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1.  Isolated Left Ventricular Apical Hypoplasia with Infundibular Pulmonary and Aortic Stenosis: a Rare Combination 
Korean Journal of Radiology  2013;14(6):874-877.
Isolated left ventricular (LV) apical hypoplasia is a rare congenital cardiac anomaly which is not accompanied by other cardiac abnormalities, with the exception of two cases. We report a case of a 33-year-old male patient with isolated LV apical hypoplasia combined with infundibular pulmonary stenosis and aortic stenosis. We review a literature focusing on the characteristic magnetic resonance features and combined cardiac abnormalities.
PMCID: PMC3835633  PMID: 24265561
Isolated left ventricular apical hypoplasia; Pulmonary subvascular stenosis; Aortic valve stenosis; Magnetic resonance imaging; Congenital heart disease
2.  Serum Ferritin Is Differentially Associated with Anti-oxidative Status and Insulin Resistance in Healthy Obese and Non-obese Women 
Korean Journal of Family Medicine  2012;33(4):205-210.
Ferritin is known to be associated with insulin resistance (IR) and oxidative stress; however, recent studies have shown that there is an association between ferritin and anti-oxidative status. To date, the biphasic response of ferritin to oxidative stress has not been fully evaluated. Thus, we investigated the association between ferritin and IR and anti-oxidative status in obese and non-obese women.
We evaluated the homeostasis model assessment of insulin resistance (HOMA-IR) and total anti-oxidant status (TAS) in a total of 111 healthy women between the ages of 32 and 68 years.
In all of the study subjects, ferritin levels were positively correlated with age (r = 0.38, P < 0.001), body mass index (r = 0.24, P = 0.01), TAS (r = 0.38, P < 0.001) and HOMA-IR (r = 0.20, P = 0.04). In the subgroup analysis, ferritin levels were correlated with age (r = 0.39, P < 0.001) and TAS (r = 0.43, P < 0.001) in the non-obese group and with insulin (r = 0.50, P = 0.02) and HOMA-IR (r = 0.52, P = 0.01) levels in the obese group. On stepwise multiple linear regression analysis, ferritin was found to be independently associated with TAS (B = 177.16, P < 0.0001) in the non-obese group and independently associated with HOMA-IR (B = 30.36, P = 0.01) in the obese group.
Our findings suggest ferritin is associated with IR in obese women and with anti-oxidative status in non-obese women. Further studies are warranted to elucidate the precise role of ferritin in obesity.
PMCID: PMC3418339  PMID: 22916322
Ferritins; Obesity; Oxidative Stress
3.  Adiponectin in Women with Polycystic Ovary Syndrome 
Korean Journal of Family Medicine  2011;32(4):243-248.
Though adiponectin has been associated with insulin resistance and cardiovascular risk factors, the relationship between adiponectin and polycystic ovary syndrome (PCOS) remains controversial. The aim of this study was to compare adiponectin level in women with PCOS and without PCOS, and to investigate the relationship between adiponectin level and metabolic variables including insulin resistance.
60 women with PCOS were enrolled along with a control group of 80 healthy women, matched for age and body mass index (BMI). We measured hormonal and metabolic parameters, as well as the plasma adiponectin concentration of each participant. We estimated the insulin sensitivity according to the quantitative insulin sensitivity check index (QUICKI).
The PCOS group displayed significantly lower level of adiponectin (P < 0.001) after adjustment for age, BMI, mean blood pressure, fasting glucose, fasting insulin, and several metabolic parameters. Adiponectin levels were positively correlated with QUICKI in the PCOS group (P < 0.001) and the control group (P = 0.03). Following step-wise multiple regression analysis, however, adiponectin level was positively correlated with QUICKI in the control group only (P = 0.03). In addition, adiponectin level was found to be independently associated with HDL-cholesterol level (P < 0.001) and BMI (P = 0.02) in the PCOS group and independently associated with HDL-cholesterol (P = 0.02) in the control group.
We report decreased adiponectin level in PCOS patients in relation to controls independently of insulin resistance or other metabolic factors. And adiponectin is associated with both lipid metabolism and obesity, which, in turn, is related to insulin resistance in PCOS. Further studies are needed to clarify the mechanism of adiponectin in PCOS.
PMCID: PMC3383132  PMID: 22745860
Adiponectin; Polycystic Ovary Syndrome; Insulin Resistance
4.  Clinical Predictors of Novel Influenza A (H1N1) Infection in Korea 
Yonsei Medical Journal  2010;51(6):895-900.
Pandemic influenza A (H1N1) virus has spread rapidly and prompt diagnosis is needed for successful treatment and prevention of transmission. We investigated clinical predictors, validated the use of previous criteria with laboratory tests, and evaluated the clinical criteria for H1N1 infection in the Korean population.
Materials and Methods
We analyzed clinical and laboratory evaluation data from outpatient clinics at Severance Hospital in Seoul, Korea between November 11 and December 5, 2009.
This analysis included a total of 828 patients. Of these, 372 (44.9%) patients were confirmed with H1N1 infection by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). The most common and predictive symptom was cough (90.3%, OR 8.87, 95% CI 5.89-13.38) and about 40% of H1N1-positive patients were afebrile. The best predictive model of H1N1 infection was cough plus fever or myalgia. The sensitivities, specificities, positive predictive values, and negative predictive values of our suggested criteria were 73.9%, 69.5%, 66.4%, and 76.6%, respectively.
Cough was the most common independent symptom in patients with laboratory-confirmed H1N1 infection, and while not perfect, the combination of cough plus fever or myalgia is suggested as clinical diagnostic criteria. Health care providers in Korea should suspect a cough without fever to be an early symptom of H1N1 infection.
PMCID: PMC2995982  PMID: 20879057
Influenza A virus (H1N1 subtype); criteria; diagnosis
5.  Distribution of Abdominal Obesity and Fitness Level in Overweight and Obese Korean Adults 
Background. Abdominal obesity and its relative distribution are known to differ in association with metabolic characteristics and cardiorespiratory fitness. This study aimed to determine an association between fitness level and abdominal adiposity in overweight and obese adults. Methods. 228 overweight and obese individuals were classified as either cardiorespiratory unfit or fit based on their recovery heart rate. Visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), the visceral-to-subcutaneous adipose tissue ratio (VAT/SAT ratio), and cardiometabolic characteristics were analyzed to examine the relationship between recovery heart rate and abdominal adiposity components. Results. After adjustments for age and sex, significant relationships of recovery heart rate and VAT, SAT, and VAT/SAT ratio were found; however, SAT was not significantly associated after further adjustment for body mass index (BMI) (r = 0.045, P = 0.499), whereas VAT (r = 0.232, P < 0.001) and VAT/SAT ratio (r = 0.214, P = 0.001) remained associated. Through stepwise multiple regression analyses after adjustment for age, sex, BMI, lifestyle factors, mean blood pressure, fasting glucose, HOMA-IR, lipid profiles, and hsCRP, recovery heart rate was identified as an independent variable associated with VAT (β = 0.204, P < 0.001) and VAT/SAT ratio (β = 0.163, P = 0.008) but not with SAT (β = 0.097, P = 0.111). Conclusions. Cardiorespiratory fitness level is independently associated with VAT and the VAT/SAT ratio but not with SAT in overweight and obese adults.
PMCID: PMC3958687  PMID: 24723950
6.  Mitochondrial DNA Copy Number in Peripheral Blood Is Independently Associated with Visceral Fat Accumulation in Healthy Young Adults 
Aims. Visceral obesity is associated with an increased risk of cardiometabolic diseases and it is important to identify the underlying mechanisms. There is growing evidence that mitochondrial dysfunction is associated with metabolic disturbances related to visceral obesity. In addition, maintaining mitochondrial DNA (mtDNA) copy number is important for preserving mitochondrial function. Therefore, we investigated the relationship between mtDNA copy number and visceral fat in healthy young adults. Methods. A total of 94 healthy young subjects were studied. Biomarkers of metabolic risk factors were assessed along with body composition by computed tomography. mtDNA copy number was measured in peripheral leukocytes using real-time polymerase chain reaction (PCR) methods. Results. The mtDNA copy number correlated with BMI (r = −0.22, P = 0.04), waist circumference (r = −0.23, P = 0.03), visceral fat area (r = −0.28, P = -0.01), HDL-cholesterol levels (r = 0.25, P = 0.02), and hs-CRP (r = 0.32, P = 0.02) after adjusting for age and sex. Both stepwise and nonstepwise multiple regression analyses confirmed that visceral fat area was independently associated with mtDNA copy number (β = -0.33, P < 0.01, β = 0.32, and P = 0.03, resp.). Conclusions. An independent association between mtDNA content and visceral adiposity was identified. These data suggest that mtDNA copy number is a potential predictive marker for metabolic disturbances. Further studies are required to understand the causality and clinical significance of our findings.
PMCID: PMC3953665
7.  Combined Impact of Cardiorespiratory Fitness and Visceral Adiposity on Metabolic Syndrome in Overweight and Obese Adults in Korea 
PLoS ONE  2014;9(1):e85742.
Obesity, especially visceral obesity, is known to be an important correlate for cardiovascular disease and increased mortality. On the other hand, high cardiorespiratory fitness is suggested to be an effective contributor for reducing this risk. This study was conducted to determine the combined impact of cardiorespiratory fitness and visceral adiposity, otherwise known as fitness and fatness, on metabolic syndrome in overweight and obese adults.
A total of 232 overweight and obese individuals were grouped into four subtypes according to their fitness level. This was measured by recovery heart rate from a step test in addition to visceral adiposity defined as the visceral adipose tissue area to subcutaneous adipose tissue area ratio (VAT/SAT ratio). Associations of fitness and visceral fatness were analyzed in comparison with the prevalence of metabolic syndrome.
The high visceral fat and low fitness group had the highest prevalence of metabolic syndrome [Odds Ratio (OR) 5.02; 95% Confidence Interval (CI) 1.85–13.61] compared with the reference group, which was the low visceral adiposity and high fitness group, after adjustments for confounding factors. Viscerally lean but unfit subjects were associated with a higher prevalence of metabolic syndrome than more viscerally obese but fit subjects (OR 3.42; 95% CI 1.27–9.19, and OR 2.70; 95% CI 1.01–7.25, respectively).
Our study shows that visceral obesity and fitness levels are cumulatively associated with a higher prevalence of metabolic syndrome in healthy overweight and obese adults. This suggests that cardiorespiratory fitness is a significant modifier in the relation of visceral adiposity to adverse metabolic outcomes in overweight and obese individuals.
PMCID: PMC3893257  PMID: 24454926
8.  Torsade de pointes in liver transplantation recipient after induction of general anesthesia: a case report 
Torsade de pointes (TdP) is an uncommon and specific form of polymorphic ventricular tachycardia, associated with a prolonged QT interval. Prolongation of the QT interval is the most widely recognized electrophysiological abnormality in patients with liver cirrhosis. We observed a case of TdP leading to cardiopulmonary resuscitation after the induction of general anesthesia, in a patient with liver cirrhosis scheduled for emergency cadaveric donor liver transplantation. The patient had mild QT prolongation on preoperative electrocardiography with a corrected QT (QTc) interval of 455 ms. Drugs used in the preoperative period can elongate cardiac repolarization. Sevoflurane and 5-hydroxytryptamine type 3 receptor antagonists such as palonsetron, used during general anesthesia may have triggered further QT prolongation, producing a fatal condition such as TdP. More caution and consideration in selecting drugs for anesthetic management are necessary for liver cirrhosis patients, especially in patients with preoperative QT prolongation.
PMCID: PMC3927008  PMID: 24567820
Heart arrest; Liver transplantation; Long QT syndrome; Torsades de pointes
9.  Dendropanoxide Induces Autophagy through ERK1/2 Activation in MG-63 Human Osteosarcoma Cells and Autophagy Inhibition Enhances Dendropanoxide-Induced Apoptosis 
PLoS ONE  2013;8(12):e83611.
Anticancer effects of dendropanoxide (DP) newly isolated from leaves and stem of Dendropanax morbifera Leveille were firstly investigated in this study. DP inhibited cell proliferation and induced apoptosis in dose- and time-dependent manner in MG-63 human osteosarcoma cells, which was dependent on the release of cytochrome c to the cytosol and the activation of caspases. Moreover, the DP-treated cells exhibited autophagy, as characterized by the punctuate patterns of microtubule-associated protein 1 light chain 3 (LC3) by confocal microscopy and the appearance of autophagic vacuoles by MDC staining. The expression levels of ATG7, Beclin-1 and LC3-II were also increased by DP treatment. Inhibition of autophagy by 3-methyladenine (3-MA) and wortmannin (Wort) significantly enhanced DP-induced apoptosis. DP treatment also caused a time-dependent increase in protein levels of extracellular signal-regulated kinase 1 and 2 (ERK1/2), and inhibition of ERK1/2 phosphorylation with U0126 resulted in a decreased DP-induced autophagy that was accompanied by an increased apoptosis and a decreased cell viability. These results indicate a cytoprotective function of autophagy against DP-induced apoptosis and suggest that the combination of DP treatment with autophagy inhibition may be a promising strategy for human osteosarcoma control. Taken together, this study demonstrated for the first time that DP could induce autophagy through ERK1/2 activation in human osteosarcoma cells and autophagy inhibition enhanced DP-induced apoptosis.
PMCID: PMC3866153  PMID: 24358301
10.  Clinical Characteristics of Pediatric Thalassemia in Korea: A Single Institute Experience 
Journal of Korean Medical Science  2013;28(11):1645-1649.
Few literatures have elaborated on the clinical characteristics of children with thalassemia from low-prevalence areas. A retrospective analysis was conducted on children genetically confirmed with thalassemia at Seoul National University Children's Hospital in Korea. Nine children (1α thalassemia trait, 6β thalassemia minor, 2β thalassemia intermedia) were diagnosed with thalassemia at median age of 4.3 yr old with median hemoglobin of 9.7 g/dL. Seven (78%) children were incidentally found to be anemic and only 2 with β thalassemia intermedia had presenting symptoms. Five children (56%) were initially misdiagnosed with iron deficiency anemia. Despite the comorbidities due to α thalassemia mental retardation syndrome, the child with α thalassemia trait had mild hematologic profile. Children with β thalassemia intermedia had the worst phenotypes due to dominantly inherited mutations. None of the children was transfusion dependent and most of them had no complications associated with thalassemia. Only 1 child (11%) with codon 60 (T→A) mutation of the HBB gene needed red blood cell transfusions. He also had splenomegaly, cholelithiasis, and calvarial vault thickening. Pediatricians in Korea must acknowledge thalassemia as a possible diagnosis in children with microcytic hypochromic hemolytic anemia. High level of suspicion will allow timely diagnosis and managements.
PMCID: PMC3835508  PMID: 24265529
α-Thalassemia; β-Thalassemia; Genotype; Phenotype; Child; Korea
11.  Nonalcoholic fatty liver disease is associated with coronary artery disease in Koreans 
AIM: To investigate whether nonalcoholic fatty liver disease (NAFLD) affects coronary artery disease (CAD) and identify candidate mediators.
METHODS: Patients who underwent coronary angiography were consecutively recruited. The patients were classified into four groups by coronary artery stenosis: A, insignificant; B, one-vessel disease; C, two-vessel disease; and D, three-vessel disease. Abdominal ultrasonography was performed to determine the presence of a fatty liver and categorize by grade: 0, no evidence; 1, mild; 2, moderate; and 3, severe. We measured not only known CAD risk factors, but also serum insulin, HOMA-index, adiponectin, interleukin-6, tumor necrosis factor-α and high-sensitivity C-reactive protein levels.
RESULTS: Of the 134 patients who met the inclusion criteria, 82 (61.2%) had ultrasonographically diagnosed NAFLD. Among the 46 patients with CAD, 37 (80.4%) had evidence of a fatty liver. The two groups (A vs B-D) were significantly different in terms of age, total cholesterol, triglycerides, low-density lipoprotein levels and fatty liver. Coronary artery stenosis was strongly associated with fatty liver in a grade-dependent manner (P = 0.025). In binary logistic regression, NAFLD was a significant independent predictor of CAD (P = 0.03, OR = 1.685; 95%CI: 1.051-2.702). Among the candidate mediators, the serum adiponectin level showed a trend toward lowering based on CAD progression (P = 0.071).
CONCLUSION: NAFLD is an independent risk factor for CAD in a grade-dependent manner. Moreover, adiponectin might be related to the pathogenesis of NAFLD.
PMCID: PMC3801316  PMID: 24151364
Nonalcoholic fatty liver disease; Coronary artery disease; Coronary angiography; Adiponectin; Insulin resistance
12.  Epigallocatechin Gallate Induces Expression of Heme Oxygenase-1 in Endothelial Cells via p38 MAPK and Nrf-2 that Suppresses Pro-inflammatory Actions of TNF-α 
Epigallocatechin gallate (EGCG), the major polyphenol in green tea, acutely stimulates production of nitric oxide (NO) from vascular endothelium to reduce hypertension, and improve endothelial dysfunction in SHR rats. Herein, we explored additional mechanisms whereby EGCG may mediate beneficial cardiovascular actions. When compared with vehicle-treated controls, EGCG treatment (2.5 μM, 8 h) of human aortic endothelial cells (HAEC) caused a ~3-fold increase in hemeoxygenase-1 (HO-1) mRNA and protein with comparable increases in HO-1 activity. This was unaffected by pre-treatment of cells with wortmannin, LY294002, PD98059, or L-NAME (PI 3-kinase, MEK, and NO synthase inhibitors, respectively). Pre-treatment of HAEC with SB203580 (p38 MAPK inhibitor) or siRNA knockdown of p38 MAPK completely blocked EGCG-stimulated induction of HO-1. EGCG treatment also inhibited TNF-α-stimulated expression of VCAM-1 and decreased adhesion of monocytes to HAEC. siRNA knockdown of HO-1, p38 MAPK, or Nrf-2 blocked these inhibitory actions of EGCG. In HAEC transiently transfected with a human HO-1 promoter luciferase reporter (or an isolated Nrf-2 responsive region), luciferase activity increased in response to EGCG. This was inhibitable by SB203580 pre-treatment. EGCG-stimulated expression of HO-1 and Nrf-2 was blocked by siRNA knockdown of Nrf-2 or p38 MAPK. Finally, liver from mice chronically treated with EGCG had increased HO-1 and decreased VCAM-1 expression. Thus, in vascular endothelium, EGCG requires p38 MAPK to increase expression of Nrf-2 that drives expression of HO-1 resulting in increased HO-1 activity. Increased HO-1 expression may underlie anti-inflammatory actions of EGCG in vascular endothelium that may help mediate beneficial cardiovascular actions of green tea.
PMCID: PMC3296830  PMID: 22137262
Epigallocatechin gallate (EGCG); hemeoxygenase-1; p38 kinase; nuclear factor-E2-related factor-2; endothelium
13.  The Effect of Gingko Biloba on Hearing in Mice with Noise-Induced Temporary Threshold Shift 
Korean Journal of Audiology  2013;17(2):74-77.
Background and Objectives
Gingko biloba extract is known for enhancing blood circulation, scavenging free radicals, and antagonizing against platelet-activating factor. This study evaluated the effect of Gingko biloba on the noise-induced temporary threshold shift of hearing.
Materials and Methods
Temporary threshold shift was induced by exposing mice to 110 dB SPL sound for 1 hour. The experimental group consisted of mice fed Gingko biloba [3 mg/kg, 6 mg/kg, and 12 mg/kg in 0.5% carboxymethyl cellulose (CMC)] for 7 days before noise exposure. CMC solution without Gingko biloba was fed to control mice. Hearing threshold was measured by auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE).
The hearing threshold increased after noise exposure and recovered to normal within 5 days in all groups. Compared to control mice (fed CMC solution only), mice fed Gingko biloba showed more rapid recovery of ABR threshold at 16 kHz in all three experimental groups. At the other frequencies, there was no significant change in hearing recovery in the Gingko biloba groups. There was no difference in DPOAE between groups.
Temporary threshold shift of hearing after noise exposure was partly affected by oral Gingko biloba.
PMCID: PMC3936537  PMID: 24653910
Hearing loss; Noise-induced; Temporary threshold shift; Gingko biloba; Hearing
14.  Pharmacogenetic Study of Deferasirox, an Iron Chelating Agent 
PLoS ONE  2013;8(5):e64114.
Transfusion-associated iron overload induces systemic toxicity. Deferasirox, a convenient long acting oral agent, has recently been introduced in clinical practice with a promising efficacy. But there are some patients who experience drug-related toxicities and cannot tolerate it. To investigate effect of genetic variations on the toxicities and find optimal target population, we analyzed the genetic polymorphisms of UDP-glucuronosyltransferase 1A (UGT1A) subfamily, multi-drug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP). A total of 20 functional genetic polymorphisms were analyzed in 98 patients who received deferasirox to reduce transfusion-induced iron overload. We retrospectively reviewed the medical records to find out the drug-related toxicities. Fifteen (15.3%) patients developed hepatotoxicity. Patients without wild-type allele carrying two MRP2 haplotypes containing −1774 del and/or −24T were at increased risk of developing hepatotoxicity compared to patients with the wild-type allele on multivariate analysis (OR = 7.17, 95% CI = 1.79–28.67, P = 0.005). Creatinine elevation was observed in 9 patients (9.2%). Body weight ≥40 kg and homozygosity for UGT1A1*6 were risk factors of creatinine elevation (OR = 8.48, 95% CI = 1.7–43.57, P = 0.010 and OR = 14.17, 95% CI = 1.34–150.35, P = 0.028). Our results indicate that functional genetic variants of enzymes to metabolize and transport deferasirox are associated with drug-related toxicities. Further studies are warranted to confirm the results as the pharmacogenetic biomarkers of deferasirox.
PMCID: PMC3667856  PMID: 23737969
15.  Effects of veraguensin and galgravin on osteoclast differentiation and function 
Cytotechnology  2012;64(3):315-322.
The dried flower buds of Magnolia sp. are widely used as herbal medicines because of their anti-inflammatory, anti-malarial and anti-platelet activities. Here, we found that veraguensin and galgravin, lignan compounds derived from Magnolia sp., dose-dependently inhibited osteoclast formation in co-cultures of bone marrow cells and osteoblastic cells. These compounds also inhibited receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation in RAW264.7 cells and bone marrow macrophages. In the RANKL-induced signaling pathway, veraguensin and galgravin reduced p38 phosphorylation and suppressed the expression of c-Fos, a key transcription factor for osteoclastogenesis. Veraguensin and galgravin also inhibited osteoclastic pit formation, which was accompanied by decreased mature osteoclast viability. In conclusion, these results indicate that veraguensin and galgravin can inhibit bone resorption and may offer novel compounds for the development of drugs to treat bone-destructive diseases such as osteoporosis.
PMCID: PMC3386385  PMID: 22526488
Veraguensin.; Galgravin; RANKL; Osteoclast; p38; c-Fos
16.  Staphylococcal enterotoxin specific IgE and asthma: a systematic review and meta-analysis 
Asia Pacific Allergy  2013;3(2):120-126.
Recent literature suggests that Staphylococcal enterotoxin specific IgE may be a risk factor for asthma.
To investigate the associations between Staphylococcal enterotoxin sensitization and asthma.
A systematic review and meta-analysis was performed for relevant case-control or population-based studies, published in the peer-reviewed journals until February 2013. Data were extracted on study designs, subjects, definitions and the prevalence of Staphylococcal enterotoxin sensitization.
A total of 683 studies were initially identified, of which 7 studies finally met the inclusion criteria (5 case-control and 2 population-based studies). All the included studies reported higher prevalence of the sensitization in asthmatics than in controls, despite clinical and methodological heterogeneity. In a meta-analysis, the pooled odds ratio of the sensitization for asthma was 2.95 (95% confidence intervals 2.28-3.82).
Staphylococcal enterotoxin sensitization was significantly associated with asthma. The mechanisms of associations warrant further elucidation.
PMCID: PMC3643054  PMID: 23667836
Asthma; Staphylococcus; Meta-analysis
17.  Cardiopulmonary Fitness Is Independently Associated with Insulin Resistance in Non-Diabetes Mellitus Patients of a University Hospital in Korea 
Korean Journal of Family Medicine  2013;34(2):139-144.
Insulin resistance, decreased response of peripheral tissue to normal insulin levels, is known to be related to cardiometabolic diseases. Cardiopulmonary fitness is also considered to be related to these comorbidities. Therefore, we investigated the relationship between insulin resistance and cardiopulmonary fitness by performing a 3-minute step test in a Korean non-diabetes mellitus (DM) population.
A total of 118 non-DM subjects were enrolled during their routine health check-up. Insulin resistance was measured by calculating homeostatic model assessment-insulin resistance (HOMA-IR), and a 3-minute step test was performed to measure cardiopulmonary fitness.
Post-60 seconds exercise heart rate after 3-minute test (R60 heart rate) was correlated with age (r = -0.21, P = 0.02), education (r = 0.17, P = 0.04), body mass index (r = 0.23, P = 0.01), waist circumference (r = 0.28, P < 0.01), fasting insulin (r = 0.28, P < 0.01), HOMA-IR (r = 0.25, P < 0.01), low density lipoprotein-cholesterol (r = 0.28, P < 0.01), high sensitivity C-reactive protein levels (r = 0.22, P = 0.02), and baseline heart rate (r = 0.56, P < 0.01). In a step-wise multiple regression analysis, baseline heart rate (β = 0.79, P < 0.001), HOMA-IR (β = 0.65, P = 0.02), and systolic blood pressure (β = 0.15, P = 0.03) were identified as explanatory variables for R60 heart rates.
Our results suggested that cardiopulmonary fitness was associated with insulin resistance in non-DM patients of a university hospital in Korea. Further studies are needed to elucidate the underlying mechanisms.
PMCID: PMC3611102  PMID: 23560213
Insulin Resistance; Physical Fitness; Exercise Test
18.  Impact of Diabetes on Oncologic Outcome of Colorectal Cancer Patients: Colon vs. Rectal Cancer 
PLoS ONE  2013;8(2):e55196.
To evaluate the impact of diabetes on outcomes in colorectal cancer patients and to examine whether this association varies by the location of tumor (colon vs. rectum).
Patients and methods
This study includes 4,131 stage I-III colorectal cancer patients, treated between 1995 and 2007 (12.5% diabetic, 53% colon, 47% rectal) in South Korea. Cox proportional hazards modeling was used to determine the prognostic influence of DM on survival endpoints.
Colorectal cancer patients with DM had significantly worse disease-free survival (DFS) [hazard ratio (HR) 1.17, 95% confidence interval (CI): 1.00–1.37] compared with patients without DM. When considering colon and rectal cancer independently, DM was significantly associated with worse overall survival (OS) (HR: 1.46, 95% CI: 1.11–1.92), DFS (HR: 1.45, 95% CI: 1.15–1.84) and recurrence-free survival (RFS) (HR: 1.32, 95% CI: 0.98–1.76) in colon cancer patients. No association for OS, DFS or RFS was observed in rectal cancer patients. There was significant interaction of location of tumor (colon vs. rectal cancer) with DM on OS (P = 0.009) and DFS (P = 0.007).
This study suggests that DM negatively impacts survival outcomes of patients with colon cancer but not rectal cancer.
PMCID: PMC3566217  PMID: 23405123
20.  Successful Treatment of Primary Central Nervous System Lymphoma without Irradiation in Children: Single Center Experience 
Journal of Korean Medical Science  2012;27(11):1378-1384.
Primary CNS lymphoma (PCNSL) is a very uncommon disease in children, and usually treated by chemotherapy, combined with focal or craniospinal radiotherapy (RT). However, adverse effects of RT are a concern. We evaluated the outcomes of childhood PCNSL, treated with systemic and intrathecal chemotherapy, but without RT. For fifteen years, six patients among 175 of non-Hodgkin lymphoma were diagnosed as PCNSL in Seoul National University Children's Hospital and we analyzed their medical records retrospectively. Their male:female ratio was 5:1, and median age was 10.1 yr. The primary sites were the sellar area in three patients, parietal area in one, cerebellum in one, and multiple areas in one. Their pathologic diagnoses were diffuse large B-cell lymphoma in three patients, Burkitt lymphoma in two, and undifferentiated B-cell lymphoma in one. Five were treated with the LMB96 treatment protocol, and one was treated with the CCG-106B protocol. None had RT as a first-line treatment. One patient had a local relapse and received RT and salvage chemotherapy, without success. No patient had treatment-related mortality. Their estimated 5-yr event-free and overall survival rates were both 83.3%. In conclusion, PCNSL is a rare disease in childhood, but successfully treated by chemotherapy without RT.
PMCID: PMC3492674  PMID: 23166421
Primary CNS Lymphoma; Children; Irradiation
21.  Protective effect of the methanol extract from Cryptotaenia japonica Hassk. against lipopolysaccharide-induced inflammation in vitro and in vivo 
In folk medicine, the aerial part of Crytotaenia japonica Hassk. (CJ), is applied for treatment of the common cold, cough, urinary problems, pneumonia, and skin rashes. In this paper, the in vitro and in vivo anti-inflammatory activity of CJ methanol extract was tested using lipopolysaccharide (LPS)-induced inflammatory models.
We measured nitric oxide (NO), inducible NO synthase (iNOS), and inflammatory cytokine levels from LPS-stimulated mouse peritoneal macrophages. Also, several cellular signaling molecules which regulate the expressions of these inflammatory markers were examined. Finally, we tested whether oral administration of CJ methanol extract might affect the serum cytokine levels in LPS-injected mice.
CJ methanol extract reduced NO release via iNOS protein inhibition. The extract was also shown to decrease the secretions of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-12. Analysis of signaling molecules showed that CJ inhibited the phosphorylation of STAT1, p38, JNK and ERK1/2 as well as IκBα degradation. Finally, CJ decreased the serum levels of TNF-α and IL-6 in LPS-injected mice.
Our results demonstrated the anti-inflammatory activity of CJ methanol extract and its possible underlying mechanisms that involve modulation of IκBα, MAPK, and STAT1 activities.
PMCID: PMC3534510  PMID: 23110456
Cryptotaenia japonica Hassk.; Inflammation; Macrophages; iNOS; Cytokines; Signaling
22.  Serum Carcinoembryonic Antigen Is Associated with Abdominal Visceral Fat Accumulation in Female Korean Nonsmokers 
PLoS ONE  2012;7(8):e43518.
Carcinoembryonic antigen (CEA) is a tumor marker overexpressed in adenocarcinoma that has proinflammatory properties. Recent studies have reported that CEA is positively associated with carotid atherosclerosis and metabolic syndrome. Because visceral obesity is a known risk factor for cardiometabolic diseases, CEA may also be associated with visceral adiposity. Therefore, we investigated the relationship between serum CEA concentration and visceral obesity in female Korean nonsmokers.
A total of 270 Korean female nonsmokers were enrolled during their routine health check-ups. Biomarkers of metabolic risk factors were assessed along with body composition by computed tomography. Serum CEA levels were measured by using a chemiluminescence immunoassay analyzer.
Serum CEA levels correlated with visceral fat area, fasting glucose, and triglyceride levels after adjusting for age and BMI. The mean visceral fat area increased significantly with the increasing CEA tirtiles. In a step-wise multiple regression analysis, age (β = 0.26, p<0.01) and visceral fat area (β = 0.19, p = 0.03) were identified as explanatory variables for serum CEA level.
This study suggested that CEA may be a mediator that links metabolic disturbance and tumorigenesis in visceral obesity. Further studies are required to better understand the clinical and pathophysiological significance of our findings.
PMCID: PMC3428363  PMID: 22952699
23.  Cyclooxygenase-2 Expression and Its Prognostic Significance in Clear Cell Renal Cell Carcinoma 
Korean Journal of Pathology  2012;46(3):237-245.
The prognostic value of cyclooxygenase-2 (COX-2) in human renal cell carcinoma (RCC) remains unclear. The purposes of this study are to elucidate the clinical significance of COX-2 in clear cell RCC (CCRCC) and to assess the treatment effect of COX-2 inhibition on CCRCC cell lines.
Using tumor samples obtained from 137 patients who had undergone nephrectomy at Seoul National University Hospital, we evaluated COX-2 expression on immunohistochemistry. Moreover, we performed the cell proliferation assay using 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) and cell invasion assay. Thus, we evaluated the effect of meloxicam, an inhibitor of COX-2, in two human CCRCC cell lines.
Cancer-specific survival (p=0.038) and progression-free survival (p=0.031) were shorter in the COX-2 high expression group. A multivariate logistic regression model showed that COX-2 expression was an independent risk factor for pTNM stage and Fuhrman nuclear grade. The MTT assay revealed that COX-2 inhibition led to the suppression of the proliferation of CCRCC cell lines. Moreover, it also reduced their invasion capacity.
This study postulates that COX-2 is a poor prognostic indicator in human CCRCC, suggesting that COX-2 inhibition can be a potential therapy in CCRCC.
PMCID: PMC3479766  PMID: 23110009
Carcinoma, renal cell; Cyclooxygenase 2; Prognosis
24.  Chemerin and Adiponectin Contribute Reciprocally to Metabolic Syndrome 
PLoS ONE  2012;7(4):e34710.
Obesity and metabolic syndrome (MetS) are considered chronic inflammatory states. Chemerin, a novel adipokine, may play an important role in linking MetS and inflammation. We investigated the association of chemerin with inflammatory markers and with characteristics of MetS in apparently healthy overweight and obese adults. We studied 92 adults; 59 men and 33 women whose average body mass index (BMI) was 28.15±5.08 kg/m2. Anthropometric parameters, insulin resistance indices, lipid profiles, and inflammatory markers including high sensitivity C-reactive protein (hsCRP), pentraxin 3 (PTX3), adiponectin, and chemerin were measured. Controlling for age, gender, and BMI, serum chemerin level was positively correlated with body fat and serum triglyceride, and negatively correlated with adiponectin and high density lipoprotein cholesterol (HDL- C), and was not correlated with altered hsCRP or PTX3 levels. Among the low, moderate and high chemerin groups, high chemerin individuals are more likely to have lower HDL-C. Conversely, individuals in the low adiponectin group are more likely to have lower HDL-C and show more MetS phenotypic traits than moderate and high adiponectin subjects. To determine the relationships of chemerin and adiponectin to MetS and its components, participants were stratified into four groups based on their chemerin and adiponectin levels (high chemerin/high adiponectin, high chemerin/low adiponectin, low chemerin/high adiponectin, or low chemerin/low adiponectin). Participants who were in the high chemerin/low adiponectin group more likely to have dyslipidemia and MetS (OR: 5.79, 95% CI:1.00–33.70) compared to the other three group. Our findings suggest that chemerin and adiponectin may reciprocally participate in the development of MetS.
PMCID: PMC3324504  PMID: 22509348
25.  Successful mobilization using a combination of plerixafor and G-CSF in pediatric patients who failed previous chemomobilization with G-CSF alone and possible complications of the treatment 
Peripheral blood stem cell (PBSC) mobilization, which uses plerixafor (AMD 3100), a newly developed specific inhibitor of the CXCR4 receptor, in combination with granulocyte-colony stimulating factor(G-CSF), has been shown to enhance the stem cell mobilization in adult patients, but pediatric data are scarce. We documented our experience with this drug in 6 Korean pediatric patients who had failed in chemomobilization, using G-CSF, alone. All patients were mobilized CD34+ cells (median, 11.08 × 106/kg: range, 6.34-28.97 × 106/kg) successfully within 2 to 3 cycles of apheresis, without complications. A total of 7 autologous transplantations were performed, including 1 tandem transplantation. However, 2 patients with brain tumors showed severe pulmonary complications, including spontaneous pneumomediastinum. This is the first study of PBSC mobilization with plerixafor in Asian pediatric patients. Furthermore our study suggests that mobilization with plerixafor may be effective in Korean pediatric patients, who have previously been heavily treated and have failed PBSC mobilization with classical chemomobilization, using G-CSF. However, further studies are needed to examine the possible complications of autologous transplantation, using a mobilized plerixafor product in children.
PMCID: PMC3361468  PMID: 22458355
Plerixafor; Hematopoietic Stem Cell Mobilization; Pediatrics; Complications; Interstitial Lung Diseases

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