Publications by authors named "Eun Jung Cho"

148 Publications

Recent Trends in Creatinine Assays in Korea: Long-Term Accuracy-Based Proficiency Testing Survey Data by the Korean Association of External Quality Assessment Service (2011-2019).

Ann Lab Med 2021 Jul;41(4):372-379

Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.

Background: Accurate serum creatinine (Cr) concentration measurement is essential for evaluating kidney function. In 2011, the Korean Association of External Quality Assessment Service (KEQAS) launched an accuracy-based Cr proficiency testing (ABCr PT) survey. We analyzed long-term data of the KEQAS ABCr PT survey collected between 2011 and 2019 to assess recent trends in Cr assays in Korea.

Methods: The ABCr PT survey including three commutable fresh-frozen serum samples was performed twice a year. The target Cr concentration was assigned using isotope-dilution mass spectrometry. We analyzed data obtained from the participating laboratories, calculated the yearly bias, and evaluated bias trends for the major reagents and instruments. Outliers were excluded from all analysis.

Results: The mean percentage bias based on the total data of all participating laboratories was 10.8% in the 2011-A survey and 0.2% in 2019-B survey. Bias for the major reagents and instruments differed depending on the manufacturer. Enzymatic assays generally showed desirable bias ranging from -3.9% to 3.2% at all Cr concentrations and lower interlaboratory variability than non-enzymatic assays (enzymatic vs. non-enzymatic, 3.3%-7.2% vs. 6.3%-9.1%).

Conclusions: Although the mean percentage bias of Cr assays tends to decrease over time, it is necessary to continuously strive to improve Cr assay accuracy, especially at low concentrations.
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http://dx.doi.org/10.3343/alm.2021.41.4.372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884186PMC
July 2021

Impact of water consumption on renal function in the general population: a cross-sectional analysis of KNHANES data (2008-2017).

Clin Exp Nephrol 2021 Apr 4;25(4):376-384. Epub 2021 Jan 4.

Department of Internal Medicine, Korea University Guro Hospital, Gurodong-ro 148, Guro-gu, Seoul, 08308, South Korea.

Background: The renoprotective effect of water intake remains unclear. We aimed to investigate the relationship between water intake and renal impairment in the Korean general population, focusing on individual differences in body fluid distribution and risk of chronic dehydration.

Methods: We conducted a cross-sectional analysis of the 2008-2017 Korea National Health and Nutrition Examination Survey (KNHANES). Adult participants who had body weight and serum creatinine data and had answered 24-h recall nutritional survey were included. Four water intake groups were defined by daily total water intake per body weight: lowest (< 20 mL/kg/day), low-moderate (20-29.9 mL/kg/day), high-moderate (30-49.9 mL/kg/day), and highest (≥ 50 mL/kg/day). We assessed the risk of renal impairment (estimated glomerular filtration rate ≤ 60 mL/min/1.73 m) according to water intake.

Results: In total of 50,113 participants, 3.9% had renal impairment. The risk of renal impairment gradually decreased as water intake increased. After adjustment of sodium intake, the trend of renoprotective effect was remained in low-moderate and high-moderate water intake group compared to low intake group, whereas no significant impact was observed with the highest water intake due to concurrent intake of high sodium. In subgroup analysis, the renoprotective effect of water intake was significant in the participants with elderly, male and daily sodium intake over 2 g/day.

Conclusions: High daily water intake is renoprotective. Our data may provide an important basis for determining the amount of water intake needed to prevent renal impairment, considering variations in body weight, body composition and risk of chronic dehydration.
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http://dx.doi.org/10.1007/s10157-020-01997-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966133PMC
April 2021

Serum Krebs von den Lungen-6 level predicts disease progression in interstitial lung disease.

PLoS One 2020 17;15(12):e0244114. Epub 2020 Dec 17.

Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Disease progression (DP) in interstitial lung disease (ILD) is variable and difficult to predict. In previous reports, serum Krebs von den Lungen-6 (KL-6) was suggested to be useful in diagnosing and predicting survival in ILD. The aim of our study was to investigate the usefulness of serum KL-6 as a predictor of DP in ILD. Clinical data of 199 patients with ILD (idiopathic pulmonary fibrosis: 22.8%) were prospectively collected and serum KL-6 levels were measured. DP was defined as a relative decline in forced vital capacity (FVC) ≥ 10%, acute exacerbation, or death during follow-up. The median follow-up period was 11.1 months. The mean age of the subjects was 62.2 years, and 59.8% were male. DP occurred in 21.6% of patients. The progressed group showed lower FVC, lower diffusing capacity for carbon monoxide, lower the minimum oxygen saturation during the 6-minute walk test, higher fibrosis scores on high-resolution computed tomography, and higher KL-6 levels (826.3 vs. 629.0 U/mL; p < 0.001) than those of the non-progressed group. In receiver operating characteristic curve analysis, serum KL-6 levels were a significant predictor of DP in ILD (area under the curve = 0.629, p = 0.009, and the optimal cut-off level was 811 U/mL). In multivariable Cox analysis, high serum KL-6 levels (≥ 800 U/mL) were only independently associated with DP in ILD (HR 2.689, 95% CI 1.445-5.004, P = 0.002). Serum KL-6 levels might be useful to predict DP in patients with ILD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244114PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746162PMC
March 2021

Histone acylation marks respond to metabolic perturbations and enable cellular adaptation.

Exp Mol Med 2020 12 11;52(12):2005-2019. Epub 2020 Dec 11.

School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, 440-746, Republic of Korea.

Acetylation is the most studied histone acyl modification and has been recognized as a fundamental player in metabolic gene regulation, whereas other short-chain acyl modifications have only been recently identified, and little is known about their dynamics or molecular functions at the intersection of metabolism and epigenetic gene regulation. In this study, we aimed to understand the link between nonacetyl histone acyl modification, metabolic transcriptional regulation, and cellular adaptation. Using antibodies specific for butyrylated, propionylated, and crotonylated H3K23, we analyzed dynamic changes of H3K23 acylation upon various metabolic challenges. Here, we show that H3K23 modifications were highly responsive and reversibly regulated by nutrient availability. These modifications were commonly downregulated by the depletion of glucose and recovered based on glucose or fatty acid availability. Depletion of metabolic enzymes, namely, ATP citrate lyase, carnitine acetyltransferase, and acetyl-CoA synthetase, which are involved in Ac-CoA synthesis, resulted in global loss of H3K23 butyrylation, crotonylation, propionylation, and acetylation, with a profound impact on gene expression and cellular metabolic states. Our data indicate that Ac-CoA/CoA and central metabolic inputs are important for the maintenance of histone acylation. Additionally, genome-wide analysis revealed that acyl modifications are associated with gene activation. Our study shows that histone acylation acts as an immediate and reversible metabolic sensor enabling cellular adaptation to metabolic stress by reprogramming gene expression.
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http://dx.doi.org/10.1038/s12276-020-00539-xDOI Listing
December 2020

Relationship Between Rotavirus P[6] Infection in Korean Neonates and Histo-Blood Group Antigen: a Single-Center Study.

Ann Lab Med 2021 Mar;41(2):181-189

Department of Laboratory Medicine, Hallym University Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Hwaseong, Korea.

Background: Rotaviruses are a major cause of pediatric gastroenteritis. The rotavirus P[6] genotype is the most prevalent genotype isolated from Korean neonates but has rarely been reported in other countries. Histo-blood group antigen (HBGA) is known to play an important role in rotavirus infection. We investigated the relationship between rotavirus genotype and HBGA-Lewis blood type in Korean children and explored the reasons for the predominance of rotavirus P[6] strain in Korean neonates.

Methods: Blood and stool samples were collected from 16 rotavirus-infected patients. Rotavirus G (VP7) and P (VP4) genotyping was performed using reverse transcription-PCR and sequencing. Lewis antigen phenotypes (Le/Le) were tested, and HBGA-Lewis genotype was determined by sequencing the secretor () and Lewis () genes. Deduced amino acid sequences and three-dimensional structures of the VP8* portion of the rotavirus VP4 protein were analyzed.

Results: All P[6] rotaviruses were isolated from neonates under one month of age, who were negative or weakly positive for the Le antigen. However, 10 of the 11 non-P[6] rotaviruses were isolated from older children who were Le antigen-positive. The VP8* amino acid sequences differed among P[6], P[4], and P[8] genotypes. Korean P[6] strains showed a unique VP8* sequence with amino acid substitutions, including Y169>L169, which differed from the sequences of P[6] strains from other countries.

Conclusions: The predominance of the rotavirus P[6] genotype in Korean neonates may be related to the interaction between HBGA-Lewis antigen and the VP8* portion of the VP4 protein, and this information will be helpful in future neonatal vaccine development.
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http://dx.doi.org/10.3343/alm.2021.41.2.181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591292PMC
March 2021

Application and optimization of reference change values for Delta Checks in clinical laboratory.

J Clin Lab Anal 2020 Dec 30;34(12):e23550. Epub 2020 Aug 30.

Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: Delta check is a patient-based QC tool for detecting errors by comparing current and previous test results of patient. Reference change value (RCV) is adopted in guidelines as method for delta check, but the performance is not verified. We applied RCV-based delta check method to patients' data and modified for application.

Materials And Methods: Reference change value were calculated using results of internal QC materials and biological variation data. Test results of 17 analytes in inpatients, outpatients, and health examination recipients were collected. The detection rates of currently used delta check method and those of RCV-based method were compared, and the methods were modified.

Results: Reference change value-based method had higher detection rates compared to conventional method. Applied modifications reduced detection rates. Removing the pairs of results within reference interval reduced detection rates (0.42% ~ 10.92%). When RCV was divided by time interval, the detection rates were similar to prior rates in outpatients (0.19% ~ 1.34%). Using RCV multiplied by twice the upper limit of reference value as cutoff reduced the detection rate (0.07% ~ 1.58%).

Conclusions: Reference change value is a robust criterion for delta check and included in clinical laboratory practice guideline. However, RCV-based method generates high detection rates which increase workload. It needs modification for use in clinical laboratories.
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http://dx.doi.org/10.1002/jcla.23550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755783PMC
December 2020

An ensemble approach of urine sediment image analysis and NMP22 test for detection of bladder cancer cells.

J Clin Lab Anal 2020 Aug 10;34(8):e23345. Epub 2020 Jul 10.

Department of Laboratory Medicine, Uijeongbu St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.

Background: Bladder cancer is the eighth most common cancer and the second most common urological cancer in Korean males. Current diagnostic tools for bladder cancer include cystoscopy (an upper tract study), urine cytology, and nuclear matrix protein 22 (NMP22) test. In this study, we evaluated the detection rate of atypical/malignant urothelial cells in urinary sediment images when flagged for positive NMP22 test.

Methods: NMP22 was measured by NMP22 BladderChek Test (Abbott Laboratories) and urine chemical and sediment analysis were performed by fully automated cobas 6500 urine analyzer (Roche Diagnostics). Specimens that met the manual microscopic examination (MME) criteria were then subjected to an on-screen review of images. We subsequently reviewed sediment images and examined under the microscopy for the flagged cases.

Results: Of the 1217 patients, 345 (28.3%) had positive NMP22 results, whereas 872 (71.7%) had negative results. Out of the positive results, 154 (12.7%) were positive and 191 (15.7%) weakly positive for NMP22. Screened review of flagged specimens (ie, positive NMP22 result) with sediment imaging analysis revealed that suspicious urothelial carcinoma cells were detected in only two cases (0.8%). In the NMP22 negative flagged cases, the suspicious neoplastic cells were not found.

Conclusions: Our findings suggest that the NMP22 test should be added to the flagging criteria for MME to improve diagnostic accuracy. The combination of urine sediment imaging analysis and NMP22 test can significantly assist technicians in the review of specimens.
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http://dx.doi.org/10.1002/jcla.23345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439416PMC
August 2020

Clinical Predictors Implicated in the Incidence of Acute Pyelonephritis during the Antepartum Period: A Population-Based Cohort Study.

Kidney Blood Press Res 2020 20;45(2):297-306. Epub 2019 Dec 20.

School of Industrial Management Engineering, Korea University, Seoul, Republic of Korea,

Introduction: Acute pyelonephritis (APN) is a common infection during pregnancy that increases the risk of unfavorable maternal and fetal outcomes. However, it has not been clearly elucidated which demographic and clinical characteristics are associated with the incidence of APN during pregnancy.

Objective: This population-based cohort study aimed to determine the risk factors for APN during pregnancy.

Methods: Using the database of the Health Insurance Review and Assessment Service of South Korea, we enrolled Korean women who delivered infants between 2010 and 2014 in Korea and had complete health examination records within 1 year of pregnancy. We performed multivariate logistic regression analysis to evaluate the risk factors for APN during pregnancy.

Results: Of 370,248 women, 2,526 (0.7% of the total participants) were treated for APN while in hospitalization during pregnancy. Younger age, history of previous APN within 1 year of pregnancy, and abnormal results of health examination before pregnancy, such as high fasting glucose level (>100 mg/dL) and proteinuria, were associated with an increased risk of APN during pregnancy.

Conclusion: Certain maternal demographic and clinical characteristics were associated with the incidence of APN during pregnancy, and these should be monitored closely during antenatal care.
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http://dx.doi.org/10.1159/000503788DOI Listing
November 2020

Explantation of Adjustable Gastric Bands: An Observation Study of 10 Years of Experience at a Tertiary Center.

Yonsei Med J 2019 Aug;60(8):782-790

Department of Surgery, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea.

Purpose: Although laparoscopic adjustable gastric bands are considered a standard treatment for severe obesity, their use remains controversial. We evaluated rates of band explantation and the incidences of complications leading to and following band explantation.

Materials And Methods: This retrospective review was performed on patients that underwent adjustable gastric band explantation. For each of the three groups of patients that underwent explantation, we compared demographic and anthropometric data, band duration in situ, operative approach, and morbidities.

Results: Between January 2009 and October 2018, a total of 267 patients underwent primary laparoscopic adjustable gastric band surgery. Of these 267 patients, 99 (37.1%) underwent band explantation. Numbers (%) of patients in the slippage (SL), band erosion (BE), and intolerance (IT) groups were 13 (13.1%), 39 (39.4), and 47 (47.5%), respectively. Mean %EBMIL values at explantation in these groups were 74.6±45.5, 79.7±40.3, and 36.1±46.0, respectively (<0.001), and mean times for maintaining bands in situ were 45.1±28.0, 39.4±24.3, and 51.2±22.7 months, respectively. Isolated band removal was performed for slippage (SLi, n=12), band erosion (BEi, n=39), and intolerance (ITi, n=31). The numbers (%) of patients in the SLi, BEi, and ITi groups that experienced a surgical complication (Clavien-Dindo class ≥1) were 0 (0.0%), 24 (61.5%), and 3 (9.7%), respectively (<0.001). In the BEi group, four patients (4/39, 10.3%) underwent reoperation after AGB removal.

Conclusion: During our 10 years of experience, 37.1% of adjustable gastric band had to be removed. Intra-abdominal abscess and intragastric bleeding were rare but serious complications after explantation. Potential candidates for adjustable gastric band should be informed of the high long-term risk of band explantation and its associated morbidities.
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http://dx.doi.org/10.3349/ymj.2019.60.8.782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660444PMC
August 2019

Small Red Blood Cell Fraction on the UF-1000i Urine Analyzer as a Screening Tool to Detect Dysmorphic Red Blood Cells for Diagnosing Glomerulonephritis.

Ann Lab Med 2019 05;39(3):271-277

Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Background: Dysmorphic red blood cells (dRBCs) are first-line biomarkers for detecting glomerulonephritis (GN) in patients with hematuria. The UF-1000i system (Sysmex, Kobe, Japan), based on flow cytometry, provides small red blood cell (RBC) values (UF-1000i [UF]-%sRBCs). We evaluated the clinical application of UF-%sRBCs for detecting %dRBCs and GN.

Methods: Urine samples of 103 patients (47 with GN; 56 without GN [NGN]) were analyzed using UF-1000i urinalysis, phase-contrast microscopy (PCM), and urine chemistry. Serum creatinine (mg/dL), serum albumin (g/dL), serum protein (mg/dL), urine protein (mg/dL), and urea nitrogen (mg/dL) levels were measured using an automated chemical analyzer. To determine the cut-off level of predicting GN, ROC curve was analyzed.

Results: UF-%sRBCs, %dRBCs, urine protein, serum creatinine, and estimated-glomerular filtration rate differed between the GN and NGN groups, with the greatest differences detected for UF-%sRBCs and %dRBCs (<0.0001). In ROC curve analysis, urine protein had the highest area under the curve (0.828), followed by %dRBCs (0.771) and UF-%sRBCs (0.745). To screen for GN, the best cut-off values of UF-%sRBCs and %dRBCs were >40.5% and >6.7%, respectively. %dRBCs (=0.0001) and UF-%sRBCs (=0.0006) differed between the GN and NGN groups in patients with isolated hematuria but without proteinuria.

Conclusions: UF-%sRBCs had similar diagnostic power to %dRBCs determined by PCM for identifying patients with GN. UF-%sRBCs may be more useful for diagnosing GN in patients with isolated hematuria. Predicting %dRBCs using UF-1000i will provide information on possible GN in patients presenting with asymptomatic hematuria.
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http://dx.doi.org/10.3343/alm.2019.39.3.271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340839PMC
May 2019

Analytical and Clinical Performance of the Nanopia Krebs von den Lungen 6 Assay in Korean Patients With Interstitial Lung Diseases.

Ann Lab Med 2019 05;39(3):245-251

Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: Krebs von den Lungen 6 (KL-6) is a sensitive marker for diagnosing, monitoring, and predicting the prognoses of interstitial lung diseases (ILDs). This study aimed to evaluate the performance of the Nanopia KL-6 assay (Sekisui Medical, Tokyo, Japan) and to test the relationship between KL-6 concentrations and clinical results.

Methods: In total, 230 patients diagnosed as having ILDs were enrolled. All underwent high-resolution computed tomography (HRCT) followed by the pulmonary function test (PFT). We also enrolled 116 disease controls and 200 healthy controls. Evaluation of the Nanopia KL-6 assay involved determination of precision, linearity, and limit of quantification (LOQ). Results from the Nanopia KL-6 assay were compared with those from ELISA and correlated with the HRCT and PFT results.

Results: The within-laboratory precisions were <2% of CV, and linearity was acceptable between 52.2 and 4,966.5 U/mL. The LOQ was 45.2 U/mL. Nanopia and ELISA results were strongly correlated (=0.979). The average concentration of KL-6 was greater in ILD patients (711.5 U/mL) than in the disease (168.4 U/mL) and healthy (209.4 U/mL) controls. Serum KL-6 concentrations were strongly and moderately correlated with the extent of lung involvement and presence of typical HRCT abnormalities, respectively, and moderately correlated with PFT parameters.

Conclusions: The overall analytical and clinical performance of the Nanopia KL-6 assay was acceptable. Our study is the first to compare assay platforms and show correlations between KL-6 concentrations and HRCT or PFT results in Korean ILD patients.
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http://dx.doi.org/10.3343/alm.2019.39.3.245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340849PMC
May 2019

Revisional surgery after removal of eroded adjustable gastric bands.

Asian J Surg 2019 Jun 24;42(6):688-695. Epub 2018 Nov 24.

Department of Surgery, Gachon University Gil Hospital, Gachon University of College Medicine, Incheon, South Korea. Electronic address:

Background: The aim of the study is to present surgical techniques and treatment outcomes for re-banding and sleeve gastrectomy as a revisional surgery after removing eroded adjustable gastric bands.

Methods: A retrospective analysis was performed to study laparoscopic re-banding or sleeve gastrectomy as revisional surgery for band erosion. Main outcome measures were success of therapeutic strategies, morbidity, body mass index, and percentage total excess weight loss before and after revision.

Results: From March 2013 to June 2017, a total of 11 patients underwent the revisional surgery. Six patients underwent sleeve gastrectomy at median 15.7 months (13.2-73.3 months) after band removal, and 5 patients gastric re-banding at median 5.4 months (3.1-43.8 months). One of the six patients that underwent sleeve gastrectomy was diagnosed to have a minor leak. No other critical postoperative complication was observed in each group. Median BMI at revision in the sleeve gastrectomy group was 32.7 kg/m (31.2-40.8 kg/m). Median follow-up after revision was 33.8 months (15.5-63.7 months), and at last follow-up, median BMI was 26.4 kg/m (23.6-34.6 kg/m), and median %TWL was 17.6% (9.5-31.5%). In the rebanding group, median BMI at revision was 30.7 kg/m (27.0-41.4 kg/m). Median follow-up after revision was 25.5 months (13.5-45.4 months), and at last follow-up, median BMI was 23.5 kg/m (22.0-30.1 kg/m) and median %TWL was 23.9% (9.1-29.0%).

Conclusion: Given the surgical techniques adopted, both re-banding and sleeve gastrectomy were found to be safe and effective revisional surgery after removal of eroded gastric band.
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http://dx.doi.org/10.1016/j.asjsur.2018.11.003DOI Listing
June 2019

Association between Body Mass Index and Gastric Cancer Risk According to Effect Modification by Helicobacter pylori Infection.

Cancer Res Treat 2019 Jul 21;51(3):1107-1116. Epub 2018 Nov 21.

Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.

Purpose: Few studies investigated roles of body mass index (BMI) on gastric cancer (GC) risk according to Helicobacter pylori infection status. This study was conducted to evaluate associations between BMI and GC risk with consideration of H. pylori infection information.

Materials And Methods: We performed a case-cohort study (n=2,458) that consists of a subcohort, (n=2,193 including 67 GC incident cases) randomly selected from the Korean Multicenter Cancer Cohort (KMCC) and 265 incident GC cases outside of the subcohort. H. pylori infection was assessed using an immunoblot assay. GC risk according to BMI was evaluated by calculating hazard ratios (HRs) and their 95% confidence intervals (95% CIs) using weighted Cox hazard regression model.

Results: Increased GC risk in lower BMI group (< 23 kg/m2) with marginal significance, (HR, 1.32; 95% CI, 0.98 to 1.77) compared to the reference group (BMI of 23-24.9 kg/m2) was observed. In the H. pylori non-infection, both lower (< 23 kg/m2) and higher BMI (≥ 25 kg/m2) showed non-significantly increased GC risk (HR, 10.82; 95% CI, 1.25 to 93.60 and HR, 11.33; 95% CI, 1.13 to 113.66, respectively). However, these U-shaped associations between BMI and GC risk were not observed in the group who had ever been infected by H. pylori.

Conclusion: This study suggests the U-shaped associations between BMI and GC risk, especially in subjects who had never been infected by H. pylori.
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http://dx.doi.org/10.4143/crt.2018.182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639215PMC
July 2019

Red Blood Cell Alloimmunization in Korean Patients With Myelodysplastic Syndrome and Liver Cirrhosis.

Ann Lab Med 2019 Mar;39(2):218-222

Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Red blood cell (RBC) alloimmunization varies across human populations and ethnic groups. We evaluated the characteristics of RBC alloimmunization and compared the risk of alloimmunization in Korean patients with myelodysplastic syndrome (MDS) and liver cirrhosis (LC), two representative diseases in which chronic transfusion is required. In total, 115 MDS patients and 202 LC patients transfused with RBCs between 2013 and 2015 were retrospectively included. Twenty patients (6.3%) were newly alloimmunized (five MDS patients, 4.3%; 15 LC patients, 7.4%). The median number of RBC units transfused in alloimmunized patients was nine (interquartile range, 4-15 units). As the number of transfused RBC units increased, the cumulative risk of alloimmunization was higher in LC than in MDS patients (=0.001). The most common alloantibody detected in patients was anti-E (45%), followed by anti-c (17%), anti-e (10%), anti-C (7%), anti-Fy (7%), and anti-Jk (7%). The present data indicate the need for matching of extended RBC antigens (Rh, Duffy, and Kidd systems) for chronically transfused patients with MDS and LC in Korea.
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http://dx.doi.org/10.3343/alm.2019.39.2.218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240531PMC
March 2019

Long non-coding RNA ChRO1 facilitates ATRX/DAXX-dependent H3.3 deposition for transcription-associated heterochromatin reorganization.

Nucleic Acids Res 2018 12;46(22):11759-11775

School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 16419, Republic of Korea.

Constitutive heterochromatin undergoes a dynamic clustering and spatial reorganization during myogenic differentiation. However the detailed mechanisms and its role in cell differentiation remain largely elusive. Here, we report the identification of a muscle-specific long non-coding RNA, ChRO1, involved in constitutive heterochromatin reorganization. ChRO1 is induced during terminal differentiation of myoblasts, and is specifically localized to the chromocenters in myotubes. ChRO1 is required for efficient cell differentiation, with global impacts on gene expression. It influences DNA methylation and chromatin compaction at peri/centromeric regions. Inhibition of ChRO1 leads to defects in the spatial fusion of chromocenters, and mislocalization of H4K20 trimethylation, Suv420H2, HP1, MeCP2 and cohesin. In particular, ChRO1 specifically associates with ATRX/DAXX/H3.3 complex at chromocenters to promote H3.3 incorporation and transcriptional induction of satellite repeats, which is essential for chromocenter clustering. Thus, our results unveil a mechanism involving a lncRNA that plays a role in large-scale heterochromatin reorganization and cell differentiation.
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http://dx.doi.org/10.1093/nar/gky923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6294499PMC
December 2018

Accuracy evaluation of Roche and Siemens tacrolimus and cyclosporine assays in comparison with liquid chromatography-tandem mass spectrometry.

Scand J Clin Lab Invest 2018 Oct 1;78(6):431-438. Epub 2018 Oct 1.

b Department of Laboratory Medicine , University of Ulsan College of Medicine and Asan Medical Center , Seoul , Korea.

Therapeutic drug monitoring of tacrolimus and cyclosporine is crucial to the success of organ transplantation. We evaluated the analytical performances and accuracy of two commercially available tacrolimus and cyclosporine assays (Roche ISD and Siemens) in comparison with liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 342 leftover whole blood samples requested for tacrolimus or cyclosporine assays were stored at -20 °C until analysis. Repeatability and between-run imprecision were evaluated using quality control materials provided by the manufacturer. Ring trial samples were used for the assessment of recovery. The results of the Roche ISD assay were compared with those of Siemens tacrolimus and cyclosporine assays and LC-MS/MS. Repeatability and between-run imprecision were 2.1-5.3% and 2.6-7.5%, respectively. Recovery of Roche ISD was 85.7 - 90.6% for cyclosporine and 96.2-98.5% for tacrolimus. The two immunoassays showed slight positive biases relative to LC-MS/MS for cyclosporine. For tacrolimus, Roche ISD produced virtually identical results to those of LC-MS/MS, whereas Siemens showed proportional differences, especially in patients receiving kidney transplantation. The analytical performances of Roche ISD were generally acceptable, especially regarding accuracy. Clinical laboratory staff should be aware of the strengths and weaknesses of commercial immunoassays in order to ensure accurate results.
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http://dx.doi.org/10.1080/00365513.2018.1472801DOI Listing
October 2018

Cyclin-dependent kinase 1 activity coordinates the chromatin associated state of Oct4 during cell cycle in embryonic stem cells.

Nucleic Acids Res 2018 07;46(13):6544-6560

National Creative Research Center for Epigenome Reprogramming Network, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.

Cyclin-dependent kinase 1 (Cdk1) is indispensable for embryonic stem cell (ESC) maintenance and embryo development. Even though some reports have described a connection between Cdk1 and Oct4, there is no evidence that Cdk1 activity is directly linked to the ESC pluripotency transcription program. We recently reported that Aurkb/PP1-mediated Oct4 resetting is important to cell cycle maintenance and pluripotency in mouse ESCs (mESCs). In this study, we show that Cdk1 is an upstream regulator of the Oct4 phosphorylation state during cell cycle progression, and it coordinates the chromatin associated state of Oct4 for pluripotency-related gene expression within the cell cycle. Upon entry into mitosis, Aurkb in the chromosome passenger complex becomes fully activated and PP1 activity is inhibited downstream of Cdk1 activation, leading to sustaining Oct4(S229) phosphorylation and dissociation of Oct4 from chromatin during the mitotic phase. Cdk1 inhibition at the mitotic phase abnormally results in Oct4 dephosphorylation, chromosome decondensation and chromatin association of Oct4, even in replicated chromosome. Our study results suggest a molecular mechanism by which Cdk1 directly links the cell cycle to the pluripotency transcription program in mESCs.
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http://dx.doi.org/10.1093/nar/gky371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6061841PMC
July 2018

Abundance of C-terminal binding protein isoform is a prerequisite for exit from pluripotency in mouse embryonic stem cells.

FASEB J 2018 Jun 12:fj201700837RRRR. Epub 2018 Jun 12.

Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science, Seoul National University, Seoul, South Korea.

Unlike lower organisms, mammals have 2 C-terminal binding protein (Ctbp) isoforms, Ctbp1 and Ctbp2. Ctbp2 is revealed as a key factor involved in determining cell fate decisions by regulating the epigenetic state in active embryonic stem cell (ESC) genes. However, the molecular mechanism underlying how Ctbp1 and Ctbp2 have different roles remains elusive. Here we demonstrate that Ctbp isoform abundance is important for mouse embryonic ESCs (mESCs) to exit from pluripotency. Temporal expression patterns of Ctbp isoforms were quite different; Ctbp2 is more highly expressed in mESCs and decreases during differentiation, while Ctbp1 is constantly expressed at a lower level. Ctbp2 knockdown, but not Ctbp1 knockdown, in mESCs resulted in impaired exit from pluripotency. Interestingly, Ctbp1 and Ctbp2 overexpression in Ctbp2-knockdown mESCs leads to exiting from pluripotency in a manner similar to that of wild-type mESCs. Quantification of Ctbp1 and Ctbp2 revealed that differentiation ability correlates with abundance of Ctbp isoform in undifferentiated mESCs, suggesting that a sufficient amount of Ctbp isoform is a prerequisite for exiting from pluripotency. The results support the contention that 2 redundant Ctbp isoforms regulate elaborate differentiation via temporally distinctive regulatory patterns in mESCs.-Suh, M. Y., Kim, T. W., Lee, H.-T., Shin, J., Kim, J.-H., Jang, H., Kim, H. J., Kim, S.-T., Cho, E.-J., Youn, H.-D. Abundance of C-terminal binding protein isoform is a prerequisite for exit from pluripotency in mouse embryonic stem cells.
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http://dx.doi.org/10.1096/fj.201700837RRRRDOI Listing
June 2018

Zinc finger proteins orchestrate active gene silencing during embryonic stem cell differentiation.

Nucleic Acids Res 2018 07;46(13):6592-6607

National Creative Research Center for Epigenome Reprogramming Network, Department of Biomedical Sciences, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.

Transcription factors and chromatin remodeling proteins control the transcriptional variability for ESC lineage commitment. During ESC differentiation, chromatin modifiers are recruited to the regulatory regions by transcription factors, thereby activating the lineage-specific genes or silencing the transcription of active ESC genes. However, the underlying mechanisms that link transcription factors to exit from pluripotency are yet to be identified. In this study, we show that the Ctbp2-interacting zinc finger proteins, Zfp217 and Zfp516, function as linkers for the chromatin regulators during ESC differentiation. CRISPR-Cas9-mediated knock-outs of both Zfp217 and Zfp516 in ESCs prevent the exit from pluripotency. Both zinc finger proteins regulate the Ctbp2-mediated recruitment of the NuRD complex and polycomb repressive complex 2 (PRC2) to active ESC genes, subsequently switching the H3K27ac to H3K27me3 during ESC differentiation for active gene silencing. We therefore suggest that some zinc finger proteins orchestrate to control the concise epigenetic states on active ESC genes during differentiation, resulting in natural lineage commitment.
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http://dx.doi.org/10.1093/nar/gky454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6061687PMC
July 2018

The efficient workflow to decrease the manual microscopic examination of urine sediment using on-screen review of images.

Clin Biochem 2018 Jun 12;56:70-74. Epub 2018 Apr 12.

Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address:

Background: The manual microscopic examination (MME) of urine sediment is labor-intensive, time-consuming, and imprecise. Therefore, automated urinalysis systems based on flow cytometry or digital imaging techniques could replace MME. The purpose of this study was to evaluate the rate of MME using two automated urine sediment analyzers, alone and in combination.

Methods: This study was conducted using the freshly collected urine specimens of 1055 in-patients and 1119 out-patients. All samples were analyzed using UF-1000i (Sysmex Corporation) and Cobas 6500 instrument (Roche Diagnostics International). The rate of MME was evaluated using two analyzers, both individually and in combination.

Results: Using the UF-1000i alone, 34.2% and 16.8%, respectively, of in- and out-patient samples were analyzed by MME, compared to 15.6% and 3.7%, respectively, using the Cobas 6500. In combined assay using the UF-1000i followed by the Cobas 6500, 27.9% and 11.3% in-patient samples required on-screen review and MME, respectively. And the respective rates were 10.3% and 2.7% of out-patient. Samples using the Cobas 6500 followed by the UF-1000i, 42.3% and 11.3% in-patient needed on-screen review and MME, respectively. And the respective rates were 18.9% and 2.7% of out-patient samples.

Conclusions: Use of the Cobas 6500 compared to the UF-1000i resulted in decreases in the rate of MME from 34.2% to 15.6% for in-patient samples, and from 16.8% to 3.7% for out-patient samples. Use of the Cobas 6500 reduced the rate of MME, and compared to use of only the Cobas 6500, the combined use resulted in a reduction in the rate of on-screen review.
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http://dx.doi.org/10.1016/j.clinbiochem.2018.04.008DOI Listing
June 2018

Performance of the Dimension TAC assay and comparison of multiple platforms for the measurement of tacrolimus.

J Clin Lab Anal 2018 May 17;32(4):e22357. Epub 2017 Nov 17.

Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background: Therapeutic monitoring of tacrolimus is essential for reducing organ rejection and adverse effects. The measurement of tacrolimus in whole blood is taken by many automated platforms. We evaluated the analytical performance of the Dimension TAC assay, which is an upgraded reagent from the previous Dimension TACR assay.

Methods: The evaluations involved determination of precision, linearity, detection capability, and reagent lot-to-lot variability between three lot numbers. Correlation studies were conducted using the Dimension TACR assay, Architect, Elecsys assay, and MassTrak LC-MS/MS.

Results: The total coefficient of variation was below 10%. Acceptable linearity was observed in their respective reportable ranges. The limit of blank, limit of detection, and limit of quantification were 0.29, 0.47, and 0.81 ng/mL, respectively. Correlation analysis indicated that the Dimension TAC assay results were comparable to that of the Dimension TACR assay, Architect, and Elecsys results in liver and heart transplant patients. In kidney transplant patients, the Dimension TAC assay showed the poor correlation with Architect and Elecsys. The results from these assays were slightly higher than that of MassTrak. We found little lot-to-lot reagent variation among the reagents evaluated.

Conclusion: The overall analytical performance of the Dimension TAC assay is acceptable for therapeutic monitoring in clinical practice. Our study that compared different platforms may provide some useful information regarding which test method to use.
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http://dx.doi.org/10.1002/jcla.22357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817031PMC
May 2018

Ctbp2-mediated β-catenin regulation is required for exit from pluripotency.

Exp Mol Med 2017 10 13;49(10):e385. Epub 2017 Oct 13.

National Creative Research Center for Epigenome Reprogramming Network, Department of Biomedical Sciences, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.

The canonical Wnt pathway is critical for embryonic stem cell (ESC) pluripotency and aberrant control of β-catenin leads to failure of exit from pluripotency and lineage commitments. Hence, maintaining the appropriate level of β-catenin is important for the decision to commit to the appropriate lineage. However, how β-catenin links to core transcription factors in ESCs remains elusive. C-terminal-binding protein (CtBP) in Drosophila is essential for Wnt-mediated target gene expression. In addition, Ctbp acts as an antagonist of β-catenin/TCF activation in mammals. Recently, Ctbp2, a core Oct4-binding protein in ESCs, has been reported to play a key role in ESC pluripotency. However, the significance of the connection between Ctbp2 and β-catenin with regard to ESC pluripotency remains elusive. Here, we demonstrate that C-terminal-binding protein 2 (Ctbp2) associates with major components of the β-catenin destruction complex and limits the accessibility of β-catenin to core transcription factors in undifferentiated ESCs. Ctbp2 knockdown leads to stabilization of β-catenin, which then interacts with core pluripotency-maintaining factors that are occupied by Ctbp2, leading to incomplete exit from pluripotency. These findings suggest a suppressive function for Ctbp2 in reducing the protein level of β-catenin, along with priming its position on core pluripotency genes to hinder β-catenin deposition, which is central to commitment to the appropriate lineage.
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http://dx.doi.org/10.1038/emm.2017.147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668466PMC
October 2017

Direct interaction of menin leads to ubiquitin-proteasomal degradation of β-catenin.

Biochem Biophys Res Commun 2017 10 4;492(1):128-134. Epub 2017 Aug 4.

School of Pharmacy, Sungkyunkwan University, Suwon 440-746, South Korea. Electronic address:

Menin, encoded by the multiple endocrine neoplasia type 1 (MEN1) gene, is a tumor suppressor and transcription regulator. Menin interacts with various proteins as a scaffold protein and is proposed to play important roles in multiple physiological and pathological processes by controlling gene expression, proliferation, and apoptosis. The mechanisms underlying menin's suppression of tumorigenesis are largely elusive. In this study, we showed that menin was essential for the regulation of canonical Wnt/β-catenin signaling in cultured cells. The C-terminal domain of menin was able to directly interact with and promote ubiquitin-mediated degradation of β-catenin. We further revealed that overexpression of menin down-regulated the transcriptional activity of β-catenin and target gene expression. Moreover, menin efficiently inhibited β-catenin protein levels, transcriptional activity, and proliferation of human renal carcinoma cells with an activated β-catenin pathway. Taken together, our results provide novel molecular insights into the tumor suppressor activity of menin, which is partly mediated by proteasomal degradation of β-catenin and inhibition of Wnt/β-catenin signaling.
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http://dx.doi.org/10.1016/j.bbrc.2017.08.011DOI Listing
October 2017

Accuracy Assessment of Five Equations Used for Estimating the Glomerular Filtration Rate in Korean Adults.

Ann Lab Med 2017 Sep;37(5):371-380

Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea.

Background: We aimed to assess the performance of the five creatinine-based equations commonly used for estimates of the glomerular filtration rate (eGFR), namely, the creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPIcr), Asian CKD-EPI, revised Lund-Malmö (revised LM), full age spectrum (FAS), and Korean FAS equations, in the Korean population.

Methods: A total of 1,312 patients, aged 20 yr and above who underwent ⁵¹Cr-EDTA GFR measurements (mGFR), were enrolled. The bias (eGFR-mGFR) and precision (root mean square error [RMSE]) were calculated. The accuracy (P30) of four eGFR equations was compared to that of the CKD-EPIcr equation. P30 was defined as the percentage of patients whose eGFR was within±30% of the mGFR.

Results: The mean bias (mL·min⁻¹·1.73 m⁻²) of the five eGFR equation was as follows: CKD-EPIcr, -0.6; Asian CKD-EPI, 2.7; revised LM, -6.5; FAS, -2.5; and Korean FAS, -0.2. The bias of the Asian CKD-EPI, revised LM, and FAS equations showed a significant difference from zero (P<0.001). The RMSE values were as follows: CKD-EPIcr, 15.6; Asian CKD-EPI, 15.6; revised LM, 17.9; FAS, 16.3; and Korean FAS, 15.8. There were no significant differences in the P30 except for the Asian CKD-EPI equation: CKD-EPIcr, 76.6%; Asian CKD-EPI, 74.7%; revised LM, 75.8%; FAS, 76.0%; and Korean FAS, 75.8%.

Conclusions: The CKD-EPIcr and Korean FAS equations showed equivalent analytical and clinical performances in the Korean adult population.
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http://dx.doi.org/10.3343/alm.2017.37.5.371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5500735PMC
September 2017

Efficient reporting of the estimated glomerular filtration rate without height in pediatric patients with cancer.

Clin Chem Lab Med 2017 Oct;55(12):1891-1897

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Background: The updated bedside Schwartz equation requires constant, serum creatinine concentration and height measurements to calculate the estimated glomerular filtration rate (eGFR) in pediatric patients. Unlike the serum creatinine levels, obtaining height information from the laboratory information system (LIS) is not always possible in a clinical laboratory. Recently, the height-independent eGFR equation, the full age spectrum (FAS) equation, has been introduced. We evaluated the performance of height-independent eGFR equation in Korean children with cancer.

Methods: A total of 250 children who underwent chromium-51-ethylenediamine tetra acetic-acid (51Cr-EDTA)-based glomerular filtration rate (GFR) measurements were enrolled. The 51Cr-EDTA GFR was used as the reference GFR. The bias (eGFR - measured GFR), precision (root mean square error [RMSE]) and accuracy (P30) of the FAS equations were compared to those of the updated Schwartz equation. P30 was defined as the percentage of patients whose eGFR was within ±30% of the measured GFR.

Results: The FAS equation showed significantly lower bias (mL/min/1.73 m2) than the updated Schwartz equation (4.2 vs. 8.7, p<0.001). The RMSE and P30 were: updated Schwartz of 43.8 and 64.4%, respectively, and FAS of 42.7 and 66.8%, respectively.

Conclusions: The height-independent eGFR-FAS equation was less biased and as accurate as the updated Schwartz equation in Korean children. The use of the height-independent eGFR equation will allow for efficient reporting of eGFR through the LIS in clinical laboratories.
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http://dx.doi.org/10.1515/cclm-2016-1151DOI Listing
October 2017

Corrigendum to "The 99th percentile values of six cardiac troponin assays established for a reference population using strict selection criteria" [Clin. Chim. Acta 464 (2017) 1-5].

Clin Chim Acta 2017 05 2;468:32. Epub 2017 Feb 2.

Department of Laboratory Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea. Electronic address:

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http://dx.doi.org/10.1016/j.cca.2017.01.031DOI Listing
May 2017

A new strategy for calculating the risk of ovarian malignancy algorithm (ROMA).

Clin Chem Lab Med 2017 Jul;55(8):1209-1214

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Background: Reliable quantitative measurements of HE4 and CA125 levels are required to calculate the risk of ovarian malignancy algorithm (ROMA) value. We suggest a new reporting strategy for interpreting ROMA values based on analytical measurement range (AMR) and qualified-intervals of the HE4 and CA125 results.

Methods: HE4 and CA125 assays from Abbott and Roche were used. The AMRs and the qualified-intervals were as follows: Architect HE4 assay, 20-1500 and 17.2-2637.8 pmol/L; Architect CA125 II assay, 1-1000 and 3.9-14,163.0 U/mL; Elecsys HE4 assay, 15-1500 and 28.8-3847 pmol/L; Elecsys CA125 II assay, 0.6-5000 and 6.5-5000 U/mL. These values were used to simulate the ROMA values.

Results: Reporting algorithm for the ROMA value could be classified into three categories. (1) If quantitative HE4 and CA125 levels are reliable, the numerical ROMA value can be reported. (2) If HE4 value is <20 and <28.8 for Abbott and Roche in premenopausal woman, the ROMA value should be reported as "low risk" regardless of the CA125 result. In postmenopausal woman, however, it should be reported as "low risk" (CA125<203.0 and <165.8 for Abbott and Roche) or "undetermined" (vice-versa value). (3) If CA125 value is <3.9 and <6.5 for Abbott and Roche, it should be reported as "low risk" (premenopausal HE4<51.5 and <62.2, postmenopausal HE4<323.0 and <281.5 for Abbott and Roche) or "undetermined" (vice-versa value).

Conclusions: New reporting strategy will provide more informative reporting of ROMA values in clinical practice.
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http://dx.doi.org/10.1515/cclm-2016-0582DOI Listing
July 2017

Effects of Catechol O-Methyl Transferase Inhibition on Anti-Inflammatory Activity of Luteolin Metabolites.

J Food Sci 2017 Feb 10;82(2):545-552. Epub 2017 Jan 10.

Research Group of Nutraceuticals for Metabolic Syndrome, Korea Food Research Inst., Gyeonggi, 463-746, Republic of Korea.

Although luteolin is known to have potent anti-inflammatory activities, much less information has been provided on such activities of its hepatic metabolites. Luteolin was subjected to hepatic metabolism in HepG2 cells either without or with catechol O-methyl transferase (COMT) inhibitor. To identify hepatic metabolites of luteolin without (luteolin metabolites, LMs) or with COMT inhibitor (LMs+CI), metabolites were treated by β-glucuronidase and sulfatase, and found that they were composed of glucuronide and sulfate conjugates of diosmetin in LMs or these conjugates of luteolin in LMs+CI. LMs and LMs+CI were examined for their anti-inflammatory activities on LPS stimulated Raw 264.7 cells. Expression of iNOS and production of nitric oxide and pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 were suppressed more effectively by the treatment with LMs+CI than LMs. Our data provide a new insight on possible improvement in functional properties of luteolin on target cells by modifying their metabolic pathway in hepatocytes.
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http://dx.doi.org/10.1111/1750-3841.13620DOI Listing
February 2017

TonEBP suppresses adipocyte differentiation via modulation of early signaling in 3T3-L1 cells.

Korean J Physiol Pharmacol 2016 Nov 28;20(6):649-655. Epub 2016 Oct 28.

Department of Physiology, Chungnam National University School of Medicine, Daejeon 35015, Korea.

TonEBP belongs to the Rel family of transcription factors and plays important roles in inflammation as well as kidney homeostasis. Recent studies suggest that TonEBP expression is also involved in differentiation of several cell types such as myocytes, chondrocytes, and osteocytes. In this study, we investigated the roles of TonEBP during adipocyte differentiation in 3T3-L1 cells. TonEBP mRNA and protein expression was dramatically reduced during adipocyte differentiation. Sustained expression of TonEBP using an adenovirus suppressed the formation of lipid droplets as well as the expression of FABP4, a marker of differentiated adipocytes. TonEBP also inhibited the expression of PPARγ, a known master regulator of adipocytes. RNAi-mediated knock down of TonEBP promoted adipocyte differentiation. However, overexpression of TonEBP did not affect adipogenesis after the initiation of differentiation. Furthermore, TonEBP expression suppressed mitotic clonal expansion and insulin signaling, which are required early for adipocyte differentiation of 3T3-L1 cells. These results suggest that TonEBP may be an important regulatory factor in the early phase of adipocyte differentiation.
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http://dx.doi.org/10.4196/kjpp.2016.20.6.649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5106399PMC
November 2016

The 99th percentile values of six cardiac troponin assays established for a reference population using strict selection criteria.

Clin Chim Acta 2017 Jan 5;464:1-5. Epub 2016 Nov 5.

Department of Laboratory Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea. Electronic address:

Background: Since the 99th percentile reference limit for cardiac troponin (Tn) can vary depending on the reference population, Sandoval et al. published systematic selection criteria. In this study, these systematic criteria were applied for the first time to obtain the 99th percentile reference limits for 6 Tn tests.

Methods: The reference population was selected in accordance with the systematic criteria, and reference limits were set with respect to the six types of Tn assays. The coefficient of variation (CV) at the reference limit was determined using 3-4 concentrations of frozen serum.

Results: In total, 641 South Koreans (303 males, 338 females) were selected as the reference population. The 99th percentile reference limit of Tn in the six assays ranged from 13.4 to 34.2pg/ml. The measurable fractions among the reference population ranged from 1.3% to 80.5%. The CVs at the reference limit ranged from 5.3% to 43.0%, and three were <10%.

Conclusions: In this study, a reference population was selected for the first time in accordance with the systematic criteria of Sandoval et al., and the reference limit for South Koreans was established. The values obtained in this study are different from those proposed by manufacturers, which confirms the importance of having a reference population. Four out of six assays did not fulfill the criteria for high-sensitivity tests.
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http://dx.doi.org/10.1016/j.cca.2016.11.004DOI Listing
January 2017