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1.  Association between obesity-related adipokines and colorectal cancer: A case-control study and meta-analysis 
AIM: To examine the association between obesity-related adipokines (adiponectin, leptin, resistin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) and colorectal cancer (CRC) risk.
METHODS: Serum levels of adipokines were measured in 100 CRC patients and age- and sex-matched controls for the data analysis. Unconditional logistic regression models were used for estimating ORs and 95%CIs related to each adipokine. For the meta-analysis, studies published before July 2013 available on Medline/PubMed and EMBASE were retrieved. The analysis included a total of 17 relevant studies (including the present case-control study): nine studies on adiponectin and eight on leptin. The effect sizes of ORs and 95%CIs were estimated using RevMan 5.1. Heterogeneity was evaluated using Cochran’s Q-test and I2 statistics.
RESULTS: Among the five adipokines, only resistin levels were significantly higher in cases than in controls (P < 0.001). The case-control study results showed no association between adiponectin and CRC and a negative association between leptin and CRC. However, the results of the meta-analysis showed a significant inverse association between adiponectin and CRC (OR = 0.91, 95%CI: 0.83-1.00, P = 0.04) and no association between CRC and leptin. After stratification by study design, an inverse association between adiponectin and CRC was observed in prospective studies only (OR = 0.90, 95%CI: 0.82-0.99, P = 0.03), whereas the association between leptin and CRC was inconsistent (prospective studies: OR = 1.14, 95%CI: 1.02-1.27, P = 0.02 and retrospective studies: OR = 0.47, 95%CI: 0.29-0.74, P = 0.001). The associations of resistin and TNF-α with CRC risk were positive, but no association was observed for IL-6.
CONCLUSION: Our results suggest a negative association of leptin, positive associations of resistin and TNF-α, and null associations of adiponectin and IL-6 with CRC. However, further studies with larger number of prospective approaches are needed.
doi:10.3748/wjg.v20.i24.7941
PMCID: PMC4069321  PMID: 24976730
Obesity; Colorectal cancer; Cancer risk; Adipokines; Obesity-related adipokines
2.  Plasma Osteopontin Is a Useful Diagnostic Biomarker for Advanced Non-Small Cell Lung Cancer 
Background
Osteopontin (OPN) and carbonic anhydrase IX (CAIX), which are expressed on the surface of tumor cells, are associated with hypoxia during tumor development and progression. However, the roles of these proteins in the plasma of patients with non-small cell lung cancer (NSCLC) are poorly understood. Herein, we hypothesized that plasma OPN and CAIX levels could be used as diagnostic and prognostic tumor markers in patients with NSCLC.
Methods
Fifty-three patients with NSCLC and 50 healthy control subjects were enrolled. We selected controls without malignancy and matched them with NSCLC patient cases according to age and gender. Blood samples were collected at the time of diagnosis; the plasma levels of OPN and CAIX were measured by enzyme-linked immunosorbent assays.
Results
The plasma levels of OPN in the patients with NSCLC were significantly elevated as compared to those in the controls (p=0.016). However, there was no difference in the plasma level of CAIX between the NSCLC patients and controls. NSCLC patients with a distant metastasis had a remarkable increase in plasma OPN compared with patients without metastasis (p=0.026), but no such correlation was found for CAIX. There was no difference in overall survival rates according to the plasma level of OPN between the two groups (by Kaplan-Meier survival analysis).
Conclusion
Plasma OPN levels were elevated in patients with NSCLC as compared with the controls, with greater elevation of OPN levels in the advanced stages of disease. Therefore, plasma OPN may have utility as a diagnostic, but not prognostic, biomarker of advanced NSCLC.
doi:10.4046/trd.2013.75.3.104
PMCID: PMC3790021  PMID: 24101934
Osteopontin; CA9 Protein, Human; Lung Neoplasms
4.  Increased intestinal macromolecular permeability and urine nitrite excretion associated with liver cirrhosis with ascites 
AIM: To determine intestinal permeability, the serum tumor necrosis factor (TNF)-α level and urine nitric oxide (NO) metabolites are altered in liver cirrhosis (LC) with or without ascites.
METHODS: Fifty-three patients with LC and 26 healthy control subjects were enrolled in the study. The intestinal permeability value is expressed as the percentage of polyethylene glycol (PEG) 400 and 3350 retrieval in 8-h urine samples as determined by high performance liquid chromatography. Serum TNF-α concentrations and urine NO metabolites were determined using an enzyme-linked immunosorbent assay (ELISA) and Greiss reaction method, respectively.
RESULTS: The intestinal permeability index was significantly higher in patients with LC with ascites than in healthy control subjects or patients with LC without ascites (0.88 ± 0.12 vs 0.52 ± 0.05 or 0.53 ± 0.03, P < 0.05) and correlated with urine nitrite excretion (r = 0.98). Interestingly, the serum TNF-α concentra-tion was significantly higher in LC without ascites than in control subjects or in LC with ascites (198.9 ± 55.8 pg/mL vs 40.9 ± 12.3 pg/mL or 32.1 ± 13.3 pg/mL, P < 0.05). Urine nitrite excretion was significantly higher in LC with ascites than in the control subjects or in LC without ascites (1170.9 ± 28.7 μmol/L vs 903.1 ± 55.1 μmol/L or 956.7 ± 47.7 μmol/L, P < 0.05).
CONCLUSION: Increased intestinal macromolecular permeability and NO is probably of importance in the pathophysiology and progression of LC with ascites, but the serum TNF-α concentration was not related to LC with ascites.
doi:10.3748/wjg.14.3884
PMCID: PMC2721447  PMID: 18609714
Intestinal permeability; Tumor necrosis factor-α; Nitric oxide; Liver cirrhosis; Ascites
5.  Genome-wide association analysis identifies six new loci associated with forced vital capacity 
Loth, Daan W. | Artigas, María Soler | Gharib, Sina A. | Wain, Louise V. | Franceschini, Nora | Koch, Beate | Pottinger, Tess | Smith, Albert Vernon | Duan, Qing | Oldmeadow, Chris | Lee, Mi Kyeong | Strachan, David P. | James, Alan L. | Huffman, Jennifer E. | Vitart, Veronique | Ramasamy, Adaikalavan | Wareham, Nicholas J. | Kaprio, Jaakko | Wang, Xin-Qun | Trochet, Holly | Kähönen, Mika | Flexeder, Claudia | Albrecht, Eva | Lopez, Lorna M. | de Jong, Kim | Thyagarajan, Bharat | Alves, Alexessander Couto | Enroth, Stefan | Omenaas, Ernst | Joshi, Peter K. | Fall, Tove | Viňuela, Ana | Launer, Lenore J. | Loehr, Laura R. | Fornage, Myriam | Li, Guo | Wilk, Jemma B. | Tang, Wenbo | Manichaikul, Ani | Lahousse, Lies | Harris, Tamara B. | North, Kari E. | Rudnicka, Alicja R. | Hui, Jennie | Gu, Xiangjun | Lumley, Thomas | Wright, Alan F. | Hastie, Nicholas D. | Campbell, Susan | Kumar, Rajesh | Pin, Isabelle | Scott, Robert A. | Pietiläinen, Kirsi H. | Surakka, Ida | Liu, Yongmei | Holliday, Elizabeth G. | Schulz, Holger | Heinrich, Joachim | Davies, Gail | Vonk, Judith M. | Wojczynski, Mary | Pouta, Anneli | Johansson, Åsa | Wild, Sarah H. | Ingelsson, Erik | Rivadeneira, Fernando | Völzke, Henry | Hysi, Pirro G. | Eiriksdottir, Gudny | Morrison, Alanna C. | Rotter, Jerome I. | Gao, Wei | Postma, Dirkje S. | White, Wendy B. | Rich, Stephen S. | Hofman, Albert | Aspelund, Thor | Couper, David | Smith, Lewis J. | Psaty, Bruce M. | Lohman, Kurt | Burchard, Esteban G. | Uitterlinden, André G. | Garcia, Melissa | Joubert, Bonnie R. | McArdle, Wendy L. | Musk, A. Bill | Hansel, Nadia | Heckbert, Susan R. | Zgaga, Lina | van Meurs, Joyce B.J. | Navarro, Pau | Rudan, Igor | Oh, Yeon-Mok | Redline, Susan | Jarvis, Deborah | Zhao, Jing Hua | Rantanen, Taina | O’Connor, George T. | Ripatti, Samuli | Scott, Rodney J. | Karrasch, Stefan | Grallert, Harald | Gaddis, Nathan C. | Starr, John M. | Wijmenga, Cisca | Minster, Ryan L. | Lederer, David J. | Pekkanen, Juha | Gyllensten, Ulf | Campbell, Harry | Morris, Andrew P. | Gläser, Sven | Hammond, Christopher J. | Burkart, Kristin M. | Beilby, John | Kritchevsky, Stephen B. | Gudnason, Vilmundur | Hancock, Dana B. | Williams, O. Dale | Polasek, Ozren | Zemunik, Tatijana | Kolcic, Ivana | Petrini, Marcy F. | Wjst, Matthias | Kim, Woo Jin | Porteous, David J. | Scotland, Generation | Smith, Blair H. | Viljanen, Anne | Heliövaara, Markku | Attia, John R. | Sayers, Ian | Hampel, Regina | Gieger, Christian | Deary, Ian J. | Boezen, H. Marike | Newman, Anne | Jarvelin, Marjo-Riitta | Wilson, James F. | Lind, Lars | Stricker, Bruno H. | Teumer, Alexander | Spector, Timothy D. | Melén, Erik | Peters, Marjolein J. | Lange, Leslie A. | Barr, R. Graham | Bracke, Ken R. | Verhamme, Fien M. | Sung, Joohon | Hiemstra, Pieter S. | Cassano, Patricia A. | Sood, Akshay | Hayward, Caroline | Dupuis, Josée | Hall, Ian P. | Brusselle, Guy G. | Tobin, Martin D. | London, Stephanie J.
Nature genetics  2014;46(7):669-677.
Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10−8) with FVC in or near EFEMP1, BMP6, MIR-129-2/HSD17B12, PRDM11, WWOX, and KCNJ2. Two (GSTCD and PTCH1) loci previously associated with spirometric measures were related to FVC. Newly implicated regions were followed-up in samples of African American, Korean, Chinese, and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and pathogenesis of restrictive lung disease.
doi:10.1038/ng.3011
PMCID: PMC4140093  PMID: 24929828
6.  Three-month Treatment Response and Exacerbation in Chronic Obstructive Pulmonary Disease 
The aim of this study was to investigate relationships between acute exacerbation and Forced Expiratory Volume 1 second (FEV1) improvement after treatment with combined long-acting beta-agonist (LABA) and inhaled corticosteroid (ICS) in patients with chronic obstructive pulmonary disease (COPD). A total of 137 COPD patients were classified as responders or nonresponders according to FEV1 improvement after 3 months of LABA/ICS treatment in fourteen referral hospitals in Korea. Exacerbation occurrence in these two subgroups was compared over a period of 1 yr. Eighty of the 137 COPD patients (58.4%) were classified as responders and 57 (41.6%) as nonresponders. Acute exacerbations occurred in 25 patients (31.3%) in the responder group and in 26 patients (45.6%) in the nonresponder group (P=0.086). FEV1 improvement after LABA/ICS treatment was a significant prognostic factor for fewer acute exacerbations in a multivariate Cox proportional hazard model adjusted for age, sex, FEV1, smoking history, 6 min walk distance, body mass index, exacerbation history in the previous year, and dyspnea scale.Three-month treatment response to LABA/ICS might be a prognostic factor for the occurrence of acute exacerbation in COPD patients.
Graphical Abstract
doi:10.3346/jkms.2015.30.1.54
PMCID: PMC4278027  PMID: 25552883
Pulmonary Disease, Chronic Obstructive; Forced Expiratory Volume; Disease Progression
7.  Lesion localization of global aphasia without hemiparesis by overlapping of the brain magnetic resonance images 
Neural Regeneration Research  2014;9(23):2081-2086.
Global aphasia without hemiparesis is a striking stroke syndrome involving language impairment without the typically manifested contralateral hemiparesis, which is usually seen in patients with global aphasia following large left perisylvian lesions. The objective of this study is to elucidate the specific areas for lesion localization of global aphasia without hemiparesis by retrospectively studying the brain magnetic resonance images of six patients with global aphasia without hemiparesis to define global aphasia without hemiparesis-related stroke lesions before overlapping the images to visualize the most overlapped area. Talairach coordinates for the most overlapped areas were converted to corresponding anatomical regions. Lesions where the images of more than three patients overlapped were considered significant. The overlapped global aphasia without hemiparesis related stroke lesions of six patients revealed that the significantly involved anatomical lesions were as follows: frontal lobe, sub-gyral, sub-lobar, extra-nuclear, corpus callosum, and inferior frontal gyrus, while caudate, claustrum, middle frontal gyrus, limbic lobe, temporal lobe, superior temporal gyrus, uncus, anterior cingulate, parahippocampal, amygdala, and subcallosal gyrus were seen less significantly involved. This study is the first to demonstrate the heterogeneous anatomical involvement in global aphasia without hemiparesis by overlapping of the brain magnetic resonance images.
doi:10.4103/1673-5374.147935
PMCID: PMC4316473  PMID: 25657725
nerve regeneration; global aphasia without hemiparesis; global aphasia; stroke; hemiparesis; brain; magnetic resonance imaging; neural regeneration
8.  Antimicrobial Activity of Peptides Derived from Olive Flounder Lipopolysaccharide Binding Protein/Bactericidal Permeability-Increasing Protein (LBP/BPI) 
Marine Drugs  2014;12(10):5240-5257.
We describe the antimicrobial function of peptides derived from the C-terminus of the olive flounder LBP BPI precursor protein. The investigated peptides, namely, ofLBP1N, ofLBP2A, ofLBP4N, ofLBP5A, and ofLBP6A, formed α-helical structures, showing significant antimicrobial activity against several Gram-negative bacteria, Gram-positive bacteria, and the yeast Candida albicans, but very limited hemolytic activities. The biological activities of these five analogs were evaluated against biomembranes or artificial membranes for the development of candidate therapeutic agents. Gel retardation studies revealed that peptides bound to DNA and inhibited migration on an agarose gel. In addition, we demonstrated that ofLBP6A inhibited polymerase chain reaction. These results suggested that the ofLBP-derived peptide bactericidal mechanism may be related to the interaction with intracellular components such as DNA or polymerase.
doi:10.3390/md12105240
PMCID: PMC4210897  PMID: 25329706
antimicrobial peptide; LPS-binding protein; bactericidal permeability-increasing protein; analogs; antimicrobial mechanism
9.  Characterization, Expression Profile, and Promoter Analysis of the Rhodeus uyekii Vitellogenin Ao1 Gene 
The fish Vitellogenin (Vg) gene has been applied as a biomarker for exposure to estrogenic compounds in the aquatic environment. In this study, we cloned and characterized Vg cDNA from the Korean rose bitterling Rhodeus uyekii (Ru-Vg). The Ru-Vg cDNA encodes a 1424-amino-acid polypeptide that belongs to the VgAo1 family and contains a putative signal peptide, lipovitellin I, phosvitin, and lipovitellin II, but does not contain the vWFD domain or the C-terminal peptide. The deduced Ru-Vg protein has high amino acid identity (73.97%–32.17%) with fish Vg proteins. Pairwise alignment and phylogenetic analysis revealed that Ru-Vg is most closely related to Acheilognathus yamatsutae Vg. Ru-Vg transcripts were detected using quantitative polymerase chain reaction in all tissues tested, with the highest level of expression observed in the ovary. Ru-Vg mRNA was upregulated in R. uyekii hepatopancreas cells in response to treatment with 17β-estradiol (E2) or 17α-ethinylestradiol (EE2). Luciferase reporter expression, driven by the 5'-regulatory region of the Ru-Vg gene spanning from −1020 bp to the start codon was induced by the estrogen receptor and was synergistically activated by treatment with E2 or EE2. These results suggest that R. uyekii and the Ru-Vg gene may be useful as biomarkers for exposure to E2 or EE2.
doi:10.3390/ijms151018804
PMCID: PMC4227248  PMID: 25329620
17β-Estradiol; 17α-Ethinylestradiol; Korean rose bitterling; promoter assay; Rhodeus uyekii; vitellogenin
10.  Influence of Environmental Exposures on Patients with Chronic Obstructive Pulmonary Disease in Korea 
Background
Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation and results from environmental factors and genetic factors. Although cigarette smoking is a major risk factor, other environmental exposures can influence COPD. The purpose of this study is to investigate the clinical characteristics of COPD according to the history of environmental exposure.
Methods
The study population comprised of 347 subjects with COPD who were recruited from the pulmonary clinics of 14 hospitals within the Korean Obstructive Lung Disease Study Group. We classified environmental exposures according to history of living near factory, and direct exposure history to firewood or briquette. According to living environmental exposures, we compared the frequency of respiratory symptoms, pulmonary function, quality of life, exercise capacity, and computed tomography phenotypes.
Results
Thirty-one subjects (8.9%) had history of living near factory, 271 (78.3%) had exposure history to briquette, and 184 (53.3%) had exposure history to firewood. Patients with history of living near a factory had a significantly longer duration of sputum, while patients with exposure to firewood tended to have lower forced expiratory volume in one second, and patients with exposure to briquette tended to have lower six minute walk distance.
Conclusion
COPD subjects with the history of living near factory had more frequent respiratory symptoms such as sputum. Our data suggest that environmental exposure may influence clinical phenotype of COPD.
doi:10.4046/trd.2014.76.5.226
PMCID: PMC4050070
Pulmonary Disease, Chronic Obstructive; Environmental Exposure; Air Pollutants; Occupational Exposure; Fossil Fuels
11.  The Autographa californica Multiple Nucleopolyhedrovirus ORF78 Is Essential for Budded Virus Production and General Occlusion Body Formation 
Journal of Virology  2013;87(15):8441-8450.
ORF78 (ac78) of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is a baculovirus core gene of unknown function. To determine the role of ac78 in the baculovirus life cycle, an AcMNPV mutant with ac78 deleted, Ac78KO, was constructed. Quantitative PCR analysis revealed that ac78 is a late gene in the viral life cycle. After transfection into Spodoptera frugiperda cells, Ac78KO produced a single-cell infection phenotype, indicating that no infectious budded viruses (BVs) were produced. The defect in BV production was also confirmed by both viral titration and Western blotting. However, viral DNA replication was unaffected, and occlusion bodies were formed. An analysis of BVs and occlusion-derived viruses (ODVs) revealed that AC78 is associated with both forms of the virions and is an envelope structural protein. Electron microscopy revealed that AC78 also plays an important role in the embedding of ODV into the occlusion body. The results of this study demonstrate that AC78 is a late virion-associated protein and is essential for the viral life cycle.
doi:10.1128/JVI.01290-13
PMCID: PMC3719795  PMID: 23698311
12.  Combined blockade of HER2 and VEGF exerts greater growth inhibition of HER2-overexpressing gastric cancer xenografts than individual blockade 
Gastric cancer overexpressing the human epidermal growth factor 2 (HER2) protein has a poor outcome, although a combination of chemotherapy and the anti-HER2 antibody trastuzumab has been approved for the treatment of advanced gastric cancer. Vascular endothelial growth factor (VEGF) expression in gastric cancer is correlated with recurrence and poor prognosis; however, the anti-VEGF antibody bevacizumab has shown limited efficacy against gastric cancer in clinical trials. In this study, we evaluated the antitumor effects of trastuzumab; VEGF-Trap binding to VEGF-A, VEGF-B and placental growth factor (PlGF); and a combination of trastuzumab and VEGF-Trap in a gastric cancer xenograft model. Although trastuzumab and VEGF-Trap each moderately inhibited tumor growth, the combination of these agents exerted greater inhibition compared with either agent alone. Immunohistochemical analyses indicated that the reduction in tumor growth was associated with decreased proliferation and increased apoptosis of tumor cells and decreased tumor vascular density. The combined treatment resulted in fewer proliferating tumor cells, more apoptotic cells and reduced tumor vascular density compared with treatment with trastuzumab or VEGF-Trap alone, indicating that trastuzumab and VEGF-Trap had additive inhibitory effects on the tumor growth and angiogenesis of the gastric cancer xenografts. These data suggest that trastuzumab in combination with VEGF-Trap may represent an effective approach to treating HER2-overexpressing gastric cancer.
doi:10.1038/emm.2013.111
PMCID: PMC3849567  PMID: 24176949
combination treatment; gastric cancer; HER2; trastuzumab; VEGF-Trap
13.  Genome Sequence of Marine Bacterium Idiomarina sp. Strain 28-8, Isolated from Korean Ark Shells 
Genome Announcements  2013;1(5):e00772-13.
Idiomarina sp. strain 28-8 is an aerobic, Gram-negative, flagellar bacterium isolated from the bodies of ark shells (Scapharca broughtonii) collected from underwater sediments in Gangjin Bay, South Korea. Here, we present the draft genome sequence of Idiomarina sp. 28-8 (2,971,606 bp, with a G+C content of 46.9%), containing 2,795 putative coding sequences.
doi:10.1128/genomeA.00772-13
PMCID: PMC3790083  PMID: 24092779
14.  Acute Bilateral Visual Loss Related to Orthostatic Hypotension 
A 50-year-old man had undergone lumbar vertebral surgery and was confined to bed in the supine position for three months. When he sat up from the prolonged supine position, he showed clinical signs of orthostatic hypotension and reported decreased vision in both eyes. He also had underlying anemia. Ophthalmologic findings suggested bilateral anterior ischemic optic neuropathy (ION) as the cause of the visual loss. Although there are numerous reports of ION in the setting of hemodynamic compromise, such as systemic hypotension, cases of ION-associated orthostatic hypotension are very rare.
doi:10.3341/kjo.2013.27.5.372
PMCID: PMC3782584  PMID: 24082776
Ischemic optic neuropathy; Optic disc edema; Orthostatic hypotension; Visual loss
15.  Neural Substrate Responsible for Crossed Aphasia 
Journal of Korean Medical Science  2013;28(10):1529-1533.
Crossed aphasia (CA) refers to language impairment secondary to right hemisphere lesion. Imaging analysis on the lesion location of CA has not yet been reported in the literature. This study was proposed to analyze the most prevalent lesion site related to CA. Brain MRI of 7 stroke patients satisfying the criteria for CA were used to define Region of interest (ROIs) before overlaying the images to visualize the most overlapped area. Talairach coordinates for the most overlapped areas were converted to corresponding anatomical regions. Anatomical lesions where more than 3 patients' images were overlapped were considered significant. The overlayed ROIs of 7 patients revealed the lentiform nucleus as the most frequently involved area, overlapping in 6 patients. Our study first demonstrates the areas involved in CA by lesion mapping using brain MRI, and lentiform nucleus is the responsible neural substrate for crossed aphasia.
doi:10.3346/jkms.2013.28.10.1529
PMCID: PMC3792610  PMID: 24133361
Aphasia; Stroke; Lentiform Nucleus; Crossed Aphasia
16.  Seasonal Variation in Skin Sensitivity to Aeroallergens 
Purpose
We previously demonstrated seasonal variation in sensitization to aeroallergens in a small group of patients with exercise-induced asthma. This study was performed to confirm the relationship in a much larger population.
Methods
The charts of 1,891 patients who received allergy skin prick tests were reviewed retrospectively. The test results from subjects aged ≤60 years were compared between the groups classified according to the season when the patients received the tests (spring: March-May, summer: June-August, fall: September-November, winter: December-February). The data from 25 respiratory allergy patients who received the tests two or more times and showed a positive response at least once were analyzed longitudinally.
Results
The most prevalent among 29 tested aeroallergens were house dust mites (HDMs) Dermatophagoides pteronyssinus and D. farinae. The skin sensitization rates to D. pteronyssinus (23.2% vs. 32.1%, P=0.004) and D. farinae (22.2% vs. 30.2%, P=0.009) were significantly lower in the summer and higher in the fall (38.3% vs. 26.6% and 35.6% vs. 25.3%; P=0.001 respectively) than those in other seasons in patients with a respiratory allergy (n=1,102). The sensitization rates to weed pollens in the fall (13.9% vs. 8.3%, P=0.006) and to Aspergillus fumigatus in the winter (2.9% vs. 0.7%, P=0.005) were significantly higher. In patients with non-respiratory allergy such as urticaria/anaphylaxis (n=340), the D. farinae sensitization rate was significantly lower in the summer also but higher in the spring. The trend of the HDM sensitization rate being lower in the summer and higher in the fall was observed in the longitudinal study.
Conclusions
Skin sensitivity to aeroallergens such as HDMs, pollens, and molds demonstrates seasonal variation in respiratory allergy patients. Non-respiratory allergy patients also showed seasonal variation in sensitivity to aeroallergens, which might be related to the "priming" effect of allergens.
doi:10.4168/aair.2013.5.5.301
PMCID: PMC3756177  PMID: 24003387
Seasonal variation; skin sensitivity; aeroallergens; allergy
17.  Bilateral central serous chorioretinopathy with retinal pigment epithelium tears following epidural steroid injection 
Indian Journal of Ophthalmology  2013;61(9):514-515.
The cause of central serous chorioretinopathy (CSC) is mostly idiopathic. Other cause such as stressful event or use of corticosteroid has been associated with severe form of CSC. Atypical presentation of CSC has widespread degeneration of retinal pigment epithelium (RPE) or bullous retinal detachment. In this report, we describe a case of bilateral CSC with RPE tear after epidural steroid injection.
doi:10.4103/0301-4738.119441
PMCID: PMC3831769  PMID: 24104712
Central serous chorioretinopathy; epidural steroid; retinal pigment epithelium detachment; retinal pigment epithelium tear
18.  Caruncular Abscess Due to Actinomycosis 
The authors report a caruncular abscess caused by actinomycosis. A 47-year-old woman was admitted with persistent purulent discharge from the caruncle of the left eye for a duration of six months. Excisional drainage was performed, and 'sulfur granules' were observed, consistent with actinomyces infection. Intraoperative lacrimal probing and irrigation were performed to confirm that the abscess and canaliculus were not connected. Oral and topical antibiotics were administered postoperatively; the lesion resolved with no evidence of recurrence, and the symptom improved.
doi:10.3341/kjo.2013.27.4.288
PMCID: PMC3730072  PMID: 23908576
Abscess; Actinomycosis; Caruncle; Lacrimal apparatus
19.  Molecular and Functional Analyses of the Fast Skeletal Myosin Light Chain2 Gene of the Korean Oily Bitterling, Acheilognathus koreensis 
We identified and characterized the primary structure of the Korean oily bitterling Acheilognathus koreensis fast skeletal myosin light chain 2 (Akmlc2f), gene. Encoded by seven exons spanning 3955 bp, the deduced 168-amino acid AkMLC2f polypeptide contained an EF-hand calcium-binding motif and showed strong homology (80%–98%) with the MLC2 proteins of Ictalurus punctatus and other species, including mammals. Akmlc2f mRNA was highly enriched in skeletal muscles, and was detectable in other tissues. The upstream regions of Akmlc2f included a TATA box, one copy of a putative MEF-2 binding site and several putative C/EBPβ binding sites. The functional activity of the promoter region of Akmlc2f was examined using luciferase and red fluorescent protein reporters. The Akmlc2f promoter-driven reporter expressions were detected and increased by the C/EBPβ transcription factor in HEK293T cells. The activity of the promoter of Akmlc2f was also confirmed in the developing zebrafish embryo. Although the detailed mechanism underlying the expression of Akmlc2f remains unknown, these results suggest the muscle-specific expression of Akmlc2f transcript and the functional activation of Akmlc2f promoter by C/EBPβ.
doi:10.3390/ijms140816672
PMCID: PMC3759931  PMID: 23945561
Acheilognathus koreenis; C/EBPβ; expression; Korean oily bitterling; myosin light chain 2; promoter assay
20.  NeuroBactrus, a Novel, Highly Effective, and Environmentally Friendly Recombinant Baculovirus Insecticide 
A novel recombinant baculovirus, NeuroBactrus, was constructed to develop an improved baculovirus insecticide with additional beneficial properties, such as a higher insecticidal activity and improved recovery, compared to wild-type baculovirus. For the construction of NeuroBactrus, the Bacillus thuringiensis crystal protein gene (here termed cry1-5) was introduced into the Autographa californica nucleopolyhedrovirus (AcMNPV) genome by fusion of the polyhedrin–cry1-5–polyhedrin genes under the control of the polyhedrin promoter. In the opposite direction, an insect-specific neurotoxin gene, AaIT, from Androctonus australis was introduced under the control of an early promoter from Cotesia plutellae bracovirus by fusion of a partial fragment of orf603. The polyhedrin–Cry1-5–polyhedrin fusion protein expressed by the NeuroBactrus was not only occluded into the polyhedra, but it was also activated by treatment with trypsin, resulting in an ∼65-kDa active toxin. In addition, quantitative PCR revealed that the neurotoxin was expressed from the early phase of infection. NeuroBactrus showed a high level of insecticidal activity against Plutella xylostella larvae and a significant reduction in the median lethal time against Spodoptera exigua larvae compared to those of wild-type AcMNPV. Rerecombinant mutants derived from NeuroBactrus in which AaIT and/or cry1-5 were deleted were generated by serial passages in vitro. Expression of the foreign proteins (B. thuringiensis toxin and AaIT) was continuously reduced during the serial passage of the NeuroBactrus. Moreover, polyhedra collected from S. exigua larvae infected with the serially passaged NeuroBactrus showed insecticidal activity similar to that of wild-type AcMNPV. These results suggested that NeuroBactrus could be recovered to wild-type AcMNPV through serial passaging.
doi:10.1128/AEM.02781-12
PMCID: PMC3536103  PMID: 23064343
21.  Pulmonary actinomycosis during the first decade of 21st century: cases of 94 patients 
BMC Infectious Diseases  2013;13:216.
Background
Pulmonary actinomycosis is a chronic pulmonary infection caused by Actinomyces. Both improving oral hygiene and early application of antibiotics to the case of suspicious pulmonary infections result in changes in incidences and presentations of pulmonary actinomycosis. However, there are little reports dealt with the recent clinical characteristics of pulmonary actinomycosis. This study aimed to review the characteristics of pulmonary actinomycosis occurred during the first decade of 21st century.
Methods
This retrospective study was performed on 94 subjects with pulmonary actinomycosis diagnosed pathologically from January 2000 to December 2010 in 13 hospitals in Korea.
Results
The data of the study showed that pulmonary actinomycosis occurs frequently in middle to old-aged males (mean age; 57.7 years old) and that the most common symptoms are cough, hemoptysis, and sputum production. Various radiologic features such as the consolidation with central low attenuation (74.5%) and no regional predominance were also observed. Most of patients recovered completely with medical and/or surgical treatment, reaching approximately 98% cure rate.
Conclusions
The results demonstrate that pulmonary actinomycosis is one of the cautious pulmonary diseases. More importantly, in cases of persistent hemoptysis or for differential diagnosis from lung malignancy, our data have revealed that surgical resection appears to be a useful intervention and that radiologic diagnosis may not provide decisive information. These findings indicate that it is important for the clinicians to include pulmonary actinomycosis as one of differential diagnoses for refractory pulmonary abnormal lesions to the current usual management.
doi:10.1186/1471-2334-13-216
PMCID: PMC3658925  PMID: 23672372
Actinomycosis; Lung; Hemoptysis; Diagnosis; Treatment
22.  Feasibility of Video Clip Analysis on Effect of Botulinum Toxin-A Injection for Post-Stroke Upper Limb Spasticity 
Toxins  2013;5(5):983-991.
Existing functional evaluation tools do not accurately reveal the improved function following botulinum toxin A (BTX-A) injection for post-stroke upper limb spasticity. With the aim of developing an alternate method of measuring functional improvement following BTX-A injection, this study tested the feasibility, validity and reliability of video clip analysis performed by the clinicians. Seventy-nine patients administered BTX-A due to post-stroke upper limb spasticity, were retrospectively evaluated using video clip analysis. Pre- and post-injection video clips recorded at 1-month intervals were randomly allocated and sent to three blinded physician evaluators who were asked to choose the one that seemed more improved in terms of hand motion and associated upper limb reaction during gait. The three physicians chose the post-injection video clip as depicting improved hand motion (82.3%, 79.7%, and 72.2%) and associated upper limb reaction during gait (73.4%, 70.9%, and 70.9%). Kappa and intraclass correlation coefficient as a measure of interrater reliability among the three physicians was 0.86 and 0.79 for the hand, and 0.92 and 0.92 for associated upper limb reaction during gait, respectively. The percent overall agreement of the physicians was 78.1% and 71.7% for hand function and associated upper limb reaction, respectively. Retrospective pre- and post-BTX-A injection video clip analyses is a clinically feasible alternative method to evaluate the improvement following BTX-A injection for post-stroke upper limb spasticity, especially in busy clinical practice setting.
doi:10.3390/toxins5050983
PMCID: PMC3709274  PMID: 23666198
botulinum toxin A; injection; spasticity; upper limb; video; stroke
23.  Kimura Disease Involving a Caruncle 
A 35-year-old woman presented with history of a painless, slow-growing nodule in a left eye caruncle over the last 2 months. The visual acuity was 20 / 20 and the ocular movements were in the normal range. The venereal disease research laboratory test, erythrocyte sedimentation rate, serum angiotensin converting enzyme level, and chest radiograph were all normal. An excisional biopsy was done to confirm the diagnosis. A 1.3 × 0.5 × 0.3 cm sized nodule was extracted and sent for histopathologic examination. Hematoxylin-eosin staining showed follicular hyperplasia with perifollicular fibrosis, an eosinophil infiltrate, and proliferation of capillary vessels. The capillaries were lined by normal-appearing, flat, spindle-shaped endothelial cells. On the basis of these histopathologic findings, the diagnosis of Kimura disease in a caruncle was established. This is the first report describing Kimura disease localized to a caruncle. Kimura disease should be suspected and included in the differential diagnosis of a caruncular mass lesion.
doi:10.3341/kjo.2013.27.2.137
PMCID: PMC3596619  PMID: 23543681
Angiolymphoid hyperplasia with eosinophilia; Asian continental ancestry group; Caruncle; Women
24.  Characteristics of stable chronic obstructive pulmonary disease patients in the pulmonology clinics of seven Asian cities 
Background and objectives
Chronic obstructive pulmonary disease (COPD) is responsible for significant morbidity and mortality worldwide. We evaluated the characteristics of stable COPD patients in the pulmonology clinics of seven Asian cities and also evaluated whether the exposure to biomass fuels and dusty jobs were related to respiratory symptoms, airflow limitation, and quality of life in the COPD patients.
Methods
This cross-sectional observational study recruited 922 COPD patients from seven cities of Asia. The patients underwent spirometry and were administered questionnaires about their exposure to cigarette smoking, biomass fuels, and dusty jobs in addition to respiratory symptoms and health related quality of life.
Results
Of the patients, there appeared to be variations from city to city in the history of exposure to biomass fuels and dusty jobs and also in respiratory symptoms of cough, phlegm, wheeze, and dyspnea. These symptoms were more frequent in those COPD patients with a history of exposure to biomass fuels than without and those with a history of exposure to dusty jobs than without (P < 0.01 for all comparisons). Airflow limitation was more severe in those COPD patients with a history of exposure to biomass fuels than without (52.2% predicted versus 55.9% of post-bronchodilator forced expiratory volume in 1 second [FEV1], P = 0.009); quality of life was poorer in those with exposure to biomass fuels than without (40.4 versus 36.2 of the St George’s Respiratory Questionnaire [SGRQ] total score, P = 0.001). Airflow limitation was more severe in those COPD patients with a history of exposure to dusty jobs than without (51.2% predicted versus 57.3% of post-bronchodilator FEV1, P < 0.001); quality of life was poorer in those with dusty jobs than without (41.0 versus 34.6 of SGRQ score, P = 0.006).
Conclusion
In Asian cities, the characteristics of COPD patients vary and the history of exposure to biomass fuels or dusty jobs was related to frequency of symptoms, severe airflow limitation, and poor quality of life.
PMCID: PMC3553655  PMID: 23378753
COPD; Asia; biomass; dust
25.  Depression and Life Quality in Chronic Renal Failure Patients with Polyneuropathy on Hemodialysis 
Annals of Rehabilitation Medicine  2012;36(5):702-707.
Objective
To investigate the relationship between severity of peripheral polyneuropathy (PPN) and degree of depression and quality of life in chronic renal failure (CRF) patients on hemodialysis (HD).
Method
Forty seven chronic renal failure patients on hemodialysis were recruited (22 male, 25 female, mean age of 63.17±12.52) and etiology, disease duration, hemodialysis duration, creatinine and hemoglobin were recorded. Motor and sensory nerve conduction studies were carried out on bilateral median, ulnar, tibial and peroneal nerves for diagnosis of polyneuropathy according to our laboratory criteria. The Korean version of Beck depression inventory (BDI) questionnaire translated into Korean for diagnosis of depression, and Korean version of Short Form 36 health survey (SF-36) questionnaire for measurement of general health level were measured in those diagnosed with uremic PPN.
Results
Out of 52 patients, 47 were diagnosed with polyneuropathy and mean score for BDI was 18.49±9.18. Mean scores for each of Mental Component Summary (MCS) and Physical Component Summary (PCS) of SF-36 were 50.84±15.42 and 47.41±18.68. The correlation between the scores and polyneuropathy were analyzed by Pearson coefficient. The MCS score was the significant (p<0.05) correlation parameter with depression (R=-0.635) and the PCS score was the only parameter with a significant (p<0.05) correlation with polyneuropathy (R=-0.340).
Conclusion
Uremic polyneuropathy is commonly observed in chronic renal failure patients on hemodialysis. Depression in CRF with uremic PPN is affected by psychological factors other than the PPN itself.
doi:10.5535/arm.2012.36.5.702
PMCID: PMC3503947  PMID: 23185736
Neuropathy; Chronic renal failure; Depression; Quality of life

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