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ABSTRACT: ABSTRACT Although neutropenia recovery is associated with deterioration of preexisting acute lung injury (ALI), there are few reports of the preventive strategies. Statins have been found to attenuate inflammatory responses in murine models of lipopolysaccharide (LPS)-induced ALI. The aim of this study was to determine whether pravastatin could attenuate ALI during neutropenia recovery in mice. Cyclophosphamide was administered to mice to induce neutropenia. Mice were given intratracheal LPS 7 days after cyclophosphamide administration, after which pravastatin was administered by intraperitoneal injection. In order to study the effects of pravastatin, mice were killed on day 5. Pravastatin attenuated the pulmonary edema and histopathological changes of LPS-induced lung injury. The accumulation of neutrophils and the concentrations of TNF-α, IL-1β, IL-6, and MPO in BAL fluids were also effectively inhibited by pravastatin. The expression levels of Toll-like receptor 4, nuclear factor kappa B, tumor growth factor-β and matrix metalloproteinase-9 were significantly reduced by pravastatin. Taken together, pravastatin significantly attenuated LPS-induced ALI during neutropenia recovery. These results provide evidence for the potential of pravastatin in the treatment of ALI during neutropenia recovery.
Experimental Lung Research 01/2013; · 1.22 Impact Factor
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ABSTRACT: Recent evidence suggests that acetylcholine acting through muscarinic receptors may play an inhibitory role in the mechanisms that drive the structural changes in the airways called airway remodeling. The novel anticholinergic drug tiotropium bromide, which selectively antagonizes muscarinic receptors, especially the M3 subtype, and is long acting, could be beneficial in attenuating airway remodeling in chronic asthma.
To investigate the effect of tiotropium bromide on parameters of airway remodeling, including smooth muscle hypertrophy and peribronchial thickening, in a mouse model of chronic asthma.
To develop the murine models of acute and chronic asthma, BALB/c mice were sensitized and challenged to ovalbumin for 1 and 3 months, respectively. The effect of tiotropium bromide (0.1mM in 50 μL of phosphate-buffered saline) on pulmonary inflammation and remodeling was evaluated. The expression of muscarinic receptors M2 and M3 was analyzed.
In the chronic asthma model, the tiotropium-treated group significantly decreased smooth muscle thickening and peribronchial collagen deposition. As for pulmonary inflammation, the chronic asthma model had a reduction of inflammatory cells and T(H)2 cytokines by tiotropium bromide, but the effects in the asthma acute model were reversed. In the chronic asthma model, expression of the M3 receptor was inhibited and that of the M2 receptor was elevated by the administration of tiotropium bromide.
This study suggests that tiotropium bromide might have an inhibitory effect on airway remodeling in a murine model of chronic asthma. Differential effects on muscarinic receptor subtypes may explain why tiotropium bromide has different effects on acute and chronic asthma.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 07/2012; 109(1):29-35. · 2.83 Impact Factor
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ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is a lethal parenchymal lung disease characterized by myofibroblast proliferation. Alveolar epithelial cells (AECs) are thought to produce myofibroblasts through the epithelial to mesenchymal transition (EMT). Receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface receptors whose activation is associated with renal fibrosis during diabetes and liver fibrosis. RAGE is expressed at low basal levels in most adult tissues except the lung. In this study, we evaluated the interaction of ligand advanced glycation end products (AGE) with RAGE during the epithelial to myofibroblast transition in rat AECs. Our results indicate that AGE inhibited the TGF-β-dependent alveolar EMT by increasing Smad7 expression, and that the effect was abolished by RAGE siRNA treatment. Thus, the induction of Smad7 by the AGE-RAGE interaction limits the development of pulmonary fibrosis by inhibiting TGF-β-dependent signaling in AECs.
Experimental and Molecular Medicine 07/2011; 43(9):517-24. · 2.48 Impact Factor
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ABSTRACT: The tyrosine kinase inhibitor imatinib mesylate was developed as an inhibitor of the kinase activity of BCR-ABL. However, imatinib also has potent inhibitory activity against the platelet-derived growth factor receptor (PDGFR). Nilotinib is approved for treating patients with chronic myeloid leukemia showing resistance or intolerance to imatinib. Like imatinib, nilotinib selectively inhibits the tyrosine kinase activity of PDGFR.
We examined the effect of imatinib and nilotinib on acute lung injury and pulmonary fibrosis in a mouse model.
Mice were treated by intratracheal instillation of bleomycin. Imatinib or nilotinib were administered by oral gavage. To study the early inflammatory and late fibrotic phases of lung injury, mice were sacrificed on days 3, 7, 14 and 21 after bleomycin instillation. Results: Histopathology showed that imatinib and nilotinib attenuated the extent of lung injury and fibrosis. The numbers of inflammatory cells and levels of IL-6, IL-1β and tumor necrosis factor-α were decreased in the imatinib and nilotinib groups on days 3 and 7. Imatinib and nilotinib therapy significantly reduced the levels of hydroxyproline on days 14 and 21, which was accompanied by decreased expression levels of transforming growth factor (TGF)-β1 and PDGFR-β. Imatinib and nilotinib also significantly reduced the expression levels of the genes for TGF-β1 and platelet-derived growth factor (PDGF). Imatinib and nilotinib treatment also significantly inhibited the PDGF-induced proliferation of lung fibroblasts in vitro. When imatinib or nilotinib was given 7 days after the instillation of bleomycin, only nilotinib attenuated pulmonary fibrosis.
Imatinib and nilotinib attenuated bleomycin-induced acute lung injury and pulmonary fibrosis in mice. In a therapeutic model, nilotinib showed more potent antifibrotic effects than imatinib.
Respiration 06/2011; 82(3):273-87. · 2.26 Impact Factor
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Chin Kook Rhee,
Jin Woo Kim,
Chan Kwon Park,
Joo Sang Kim,
Ji Young Kang,
Seung Joon Kim,
Seok Chan Kim,
Soon Suk Kwon,
Young Kyoon Kim,
Sung Hak Park, Sook Young Lee
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ABSTRACT: Asthma is characterized by airway hyperresponsiveness (AHR), inflammation and remodeling. The tyrosine kinase inhibitor imatinib mesylate was developed to inhibit BCR-ABL kinase activity; however, it also has potent inhibitory activity against the c-Kit and platelet-derived growth factor receptors. The present study aimed to determine whether imatinib suppresses airway smooth muscle (ASM) remodeling and whether its effect is associated with growth factors such as transforming growth factor (TGF)-β1 and stem cell factor (SCF).
We developed a mouse model of airway remodeling, which includes smooth muscle thickening, in which ovalbumin (OVA)-sensitized mice were repeatedly exposed to intranasal OVA administration twice a week for 3 months. Mice were treated with imatinib during the OVA challenge.
Mice chronically exposed to OVA developed sustained eosinophilic airway inflammation and AHR compared with control mice. In addition, the mice chronically exposed to OVA developed features of airway remodeling, including thickening of the peribronchial smooth muscle layer. Administration of imatinib significantly inhibited the development of AHR, eosinophilic inflammation and, importantly, ASM remodeling in mice chronically exposed to OVA. Imatinib treatment significantly reduced the levels of interleukin-4, -5 and -13. In addition, TGF-β1 and SCF were significantly reduced in the imatinib-treated animals.
These results suggest that imatinib administration can prevent not only airway inflammation, but also airway remodeling associated with chronic allergen challenge. Imatinib may provide a clinically attractive therapy for chronic severe asthma.
International Archives of Allergy and Immunology 02/2011; 155(3):243-51. · 2.40 Impact Factor
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Jin Woo Kim,
Chin Kook Rhee,
Tae Jung Kim,
Yong Hyun Kim,
Sang Haak Lee,
Hyung Kyu Yoon,
Seok Chan Kim, Sook Young Lee,
Soon Suk Kwon,
Kwan Hyung Kim,
Young Kyoon Kim
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ABSTRACT: 1. Pravastatin is best known for its antilipidemic action. Recent studies have shown that statins have immunomodulatory and anti-inflammatory effects. The present study aimed to determine whether or not pravastatin can attenuate acute lung injury and fibrosis in a mouse model. 2. Bleomycin was given to C57BL6 mice through intratracheal instillation. Pravastatin was given through intraperitoneal injection. To study the effect of pravastatin on the early inflammatory phase and the late fibrotic phase, mice were killed on days 3, 7, 14 and 21. 3. Pravastatin attenuated the histopathological change of bleomycin-induced lung injury and fibrosis. The accumulation of neutrophils and increased production of tumor necrosis factor-α in bronchoalveolar lavage fluid were inhibited in the early inflammatory phase. Pravastatin effectively inhibited the increase of lung hydroxyproline content induced by bleomycin. Furthermore, pravastatin reduced the increased expression of transforming growth factor (TGF)-β1, connective tissue growth factor (CTGF), RhoA and cyclin D1. The increased levels of TGF-β1 and CTGF mRNA expression were also significantly inhibited by pravastatin. 4. Pravastatin effectively attenuated bleomycin-induced lung injury and pulmonary fibrosis in mice. Our results provide evidence for the therapeutic potential of pravastatin in the treatment of acute lung injury and pulmonary fibrosis.
Clinical and Experimental Pharmacology and Physiology 11/2010; 37(11):1055-63. · 1.85 Impact Factor
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Ji Young Kang,
Jin Woo Kim,
Ju Sang Kim,
Seung Joon Kim,
Sang Haak Lee,
Soon Suk Kwon,
Young Kyoon Kim,
Hwa Sik Moon,
Jeong Sup Song,
Sung Hak Park, Sook Young Lee
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ABSTRACT: Airway remodeling is one of the cardinal features of asthma and is thought to play a pivotal role in refractory or persistent asthma. Immunoglobulin E (IgE) has a major effect on the pathogenesis of asthma. The aim of this study was to investigate the effects of anti-IgE antibody not only on airway inflammation and bronchial hyperresponsiveness, but also on airway remodeling in a murine model of chronic asthma.
The authors developed a mouse model of chronic asthma in which ovalbumin (OVA)-sensitized female BALB/c-mice were exposed to intranasal OVA administration twice a week for 3 months. Anti-IgE antibodies were administered intravenously starting on the 38th day and once a month thereafter for 3 months during the intranasal OVA challenge.
Mice that were chronically exposed to OVA developed sustained eosinophilic airway inflammation and airway hyperresponsiveness (AHR) to methacholine and showed increased levels of collagen, hydroxyproline, and alpha-smooth muscle actin, as compared with control mice. Treatment with anti-IgE antibody inhibited the development of AHR, eosinophilic inflammation, and airway remodeling. Moreover, anti-IgE antibody treatment reduced the levels of interleukin (IL)-5 and IL-13 in the bronchoalveolar lavage fluids, although it did not affect the levels of IL-10, transforming growth factor-beta, and activin A.
These results suggest that anti-IgE antibody treatment modulates the airway inflammation and remodeling associated with chronic allergen challenge. The inhibition of inflammation may be related to the regulation of Th2 cytokines. However, the mechanisms underlying the blocking of airway remodeling by anti-IgE antibody remain to be elucidated.
Journal of Asthma 05/2010; 47(4):374-80. · 1.52 Impact Factor
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Seung Joon Kim,
Jin Woo Kim,
Yong Hyun Kim,
Sang Haak Lee,
Hyoung Kyu Yoon,
Chi Hong Kim,
Joong Hyun Ahn,
Jung Mi Lee,
Jin Sook Kim,
Seok Chan Kim, Sook Young Lee,
Soon Seog Kwon,
Young Kyoon Kim
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ABSTRACT: Tranilast has been used in allergic diseases because of its inhibitory effect on mast cells; it also has an anti-fibrotic effect in several diseases. Pentoxifylline (PTX), a methylxanthine derivative, is a potent anti-inflammatory drug that is known to manifest its effect through the inhibition of Th1 cytokine, but with an uncertain effect on Th2 cytokine. Seven-week-old female BALB/c mice were studied as a chronic asthma model. The mice were challenged with house dust mite (HDM) antigen for 7 weeks. Each group of mice was given an intraperitoneal injection of tranilast, PTX, or tranilast plus PTX before antigen administration. In this mouse model of chronic asthma, tranilast, and PTX each had an inhibitory effect on airway remodeling as well as on airway hyperresponsiveness (AHR) and airway inflammation. The improved events of these drugs were related with the inhibition of the Th2 cytokine IL-13 and TGF-beta 1. Immunohistochemical analysis showed that decreases in the peribronchial trichrome stained area in each treatment group were associated with improvements in the peribronchial smooth muscle hyperplasia, collagen type I, and collagen type III deposition. These drugs could have potential beneficial effects on chronic asthma, especially with respect to airway remodeling.
Journal of Asthma 11/2009; 46(9):884-94. · 1.52 Impact Factor
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Hae-Seong Nam, Sook Young Lee,
Seung Jun Kim,
Ju Sang Kim,
Soon Seog Kwon,
Young Kyoon Kim,
Kwan Hyung Kim,
Hwa Sik Moon,
Jeong Sup Song,
Sung Hak Park,
Seok Chan Kim
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ABSTRACT: Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that has been implicated in many aspects of the airway pathology in asthma. TNF-alpha blocking strategies are now being tried in asthma patients. This study investigated whether TNF-alpha blocking therapy inhibits airway inflammation and airway hyperresponsiveness (AHR) in a mouse model of asthma. We also evaluated the effect of TNF-alpha blocking therapy on cytokine production and adhesion molecule expression.
Ovalbumin (OVA) sensitized BALB/c female mice were exposed to intranasal OVA administration on days 31, 33, 35, and 37. Mice were treated intraperitoneally with soluble TNF-alpha receptor (sTNFR) during the OVA challenge.
There were statistically significant decreases in the numbers of total cell and eosinophil in bronchoalveolar lavage fluid (BALF) in the sTNFR treated group compared with the OVA group. However, sTNFR-treatment did not significantly decrease AHR. Anti-inflammatory effect of sTNFR was accompanied with reduction of T helper 2 cytokine levels including interleukin (IL)-4, IL-5 and IL-13 in BALF and vascular cell adhesion molecule 1 expression in lung tissue.
These results suggest that sTNFR treatment can suppress the airway inflammation via regulation of Th2 cytokine production and adhesion molecule expression in bronchial asthma.
Yonsei medical journal 09/2009; 50(4):569-75. · 0.77 Impact Factor
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ABSTRACT: Therapeutic modalities of airway remodeling in asthma have proved to be unsuccessful regarding reversing the previously established chronic airway changes. Recently, the potential of plasmid DNA to inhibit the Th2 immune response has been demonstrated in animal models of asthma. Bacillus Calmette-Guerin (BCG) immunization also induced immunomodulation, which appeared to be reliant on the properties of the interferon-gamma that was produced. Mice were immunized with house dust mite extract (HDM). At the 3 week point, we injected BCG subcutaneously into mice on three successive weeks. One week after the BCG injection, we immunized mice with the DNA plasmid encoding for murine T-cell epitope on Dermatophagoide pteronyssinus 2 thrice weekly. At 9 weeks after immunization, we measured airway responsiveness. Twenty four hours later, we performed bronchoalveolar lavage and histological examinations. Co-administration of DNA vaccination and BCG resulted in a partial suppression of the overproduction of goblet cells and the thickness of the peribronchial smooth muscle in ongoing allergic responses. In the bronchoalveolar lavage fluid, the number of total cells and eosinophils was reduced, and regarding the change of cytokines, the concentration of IL-4 was also decreased, but interferon-gamma was increased in the co-administration group, opposed to the asthma group. These results suggest that co-administration of vaccination with the DNA encoding T-cell epitope and BCG are effective regarding ongoing allergic response and might constitute an ideal method for combating allergic disease in the future.
Journal of Asthma 07/2009; 43(5):345-53. · 1.52 Impact Factor
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ABSTRACT: Endoscopic thoracic sympathectic denervation (ESD) is a procedure used in primary hyperhidrosis and upper extremity ischemia. Bronchial tone is affected by the sympathetic and parasympathetic nervous systems and bronchial asthma is associated with an imbalance between them. The aim of this study was to evaluate the effects of ESD on pulmonary function and bronchial hyperresponsiveness (BHR).
Fifty-eight patients with primary hyperhidrosis (n = 54) or upper limb ischemia (n = 4) were included. Spirometry and bronchial provocation test with methacholine was performed before and 4 weeks after ESD.
Forced expiratory volume in 1 second (FEV(1)) and forced vital capacity (FVC) were significantly decreased early after ESD (from 4.67 +/- 0.84 L and 4.36 +/- 0.85 L to 4.12 +/- 0.78 L and 3.84 +/- 0.82 L, respectively), although no patient complained of an aggravation of respiratory symptoms. Twelve patients (21%) had a positive response to methacholine provocation preoperatively, and all remained positive post surgery. The provocative concentration of methacholine, which brought about a 20% decrease in the FEV(1) in the patients, was not significantly changed after surgery (from 5.1 +/- 4.3 to 4.6 +/- 4.6). Of 46 patients who had a negative result for methacholine challenge preoperatively, 12 (26%) became positive after surgery. In terms of the level of sympathectomy, T3 sympathectomy significantly increased the ratio of patients exhibiting a positive response to methacholine (from 19% to 34%, respectively) (p < 0.005).
Thoracic sympathectomy can adversely affect lung function early after surgery, although the clinical significance is uncertain. It may also exert an influence on the development of bronchial hyperresponsiveness, especially when performed at the T3 level.
Journal of Asthma 04/2009; 46(3):276-9. · 1.52 Impact Factor
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ABSTRACT: Asthma is characterized by airway hyperresponsiveness (AHR), inflammation and remodeling. Peroxisome proliferator-activated receptors (PPARs) were reported to regulate inflammatory responses in many cells. In this study we examined the effect of a PPAR-gamma agonist on the airway smooth muscle and the production of transforming growth factor (TGF)-beta1 and vascular endothelial growth factor (VEGF).
We developed a mouse model of airway remodeling including smooth muscle thickening in which ovalbumin (OVA)-sensitized mice were repeatedly exposed to intranasal OVA administration twice a week for 3 months. Mice were treated intranasally with ciglitazone during OVA challenge.
Mice chronically exposed to OVA developed sustained eosinophilic airway inflammation and AHR to methacholine compared with control mice. In addition, the mice chronically exposed to OVA developed features of airway remodeling, including thickening of the peribronchial smooth muscle layer. Administration of ciglitazone intranasally significantly inhibited the development of AHR, eosinophilic inflammation, and importantly, airway smooth muscle remodeling in mice chronically exposed to OVA. However, intranasal ciglitazone treatment did not reduce the level of TGF-beta1 and VEGF in bronchoalveolar lavage fluid.
These results suggest that intranasal administration of ciglitazone can prevent not only airway inflammation, but also airway remodeling associated with chronic allergen challenge. The mechanism might not be related to VEGF and TGF production. Further study is needed.
International Archives of Allergy and Immunology 12/2008; 148(4):289-96. · 2.40 Impact Factor
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ABSTRACT: Extranodal marginal zone lymphoma is a low-grade B cell lymphoma that presents with an indolent clinicopathologic nature. Although this tumor can occur in various sites, including the gastrointestinal tract and lungs, it develops and spreads extremely rarely along the trachea and central airway. We report a case of extranodal lymphoma of mucosa-associated lymphoid tissue with tracheobronchial involvement. An 83-year-old woman presented with a cough and dyspnea. Bronchoscopic evaluation confirmed diffuse, multiple nodular lesions in both the trachea and large bronchi, and she was diagnosed with an extranodal marginal zone lymphoma of the tracheobronchial tree. After systemic chemotherapy, she survived for more than 18 months.
Yonsei Medical Journal 11/2008; 49(5):860-3. · 1.14 Impact Factor
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ABSTRACT: Type 2N von Willebrand disease (vWD) can be confused with hemophilia A due to decreased factor VIII levels and a bleeding tendency, and differential diagnosis is of importance for providing the optimal treatment and genetic counseling. For the accurate diagnosis of type 2N vWD, von Willebrand Factor (vWF) function tests, multimer assay and gene mutation analysis are needed. The patient was a 38-yr-old Nepalese woman with a history of bleeding manifestations from childhood, such as hemarthrosis, intramuscular hematoma, and menorrhagia. Family history revealed that her mother and elder brothers also had bleeding manifestations from childhood. When she had a laparotomy in 1991, she was diagnosed as hemophilia A with factor VIII level of 3.6% and was transfused with whole blood, factor VIII and cryoprecipitates. In June 2007, she was admitted to our hospital for further evaluation of bleeding tendency. Blood tests revealed normal CBC; bleeding time, 2 min; PT, 14.9 sec (11-14 sec); aPTT, 51.2 sec (24-38 sec); and factor VIII, 4.9% (50-150%). The prolonged aPTT was corrected by 1:1 mixing test to the levels of 106% and 84%, respectively, before and after 2 hr-incubation at 37degrees C. No abnormalities were found in the vWF antigen level (71.3%), ristocetin cofactor assay (130.4%), and multimer assay. Direct DNA sequencing of the VWF gene revealed homozygous missense mutation located in exon 19, c.2446C>T (p.Arg816Trp), confirming the diagnosis of type 2N vWD.
The Korean Journal of Laboratory Medicine 08/2008; 28(4):258-61. · 0.63 Impact Factor
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ABSTRACT: Airway smooth muscle growth contributes to the mechanism of airway hyperresponsiveness (AHR) in asthma. Although current steroid use demonstrates anti-inflammatory activity, there is little reported on the action of corticosteroid on smooth muscle of the asthmatic airway. The present study investigated the effect of inhaled corticosteroid on the thickening of airway smooth muscle in bronchial asthma. We developed a mouse model of airway remodeling including smooth muscle thickening in which ovalbumin (OVA)-sensitized female BALB/c-mice were repeatedly exposed to intranasal OVA administration twice a week for 3 months. Mice were treated intranasally with fluticasone during the OVA challenge. Mice chronically exposed to OVA developed sustained eosinophilic airway inflammation compared with control mice. In addition, the mice chronically exposed to OVA developed features of airway remodeling, including thickening of the peribronchial smooth muscle layer. Intranasal administration of fluticasone inhibited the development of eosinophilic inflammation, and importantly, thickening of the smooth muscle layer. Moreover, intranasal fluticasone treatment reduced the transforming growth factor (TGF)-beta 1 level in bronchoalveolar lavage fluid and regulated active TGF-beta 1 signaling with a reduction in the expression of phospho-Smad2/3 and the concomitant up-regulation of Smad7 in lung tissue sections. These results suggest that intranasal administration of fluticasone can modulate the remodeling of airway smooth muscle via regulation of TGF-beta 1 production and active TGF-beta 1 signaling.
Pulmonary Pharmacology & Therapeutics 02/2008; 21(1):14-9. · 2.80 Impact Factor
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Joong Hyun Ahn,
Chi Hong Kim,
Yong Hyun Kim,
Seung Joon Kim, Sook Young Lee,
Young Kyoon Kim,
Kwan Hyoung Kim,
Hwa Sik Moon,
Jeong Sup Song,
Sung Hak Park,
Soon Seog Kwon
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ABSTRACT: Although animal models with ovalbumin have been used to study chronic asthma, there are difficulties in inducing recurrence as well as in maintaining chronic inflammation in this system. Using a murine model of house dust mite (HDM)-induced bronchial asthma, we examined the airway remodeling process in response to the chronic exposure to HDM. During the seventh and twelfth weeks of study, HDM were inhaled through the nose for three consecutive days and airway responsiveness was measured. Twenty-four hours later, bronchoalveolar lavage and histological examination were performed. The degree of overproduction of mucus, subepithelial fibrosis, and the thickness of the peribronchial smooth muscle in the experimental group was clearly increased compared to the control group. In addition, HDM-exposed mice demonstrated severe airway hyperreactivity to methacholine. In the bronchoalveolar lavage fluid, the number of total cells and eosinophils was increased; during the twelfth week, the number of neutrophils increased in the experimental group. With regard to changes in cytokines, the concentrations of IL-4, IL- 13, and transforming growth factor-beta (TGF-beta) were increased in the experimental group. The data suggest that eosinophils, IL-4, IL-13, and TGF-beta might play an important role in the airway remodeling process and that neutrophils may be involved with increased exposure time.
Journal of Korean Medical Science 01/2008; 22(6):1026-33. · 0.99 Impact Factor
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ABSTRACT: Rotavirus is the most common cause of childhood gastroenteritis during winter season. Rapid, accurate diagnosis is essential for preventing severe complications of rotaviral gastroenteritis. The sensitivity and specificity of five detection test kits for rotavirus including latex agglutination (LAT), enzyme immunoassay (EIA) and three immunochromatographic methods (ICG) were evaluated in this study.
A total of 95 stool samples collected from patients with acute gastroenteritis were studied. The test kits were as follows: LAT (Slidex latex, bioMerieux Vitek, France); three kinds of ICG (Dipstick ROTA, Eiken, Japan; SAS Rota Test, SA Scientific, Inc., USA; and ASAN Easy Test Rota strip, ASAN Pharmaceutical., Korea); and EIA (VIDAS Rotavirus, bioMerieux Vitek). The samples showing discordant results were reevaluated by reverse-transcription (RT) PCR and clinical manifestations.
Of a total of 95 cases, 56 (58.9%) were positive and 39 (41.1%) were negative. Thirteen cases showed discordant results. Sensitivity and specificity were, respectively, 85.7% and 100% for LAT, 100% and 95% for both of Dipstick ROTA and SAS Rota, 86.7% and 87.5% for ASAN Rota strip and 98.1% and 97.3% for EIA.
LAT was rapid and easy to perform and showed the lowest sensitivity among the five test kits. ICG showed a good agreement with EIA and RT-PCR. EIA was the best in respect of sensitivity and specificity, but difficulty in interpretations of equivocal results and time-consuming procedures were limitations. In conclusion, ICG, which is easy to perform at a low cost, may be an optimal method in place of LAT for the detection of rotavirus.
The Korean Journal of Laboratory Medicine 01/2008; 27(6):437-41. · 0.63 Impact Factor
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Seung Joon Kim,
Chi Hong Kim,
Joong Hyun Ahn,
Myung Sook Kim,
Seok Chan Kim, Sook Young Lee,
Soon Seog Kwon,
Young Kyoon Kim,
Kwan Hyoung Kim,
Hwa Sik Moon,
Jeong Sup Song,
Sung Hak Park
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ABSTRACT: During the course of establishing an animal model of chronic asthma, we tried to elucidate the time sequence of airway hyperresponsiveness (AHR), airway inflammation, airway remodeling, and associated cytokines. Seven-week-old female BALB/c mice were studied as a chronic asthma model using ovalbumin (OVA). After sensitization, mice were exposed twice weekly to aerosolized OVA, and were divided into three groups depending on the duration of 4 weeks, 8 weeks, and 12 weeks. At each time point, airway responsiveness, inflammatory cells, cytokines in bronchoalveolar lavage fluids (BALF), serum OVA-specific IgE, IgG1, IgG2a, and histological examination were carried out. AHR to methacholine, increased levels of OVA-specific IgG1 and IgG2a, and goblet cell hyperplasia were continuously sustained at each time point of weeks. In contrast, we observed a time-dependent decrease in serum OVA-specific IgE, BALF eosinophils, BALF cytokines such as IL-13, transforming growth factor-beta1, and a time-dependent increase in BALF promatrix metalloproteinase-9 and peribronchial fibrosis. In this OVA-induced chronic asthma model, we observed airway remodelings as well as various cytokines and inflammatory cells being involved in different time-dependent manners. However, increased airway fibrosis did not directly correlate with a further increase in airway hyperresponsiveness.
Journal of Korean Medical Science 05/2007; 22(2):183-91. · 0.99 Impact Factor
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ABSTRACT: Vascular endothelial growth factor (VEGF) is a potent proangiogenic cytokine, and it also increases vascular permeability. It is well known that VEGF levels are increased in the airway of asthmatic patients. Hypoxia-inducible factor (HIF) induces a rapid and strong increase in VEGF expression.
To evaluate the relationship between VEGF level and clinical characteristics and to determine whether VEGF expression is associated with HIF expression in asthmatic patients.
Bronchoscopy was performed on 30 asthmatic patients and 14 control subjects. The concentration of VEGF in the bronchoalveolar lavage fluid (BALF) was examined using enzyme-linked immunosorbent assay. We measured VEGF, HIF-1alpha, and HIF-2alpha expression on biopsy specimens by means of immunoreactivity.
The VEGF level in the BALF was significantly higher in asthmatic patients than in controls. The VEGF level correlated with eosinophil counts in the BALF in asthmatic subjects (r = 0.501; P < .01). However, the VEGF level did not correlate with percentage of forced expiratory volume in 1 second and airway hyperresponsiveness. Asthmatic patients exhibited higher VEGF, HIF-1alpha, and HIF-2alpha immunoreactivity in the submucosa than did controls. Furthermore, VEGF expression correlated significantly with HIF-1alpha (r = 0.614; P = .02) and HIF-2alpha (r = 0.881; P = .001) expression.
These findings suggest that VEGF may play an important role in inflammation and that VEGF level is related to HIF in bronchial asthma.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 01/2007; 97(6):794-9. · 2.83 Impact Factor
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ABSTRACT: Matrix metalloproteinase (MMP)-9 plays an important role in the pathogenesis of bronchial asthma. Neovastat, having significant antitumor and antimetastatic properties, is classified as a naturally occurring multifunctional antiangiogenic agent. We evaluated the therapeutic effect of Neovastat on airway inflammation in a mouse model of asthma. BALB/c mice were immunized subcutaneously with ovalbumin (OVA) on days 0, 7, 14, and 21 and challenged with inhaled OVA on days 26, 29, and 31. Neovastat was administrated by gavage (5 mg/kg body weight) three times with 12 h intervals, beginning 30 min before OVA inhalation. On day 32, mice were challenged with inhaled methacholine, and enhanced pause (Penh) was measured as an index of airway hyperresponsiveness. The severity of airway inflammation was determined by differential cell count of bronchoalveolar lavage (BAL) fluid. The MMP-9 concentration in BAL fluid samples was measured by ELISA, and MMP-9 activity was measured by zymography. The untreated asthma group showed an increased inflammatory cell count in BAL fluid and Penh value compared with the normal control group. Mice treated with Neovastat had significantly reduced Penh values and inflammatory cell counts in BAL fluid compared with untreated asthmatic mice. Furthermore, mice treated with Neovastat showed significantly reduced MMP-9 concentrations and activity in BAL fluid. These results demonstrate that Neovastat might have new therapeutic potential for airway asthmatic inflammation.
The Journal of Microbiology 03/2005; 43(1):11-6. · 1.10 Impact Factor
