The generation of induced pluripotent stem cells (iPSCs) derived from patients' somatic cells provides a new paradigm for studying human genetic diseases. Human iPSCs which have similar properties of human embryonic stem cells (hESCs) provide a powerful platform to recapitulate the disease-specific cell types by using various differentiation techniques. This promising technology has being realized the possibility to explore pathophysiology of many human genetic diseases at the molecular and cellular levels. Furthermore, disease-specific human iPSCs can also be used for patient-based drug screening and new drug discovery at the stage of the pre-clinical test in vitro. In this review, we summarized the concept and history of cellular reprogramming or iPSC generation and highlight recent progresses for disease modeling using patient-specific iPSCs.
Drug Discovery ; Drug Evaluation, Preclinical ; Embryonic Stem Cells ; Humans ; Induced Pluripotent Stem Cells ; Nuclear Reprogramming

The generation of induced pluripotent stem cells (iPSCs) derived from patients' somatic cells provides a new paradigm for studying human genetic diseases. Human iPSCs which have similar properties of human embryonic stem cells (hESCs) provide a powerful platform to recapitulate the disease-specific cell types by using various differentiation techniques. This promising technology has being realized the possibility to explore pathophysiology of many human genetic diseases at the molecular and cellular levels. Furthermore, disease-specific human iPSCs can also be used for patient-based drug screening and new drug discovery at the stage of the pre-clinical test in vitro. In this review, we summarized the concept and history of cellular reprogramming or iPSC generation and highlight recent progresses for disease modeling using patient-specific iPSCs.
Drug Discovery ; Drug Evaluation, Preclinical ; Embryonic Stem Cells ; Humans ; Induced Pluripotent Stem Cells ; Nuclear Reprogramming

Although microRNAs have emerged as key regulators in diverse cellular processes, the roles of microRNAs are poorly understood in human embryonic stem cells (hESCs) during differentiation into specialized cell types. In this study, we used a microRNA array with 799 human microRNA probes to examine the expression profiles of microRNAs in hESCs during differentiation into endodermal and mesodermal lineages in vitro. Among the microRNAs analyzed, 7 and 20 microRNAs were enriched in the developmental process of hESCs into mesodermal and endodermal lineages, respectively. In particular, the expression levels of miR-200 family, which is known to regulate the epithelial to mesenchymal transition (EMT), gradually increased in hESCs during differentiation into hepatocytes while they gradually decreased during differentiation into vascular endothelial cells. Downregulation of ZEB1, a direct target of miR-200 family, and E-CADHERIN, a target protein of ZEB1, was observed in hESCs during differentiation into endodermal and mesodermal lineages, respectively. These results indicate that miR-200 family has an important role in determining the cell fate between endodermal and mesodermal lineages from the pluripotent state.
Cadherins ; Down-Regulation ; Endoderm ; Endothelial Cells ; Hepatocytes ; Human Embryonic Stem Cells* ; Humans ; Humans* ; In Vitro Techniques* ; Mesoderm ; MicroRNAs

BACKGROUND AND OBJECTIVES: We sought to evaluate nationwide trends, characteristics, and clinical outcomes in patients undergoing percutaneous coronary intervention (PCI) in Korea. METHODS: From National Health Insurance claims data in Korea, 81,115 patients, who underwent PCI for the first episode of coronary artery disease between 2011 and 2015, were enrolled. Patients were categorized into angina (n=49,288) or acute myocardial infarction (AMI, n=31,887) groups and analyzed. RESULTS: The mean age of patients was 64.4±12.2 years and 56,576 (69.7%) were men. Diabetes, hyperlipidemia, and hypertension were observed in 27,086 (33.4%), 30,675 (37.8%), and 45,389 (56.0%) patients, respectively. There was a 10% increase in the number of patients undergoing PCI for angina between 2011–2012 and 2014–2015 (11,105 vs. 13,261; p=0.021). However, the number of patients undergoing PCI for AMI marginally decreased between 2011–2012 and 2014–2015 (8,068 vs. 7,823; p=0.052). In procedures, drug-eluting stent was the most frequently used device (93.2%), followed by balloon angioplasty (5.5%) and bare metal stents (1.3%). The mean number of stents per patient was 1.39±0.64. At discharge, dual-anti platelet therapy, statin, beta-blockers, and angiotensin converting enzyme inhibitor or angiotensin receptor blocker were provided to 76,292 (94.1%), 71,411 (88.0%), 57,429 (70.8%), and 54,418 (67.1%) patients, respectively. The mean in-hospital and 1-year total medical costs were 8,628,768±4,832,075 and 13,128,158±9,758,753 Korean Won, respectively. In-hospital mortality occurred in 2,094 patients (2.6%). CONCLUSIONS: Appropriate healthcare strategies reflecting trends, characteristics, and clinical outcomes of PCI are needed in Korea.
Angina Pectoris ; Angioplasty, Balloon ; Angiotensins ; Blood Platelets ; Coronary Artery Disease ; Delivery of Health Care ; Drug-Eluting Stents ; Hospital Mortality ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Hyperlipidemias ; Hypertension ; Korea ; Male ; Myocardial Infarction ; National Health Programs ; Peptidyl-Dipeptidase A ; Percutaneous Coronary Intervention ; Stents

BACKGROUND AND OBJECTIVES: We sought to evaluate nationwide trends, characteristics, and clinical outcomes in patients undergoing percutaneous coronary intervention (PCI) in Korea. METHODS: From National Health Insurance claims data in Korea, 81,115 patients, who underwent PCI for the first episode of coronary artery disease between 2011 and 2015, were enrolled. Patients were categorized into angina (n=49,288) or acute myocardial infarction (AMI, n=31,887) groups and analyzed. RESULTS: The mean age of patients was 64.4±12.2 years and 56,576 (69.7%) were men. Diabetes, hyperlipidemia, and hypertension were observed in 27,086 (33.4%), 30,675 (37.8%), and 45,389 (56.0%) patients, respectively. There was a 10% increase in the number of patients undergoing PCI for angina between 2011–2012 and 2014–2015 (11,105 vs. 13,261; p=0.021). However, the number of patients undergoing PCI for AMI marginally decreased between 2011–2012 and 2014–2015 (8,068 vs. 7,823; p=0.052). In procedures, drug-eluting stent was the most frequently used device (93.2%), followed by balloon angioplasty (5.5%) and bare metal stents (1.3%). The mean number of stents per patient was 1.39±0.64. At discharge, dual-anti platelet therapy, statin, beta-blockers, and angiotensin converting enzyme inhibitor or angiotensin receptor blocker were provided to 76,292 (94.1%), 71,411 (88.0%), 57,429 (70.8%), and 54,418 (67.1%) patients, respectively. The mean in-hospital and 1-year total medical costs were 8,628,768±4,832,075 and 13,128,158±9,758,753 Korean Won, respectively. In-hospital mortality occurred in 2,094 patients (2.6%). CONCLUSIONS Appropriate healthcare strategies reflecting trends, characteristics, and clinical outcomes of PCI are needed in Korea.

BACKGROUND AND OBJECTIVES: Genomic imprinting is an inheritance phenomenon by which a subset of genes are expressed from one allele of two homologous chromosomes in a parent of origin-specific manner. Even though fine-tuned regulation of genomic imprinting process is essential for normal development, no other means are available to study genomic imprinting in human during embryonic development. In relation with this bottleneck, differentiation of human embryonic stem cells (hESCs) into specialized lineages may be considered as an alternative to mimic human development. METHODS AND RESULTS: In this study, hESCs were differentiated into three lineage cell types to analyze temporal and spatial expression of imprinted genes. Of 19 imprinted genes examined, 15 imprinted genes showed similar transcriptional level among two hESC lines and two human induced pluripotent stem cell (hiPSC) lines. Expressional patterns of most imprinted genes were varied in progenitors and fully differentiated cells which were derived from hESCs. Also, no consistence was observed in the expression pattern of imprinted genes within an imprinting domain during in vitro differentiation of hESCs into three lineage cell types. CONCLUSIONS: Transcriptional expression of imprinted genes is regulated in a cell type-specific manner in hESCs during in vitro differentiation.
Alleles ; Embryonic Development ; Embryonic Stem Cells* ; Female ; Genomic Imprinting ; Human Development ; Humans ; Parents ; Pluripotent Stem Cells ; Pregnancy ; Wills

BACKGROUND: The size and depth of the double-lumen tube (DLT) are important for one-lung ventilation (OLV). In patients of a short stature, it is difficult to perform OLV successfully. We designed this study to evaluate the dimensions and margin of safety of the left main bronchi in patients of a short stature for appropriate OLV. METHODS: Chest computed tomography (CT) scans of 241 patients (22 male, 219 female) of a short stature (height below 155 cm) were analyzed retrospectively. The diameters of the trachea (DT), the right and left main bronchi (DR and DL), and the lengths of the right and left main bronchi (LR and LL) were measured at the coronal section of the chest CT scans using a picture archiving communication system program. RESULTS: There were no significant correlations between the heights and lengths of the right and left main bronchi. In addition, the ages and weights of the patients showed no significant correlations with the airway dimensions. The lengths of the bronchial lumen of the left-sided Mallinckrodt DLT show variations of 3 to 5.5 mm with tubes of identical sizes. The margin of safety is 13.8 +/- 4.1 mm assuming that appropriately sized DLTs are inserted. CONCLUSIONS: For successful and safe OLV in patients of a short stature, anesthesiologists should consider the length of the main bronchus and the actual length of the bronchial lumen of the DLT.
Body Height ; Bronchi ; Humans ; Male ; One-Lung Ventilation ; Retrospective Studies ; Thorax ; Tomography, X-Ray Computed ; Trachea ; Weights and Measures

BACKGROUND: The aim of this study was to measure the effect of smoking on bronchial mucus transport velocity with bronchoscope under total intravenous anesthesia. METHODS: Twenty six ASA physical status I male patients (13 smokers and 13 nonsmokers) were enrolled into this study. They scheduled to undergo elective orthopedic surgery and were operated under total intravenous anesthesia using propofol and remifentanil. Single drop (approximately 0.02 cc) of methylene blue was applied to the posterior mucosal surface of right main bronchus 5 cm away from carina by the bronchoscope with epidural catheter 30 minutes after tracheal intubation. Two, four minutes after methylene blue application, the transport of methylene blue was observed. Six minutes after methylene blue application, the distance of methylene blue movement was measured. RESULTS: Mean bronchial mucus transport distance and velocity of methylene blue in smoker group vs nonsmoker group was 9.1 +/- 5.5 mm and 1.5 +/- 1.0 mm/min vs 24.3 +/- 15.2 mm and 4.1 +/- 2.5 mm/min respectively. Mean bronchial mucus transport distance of methylene blue in the smoker group was shorter than that in the nonsmoker group (P value < 0.05). Mean bronchial mucus transport velocity of methylene blue in the smoker group was slower than that in the nonsmoker group (P < 0.05). CONCLUSIONS: Smoking may delay transport of bronchial secretion in terms of bronchial mucus transport velocity under total intravenous anesthesia.
Anesthesia, Intravenous ; Bronchi ; Bronchoscopes ; Catheters ; Humans ; Intubation ; Male ; Methylene Blue ; Mucus ; Orthopedics ; Piperidines ; Propofol ; Smoke ; Smoking

In spite of the American Heart Association recommendations for blood pressure measurement, many physicians measure blood pressure in only one arm that is easy to access at the time of measurement. This practice can lead to incorrect management with significant interarm blood pressure difference. We report a case of a 51 years old man who was scheduled to undergo vascular bypass graft under combined spinal-epidural anesthesia. In 60 minutes after anesthesia, the blood pressure of left arm dropped from 110/65 mmHg to 74/45 mmHg. The blood pressure was still 80/50 mmHg after two injections of ephedrine. After checking radial pulse tone strength, we found significant interarm blood pressure difference. The blood pressure of right arm was 150/70 mmHg. Postoperative CT angiogram revealed significant stenotic portion in the left subclavian artery. This case emphasizes the importance of bilateral blood pressure measurement, especially in patients with peripheral vascular disease.
American Heart Association ; Anesthesia ; Arm ; Blood Pressure ; Ephedrine ; Humans ; Peripheral Vascular Diseases ; Subclavian Artery ; Subclavian Steal Syndrome ; Transplants