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1.  Respiratory Review of 2014: Tuberculosis and Nontuberculous Mycobacterial Pulmonary Disease 
Since tuberculosis (TB) remains a major global health concern and the incidence of multi-drug resistant (MDR)-TB is increasing globally, new modalities for the detection of TB and drug resistant TB are needed to improve TB control. The Xpert MTB/RIF test can be a valuable new tool for early detection of TB and rifampicin resistance, with a high sensitivity and specificity. Late-generation fluoroquinolones, levofloxacin, and moxifloxacin, which are the principal drugs for the treatment of MDR-TB, show equally high efficacy and safety. Systemic steroids may reduce the overall TB mortality attributable to all forms of TB across all organ systems, although inhaled corticosteroids can increase the risk of TB development. Although fixed dose combinations were expected to reduce the risk of drug resistance and increase drug compliance, a recent meta-analysis found that they might actually increase the risk of relapse and treatment failure. Regarding treatment duration, patients with cavitation and culture positivity at 2 months of TB treatment may require more than 6 months of standard treatment. New anti-TB drugs, such as linezolid, bedaquiline, and delamanid, could improve the outcomes in drug-resistant TB. Nontuberculous mycobacterial lung disease has typical clinical and immunological phenotypes. Mycobacterial genotyping may predict disease progression, and whole genome sequencing may reveal the transmission of Mycobacterium abscessus. In refractory Mycobacterium avium complex lung disease, a moxifloxacin-containing regimen was expected to improve the treatment outcome.
doi:10.4046/trd.2014.77.4.161
PMCID: PMC4217031  PMID: 25368661
Tuberculosis; Nontuberculous Mycobacteria; Tuberculosis, Multidrug-Resistant; Diagnosis; Antitubercular Agents
2.  Pleural Infection and Empyema 
Increasing incidence of pleural infection has been reported worldwide in recent decades. The pathogens responsible for pleural infection are changing and differ from those in community acquired pneumonia. The main treatments for pleural infection are antibiotics and drainage of infected pleural fluid. The efficacy of intrapleural fibrinolytics remains unclear, although a recent randomized control study showed that the novel combination of tissue plasminogen activator and deoxyribonuclease had improved clinical outcomes. Surgical drainage is a critical treatment in patient with progression of sepsis and failure in tube drainage.
doi:10.4046/trd.2014.76.4.160
PMCID: PMC4021262  PMID: 24851128
Empyema; Etiology; Drainage; Fibrinolytic Agents
3.  Endobronchial Schwannoma Treated by Rigid Bronchoscopy with Argon Plasma Coagulation 
Primary endobronchial schwannomas are extremely rare tumors that originate from Schwann cells. We report a case of primary endobronchial schwannoma. A 44-year-old woman, without respiratory symptoms, was presented with a nodule in the left main bronchus on her chest computed tomography scan. The nodule was removed by a rigid bronchoscopy with argon plasma coagulation. Biopsy confirmed the diagnosis of schwannoma. There was no recurrence during her 4-month follow-up.
doi:10.4046/trd.2012.73.3.174
PMCID: PMC3492403  PMID: 23166551
Neurilemmoma; Bronchi; Bronchoscopy
4.  Bacterial Pathogens of Ventilator Associated Pneumonia in a Tertiary Referral Hospital 
Background
This study evaluates the bacterial pathogens of Ventilator-associated pneumonia (VAP) in a tertiary referral hospital.
Methods
A total of 109 bacterial pathogens from 91 adult patients with VAP, who were admitted to the medical intensive care unit from January 2008 to December 2009, were examined. Clinical characteristics, bacterial pathogens, and resistance profiles were analyzed.
Results
Staphylococcus aureus (44%) was the most frequently isolated. Acinetobacter baumanii (30%), Pseudomonas aeruginosa (12%), Stenotrophomonas maltophilia (7%), Klebsiella pneumoniae (6%), and Serratia marcescens (2%) were isolated from the transtracheal aspirates or bronchoalveolar lavage in patients with VAP. There was no significant difference of bacterial pathogens between early and late onset VAP. All isolated S. aureus were methicillin resistant S. aureus; the imipenem resistance rate of A. baumanii was 69%.
Conclusion
The two most frequent pathogens of VAP were S. aureus and A. baumanii. There were no pathogenic differences between early and late onset VAP.
doi:10.4046/trd.2012.73.1.32
PMCID: PMC3475477  PMID: 23101022
Pneumonia, Ventilator Associated; Staphylococcus aureus; Acinetobacter baumanii
5.  Recent advances in targeted endoscopic imaging: Early detection of gastrointestinal neoplasms 
Molecular imaging has emerged as a new discipline in gastrointestinal endoscopy. This technology encompasses modalities that can visualize disease-specific morphological or functional tissue changes based on the molecular signature of individual cells. Molecular imaging has several advantages including minimal damage to tissues, repetitive visualization, and utility for conducting quantitative analyses. Advancements in basic science coupled with endoscopy have made early detection of gastrointestinal cancer possible. Molecular imaging during gastrointestinal endoscopy requires the development of safe biomarkers and exogenous probes to detect molecular changes in cells with high specificity anda high signal-to-background ratio. Additionally, a high-resolution endoscope with an accurate wide-field viewing capability must be developed. Targeted endoscopic imaging is expected to improve early diagnosis and individual therapy of gastrointestinal cancer.
doi:10.4253/wjge.v4.i3.57
PMCID: PMC3309894  PMID: 22442742
Autofluorescence endoscopy; Confocal endomicroscopy; Endoscopy; Molecular imaging; Molecular probes, Near-infrared fluorescence imaging; Targeted endoscopic imaging
6.  A Case of Pulmonary Alveolar Microlithiasis 
Journal of Korean Medical Science  2011;26(10):1391-1393.
Pulmonary alveolar microlithiasis (PAM) is a rare disease with unknown etiology and pathogenesis. It is characterized by diffuse, innumerable, and minute calculi, called microlithiasis in the alveoli. More than half of reported cases are asymptomatic at the time of diagnosis. We describe the first case of PAM in Korea. A 19-yr-old man without respiratory symptoms presented with interstitial thickening on the chest radiograph. His chest high resolution CT scan showed diffusely scattered, ill defined tiny micronodules and interstitial thickening. Open lung biopsy confirmed the diagnosis of PAM. He was followed up for 6 months without treatment, and no progression was noticed.
doi:10.3346/jkms.2011.26.10.1391
PMCID: PMC3192355  PMID: 22022196
Calcinosis; Lung diseases; Computed Tomography
7.  Treatment Outcome of Combination Therapy Including Clarithromycin for Mycobacterium avium Complex Pulmonary Disease 
Background/Aims
The frequency of nontuberculous mycobacteria pulmonary disease in HIV-negative patients is increasing; the most common pathogen in Korea is the Mycobacterium avium complex (MAC). However, few studies have evaluated the treatment outcome of MAC pulmonary disease in Korea.
Methods
The efficacy of a clarithromycin-containing regimen for MAC pulmonary disease was studied in 42 patients treated for more than 6 months between January 2005 and December 2008. All patients were treated with a regimen consisting of clarithromycin, rifampin, and ethambutol. Streptomycin was added in 10 patients.
Results
Among the 42 patients, a negative culture conversion was achieved in 33 (78.6%), and the median duration of treatment in these patients was 19 months (interquartile range [IQR], 16 to 22). Of the 33 patients with a negative culture conversion, 14 completed treatment. During the follow-up period (median, 10 months; IQR, 4 to 20) for the 14 patients, one relapsed at 24 months after treatment completion. The culture conversion rate was significantly higher in patients who were treated with more than 500 mg/day clarithromycin (87.1% vs. 54.5%, p = 0.038).
Conclusions
The combined regimen including clarithromycin was effective against MAC pulmonary disease. High-dose clarithromycin of more than 500 mg/day may improve the outcome of patients with MAC pulmonary disease.
doi:10.3904/kjim.2011.26.1.54
PMCID: PMC3056256  PMID: 21437163
Mycobacterium avium complex; Treatment outcome; Clarithromycin
8.  Risk Factors for Death during Pulmonary Tuberculosis Treatment in Korea: A Multicenter Retrospective Cohort Study 
Journal of Korean Medical Science  2014;29(9):1226-1231.
The data regarding risk factors for death during tuberculosis (TB) treatment are inconsistent, and few studies examined this issue in Korea. The purpose of this study was to evaluate baseline prognostic factors for death during treatment of adult patients with pulmonary TB in Korea. A multicenter retrospective cohort study of 2,481 patients who received TB treatment at eight hospitals from January 2009 to December 2010 was performed. Successful treatment included cure (1,129, 45.5%) and treatment completion (1,204, 48.5%) in 2,333 patients (94.0%). Unsuccessful treatment included death (85, 3.4%) and treatment failure (63, 2.5%) occurred in 148 patients (6.0%). In multivariate analysis, male sex, anemia, dyspnea, chronic heart disease, malignancy, and intensive care unit (ICU) admission were significant risk factors for death during TB treatment. Therefore, male sex, anemia, dyspnea, chronic heart disease, malignancy, and ICU admission could be baseline prognostic factors for death during treatment of adult patients with pulmonary TB in Korea.
Graphical Abstract
doi:10.3346/jkms.2014.29.9.1226
PMCID: PMC4168175  PMID: 25246740
Tuberculosis, Pulmonary; Therapeutics; Mortality, Korea
9.  Trastuzumab-Conjugated Liposome-Coated Fluorescent Magnetic Nanoparticles to Target Breast Cancer 
Korean Journal of Radiology  2014;15(4):411-422.
Objective
To synthesize mesoporous silica-core-shell magnetic nanoparticles (MNPs) encapsulated by liposomes (Lipo [MNP@m-SiO2]) in order to enhance their stability, allow them to be used in any buffer solution, and to produce trastuzumab-conjugated (Lipo[MNP@m-SiO2]-Her2Ab) nanoparticles to be utilized in vitro for the targeting of breast cancer.
Materials and Methods
The physiochemical characteristics of Lipo[MNP@m-SiO2] were assessed in terms of size, morphological features, and in vitro safety. The multimodal imaging properties of the organic dye incorporated into Lipo[MNP@m-SiO2] were assessed with both in vitro fluorescence and MR imaging. The specific targeting ability of trastuzumab (Her2/neu antibody, Herceptin®)-conjugated Lipo[MNP@m-SiO2] for Her2/neu-positive breast cancer cells was also evaluated with fluorescence and MR imaging.
Results
We obtained uniformly-sized and evenly distributed Lipo[MNP@m-SiO2] that demonstrated biological stability, while not disrupting cell viability. Her2/neu-positive breast cancer cell targeting by trastuzumab-conjugated Lipo[MNP@m-SiO2] was observed by in vitro fluorescence and MR imaging.
Conclusion
Trastuzumab-conjugated Lipo[MNP@m-SiO2] is a potential treatment tool for targeted drug delivery in Her2/neu-positive breast cancer.
doi:10.3348/kjr.2014.15.4.411
PMCID: PMC4105802  PMID: 25053899
Breast cancer; Drug delivery; Iron oxide nanoparticles; Magnetic resonance imaging; Trastuzumab
10.  Diagnosis of Pulmonary Tuberculosis and Nontuberculous Mycobacterial Lung Disease in Korea 
The recovery of nontuberculous mycobacteria (NTM) from respiratory specimens and the number of patients with NTM lung disease have been rapidly increasing in Korea. An early differential diagnosis of NTM lung disease from pulmonary tuberculosis (TB) is important, as the therapeutic regimen differs from that of pulmonary TB, and it is not necessary to track the contacts of patients with NTM lung disease. However, differentiating NTM lung disease from pulmonary TB remains difficult, because the clinical presentations of the two diseases are similar and a definite diagnosis of NTM lung disease based on sputum culture takes time. This review focuses on the changing epidemiology, clinical and radiographic manifestation, and laboratory diagnosis of pulmonary TB and NTM lung disease in Korea.
doi:10.4046/trd.2014.77.1.1
PMCID: PMC4127406  PMID: 25114696
Tuberculosis, Pulmonary; Nontuberculous Mycobacteria; Epidemiology; Diagnosis; Korea
11.  Prevalence of Chronic Sputum and Associated Factors in Korean Adults 
Journal of Korean Medical Science  2014;29(6):825-830.
Chronic sputum is a troublesome symptom in many respiratory diseases. The prevalence of chronic sputum varies from 1.2% to 13% according to the country. The purpose of this study was to estimate the prevalence of chronic sputum and to find its associated factors in a general Korean population. We analyzed the data of the Korea National Health and Nutrition Examination Survey 2010 and 2011. A total number of 6,783 subjects aged 40 yr or more were enrolled in this study with 3,002 men and 3,781 women. As a result, the prevalence of chronic sputum was 6.3% (n=430). Significant risk factors for chronic sputum by multivariate analysis were: age (≥70 yr) (odds ratio [OR], 1.954; 95% confidence interval [CI], 1.308-2.917), current smoking (OR, 4.496; 95% CI, 3.001-6.734), chronic obstructive pulmonary disease (COPD) (OR, 1.483; 95% CI, 1.090-2.018), and tuberculosis (OR, 1.959; 95% CI, 1.307-2.938). In conclusion, the prevalence of chronic sputum in Korea was in the intermediate range compared with other countries. Smoking is a preventable risk factor identified in this study, and major respiratory diseases, such as COPD and tuberculosis, should be considered in subjects with chronic sputum.
Graphical Abstract
doi:10.3346/jkms.2014.29.6.825
PMCID: PMC4055817  PMID: 24932085
Chronic Sputum; Prevalence; Associated Factor
12.  N-(p-Coumaryol)-Tryptamine Suppresses the Activation of JNK/c-Jun Signaling Pathway in LPS-Challenged RAW264.7 Cells 
Biomolecules & Therapeutics  2014;22(3):200-206.
N-(p-Coumaryol) tryptamine (CT), a phenolic amide, has been reported to exhibit anti-oxidant and anti-inflammatory activities. However, the underlying mechanism by which CT exerts its pharmacological properties has not been clearly demonstrated. The objective of this study is to elucidate the anti-inflammatory mechanism of CT in lipopolysaccharide (LPS)-challenged RAW264.7 macrophage cells. CT significantly inhibited LPS-induced extracellular secretion of pro-inflammatory mediators such as nitric oxide (NO) and PGE2, and protein expressions of iNOS and COX-2. In addition, CT significantly suppressed LPS-induced secretion of pro-inflammatory cytokines such as TNF-α and IL-1β. To elucidate the underlying anti-inflammatory mechanism of CT, involvement of MAPK and Akt signaling pathways was examined. CT significantly attenuated LPS-induced activation of JNK/c-Jun, but not ERK and p38, in a concentration-dependent manner. Interestingly, CT appeared to suppress LPS-induced Akt phosphorylation. However, JNK inhibition, but not Akt inhibition, resulted in the suppression of LPS-induced responses, suggesting that JNK/c-Jun signaling pathway significantly contributes to LPS-induced inflammatory responses and that LPS-induced Akt phosphorylation might be a compensatory response to a stress condition. Taken together, the present study clearly demonstrates CT exerts anti-inflammatory activity through the suppression of JNK/c-Jun signaling pathway in LPS-challenged RAW264.7 macrophage cells.
doi:10.4062/biomolther.2014.013
PMCID: PMC4060082  PMID: 25009700
N-(p-Coumaroyl) tryptamine; RAW 264.7 cells; Lipopolysaccharide; iNOS; COX-2; JNK; c-Jun
13.  Phosphorylation of Akt Mediates Anti-Inflammatory Activity of 1-p-Coumaroyl β-D-Glucoside Against Lipopolysaccharide-Induced Inflammation in RAW264.7 Cells 
Hydroxycinnamic acids have been reported to possess numerous pharmacological activities such as antioxidant, anti-inflammatory, and anti-tumor properties. However, the biological activity of 1-p-coumaroyl β-D-glucoside (CG), a glucose ester derivative of p-coumaric acid, has not been clearly examined. The objective of this study is to elucidate the anti-inflammatory action of CG in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. In the present study, CG significantly suppressed LPS-induced excessive production of pro-inflammatory mediators such as nitric oxide (NO) and PGE2 and the protein expression of iNOS and COX-2. CG also inhibited LPS-induced secretion of pro-inflammatory cytokines, IL-1β and TNF-α. In addition, CG significantly suppressed LPS-induced degradation of IκB. To elucidate the underlying mechanism by which CG exerts its anti-inflammatory action, involvement of various signaling pathways were examined. CG exhibited significantly increased Akt phosphorylation in a concentration-dependent manner, although MAPKs such as Erk, JNK, and p38 appeared not to be involved. Furthermore, inhibition of Akt/PI3K signaling pathway with wortmannin significantly, albeit not completely, abolished CG-induced Akt phosphorylation and anti-inflammatory actions. Taken together, the present study demonstrates that Akt signaling pathway might play a major role in CG-mediated anti-inflammatory activity in LPS-stimulated RAW264.7 macrophage cells.
doi:10.4196/kjpp.2014.18.1.79
PMCID: PMC3951828  PMID: 24634601
1-p-coumaroyl β-D-glucoside (CG); Akt; COX-2; iNOS; Lipopolysaccharide; NF-κB; RAW264.7 cells
14.  Methyl p-Hydroxycinnamate Suppresses Lipopolysaccharide-Induced Inflammatory Responses through Akt Phosphorylation in RAW264.7 Cells 
Biomolecules & Therapeutics  2014;22(1):10-16.
Derivatives of caffeic acid have been reported to possess diverse pharmacological properties such as anti-inflammatory, anti-tumor, and neuroprotective effects. However, the biological activity of methyl p-hydroxycinnamate, an ester derivative of caffeic acid, has not been clearly demonstrated. This study aimed to elucidate the anti-inflammatory mechanism of methyl p-hydroxycinnamate in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Methyl p-hydroxycinnamate significantly inhibited LPS-induced excessive production of pro-inflammatory mediators such as nitric oxide (NO) and PGE2 and the protein expression of iNOS and COX-2. Methyl p-hydroxycinnamate also suppressed LPS-induced overproduction of pro-inflammatory cytokines such as IL-1β and TNF-α. In addition, methyl p-hydroxycinnamate significantly suppressed LPS-induced degradation of IκB, which retains NF-κB in the cytoplasm, consequently inhibiting the transcription of pro-inflammatory genes by NF-κB in the nucleus. Methyl p-hydroxycinnamate exhibited significantly increased Akt phosphorylation in a concentration-dependent manner. Furthermore, inhibition of Akt signaling pathway with wortmaninn abolished methyl p-hydroxycinnamate-induced Akt phosphorylation. Taken together, the present study clearly demonstrates that methyl p-hydroxycinnamate exhibits anti-inflammatory activity through the activation of Akt signaling pathway in LPS-stimulated RAW264.7 macrophage cells.
doi:10.4062/biomolther.2013.095
PMCID: PMC3936424  PMID: 24596616
Methyl p-hydroxycinnamate; RAW 264.7 cells; Lipopolysaccharide; iNOS; COX-2; NF-κB
15.  Was 2009 Pandemic Influenza A (H1N1) Mild Among Pregnant Korean Women? 
Chonnam Medical Journal  2013;49(2):96-99.
Clinical and laboratory data from Western countries suggest that pregnant women are at an increased risk for severe illness and complications associated with 2009 pandemic influenza A (H1N1). However, previous data among Korean women suggested a less severe outcome. In this study performed at a single referral center in Korea, rates of admission, pneumonia, intensive care unit admission, and death related to 2009 pandemic influenza A (H1N1) were significantly higher in 33 pregnant women than in 723 nonpregnant women of reproductive age (p<0.05 each). We report two cases of 2009 pandemic influenza A (H1N1) in pregnant Korean women who were admitted to the intensive care unit because of severe pneumonia that led to maternal and fetal death in one of the patients. This case series suggests that pregnant Korean women were also at increased risk of severe illness and complications during the 2009 pandemic influenza A (H1N1) outbreak.
doi:10.4068/cmj.2013.49.2.96
PMCID: PMC3759690  PMID: 24010074
Pandemics; Influenza; H1N1; Pregnancy
16.  Differences in classification of COPD group using COPD assessment test (CAT) or modified Medical Research Council (mMRC) dyspnea scores: a cross-sectional analyses 
Background
The GOLD 2011 document proposed a new classification system for COPD combining symptom assessment by COPD assessment test (CAT) or modified Medical Research Council (mMRC) dyspnea scores, and exacerbation risk. We postulated that classification of COPD would be different by the symptom scale; CAT vs mMRC.
Methods
Outpatients with COPD were enrolled from January to June in 2012. The patients were categorized into A, B, C, and D according to the GOLD 2011; patients were categorized twice with mMRC and CAT score for symptom assessment, respectively. Additionally, correlations between mMRC scores and each item of CAT scores were analyzed.
Results
Classification of 257 patients using the CAT score vs mMRC scale was as follows. By using CAT score, 60 (23.3%) patients were assigned to group A, 55 (21.4%) to group B, 21 (8.2%) to group C, and 121 (47.1%) to group D. On the basis of the mMRC scale, 97 (37.7%) patients were assigned to group A, 18 (7.0%) to group B, 62 (24.1%) to group C, and 80 (31.1%) to group D. The kappa of agreement for the GOLD groups classified by CAT and mMRC was 0.510. The mMRC score displayed a wide range of correlation with each CAT item (r = 0.290 for sputum item to r = 0.731 for dyspnea item, p < 0.001).
Conclusions
The classification of COPD produced by the mMRC or CAT score was not identical. Care should be taken when stratifying COPD patients with one symptom scale versus another according to the GOLD 2011 document.
doi:10.1186/1471-2466-13-35
PMCID: PMC3680333  PMID: 23731868
COPD; CAT; mMRC scores
17.  Aromadendrin Inhibits Lipopolysaccharide-Induced Nuclear Translocation of NF-κB and Phosphorylation of JNK in RAW 264.7 Macrophage Cells 
Biomolecules & Therapeutics  2013;21(3):216-221.
Aromadendrin, a flavonol, has been reported to possess a variety of pharmacological activities such as anti-inflammatory, antioxidant, and anti-diabetic properties. However, the underlying mechanism by which aromadendrin exerts its biological activity has not been extensively demonstrated. The objective of this study is to elucidate the anti-inflammatory mechanism of aromadedrin in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Aromadendrin significantly suppressed LPS-induced excessive production of pro-inflammatory mediators such as nitric oxide (NO) and PGE2. In accordance, aromadendrin attenuated LPSinduced overexpression iNOS and COX-2. In addition, aromadendrin significantly suppressed LPS-induced degradation of IκB, which sequesters NF-κB in cytoplasm, consequently inhibiting the nuclear translocation of pro-inflammatory transcription factor NF- κB. To elucidate the underlying signaling mechanism of anti-inflammatory activity of aromadendrin, MAPK signaling pathway was examined. Aromadendrin significantly attenuated LPS-induced activation of JNK, but not ERK and p38, in a concentration-dependent manner. Taken together, the present study clearly demonstrates that aromadendrin exhibits anti-inflammatory activity through the suppression of nuclear translocation of NF-κB and phosphorylation of JNK in LPS-stimulated RAW 264.7 macrophage cells.
doi:10.4062/biomolther.2013.023
PMCID: PMC3830120  PMID: 24265867
Aromadendrin; COX-2; iNOS; JNK; Lipopolysaccharide; NF-κB; RAW 264.7 cells
18.  Clinical characteristics and treatment outcomes of tuberculosis in the elderly: a case control study 
BMC Infectious Diseases  2013;13:121.
Background
The purpose of this study was to evaluate the differences in clinical characteristics and treatment outcomes between older and younger tuberculosis (TB) patients in Korea.
Methods
We retrospectively analyzed the medical records of 271 younger (20–64 years old at diagnosis) and 199 older (≥65 years) TB patients who had been newly diagnosed and treated at Chonnam National University Hospital from May 2008 to August 2010.
Results
Dyspnea and comorbid medical conditions were more frequent and positive TB culture rates were higher in older TB patients. In chest computed tomography (CT) scans of pulmonary TB patients, older patients were less likely to have micronodules (<7 mm in diameter), nodules (<30 mm in diameter), masses (>30 mm in diameter), and cavities compared with younger patients, but were more likely to have consolidations. Incidence of adverse drug reactions did not differ between the two groups, except for severe gastrointestinal disorders. There were no significant differences in favorable treatment outcomes between younger and older TB patients (97% vs. 94%, respectively; p = 0.251).
Conclusions
Older TB patients had more frequent dyspnea and less frequent active TB findings on chest CT. Treatment success and adverse drug reaction rates were similar in older and younger TB patients.
doi:10.1186/1471-2334-13-121
PMCID: PMC3599150  PMID: 23510403
Age; Clinical presentations; Diagnosis; Treatment outcome; Tuberculosis
19.  Repeated Favorable Responses to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors in a Case of Advanced Lung Adenocarcinoma 
The presence of epidermal growth factor receptor (EGFR) mutation is a prognostic and predictive marker for EGFR-tyrosine kinase inhibitor (TKI) therapy. However, inevitably, relapse occurs due to the development of acquired resistance, such as T790M mutation. We report a case of repeated responses to EGFR-TKIs in a never-smoked woman with adenocarcinoma. After six cycles of gemcitabine and cisplatin, the patient was treated by gefitinib for 4 months until progression. Following the six cycles of third-line pemetrexed, gefitinib retreatment was initiated and continued with a partial response for 6 months. After progression, she was recruited for an irreversible EGFR inhibitor trial, and the time to progression was 11 months. Although EGFR direct sequencing on the initial diagnostic specimen revealed a wild-type, we performed a rebiopsy from the progressed subcarinal node at the end of the trial. The result of peptide nucleic acid clamping showed L858R/L861Q.
doi:10.4046/trd.2013.74.3.129
PMCID: PMC3617133  PMID: 23579627
Adenocarcinoma; Receptor, Epidermal Growth Factor; Gefitinib
20.  Mycobacterium avium lung disease combined with a bronchogenic cyst in an immunocompetent young adult 
We report a very rare case of a bronchogenic cyst combined with nontuberculous mycobacterial pulmonary disease in an immunocompetent patient. A 21-year-old male was referred to our institution because of a cough, fever, and worsening of abnormalities on his chest radiograph, despite anti-tuberculosis treatment. Computed tomography of the chest showed a large multi-cystic mass over the right-upper lobe. Pathological examination of the excised lobe showed a bronchogenic cyst combined with a destructive cavitary lesion with granulomatous inflammation. Microbiological culture of sputum and lung tissue yielded Mycobacterium avium. The patient was administered anti-mycobacterial treatment that included clarithromycin.
doi:10.3904/kjim.2013.28.1.94
PMCID: PMC3543967  PMID: 23346002
Nontuberculous mycobacteria; Bronchogenic cyst; Mycobacterium avium complex
21.  3,4,5-Trihydroxycinnamic Acid Inhibits Lipopolysaccharide-Induced Inflammatory Response through the Activation of Nrf2 Pathway in BV2 Microglial Cells 
Biomolecules & Therapeutics  2013;21(1):60-65.
3,4,5-Trihydroxycinnamic acid (THC) is a derivative of hydroxycinnamic acids, which have been reported to possess a variety of biological properties such as anti-inflammatory, anti-tumor, and neuroprotective activities. However, biological activity of THC has not been extensively examined. Recently, we reported that THC possesses anti-inflammatory activity in LPS-stimulated BV2 microglial cells. However, its precise mechanism by which THC exerts anti-inflammatory action has not been clearly identified. Therefore, the present study was carried out to understand the anti-inflammatory mechanism of THC in BV2 microglial cells. THC effectively suppressed the LPS-induced induction of pro-inflammatory mediators such as NO, TNF-α, and IL-1β. THC also suppressed expression of MCP-1, which plays a key role in the migration of activated microglia. To understand the underlying mechanism by which THC exerts these anti-inflammatory properties, involvement of Nrf2, which is a cytoprotective transcription factor, was examined. THC resulted in increased phosphorylation of Nrf2 with consequent expression of HO-1 in a concentration-dependent manner. THC-induced phosphorylation of Nrf2 was blocked with SB203580, a p38 MAPK inhibitor, indicating that p38 MAPK is the responsible kinase for the phosphorylation of Nrf2. Taken together, the present study for the first time demonstrates that THC exerts anti-inflammatory properties through the activation of Nrf2 in BV2 microglial cells, suggesting that THC might be a valuable therapeutic adjuvant for the treatment of inflammation-related disorders in the CNS.
doi:10.4062/biomolther.2012.091
PMCID: PMC3762302  PMID: 24009860
Neuro-inflammation; 3; 4; 5-trihydroxycinnamic acid; Nrf2; Heme oxygenase-1
22.  Dysfunction of Natural Killer T Cells in Patients with Active Mycobacterium tuberculosis Infection 
Infection and Immunity  2012;80(6):2100-2108.
Natural killer T (NKT) cells are known to play a protective role in the immune responses of mice against a variety of infectious pathogens. However, little is known about the detailed information of NKT cells in patients with Mycobacterium tuberculosis infection. The aims of this study were to examine NKT cell levels and functions in patients with active M. tuberculosis infection, to investigate relationships between NKT cell levels and clinical parameters, and to determine the mechanism responsible for the poor response to α-galactosylceramide (α-GalCer). NKT cell levels were significantly lower in the peripheral blood of pulmonary tuberculosis and extrapulmonary tuberculosis patients, and the proliferative responses of NKT cells to α-GalCer were also lower in patients, whereas NKT cell levels and responses were comparable in latent tuberculosis infection subjects and healthy controls. Furthermore, this NKT cell deficiency was found to be correlated with serum C-reactive protein levels. In addition, the poor response to α-GalCer in M. tuberculosis-infected patients was found to be due to increased NKT cell apoptosis, reduced CD1d expression, and a defect in NKT cells. Notably, M. tuberculosis infection was associated with an elevated expression of the inhibitory programmed death-1 (PD-1) receptor on NKT cells, and blockade of PD-1 signaling enhanced the response to α-GalCer. This study shows that NKT cell levels and functions are reduced in M. tuberculosis-infected patients and these deficiencies were found to reflect the presence of active tuberculosis.
doi:10.1128/IAI.06018-11
PMCID: PMC3370582  PMID: 22409933
23.  A Multicenter Study of Pertussis Infection in Adults with Coughing in Korea: PCR-Based Study 
Background
Limited data on the incidence and clinical characteristics of adult pertussis infections are available in Korea.
Methods
Thirty-one hospitals and the Korean Centers for Disease Control and Prevention collaborated to investigate the incidence and clinical characteristics of pertussis infections among adults with a bothersome cough in non-outbreak, ordinary outpatient settings. Nasopharyngeal aspirates or nasopharyngeal swabs were collected for polymerase chain reaction (PCR) and culture tests.
Results
The study enrolled 934 patients between September 2009 and April 2011. Five patients were diagnosed as confirmed cases, satisfying both clinical and laboratory criteria (five positive PCR and one concurrent positive culture). Among 607 patients with cough duration of at least 2 weeks, 504 satisfied the clinical criteria of the US Centers for Disease Control and Prevention (i.e., probable case). The clinical pertussis cases (i.e., both probable and confirmed cases) had a wide age distribution (45.7±15.5 years) and cough duration (median, 30 days; interquartile range, 18.0~50.0 days). In addition, sputum, rhinorrhea, and myalgia were less common and dyspnea was more common in the clinical cases, compared to the others (p=0.037, p=0.006, p=0.005, and p=0.030, respectively).
Conclusion
The positive rate of pertussis infection may be low in non-outbreak, ordinary clinical settings if a PCR-based method is used. However, further prospective, well-designed, multicenter studies are needed.
doi:10.4046/trd.2012.73.5.266
PMCID: PMC3517945  PMID: 23236318
Adult; Cough; Incidence; Whooping Cough; Signs and Symptoms
24.  Avicularin Inhibits Lipopolysaccharide-Induced Inflammatory Response by Suppressing ERK Phosphorylation in RAW 264.7 Macrophages 
Biomolecules & Therapeutics  2012;20(6):532-537.
suppresAvicularin, quercetin-3-α-L-arabinofuranoside, has been reported to possess diverse pharmacological properties such as anti-inflammatory and anti-infectious effects. However, the underlying mechanism by which avicularin exerts its anti-inflammatory activity has not been clearly demonstrated. This study aimed to elucidate the anti-inflammatory mechanism of avicularin in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Avicularin significantly inhibited LPS-induced excessive production of pro-inflammatory mediators such as nitric oxide (NO) and PGE2 and the protein levels of iNOS and COX-2, which are responsible for the production of NO and PGE2, respectively. Avicularin also suppressed LPS-induced overproduction of pro-inflammatory cytokine IL-1β. Furthermore, avicularin significantly suppressed LPS-induced degradation of IκB, which retains NF-κB in the cytoplasm, consequently inhibiting the transcription of pro-inflammatory genes by NF-κB in the nucleus. To understand the underlying signaling mechanism of anti-inflammatory activity of avicularin, involvement of multiple kinases was examined. Avicularin significantly attenuated LPS-induced activation of ERK signaling pathway in a concentration-dependent manner. Taken together, the present study clearly demonstrates that avicularin exhibits anti-inflammatory activity through the suppression of ERK signaling pathway in LPS-stimulated RAW 264.7 macrophage cells.
doi:10.4062/biomolther.2012.20.6.532
PMCID: PMC3762284  PMID: 24009846
Avicularin; RAW 264.7 cells; Lipopolysaccharide; iNOS; COX-2; NF-κB
25.  Analysis of Patients with Hemoptysis in a Tertiary Referral Hospital 
Background
This study attempted to investigate the main causes of hemoptysis, the type of examinations used for diagnosis, the treatment modalities and outcomes.
Methods
A retrospective study was conducted on the medical records of 221 patients admitted to the Chonnam National University Hospital, between January 2005 and February 2010, with hemoptysis.
Results
Bronchiectasis (32.6%), active pulmonary tuberculosis (18.5%), fungus ball (10.8%), and lung cancer (5.9%) accounted for most causes of hemoptysis. Computed tomography scan was the most sensitive diagnostic test when employed alone, with positive yield of 93.2%. There were 161 cases of conservative treatment (72.9%), 42 cases of bronchial artery embolization (BAE) (19.0%), and 18 cases of surgery (8.1%). Regarding the amount of hemoptysis, 70 cases, out of 221 cases, were mild (31.5%), 36 cases moderate (16.2%), and 115 cases massive hemoptysis (52.0%). Most of the patients were treated conservatively, but if there was more bleeding present, BAE or surgery was more commonly performed than the conservative treatment (p≤0.0001). In the multivariate model, severe hemoptysis and lung cancer were independently associated with short-term recurrence. BAE was independently associated with long-term recurrence, and lung cancer was associated with in-hospital mortality. The overall in-hospital mortality rate was 11.3%.
Conclusion
Hemoptysis is a common symptom with a good prognosis in most cases. However, patients exhibiting massive bleeding or those with malignancy had a poorer prognosis. In-hospital mortality was strongly related to the cause, especially in lung cancer.
doi:10.4046/trd.2012.73.2.107
PMCID: PMC3492374  PMID: 23166543
Hemoptysis; Etiology; Diagnosis; Therapeutics; Treatment Outcome

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