected to primary cultures of human tracheal epithelial cells. Viral infection was confirmed by showing(More)
To examine the effects of glucocorticoid on rhinovirus (RV) infection, primary cultures of human tracheal epithelial cells were infected with either RV2 or RV14. Viral infection was confirmed by demonstrating that viral RNA in infected cells and viral titers of supernatants and lysates from infected cells increased with time. RV14 infection upregulated the(More)
Viral infection may induce the expression of heme oxygenase, resulting in increased carbon monoxide (CO) formation. CO may be produced by various cells of the upper and lower respiratory tract and may be detected in the exhaled air. Therefore, exhaled CO concentrations were measured on a CO monitor by vital capacity maneuver in subjects with upper(More)
Inflammation, protease/anti-protease imbalance and oxidative stress play important roles in the pathogenesis of emphysema. Nrf2 counteracts oxidative tissue damage and inflammation through transcriptional activation via the anti-oxidant responsive element (ARE). To clarify the protective role of Nrf2 in the development of emphysema, the susceptibility of(More)
It is recognized that genetic factors play a role in the susceptibility to COPD. COPD is characterized by airflow limitation. Chronic inflammation causes small airway disease and parenchymal destruction, leading to the airflow limitation. Polymorphisms in pro-inflammatory cytokine genes may confer a risk for the development of COPD. A case-control(More)
STUDY OBJECTIVES To investigate whether erythromycin therapy lowers the frequency of the common cold and subsequent exacerbation in patients with COPD. DESIGN Prospective, randomized, controlled, but not blinded, trial. PATIENTS One hundred nine patients with COPD were enrolled into the study. Patients were randomly assigned to erythromycin therapy or(More)