• Clinical and Experimental Pediatrics
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• v.53 no.12
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• pp.979-984
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• 2010

Recent progress in neonatal medicine has enabled survival of many extremely low-birth-weight infants. Prenatal steroids, surfactants, and non-invasive ventilation have helped reduce the incidence of the classical form of bronchopulmonary dysplasia characterized by marked fibrosis and emphysema. However, a new form of bronchopulmonary dysplasia marked by arrest of alveolarization remains a complication in the postnatal course of extremely low-birth-weight infants. To better understand this challenging complication, detailed alveolarization mechanisms should be delineated. Proper alveolarization involves the temporal and spatial coordination of a number of cells, mediators, and genes. Cross-talk between the mesenchyme and the epithelium through soluble and diffusible factors are key processes of alveolarization. Lung interstitial cells derived from the mesenchyme play a crucial role in alveolarization. Peak alveolar formation coincides with intense lung interstitial cell proliferation. Myofibroblasts are essential for secondary septation, a critical process of alveolarization, and localize to the front lines of alveologenesis. The differentiation and migration of myofibroblasts are strictly controlled by various mediators and genes. Disruption of this finely controlled mechanism leads to abnormal alveolarization. Since arrest in alveolarization is a hallmark of a new form of bronchopulmonary dysplasia, knowledge regarding the role of lung interstitial cells during alveolarization and their control mechanism will enable us to find more specific therapeutic strategies for bronchopulmonary dysplasia. In this review, the role of lung interstitial cells during alveolarization and control mechanisms of their differentiation and migration will be discussed.

• Tuberculosis and Respiratory Diseases
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• v.70 no.6
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• pp.462-473
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• 2011

Background: Smoking is a risk factor for idiopathic pulmonary fibrosis (IPF), but the mechanism of the association remains obscure. There is evidence demonstrating that plasminogen activator inhibitor-1 (PAI-1) is involved in the progression of pulmonary fibrosis. This study was to determine whether the administration of small interfering RNA (siRNA) targeting PAI-1 or PAI-1 inhibitor to the cigarette smoking extract (CSE)-exposed rat alveolar type II epithelial cells (ATII cells) limits the epithelial-mesenchymal transition (EMT). Methods: ATII cells were isolated from lung of SD-rat using percoll gradient method and cultured with 5% CSE. The EMT was determined from the ATII cells by measuring the real-time RT PCR and western blotting after the PAI-1 siRNA transfection to the cells and after administration of tiplaxtinin, an inhibitor of PAI-1. The effect of PAI-1 inhibitor was also evaluated in the bleomycin-induced rats. Results: PAI-1 was overexpressed in the smoking exposed ATII cells and was directly associated with EMT. The EMT from the ATII cells was suppressed by PAI-1 siRNA transfection or administration of tiplaxtinin. Signaling pathways for EMT by smoking extract were through the phosphorylation of SMAD2 and ERK1/2, and finally Snail expression. Tiplaxtinin also suppressed the pulmonary fibrosis and PAI-1 expression in the bleomycin-induced rats. Conclusion: Our data shows that CSE induces rat ATII cells to undergo EMT by PAI-1 via SMAD2-ERK1/2-Snail activation. This suppression of EMT by PAI-1 siRNA transfection or PAI-1 inhibitor in primary type II alveolar epithelial cells might be involved in the attenuation of bleomycin-induced pulmonary fibrosis in rats.

• Journal of Applied Biological Chemistry
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• v.65 no.4
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• pp.357-365
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• 2022

We examined the lung anti-fibrotic properties of flavanones and flavones, which are flavonoid compounds, in bleomycin- and TGF-β1-stimulated A549 cells. Taken together, treatment with Bleomycin and TGF-β1 increased intracellular ROS by increasing the expression of various NOX families in A549 cells; further, the increased ROS levels resulted in increased fibrosis markers and induced pulmonary fibrosis. Flavonoid treatment has been demonstrated to alleviate or inhibit pulmonary fibrosis by modulating Smad-dependent and -non-dependent TGF-β mechanisms by modulating intracellular NOX expression.

• Tuberculosis and Respiratory Diseases
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• v.50 no.4
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• pp.450-461
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• 2001

Background : The underlying pathogenesis of radiation-induced lung fibrosis (RTLF) has not been very well defined. However, the role of TGF-$\beta$ in the generation of RTLF has been a major focus because there is an increase in the expression of both the TGF-${\beta}m$-RNA and its protein preceding RTLF lesions. The down stream signal after a TGF-$\beta$ stimulated lung fibrosis includes the activation of many mediators such as Smad and c-Jun N-terminal kinase (JNK) through TAK1. It is we hypothesized that JNK activation may play a pivotal role in RTLF pathogenesis through increased transcription of the fibrogenic cytokines. The present study evaluates JNK activity in alveolar macrophages after irradiation and the relationship between JNK activity and the amount of collagen in the lung tissues. Methods : C57BL/6 mice(20-25 gr, males) received chlorotetracycline(2g/L) in their drinking water 1 week prior to irradiation and continuously there after. The mice were irradiated once with 1400 cGy of $60CO{\gamma}$-ray over the whole chest. The cellular composition of the whole lung bronchoalveoalr lavage fluids(BALF), elastin expression in the lung tissues, the level of hydroxyproline in lung tissues, and an in vitro JNK assay was measured before irradiation and one, four, and eight weeks after irradiation (RT). Results : The volumes of BALF retrieved from instilled 4 mL of saline with 2% heparin were 3.7-3.8 mL for each group. The cell numbers were similar before($4.1{\times}10^4{\pm}0.5{\times}10^4/mL$) and 1 week($3.1{\times}10^4{\pm}0.5{\times}10^4/mL$) after RT. At four and eight weeks after RT, the cell number reached to $14.0{\times}10^4{\pm}1.5{\times}10^4mL$ and $10.0{\times}10^4{\pm}1.3{\times}10^4/mL$, respectively. There we no changes in the lymphocytes and neutrophils population observed in the BALF after RT. The H-E stain of the lung tissues did not show any structural and fibrotic change in the lung tissues at 4 and 8 weeks after RT. In addition, the amount of elastin and collagen were not different on Verhoeff staining of the lung tissues before RT to eight weeks after RT. The hydroxyproine content was measured with the left lung dissected from the left main bronchus. The lung were homogenized and hydrolyzed with 6 N Hel for 12 hours at $110^{\circ}C$ then measured as previously described. The content of hydroxyproline, standardized with a lung protein concentration, reached a peak 4 weeks after RT, and thereafter showed a plateau. AnIn vitro JNK assay using c-$Jun_{1-79}$-GST sepharose beads were performed with the alveolar macrophages obtained from the BAL. JNK activity was not detected prior to RT, However, the JNK activity increased from one week after RT and reached a peak four weeks after RT. Conclusion : JNK may be involved in the pathogenesis because the JNK activity showed similar pattern observed with the hydroxyproine content. However, it is necessary to clarify that the JNK increases the transcription of fibrogenic cyiokines through the transcription factor.

• Journal of Yeungnam Medical Science
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• v.11 no.1
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• pp.186-192
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• 1994

Amiodarone has a potent suppressive effect on supraventricular and ventricular dysrhythmias, so has widely used as a class III antiarrhythmic agent. However, significant side effects were noted in over 50% of patients treated. Pulmonary toxicity represents the most serious adverse raeaction limiting the clinical efficacy of this new antidysrhythmic drug. A 66-year-old male had received amiodarone 200mg/day for 7 months to control high grade ventricular premature contraction and was admitted due to dyspnea on exertion for 1 week. At the time of admission end-inspiratory crepitant rale was heard on auscultation. The roentgenogram of his chest revealed reticular and granular radioopaque densities on both lower lung fields and high resonance CT revealed interstitial fibrosis and pneumonic consolidations on the periphery of the both middle and lower lobes. Trans-bronchoscopic lung biopsy revealed nonspecific intersitial fibrosis. The laboratory findings were non-specific. We present a case of amiodarone-induced interstitial pulmonary disease clinically improved by cortico-steroid therapy.

• Journal of Haehwa Medicine
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• v.29 no.1
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• pp.1-17
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• 2020

Objectives : The objectives of this study is to develop a mouse model similar to Taeeum-type by inducing Lung fibrosis with bleomycin, and to determine adequate concentration of bleomycin. Methods : The subjects were divided into six groups: normal, obesity induced group, and bleomycin administered 0.015U, 0.03U, 0.06U, and 0.09U(U/100g bw) concentrations respectively. Each concentration of bleomycin was dissolved in distilled water, and administered through Intra-Nazal-Trachea injection method. Food intake and body weight were measured at regular time weekly. At the end of the experiment, blood was gathered by cardiac puncture for biochemical examinations, organs were removed for histological examinations, and weigh and mRNA genes was analyzed. Result : Mice administered with bleomycin at 0.015U and 0.03U showed body and fat weight gain, and increased blood total cholesterol, LDL-cholesterol, glucose, and free fatty acid level. Fat related genes also showed higher level than the control group. Obesity was most strongly induced in the mice administered with 0.03U of bleomycin. On the other hand, when bleomycin was administered at concentrations above 0.06U, a model of obesity mouse was not created due to rapid emphysema inflammation and weakness. Conclusions : Mice were most vulnerable to obesity when bleomycin was administered at a concentration of 0.3 to cause liver damage. Bleomycin concentration over 0.06U did not cause obesity-induced mice, due to severe damage in liver.

• Journal of the Korean Society of Radiology
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• v.82 no.4
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• pp.826-837
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• 2021

Immunoglobulin G4-related disease (IgG4-RD) is a chronic inflammatory condition involving multiple organs, including the salivary or lacrimal glands, orbit, pancreas, bile duct, liver, kidney, retroperitoneum, aorta, lung, and lymph nodes. It is histologically characterized by tissue infiltration with lymphocytes and IgG4-secreting plasma cells, storiform fibrosis, and obliterative phlebitis. In the thoracic involvement of IgG4-RD, mediastinal lymphadenopathy and perilymphangitic interstitial thickening of the lung are the most common findings. Peribronchovascular and septal thickening and paravertebral band-like soft tissue are characteristic findings of IgG4-RD. Other findings include pulmonary nodules or masses, ground-glass opacity, alveolar interstitial thickening, pleural effusion or thickening, mass in the chest wall or mediastinum, and arteritis involving the aorta and coronary artery. Radiologic differential diagnosis of various malignancies, infections, and inflammatory conditions is needed. In this review, we describe the imaging findings of IgG4-RD and the radiologic differential diagnoses in the thorax.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.5 no.1
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• pp.77-101
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• 1999

l. Sojeokbaekchoolsan compound treatment decreased pulmonary fibrosis induced by Bleomycin. 2. At 1 and 2 days after bleomycin treatment, Sojeokbaekchoolsan compound treatment decreased the number of neutrophils in bronchoalveolar lavage than those of bleomycin alone treatment. 3. Sojeokbaekcoolsan compound treatment increased the Fc receptor mediated rosette activity of alveolar macrophage decreased by bleomycin treatment. 4, At 10 days after bleomycin treatment, Sojeokbaekchoolsan compound treatment decreased the lipid peroxidation of lung tissue than those of bleomycin alone treatment. 5. Anti-tumor activity of Sojeokbaekchoolsan and bleomycin compound group was higher than those of bleomycin alone treated group to ascitic tumor caused by Sarcoma-180 tumor cells.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.05a
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• pp.68-68
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• 2002

• Journal of the Korean Society of Radiology
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• v.81 no.3
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• pp.688-700
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• 2020

Purpose To compare the incidence, survival rate, and CT findings of acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) between patients with and without lung cancer. Materials and Methods From June 2004 to July 2018, 89 consecutive patients diagnosed with IPF were included. Among them, 26 patients had IPF with lung cancer (IPF-LCA), and 63 patients had IPF alone. The clinical characteristics and CT findings associated with IPF, lung cancer, and AE were reviewed. Surgery and chemotherapy were performed for 6 and 23 cases of lung cancer, respectively, as the first- or second-line anticancer treatment. The overall survival, CT findings, disease-free period before AE, and duration from the onset of AE to death were compared. Results The incidence of AE was 61.5% in the IPF-LCA group and 58.7% in the IPF group (p = 0.806). The mean overall survival in the IPF-LCA and IPF groups were 16.8 and 83.0 months, respectively (p < 0.001). The mean durations from the start of the lung cancer treatment to the onset of AE were 16.0 and 4.6 months in cases of surgical treatment and chemotherapy, respectively. In comparison of death from AE, the survival rate was significantly lower in the IPF-LCA group than in the IPF group (p = 0.008). In the CT findings associated with AE, the IPF-LCA group tended to have a peribronchial (p < 0.001) or asymmetric distribution (p = 0.016). Conclusion In patients with IPF who develop lung cancer, the rate of death from AE is higher than that in patients with IPF alone. They tend to have unusual CT patterns associated with AE, such as a peribronchial or asymmetric distribution.