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1.  The Reverse Nasolabial Flap with a Cartilage Graft for the Repair of a Full-Thickness Alar Defect: A Single-Stage Procedure 
Annals of Dermatology  2014;26(3):377-380.
A 65-year-old woman with a deeply infiltrating basal cell carcinoma in the right ala underwent full-thickness excision of most of the ala, including the alar rim, crease, and the adjacent cheek, leaving a 'through-and-through' defect. Reconstruction was performed by using the reverse nasolabial flap and a cartilage graft across the alar defect, harvested from the concha, to prevent nostril collapse and to maintain the alar shape. The reverse or turnover nasolabial flap is a variant of the conventional nasolabial flap; however, it may be more suited for the repair of a full-thickness, lateral alar defect. The reverse nasolabial flap functions both as an inner liner and an outer cover and the repair is performed as a single-stage procedure. Furthermore, this flap can provide both excellent function and excellent cosmetic outcome.
PMCID: PMC4069650  PMID: 24966639
Nasal cartilages; Surgical flaps
2.  US Features of Transient Small Bowel Intussusception in Pediatric Patients 
Korean Journal of Radiology  2004;5(3):178-184.
To describe the sonographic (US) and clinical features of spontaneously reduced small bowel intussusception, and to discuss the management options for small bowel intussusception based on US findings with clinical correlation.
Materials and Methods
During a five years of period, 34 small bowel intussusceptions were diagnosed on US in 32 infants and children. The clinical presentations and imaging findings of the patients were reviewed.
The clinical presentations included abdominal pain or irritability (n = 25), vomiting (n = 5), diarrhea (n = 3), bloody stool (n = 1), and abdominal distension (n = 1), in combination or alone. US showed multi-layered round masses of small (mean, 1.5±0.3 cm) diameters and with thin (mean, 3.5±1 mm) outer rims along the course of the small bowel. The mean length was 1.8±0.5 cm and peristalsis was seen on the video records. There were no visible lead points. The vascular flow signal appeared on color Doppler images in all 21 patients examined. Spontaneous reduction was confirmed by combinations of US (n = 28), small bowel series (n = 6), CT scan (n = 3), and surgical exploration (n = 2). All patients discharged with improved condition.
Typical US findings of the transient small bowel intussusception included 1) small size without wall swelling, 2) short segment, 3) preserved wall motion, and 4) absence of the lead point. Conservative management with US monitoring rather than an immediate operation is recommended for those patient with typical transient small bowel intussusceptions. Atypical US findings or clinical deterioration of the patient with persistent intussusception warrant surgical exploration.
PMCID: PMC2698160  PMID: 15467415
Children, gastrointestinal tract; Intussusception; Intestine, US
3.  Clinically Useful Diagnostic Tool of Contrast Enhanced Ultrasonography for Focal Liver Masses: Comparison to Computed Tomography and Magnetic Resonance Imaging 
Gut and Liver  2014;8(3):292-297.
To evaluate the diagnostic value of contrast (SonoVue®) enhancement ultrasonography (CEUS) and to compare this method with computed tomography (CT) and magnetic resonance imaging (MRI) in evaluating liver masses.
CEUS (n=50), CT (n=47), and MRI (n=43) were performed on 50 liver masses in 48 patients for baseline mass characterization. The most likely impression for each modality and the final diagnosis, based on the combined biopsy results (n=14), angiography findings (n=36), and clinical course, were determined. The diagnostic value of CEUS was compared to those of CT and MRI.
The final diagnosis of the masses was hepatocellular carcinoma (n=43), hemangioma (n=3), benign adenoma (n=2), eosinophilic abscess (n=1), and liver metastasis (n=1). The overall diagnostic agreement with the final diagnosis was substantial for CEUS, CT, and MRI, with κ values of 0.621, 0.763, and 0.784, respectively. The sensitivity, specificity, and accuracy were 83.3%, 87.5%, and 84.0%, respectively, for CEUS; 95.0%, 87.5%, and 93.8%, respectively, for CT; and 94.6%, 83.3%, and 93.0%, respectively for MRI. After excluding the lesions with poor acoustic sonographic windows, the sensitivity, specificity, and accuracy for CEUS were 94.6%, 87.5%, and 93.3%, respectively, with a κ value of 0.765.
If an appropriate acoustic window is available, CEUS is comparable to CT and MRI for the diagnosis of liver masses.
PMCID: PMC4026647  PMID: 24827626
Contrast enhanced ultrasonography; Liver masses
4.  Gallstones are Associated with Intima-Media Thickness of Common Carotid Arteries in Men 
Korean Journal of Family Medicine  2014;35(3):136-142.
The prevalence of gallstone disease is increasing in Korea. Gallstone disease and atherosclerosis share common risk factors. Ultrasonographic carotid intima-media thickness is an independent predictor of atherosclerosis. We measured the carotid intima-media thickness among men who had gallstones to establish the association between atherosclerosis and gallstones.
A total of 330 men who visited the health promotion center of the IS Hallym Hospital from January 2011 to July 2012 were recruited. Both abdomen and carotid ultrasonographies were performed. Demographic, anthropometric, and biochemical data were collected.
The prevalence of gallstones was 6.6%. The carotid intima-media thickness, age, and body mass index were higher in subjects with gallstones (P < 0.05 for all). After Pearson correlation analysis, gallstone, age, body mass index, and fasting blood sugar were significantly associated with carotid intima-media thickness. A statistically positive association between gallstone and carotid intima-media thickness was demonstrated in a multivariate analysis adjusted for age, body mass index, and fasting blood sugar.
Carotid intima-media thickness is higher in male subjects with gallstones, indicating that they are at greater risk for atherosclerosis.
PMCID: PMC4040431  PMID: 24921032
Gallstones; Carotid Intima-Media Thickness; Atherosclerosis; Men
6.  Lancemaside A from Codonopsis lanceolata Modulates the Inflammatory Responses Mediated by Monocytes and Macrophages 
Mediators of Inflammation  2014;2014:405158.
In this study, we aimed to examine the cellular and molecular mechanisms of lancemaside A from Codonopsis lanceolata (Campanulaceae) in the inflammatory responses of monocytes (U937 cells) and macrophages (RAW264.7 cells). Lancemaside A significantly suppressed the inflammatory functions of lipopolysaccharide- (LPS-) treated RAW264.7 cells by suppressing the production of nitric oxide (NO), the expression of the NO-producing enzyme inducible NO synthase (iNOS), the upregulation of the costimulatory molecule CD80, and the morphological changes induced by LPS exposure. In addition, lancemaside A diminished the phagocytic activity of RAW264.7 cells and boosted the neutralizing capacity of these cells when treated with the radical generator sodium nitroprusside (SNP). Interestingly, lancemaside A strongly blocked the adhesion activity of RAW264.7 cells to plastic culture plates, inhibited the cell-cell and cell-fibronectin (FN) adhesion of U937 cells that was triggered by treatment with an anti-β1-integrin (CD29) antibody and immobilized FN, respectively. By evaluating the activation of various intracellular signaling pathways and the levels of related nuclear transcription factors, lancemaside A was found to block the activation of inhibitor of κB kinase (IKK) and p65/nuclear factor- (NF-) κB. Taken together, our findings strongly suggest that the anti-inflammatory function of lancemaside A is the result of its strong antioxidative and IKK/NF-κB inhibitory activities.
PMCID: PMC3981472  PMID: 24782593
7.  Reduced-dose craniospinal radiotherapy followed by tandem high-dose chemotherapy and autologous stem cell transplantation in patients with high-risk medulloblastoma 
Neuro-Oncology  2012;15(3):352-359.
We assessed the feasibility and effectiveness of reduced-dose craniospinal (CS) radiotherapy (RT) followed by tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) in reducing late adverse effects without jeopardizing survival among children with high-risk medulloblastoma (MB).
From October 2005 through September 2010, twenty consecutive children aged >3 years with high-risk MB (presence of metastasis and/or postoperative residual tumor >1.5 cm2) were assigned to receive 2 cycles of pre-RT chemotherapy, CSRT (23.4 or 30.6 Gy) combined with local RT to the primary site (total 54.0 Gy), and 4 cycles of post-RT chemotherapy followed by tandem HDCT/autoSCT. Carboplatin-thiotepa-etoposide and cyclophosphamide-melphalan regimens were used for the first and second HDCT, respectively.
Of 20 patients with high-risk MB, 17 had metastatic disease and 3 had a postoperative residual tumor >1.5 cm2 without metastasis. The tumor relapsed/progressed in 4 patients, and 2 patients died of toxicities during the second HDCT/autoSCT. Therefore, 14 patients remained event-free at a median follow-up of 46 months (range, 23−82) from diagnosis. The probability of 5-year event-free survival was 70.0% ± 10.3% for all patients and 70.6% ± 11.1% for patients with metastases. Late adverse effects evaluated at a median of 36 months (range, 12−68) after tandem HDCT/autoSCT were acceptable.
In children with high-risk MB, CSRT dose might be reduced when accompanied by tandem HDCT/autoSCT without jeopardizing survival. However, longer follow-up is needed to evaluate whether the benefits of reduced-dose CSRT outweigh the long-term risks of tandem HDCT/autoSCT.
PMCID: PMC3578484  PMID: 23258845
autologous stem cell transplantation; high-dose chemotherapy; late effect; medulloblastoma; radiotherapy
8.  Ultraviolet B Preconditioning Enhances the Hair Growth-Promoting Effects of Adipose-Derived Stem Cells Via Generation of Reactive Oxygen Species 
Stem Cells and Development  2012;22(1):158-168.
Hypoxia induces the survival and regenerative potential of adipose-derived stem cells (ASCs), but there are tremendous needs to find alternative methods for ASC preconditioning. Therefore, this work investigated: (1) the ability of low-dose ultraviolet B (UVB) radiation to stimulate the survival, migration, and tube-forming activity of ASCs in vitro; (2) the ability of UVB preconditioning to enhance the hair growth-promoting capacity of ASCs in vivo; and (3) the mechanism of action for ASC stimulation by UVB. Although high-dose UVB decreased the proliferation of ASCs, low-dose (10 or 20 mJ/cm2) treatment increased their survival, migration, and tube-forming activity. In addition, low-dose UVB upregulated the expression of ASC-derived growth factors, and a culture medium conditioned by UVB-irradiated ASCs increased the proliferation of dermal papilla and outer root sheet cells. Notably, injection of UVB-preconditioned ASCs into C3H/HeN mice significantly induced the telogen-to-anagen transition and increased new hair weight in vivo. UVB treatment significantly increased the generation of reactive oxygen species (ROS) in cultured ASCs, and inhibition of ROS generation by diphenyleneiodonium chloride (DPI) significantly attenuated UVB-induced ASC stimulation. Furthermore, NADPH oxidase 4 (Nox4) expression was induced in ASCs by UVB irradiation, and Nox4 silencing by small interfering RNA, like DPI, significantly reduced UVB-induced ROS generation. These results suggest that the primary involvement of ROS generation in UVB-mediated ASC stimulation occurs via the Nox4 enzyme. This is the first indication that a low dose of UVB radiation and/or the control of ROS generation could potentially be incorporated into a novel ASC preconditioning method for hair regeneration.
PMCID: PMC3528093  PMID: 22784094
9.  Biocompatibility of a Novel Cyanoacrylate Based Tissue Adhesive: Cytotoxicity and Biochemical Property Evaluation 
PLoS ONE  2013;8(11):e79761.
Cyanoacrylate (CA) is most widely used as a medical and commercial tissue adhesive because of easier wound closure, good cosmetic results and little discomfort. But, CA-based tissue adhesives have some limitations including the release of cytotoxic chemicals during biodegradation. In previous study, we made prepolymerized allyl 2-CA (PACA) based tissue adhesive, resulting in longer chain structure. In this study, we investigated a biocompatibility of PACA as alternative tissue adhesive for medical application, comparing with that of Dermabond® as commercial tissue adhesive. The biocompatibility of PACA was evaluated for short-term (24 hr) and long-term (3 and 7 days) using conventional cytotoxicity (WST, neutral red, LIVE/DEAD and TUNEL) assays, hematoxylin-eosin (H&E) and Masson trichrome (MT) staining. Besides we examined the biochemical changes in cells and DNA induced by PACA and Dermabond® utilizing Raman spectroscopy which could observe the denaturation and conformational changes in protein, as well as disintegration of the DNA/RNA by cell death. In particular, we analyzed Raman spectrum using the multivariate statistical methods including principal component analysis (PCA) and support vector machine (SVM). As a result, PACA and Dermabond® tissue adhesive treated cells and tissues showed no difference of the cell viability values, histological analysis and Raman spectral intensity. Also, the classification analysis by means of PCA-SVM classifier could not discriminate the difference between the PACA and Dermabond® treated cells and DNA. Therefore we suggest that novel PACA might be useful as potential tissue adhesive with effective biocompatibility.
PMCID: PMC3838346  PMID: 24278173
10.  7,3′,4′-Trihydroxyisoflavone Ameliorates the Development of Dermatophagoides farinae-Induced Atopic Dermatitis in NC/Nga Mice 
Atopic dermatitis is an inflammatory and chronically relapsing skin disorder that commonly occurs in children; the number of atopic dermatitis patients is increasing. The cause and mechanism of atopic dermatitis have not been defined clearly, although many studies are ongoing. Epidemiological studies suggest that soybean and its isoflavones have immunoregulatory activities. Here, we report that 7,3′,4′-trihydroxyisoflavone (7,3′,4′-THIF), a major metabolite of daidzin, effectively inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 production in RAW 264.7 cells, and also reduced β-hexosaminidase secretion in RBL-2H3 cells. Moreover, 7,3′,4′-THIF significantly reduced scratching time, transepidermal water loss, and mast cell infiltration. It also decreased protease-activated receptor (PAR)-2 and IL-4 expression and increased filaggrin expression in skin lesions of NC/Nga mice. These results suggest that 7,3′,4′-THIF improves Dermatophagoides farina body extract-induced atopic dermatitis in NC/Nga mice.
PMCID: PMC3845246  PMID: 24324516
11.  Magnifying endoscopy for the diagnosis of specialized intestinal metaplasia in short-segment Barrett’s esophagus 
AIM: To determine whether magnified observation of short-segment Barrett’s esophagus (BE) is useful for the detection of specialized intestinal metaplasia (SIM).
METHODS: Thirty patients with suspected short-segment BE underwent magnifying endoscopy up to × 80. The magnified images were analyzed with respect to their pit-patterns, which were simultaneously classified into five epithelial types [I (small round), II (straight), III (long oval), IV (tubular), V (villous)] by Endo’s classification. Then, a 0.5% solution of methylene blue (MB) was sprayed over columnar mucosa. The patterns of the magnified image and MB staining were analyzed. Biopsies were obtained from the regions previously observed by magnifying endoscopy and MB chromoendoscopy.
RESULTS: Three of five patients with a type V (villous) epithelial pattern had SIM, whereas 21 patients with a non-type V epithelial patterns did not have SIM. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of pit-patterns in detecting SIM were 100%, 91.3%, 92.3%, 60% and 100%, respectively (P = 0.004). Three of the 12 patients with positive MB staining had SIM, whereas 14 patients with negative MB staining did not have SIM. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of MB staining in detecting SIM were 100%, 60.9%, 65.4%, 25% and 100%, respectively (P = 0.085). The specificity and accuracy of pit-pattern evaluation were significantly superior compared with MB staining for detecting SIM by comparison with the exact McNemar’s test (P = 0.0391).
CONCLUSION: The magnified observation of a short-segment BE according to the mucosal pattern and its classification can be predictive of SIM.
PMCID: PMC3819544  PMID: 24222952
Short-segment; Barrett’s esophagus; Magnifying endoscopy; Methylene blue chromoendoscopy; Specialized intestinal metaplasia; Dysplasia; Esophageal adenocarcinoma; Diagnosis
12.  Negative-pressure wound therapy induces endothelial progenitor cell mobilization in diabetic patients with foot infection or skin defects 
Non healing chronic wounds are difficult to treat in patients with diabetes and can result in severe medical problems for these patients and for society. Negative-pressure wound therapy (NPWT) has been adopted to treat intractable chronic wounds and has been reported to be effective. However, the mechanisms underlying the effects of this treatment have not been elucidated. To assess the vasculogenic effect of NPWT, we evaluated the systemic mobilization of endothelial progenitor cells (EPCs) during NPWT. Twenty-two of 29 consecutive patients who presented at the clinic of Seoul National Universty Hospital between December 2009 and November 2010 who underwent NPWT for diabetic foot infections or skin ulcers were included in this study. Peripheral blood samples were taken before NPWT (pre-NPWT) and 7–14 days after the initiation of NPWT (during-NPWT). Fluorescence-activated cell sorting (FACS) analysis showed that the number of cells in EPC-enriched fractions increased after NPWT, and the numbers of EPC colony forming units (CFUs) significantly increased during NPWT. We believe that NPWT is useful for treating patients with diabetic foot infections and skin ulcers, especially when these conditions are accompanied by peripheral arterial insufficiency. The systemic mobilization of EPCs during NPWT may be a mechanism for healing intractable wounds in diabetic patients with foot infections or skin defects via the formation of increased granulation tissue with numerous small blood vessels.
PMCID: PMC3849576  PMID: 24232261
diabetic foot; endothelial progenitor cell; negative-pressure wound therapy
13.  Prevalent Multidrug-resistant Nonvaccine Serotypes in Pneumococcal Carriage of Healthy Korean Children Associated with the Low Coverage of the Seven-valent Pneumococcal Conjugate Vaccine 
Our previous longitudinal multicenter-based carriage study showed that the average carriage rate of Streptococcus pneumoniae was 16.8% in 582 healthy children attending kindergarten or elementary school in Seoul, Korea. We assessed serotype-specific prevalence and antimicrobial resistance among colonizing pneumococcal isolates from young children in the era of low use of the seven-valent pneumococcal conjugate vaccine (PCV7).
Serotypes were determined by an agglutination test with specific antisera or by a multiplex polymerase chain reaction (PCR) assay. An antimicrobial susceptibility test was performed with broth microdilution in Korean 96-well panels from Dade-MicroScan (Sacramento, CA, USA).
Pneumococcal colonization patterns were dynamic and longterm persistent carriage was rare, which indicated a sequential turnover of pneumococcal strains. Of the 369 pneumococci (except for 23 killed isolates), 129 (34.9%) isolates were PCV7 vaccine serotypes (VTs); 213 (57.8%) isolates were nonvaccine serotypes (NVTs); and the remaining 27 (7.2%) isolates were nontypable (NT). The highest rates of multidrug resistance (MDR) were observed in VTs (86.0%; 111/129 isolates) and NVTs (70.0%; 149/213 isolates).
This study overall showed the frequent carriage of VTs and NVTs with MDR in healthy children attending kindergarten or elementary school. Efforts should be directed toward reducing the extensive prescription of antibiotics and using new broader vaccines to reduce the expansion of MDR strains of NVTs in our community.
PMCID: PMC3922100  PMID: 24524020
multidrug-resistant strains; nasal carriage; nonvaccine serotypes; Streptococcus pneumoniae
14.  miR-221 silencing blocks hepatocellular carcinoma and promotes survival 
Cancer research  2011;71(24):7608-7616.
Patients with advanced hepatocellular carcinoma (HCC) face a dismal prognosis due to a lack of any effective therapies. To address this situation, we conducted a preclinical investigation of the therapeutic efficacy of oligonucleotides directed against the oncogenic microRNA miR-221 which has been implicated in HCC. Of 9 chemistries evaluated, we determined that a 2′-O-methyl phosphorothioate-modified anti-miR-221 oligonucleotide was most effective at reducing proliferation in vitro. A cholesterol-modified isoform of anti-miR-221 (chol-anti-miR-221) exhibited improved pharmacokinetics and liver tissue distribution compared to unmodified oligonucleotide. Chol-anti-miR-221 significantly reduced miR-221 levels in liver within a week of intravenous administration and in situ hybridization studies confirmed accumulation of the oligonucleotide in tumor cells in vivo. Within the same period, chol-anti-miR-221 reduced tumor cell proliferation and increased markers of apoptosis and cell cycle arrest, elevating the tumor doubling time and increasing mouse survival. Taken together, our findings offer a preclinical proof of efficacy for chol-anti-miR-221 in a valid orthotopic mouse model of HCC, suggesting that this targeted agent could benefit treatment of advanced HCC patients.
PMCID: PMC3773601  PMID: 22009537
microRNA; antisense; antagomiR; HCC; liver
15.  Primary Involvement of NADPH Oxidase 4 in Hypoxia-Induced Generation of Reactive Oxygen Species in Adipose-Derived Stem Cells 
Stem Cells and Development  2011;21(12):2212-2221.
We have previously demonstrated that hypoxia stimulates adipose-derived stem cells (ASCs) through the generation of reactive oxygen species (ROS). However, the precise mechanism involved in the ROS generation by ASCs is not well understood. We sought to investigate in this work: (1) which subtype of NADPH oxidase (Nox) is primarily expressed in ASCs; (2) where Nox4 is localized in ASCs; and (3) whether silencing of Nox4 attenuates hypoxia-enhanced function of ASC. We used 2′,7′-dichlorofluorescin diacetate (DCF-DA) as an indicator of ROS generation and found that the fluorescence intensity of DCF-DA was significantly increased after hypoxia exposure (2% oxygen). In addition, hypoxia enhanced the proliferation and migration of ASCs and upregulated the mRNA expression of Oct4 and Rex1. Quantitative analysis of mRNA expression of Nox family in ASCs demonstrated that Nox4 is primarily expressed in ASCs, while immunofluorescence assay showed that Nox4 is mainly localized in the perinuclear region and overlaps with Mitotracker, a mitochondria marker. Silencing of Nox4 by siRNA treatment downregulated the RNA and protein expression of Nox4, which significantly reduced the ROS generation under hypoxia. In addition, Nox4 silencing significantly reduced the proliferation and migration of ASCs and downregulated the mRNA expression of Oct4 and Rex1. Phosphorylation of platelet-derived growth factor receptor-β, AKT, and ERK1/2 also diminished following Nox4 silencing. In a nutshell, these results suggest that Nox4 is primarily expressed in ASCs and plays a pivotal role in the hypoxia-enhanced stimulation of ASCs.
PMCID: PMC3411360  PMID: 22181007
16.  Aerosol delivery of beclin1 enhanced the anti-tumor effect of radiation in the lungs of K-rasLA1 mice 
Journal of radiation research  2012;53(4):506-515.
Radiotherapy alone has several limitations for treating lung cancer. Inhalation, a non-invasive approach for direct delivery of therapeutic agents to the lung, may help to enhance the therapeutic efficacy of radiation. Up-regulating beclin1, known as a tumor suppressor gene that plays a major role in autophagy, may sensitize tumors and lead to tumor regression in lungs of K-rasLA1 lung cancer model mice. To minimize the side-effects of radiotherapy, fractionated exposures (five times, 24-h interval) with low dose (2 Gy) of radiation to the restricted area (thorax, 2 cm) were conducted. After sensitizing the lungs with radiation, beclin1, complexed with a nano-sized biodegradable poly(ester amine), was prepared and delivered into the murine lung via aerosol three times/week for four weeks. In a histopathological analysis, animals treated with beclin1 and radiation showed highly significant tumor regression and low progression to adenocarcinoma. An increase in the number of autophagic vacuoles and secondary lysosomes was detected. Dissociation of beclin1-bcl2 stimulated autophagy activation and showed a synergistic anti-tumor effect by inhibiting the Akt-mTOR pathway, cell proliferation and angiogenesis. The combination of radiation with non-invasive aerosol delivery of beclin1 may provide a prospect for developing novel therapy regimens applicable in clinics.
PMCID: PMC3393344  PMID: 22843615
Radiation; Beclin1; aerosol delivery; lung cancer
17.  T cell transcriptional factors in allergic rhinitis and its association with clinical features 
Asia Pacific Allergy  2013;3(3):186-193.
Th2 cells are crucially important in allergic disease and the possible involvement of Treg and Th17 cells has not been clearly identified.
To identify the mRNA expression of T cell transcription factors in nasal mucosa in patients with allergic rhinitis (AR) and to reveal their correlations with clinical features.
Eighteen patients with AR and 12 controls with turbinate hypertrophy were included. mRNA expression of the following transcriptional factors in nasal mucosa were measured by quantitative polymerase chain reaction; T-bet (Th1), GATA3 (Th2), retinoic acid-related orphan receptor C (RORC; Th17), and forkhead box P3 (Foxp3; Treg). mRNA expression was compared among groups and correlation between mRNA expression level and clinical features (rhinitis symptoms, eosinophil count, and IgE) were also investigated.
GATA3 and RORC were significantly increased and Foxp3 was significantly decreased in the AR group. Moderate-to-severe AR group also had increased expression of GATA3 and RORC than mild AR group, suggesting severity of AR influence expression of transcription factors. Correlation analysis showed that none of these transcription factors were associated with severity of clinical symptoms, eosinophil counts and skin prick test severity and that IgE level was significantly correlated with expression level of GATA3 and RORC, suggesting an association of IgE production with Th2 and Th17 cells.
Increased mRNA expression of GATA3 (Th2), increased expression of RORC and decreased expression of Foxp3 may be important in pathogenesis of AR. GATA3 and RORC may be closed related with IgE level.
PMCID: PMC3736365  PMID: 23956965
Allergic rhinitis; Transcription factor; T-bet; GATA3; Retinoic acid-related orphan receptor C; Forkhead box P3
18.  Usefulness of Plasma Procalcitonin to Predict Severity in Elderly Patients with Community-Acquired Pneumonia 
Community-acquired pneumonia (CAP) is one of the leading causes of death among the elderly. Several studies have reported the clinical usefulness of serum procalcitonin, a biomarker of bacterial infection. However, the association between the levels of procalcitonin and the severity in the elderly with CAP has not yet been reported. The aim of this study was to evaluate usefulness of procalcitonin as a predictor of severity and mortality in the elderly with CAP.
This study covers 155 CAP cases admitted to Pusan National University Hospital between January 2010 and December 2010. Patients were divided into two groups (≥65 years, n=99; <65 years, n=56) and were measured for procalcitonin, C-reactive protein (CRP), white blood cell, confusion, uremia, respiratory rate, blood pressure, 65 years or older (CURB-65) and pneumonia severity of index (PSI).
The levels of procalcitonin were significantly correlated with the CURB-65, PSI in totals. Especially stronger correlation was observed between the levels of procalcitonin and CURB-65 in the elderly (procalcitonin and CURB-65, ρ=0.408 with p<0.001; procalcitonin and PSI, ρ=0.293 with p=0.003; procalcitonin and mortality, ρ=0.229 with p=0.023). The correlation between the levels of CRP or WBC and CAP severity was low. The existing cut-off value of procalcitonin was correlated with mortality rate, however, it was not correlated with mortality within the elderly.
The levels of procalcitonin are more useful than the levels of CRP or WBC to predict the severity of CAP. However, there was no association between the levels of procalcitonin and mortality in the elderly.
PMCID: PMC3672412  PMID: 23750168
Community-Acquired Infections; Aged; Pneumonia; Procalcitonin
19.  Multitargeting by curcumin as revealed by molecular interaction studies 
Natural product reports  2011;28(12):1937-1955.
Curcumin (diferuloylmethane), the active ingredient in turmeric (Curcuma longa), is a highly pleiotropic molecule with anti-inflammatory, anti-oxidant, chemopreventive, chemosensitization, and radiosensitization activities. The pleiotropic activities attributed to curcumin come from its complex molecular structure and chemistry, as well as its ability to influence multiple signaling molecules. Curcumin has been shown to bind by multiple forces directly to numerous signaling molecules, such as inflammatory molecules, cell survival proteins, protein kinases, protein reductases, histone acetyltransferase, histone deacetylase, glyoxalase I, xanthine oxidase, proteasome, HIV1 integrase, HIV1 protease, sarco (endo) plasmic reticulum Ca2+ ATPase, DNA methyltransferases 1, FtsZ protofilaments, carrier proteins, and metal ions. Curcumin can also bind directly to DNA and RNA. Owing to its β-diketone moiety, curcumin undergoes keto–enol tautomerism that has been reported as a favorable state for direct binding. The functional groups on curcumin found suitable for interaction with other macromolecules include the α, β-unsaturated β-diketone moiety, carbonyl and enolic groups of the β-diketone moiety, methoxy and phenolic hydroxyl groups, and the phenyl rings. Various biophysical tools have been used to monitor direct interaction of curcumin with other proteins, including absorption, fluorescence, Fourier transform infrared (FTIR) and circular dichroism (CD) spectroscopy, surface plasmon resonance, competitive ligand binding, Forster type fluorescence resonance energy transfer (FRET), radiolabeling, site-directed mutagenesis, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), immunoprecipitation, phage display biopanning, electron microscopy, 1-anilino-8-naphthalene-sulfonate (ANS) displacement, and co-localization. Molecular docking, the most commonly employed computational tool for calculating binding affinities and predicting binding sites, has also been used to further characterize curcumin’s binding sites. Furthermore, the ability of curcumin to bind directly to carrier proteins improves its solubility and bioavailability. In this review, we focus on how curcumin directly targets signaling molecules, as well as the different forces that bind the curcumin–protein complex and how this interaction affects the biological properties of proteins. We will also discuss various analogues of curcumin designed to bind selective targets with increased affinity.
PMCID: PMC3604998  PMID: 21979811
20.  Radical Scavenging Activity-Based and AP-1-Targeted Anti-Inflammatory Effects of Lutein in Macrophage-Like and Skin Keratinocytic Cells 
Mediators of Inflammation  2013;2013:787042.
Lutein is a naturally occurring carotenoid with antioxidative, antitumorigenic, antiangiogenic, photoprotective, hepatoprotective, and neuroprotective properties. Although the anti-inflammatory effects of lutein have previously been described, the mechanism of its anti-inflammatory action has not been fully elucidated. Therefore, in the present study, we aimed to investigate the regulatory activity of lutein in the inflammatory responses of skin-derived keratinocytes or macrophages and to elucidate the mechanism of its inhibitory action. Lutein significantly reduced several skin inflammatory responses, including increased expression of interleukin-(IL-) 6 from LPS-treated macrophages, upregulation of cyclooxygenase-(COX-) 2 from interferon-γ/tumor necrosis-factor-(TNF-) α-treated HaCaT cells, and the enhancement of matrix-metallopeptidase-(MMP-) 9 level in UV-irradiated keratinocytes. By evaluating the intracellular signaling pathway and the nuclear transcription factor levels, we determined that lutein inhibited the activation of redox-sensitive AP-1 pathway by suppressing the activation of p38 and c-Jun-N-terminal kinase (JNK). Evaluation of the radical and ROS scavenging activities further revealed that lutein was able to act as a strong anti-oxidant. Taken together, our findings strongly suggest that lutein-mediated AP-1 suppression and anti-inflammatory activity are the result of its strong antioxidative and p38/JNK inhibitory activities. These findings can be applied for the preparation of anti-inflammatory and cosmetic remedies for inflammatory diseases of the skin.
PMCID: PMC3606807  PMID: 23533312
21.  Zyflamend Sensitizes Tumor Cells to TRAIL-Induced Apoptosis Through Up-Regulation of Death Receptors and Down-Regulation of Survival Proteins: Role of ROS-Dependent CCAAT/Enhancer-Binding Protein-Homologous Protein Pathway 
Antioxidants & Redox Signaling  2012;16(5):413-427.
Aim: TNF (tumor necrosis factor)-related apoptosis-inducing ligand (TRAIL), is a selective killer of tumor cells, although its potential is limited by the development of resistance. In this article, we investigated whether the polyherbal preparation Zyflamend® can sensitize tumor cells to TRAIL. Results: We found that Zyflamend potentiated TRAIL-induced apoptosis in human cancer cells. Zyflamend manifested its effects through several mechanisms. First, it down-regulated the expression of cell survival proteins known to be linked to resistance to TRAIL. Second, Zyflamend up-regulated the expression of pro-apoptotic protein, Bax. Third, Zyflamend up-regulated the expression of death receptors (DRs) for TRAIL. Up-regulation of DRs was critical as gene-silencing of these receptors significantly reduced the effect of Zyflamend on TRAIL-induced apoptosis. The up-regulation of DRs was dependent on CCAAT/enhancer-binding protein-homologous protein (CHOP), as Zyflamend induced CHOP, its gene-silencing abolished the induction of receptors, and mutation of the CHOP binding site on DR5 promoter abolished Zyflamend-mediated DR5 transactivation. Zyflamend mediated its effects through reactive oxygen species (ROS), as ROS quenching reduced its effect. Further, Zyflamend induced DR5 and CHOP and down-regulated the expression of cell survival proteins in nude mice bearing human pancreatic cancer cells. Innovation: Zyflamend can sensitize tumor cells to TRAIL through modulation of multiple cell signaling mechanisms that are linked to ROS. Conclusion: Zyflamend potentiates TRAIL-induced apoptosis through the ROS-CHOP-mediated up-regulation of DRs, increase in pro-apoptotic protein and down-regulation of cell survival proteins. Antioxid. Redox Signal. 16, 413–427.
PMCID: PMC3261028  PMID: 22004570
22.  Is the frequency of metabolic syndrome higher in South Korean women with rheumatoid arthritis than in healthy subjects? 
To compare the frequency of metabolic syndrome (MetS) and magnitude of insulin resistance, measured by the homeostatic model assessment of insulin resistance (HOMA-IR), between South Korean women with rheumatoid arthritis (RA) and healthy subjects, and to evaluate risk factors for MetS and increased HOMA-IR in patients with RA.
In a cross-sectional setting, 84 female patients with RA and 109 age-matched healthy female subjects were consecutively recruited at a university-affiliated rheumatology center in South Korea. MetS was defined according to the Third Report of the National Cholesterol Education Program's Adult Treatment Panel (NCEP-ATP III) 2004 criteria.
The frequency of MetS did not differ significantly between patients with RA (19%) and healthy subjects (15.6%, p = 0.566), although patients with RA had a higher HOMA-IR compared with healthy subjects (p < 0.001). Patients with RA met the NCEP-ATP III 2004 criteria for high blood pressure more often than healthy subjects (44% vs. 19.3%, p < 0.001), and low high density lipoprotein cholesterol was more prevalent in healthy subjects (33%) than in patients with RA (14.3%, p = 0.004). Although no obvious risk factors for the presence of MetS were identified in patients with RA, higher serum C-reactive protein and disease activity score assessed using the 28-joint count for swelling and tenderness-erythrocyte sedimentation rate significantly contributed to a higher HOMA-IR.
Despite their increased insulin resistance, South Korean women with RA did not have a significantly higher frequency of MetS compared with that in healthy subjects.
PMCID: PMC3604611  PMID: 23526131
Arthritis, rheumatoid; Metabolic syndrome X; Insulin resistance; Cardiovascular diseases
23.  A Submucosal Tumor-Like Recurrence of Early Esophageal Cancer after Endoscopic Submucosal Dissection 
Clinical Endoscopy  2013;46(2):182-185.
Early esophageal cancer is defined as a tumor invading the mucosa with or without lymph node or distant organ metastasis. In the current guidelines for early esophageal cancer, absolute indication for endoscopic resection include lesions limited to the epithelium or lamina propria mucosa not exceeding two-thirds of the circumference, and relative indications include lesions limited to the muscularis mucosa or the upper third of the submucosal layer and not accompanied by clinical evidence of lymph node metastasis. After endoscopic submucosal dissection for early esophageal cancer, locally recurrent cancer can occur, especially in the case of incomplete resection. Here, we report a rare case of a submucosal tumor-like recurrence after endoscopic resection of early esophageal cancer.
PMCID: PMC3630314  PMID: 23614130
Esophageal neoplasms; Endosonography; Endoscopic resection; Recurrence
24.  Educational Disparities in Distribution of Cardiovascular Risk Factors and Quality of Care in Korean Adults: Korean National Health and Nutrition Survey IV 
The purpose of this study was to investigate how educational status influences cardiovascular risk factors and care of diabetes mellitus and hypertension.
From Korean National Health and Nutrition Survey IV, we obtained survey results of 6,835 men and 9,067 women more than 30 years old. We performed multivariate logistic regression to compare cardiovascular risk factors and care of hypertension and diabetes respective to educational status.
There were disparities in cardiovascular risk factors by educational status. In men, impaired fasting glucose, high triglyceride, and smoking were less frequently found in the highest educated group than in the middle educated group. In women, the prevalence of abdominal obesity, impaired fasting glucose, high blood pressure, high triglyceride, and metabolic syndrome among the highest educated group were significantly lower. The proportion of those with proper physical activity in the highest educated group was found to be less than that of the middle educated group, regardless of gender. For care of diabetes mellitus and hypertension, disease recognition and treatment were lower among the lowest educated group in men, while these disparities were not shown in women. Instead, the lowest educated group in diabetic women received screening exams for eye and kidney complications less than the middle education group. In both genders, the high education group had a higher chance of receiving education about diabetes mellitus.
There were educational disparities in cardiovascular risk factors and care of hypertension and diabetes mellitus. The disparities were found to be different by gender.
PMCID: PMC3560337  PMID: 23372903
Education; Cardiovascular Diseases; Risk Factors; Quality of Health Care
25.  Esophageal Pyogenic Granuloma: Endosonographic Findings and Endoscopic Treatments 
Clinical Endoscopy  2013;46(1):81-84.
Pyogenic granuloma is a benign inflammatory vascular lesion, mainly found in the skin and oral mucosa. A few cases of pyogenic granuloma in the gastrointestinal tract have been reported, and the esophagus was the main site in these cases. These patients were diagnosed with pyogenic granuloma after they underwent upper endoscopy and biopsy. Endoscopic resection is a favorable treatment option for esophageal pyogenic granuloma. Recently, we observed characteristic endosonographic findings in two cases with esophageal pyogenic granuloma, which were then treated successfully by endoscopic resection.
PMCID: PMC3572358  PMID: 23423701
Endosonography; Esophagus; Pyogenic granuloma

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