Yasuhiro Setoguchi - Academia.edu (original) (raw)
Papers by Yasuhiro Setoguchi
Pulmonary pharmacology & therapeutics, Jan 4, 2016
Mucolytic agents are often used in Japan to ease excessive mucus production in patients with chro... more Mucolytic agents are often used in Japan to ease excessive mucus production in patients with chronic obstructive pulmonary disease (COPD) or bronchial asthma (BA); the treatment ameliorates dyspnea and improves quality of life (QOL). Efficacy and safety of lysozyme hydrochloride (LYS), an oral mucolytic enzyme preparation, for patients with COPD or BA were investigated. This study was a placebo-controlled, double-blind, randomized, cross-over design. Twenty-four patients with COPD and twenty-four patients with BA were enrolled. LYS or placebo was administered for 28 days in each treatment period, with a 28-day washout between the first and second treatment periods. The results of spirometry, impulse oscillometry system (IOS) examination, fractional exhaled nitric oxide (FeNO) measurement, as well as the changes in the subjective symptoms, were evaluated after the treatment period. On spirometry, airway function (FEV1) improved in patients with COPD after administration of LYS (LYS v...
Expert Opinion on Pharmacotherapy, 2015
To investigate the potential beneficial effects of guideline-based pharmacological therapy on pul... more To investigate the potential beneficial effects of guideline-based pharmacological therapy on pulmonary function and quality of life (QOL) in Japanese chronic obstructive pulmonary disease (COPD) patients without prior treatment. Multicenter survey, open-label study of 49 Japanese COPD patients aged ≥ 40 years; outpatients with >10 pack years of smoking history; ratio of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) < 70%; predicted FEV1 < 80%; treated with bronchodilators and/or inhaled corticosteroids as maintenance therapy until week 48. The primary endpoint was change in pulmonary function (trough FEV1, trough FVC); secondary endpoints were QOL and physical activity at 48 weeks after initiation of therapy. Airway reversibility was confirmed in untreated patients. Significant changes over time were not observed for FEV1 and FVC, indicating lung function at initiation of treatment was maintained during the observation period. COPD assessment test scores showed statistical and clinical improvements. Cough, sputum, breathlessness, and shortness of breath were significantly improved. Lung function and QOL of untreated Japanese COPD patients improved and improvements were maintained by performing a therapeutic intervention that conformed to published guidelines.
Juntendo Medical Journal, 2001
International journal of molecular medicine, 2013
Chronic obstructive pulmonary disease (COPD) is characterized by both chronic inflammation in the... more Chronic obstructive pulmonary disease (COPD) is characterized by both chronic inflammation in the airway and systemic inflammation; however, the molecular mechanism of COPD has not been fully elucidated. By measuring microRNA (miRNA) expression in the plasma of COPD subjects, we aimed to identify the clinical relevance of plasma miRNA levels in these patients. Blood samples were obtained from COPD patients and age-matched normal controls. We initially produced plasma miRNA expression profiles using TaqMan low-density array screening. For further validation, individual qRT-PCRs were performed in 40 COPD patients and 20 healthy subjects. TaqMan low-density array screening showed that 9 miRNAs (miR-29b, miR-483-5p, miR-152, miR-629, miR-26b, miR-101, miR-106b, miR-532-5p and miR-133b) were significantly downregulated in the plasma from COPD patients when compared with normal smokers. Among these miRNAs, we focused on miR-106b. A reduction in the plasma miR-106b levels was evident in CO...
European Journal of Pediatrics, 2013
Mutations in genes critical for surfactant metabolism, including surfactant protein C (SP-C) and ... more Mutations in genes critical for surfactant metabolism, including surfactant protein C (SP-C) and ABCA3, are well-recognized causes of interstitial lung disease. Recessive mutations in ABCA3 were first attributed to fatal respiratory failure in full-term neonates, but they are also increasingly being recognized as a cause of respiratory disorders with less severe phenotypes in older children and also adults. Here, we report a 20-month-old boy with interstitial lung disease caused by two distinct ABCA3 mutations. Initial treatment with methylprednisolone was unsuccessful, but the additional administration of hydroxychloroquine was effective. The family history revealed that the patient's older brother had died of idiopathic interstitial lung disease at 6 months of age, suggesting a genetic etiology of the disease. Sequence analyses of SP-C and ABCA3 genes were performed using DNA samples from the patient himself, his parents, and his brother. These analyses revealed novel compound heterozygous mutations in the coding exons of ABCA3 in both the patient and his brother: c.2741A > G, of paternal origin, and c.3715_3716insGGGGGG, of maternal origin. Conclusion Since ABCA3 mutations seem to be a heterogeneous entity with various phenotypes, we recommend genetic testing for mutations in SP-C and ABCA3 genes to be considered in children with unexplained interstitial lung disease.
C103. PATHOGENESIS, BIOMARKERS, AND RISK FACTORS FOR INTERSTITIAL LUNG DISEASE: FROM BENCH TO BEDSIDE, 2012
European Respiratory Journal, Sep 1, 2014
International Journal of Molecular Medicine, 2015
The deletion mutation of exon 4 in surfactant protein C (SP-C), a lung surfactant protein, has be... more The deletion mutation of exon 4 in surfactant protein C (SP-C), a lung surfactant protein, has been identified in parent-child cases of familial interstitial pneumonia. It has been shown that this mutation induces endoplasmic reticulum (ER) stress. Synoviolin is an E3 ubiquitin ligase that is localized to the ER and is an important factor in the degradation of ER-related proteins. It has been demonstrated that synoviolin is involved in liver fibrosis. In the present study, we investigated the involvement of synoviolin in the pathogenesis of interstitial pneumonia caused by the exon 4 deletion in the SP-C gene. We transfected wild-type and exon 4-deleted SP-C genes into A549 human lung adenocarcinoma cells and measured the secretion of collagen, which is a representative extracellular matrix protein involved in fibrosis. Secreted collagen levels were increased in the culture medium in SP-C mutants compared to the wild-type cells. Furthermore, the transcription of mRNAs coding for factors associated with fibrosis was increased. Subsequently, to assess the involvement of synoviolin, we constructed plasmids with a luciferase gene under the control of the synoviolin promoter. The A549 cells were transfected with the construct along with the exon 4-deleted SP-C plasmid for use in the luciferase assay. We found a 1.6-fold increase in luciferase activity in the cells carrying exon 4 deleted SP-C, as well as an increase in intrinsic synoviolin expression at the mRNA and protein levels. Collagen secretion was decreased by the addition of LS-102, a synoviolin inhibitor, to the A549 culture medium following transfection with wild-type and exon 4-deleted SP-C. These results demonstrate that synoviolin is involved in the onset of interstitial pneumonia induced by exon 4-deleted SP-C, which suggests that synoviolin inhibitors may be used in the treatment of the disease.
A 35-year-old woman was admitted to our hospital because of an abnormal chest radiograph. Chest X... more A 35-year-old woman was admitted to our hospital because of an abnormal chest radiograph. Chest X-ray on admission showed multiple small nodular shadows in both lung fields but no bilateral hilar lymphadenopathy (BHL). Moreover, abdominal CT showed some nodules in the liver and spleen, and serum ACE was slightly increased to 23.3U/L (normal range: 8.3-21.4U/L). Transbronchial lung biopsy and liver biopsy resulted in a diagnosis of stage III pulmonary sarcoidosis with hepatosplenic disease. Histopathological findings demonstrated non-caseating epithelioid cell granulomas with giant cells in both specimens. Interestingly, propionibacterium acnes (P. acnes), the possible pathogen of sarcoidosis, was detected in giant cells in the lung and epitheliod cell granuloma of liver tissue. This case was of interest considering P. acnes might have been the causative pathogen.
C50. COPD: BIOMARKERS, 2012
Journal of thoracic disease, 2016
There is a scarcity of reports comparing gender differences in polysomnographic findings among As... more There is a scarcity of reports comparing gender differences in polysomnographic findings among Asian patients with sleep apnea (SA). In this study, we elucidated gender differences in the clinical features and polysomnographic findings of SA patients in Japan. We conducted a case-matched control study to compare the gender differences. A total of 4,714 patients (4,127 men; 587 women) were matched for age, apnea-hypopnea index (AHI), and body mass index (BMI). The criteria used for sex matching were (I) age ±4 years, (II) AHI ± 4 h of sleep, and (III) BMI ±2 kg/m(2). This facilitated the comparison of polysomnography sleep variables in 296 men and 296 women with SA. Compared with their male counterparts, female SA patients had a significantly higher rapid eye movement AHI [men: 27.7 (IQR, 14.3-45.2); women: 43.3 (IQR, 25.5-56.6); P<0.001], lower supine AHI [men: 29.7 (IQR, 16.8-49.5); women: 25.0 (IQR, 14.7-39.3); P=0.004], longer total sleep time (TST), and non-rapid eye movement...
Respiratory Medicine Case Reports, 2012
A 19-year-old female was admitted to our hospital because of a sudden onset fever and cough, and ... more A 19-year-old female was admitted to our hospital because of a sudden onset fever and cough, and she was diagnosed to have acute eosinophilic pneumonia (AEP). The cause was thought to be cigarette smoking, because she had started smoking just before the development of AEP and her condition improved after cigarette smoking cessation, without corticosteroid treatment. The cytokines which are thought to be involved in eosinophilic accumulation in the lungs were analyzed using bronchoalveolar lavage fluid (BALF) and serum. Of the analyzed cytokines, only regulated on activation, normal T cell expressed and secreted (RANTES) increased in the serum after the improvement. RANTES is a unique chemokine which attracts not only eosinophils, but also T cells. Interestingly, in this case, the eosinophil count in the blood increased in parallel with the lymphocyte count after the improvement. These findings are interesting because it may help to understand the pathogenesis of AEP and the role of RANTES.
European Respiratory Journal, 2015
Nihon rinsho. Japanese journal of clinical medicine, 1996
Nitric oxide (NO) is a messenger molecule involved in diverse processes in many tissues. For exam... more Nitric oxide (NO) is a messenger molecule involved in diverse processes in many tissues. For example, NO is responsible for the bactericidal activities of macrophages, and in blood vessels it accounts for endothelium-derived relaxing factor activity. Recently, inhalation of NO gas was reported to improve the acute pulmonary arterial hypertension. Based on this knowledge, recombinant expression of endothelial nitric oxide synthase (eNOS) in lung may have profound effects on pulmonary vasomotor function and pulmonary arterial smooth muscle proliferation and platelet adhesion. On the basis of this concept, we evaluate the feasibility of gene therapy for chronic pulmonary arterial hypertension using hypoxia regulatable adenoviral vector coding eNOS cDNA.
Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society, 2006
A 35-year-old woman was admitted to our hospital because of an abnormal chest radiograph. Chest X... more A 35-year-old woman was admitted to our hospital because of an abnormal chest radiograph. Chest X-ray on admission showed multiple small nodular shadows in both lung fields but no bilateral hilar lymphadenopathy (BHL). Moreover, abdominal CT showed some nodules in the liver and spleen, and serum ACE was slightly increased to 23.3U/L (normal range: 8.3-21.4U/L). Transbronchial lung biopsy and liver biopsy resulted in a diagnosis of stage III pulmonary sarcoidosis with hepatosplenic disease. Histopathological findings demonstrated non-caseating epithelioid cell granulomas with giant cells in both specimens. Interestingly, propionibacterium acnes (P. acnes), the possible pathogen of sarcoidosis, was detected in giant cells in the lung and epitheliod cell granuloma of liver tissue. This case was of interest considering P. acnes might have been the causative pathogen.
Nihon rinsho. Japanese journal of clinical medicine, 2005
Journal of dermatological science, 2003
A Th2 chemokine, thymus and activation regulated chemokine (TARC/CCL17), produced by keratinocyte... more A Th2 chemokine, thymus and activation regulated chemokine (TARC/CCL17), produced by keratinocytes, is implicated in the development of atopic dermatitis by recruiting CLA(+)CCR4(+) lymphocytes into lesional skin and its expression was induced by proinflammatory cytokines such as interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). However, it remains unknown how TARC expression is negatively regulated in keratinocytes. We sought to determine whether transforming growth factor-beta 1 (TGF-beta 1) regulated TARC expression in keratinocytes. The effect of TGF-beta 1 on mRNA and protein expression of IFN-gamma and TNF-alpha-induced TARC in a human keratinocyte cell line, HaCaT cells, was evaluated by using RT-PCR and ELISA. Adenovector-mediated gene transfer was used to determine the effect of Smad proteins on TARC expression in HaCaT cells. TGF-beta 1 inhibited mRNA and protein expression of IFN-gamma and TNF-alpha-induced TARC in HaCaT cells. The inhibitory effec...
Cornea, 2003
The inhibitory activity of transforming growth factor-beta2 (TGF-beta2) on corneal endothelial ce... more The inhibitory activity of transforming growth factor-beta2 (TGF-beta2) on corneal endothelial cell proliferation is thought to be a cause of the limited regenerative capacity of corneal endothelial cells that may be related to impaired corneal transparency when many corneal endothelial cells are lost due to various stresses. We determined whether Smad7, an intracellular antagonist of TGF-beta signaling, regulated the inhibitory activity of TGF-beta2 or aqueous humor on corneal endothelial cell proliferation. The effect of Smad7 on TGF-beta2- or aqueous humor-mediated inhibition of corneal endothelial cell proliferation was evaluated using thymidine uptake assay with cultured rabbit corneal endothelial cells infected with adenovirus carrying Smad7. Expression of Smad or cell cycle-related proteins was detected by immunoblotting. In addition, a small scrape wound was made across a monolayer of Smad7-expressing cultured rabbit corneal endothelial cells to examine the effect of Smad7 o...
Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society, 2002
A 71-year-old man was referred to our hospital complaining of cough. Chest radiography revealed a... more A 71-year-old man was referred to our hospital complaining of cough. Chest radiography revealed a mass opacity in the right upper lung field. A transbronchial biopsy specimen revealed non-specific inflammatory changes. Percutaneous lung aspiration biopsy under ultrasound guidance demonstrated gram-positive rods, suggesting actinomyces. On the diagnosis of pulmonary actinomycosis, the patient was treated with penicillin-G and his symptoms were relieved. In a three-month follow-up, the mass shadow in the right upper lung field was found to have increased in size. Squamous cell lung cancer was diagnosed on the basis of repeated transbronchial tumor biopsies, and right upper lobectomy was performed. Most cases of pulmonary actinomycosis have been diagnosed from post-surgical tumor specimens taken on suspicion of the presence of lung cancer. However, the lung cancer in this case was difficult to diagnose because the lung cancer was co-existent with pulmonary actinomycosis.
Pulmonary pharmacology & therapeutics, Jan 4, 2016
Mucolytic agents are often used in Japan to ease excessive mucus production in patients with chro... more Mucolytic agents are often used in Japan to ease excessive mucus production in patients with chronic obstructive pulmonary disease (COPD) or bronchial asthma (BA); the treatment ameliorates dyspnea and improves quality of life (QOL). Efficacy and safety of lysozyme hydrochloride (LYS), an oral mucolytic enzyme preparation, for patients with COPD or BA were investigated. This study was a placebo-controlled, double-blind, randomized, cross-over design. Twenty-four patients with COPD and twenty-four patients with BA were enrolled. LYS or placebo was administered for 28 days in each treatment period, with a 28-day washout between the first and second treatment periods. The results of spirometry, impulse oscillometry system (IOS) examination, fractional exhaled nitric oxide (FeNO) measurement, as well as the changes in the subjective symptoms, were evaluated after the treatment period. On spirometry, airway function (FEV1) improved in patients with COPD after administration of LYS (LYS v...
Expert Opinion on Pharmacotherapy, 2015
To investigate the potential beneficial effects of guideline-based pharmacological therapy on pul... more To investigate the potential beneficial effects of guideline-based pharmacological therapy on pulmonary function and quality of life (QOL) in Japanese chronic obstructive pulmonary disease (COPD) patients without prior treatment. Multicenter survey, open-label study of 49 Japanese COPD patients aged ≥ 40 years; outpatients with &amp;amp;amp;gt;10 pack years of smoking history; ratio of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) &amp;amp;amp;lt; 70%; predicted FEV1 &amp;amp;amp;lt; 80%; treated with bronchodilators and/or inhaled corticosteroids as maintenance therapy until week 48. The primary endpoint was change in pulmonary function (trough FEV1, trough FVC); secondary endpoints were QOL and physical activity at 48 weeks after initiation of therapy. Airway reversibility was confirmed in untreated patients. Significant changes over time were not observed for FEV1 and FVC, indicating lung function at initiation of treatment was maintained during the observation period. COPD assessment test scores showed statistical and clinical improvements. Cough, sputum, breathlessness, and shortness of breath were significantly improved. Lung function and QOL of untreated Japanese COPD patients improved and improvements were maintained by performing a therapeutic intervention that conformed to published guidelines.
Juntendo Medical Journal, 2001
International journal of molecular medicine, 2013
Chronic obstructive pulmonary disease (COPD) is characterized by both chronic inflammation in the... more Chronic obstructive pulmonary disease (COPD) is characterized by both chronic inflammation in the airway and systemic inflammation; however, the molecular mechanism of COPD has not been fully elucidated. By measuring microRNA (miRNA) expression in the plasma of COPD subjects, we aimed to identify the clinical relevance of plasma miRNA levels in these patients. Blood samples were obtained from COPD patients and age-matched normal controls. We initially produced plasma miRNA expression profiles using TaqMan low-density array screening. For further validation, individual qRT-PCRs were performed in 40 COPD patients and 20 healthy subjects. TaqMan low-density array screening showed that 9 miRNAs (miR-29b, miR-483-5p, miR-152, miR-629, miR-26b, miR-101, miR-106b, miR-532-5p and miR-133b) were significantly downregulated in the plasma from COPD patients when compared with normal smokers. Among these miRNAs, we focused on miR-106b. A reduction in the plasma miR-106b levels was evident in CO...
European Journal of Pediatrics, 2013
Mutations in genes critical for surfactant metabolism, including surfactant protein C (SP-C) and ... more Mutations in genes critical for surfactant metabolism, including surfactant protein C (SP-C) and ABCA3, are well-recognized causes of interstitial lung disease. Recessive mutations in ABCA3 were first attributed to fatal respiratory failure in full-term neonates, but they are also increasingly being recognized as a cause of respiratory disorders with less severe phenotypes in older children and also adults. Here, we report a 20-month-old boy with interstitial lung disease caused by two distinct ABCA3 mutations. Initial treatment with methylprednisolone was unsuccessful, but the additional administration of hydroxychloroquine was effective. The family history revealed that the patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s older brother had died of idiopathic interstitial lung disease at 6 months of age, suggesting a genetic etiology of the disease. Sequence analyses of SP-C and ABCA3 genes were performed using DNA samples from the patient himself, his parents, and his brother. These analyses revealed novel compound heterozygous mutations in the coding exons of ABCA3 in both the patient and his brother: c.2741A &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; G, of paternal origin, and c.3715_3716insGGGGGG, of maternal origin. Conclusion Since ABCA3 mutations seem to be a heterogeneous entity with various phenotypes, we recommend genetic testing for mutations in SP-C and ABCA3 genes to be considered in children with unexplained interstitial lung disease.
C103. PATHOGENESIS, BIOMARKERS, AND RISK FACTORS FOR INTERSTITIAL LUNG DISEASE: FROM BENCH TO BEDSIDE, 2012
European Respiratory Journal, Sep 1, 2014
International Journal of Molecular Medicine, 2015
The deletion mutation of exon 4 in surfactant protein C (SP-C), a lung surfactant protein, has be... more The deletion mutation of exon 4 in surfactant protein C (SP-C), a lung surfactant protein, has been identified in parent-child cases of familial interstitial pneumonia. It has been shown that this mutation induces endoplasmic reticulum (ER) stress. Synoviolin is an E3 ubiquitin ligase that is localized to the ER and is an important factor in the degradation of ER-related proteins. It has been demonstrated that synoviolin is involved in liver fibrosis. In the present study, we investigated the involvement of synoviolin in the pathogenesis of interstitial pneumonia caused by the exon 4 deletion in the SP-C gene. We transfected wild-type and exon 4-deleted SP-C genes into A549 human lung adenocarcinoma cells and measured the secretion of collagen, which is a representative extracellular matrix protein involved in fibrosis. Secreted collagen levels were increased in the culture medium in SP-C mutants compared to the wild-type cells. Furthermore, the transcription of mRNAs coding for factors associated with fibrosis was increased. Subsequently, to assess the involvement of synoviolin, we constructed plasmids with a luciferase gene under the control of the synoviolin promoter. The A549 cells were transfected with the construct along with the exon 4-deleted SP-C plasmid for use in the luciferase assay. We found a 1.6-fold increase in luciferase activity in the cells carrying exon 4 deleted SP-C, as well as an increase in intrinsic synoviolin expression at the mRNA and protein levels. Collagen secretion was decreased by the addition of LS-102, a synoviolin inhibitor, to the A549 culture medium following transfection with wild-type and exon 4-deleted SP-C. These results demonstrate that synoviolin is involved in the onset of interstitial pneumonia induced by exon 4-deleted SP-C, which suggests that synoviolin inhibitors may be used in the treatment of the disease.
A 35-year-old woman was admitted to our hospital because of an abnormal chest radiograph. Chest X... more A 35-year-old woman was admitted to our hospital because of an abnormal chest radiograph. Chest X-ray on admission showed multiple small nodular shadows in both lung fields but no bilateral hilar lymphadenopathy (BHL). Moreover, abdominal CT showed some nodules in the liver and spleen, and serum ACE was slightly increased to 23.3U/L (normal range: 8.3-21.4U/L). Transbronchial lung biopsy and liver biopsy resulted in a diagnosis of stage III pulmonary sarcoidosis with hepatosplenic disease. Histopathological findings demonstrated non-caseating epithelioid cell granulomas with giant cells in both specimens. Interestingly, propionibacterium acnes (P. acnes), the possible pathogen of sarcoidosis, was detected in giant cells in the lung and epitheliod cell granuloma of liver tissue. This case was of interest considering P. acnes might have been the causative pathogen.
C50. COPD: BIOMARKERS, 2012
Journal of thoracic disease, 2016
There is a scarcity of reports comparing gender differences in polysomnographic findings among As... more There is a scarcity of reports comparing gender differences in polysomnographic findings among Asian patients with sleep apnea (SA). In this study, we elucidated gender differences in the clinical features and polysomnographic findings of SA patients in Japan. We conducted a case-matched control study to compare the gender differences. A total of 4,714 patients (4,127 men; 587 women) were matched for age, apnea-hypopnea index (AHI), and body mass index (BMI). The criteria used for sex matching were (I) age ±4 years, (II) AHI ± 4 h of sleep, and (III) BMI ±2 kg/m(2). This facilitated the comparison of polysomnography sleep variables in 296 men and 296 women with SA. Compared with their male counterparts, female SA patients had a significantly higher rapid eye movement AHI [men: 27.7 (IQR, 14.3-45.2); women: 43.3 (IQR, 25.5-56.6); P<0.001], lower supine AHI [men: 29.7 (IQR, 16.8-49.5); women: 25.0 (IQR, 14.7-39.3); P=0.004], longer total sleep time (TST), and non-rapid eye movement...
Respiratory Medicine Case Reports, 2012
A 19-year-old female was admitted to our hospital because of a sudden onset fever and cough, and ... more A 19-year-old female was admitted to our hospital because of a sudden onset fever and cough, and she was diagnosed to have acute eosinophilic pneumonia (AEP). The cause was thought to be cigarette smoking, because she had started smoking just before the development of AEP and her condition improved after cigarette smoking cessation, without corticosteroid treatment. The cytokines which are thought to be involved in eosinophilic accumulation in the lungs were analyzed using bronchoalveolar lavage fluid (BALF) and serum. Of the analyzed cytokines, only regulated on activation, normal T cell expressed and secreted (RANTES) increased in the serum after the improvement. RANTES is a unique chemokine which attracts not only eosinophils, but also T cells. Interestingly, in this case, the eosinophil count in the blood increased in parallel with the lymphocyte count after the improvement. These findings are interesting because it may help to understand the pathogenesis of AEP and the role of RANTES.
European Respiratory Journal, 2015
Nihon rinsho. Japanese journal of clinical medicine, 1996
Nitric oxide (NO) is a messenger molecule involved in diverse processes in many tissues. For exam... more Nitric oxide (NO) is a messenger molecule involved in diverse processes in many tissues. For example, NO is responsible for the bactericidal activities of macrophages, and in blood vessels it accounts for endothelium-derived relaxing factor activity. Recently, inhalation of NO gas was reported to improve the acute pulmonary arterial hypertension. Based on this knowledge, recombinant expression of endothelial nitric oxide synthase (eNOS) in lung may have profound effects on pulmonary vasomotor function and pulmonary arterial smooth muscle proliferation and platelet adhesion. On the basis of this concept, we evaluate the feasibility of gene therapy for chronic pulmonary arterial hypertension using hypoxia regulatable adenoviral vector coding eNOS cDNA.
Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society, 2006
A 35-year-old woman was admitted to our hospital because of an abnormal chest radiograph. Chest X... more A 35-year-old woman was admitted to our hospital because of an abnormal chest radiograph. Chest X-ray on admission showed multiple small nodular shadows in both lung fields but no bilateral hilar lymphadenopathy (BHL). Moreover, abdominal CT showed some nodules in the liver and spleen, and serum ACE was slightly increased to 23.3U/L (normal range: 8.3-21.4U/L). Transbronchial lung biopsy and liver biopsy resulted in a diagnosis of stage III pulmonary sarcoidosis with hepatosplenic disease. Histopathological findings demonstrated non-caseating epithelioid cell granulomas with giant cells in both specimens. Interestingly, propionibacterium acnes (P. acnes), the possible pathogen of sarcoidosis, was detected in giant cells in the lung and epitheliod cell granuloma of liver tissue. This case was of interest considering P. acnes might have been the causative pathogen.
Nihon rinsho. Japanese journal of clinical medicine, 2005
Journal of dermatological science, 2003
A Th2 chemokine, thymus and activation regulated chemokine (TARC/CCL17), produced by keratinocyte... more A Th2 chemokine, thymus and activation regulated chemokine (TARC/CCL17), produced by keratinocytes, is implicated in the development of atopic dermatitis by recruiting CLA(+)CCR4(+) lymphocytes into lesional skin and its expression was induced by proinflammatory cytokines such as interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). However, it remains unknown how TARC expression is negatively regulated in keratinocytes. We sought to determine whether transforming growth factor-beta 1 (TGF-beta 1) regulated TARC expression in keratinocytes. The effect of TGF-beta 1 on mRNA and protein expression of IFN-gamma and TNF-alpha-induced TARC in a human keratinocyte cell line, HaCaT cells, was evaluated by using RT-PCR and ELISA. Adenovector-mediated gene transfer was used to determine the effect of Smad proteins on TARC expression in HaCaT cells. TGF-beta 1 inhibited mRNA and protein expression of IFN-gamma and TNF-alpha-induced TARC in HaCaT cells. The inhibitory effec...
Cornea, 2003
The inhibitory activity of transforming growth factor-beta2 (TGF-beta2) on corneal endothelial ce... more The inhibitory activity of transforming growth factor-beta2 (TGF-beta2) on corneal endothelial cell proliferation is thought to be a cause of the limited regenerative capacity of corneal endothelial cells that may be related to impaired corneal transparency when many corneal endothelial cells are lost due to various stresses. We determined whether Smad7, an intracellular antagonist of TGF-beta signaling, regulated the inhibitory activity of TGF-beta2 or aqueous humor on corneal endothelial cell proliferation. The effect of Smad7 on TGF-beta2- or aqueous humor-mediated inhibition of corneal endothelial cell proliferation was evaluated using thymidine uptake assay with cultured rabbit corneal endothelial cells infected with adenovirus carrying Smad7. Expression of Smad or cell cycle-related proteins was detected by immunoblotting. In addition, a small scrape wound was made across a monolayer of Smad7-expressing cultured rabbit corneal endothelial cells to examine the effect of Smad7 o...
Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society, 2002
A 71-year-old man was referred to our hospital complaining of cough. Chest radiography revealed a... more A 71-year-old man was referred to our hospital complaining of cough. Chest radiography revealed a mass opacity in the right upper lung field. A transbronchial biopsy specimen revealed non-specific inflammatory changes. Percutaneous lung aspiration biopsy under ultrasound guidance demonstrated gram-positive rods, suggesting actinomyces. On the diagnosis of pulmonary actinomycosis, the patient was treated with penicillin-G and his symptoms were relieved. In a three-month follow-up, the mass shadow in the right upper lung field was found to have increased in size. Squamous cell lung cancer was diagnosed on the basis of repeated transbronchial tumor biopsies, and right upper lobectomy was performed. Most cases of pulmonary actinomycosis have been diagnosed from post-surgical tumor specimens taken on suspicion of the presence of lung cancer. However, the lung cancer in this case was difficult to diagnose because the lung cancer was co-existent with pulmonary actinomycosis.