-
[show abstract]
[hide abstract]
ABSTRACT: Recent reports have suggested that metformin has anti-inflammatory and anti-tissue remodeling properties. We investigated the potential effect of metformin on airway inflammation and remodeling in asthma. The effect of metformin treatment on airway inflammation and pivotal characteristics of airway remodeling were examined in a murine model of chronic asthma generated by repetitive challenges with ovalbumin and fungal-associated allergenic protease. To investigate the underlying mechanism of metformin, oxidative stress levels and AMP-activated protein kinase (AMPK) activation were assessed. To further elucidate the role of AMPK, we examined the effect of 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside (AICAR) as a specific activator of AMPK and employed AMPKα1-deficient mice as an asthma model. The role of metformin and AMPK in tissue fibrosis was evaluated using a bleomycin-induced acute lung injury model and in vitro experiments with cultured fibroblasts. Metformin suppressed eosinophilic inflammation and significantly reduced peribronchial fibrosis, smooth muscle layer thickness, and mucin secretion. Enhanced AMPK activation and decreased oxidative stress in lungs was found in metformin-treated asthmatic mice. Similar results were observed in the AICAR-treated group. In addition, the enhanced airway inflammation and fibrosis in heterozygous AMPKα1-deficient mice were induced by both allergen and bleomycin challenges. Fibronectin and collagen expression was diminished by metformin through AMPKα1 activation in cultured fibroblasts. Therefore metformin reduced both airway inflammation and remodeling at least partially through the induction of AMPK activation and decreased oxidative stress. These data provide insight into the beneficial role of metformin as a novel therapeutic drug for chronic asthma.
Biochemical pharmacology 10/2012; · 4.25 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: There is a need for new anti-asthmatic medications with fewer side effects. NDC-052, an extract of the medicinal herb Magnoliae flos, which has a long history of clinical use, was recently found to have anti-inflammatory effects. Herein, we evaluated the effects of NDC-052 as an add-on therapy in patients with mild to moderate asthma using inhaled corticosteroids (ICS).
In a non-comparative, multi-center trial, 148 patients taking ICS received NDC-052 for eight weeks. We evaluated their forced expiratory volume in one second (FEV1), morning and evening peak expiratory flow rate (AM and PM PEFR), AM/PM asthma symptom scores, visual analogue symptom (VAS) scores, night-time wakening, frequency of short-acting β2-agonist usage, and adverse events.
After eight weeks, both AM and PM PEFRs were significantly improved. Asthma symptom scores, VAS scores, the frequency of nights without awakening, and the frequency of β2-agonist use were also reduced. Most of the adverse drug reactions were mild and resolved spontaneously.
The addition of NDC-052 to ICS had a beneficial effect on asthma control in patients with mild to moderate asthma, with good tolerability and fewer side effects. Further studies are necessary to evaluate the effects of NDC-052 in patients with severe and/or refractory asthma.
The Korean Journal of Internal Medicine 03/2012; 27(1):84-90.
-
[show abstract]
[hide abstract]
ABSTRACT: Chlamydophila pneumoniae infection has been suggested to be associated with severe asthma characterized by persistent airway limitation, which may be related to airway remodelling. We investigated whether C. pneumoniae infection affected the secretion of metalloproteinase-9 (MMP9) and tissue inhibitor metalloproteinase-1 (TIMP1), and altered the responsiveness of inflammatory cells to corticosteroids. Human peripheral blood mononuclear cells (PBMCs) were cultured in vitro in the presence or absence of C. pneumoniae. Secretion of both MMP9 and TIMP1 was strongly suppressed by dexamethasone treatment in uninfected cells. MMP9 secretion was also significantly inhibited by dexamethasone in C. pneumoniae-infected cells, but TIMP1 secretion was not; hence the MMP9 to TIMP1 ratio decreased. Interestingly, expression of human glucocorticoid receptor β, which is believed to confer resistance to corticosteroids, was enhanced by dexamethasone treatment in C. pneumoniae-infected PBMCs. We conclude that C. pneumoniae infection may promote airway remodelling by decreasing the ratio of MMP9 to TIMP1 secreted by inflammatory cells, and by altering cellular responsiveness to corticosteroids.
Journal of Medical Microbiology 01/2012; 61(Pt 5):705-11. · 2.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Oxidative stress is involved in the pathogenesis of asthma, and peroxiredoxins (PRDX) may be critical in controlling intracellular oxidative stress. The aim of this study was to evaluate expressions of PRDX and their hyperoxidized forms in asthmatic individuals.
The levels of expression of PRDX1, PRDX2, PRDX3, and PRDX6 and their hyperoxidized forms (PRDX-SO(3)) were measured in PBMCs from asthma patients and control subjects. In addition, cells from these subjects were treated with hydrogen peroxide (H(2)O(2)) and their intracellular concentrations of reactive oxygen species (ROS) were measured.
The ratios of hyperoxidized to total PRDX (PRDX-SO(3/)PRDX) in PBMCs were significantly higher in asthma patients than in normal subjects and were correlated with disease severity, with the highest ratio seen in patients with severe asthma. Furthermore, H(2)O(2) treatment of PBMCs, particularly lymphocytes, increased intracellular ROS concentrations with greater and more persistent increases observed in cells from asthmatic than from control subjects.
Hyperoxidation of PRDX may serve as a biomarker of asthma severity and may predict enhanced susceptibility to oxidative stress load in PBMCs of asthmatics.
Life sciences 01/2012; 90(13-14):502-8. · 2.56 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Unexplained chronic cough is a common condition without specific causes. A hyperreactivity of the cough reflex has been suggested as a mechanism for inducing chronic cough. We hypothesized that nitrosative stress in the upper airway might play a role in cough hypersensitivity by causing neurochemical abnormalities.
Fifty-one patients with unexplained chronic cough and 27 controls were enrolled. A capsaicin cough provocation test was performed to determine cough sensitivity. Nitrosative stress in the upper airway was assessed by quantifying 3-nitrotyrosine (3-NT) immunostaining in nasal epithelial cells (NECs) and measuring nasal nitric oxide (nNO). The effect of NO on airway epithelium was investigated by measuring the levels of substance P (SP) in nasal lavage fluid and evaluating SP expression in airway epithelial cells.
Based on the results of the capsaicin test, patients were divided into two groups: a cough hypersensitivity (CHS) group and a normal cough sensitivity (NCS) group. The levels of 3-NT immunoreactivity in NECs were significantly higher in CHS (49 ± 2.9%) than in NCS (27 ± 3.3%) and controls (12 ± 1.6%), a pattern that was also reflected in the values of nNO (350 ± 43, 215 ± 23, and 138 ± 23 ppb in CHS, NCS, and controls, respectively). SP concentration was also elevated in nasal lavage fluids from CHS (746 ± 28 pg/mL) compared with that from NCS (624 ± 40 pg/mL) and controls (526 ± 41 pg/mL). SP expression in airway epithelial cells was greatly enhanced by exposure to NO donor, which was attenuated by pretreatment with either NO scavenger or NO synthase inhibitor.
Increased nitrosative stress in the upper airway may play a role in the pathogenesis of unexplained chronic cough with CHS through enhanced secretion of SP.
American Journal of Rhinology and Allergy 01/2012; 26(1):e10-4.
-
[show abstract]
[hide abstract]
ABSTRACT: Airway remodeling may be responsible for irreversible airway obstruction in asthma, and a low post-bronchodilator FEV1/FVC ratio can be used as a noninvasive marker of airway remodeling. We investigated correlations between airway wall indices on computed tomography (CT) and various clinical indices, including post-bronchodilator FEV1/FVC ratio, in patients with asthma.
Volumetric CT was performed on 22 stable asthma patients who were taking inhaled corticosteroids. Airway dimensions were measured at four segmental bronchi using in-house software based on the full-width/half-maximum method. Parameters included luminal area, wall thickness (WT), wall thickness percentage (WT%), wall area percentage (WA%), bronchial-to-arterial diameter (BA) ratio on inspiration CT, airway collapsibility (AC), and air trapping index (ATI). Correlations were analyzed between CT parameters and clinical indices, including %FEV1, FEV1/FVC, FEF(25-75%), and post-bronchodilator FEV1/FVC ratio.
Post-bronchodilator FEV1/FVC showed significant correlations with WT%, WT, BA ratio, AC, and ATI (r=-0.503, -0.576, 0.454, 0.475, and -0.610, respectively). WT showed negative correlations with FEV1/FVC and FEF(25-75%) (r=-0.431 and -0.581), and WT% was negatively correlated with %FEV1, FEV1/FVC, and FEF(25-75%) (r=-0.434, -0.431, and -0.540, respectively). WA% showed correlations with FEF(25-75%) and body mass index (r=-0.459 and 0.453). The BA ratio was positively correlated with %FEV1 (r=0.459) and FEF(25-75%) (r=0.479). AC showed strong positive correlation with FEV1/FVC (r=0.592), and ATI showed negative correlations with FEV1/FVC (r=-0.534) and FEF(25-75%) (r=-0.591).
WT%, WT, BA ratio, and AC on inspiration and expiration CT are good indices for measuring airway remodeling defined by post-bronchodilator FEV1/FVC in stable asthma patients treated with inhaled corticosteroids.
Allergy, asthma & immunology research 04/2011; 3(2):111-7. · 1.91 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Mucus hypersecretion is a clinically important manifestation of chronic inflammatory airway diseases, such as asthma and Chronic obstructive pulmonary disease (COPD). Mucin production in airway epithelia is increased under conditions of oxidative stress. Src homology 2 domain-containing protein tyrosine phosphatase (SHP)-1 suppression is related to the development of airway inflammation and increased ROS levels. In this study, we investigated the role of SHP-1 in mucin secretion triggered by oxidative stress. Human lung mucoepidermoid H292 carcinoma cells were transfected with specific siRNA to eliminate SHP-1 gene expression. Cultured cells were treated with hydrogen peroxide (H(2)O(2)), and Mucin 5AC(MUC5AC) gene expression and mucin production were determined. Activation of p38 mitogen activated protein kinase (MAPK) in association with MUC5AC production was evaluated. N-acetylcysteine (NAC) was employed to determine whether antioxidants could block MUC5AC production. To establish the precise role of p38, mucin expression was observed after pre-treatment of SHP-1-depleted H292 cells with the p38 chemical blocker. We investigated the in vivo effects of oxidative stress on airway mucus production in SHP-1-deficient heterozygous (mev/+) mice. MUC5AC expression was enhanced in SHP-1 knockdown H292 cells exposed to H(2)O(2), compared to that in control cells. The ratio between phosphorylated and total p38 was significantly increased in SHP-1-deficient cells under oxidative stress. Pre-treatment with NAC suppressed both MUC5AC production and p38 activation. Blockage of p38 MAPK led to suppression of MUC5AC mRNA expression. Notably, mucin production was enhanced in the airway epithelia of mev/+ mice exposed to oxidative stress. Our results clearly indicate that SHP-1 plays an important role in airway mucin production through regulating oxidative stress.
Biochemical and Biophysical Research Communications 02/2010; 393(1):137-43. · 2.48 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: It has been shown that CA repeats in the 3'-untranslated region (UTR) of bcl-2 mRNA contribute the constitutive decay of bcl-2 mRNA and that hnRNP L (heterogenous nuclear ribonucleoprotein L) interacts with CA repeats in the 3'-UTR of bcl-2 mRNA, both in vitro and in vivo. The aim of this study was to determine whether the alteration of hnRNP L affects the stability of bcl-2 mRNA in vivo. Human breast carcinoma MCF-7 cells were transfected with hnRNP L-specific shRNA or hnRNP L-expressing vector to decrease or increase hnRNP L levels, respectively, followed by an actinomycin D chase. An RT-PCR analysis showed that the rate of degradation of endogenous bcl-2 mRNA was not affected by the decrease or increase in the hnRNP L levels. Furthermore, during apoptosis or autophagy, in which bcl-2 expression has been reported to decrease, no difference in the degradation of bcl-2 mRNA was observed between control and hnRNP L-knock down MCF-7 Cells. On the other hand, the levels of AUF-1 and nucleolin, transacting factors for ARE in the 3'UTR of bcl-2 mRNA, were not significantly affected by the decrease in hnRNP L, suggesting that a disturbance in the quantitative balance between these transacting factors is not likely to interfere with the effect of hnRNP L. Collectively, the findings indicate that the decay of bcl-2 mRNA does not appear to be directly controlled by hnRNP L in vivo.
Korean Journal of Physiology and Pharmacology 02/2010; 14(1):15-20. · 0.96 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Chlamydophila pneumoniae infection in the airways is thought to be associated with the pathogenesis of asthma, especially in non-atopic severe asthma with irreversible airway obstruction that may be related to airway remodeling. Here, we investigated whether C. pneumoniae infection enhances the secretion of critical chemical mediators for airway remodeling, such as VEGF, TGF-beta, and TIMP-1, in human bronchial epithelial cells (BECs) in a Th2-dominant microenvironment.
Human bronchial epithelial cells (BEAS-2B cells) were infected with C. pneumoniae strain TW183 and cultured in both a Th1-dominant microenvironment with INF-gamma and a Th2-dominant microenvironment with IL-4 or IL-13 added to the culture medium. The VEGF, TGF-beta, and TIMP-1 levels in the culture supernatants were measured using enzyme-linked immunosorbent assays (ELISA). The activation of NF-kappaB in each experimental condition was determined using an electrophoretic mobility shift assay.
Chlamydophila pneumoniae-infected BECs showed enhanced secretion of VEGF, TGF-beta, and TIMP-1 compared with non-infected BECs. The levels of cytokines secreted from BECs were increased more when IL-13 was added to the culture medium. C. pneumoniae-infected BECs also showed increased NF-kappaB activation.
These results suggest that C. pneumoniae plays a role in the pathogenesis of airway remodeling in asthma, revealing a Th2-dominant immune response. Further studies are required to clarify the precise mechanism of C. pneumoniae infection in airway remodeling.
Allergy, asthma & immunology research 01/2010; 2(1):41-7. · 1.91 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Asthma presents with heterogeneous features, and patients show various phenotypes of differing severities. Therefore, it is necessary to define reliable predictable clinical factors that influence severity. To date, few large-scale studies have gathered clinical data on adult asthma patients in Asia.
To establish an adult asthma cohort in Korea and to define significant factors associated with asthma severity and exacerbation.
Researchers from 11 university hospitals have established an asthma cohort termed the COhort for Reality and Evolution of adult Asthma in Korea (COREA). We classified the severity of asthma into 3 groups: mild, moderate, and severe. In this article, the first analysis of our cohort, we evaluate various clinical factors associated with the severity and exacerbation of asthma using data from 1,260 asthma patients.
Physician-evaluated severity of asthma was associated with a history of asthma exacerbation (P < .001), a history of smoking (P < .001), symptom duration (P = .007), and treatment duration (P < .001). It was also significantly correlated with predicted forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) values and FEV1/FVC ratio (all P < .001). Previous exacerbation was associated with smoking (P = .02), predicted FVC and FEV1 values (both P < .001), FEV1/FVC ratio (P = .02), airway hyperresponsiveness (P = .002), and duration of disease (P < .001).
Previous exacerbation, duration of disease, and decrease in lung function were important clinical indices associated with asthma severity in the COREA study patients. Our long-term follow-up study is expected to soon yield more accurate and detailed outcomes.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 10/2009; 103(4):311-7. · 2.83 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The exact pathogenic role of oxidative stress in the development of allergic airway inflammation is still largely unknown.
To investigate a possible link between increased pulmonary oxidative stress and the pivotal features of asthma during the mounting of an allergic inflammatory response.
To determine the relationship between oxidative stress and allergic inflammatory responses, we evaluated the sequential kinetics of oxidative stress in the lung, the development of airway inflammation, mucin hypersecretion, and airway hyperresponsiveness (AHR) in an ovalbumin (OVA)-sensitized and challenged mouse with and without antioxidant. Parameters were measured at 9 points for more than 28 days, starting from the first day of OVA challenge with or without antioxidant treatment. The ratio of reduced to oxidized glutathione in the lungs and levels of intracellular reactive oxygen species (ROS) in the bronchial epithelium were serially measured. Bronchoalveolar lavage fluid cells, histopathologic features, and AHR were analyzed at the same time points.
The reduced to oxidized glutathione ratio was reduced from immediately after OVA challenge to day 1, remained at this level until day 1, and rapidly recovered to the normal level after more than 2 days. Intracellular ROS levels in the bronchial epithelium followed similar kinetics. The inflammatory cells in bronchoalveolar lavage fluid reached a maximum of 3 days and decreased progressively thereafter. Histopathologic examination revealed that substantial airway inflammation persisted through day 28. The proportion of mucin-producing epithelial cells significantly increased after day 1, reached a maximum at day 3, and remained at this level until day 5. The AHR peaked on day 1 and normalized within 5 days. The pretreatment of antioxidant significantly reduced not only the increased ROS levels but also development of other phenotypes of asthma.
These results indicate that increased oxidative stress in the lung precedes other pivotal phenotypes of allergic airway disease, suggesting a critical role for increased oxidative stress in the induction of allergic airway inflammation.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 09/2009; 103(3):238-47. · 2.83 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Although asthmatic patients frequently smoke cigarettes, the effect of smoking on asthmatic lungs has not been extensively studied. Vascular endothelial growth factor (VEGF) has been suggested to play a role in the pathogenesis of asthma and emphysema.
To determine whether the level of airway VEGF might be related to emphysematous lung changes in asthmatic patients with a history of smoking.
Pulmonary function tests and volumetric computed tomography (CT) of the lungs were performed in 10 ex-smoking and 15 nonsmoking asthmatic patients. Levels of VEGF were evaluated in the supernatants of induced sputum using an enzyme-linked immunosorbent assay method in these 25 asthmatic patients and in 10 healthy nonsmoking controls. Associations among sputum VEGF levels, emphysema indices on CT, and clinical variables were analyzed.
Ex-smoking asthmatic patients showed a higher emphysema index on volumetric CT and a decreased mean forced expiratory volume in 1 second to forced vital capacity ratio compared with nonsmoking asthmatic patients. Sputum VEGF levels in asthmatic patients with a history of smoking were significantly lower than those in nonsmoking asthmatic patients but remained higher than those in control subjects. Furthermore, the emphysema index was significantly correlated with sputum VEGF levels in asthmatic patients.
Lower VEGF levels in the airway might bea surrogate marker for emphysematous changes in the lungs, especially in asthmatic patients with a history of smoking.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 08/2009; 103(1):51-6. · 2.83 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Chlamydophila pneumoniae may contribute to the pathogenesis of asthmatic airway inflammation through chemical mediators secreted by C. pneumoniae-infected bronchial epithelial cells (BECs). Recently, CCL20 and vascular endothelial growth factor (VEGF) were reported to be released from BECs and to play a role in the pathogenesis of asthma.
To determine if C. pneumoniae infection of BECs induces the secretion of CCL20 and VEGF, we measured that by ELISA in human BECs infected with C. pneumoniae. Transcripts of CCL20 and VEGF were assayed by semi-quantitative RT-PCR. To investigate the underlying mechanism, the activation of MAPK and intracellular reactive oxygen species (ROS) in these C. pneumoniae-infected BECs was measured, as well as the effects of inhibitors of MAPK and ROS on CCL20 and VEGF expression.
Compared with non-infected BECs, C. pneumoniae-infected BECs showed enhanced secretion of CCL20 and VEGF. C. pneumoniae-infected BECs also showed enhanced intracellular ROS and an increased ratio of phosphorylated to non-phosphorylated p38. Inhibition of p38 suppressed CCL20 and VEGF secretion, as did a NADPH oxidase blocker and an antioxidant, in C. pneumoniae-infected BECs.
C. pneumoniae infection of BECs may play a role in the pathogenesis of asthma through the enhanced production of CCL20 and VEGF. The association between increased cytokine production and increased intracellular ROS suggests that antioxidants may benefit asthmatics in selected situations.
Journal of Clinical Immunology 06/2009; 29(5):629-36. · 3.08 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Previous observations suggest that Bis, a Bcl-2-binding protein, may play a role the neuronal and glial differentiation in vivo. To examine this further, we investigated Bis expression during the in vitro differentiation of P19 embryonic carcinoma cells induced by retinoic acid (RA). Western blotting and RT-PCR assays showed that Bis expression was temporarily decreased during the free floating stage and then began to increase on day 6 after the induction of differentiation. Double immunostaining indicated that Bis-expressing cells do not express several markers of differentiation, including NeuN, MAP-2 and Tuj-1. However, some of the Bis-expressing cells also were stained with GFAP-antibodies, indicating that Bis is involved glial differentiation. Using an shRNA strategy, we developed bis-knock down P19 cells and compared them with control P19 cells for the expression of NeuroD, Mash-1 and GFAP during RA-induced differentiation. Among these, only GFAP induction was significantly attenuated in P19-dnbis cells and the population showing GFAP immunoreactivity was also decreased. It is noteworthy that distribution of mature neurons and migrating neurons was disorganized, and the close association of migrating neuroblasts with astrocytes was not observed in P19-dnbis cells. These results suggest that Bis is involved in the migration-inducing activity of glial cells.
Korean Journal of Physiology and Pharmacology 06/2009; 13(3):251-6. · 0.96 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Chlorhexidine is widely used as an antiseptic and disinfectant in medical and nonmedical environments. Although the sensitization rate seems to be low, its ubiquitous use raises the possibility of sensitization in many patients and medical care workers. We describe a patient with anaphylaxis during digital rectal examination with chlorhexidine jelly. Urticaria, angioedema, dyspnea, and hypotension developed within a few minutes of the rectal examination. The patient fully recovered after treatment with epinephrine and corticosteroids. Skin tests for chlorhexidine were undertaken 5 weeks later, showing positive prick and intradermal skin tests. Within 30 min of the skin test, the patient complained of febrile sensation, chest tightness, angioedema, and urticaria on the face and trunk. An enzyme allergosorbent test for latex was negative. We present this case to alert clinicians about hypersensitivity to chlorhexidine that could potentially be life-threatening. We suggest that chlorhexidine should be recognized as a causative agent of anaphylaxis during procedural interventions.
Journal of Korean Medical Science 07/2008; 23(3):526-8. · 0.99 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study was conducted to evaluate the effectiveness of a computerized surveillance system for adverse drug events (ADEs) reinforced with mandatory reporting of all past drug hypersensitivity reactions (DHSRs) and supervision of the processes by allergy specialists in a university hospital.
All information on both prior and newly developed DHSRs was collected via the surveillance system described above and compared with the data from previous system based on voluntary reporting of DHSRs by attending physicians.
The report rate of past DHSRs was greatly increased and the estimated incidence of new events decreased under the new system. The occurrence rate of new DHSRs during hospitalization, which were caused by the repeated administration of the agents previously suspected as culprit drugs enormously, decreased from 15% of previous system to 1% of new system.
The mandatory reporting system for past DHSRs and the supervision by allergy specialists appear to be important in improving the management of patients with drug hypersensitivity and in preventing the occurrence of DHSRs in a general hospital.
Pharmacoepidemiology and Drug Safety 06/2008; 17(9):919-25. · 2.53 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Although the recruitment of macrophages to the lung is a central feature of airway inflammation, its function in ongoing T(h)2 cell-mediated eosinophilic airway inflammation remains controversial. Here, we have demonstrated that the allergen-induced CD11b(+) CD11c(int) macrophage expressing CC chemokine receptor 3 (CCR3) in the lung performs a crucial function in the induction of eosinophilic asthma in a murine model. In the lungs of normal mice, residential cells evidencing high granularity phenotypically evidenced CD11b(int) CD11c(+) or CD11b(+) CD11c(int) cells, appearing at a 2:1 ratio. After allergen challenge, however, this reverses dramatically, up to a ratio of one to six. Approximately 91% of increased CD11b(+) CD11c(int) cells evidenced the expression of the CCR3 eotaxin receptor, but not other chemokine receptors, such as CCR5 and CXCR4. Interestingly, the CD11b(+) CD11c(int) cells purified from the lungs of OVA (ovalbumin)-sensitized and challenged mice evidenced higher antigen-presenting activity than was observed in CD11b(int) CD11c(+) cells. In order to investigate the in vivo function of CD11b(+) CD11c(int) cells, the cells were isolated from the lungs of OVA-sensitized and challenged mice and then adoptively transferred prior to the allergen challenge of normal mice. In the CD11b(+) CD11c(int)-transferred mice airway hyperresponsiveness, eosinophilic inflammation in the lung and T(h)2 cytokine secretion in the bronchoalveolar lavage fluids were significantly enhanced as the result of OVA challenge, as compared with the mice that received OVA-primed CD90(+) T cells or CD11b(int) CD11c(+) cells. These findings show that CD11b(+) CD11c(int) macrophages expressing CCR3 as key pro-inflammatory cells are both necessary and sufficient for allergen-specific T cell stimulation during ongoing eosinophilic airway inflammation.
International Immunology 01/2008; 19(12):1371-81. · 3.41 Impact Factor
-
Jeong Woo Lim, Chan Sun Park,
Jung Min Ahn,
Mi Hyun Yu,
Taeg Soo Kim,
Young-Suk Lim,
Seok Won Chung,
Gang Mo Kim,
Young-Hwa Chung,
Yung Sang Lee,
Dong Jin Suh
[show abstract]
[hide abstract]
ABSTRACT: Hepatitis E virus is an enterically transmitted virus that causes endemic cases of acute hepatitis in many countries in Africa, and Southeast and Central Asia. Sporadic cases of acute hepatitis E also have been reported in developed countries. In non-endemic areas, most of the sporadic cases of hepatitis E are introduced from the endemic areas. Until now, only three cases of acute hepatitis E have been reported in Korea. Recently, we experienced nine cases of acute hepatitis, in which serologic studies showed positive of IgM anti-HEV. We report these as cases of acute hepatitis E. These cases suggest that HEV infection occurs sporadically in Korea and should be considered as a cause of cryptogenic acute hepatitis.
The Korean Journal of Hepatology 07/2006; 12(2):230-6.
-
Nae Yun Heo,
Young Suk Lim,
Jeong Min Kang,
Se Il Oh, Chan Sun Park,
Seok Won Jung,
Yoon Sun Lee,
Kang Mo Kim,
Han Chu Lee,
Young Hwa Chung,
Yung Sang Lee,
Dong Jin Suh
[show abstract]
[hide abstract]
ABSTRACT: Striking geographic differences have been noted in the etiology of fulminant hepatic failure (FHF). The prognosis of patients with FHF who do not receive liver transplantation in a timely manner is quite dismal. This study intended to identify the etiology and outcome of FHF in Korean adults and to examine the role of urgent living-donor liver transplantation (LDLT) for treating this unique situation.
We identified all the adult FHF patients who were referred to our unit between 1999 and 2004. FHF was defined as severe acute hepatitis complicated by the rapid development of hepatic encephalopathy within 8 weeks of the initial symptoms in the patients without a previous history of liver disease.
One hundred fourteen patients (47 males and 67 females) were identified. The mean age was 39.5+/-15.3 years. Drugs were the most common cause (28.1%) of FHF (herbal medications, 9.6%), and acute viral infection accounted for 23.7% (HBV accounted for 15.8%). Indeterminate etiologies were noted in 34%. The 90-day survival rate of the nontransplant group was only 15%. Fourteen patients received liver transplants (13 right-lobe LDLT, 1 cadaveric whole liver), and 12 of these (85.7%) survived and showed good graft function during 22 months of median follow-up.
Although the causes of FHF in Korea were diverse, HBV infection and herbal medications were responsible for a significant proportion of the cases. Since urgent LDLT improved the overall survival rate of patients with FHF, this should be considered as an important treatment option for patients suffering with FHF.
The Korean Journal of Hepatology 04/2006; 12(1):82-92.
-
[show abstract]
[hide abstract]
ABSTRACT: In the title compound, C(13)H(14)BN(3)O, the aziridine ring is an almost equilateral triangle, the C-C distance being slightly shorter than the C-N distances, probably because of the dative B-N bond. The five-membered ring, composed of two C atoms and N, B and O atoms, is fused with the aziridine ring to form a six-membered ring with a chair conformation.
Acta Crystallographica Section C Crystal Structure Communications 01/2004; 59(Pt 12):o659-60. · 0.52 Impact Factor
