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1.  An ethyl acetate fraction derived from Houttuynia cordata extract inhibits the production of inflammatory markers by suppressing NF-кB and MAPK activation in lipopolysaccharide-stimulated RAW 264.7 macrophages 
Houttuynia cordata Thunb. (Saururaceae) has been used in traditional medicine for treatment of inflammatory diseases. This study evaluated the anti-inflammatory effects of an ethyl acetate fraction derived from a Houttuynia cordata extract (HCE-EA) on the production of inflammatory mediators and the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages.
To measure the effects of HCE-EA on pro-inflammatory cytokine and inflammatory mediator’s expression in RAW 264.7 cells, we used the following methods: cell viability assay, Griess reagent assay, enzyme-linked immunosorbent assay, real-time polymerase chain reaction and western blotting analysis.
HCE-EA downregulated nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin (IL-6) production in the cells, as well as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. Furthermore, HCE-EA suppressed nuclear translocation of the NF-κB p65 subunit, which correlated with an inhibitory effect on IκBα (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha) phosphorylation. HCE-EA also attenuated the activation of MAPKs (p38 and JNK).
Our results suggest that the anti-inflammatory properties of HCE-EA may stem from the inhibition of pro-inflammatory mediators via suppression of NF-κB and MAPK signaling pathways.
PMCID: PMC4099023  PMID: 25012519
Houttuynia cordata; Inducible nitric oxide synthase; Cyclooxygenase-2; Nuclear factor-κB; Mitogen-activated protein kinase
2.  Prevalence of Systemic Lupus Erythematosus in South Korea: An Administrative Database Study 
Journal of Epidemiology  2014;24(4):295-303.
Systemic lupus erythematosus (SLE) is a rare autoimmune disease for which a population-based survey on the prevalence of the disease in South Korea has not yet been conducted. Our goal was to estimate the nationwide prevalence of SLE.
The International Classification of Diseases, Tenth Revision (ICD-10) code for SLE diagnosis—M32—was tentatively given when patients were suspected to have SLE before 2009. As such, the positive predictive value (PPV) of the M32 code shown in medical bills reflecting true SLE was uncertain. We attempted to estimate the prevalence of SLE in South Korea using national administrative database data from 2004–2006. We approximated the actual number of SLE patients by analyzing a list of SLE-coded patients provided by the National Health Insurance (NHI) and Health Insurance Review and Assessment Service. Prevalence was estimated by multiplying the PPV of the M32 diagnostic code by the number of patients receiving the code. The PPV was determined by three methods: direct investigation of the medical records of patients randomly selected from the SLE-coded patients list; assessment of all SLE patients treated at 56 selected hospitals in South Korea; and extrapolation from sub-groups at a single institute to the sub-groups of the national NHI data.
The estimated number of national SLE cases was between 9000 and 11 000, depending on the method of ascertainment, corresponding to a prevalence of 18.8–21.7 per 100 000 people.
This is the first report of a nationwide prevalence survey of SLE in South Korea. National databases may serve as a resource for epidemiologic studies of rare autoimmune diseases like SLE.
PMCID: PMC4074634  PMID: 24857955
systemic lupus erythematosus; prevalence; epidemiology
3.  The Cohort for Childhood Origin of Asthma and allergic diseases (COCOA) study: design, rationale and methods 
BMC Pulmonary Medicine  2014;14:109.
This paper describes the background, aim, and design of a prospective birth-cohort study in Korea called the COhort for Childhood Origin of Asthma and allergic diseases (COCOA). COCOA objectives are to investigate the individual and interactive effects of genetics, perinatal environment, maternal lifestyle, and psychosocial stress of mother and child on pediatric susceptibility to allergic diseases.
The participants in COCOA represents a Korean inner-city population. Recruitment started on 19 November, 2007 and will continue until 31 December, 2015. Recruitment is performed at five medical centers and eight public-health centers for antenatal care located in Seoul. Participating mother-baby pairs are followed from before birth to adolescents. COCOA investigates whether the following five environmental variables contribute causally to the development and natural course of allergic diseases: (1) perinatal indoor factors (i.e. house-dust mite, bacterial endotoxin, tobacco smoking, and particulate matters 2.5 and 10), (2) perinatal outdoor pollutants, (3) maternal prenatal psychosocial stress and the child’s neurodevelopment, (4) perinatal nutrition, and (5) perinatal microbiome. Cord blood and blood samples from the child are used to assess whether the child’s genes and epigenetic changes influence allergic-disease susceptibility. Thus, COCOA aims to investigate the contributions of genetics, epigenetics, and various environmental factors in early life to allergic-disease susceptibility in later life. How these variables interact to shape allergic-disease susceptibility is also a key aim.
The COCOA data collection schedule includes 11 routine standardized follow-up assessments of all children at 6 months and every year until 10 years of age, regardless of allergic-disease development. The mothers will complete multiple questionnaires to assess the baseline characteristics, the child’s exposure to environmental factors, maternal pre- and post-natal psychological stress, and the child’s neurodevelopment, nutritional status, and development of allergic and respiratory illnesses. The child’s microbiome, genes, epigenetics, plasma cytokine levels, and neuropsychological status, the microbiome of the residence, and the levels of indoor and outdoor pollutants are measured by standard procedures.
The COCOA study will improve our understanding of how individual genetic or environmental risk factors influence susceptibility to allergic disease and how these variables interact to shape the phenotype of allergic diseases.
PMCID: PMC4099383  PMID: 24990471
Cohort study; Gene-environment interaction; Allergy; Microbiota; Nutritional Status; Psychologic stress
4.  Prognosis of early mucinous gastric carcinoma 
Little is known about the clinicopathological features of early mucinous gastric carcinoma (MGC). The purpose of this study was to compare the clinicopathological features and prognosis between patients with early MGC and those with early nonmucinous gastric carcinoma (NMGC).
We reviewed the records of 2,732 patients diagnosed with gastric carcinoma who were treated surgically. There were 14 patients (0.5%) with early MGC and 958 with early NMGC.
Early MGC patients had a higher prevalence of elevated type (71.4%) compared with early NMGC patients (29.5%). More early MGC patients had submucosal carcinoma, compared with early NMGC patients (78.6% vs. 64.1%). The overall 5-year survival of the patients with early MGC was 97.2% as compared with 92.7% for the patients with early NMGC (P < 0.01). The statistically significant prognostic parameters influencing the 5-year survival rate according to Cox's proportional hazard regression model were: age (risk ratio, 2.22; 95% confidence interval [CI], 1.62-3.04; P < 0.01); sex (risk ratio, 1.97; 95% CI, 1.42-2.73; P < 0.01); and lymph node metastases (risk ratio, 1.88; 95% CI, 1.28-2.77; P < 0.01).
Patients with early MGC had a better prognosis than those with early NMGC. Mucinous histology itself appears not to be an independent prognostic factor. Therefore, early detection is important for improving the prognosis for patients with gastric carcinoma regardless of tumor histology.
PMCID: PMC4091442  PMID: 25025020
Gastric neoplasm; Mucinous; Prognosis; Tumor histology
5.  The Positive Effects of One-Hour Intravenous Administration of Bortezomib on Peripheral Neuropathy in Multiple Myeloma Patients 
BioMed Research International  2014;2014:237698.
Bortezomib-induced peripheral neuropathy (BiPN) in multiple myeloma (MM) patients is a common and serious side effect. Currently, it has been reported that subcutaneous (SC) administration of bortezomib decreases the incidence of BiPN as compared to standard intravenous (IV) bolus injection without any differences in efficacy. However, there are reports of severe injection site reaction following SC administration of bortezomib. The aim of this study was to evaluate the response rate and incidence of BiPN following one-hour IV infusion of bortezomib. The data was retrospectively collected from MM patients who had been treated with IV administration of bortezomib for one hour. Twenty-three patients were evaluated (median age 72 years, 13 males). The median number of treatment cycles was 5 (range 2–10). The cumulative bortezomib dose was 26.0 mg/m2 (14.3–66.3) and percent of actual per expected cumulative dose was 90% (50–100). The overall response (complete response plus partial response) rate was 65%. The incidence of BiPN was 57% (n = 13) and incidence of severe neuropathy was 4% (n = 1). One-hour IV infusion of bortezomib was an effective regimen for MM with reduced incidence of severe BiPN. This route of administration of bortezomib could be an alternative mode of delivery for patients with severe injection site reactions following SC administration.
PMCID: PMC4065765  PMID: 24995276
6.  Clinical characteristics and treatment outcome of acute myeloid leukemia in elderly patients in Korea: a retrospective analysis 
Blood research  2014;49(2):95-99.
The clinical characteristics of elderly patients with AML differ from those of younger patients, resulting in poorer survival and treatment outcomes. We analyzed retrospectively the clinical data of AML patients 65 years old and above to describe patients' characteristics and treatment patterns, and to define meaningful prognostic factors of survival in the Korean population.
Basic patients' characteristics, clinical outcomes according to treatments, and prognostic factors associated with survival and treatment intensity were examined in a total of 168 patients diagnosed in 5 institutes between 1996 and 2012 as having AML.
Herein, 84 patients (50.0%) received high-intensity regimens (HIR), 18 (10.7%) received low-intensity regimens (LIR), and 66 (39.3%) received supportive care (SC) only. The median survival of all patients was 4.5 months; and median survival times with HIR, LIR, and SC were 6.8 months, 10.2 months, and 1.6 months, respectively. Median survival times with HIR and LIR were significantly longer than that with SC (P<0.0001 and P=0.006, respectively). Multivariate analysis identified age, Eastern Cooperative Oncology Group-performance status (ECOG-PS), hemoglobin (Hb) level, and serum creatinine (Cr) level as statistically significant prognostic factors for survival. In the HIR group, prognostic factors for survival were ECOG-PS, Hb level, and C-reactive protein level.
Even in elderly AML patients, an intensive treatment regimen could be beneficial with careful patient selection. Further prospective studies designed to identify specific prognostic factors are required to establish an optimal treatment strategy for elderly AML patients.
PMCID: PMC4090344  PMID: 25025010
Acute myeloid leukemia; Survival; Prognosis; Chemotherapy; Elderly
7.  Extremely Efficient Liquid Exfoliation and Dispersion of Layered Materials by Unusual Acoustic Cavitation 
Scientific Reports  2014;4:5133.
Layered materials must be exfoliated and dispersed in solvents for diverse applications. Usually, highly energetic probe sonication may be considered to be an unfavourable method for the less defective exfoliation and dispersion of layered materials. Here we show that judicious use of ultrasonic cavitation can produce exfoliated transition metal dichalcogenide nanosheets extraordinarily dispersed in non-toxic solvent by minimising the sonolysis of solvent molecules. Our method can also lead to produce less defective, large graphene oxide nanosheets from graphite oxide in a short time (within 10 min), which show high electrical conductivity (>20,000 S m−1) of the printed film. This was achieved by adjusting the ultrasonic probe depth to the liquid surface to generate less energetic cavitation (delivered power ~6 W), while maintaining sufficient acoustic shearing (0.73 m s−1) and generating additional microbubbling by aeration at the liquid surface.
PMCID: PMC4038810  PMID: 24875584
8.  Clinical and Genetic Aspects in Twelve Korean Patients with Adrenomyeloneuropathy 
Yonsei Medical Journal  2014;55(3):676-682.
This study was designed to investigate the characteristics of Korean adrenomyeloneuropathy (AMN) patients.
Materials and Methods
We retrospectively selected 12 Korean AMN patients diagnosed by clinical analysis and increased plasma content of very long chain fatty acids.
All 12 patients were men. Patient ages at symptom onset ranged from 18 to 55 years. Family history was positive in two patients. The phenotype distributions consisted of AMN without cerebral involvement in seven patients, AMN with cerebral involvement in two patients, and the spinocerebellar phenotype in three patients. Nerve conduction studies revealed abnormalities in four patients and visual evoked tests revealed abnormalities in three patients. Somatosensory evoked potential tests revealed central conduction defects in all of the tested patients. Spinal MRI showed diffuse cord atrophy or subtle signal changes in all 12 patients. Brain MRI findings were abnormal in six of the nine tested patients. These brain abnormalities reflected the clinical phenotypes. Mutational analysis identified nine different ABCD1 mutations in 10 of 11 tested patients. Among them, nine have been previously reported and shown to be associated with various phenotypes; one was a novel mutation.
In conclusion, the present study is the first to report on the clinical and mutational spectrum of Korean AMN patients, and confirms various clinical presentations and the usefulness of brain MRI scan.
PMCID: PMC3990087  PMID: 24719134
Adrenoleukodystrophy; adrenomyeloneuropathy; ataxia; very long chain fatty acid; ABCD1
9.  Silencing of KIF14 interferes with cell cycle progression and cytokinesis by blocking the p27Kip1 ubiquitination pathway in hepatocellular carcinoma 
Although it has been suggested that kinesin family member 14 (KIF14) has oncogenic potential in various cancers, including hepatocellular carcinoma (HCC), the molecular mechanism of this potential remains unknown. We aimed to elucidate the role of KIF14 in hepatocarcinogenesis by knocking down KIF14 in HCC cells that overexpressed KIF14. After KIF14 knockdown, changes in tumor cell growth, cell cycle and cytokinesis were examined. We also examined cell cycle regulatory molecules and upstream Skp1/Cul1/F-box (SCF) complex molecules. Knockdown of KIF14 resulted in suppression of cell proliferation and failure of cytokinesis, whereas KIF14 overexpression increased cell proliferation. In KIF14-silenced cells, the levels of cyclins E1, D1 and B1 were profoundly decreased compared with control cells. Of the cyclin-dependent kinase inhibitors, the p27Kip1 protein level specifically increased after KIF14 knockdown. The increase in p27Kip1 was not due to elevation of its mRNA level, but was due to inhibition of the proteasome-dependent degradation pathway. To explore the pathway upstream of this event, we measured the levels of SCF complex molecules, including Skp1, Skp2, Cul1, Roc1 and Cks1. The levels of Skp2 and its cofactor Cks1 decreased in the KIF14 knockdown cells where p27Kip1 accumulated. Overexpression of Skp2 in the KIF14 knockdown cells attenuated the failure of cytokinesis. On the basis of these results, we postulate that KIF14 knockdown downregulates the expression of Skp2 and Cks1, which target p27Kip1 for degradation by the 26S proteasome, leading to accumulation of p27Kip1. The downregulation of Skp2 and Cks1 also resulted in cytokinesis failure, which may inhibit tumor growth. To the best of our knowledge, this is the first report that has identified the molecular target and oncogenic effect of KIF14 in HCC.
PMCID: PMC4044675  PMID: 24854087
cell cycle; cytokinesis; hepatocellular carcinoma; KIF14; p27kip1; ubiquitination
10.  Development of a Multiplex and Cost-Effective Genotype Test toward More Personalized Medicine for the Antiplatelet Drug Clopidogrel 
There has been a wide range of inter-individual variations in platelet responses to clopidogrel. The variations in response to clopidogrel can be driven by genetic polymorphisms involved in the pathway of absorption, distribution, metabolism, excretion, and the target receptor P2Y12. A set of genetic variants known for causing variations in clopidogrel responses was selected, which included CYP2C19*2, *3, *17, CYP2B6*4, *6, *9, CYP3A4*18, CYP3A5*3, MDR1 2677G > T/A, 3435C > T, and P2Y12 H2 (742T > C). The simultaneous detection of these 10 variants was developed by using a multiplex PCR and single-base extension (MSSE) methodology. The newly developed genotyping test was confirmed by direct DNA sequencing in the representative positive control samples and validated in an extended set of 100 healthy Korean subjects. Genotyping results from the developed MSSE exhibited a perfect concordance with the direct DNA sequencing data and all of variants tested in 100 healthy Korean subjects were in agreement with Hardy-Weinberg equilibrium (p > 0.05). The present molecular diagnostic studies provide an accurate, convenient, and fast genotyping method for the detection of multiple variants. This would be helpful for researchers, as well as clinicians, to use genetic information toward more personalized medicine of clopidogrel and other antiplatelet drugs in the future.
PMCID: PMC4057700  PMID: 24857912
clopidogrel; genotypes; CYP2C19; P2Y12; SNaPshot; pharmacogenetics
11.  Electrically Robust Metal Nanowire Network Formation by In-Situ Interconnection with Single-Walled Carbon Nanotubes 
Scientific Reports  2014;4:4804.
Modulation of the junction resistance between metallic nanowires is a crucial factor for high performance of the network-structured conducting film. Here, we show that under current flow, silver nanowire (AgNW) network films can be stabilised by minimizing the Joule heating at the NW-NW junction assisted by in-situ interconnection with a small amount (less than 3 wt%) of single-walled carbon nanotubes (SWCNTs). This was achieved by direct deposition of AgNW suspension containing SWCNTs functionalised with quadruple hydrogen bonding moieties excluding dispersant molecules. The electrical stabilisation mechanism of AgNW networks involves the modulation of the electrical transportation pathway by the SWCNTs through the SWCNT-AgNW junctions, which results in a relatively lower junction resistance than the NW-NW junction in the network film. In addition, we propose that good contact and Fermi level matching between AgNWs and modified SWCNTs lead to the modulation of the current pathway. The SWCNT-induced stabilisation of the AgNW networks was also demonstrated by irradiating the film with microwaves. The development of the high-throughput fabrication technology provides a robust and scalable strategy for realizing high-performance flexible transparent conductor films.
PMCID: PMC3999447  PMID: 24763208
12.  Ultra-High Performance, High-Temperature Superconducting Wires via Cost-effective, Scalable, Co-evaporation Process 
Scientific Reports  2014;4:4744.
Long-length, high-temperature superconducting (HTS) wires capable of carrying high critical current, Ic, are required for a wide range of applications. Here, we report extremely high performance HTS wires based on 5 μm thick SmBa2Cu3O7 − δ (SmBCO) single layer films on textured metallic templates. SmBCO layer wires over 20 meters long were deposited by a cost-effective, scalable co-evaporation process using a batch-type drum in a dual chamber. All deposition parameters influencing the composition, phase, and texture of the films were optimized via a unique combinatorial method that is broadly applicable for co-evaporation of other promising complex materials containing several cations. Thick SmBCO layers deposited under optimized conditions exhibit excellent cube-on-cube epitaxy. Such excellent structural epitaxy over the entire thickness results in exceptionally high Ic performance, with average Ic over 1,000 A/cm-width for the entire 22 meter long wire and maximum Ic over 1,500 A/cm-width for a short 12 cm long tape. The Ic values reported in this work are the highest values ever reported from any lengths of cuprate-based HTS wire or conductor.
PMCID: PMC3994444  PMID: 24752189
13.  Body Mass Index and Mortality in Korean Intensive Care Units: A Prospective Multicenter Cohort Study 
PLoS ONE  2014;9(4):e90039.
The level of body mass index (BMI) that is associated with the lowest mortality in critically ill patients in Asian populations is uncertain. We aimed to examine the association of BMI with hospital mortality in critically ill patients in Korea.
We conducted a prospective multicenter cohort study of 3,655 critically ill patients in 22 intensive care units (ICUs) in Korea. BMI was categorized into five groups: <18.5, 18.5 to 22.9, 23.0 to 24.9 (the reference category), 25.0 to 29.9, and ≥30.0 kg/m2.
The median BMI was 22.6 (IQR 20.3 to 25.1). The percentages of patients with BMI<18.5, 18.5 to 22.9, 23.0 to 24.9, 25.0 to 29.9, and ≥30.0 were 12, 42.3, 19.9, 22.4, and 3.3%, respectively. The Cox-proportional hazard ratios with exact partial likelihood to handle tied failures for hospital mortality comparing the BMI categories <18.5, 18.5 to 22.9, 25.0 to 29.9, and ≥30.0 with the reference category were 1.13 (0.88 to 1.44), 1.03 (0.84 to 1.26), 0.96 (0.76 to 1.22), and 0.68 (0.43 to 1.08), respectively, with a highly significant test for trend (p = 0.02).
A graded inverse association between BMI and hospital mortality with a strong significant trend was found in critically ill patients in Korea.
PMCID: PMC3991578  PMID: 24747262
14.  Predictors of high score patient-reported barriers to controlling cancer pain: a preliminary report 
Pain is one of the most common and devastating symptoms in cancer patients, and misunderstandings on the patient’s part can cause major obstacles in pain management.
We evaluated factors associated with patient’s high barrier score to managing cancer-associated pain by having 201 patients complete the Korean Barriers Questionnaire II, the Brief Pain Inventory—Korean, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, and the Korean Beck Depression Inventory. The Pain Management Index (PMI) was also assessed.
The patients were from nine oncology clinics in university hospitals and a veterans’ hospital in South Korea. The median pain score (0–10 scale) was 4, with a median percentage of pain improvement during the last 24 h of 70 %. A total of 150 patients (75 %) received strong opioids, and 177 (88 %) achieved adequate analgesia (positive PMI). Mean scores ± SD for the Barriers Questionnaire II ranged from 1.5 ± 1 to 2.8 ± 1.1, with the harmful effects subscale the highest. In the multiple regression model, depression was significantly associated with total barrier score to pain management (p < 0.0001). Pain reduction was significantly associated with the fatalism subscale.
Depression was associated with high barrier score in patients with cancer pain. Management of cancer pain should include screening for depression, and management of depression could reduce patient-reported barriers to pain management.
PMCID: PMC3881357  PMID: 23151648
Cancer; Depression; Pain management
15.  Primary Bronchial Granular Cell Tumor in an Adult Male 
We report a rare case of granular cell tumor arising in the left lower lobe (LLL) bronchus with secondary obstructive change in a 60-year-old male. The patient was found to have a nodule in the LLL on a computed tomography scan, three months prior to his presentation to the Asan Medical Center. Bronchoscopic biopsies revealed a granular cell tumor. After undergoing LLL lobectomy with bronchoplasty, the patient has not experienced any tumor recurrence.
PMCID: PMC4000886  PMID: 24782979
Granular cell tumor; Bronchial tumor
16.  Parkinsonism as late sequela of organophosphate intoxication 
Delayed morphologic and metabolic change of organophosphate intoxication is rarely reported than those of acute episode. The patient was a 52-year-old woman who had a history of acute organophosphate intoxication, which paralyzed her for one week when she was 25 years old. She recovered slowly to near normal after one year. After 22 years of the acute episode, tremor developed in 2007 followed by bradykinesia, rigidity, and postural instabilities. Brain MRI showed linear atrophy in bilateral striatal area and multiple cysts in anterior caudate nucleus. F-18 fluorodeoxyglucose positron emission tomography revealed multiple hypometabolic areas in bilateral striatum, cerebellar hemisphere, and occipital area.
PMCID: PMC4013729  PMID: 24812459
Cerebellum; F-18 positron-emission tomography; metabolism; organophsphate; parkinsonism; striatum
17.  Validity of Korean Versions of the Multiple Sclerosis Impact Scale and the Multiple Sclerosis International Quality of Life Questionnaire 
Background and Purpose
Assessment of the health-related quality of life (HRQoL) is important in clinical evaluations of multiple sclerosis (MS) patients for quantifying the impact of illness and treatment on their daily lives. Although MS-specific HRQoL instruments have been used internationally, there are no data regarding HRQoL instruments specifically designed for patients with MS in Korea. The objective of this study was to determine the reliability and validity of the Korean Multiple Sclerosis Impact Scale (MSIS-29) and the Multiple Sclerosis International Quality of Life (MusiQoL) questionnaire.
Fifty-six patients with MS were recruited from June 2009 to February 2010 at the National Cancer Center in Korea. The original English versions of the MSIS-29 scale and the MusiQoL questionnaire were translated into Korean and evaluated for their acceptability, reliability, and validity.
The patients wereaged 36.5±8.6 years (mean±SD; range, 20-56 years). Their score on the Expanded Disability Status Scale was 2.0±1.9 (mean; range, 0-7.5), and their disease duration was 5.2±4.7 years (mean±SD; range, 1-24 years). The Korean versions of the MSIS-29 and MusiQoL questionnaires showed satisfactory psychometric properties, including construct validity (item-internal consistencies of 0.59-0.95 and 0.59-0.92, respectively; item-discriminant validities of 95-100% and 93.8-100%), internal consistency (Cronbach's alpha coefficients of 0.96-0.97 and 0.77-0.96), reliability (intraclass correlation coefficients of 0.78-0.90 and 0.50-0.93), unidimensionality (Loevinger scalability coefficients of 0.70-0.78 and 0.63-0.90), and acceptability. External validity testing indicated the presence of significant correlations between similar aspects of the two questionnaires.
The Korean translated versions of the MSIS-29 and MusiQoL questionnaires demonstrated reliability and validity for measuring HRQoL in Korean patients with MS.
PMCID: PMC4017018  PMID: 24829601
multiple sclerosis; health-related quality of life; MSIS-29; MusiQoL
18.  Advances in Systems Biology Approaches for Autoimmune Diseases 
Immune Network  2014;14(2):73-80.
Because autoimmune diseases (AIDs) result from a complex combination of genetic and epigenetic factors, as well as an altered immune response to endogenous or exogenous antigens, systems biology approaches have been widely applied. The use of multi-omics approaches, including blood transcriptomics, genomics, epigenetics, proteomics, and metabolomics, not only allow for the discovery of a number of biomarkers but also will provide new directions for further translational AIDs applications. Systems biology approaches rely on high-throughput techniques with data analysis platforms that leverage the assessment of genes, proteins, metabolites, and network analysis of complex biologic or pathways implicated in specific AID conditions. To facilitate the discovery of validated and qualified biomarkers, better-coordinated multi-omics approaches and standardized translational research, in combination with the skills of biologists, clinicians, engineers, and bioinformaticians, are required.
PMCID: PMC4022781  PMID: 24851096
Autoimmune diseases; Systems biology; Multi-omics; Biomarker; Translational research; Network analysis
19.  Clinical Features and Treatment of Collecting Duct Carcinoma of the Kidney from the Korean Cancer Study Group Genitourinary and Gynecology Cancer Committee 
Collecting duct carcinoma (CDC) of the kidney is an aggressive disease with a poor prognosis, accountings for less than 1% of all renal cancers. To date, no standard therapy for CDC has been established. The aim of this study is an investigation of clinicopathologic findings of CDC and correlation of the disease status with a prognosis.
Materials and Methods
From 1996 to 2009, 35 patients with CDC were treated at eight medical centers. The diagnosis of CDC was made based on nephrectomy in 27 cases and renal biopsy in eight cases.
Median PFS and OS for all patients were 5.8 months (95% CI 3.5 to 9.2) and 54.4 months (95% CI 0 to 109.2), respectively. The OS of patients with Stages I-III was 69.9 months (95% CI 54.0 to 85.8), while that of patients with Stage IV was 8.6 months (95% CI 0 to 23.3), which showed a statistically significant difference (p=0.01). In addition, among patients with Stage IV, the OS of patients who received a palliative treatment (immunotherapy, chemotherapy, or targeted therapy) was 18.4 months, which was higher than the OS of patients without treatment of 4.5 months.
CDC is a highly aggressive form of renal cell carcinoma. Despite most of the treatments, PFS and OS were short, however, there were some long-term survivors, therefore, conduct of additional research on the predictive markers of the several clinical, pathological differences and their treatments will be necessary.
PMCID: PMC4022822  PMID: 24851105
Renal cell carcinoma; Kidney; Treatment; Prognosis
20.  Diffuse Infiltrative Primary Cardiac Lymphoma with Delayed Extracardiac Involvement 
Chonnam Medical Journal  2014;50(1):27-30.
Primary cardiac lymphoma (PCL) is an extremely rare and fatal neoplasm of the heart. Traditionally, it is defined as lymphoma involving the heart or pericardium. PCL has a poor prognosis because of the diagnostic difficulty and its location. We present the case of a 48-year-old man who presented with pericardial effusion and diffuse cardiac wall thickening. We first suspected infiltrative heart disease. However, even after performing a biopsy, we could not establish an accurate diagnosis. After 20 months, primary cardiac diffuse large B cell lymphoma (DLBCL) was diagnosed by cervical lymph node biopsy. In this case, after chemotherapy, the DLBCL lesions, including cardiac wall thickening, improved. The treatment outcome suggests that the diagnosis was diffuse infiltrative PCL with delayed extracardiac involvement.
PMCID: PMC4022795  PMID: 24855605
Heart; Lymphoma; Diagnosis
21.  CD58 polymorphisms associated with the risk of neuromyelitis optica in a Korean population 
BMC Neurology  2014;14:57.
Neuromyelitis optica (NMO) is a serious inflammatory demyelinating disease (IDD), characterized by the inflammation and demyelination of optic nerves and spinal cords, which subsequently leads to the loss of function. In a previous genome-wide association study, cluster of differentiation 58 (CD58) region was found to be susceptible for the risk of multiple sclerosis (MS) in Caucasian, and the association between CD58 variants and MS was replicated in Americans. However, no study has been conducted to explore the possible association between CD58 and NMO yet. Thus, this study aimed to investigate the association of CD58 polymorphisms with the risk of NMO in a Korean population.
Using TaqMan assay, 6 single nucleotide polymorphisms (SNPs) were genotyped in 98 NMO patients and 237 normal controls (N = 336). Logistic regression analysis was conducted to find a possible association between CD58 polymorphisms and NMO.
The analysis results showed that 6 variations (rs2300747, rs1335532, rs12044852, rs1016140, CD58_ht1, and CD58_ht3) showed significant associations (P = 0.002 ~ 0.008, Pcorr = 0.01 ~ 0.04).
The genetic variations in CD58 may be associated with the susceptibility of NMO in a Korean population. Based on previous studies, we suspect that the A allele of rs2300747 may decrease CD58 RNA expression, thus increasing NMO risk. Also, we deduced that the G allele of rs1016140 caused an increase of T cell activity, which in turn eased the access of AQP4 antibody into central nervous system (CNS) and ultimately leading to NMO development.
PMCID: PMC3998011  PMID: 24655566
CD58; NMO; SNP; Haplotype
22.  Usefulness of N-terminal pro-B-type natriuretic peptide in patients admitted to the intensive care unit: a multicenter prospective observational study 
BMC Anesthesiology  2014;14:16.
The role of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) as a prognostic factor in patients admitted to the intensive care unit (ICU) is not yet fully established. We aimed to determine whether NT-pro-BNP is predictive of ICU mortality in a multicenter cohort of critically ill patients.
A total of 1440 patients admitted to 22 ICUs (medical, 14; surgical, six; multidisciplinary, two) in 15 tertiary or university-affiliated hospitals between July 2010 and January 2011 were assessed. Patient data, including NT-pro-BNP levels and Simplified Acute Physiology Score (SAPS) 3 scores, were recorded prospectively in a web-based database.
The median age was 64 years (range, 53–73 years), and 906 (62.9%) patients were male. The median NT-pro-BNP level was 341 pg/mL (104–1,637 pg/mL), and the median SAPS 3 score was 57 (range, 47–69). The ICU mortality rate was 18.9%, and hospital mortality was 24.5%. Hospital survivors showed significantly lower NT-pro-BNP values than nonsurvivors (245 pg/mL [range, 82–1,053 pg/mL] vs. 875 pg/mL [241–5,000 pg/mL], respectively; p < 0.001). In prediction of hospital mortality, the area under the curve (AUC) for NT-pro-BNP was 0.67 (95% confidence interval [CI], 0.64–0.70) and SAPS 3 score was 0.83 (95% CI, 0.81–0.85). AUC increment by adding NT-pro-BNP is minimal and likely no different to SAPS 3 alone.
The NT-pro-BNP level was more elevated in nonsurvivors in a multicenter cohort of critically ill patients. However, there was little additional prognostic power when adding NT-pro-BNP to SAPS 3 score.
PMCID: PMC3975327  PMID: 24612820
N-terminal pro-B-type natriuretic peptide; Intensive care unit; Critical care; Prognosis
23.  Incidences of Serious Infections and Tuberculosis among Patients Receiving Anti-Tumor Necrosis Factor-α Therapy 
Yonsei Medical Journal  2014;55(2):442-448.
Anti-tumor necrosis factor-alpha (TNF-α) medications represent a major advancement in the management of chronic inflammatory diseases. However, these agents are associated with increased risks of tuberculosis (TB) and other serious infections. The aim of this study was to evaluate the incidences of such disease among tertiary hospitals in Korea.
Materials and Methods
We retrospectively studied patients who received anti-TNF-α therapy; we reviewed serious infections including TB that developed within 6 months after initiation of anti-TNF-α therapy. Data concerning patient demographics, types of anti-TNF-α agents, concomitant immunosuppressive drugs use, and infection details were collected.
A total 175 patients treated with infliximab (n=72) or adalimumab (n=103) with the following conditions were enrolled: Crohn's disease, 34 (19.4%); ulcerative colitis, 20 (11.4%); ankylosing spondylitis, 82 (46.9%); and rheumatoid arthritis, 39 (22.2%). There were 18 cases (6.0%) of serious infections. The most common site of serious infection was the intra-abdomen (n=6), followed by TB (n=3), skin and soft tissue (n=3), bone and joints (n=2), ocular neurons (n=2), lower respiratory tract (n=1), and urinary tract (n=1). Of the 175 patients, only 3 cases showed development of TB. Furthermore, of all those who developed TB, none had taken anti-TB chemoprophylaxis prior to treatment with an anti-TNF agent due to negative screening results.
Serious infections with anti-TNF-α therapy were uncommon among tertiary hospitals in Korea; TB was the second most frequent infection. Nevertheless, there were no TB reactivations after anti-TB chemoprophylaxis. Accordingly, physicians should be aware of TB in subjects undergoing anti-TNF-α therapy, especially in countries with a high prevalence of TB.
PMCID: PMC3936648  PMID: 24532516
Tumor necrosis factor-alpha; tuberculosis; infection
24.  Clinical Application of Electrogastrography in Patients with Stomach Cancer Who Undergo Distal Gastrectomy 
Journal of Gastric Cancer  2014;14(1):47-53.
Electrogastrography is a method of measuring action potentials of the stomach. The purpose of this study was to investigate early postoperative changes in the electrogastrography and determine the correlation between electrogastrography and quality of life of patients with stomach cancer who underwent distal gastrectomy.
Materials and Methods
This study analyzed 20 patients with stomach cancer who underwent electrogastrography and quality of life was measured 1, 12, and 24 weeks after the operation. Quality of life-C30 version 3.0 and quality of life-STO22, were used.
Fasting and postprandial mean dominant frequency at 1 week after the operation was 2.7 and 2.7 cycles per minute, and 2.8 and 2.7 cycles per minute at 12 weeks, 2.6 and 2.8 cycles per minute at 24 weeks. Fasting and postprandial mean dominant power at 1 week was 36.5 and 36.4 dB, 36.3 and 40.1 dB at 12 weeks and 40.9 and 42.3 dB at 24 weeks. The percentage of tachygastria was increased whereas the percentage of bradygradia was decreased during the postoperative periods (P<0.05). Global health, physical, emotional and social functioning scales were improved, but role and cognitive functioning were not changed. Pain, insomnia, diarrhea and financial difficulties were significantly improved according to the postoperative periods (P<0.05). The correlation between the STO22 and electrogastrography parameters was not significant (P>0.05).
These may suggest that electrogastrography is a simple and noninvasive method and may be applicated for evaluating motility and autonomic functions of the remnant stomach.
PMCID: PMC3996249  PMID: 24765537
Electrogastrography; Stomach neoplasms; Distal gastrectomy
25.  Immunostimulatory Effect of Fermented Red Ginseng in the Mouse Model 
In this study, Woongjin fermented red ginseng extract (WFRG) was evaluated for its potential ability to act as an adjuvant for the immune response of mice. For the in vitro study, macrophages were treated with serial concentrations (1 μg/mL, 10 μg/mL, and 100 μg/mL) of WFRG. For in vivo studies, mice were administered different concentrations (10 mg/kg/day, 100 mg/kg/day, and 200 mg/kg/day) of WFRG orally for 21 days. In vitro, the production of nitric oxide and TNF-α by RAW 264.7 cells increased in a dose-dependent manner. In vivo, WFRG enhanced the proliferation of splenocytes induced by two mitogens (i.e., concanavalin A and lipopolysaccharide [LPS]) and increased LPS-induced production of TNF-α and IL-6, but not IL-1β. In conclusion, WFRG has the potential to modulate immune function and should be further investigated as an immunostimulatory agent.
PMCID: PMC3999803  PMID: 24772404
fermented red ginseng; immune responses; saponin; cytokine; anti-cancer

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