Background and Objectives: DNA methyltransferases (Dnmts) play an important role in regulating DNA methylation during early developmental processes and cellular differentiation. In this study, we aimed to investigate the role of Dnmts in neural differentiation of embryonic stem cells (ESCs) and in maintenance of the resulting neural stem cells (NSCs). Methods: and Results: We used three types of Dnmt knockout (KO) ESCs, including Dnmt1 KO, Dnmt3a/3b double KO (Dnmt3 DKO), and Dnmt1/3a/3b triple KO (Dnmt TKO), to investigate the role of Dnmts in neural differentiation of ESCs. All three types of Dnmt KO ESCs could form neural rosette and differentiate into NSCs in vitro. Interestingly, however, after passage three, Dnmt KO ESC-derived NSCs could not maintain their self-renewal and differentiated into neurons and glial cells. Conclusions Taken together, the data suggested that, although deficiency of Dnmts had no effect on the differentiation of ESCs into NSCs, the latter had defective maintenance, thereby indicating that Dnmts are crucial for self-renewal of NSCs.

Background/Aims: We aimed to compare the effectiveness and safety of Janus kinase inhibitors (JAKi) vs. biologic disease- modifying antirheumatic drugs (bDMARD) in Korean patients with rheumatoid arthritis (RA) who had an inadequate response to conventional synthetic DMARDs. Methods: A quasi-experimental, multi-center, prospective, non-randomized study was conducted to compare response rates between JAKi and bDMARDs in patients with RA naïve to targeted therapy. An interim analysis was performed to estimate the proportion of patients achieving low disease activity (LDA) based on disease activity score (DAS)–28– erythroid sedimentation rate (ESR) (DAS28-ESR) at 24 weeks after treatment initiation and to evaluate the development of adverse events (AEs). Results: Among 506 patients enrolled from 17 institutions between April 2020 and August 2022, 346 (196 JAKi group and 150 bDMARD group) were included in the analysis. After 24 weeks of treatment, 49.0% of JAKi users and 48.7% of bDMARD users achieved LDA (p = 0.954). DAS28-ESR remission rates were also comparable between JAKi and bDMARD users (30.1% and 31.3%, respectively; p = 0.806). The frequency of AEs reported in the JAKi group was numerically higher than that in the bDMARDs group, but the frequencies of serious and severe AEs were comparable between the groups. Conclusions Our interim findings reveal JAKi have comparable effectiveness and safety to bDMARDs at 24 weeks after treatment initiation.

OBJECTIVE: To estimate drug persistency and the safety of TNF blocker in Korean patients with rheumatoid arthritis. METHODS: Data were extracted from medical records of rheumatoid arthritis patients who had treated with TNF blocker or are currently using TNF blocker at Hanyang University Hospital for Rheumatic Diseases from December 2000 to November 2009 (REtrospective study for Safety and Efficacy of Anti-RA treatment with biologiCs, RESEARCh). Comprehensive chart reviews were undertaken on all patients and data on drug usages and response of TNF blocker was collected at initiation, 3 months and the time of data collection. Persistency with treatment was examined using life-table analysis and multivariate Cox proportional hazard models were developed to examine potential predictors of discontinuation of TNF blocker. RESULTS: A total of 268 patients were enrolled in this retrospective study. Among them 180 patients were included in the analysis of drug persistency. The 1-year and 5-year drug persistency of TNF blocker was 74% and 46%, respectively. Concomitant use of methotrexate (hazard ratio 0.46, 95% CI 0.27-0.80) was associated with higher persistence. Comparing to etanercept, adalimumab is an independent risk factor for discontinuation (hazard ratio 2.63, 95% CI 1.43-4.84). CONCLUSION: Five-year drug persistency of TNF blocker was 46% and concomitant use of methotrexate is associated with higher persistence.
Antibodies, Monoclonal, Humanized ; Arthritis, Rheumatoid ; Biological Agents ; Data Collection ; Humans ; Immunoglobulin G ; Medical Records ; Methotrexate ; Proportional Hazards Models ; Receptors, Tumor Necrosis Factor ; Retrospective Studies ; Rheumatic Diseases ; Risk Factors ; Adalimumab ; Etanercept

Marssonina coronaria associated with apple blotch disease causes severe premature defoliation, and is widely distributed in Korea. Thirteen isolates were collected from orchards located in Gyeongbuk Province from 2005~2007. All isolates displayed over 99.6% and 99.2% sequence similarity to each other in internal transcribed spacer regions and partial sequences of 28S rDNA, respectively. The isolates were phylogenetically closely related to Chinese isolates. Selected isolates did not differ in their pathogenicity. The optimum conditions for fungal growth were 20degrees C and pH 6 on peptone potato dextrose agar (PPDA). Peptone and mannose were the best nitrogen and carbon source, respectively. Fungal growth was better on PPDA than on common potato dextrose agar. This study provides valuable information for integrated disease management program and facilitates the routine culturing of M. coronaria.
Agar ; Asian Continental Ancestry Group ; Carbon ; Diazonium Compounds ; Disease Management ; DNA, Ribosomal ; Glucose ; Humans ; Hydrogen-Ion Concentration ; Korea ; Mannose ; Nitrogen ; Peptones ; Phylogeny ; Pyridines ; Solanum tuberosum

Alcoholism is caused by a complex interaction between genetic and environmental factors. Findings obtained from several studies indicate that some tissue damage occurring in alcohol abusers is due to the generation of reactive oxygen species during the ethanol metabolism The objective of this study was to examine the associations between the polymorphisms of glutathione S-transferase (GST) M1 and T1 genes and Korean male patients with alcoholism. We investigated the distribution of deletion of GSTM1 and GSTT1 in Korean male patients diagnosed with alcoholism (n=133) and Korean male control subject without alcoholism (n=91) with polymerase chain reaction (PCR) method. GSTM1 showed significant associations with alcoholism susceptibility (p=0.0002). But GSTT1 showed no significant associations (p=0.0948). In combined analysis, both gene deletion and GSTM1 deletion were associated with alcoholism (p<0.0001 and p<0.0150). These results suggest that GSTM1 gene deletion might play an important role in risk for alcoholism.
Alcoholism ; Ethanol ; Gene Deletion ; Glutathione Transferase ; Humans ; Male ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Reactive Oxygen Species

Pre-B-cell leukemia transcription factor 1 (PBX1), which is located on chromosome 1q23, was recently reported to be associated with type 2 diabetes mellitus. We examined whether single nucleotide polymorphisms (SNPs) of the PBX1 gene are associated with overweight/obesity in a Korean population. We genotyped 66 SNPs in the PBX1 gene and investigated their association with clinical phenotypes found in 214 overweight/obese subjects and 160 control subjects using the Affymetrix Targeted Genotyping chip array. Seven SNPs (g.+75186C>T, g.+78350C>A, g.+80646C>T, g.+138004C>T, g.+185219G>A, g.+191272A>C, and g.+265317T>A) were associated with the risk of obesity in three models (codominant, dominant, and recessive) (P=0.007-0.05). Haplotype 1 (CAC) and 3 (TAC) of block 3 and haplotype 2 (GGAAT) of block 10 were also strongly associated with the risk of obesity. In the control group, subjects that had homozygote for the major allele for both g.+185219G>A and g.+191272A>C showed lower high density lipoprotein-cholesterol (HDL-C) level compared to those possessing the minor allele, suggesting that the association between the homozygote for the major allele for both g.+185219G>A and g.+191272A>C and HDL-C is attributable to the increased risk of obesity. This study suggests that the PBX1 gene is a possible risk factor in overweight/obese patients.
Alleles ; Diabetes Mellitus, Type 2 ; Haplotypes ; Homozygote ; Humans ; Obesity ; Phenotype ; Polymorphism, Single Nucleotide ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; Risk Factors ; Transcription Factors

We investigated the effect by the chemical fixative on human fibroblast cells (HFCs) in order to make nano-scale images using by the atomic force microscopy (AFM). The cell fixation needed to be optimized as prerequisite step for the preparation before analysis. AFM imaging after optimal wet fixation can provide practical, simple and fast technique for scanning living cells. In this study, AFM images - topography and amplitude - and the optic images of HFCs which were fixed with phosphate buffered saline (PBS), 2:1 ethanol:acetic acid, 4% glutaraldehyde and 37% formaldehyde were compared respectively. The final effect by washing with PBS or distilled water (D.W.) was examined after 4% glutaraldehyde fixation. To determine the optimal fixation method for HFCs, we performed quantitative and qualitative analysis by the height profile, the presence of artifacts and the morphology of well-conserved fibroblastic topography image by AFM. From AFM image which showed fibroblastic cellular morphology and differential height value of cytoplasm (670+/-47 nm, n=10) and nucleus (847+/-32 nm, n=10) in HFCs, we proposed that wet fixation by 4% glutaraldehyde, followed by final washing with PBS, could be the most suitable preparation for AFM imaging of HFCs, which enable us to approach easily on living cells with the least shrinkage.
Artifacts ; Cytoplasm ; Fibroblasts ; Formaldehyde ; Glutaral ; Humans ; Microscopy, Atomic Force ; Water

Granulocytic sarcoma is an extramedullary tumor composed of immature cells of the granulocytic series known to occur in patients with myelodysplastic syndrome, chronic myeloid leukemia, or acute myeloid leukemia. and occasionally it has been presented without overt leukemia. Involvement of pancreas and kidney is relatively rare in granulocytic sarcoma. We present an extremely rare case of granulocytic sarcoma of pancreas and kidney in a 56-year-old male patient of acute myeloid leukemia presenting with obstructive jaundice due to a pancreatic mass and peri-lymphadenopathy consisting of myeloblast and review the literatures. It should be kept in mind that granulocytic sarcoma is a possible cause of obstructive jaundice in patient with acute myeloid leukemia.
Granulocyte Precursor Cells ; Humans ; Jaundice* ; Jaundice, Obstructive ; Kidney* ; Leukemia ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Leukemia, Myeloid, Acute ; Male ; Middle Aged ; Myelodysplastic Syndromes ; Pancreas* ; Sarcoma, Myeloid*

PURPOSE: Recently established in 1997, Sungkyunkwan University School of Medicine was the first medical school in Korea to adopt problem-based learning (PBL) as a core curriculum from the very beginning. The purpose of this study was to evaluate the PBL curriculum from the viewpoint of the medical students. METHODS: This study used a qualitative approach to understand students' perceptions of the positive aspects of PBL. A total of 22 second-year medical students at Sungkynkwan medical school were surveyed. Student perceptions were obtained from questionnaires and face-to-face interviews. The interview was designed to evoke more personal and in-depth responses. RESULTS: Students' perceptions of the effects of PBL were found to be very favorable. Most students showed positive responses on the issues of more active learning attitude, self-directed learning, motivation to study, improved problem solving, and integrated learning. CONCLUSION: The results of this study demonstrated that the students had a good understanding of PBL and experienced its positive aspects of PBL approach. It might be concluded that PBL was successfully implemented into the curriculum and specific and expected effects of PBL accomplished.
Curriculum* ; Evaluation Studies as Topic* ; Humans ; Korea ; Learning ; Motivation ; Problem Solving ; Problem-Based Learning* ; Schools, Medical ; Students, Medical ; Surveys and Questionnaires

OBJECTIVE: Few studies have examined the impact of chronic diseases on populations using a comprehensive health-related quality of life (HRQOL) in Korea. We assessed HRQOL of patients with 16 common chronic diseases. METHODS: We interviewed patients with chronic diseases (n=980) and healthy control (n=288) using two HRQOL measurements: Korean Medical Outcome Study Short Form-36 (KSF-36) and Korena EuroQol-5 Dimensions (KEQ-5D), and questions on sociodemographic and clinical characteristics. RESULTS: Each illness had a distinctive profile. Among disease groups, the KSF-36 global health score was highest in DM and lowest in fibromyalgia. The KSF-36 physical component summary score was highest in DM and lowest in osteoarthritis . The KSF-36 mental component summary score was highest in hypertension and lowest in fibromyalgia. The KEQ-5D utility score was highest in DM and lowest in fibromyalgia. The KEQ-5D visual analog score was highest in DM and lowest in liver cirrhosis. In correlation analysis, the KSF-36 physical component summary, mental component summary and five domains in KEQ-5D were well correlated with each others. CONCLUSION: Health related quality of life in Korean patients with chronic disease is lower than healthy control. Patients with hypertension and DM registered the two highest scores in global health but patients with fibromyalgia reported the worst health experience in global health.We can compare the profiles of the groups and determine the relative impact on the patients of the various diseases and these data will provide a baseline of the current health related quality of life of individuals suffering from a variety of conditions.
Chronic Disease* ; Fibromyalgia ; Humans ; Hypertension ; Korea ; Liver Cirrhosis ; Osteoarthritis ; Outcome Assessment (Health Care) ; Quality of Life*