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Background: There have been few studies to verify factors associated with a false-negative interferon-gamma release assay (IGRA) in patients with tuberculous pleurisy. We investigated the clinical relevance of false-negative results of the blood QuantiFERON-TB Gold In-Tube (QFT-GIT) assay and its risk factors in patients diagnosed with pleural tuberculosis (TB)., Methods: Medical records of 650 pleural TB patients in a tertiary hospital between January 2009 and December 2020 were reviewed retrospectively. Patients who underwent the blood QFT-GIT assay and pleural fluid analysis before starting anti-TB medication were included., Results: Of 199 patients with pleural TB who were performed QFT-GIT assay, 36 (18.1%) were false-negative results. These patients tended to be older than those with a positive result (P=0.060). The QFT-GIT-false-negative group of had significantly more comorbidities such as end-stage renal disease (ESRD), haematological cancer or pneumoconiosis than the QFT-GIT-positive group. Hypoproteinaemia and pH >6 in pleural fluid were associated with a false-negative QFT-GIT. Of the 199 patients, 163 (81.9%) were cured or completed anti-TB treatment; 13 patients (6.5%) died. The QFT-GIT-negative patients had significantly worse outcomes including mortality [unfavourable outcome: 33.3% (12/36 patients) in QFT-GIT-negative groups vs. 14.7% (24/163 patients) in QFT-GIT-positive groups, P<0.017; overall mortality: 16.7% (6/36 patients) vs. 4.3% (7/163 patients), respectively, P<0.015]., Conclusions: In pleural TB, a false-negative QFT-GIT result was 18.1% in a country of intermediate TB incidence. This discordant result in GFT-GIT was associated with ESRD, pneumoconiosis, hypoproteinaemia and a poor outcome. Clinicians should keep in mind the possibility of false-negativity in the blood IGRA test, especially in specific situations and its impact on TB outcome in managing patients with pleural TB., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-21-1723/coif). The authors have no conflicts of interest to declare., (2022 Journal of Thoracic Disease. All rights reserved.)

Purpose: Bronchoscopy is widely used for microbiological diagnosis of patients with minimal sputum production. However, the usefulness of bronchoscopy in patient groups who benefit from subsequent microbiological confirmation has not been established., Patients and Methods: We retrospectively analyzed Korean tuberculosis (TB) cohort data from September 2018 to October 2019 to evaluate the usefulness of bronchoscopy in patients with microbiologically negative pulmonary TB (based on initial sputum polymerase chain reaction and culture results). The primary outcome was the proportion of microbiological diagnoses made after bronchoscopy. Secondary outcomes were the predictors of microbiological confirmation and the percentage of additional resistance detection after bronchoscopy., Results: A total of 5194 patients were diagnosed with pulmonary TB, 937 of whom were microbiologically negative for pulmonary TB based on the initial sputum findings. Of these, 319 patients underwent bronchoscopy, and further microbiological confirmation was achieved in 157 (49.1%) patients. The predictors of microbiological confirmation after bronchoscopy were age >65 years, female sex, and low body mass index (BMI). The rate of additional resistance detection was 10.5% (multidrug resistant/rifampin-resistant 3.8%; isoniazid-resistant 5.7%)., Conclusion: Bronchoscopy can be used for the detection of resistant pathogens. Bronchoscopy should be considered for microbiologically negative pulmonary TB in women aged >65 years and with low BMI for subsequent microbiological confirmation., Competing Interests: The authors declare no conflicts of interest in this work., (© 2022 Oh et al.)

Delpazolid, an oxazolidinone, has been studied in non-clinical studies of efficacy and toxicity and Phase 1 clinical studies. Delpazolid has in vitro activity against Gram-positive bacteria, including Mycobacterium tuberculosis. This study evaluated the bactericidal activity, safety, and pharmacokinetics of delpazolid in patients with pulmonary tuberculosis (TB). Seventy-nine subjects, aged 19 to 75 years with newly diagnosed smear-positive TB with no prior treatment for the current episode and no confirmed resistance to rifampin or isoniazid, were randomized to receive delpazolid 800 mg once a day (QD), 400 mg twice a day (BID), 800 mg BID or 1,200 mg QD or an active control of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) or linezolid 600 mg BID. The primary endpoint was the average daily reduction in log transformed bacterial load, assessed on 7H11 solid-media culture, from days 0 to 14. The average daily decline in log-CFU was 0.044 ± 0.016, 0.053 ± 0.017, 0.043 ± 0.016, and 0.019 ± 0.017, for the delpazolid 800 mg QD, 400 mg BID, 800 mg BID, and the 1,200 mg QD groups, respectively. The average daily decline in log-CFU was 0.192 ± 0.028 for the HRZE group and 0.154 ± 0.023 for the linezolid 600 mg BID group. Three serious adverse events (SAE) were reported, one each in the delpazolid 400 mg BID group (death due to worsening of TB at day 2), the HRZE group (hospitalization due to pleural effusion) and the linezolid group (hyperkalemia); none of the SAEs were assessed as related to study drugs. This study has been registered at ClinicalTrials.gov with registration number NCT02836483.

Background: The coronavirus disease 2019 (COVID-19) pandemic caused disruptions to healthcare systems, consequently endangering tuberculosis (TB) control. We investigated delays in TB treatment among notified patients during the first wave of the COVID-19 pandemic in Korea., Methods: We systemically collected and analyzed data from the Korea TB cohort database from January to May 2020. Groups were categorized as 'before-pandemic' and 'during-pandemic' based on TB notification period. Presentation delay was defined as the period between initial onset of symptoms and the first hospital visit, and healthcare delay as the period between the first hospital visit and anti-TB treatment initiation. A multivariate logistic regression analysis was performed to evaluate factors associated with delays in TB treatment., Results: Proportion of presentation delay > 14 days was not significantly different between two groups (48.3% vs. 43.7%, P = 0.067); however, proportion of healthcare delay > 5 days was significantly higher in the during-pandemic group (48.6% vs. 42.3%, P = 0.012). In multivariate analysis, the during-pandemic group was significantly associated with healthcare delay > 5 days (adjusted odds ratio = 0.884, 95% confidence interval = 0.715-1.094)., Conclusion: The COVID-19 pandemic was associated with healthcare delay of > 5 days in Korea. Public health interventions are necessary to minimize the pandemic's impact on the national TB control project., Competing Interests: All authors have no potential conflicts of interest., (© 2022 The Korean Academy of Medical Sciences.)

Background: To improve the rehabilitation team's awareness of patient mobility and participation by enhancing communication between therapists and nurses and conducting patient education., Methods: This study used a non-equivalent control group with a non-synchronized design. To facilitate communication between therapists and nurses, we used a manual for mobility management to improve the sharing of information on the functional status of patients. We also implemented patient education to improve their awareness of mobility and participation. Finally, we conducted newly devised surveys related to patient functional status and awareness that were applied by therapists and nurses., Results: The nurses reported significantly lower functional levels of patients compared to those assessed by therapists. After the intervention, the kappa values representing the concordance between therapists and nurses improved to almost perfect agreement for transfer ability (κ=0.836), mobility (κ=0.664), and toileting (κ=1.000). We also observed a statistically significant increase in questionnaire scores with respect to nurses' awareness (p<0.05)., Conclusion: Improving communication among the rehabilitation team, including nurses through the use of a continuous education program, was effective in promoting the mobility and functional level of patients in the inpatient ward.

In 2017, the Korean government launched an unprecedentedly large-scaled latent tuberculosis infection (LTBI) screening project which covered more than a million individuals in congregate settings. A total of 1,047,689 participants of source population (n = 2,336,157) underwent LTBI testing from 2017 to 2018. The overall LTBI test uptake rate during this project was 44.8%. Workers in daycare centers (83.5%) and kindergartens (78.9%) showed high participation rate. A total of 1,012,206 individuals with valid results of interferon-gamma release assay (IGRA) were selected to constitute the IGRA cohort. Most of the enrolled participants in the IGRA cohort were in their working age. Approximately, three-quarters of total enrolled population were female. Investigating the LTBI prevalence, stages of LTBI care cascade, natural history of LTBI, efficacy of LTBI treatment and cost-effectiveness of LTBI screening are feasible within this IGRA cohort., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

Background/aims: Current asthma therapies remain unsatisfactory for controlling airway remodelling in asthma. MicroRNA-21 is a key player in asthma pathogenesis, but the molecular mechanisms underlying its effects on airway remodelling are not completely understood. We investigated the effects of inhibition of microRNA-21 on allergic airway inflammation and remodelling., Methods: Female BALB/c mice were divided into four groups: control, ovalbumin-sensitized and -challenged for 3 months, microRNA-negative control-treated ovalbumin-treated, and microRNA-21 inhibitor-treated ovalbumin-treated groups. Parameters related to airway remodelling, cytokine production, airway inflammation, and airway hyperresponsiveness were compared between groups. Human bronchial smooth muscle cells were used in a mechanism study., Results: In this asthma model, ovalbumin-sensitized and -challenged mice exhibited allergic airway inf lammation and airway remodelling. MicroRNA-21 inhibitor-treated mice had fewer inflammatory cells, lower TH2 cytokine production, and suppressed parameters related to remodelling such as goblet cell hyperplasia, collagen deposition, hydroxyproline content, and expression of smooth muscle actin. Inhibition of microRNA-21 decreased transforming growth factor β1 expression and induced Smad7 expression in lung tissue. In human bronchial smooth muscle cells stimulated with transforming growth factor β1, microRNA-21 inhibition upregulated Smad7 expression and decreased markers of airway remodelling., Conclusion: Inhibition of microRNA-21 had both anti-inflammatory and anti-remodelling effects in this model of ovalbumin-induced chronic asthma. Our data suggest that the microRNA-21-transforming growth factor β1-Smad7 axis modulates the pathogenesis of ovalbumin-induced chronic asthma and in human bronchial smooth muscle cells. MicroRNA-21 inhibitors may be a novel therapeutic target in patients with allergic asthma, especially those with airway remodelling.

Small extracellular vesicles (sEVs) are nanometer-sized membranous vesicles secreted by cells, with important roles in physiological and pathological processes. Recent research has established the application of sEVs as therapeutic vehicles in various conditions, including heart disease. However, the high risk of off-target effects is a major barrier for their introduction into the clinic. This study evaluated the use of modified sEVs expressing high levels of cardiac-targeting peptide (CTP) for therapeutic small interfering RNA (siRNA) delivery in myocarditis, an inflammatory disease of heart. sEVs were extracted from the cell culture medium of HEK293 cells stably expressing CTP-LAMP2b (referred to as C-sEVs). The cardiac targeting ability of C-sEVs with the highest CTP-LAMP2b expression was >2-fold greater than that of normal sEVs (N-sEVs). An siRNA targeting the receptor for advanced glycation end products (RAGE) (siRAGE) was selected as a therapeutic siRNA and loaded into C-sEVs. The efficiency of cardiac-specific siRNA delivery via C-sEVs was >2-fold higher than that via N-sEVs. Furthermore, siRAGE-loaded C-sEVs attenuated inflammation in both cell culture and an in vivo model of myocarditis. Taken together, C-sEVs may be a useful drug delivery vehicle for the treatment of heart disease., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Curcumin exerts therapeutic effects in heart disease, but has limited bioavailability. Extracellular vesicles (EVs) have gained attention as nanovehicles; however, the poor targeting ability of systemically administered EVs still remains a crucial issue. Herein, we generated heart-targeted EVs (CTP-EVs) by functionalizing EVs surface with cardiac targeting peptide (CTP) using genetic modification of EVs-secreting cells, and further loaded curcumin into CTP-EVs (CTP-EVs-Cur). Consequently, CTP-EVs were able to specifically deliver curcumin to the heart. In addition, curcumin-loaded CTP-EVs possess improved bioavailability, and are fully functional with a high cardioprotective efficiency. Moreover, we loaded miR-144-3p in CTP-EVs-Cur following validation of miR-144-3p as a major contributor in curcumin-mediated therapeutic effects. The simultaneous packing of curcumin and miR-144-3p in CTP-EVs not only retains the active heart-targeting ability but also achieves enhanced cardioprotective effects both in vitro and in vivo, indicating the possibility of combining and sustaining their therapeutic potential by simultaneously loading in CTP-EVs. Therefore, CTP-EVs could be a potential and effective strategy for the delivery of therapeutic molecules, thereby providing a promising nanomedicine for MI therapy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: MicroRNA-21 (miR-21) influences the Th2 immune pathway by suppressing the expressions of interleukin (IL)-12 and interferon (IFN)-γ. The effects of miR-21 suppression on alveolar macrophage polarization and airway inflammation are not known., Methods: BALB/c and miR-21 knockout (KO) mice were sensitized and challenged with ovalbumin (OVA). The anti-miR-21 antagomir was administered to BALB/c mice by intranasal inhalation from the day of OVA sensitization. Changes in cell counts, cytokine levels in bronchoalveolar lavage fluid (BALF), and airway hyperresponsiveness (AHR) were examined. Total, M1, and M2 macrophages were examined in the lung tissues by immunohistochemistry (IHC). M2 macrophages from the OVA mice lung were inhaled into the anti-miR-21 antagomir-treated asthmatic mice. Moreover, the polarization of M0 to M2 macrophages upon IL-4 stimulation was analyzed after anti-miR-21 antagomir transfection., Results: The miR-21 KO mice showed decreases in AHR, total cell and eosinophil counts in BALF, and in the levels of IL-4, IL-5, IL-10, and IL-13. Expression of IL-12 and IFN-γ were increased in the miR-21 KO mice. Peribronchial inflammation and goblet cell dysplasia were significantly decreased in the lung tissues of miR-21 KO OVA mice compared to the wild type OVA mice. IHC for M1, M2, and total macrophage in the lung tissues showed that miR-21 inhalation suppressed alveolar M2 macrophages in KO mice. M2 macrophage inhalation restored AHR and eosinophilic airway inflammation in the miR-21 antagomir-treated mice. Moreover, anti-miR-21 antagomir transfection decreased the expression of M2 markers and increased the expression of M1 markers in M0 macrophages after IL-4 stimulation., Conclusions: The results suggest that miR-21 antagonism could suppress alveolar M2 macrophage polarization, decreasing not only the Th2 eosinophilic airway inflammation but also AHR and airway remodeling process., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2021 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Background: There are limited data on the association between bronchial colonization and respiratory infections in people with lung cancer requiring cytotoxic chemotherapy. We investigated whether bronchial colonization in initial bronchoscopy specimens can predict the development of pneumonia after chemotherapy in patients with lung cancer., Methods: Four hundred thirteen patients with lung cancer included in the Catholic Medical Center lung cancer registry were enrolled from March 2015 to August 2018. Demographic data, microbiology results, development of pneumonia after chemotherapy, and clinical information about lung cancer were analyzed retrospectively., Results: A total of 206 lung cancer patients treated with chemotherapy were included in the analysis. Forty patients (19.4%) had positive results for the bronchial washing culture during the initial evaluation of lung cancer. The most common organisms were Klebsiella pneumoniae (n=14) and Streptococcus pneumoniae (n=6) in the surveillance culture, and Pneumocystis jirovecii (n=12) and Staphylococcus aureus (n=8) at the time of pneumonia development. Eighty-nine patients (43.2%) had pneumonia after chemotherapy, but the occurrence of pneumonia did not differ according to the colonization. There were no patients for whom the initial isolated organism was a causative microbe for the development of pneumonia after or during chemotherapy. The pneumonia group had poorer prognosis than the non-pneumonia group (378 vs. 705 days, P=0.0004)., Conclusions: Microbial colonization in bronchoscopy specimens was not associated with pneumonia development or mortality after chemotherapy for lung cancer. This finding suggests that testing surveillance culture may not be helpful for predicting pneumonia or improving survival in lung cancer patients with chemotherapy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-2722). The authors have no conflicts of interest to declare., (2021 Journal of Thoracic Disease. All rights reserved.)

Background: The national Public-Private Mix (PPM) tuberculosis (TB) control project provides for the comprehensive management of TB patients at private hospitals in South Korea. Surveillance and monitoring of TB under the PPM project are essential toward achieving TB elimination goals., Methods: TB is a nationally notifiable disease in South Korea and is monitored using the surveillance system. The Korea Centers for Disease Control and Prevention quarterly generates monitoring indicators for TB management, used to evaluate activities of the PPM hospitals by the central steering committee of the national PPM TB control project. Based on the notification date, TB patients at PPM hospitals were enrolled in each quarter, forming a cohort, and followed up for at least 12 months to identify treatment outcomes. This report analyzed the dataset of cohorts the first quarter of 2016 through the fourth quarter of 2017., Results: The coverage of sputum, smear, and culture tests among the pulmonary TB cases were 92.8% and 91.5%, respectively. The percentage of positive sputum smear and culture test results were 30.7% and 61.5%, respectively. The coverage of drug susceptibility tests among the culture-confirmed cases was 92.8%. The treatment success rate among the smear-positive drug-susceptible cases was 83.2%. The coverage of latent TB infection treatment among the childhood TB contacts was significantly higher than that among the adult contacts (85.6% vs. 56.0%, p=0.001)., Conclusion: This is the first official report to analyze monitoring indicators, describing the current status of the national PPM TB control project. To sustain its effect, strengthening the monitoring and evaluation systems is essential.

Idiopathic nonspecific interstitial pneumonia (NSIP) is one of the varieties of idiopathic interstitial pneumonias. Diagnosis of idiopathic NSIP can be done via multidisciplinary approach in which the clinical, radiologic, and pathologic findings were discussed together and exclude other causes. Clinical manifestations include subacute or chronic dyspnea and cough that last an average of 6 months, most of which occur in non-smoking, middle-aged women. The common findings in thoracic high-resolution computed tomography in NSIP are bilateral reticular opacities, traction bronchiectasis, reduced volume of the lobes, and ground-glass opacity in the lower lungs. These lesions can involve diffuse bilateral lungs or subpleural area. Unlike usual interstitial pneumonia, honeycombing is sparse or absent. Pathology shows diffuse interstitial inflammation and fibrosis which are temporally homogeneous, namely NSIP pattern. Idiopathic NSIP is usually treated with steroid only or combination with immunosuppressive agents such as azathioprine, cyclophosphamide, cyclosporine, and mycophenolate mofetil. Prognosis of idiopathic NSIP is better than idiopathic pulmonary fibrosis. Many studies have reported a 5-year survival rate of more than 70%., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright©2019. The Korean Academy of Tuberculosis and Respiratory Diseases.)

Objectives: The aim of this study was to compare differences in perception and knowledge of child abuse and child disciplinary practices according to the history of child abuse victimization., Methods: A questionnaire survey on child abuse was conducted with 491 adults raising children. We compared the perception and knowledge of child abuse and child disciplinary practices between two groups of adults with and without a history of childhood abuse victimization., Results: The group with a history of childhood abuse had lower levels of knowledge of child abuse (F=6.990, p<0.01) and engaged in more negative disciplinary practices (F=5.974, p<0.05) than those without. However, no differences in the perception of child abuse were observed between the two groups., Conclusion: The results suggest that adults with a history of childhood abuse have lower levels of knowledge of child abuse and use more negative disciplinary practices in raising their children. This highlights the need to administer not only educational but also more direct hands-on interventions to vulnerable parents in order to foster healthy parenting and disciplinary practices., Competing Interests: Conflicts of Interest The authors have no potential conflicts of interest to disclose., (Copyright: © Journal of the Korean Academy of Child and Adolescent Psychiatry.)

Background: The widespread use of molecular, genotypic drug susceptibility tests (DSTs) for antituberculosis (anti-TB) drugs has led to the dilemma of interpreting discordant results between genotypic and conventional, phenotypic DSTs. We investigated the clinical characteristics, including treatment patterns and outcomes, of TB patients with a genotype-phenotype discrepancy in susceptibility to isoniazid (INH) or rifampicin (RIF)., Methods: We retrospectively reviewed the medical records of TB patients who had results for 2 DSTs (genotypic method, MTBDR plus test for INH and RIF, and phenotypic method) treated between August 2010 and October 2016 in a tertiary university hospital., Results: Among 1,069 TB patients, 63 (5.9%) had discrepant results for the 2 DSTs. Of the 57 multidrug-resistant (MDR) TB cases diagnosed by either DST, 18 (31.6%) showed discordant results for INH or RIF. The most frequent pattern of discordance was genotypic susceptibility with phenotypic resistance to INH. RIF-discordant subjects with genotypic resistance were more likely to have been exposed previously to anti-TB drugs and to have an MDR TB diagnosis and concurrent INH resistance. Forty-five of the 54 patients managed in our hospital (83.3%) had a favorable outcome with a mean treatment duration of 14.0 months. Ten of the 16 INH-discrepant patients with a genotypic mutation continued taking INH, but more than half patients in the RIF-discrepant group (8/14) with a genotypic mutation discontinued taking RIF., Conclusions: Despite the low frequency, discordant results were obtained between the genotypic and phenotypic DSTs for INH or RIF, especially for patients with MDR TB or INH resistance. Furthermore, it seemed that RIF discrepancy with a genotypic mutation might have a greater impact on the clinical outcome than INH discrepancy., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background/objective: Asthma is a chronic airway disease characterized by airway eosinophilic inflammation and remodeling, which are associated with a loss in lung function. Although both contribute significantly to asthma pathogenesis, mechanistic studies and drug discovery have focused on inflammatory targets. In this study, we investigated the effect of the leukotriene receptor antagonist pranlukast on allergic airway inflammation and remodeling in vivo and in vitro., Method: Four groups of female BALB/c mice (control; ovalbumin [OVA]-sensitized and -challenged; dimethyl sulfoxide [DMSO]-treated OVA; and pranlukast-treated OVA) were examined. Lung pathology, cytokine production, and airway hyperresponsiveness (AHR) measurements were compared among these groups. A human fetal lung fibroblast HFL-1 cell line was used in the peribranchial fibrosis analysis., Results: OVA-sensitized and -challenged mice exhibited allergic airway inflammation and significant increases in Th2 cytokines. Pranlukast-treated mice showed significant attenuation of allergic airway inflammation. The pranlukast treatment decreased AHR and attenuated airway remodeling to goblet cell hyperplasia, collagen deposition, α-smooth muscle actin expression, and pro-fibrotic gene expression. We further demonstrated that pranlukast not only inhibited transforming growth factor-beta 1 (TGF-β1)-induced Smad signaling in human fetal lung fibroblast cells but also simultaneously reduced collagen synthesis and pro-fibrotic gene expression., Conclusions: The leukotriene receptor antagonist pranlukast can reduce airway inflammation and remodeling by inhibiting TGF-β/Smad signaling in an OVA-sensitized and -challenged asthma mouse model, thus suppressing AHR., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

A Gram-negative, facultative anaerobic, rod-shaped, motile by means of a polar flagellum, greenish-yellow-pigmented bacterial strain (designated strain JJ3220 T ) was isolated from an artificial lake in South Korea and characterized using a polyphasic approach. The 16S rRNA gene sequence of strain JJ3220 T indicated that the isolate belongs to the family Rhodocyclaceae, and that it exhibits 96.4% similarity to Uliginosibacterium paludis KBP-13 T . The major cellular fatty acids of the novel strain were C 14:0 , C 16:0 , and summed feature 3 (C 16:1 ω6c and/or C 16:1 ω7c). Strain JJ3220 T had flexirubin-type pigments. The DNA G+C content of the strain was 62.8%. The major respiratory quinone and major polar lipid of strain JJ3220 T were ubiquinone-8 and phosphatidylethanolamine, respectively. Based on the morphological and physiological properties and biochemical evidence presented, it can be concluded that strain JJ3220 T represents a novel species of the genus Uliginosibacterium. The type strain Uliginosibacterium flavum is JJ3220 T (=KACC 17644 T =JCM 19465 T ).

A Gram stain-negative, yellowish green-pigmented, facultatively anaerobic, motile, curved rod-shaped bacterium designated as strain JJ016 T was isolated from an artificial lake in South Korea, and characterized using a polyphasic approach. The 16S rRNA gene sequence of strain JJ016 T indicated that the isolate belonged to the family Rhodocyclaceae and exhibited 95.0% identity to Uliginosibacterium gangwonense 5YN10-9 T . The major cellular fatty acids of the novel strain were summed feature 3 (C 16:1 ω6c and/or C 16:1 ω7c), C 16:0 , C 14:0 , and summed feature 8 (C 18:1 ω7c and/or C 18:1 ω6c). The DNA G+C content of strain JJ016 T was 61.9 mol%. The major respiratory quinone and major polar lipid of strain JJ016 T were ubiquinone-8 and phosphatidylethanolamine, respectively. Based on the morphological and physiological properties and the biochemical evidence presented, we concluded that strain JJ016 T represents a novel species of a new genus in the family Rhodocyclaceae, for which the name Viridibacterium curvum gen. nov., sp. nov. is proposed. The type strain is JJ016 T (=KACC 16899 T =JCM 18715 T ).

Background/aims: Asthma is characterized by airway hyperresponsiveness, inflammation, and remodeling. Peroxisome proliferator-activated receptors have been reported to regulate inflammatory responses in many cells. In this study, we examined the effects of intranasal rosiglitazone on airway remodeling in a chronic asthma model., Methods: 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 per week for 3 months. Mice were treated intranasally with rosiglitazone with or without an antagonist during OVA challenge. We determined airway inflammation and the degree of airway remodeling by smooth muscle actin area and collagen deposition., Results: Mice chronically exposed to OVA developed sustained eosinophilic airway inflammation, compared with control mice. Additionally, the mice developed features of airway remodeling, including thickening of the peribronchial smooth muscle layer. Administration of rosiglitazone intranasally inhibited the eosinophilic inflammation significantly, and, importantly, airway smooth muscle remodeling in mice chronically exposed to OVA. Expression of Toll-like receptor (TLR)-4 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was increased in the OVA group and decreased in the rosiglitazone group. Co-treatment with GW9660 (a rosiglitazone antagonist) and rosiglitazone increased the expression of TLR-4 and NF-κB., Conclusions: These results suggest that intranasal administration of rosiglitazone can prevent not only air way inf lammation but also air way remodeling associated with chronic allergen challenge. This beneficial effect is mediated by inhibition of TLR-4 and NF-κB pathways.

A 57-year-old woman presented with cough and dyspnea for 2 months. Computed tomography of the chest showed diffuse ground-glass opacities in both lungs. Histologic examination via thoracoscopic lung biopsy revealed atypical lymphoproliferative lesion. Her symptoms and radiologic findings of the chest improved just after lung biopsy without any treatment. Therefore, she was discharged and monitored at an outpatient clinic. Two months later, pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma was confirmed by the detection of API2-MALT1 translocation in fluorescent in situ hybridization analysis. Although the lung lesions resolved spontaneously, she received chemotherapy due to bone marrow involvement in her staging workup. Pulmonary MALT lymphoma is rare. Nodular or consolidative patterns are the most frequent radiologic findings. Although the disease has an indolent growth, it rarely resolves without treatment. We report an unusual case of pulmonary MALT lymphoma with diffuse interstitial abnormalities on image and spontaneous regression on clinical course.

The clinical importance of the isolation of nontuberculous mycobacteria (NTM) from respiratory specimens of stem cell transplant (SCT) recipients is not clear. We investigated the characteristics and clinical impact of NTM isolation in this population. Medical records of adult patients who underwent SCT at the blood and marrow transplantation center at a University Hospital in South Korea between January 2004 and December 2013 were retrospectively reviewed. Twenty-five of 2,658 patients were enrolled, an incidence of 0.94%. The most common NTM species isolated were Mycobacterium avium complex (n = 15) and Mycobacterium abscessus (n = 5). Sixteen patients were co-infected with other pathogens, including Aspergillus species (10 cases). Nonspecific pneumonia and cavitary pneumonia were the most common radiologic patterns. Sixteen patients had underlying lung graft-versus-host disease, including bronchiolitis obliterans (10 cases) with moderate obstructive lung defects. Whereas two of 10 patients who were treated for NTM died as a result of NTM progression, one of 15 patients who were not treated died of the same cause. This study shows that the incidence of respiratory NTM detection in SCT recipients was low and its virulence was not higher than expected. As patients frequently had concomitant infections and underlying lung diseases that made radiologic evaluation more difficult, we suggest that it would be advantageous to perform repeated microbiologic studies when NTM infection is clinically suspected.

A Bacillus species that produces 2,3-butanediol (2,3-BD), termed BRC1, was newly isolated, and a 2,3-BD dehydrogenase (Bdh) from this species was identified and characterized at the molecular and biochemical level. Sequence analysis revealed that Bdh is homologous to D-2,3-BD dehydrogenases. An analysis of the enzymatic properties of Bdh overexpressed in Escherichia coli confirmed the molecular results, showing preferred activity toward D-2,3-BD. Optimum pH, temperature, and kinetics determined for reductive and oxidative reactions support the preferential production of 2,3-BD during cell growth. Overexpression of bdh under the control of a xylose-inducible promoter resulted in increased enzyme activity and enhanced 2,3-BD production in Bacillus sp. BRC1. Additionally, a hydrolysate of cellulosic material, (empty palm fruit bunches), was successfully used for the enhanced production of 2,3-BD in the recombinant Bacillus strain.

Pulmonary infections are a major cause of morbidity and mortality in patients with hematologic malignancy. Bronchoscopy is at present still the traditional first investigation in immunosuppressed patients that have developed pulmonary infiltrates. There is limited data available on the validity of fiberoptic bronchoscopy (FOB) with bronchoalveolar lavage (BAL) to determine the etiology of pulmonary infiltrates with concurrent hematologic malignancy. We retrospectively analyzed the microbiological results of 206 bronchoscopic examinations and treatment changes used in 187 patients with hematologic malignancy and pulmonary infiltrates. Bacteria, fungi, and viruses were found in 85 (41.3 %), 49 (23.8 %), and 55 (28.6 %) of cases, respectively, and overall yield of bronchoscopy was 65.0 %. We compared the microbiological findings with respect to neutropenia, hematopoietic stem cell transplantation (HSCT) status, and the type of malignancy. There were significantly more bacterial and viral infections detected in post-HSCT patients, and more viruses were detected in patients without neutropenia. Galactomannan (GM) was measured in 149 BAL samples. With a GM index threshold of ≥0.5, the sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) of the BAL GM assay were 93.94 %, 86.21 %, 65.96 %, and 98.04 %, respectively. Treatment was modified in 62 cases (30.1 %). There was no significant relationship of treatment modification with the underlying disease, HSCT, or neutropenia. Bronchoscopy with BAL is a valuable diagnostic tool to determine the etiology and appropriate treatment in patients with hematologic malignancy and pulmonary infiltrates. A BAL GM test is recommended when invasive pulmonary aspergillosis is suspected.

Phlorotannins are polyphenols of marine algae, particularly brown seaweed, having multiple biological activities. A reverse phase-high performance liquid chromatography method was developed for rapid and routine quantification of two major phlorotannins, dieckol and phlorofucofuroeckol-A (PFE-A), from boiling water- and organic solvent-extracts of brown seaweeds Ecklonia cava, E. stolonifera and Eisenia bicyclis. The regression equations for dieckol and PFE-A were as follows: the concentration (mg ml(-1)) = 16.56 x peak height (cm) + 0.44, and the concentration = 20.60 x peak height (cm) + 0.11, with correlation coefficients of 0.996 and 0.999, respectively. Compared to organic solvent extraction, the recovery yield of dieckol from boiling water extracts of E. cava, E. stolonifera and E. bicyclis was 86%, 93%, and 98%, respectively. The recovery yield of PFE-A was 74%, 86% and 62%, respectively. Antioxidant activity was detected in each E. bicyclis water extract (91%), followed by E. stolonifera (90%) and E. cava (74%). Dieckol and PFE-A showed almost 9- and 7-fold stronger antioxidant activity than the standard butylhydroxytoluene, and 6-and 4-fold greater than L-ascorbic acid in molar concentration, respectively.

Two strains, designated GCR0103(T) and GYR3121(T), were isolated from seawater of the Saemangeum Embankment in Jeollabuk-do, Korea. The cells of the two strains were Gram-reaction-negative and non-motile, and formed multicellular filaments. The colonies of the two strains were pink-pigmented and able to grow at 15-37 °C (optimum 25 °C) on R2A and NA medium. Strains GCR0103(T) and GYR3121(T) grew at pH 6.5-10 (optimum pH 7.5) and pH 5.5-9.5 (optimum pH 7.5), and within NaCl ranges of 0-0.4% and 0-1%, respectively. The polar lipid profiles of the two strains contained phosphatidylethanolamine, five unknown aminolipids, an unknown phospholipid and four or five unknown lipids. The DNA G+C contents of strains GCR0103(T) and GYR3121(T) were 56.0 and 54.5 mol%, respectively. The respiratory quinone detected in both strains was MK-7. The 16S rRNA gene sequence similarity between GCR0103(T) and GYR3121(T) was 95.5 %. The 16S rRNA gene sequence similarities of the two strains to closely related reference strains were less than 89 %. Phylogenetic analysis based on 16S rRNA genes showed that GCR0103(T) and GYR3121(T) formed a distinct phyletic line in the family Cytophagaceae. On the basis of the phenotypic, chemotaxonomic and phylogenetic properties, strains GCR0103(T) and GYR3121(T) represent two novel species in a new genus within the family Cytophagaceae, for which the names Nibrella saemangeumensis gen. nov., sp. nov. and Nibrella viscosa sp. nov. are proposed. The type strain of Nibrella saemangeumensis is GCR0103(T) ( = KACC 16453(T) = JCM 17927(T)) and the type strain of Nibrella viscosa is GYR3121(T) ( = KACC 16447(T) = JCM 17925(T)).

Background: Conventional biomarkers cannot always establish the cause of pleural effusions; thus, alternative tests permitting rapid and accurate diagnosis are required. The primary aim of this study is to assess the ability of pentraxin-3 (PTX3) in order to diagnose the cause of pleural effusion and compare its efficacy to that of other previously identified biomarkers., Methods: We studied 118 patients with pleural effusion, classified as transudates and exudates including malignant, tuberculous, and parapneumonic effusions (MPE, TPE, and PPE). The levels of PTX3, C-reactive protein (CRP), procalcitonin (PCT) and lactate in the pleural fluid were assessed., Results: The levels of pleural fluid PTX3 were significantly higher in patients with PPE than in those with MPE or TPE. PTX3 yielded the most favorable discriminating ability to predict PPE from MPE or TPE by providing the following: area under the curve, 0.74 (95% confidence interval, 0.63-0.84), sensitivity, 62.07%; and specificity, 81.08% with a cut-off point of 25.00 ng/mL., Conclusion: Our data suggests that PTX3 may allow improved differentiation of PPE from MPE or TPE compared to the previously identified biomarkers CRP and PCT.

Imatinib mesylate is a targeted therapy that acts by inhibiting tyrosine kinase of the bcr-abl fusion oncoprotein, which is specific to chronic myeloid leukemia (CML), and the c-transmembrane receptor, which is specific to gastrointestinal stromal tumors. Interstitial pneumonitis is a rare adverse event of imatinib therapy. It is clinically difficult to distinguish from infectious pneumonia, which can frequently occur due to the underlying disease. The standard treatment for imatinib-induced pneumonitis is to discontinue the medication and optionally administer corticosteroids. However, there are a few cases of successful retrial with imatinib. We describe a case of successful rechallenge of imatinib in a patient with imatinib-induced interstitial pneumonitis and CML without a recurrence of the underlying disease after 3 months of follow-up.

Incidence of nontuberculous mycobacterium (NTM) pulmonary disease is increasing with the wider recognition and development of diagnostic technology. Mycobacterium kansasii is the second most common pathogen of NTM pulmonary disease in human immunodeficiency virus (HIV)-infected patients. However in Korea, the incidence of M. kansasii pulmonary disease is relatively low, and there has been no report of M. kansasii pulmonary disease with bronchial involvement in HIV patients, to the best of our knowledge. We report a case of M. kansasii pulmonary disease presenting with endobronchial lesions in an HIV-infected patient complaining of chronic cough with bilateral enlargements of hilar lymph nodes on chest X-ray.

Objective: The aim of this study was to measure the level of nerve growth factor (NGF) in bronchial specimens from humans and to determine whether it correlated with not only clinical characteristics of asthma such as percent eosinophils, Th2 cytokine levels, and pulmonary function, but also metallopeptidase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1)., Methods: Fifty-three people participated; 42 had asthma. The participants underwent bronchoscopy and the specimens were analyzed. The participants' clinical data including pulmonary function tests were reviewed., Results: Bronchoalveolar lavage fluid (BALF) from patients with asthma had a significantly higher level of NGF compared with that from participants without asthma. NGF level showed a positive correlation with the percentage of eosinophils in both BALF and serum. The concentration of NGF did not correlate with that of Th2 cytokines interleukin (IL)-4, IL-5, and IL-13 in BALF or parameters of pulmonary function including degree of airway hyperresponsiveness (ARH). The levels of MMP-9 and TIMP-1 in BALF were higher in asthma patients than in participants without asthma. The levels of NGF correlated with TIMP-1 levels but not with MMP-9 in the whole participants., Conclusions: This study shows that NGF correlates with levels of eosinophils, a major effector cell in asthma. The high expression of NGF and TIMP-1 in asthma patients and the moderate correlation between NGF and TIMP-1 in the entire group of asthma subjects suggest a possible association between NGF and TIMP-1, which may influence asthma pathogenesis.

A Gram-stain-negative, rod-shaped, non-motile and yellow-pigmented bacterial strain, designated strain JJ013(T), was isolated from an artificial lake in Jeollabuk-do, South Korea, and characterized using a polyphasic approach. The 16S rRNA gene sequence of strain JJ013(T) indicated that the isolate belonged to the family Flavobacteriaceae and exhibited similarity levels of 96.6 % to the type strains of Flavobacterium cheonanense and Flavobacterium koreense and 96.5 % to the type strain of Flavobacterium chungnamense. Growth was observed at 20-30 °C and pH 5.0-7.0. The major cellular fatty acids of the novel strain were iso-C15 : 0 (27.5 %), iso-C15 : 1 G (17.8 %), iso-C17 : 0 3-OH (9.4 %) and iso-C15 : 0 3-OH (9.2 %). Flexirubin-type pigments were present. The DNA G+C content of strain JJ013(T) was 33.9 mol%, the major respiratory quinone was menaquinone-6 (MK-6) and the major polyamine was sym-homospermidine. The polar lipid profile of the strain JJ013(T) consisted of a phosphatidylethanolamine (PE), two unknown aminolipids (AL1-2), three unidentified lipid (L1-3) and an unknown glycolipid (GL). On the basis of the morphological and physiological properties and biochemical evidence presented, it is concluded that strain JJ013(T) represents a novel species of the genus Flavobacterium, for which the name Flavobacterium aciduliphilum sp. nov. is proposed; the type strain is JJ013(T) ( = KACC 16594(T) = JCM 18211(T)). Since C15 : 0, which is known as a predominant fatty acid of the genus Flavobacterium was not detected in the novel strain and other reference strains, we propose an emended description of the genus Flavobacterium.

A taxonomic study was carried out on a novel bacterial strain, designated MIC3010(T), which was isolated from a freshwater pond in Jeonju, Republic of Korea. Cells of the isolate were Gram-stain-negative, rod-shaped and non-motile. Comparison of the 16S rRNA gene sequences indicated that the isolate belonged to the family Flavobacteriaceae, with Flavobacterium haoranii LQY-7(T) as its closest relative, with a similarity of 94.2 %. The predominant fatty acids of strain MIC3010(T) were iso-C15 : 1 G, iso-C15 : 0 and iso-C17 : 0 3-OH. The polar lipid profile of strain MIC3010(T) revealed the presence of phosphatidylethanolamine (PE) and one unidentified lipid (L1) as major components. In addition, two aminolipids (AL1, AL2) and one glycolipid were present in small amounts. The DNA G+C content of the strain was 41.0 mol%. The strain contained MK-6 as the major quinone and sym-homospermidine as the predominant polyamine. On the basis of the evidence presented, it is concluded that strain MIC3010(T) represents a novel species of the genus Flavobacterium, for which the name Flavobacterium fontis sp. nov. is proposed. The type strain is MIC3010(T) ( = KACC 16593(T) = JCM 18212(T)).

A taxonomic study was carried out on a novel bacterial strain, designated AM1R11(T), which was isolated from seawater of Jeju Island in Korea. Cells of the isolate were found to be Gram-negative, rod-shaped and non-motile. Comparison of the 16S rRNA gene sequences indicated that the isolate belonged to the family Cytophagaceae, with Dyadobacter ginsengisoli Gsoil 043(T) as its closest relative, with a similarity of 96.6 %. It contained summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c, 36.9 %), iso-C15 : 0 (16.5 %) and C16 : 1ω5c (16.3 %) as the major fatty acids and MK-7 as the predominant menaquinone. The polar lipid profile of strain AM1R11(T) revealed the presence of phosphatidylethanolamine, one aminolipid and four unidentified lipids (L1, L2, L3 and L4). The DNA G+C content of strain AM1R11(T) was 45.1 mol%. On the basis of the evidence presented, it is concluded that strain AM1R11(T) represents a novel species of the genus Dyadobacter, for which the name Dyadobacter jejuensis sp. nov. is proposed. The type strain is AM1R11(T) ( = KACC 16446(T) = JCM 17918(T)).

A gram-negative, rod-shaped, non-motile and pink bacterial strain, designated strain GCM0142(T), was isolated from the confined seawater in the Saemangeum Tide Embankment of South Korea, and characterized using a polyphasic approach. 16S rRNA gene sequence analysis of strain GCM0142(T) indicated that the isolate belonged to the phylum Bacteroidetes and exhibited similarity levels of 94.0-96.4 % to the type strains of recognized Pontibacter species. Strain GCM0142(T) was oxidase- and catalase-positive. The major cellular fatty acids of the novel strain were summed feature 4 (comprising iso-C(17 : 1)I and/or anteiso-C(17 : 1)B, 36.8 %), iso-C(15 : 0) (22.3 %) and summed feature 3 (comprising C(16 : 1)ω7c and/or C(16 : 1)ω6c, 6.2 %). The DNA G+C content of strain GCM0142(T) was 48.9 mol% and the major quinone was MK-7. The polar lipid profile consisted of phosphatidylethanolamine, two unknown aminolipids (AL1-2), an unknown aminophospholipid, five unknown lipids (L1-5) and an unknown glycolipid. On the basis of the evidence presented, strain GCM0142(T) is considered to represent a novel species of the genus Pontibacter, for which the name Pontibacter saemangeumensis sp. nov. is proposed. The type strain is GCM0142(T) ( = KACC 16448(T) = JCM 17926(T)).

Neurotrophic factors are vital not only to support neuronal development but also to protect mature neurons from atrophy in neurodegenerative diseases. As an effort to explore natural sources that possess neurotrophic activity, we screened common marine algae for their neuritogenic activity in the developing rat hippocampal neurons in culture. Of the 22 seaweed species examined, ethanol extracts of Gelidium amansii (GAE) exhibited potent neuritogenic activity, followed by Undaria pinnatifida and Sargassum fulvellum extracts. The effects of GAE were dose dependent with an optimum concentration of 15 µg/mL. The GAE significantly promoted the initial neuronal differentiation from the stage I into the stage II and increased the indices of axonal and dendritic development such as the length, the numbers of primary processes, and branching frequencies by a minimum of twofold compared with the vehicle control. These results show that marine algae are promising candidates for neurotrophic potentials., (Copyright © 2012 John Wiley & Sons, Ltd.)

Background and Objectives: The influence of aging on the development of asthma has not been studied thoroughly. The aim of this study was to investigate age-related airway responses involving lung histology and expression of muscarinic receptors in a murine model of acute asthma., Methods: Female BALB/c mice at the ages of 6 weeks and 6, 9, and 12 months were sensitized and challenged with ovalbumin (OVA) for 1 month (n = 8-12 per group). We analyzed inflammatory cells and T-helper (Th)2 cytokines in bronchoalveolar lavage (BAL) fluid and parameters of airway remodeling and expression of muscarinic receptors in lung tissue., Results: Among the OVA groups, total cell and eosinophil numbers in BAL fluid were significantly higher in the older (6-, 9-, and 12-month-old) mice than in the young (6-week-old) mice. Interleukin (IL) 4 (IL-4) concentration increased, but IL-5 and IL-13 concentrations showed a decreased tendency, with age. IL-17 concentration tended to increase with age, which did not reach statistical significance. Periodic acid-Schiff (PAS) staining area, peribronchial collagen deposition, and area of α-smooth muscle staining were significantly higher in the 6-month older OVA group than in the young OVA group. The expression of the M3 and M2 muscarinic receptors tended to increase and decrease, respectively, with age., Conclusion: The aged mice showed an active and unique pattern not only on airway inflammation, but also on airway remodeling and expression of the muscarinic receptors during the development of acute asthma compared with the young mice. These findings suggest that the aging process affects the pathogenesis of acute asthma and age-specific approach might be more appropriate for better asthma control in a clinical practice.

A 47-year old man visited our hospital because of purulent sputum for 3 months. Chest X-ray showed destruction of both the upper lungs, and bronchoscopy revealed inflammatory change with whitish plaque on the left main bronchus through upper division of the left upper lobe. Tracheobronchial aspergillosis (TBA) was finally diagnosed as a result of histologic and microbiologic examination. However, he went abroad without medication before the diagnosis was made and visited again 10 months later. Follow-up bronchoscopy showed complete regression of the previously noted endobronchial lesion. We describe this case to consider the role of antifungal treatment in immunocompetent hosts, as well as to discuss a rare condition; TBA resolved spontaneously.

Typhlitis is a necrotizing colitis that usually occurs in neutropenic patients and develops most often in patients with hematologic malignancies such as leukemia and lymphoma. Typhlitis may proceed to bowel perforation, peritonitis and sepsis, which requires immediate treatment. Irinotecan is a semisynthetic analogue of the natural alkaloid camptothecin which prevents DNA from unwinding by inhibition of topoisomerase I. It is mainly used in colon cancer and small cell lung carcinoma (SCLC), of which the most common adverse effects are gastrointestinal toxicities. To the best of our knowledge, no case of typhlitis after chemotherapy with a standard dose of irinotecan in a solid tumor has been reported in the literature. We, herein, report the first case of typhlitis developed after chemotherapy combining irinotecan and cisplatin in a patient with SCLC.

Background: The release of interferon-gamma (IFN-γ) by T lymphocytes increases after rechallenge with Mycobacterium tuberculosis antigen, especially, at a localized site of tuberculosis (TB) infection. We aimed to compare the clincial efficacy of two commercial IFN-γ release assays from pleural fluid for the diagnosis in tuberculous pleurisy., Methods: We performed T-SPOT.TB and QuantiFERON-TB Gold tests simultaneously on pleural fluid and peripheral blood samples from patients with pleural effusion, in South Korea, an area with intermediate TB burden., Results: Thirty-six patients were enrolled prospectively, and tuberculous pleurisy was found in 21 patients. Both the numbers of IFN-γ secreting T cells and the concentration of IFN-γ were greater in the pleural tuberculous group, comparing with the non-tuberculous group. Moreover, in the tuberculous group, there was a significant difference in IFN-γ producing spot-forming cells using the T-SPOT.TB method between pleural fluid and peripheral blood. The receiver operating characteristic (ROC) curve, was the greatest for pleural fluid T-SPOT.TB test, followed by peripheral blood T-SPOT.TB test, peripheral blood QuantiFERON-TB Gold test, and pleural fluid QuantiFERON-TB Gold test (area under the ROC curve of 0.956, 0.890, 0.743, and 0.721, respectively). The T-SPOT.TB assay produced less indeterminate results than did QuantiFERON-TB Gold assay in both pleural fluid and peripheral blood., Conclusion: These findings suggest that the pleural fluid T-SPOT.TB test could be the most useful test among the IFN-γ release assays for diagnosing tuberculous pleurisy in an area with an intermediate prevalence of TB infection.

Sargassum fulvellum (Turner) C. Agardh is an edible brown macroalgae having pharmacological importance. In previous reports, we described the screening of marine algae for their neuritogenic activity in developing hippocampal neurons and found that ethanol extract of S. fulvellum (SFE) possesses promising neurite-outgrowth-promoting activity. In this study, we evaluated whether the initial neurite promoting effect of SFE was followed on the further neuronal maturation and synapse formation. SFE exhibited dose-dependent effect on neurite maturation with an optimum concentration of 5 μg/mL. The initial neuronal differentiation is significantly promoted by SFE. Subsequently, compared with control culture, SFE increased the indices of axonal and dendritic developments such as the number and the length of primary processes, and branching frequencies. In addition to its effect on neurite development, SFE significantly increased the number of puncta for postsynaptic density-95, synaptic vesicle 2, and synapse (about 35%, 67%, and 125%, respectively, of control). Moreover, SFE dose-dependently protects neurons from naturally occurring death in normal culture condition. Taken together, our data demonstrate that SFE can promote neuronal maturation and synaptogenesis and support neuronal survival, suggesting the beneficial effect of this alga in nervous system.

Background: 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., Objective: 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., Methods: 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., Results: 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., Conclusion: 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., (Copyright © 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The aim of this study was to analyze clinical situations requiring rigid bronchoscopy and evaluate usefulness of rigid bronchoscopic intervention in benign or malignant airway disorders., Methods: We retrospectively reviewed 29 patients who underwent rigid bronchoscopy from November 2007 to February 2011 at St. Paul's Hospital, The Catholic University of Korea School of Medicine., Results: Of the 29 patients, the most frequent underlying etiology was benign stenosis of trachea (n=20). Of those 20 patients, 16 had post-intubation tracheal stenosis (PITS), 2 had tracheal stenosis due to inhalation burn (IBTS) and other 2 had obstructive fibrinous tracheal pseudomembrane (OFTP). Other etiologies were airway malignancy (n=6), endobronchial stenosis due to tuberculosis (n=2), and foreign body (n=1). For treatment, silicone stent insertion was done in 16 cases of PITS and IBTS and mechanical removal was performed in 2 cases of OFTP. In 6 cases of malignant airway obstruction mechanical debulking was performed and silicone stents were inserted additionally in 2 cases. Balloon dilatation and electrocautery were used in 2 cases of endobronchial stenosis due to tuberculosis. In all cases of stent, airway obstructive symptom improved immediately. Granulation tissue formation was the most common complication., Conclusion: Tracheal stenosis was most common indication and silicone stenting was most common procedure of rigid bronchoscopy in our center. Rigid bronchoscopic procedures, at least tracheal silicone stenting, should be included in pulmonary medicine fellowship programs because it is a very effective and indispensable method to relieve critical airway obstruction which needs training to learn.

An 80% methanolic extract of Rhus verniciflua Stokes bark showed significant anti-viral activity against fish pathogenic infectious hematopoietic necrosis virus (IHNV) and viral hemorrhagic septicemia virus (VHSV) in a cell-based assay measuring virus-induced cytopathic effect (CPE). Activity-guided fractionation and isolation for the 80% methanolic extract of R. verniciflua yielded the most active ethyl acetate fraction, and methyl gallate (1) and four flavonoids: fustin (2), fisetin (3), butin (4) and sulfuretin (5). Among them, fisetin (3) exhibited high antiviral activities against both IHNV and VHSV showing EC(50) values of 27.1 and 33.3 μM with selective indices (SI = CC(50)/EC(50)) more than 15, respectively. Fustin (2) and sulfuretin (5) displayed significant antiviral activities showing EC50 values of 91.2-197.3 μM against IHNV and VHSV. In addition, the antiviral activity of fisetin against IHNV and VHSV occurred up to 5 hr post-infection and was not associated with direct virucidal effects in a timed addition study using a plaque reduction assay. These results suggested that the bark of R. verniciflua and isolated flavonoids have significant anti-viral activity against IHNV and VHSV, and also have potential to be used as anti-viral therapeutics against fish viral diseases.

Marine derived actinomycetes constituting 185 strains were screened for their antifouling activity against the marine seaweed, Ulva pertusa, and fouling diatom, Navicula annexa. Strain 291-11 isolated from the seaweed, Undaria pinnatifida, rhizosphere showed the highest antifouling activity and was identified as Streptomyces praecox based on a 16S rDNA sequence analysis. Strain 291-11 was therefore named S. praecox 291-11. The antifouling compounds from S. praecox 291-11 were isolated, and their structures were analyzed. The chemical constituents representing the antifouling activity were identified as (6S,3S)-6-benzyl-3-methyl-2,5-diketopiperazine (bmDKP) and (6S,3S)-6-isobutyl-3-methyl-2,5-diketopiperazine (imDKP) by interpreting the nuclear magnetic resonance and high-resolution mass spectroscopy data. Approximately 4.8 mg of bmDKP and 3.1 mg of imDKP were isolated from 1.2 g of the S. praecox 291-11 crude extract. Eight different compositions of culture media were investigated for culture, the TBFeC medium being best for bmDKP and TCGC being the optimum for imDKP production. Two compounds respectively showed a 17.7 and 21 therapeutic ratio (LC50/EC50) to inhibit zoospores, and two compounds respectively showed a 263 and 120.2 therapeutic ratio to inhibit diatoms.

Endobronchial metastasis from thyroid follicular carcinoma is a rare manifestation. We describe a case of 62-year-old woman who underwent total thyroidectomy due to thyroid follicular carcinoma 19 years previously. Computerized tomography and bronchoscopy suggested an endobronchial enhancing nodule in the right bronchus intermedius, resulting in right middle lobe (RML) and right lower lobe (RLL) collapse. A biopsy specimen showed thyroid follicular carcinoma identical to that taken from a specimen previously. She underwent metastectomy and high-dose radioactive iodine ablation therapy. To our knowledge, this patient represents the first case of endobronchial metastasis with a long past history of thyroid follicular carcinoma.

Multifocal skeletal tuberculosis is a very rare manifestation of tuberculous infection. The multiple bone lesions of multifocal skeletal tuberculosis are difficult to differentiate from metastasis, even when performing 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (FDG PET/CT) or magnetic resonance imaging (MRI). A 25-year-old man presented with an abnormal chest X-ray. Radiologically, there were extensive osteolytic lesions on the skull, along the entire spine and on the ribs and both iliac bones, suggesting a diagnosis of bone metastasis. On FDG PET/CT, intensely increased F-18 FDG lesions were observed. A bone biopsy with a microbiologic study revealed a tuberculous infection. Follow-up PET/CT performed after treatment showed marked improvement in the extensive FDG uptake lesions.

Elevated phospholipase D (PLD) expression prevents cell cycle arrest and apoptosis. However, the roles of PLD isoforms in cell proliferation and apoptosis are incompletely understood. Here, we investigated the physiological significance of the interaction between PLD2 and protein kinase CKII (CKII) in HCT116 human colorectal carcinoma cells. PLD2 interacted with the CKIIβ subunit in HCT116 cells. The C-terminal domain (residues 578-933) of PLD2 and the N-terminal domain of CKIIβ were necessary for interaction between the two proteins. PLD2 relocalized CKIIβ to the plasma membrane area. Overexpression of PLD2 reduced CKIIβ protein level, whereas knockdown of PLD2 led to an increase in CKIIβ expression. PLD2-induced CKIIβ reduction was mediated by ubiquitin-dependent degradation. The C-terminal domain of PLD2 was sufficient for CKIIβ degradation as the catalytic activity of PLD2 was not required. Taken together, the results indicate that the C-terminal domain of PLD2 can regulate CKII by accelerating CKIIβ degradation in HCT116 cells.

Two genes encoding MAP kinase homologs, designated as mpkB and mpkC, were isolated from Aspergillus nidulans by PCR with degenerate primers. Deletion and over-expression mutants of mpkC showed no detectable phenotypes under any external stress tested. Deletion of mpkB caused pleiotropic phenotypes including a failure in forming cleistothecia under any induction conditions for sexual development, increased Hülle cell production, slow hyphal growth and aberrant conidiophore morphology. Over-expression of mpkB led to increased cleistothecium production. While the transcripts of mpkB and mpkC were constitutively synthesized through the entire life cycle, their size and amount differed with developmental stages. An outcross test using fluorescent protein reporters showed that the mpkB deletion mutant could not form heterokaryons with wild type. Protoplast fusion experiments showed that the fusant of the mpkB mutant with wild type could undergo normal sexual development. However, heterokaryotic mycelia that were produced from a fusant between two mpkB deletion mutants could not form cleistothecia, although they did appear to form diploid nuclei. These results suggest that the MpkB MAP kinase is required for some post-karyogamy process as well as at the hyphal anastomosis stage to accomplish sexual development successfully.