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 AND OBJECTIVES: Despite significant advances in the treatment of acute myocardial infarction (MI), the prevention of sudden cardiac death (SCD), the most common mode of death in patients with MI, remains challenging. Furthermore, previous Korean MI registries did not address the issue of post-MI SCD. Additional risk stratifiers of post-MI SCD are still required to compensate for the limitation of using left ventricular ejection fraction to predict lethal arrhythmic events. SUBJECTS AND METHODS: We designed the first Korean prospective nationwide multicenter registry primarily focused on SCD; the Korean noninvasive Risk Evaluation study for sudden cardiac DEath From INfarction or heart failurE (K-REDEFINE). The registry consists of 2 groups of patients presenting with (1) acute MI or (2) acute heart failure (HF) at 25 tertiary referral cardiovascular centers. The primary endpoint of the MI group study of K-REDEFINE registry is the incidence and risk factors of post-MI SCD. In particular, the association between the risk of SCD and non-invasive Holter-based electrocardiogram (ECG) variables will be evaluated, such as T-wave alternans (marker of repolarization heterogeneity) and heart rate turbulence/variability (a marker of autonomic function). Other secondary study outcomes include atrioventricular arrhythmias, HF-related admission, repeated myocardial ischemic events, stroke, and overall deaths. CONCLUSION AND PERSPECTIVE: The K-REDEFINE registry will provide new prospects for the better management of MI patients with high risk of SCD by clarifying the burden and predictors of SCD and the clinical utility of various non-invasive ambulatory ECG-based variables in risk stratification for SCD in this patient population.
Arrhythmias, Cardiac ; Death, Sudden, Cardiac* ; Electrocardiography ; Heart Failure* ; Heart Rate ; Heart* ; Humans ; Incidence ; Infarction* ; Myocardial Infarction* ; Prospective Studies ; Referral and Consultation ; Registries ; Risk Factors ; Stroke ; Stroke Volume

BACKGROUND AND OBJECTIVES: Sudden cardiac death (SCD) is one of the most common causes of death in patients with heart failure (HF). However, there are no available data on SCD in previous Korean HF registries. Additionally, although widely used, the utility of left ventricular (LV) ejection fraction (EF) in risk stratification for SCD is limited. SUBJECTS AND METHODS: The Korean non-invasive Risk Evaluation study for sudden cardiac DEath From INfarction or heart failurE (KREDEFINE) is the first Korean prospective, nationwide multicenter registry, primarily focused on SCD. The registry consists of 2 groups of patients presenting with (1) acute HF or (2) acute myocardial infarction (MI) at 25 tertiary referral cardiovascular centers. Using the HF-group data of the K-REDEFINE registry, the incidence and risk factors of SCD in patients with HF will be assessed. In particular, the efficacy of Holter-based ECG variables, such as T-wave alternans (marker of repolarization heterogeneity) and heart rate turbulence/ variability (maker of autonomic function), in risk stratification for SCD will be evaluated. Other cardiovascular outcomes will also be analyzed, including atrioventricular arrhythmias, HF-related admission, stroke, and overall deaths. CONCLUSION AND PERSPECTIVE: The K-REDEFINE registry will pave the way for better management of patients with HF at high risk of SCD by elucidating the burden and risk factors of SCD and the clinical utility of various non-invasive ambulatory ECG-based parameters in risk stratification for SCD in this patient population.
Arrhythmias, Cardiac ; Cause of Death ; Death, Sudden, Cardiac* ; Electrocardiography ; Heart Failure* ; Heart Rate ; Heart* ; Humans ; Incidence ; Infarction* ; Myocardial Infarction ; Prospective Studies ; Referral and Consultation ; Registries ; Risk Factors ; Stroke

PURPOSE: Common conditions, such as dehydration or respiratory infection can aggravate hypoxia and are associated with interstage mortality in infants who have undergone palliative surgery for congenital heart diseases. This study was done to evaluate the efficacy of a home monitoring program (HMP) in decreasing infant mortality. METHODS: Since its inception in May 2010, all infants who have undergone palliative surgery have been enrolled in HMP. This study was a prospective observational study and infant outcomes during HMP were compared with those of previous comparison groups. Parents were trained to measure oxygen saturation, body weight and feeding volume and to contact the hospital through the hotline for emergency situations. Telephone counseling was conducted by clinical nurse specialists every week post discharge. RESULTS: Forty-one infants were enrolled in HMP. Nine hundred telephone counseling sessions were conducted. Seventy-three infants required telephone triage with the most common conditions being gastrointestinal (50.7%) and respiratory symptoms (32.9%). With HMP intervention, interstage mortality decreased from 18.6% (8/43) to 9.8% (4/41) (chi2=1.15, p=.283). CONCLUSION: Results indicate that active measures and treatments using the HMP decrease mortality rates, however further investigation is required to identify various factors that contribute to hemodynamic complications during the interstage period.
Body Temperature ; Body Weight ; Caregivers/education/psychology ; Counseling ; Female ; Heart Defects, Congenital/mortality/prevention & control/*surgery ; Heart Rate ; Hospitalization ; Hotlines ; Humans ; Infant ; Infant, Newborn ; Male ; Monitoring, Physiologic/*methods ; Oxygen Consumption ; Palliative Care ; *Program Evaluation ; Prospective Studies ; Time Factors

OBJECTIVE: To compare the clinical outcomes of patients with vitrified-thawed embryos transferred using either the 0.25 mL straw method and the pull and cut straw (PNC) method. To evaluate the clinical outcomes of patients with transferred embryos that underwent assisted hatching at the cleaved embryo (day 3) or the blastocyst (day 5) stage. METHODS: The study population consisted of women who underwent vitrified-warmed embryo transfer between May 2000 and December 2011 and assisted hatching was performed after warming of embryos. Cycles of thawing between assisted hatching treated and non treated groups were compared for survival and pregnancy rates. RESULTS: The PNC vitrification method improved survival and pregnancy rates in partial lysed embryos. While assisted hatching did not affect the developmental and clinical pregnancy rates of the vitrified-warmed blastocyst group, it did increase the pregnancy rate of poor quality vitrified-warmed cleaved embryos. CONCLUSION: These results suggest that PNC may increase the number of clinical pregnancies via the vitrification of both cleaved embryos and blastocysts. In addition, selective assisted hatching treatment of embryos that show a poor prognosis after warming may increase the rate of clinical pregnancy.
Blastocyst ; Embryo Transfer ; Embryonic Structures ; Female ; Humans ; Pregnancy ; Pregnancy Rate ; Prognosis ; Vitrification

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

OBJECTIVE: Pneumomediastinum (PnM), a rare complication of dermatomyositis and polymyositis (DM/PM), is sporadic and has an unclear pathogenesis. PnM is almost always associated with interstitial lung disease (ILD), and is a poor prognostic factor in inflammatory myositis patients. We studied the prevalence of PnM in Korean DM/PM and its clinical significance. METHODS: We retrospectively studied the medical records of 161 patients diagnosed with DM/PM meeting Bohan-Peter's criteria at Hanyang University Hospital for Rheumatic Diseases from 1995 to 2010. We collected following findings; demographic data, diagnosis, lung involvement, cause of death, and duration from diagnosis to death. RESULTS: One hundred nineteen patients (73.9%) were DM and 42 patients (26.1%) were PM. Eighty three patients (51.6%) developed ILD at diagnosis or during follow up. Eighteen patients (11.2%) died because of ILD aggravation, infection, or malignancy. The mean duration from diagnosis to death was 11.5 months, with 10 patients (6.2%) dying from from ILD aggravation but none with spontaneous PnM. 6 patients (3.7%) presented with PnM, and it was associated with ILD worsening in all cases. PnM resolved with O2 inhalation, corticosteroids, and/or immunosuppressive agents after 11 weeks (mean) of therapy. CONCLUSION: PnM is rare but associates with DM and aggravation of ILD. PnM does not usually cause fatalities and can be cured by appropriate therapy.
Adrenal Cortex Hormones ; Cause of Death ; Dermatomyositis ; Follow-Up Studies ; Humans ; Immunosuppressive Agents ; Inhalation ; Lung ; Lung Diseases, Interstitial ; Mediastinal Emphysema ; Medical Records ; Myositis ; Polymyositis ; Prevalence ; Prognosis ; Retrospective Studies ; Rheumatic Diseases

We aimed to evaluate the safety and clinical responses in Korean ankylosing spondylitis (AS) patients after three months of etanercept therapy. AS patients satisfying the Modified New York Criteria were enrolled. They were assessed for safety and clinical responses at enrollment and after three months of etanercept therapy. A total of 124 patients completed the study. After three months, the rate of ASsessment in AS International Working Group 20% improvement (ASAS 20) response was 79.8%. The rates of ASAS 40 and ASAS 5/6 responses were 58.5 and 62.8%, respectively. Significant improvement of Korean version of Bath AS Disease Activity Index (KBASDAI) (p<0.0001), Bath AS Functional Activity Index (BASFI) (p<0.0001), and Bath AS Metrology Index (BASMI) (p=0.0009) were achieved after three months. Quality of life was also significantly improved after three months, as demonstrated by scores for SF-36 (p<0.0001) and EQ-5D (p<0.0001). Erythrocyte sedimentation rate and C-reactive protein were significantly decreased (p<0.0001, p<0.0001, respectively). None of the patients developed tuberculosis and there were no serious adverse event. AS patients with inadequate response to conventional therapy showed significant clinical improvement without serious adverse events after three months of etanercept therapy.
Adult ; Blood Sedimentation ; C-Reactive Protein/metabolism ; Cohort Studies ; Female ; Humans ; Immunoglobulin G/*pharmacology ; Immunosuppressive Agents/pharmacology ; Korea ; Male ; Prospective Studies ; Quality of Life ; Receptors, Tumor Necrosis Factor ; Remission Induction ; Spondylitis, Ankylosing/*therapy ; Treatment Outcome

We report here a case of vascular Behcet's disease. 32-year-old young woman who suffered from chest pain was diagnosed with acute myocardial infarction four years before admission. At that time she manifested symtoms of Behcet's disease, such as oral ulcers, genital ulcers, multiple arthralgia, and a peculiar hyperirritability reaction to needle puncture. At this time she was admitted due to acute chest pain and intermittent abdominal pain. The diagnosis of an acute anteroseptal myocardial infarction was made on the basis of the electrocardiography findings. Cardiac catheterization revealed segmental stenosis up to 95% at the mid-left anterior descending artery without aneurysm formation at other coronary trees and there were no atherosclerotic changes. Coronary stent was inserted in the lesion. Abdominal CT showed inferior vena cava and right hepatic vein obstruction, which supports the diagnosis of Budd-Chiari syndrome. Our case demonstrated the followings which are not common to vasculo-Behcet disease; 1) initial clinicopathologic manifestations at the coronary artery, 2) abrupt total occlusion with clear cut lesion at left anterior descending artery, 3) recurrent myocardial infarctions, 4) Budd-Chiari syndrome, 5) combined superior mesenteric artery, inferior mesenteric artery and celiac trunk obstruction. Among the systemic manifestation of Behect's disease, cardiac involvement is very rare but should be considered as one of the most important features that influences the prognosis.
Abdominal Pain ; Adult ; Aneurysm ; Anterior Wall Myocardial Infarction ; Arteries ; Arthralgia ; Budd-Chiari Syndrome* ; Cardiac Catheterization ; Cardiac Catheters ; Chest Pain ; Constriction, Pathologic ; Coronary Vessels ; Diagnosis ; Electrocardiography ; Female ; Heart Diseases ; Hepatic Veins ; Humans ; Mesenteric Artery, Inferior ; Mesenteric Artery, Superior ; Myocardial Infarction* ; Needles ; Oral Ulcer ; Prognosis ; Punctures ; Stents ; Tomography, X-Ray Computed ; Ulcer ; Vena Cava, Inferior

OBJECTIVE: Juvenile rheumatoid arthritis (JRA) is classified as polyarticular, oligoarticular, and systemic onset type by clinical symptoms presented during first six months. This study was performed to investigate the clinical features and course of systemic onset JRA. METHODS: We performed a retrospective study for patients who were diagnosed as JRA between March 2000 and March 2006 according to the JRA criteria of the International League of Association for Rheumatology (ILAR). RESULTS: Of the 216 JRA patients, 33 patients (11 male/ 22 female) were systemic onset type. Because of insufficient data, 6 patients were excluded. Chief complaints at the time of diagnosis were fever (81.5%) and arthralgia (77.7%). During the disease course, all patients manifested fever and arthritis, rash (59.2%) and splenomegaly (22.2%) also occurred. Most patients had symmetric (81.5%) arthritis, and involved more than five joints (59.3%) including knee and wrist. Anemia, leukocytosis, and thrombocytosis were common laboratory abnormalities. Almost all patients had elevated level of C-reactive protein and erythrocyte sediment rate. Some patients had positive results about immunologic marker such as rheumatoid factor (3.8%), antinuclear antibody (57.7%), and antiperinuclear factor (9.5%). Therapeutic regimens included glucocorticoids (88.9%), nonsteroidal anti-inflammatory drugs (81.5%), methotrexate (81.5%), and hydroxychloroquine (55.6%). Biologic agents were applied in 5 patients, and 3 showed improvement of disease activity. Combination therapy was introduced in 18.5% of patients, and 63% of patients still required medications. CONCLUSION: In Korea, systemic onset JRA patients had variable clinical manifestations and chronic course of disease, which often extended into adulthood.
Anemia ; Antibodies, Antinuclear ; Arthralgia ; Arthritis ; Arthritis, Juvenile* ; Biological Factors ; Biomarkers ; C-Reactive Protein ; Diagnosis ; Erythrocytes ; Exanthema ; Fever ; Glucocorticoids ; Humans ; Hydroxychloroquine ; Joints ; Knee ; Korea ; Leukocytosis ; Methotrexate ; Retrospective Studies ; Rheumatoid Factor ; Rheumatology ; Splenomegaly ; Thrombocytosis ; Wrist