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1.  Activin A Promotes Hematopoietic Fated Mesoderm Development Through Upregulation of Brachyury in Human Embryonic Stem Cells 
Stem Cells and Development  2012;21(15):2866-2877.
The development of the hematopoietic system involves multiple cellular steps beginning with the formation of the mesoderm from the primitive streak, followed by emergence of precursor populations that become committed to either the endothelial or hematopoietic lineages. A number of growth factors such as activins and fibroblast growth factors (FGFs) are known to regulate the early specification of hematopoietic fated mesoderm, notably in amphibians. However, the potential roles of these factors in the development of mesoderm and subsequent hematopoiesis in the human have yet to be delineated. Defining the cellular and molecular mechanisms by which combinations of mesoderm-inducing factors regulate this stepwise process in human cells in vitro is central to effectively directing human embryonic stem cell (hESC) hematopoietic differentiation. Herein, using hESC-derived embryoid bodies (EBs), we show that Activin A, but not basic FGF/FGF2 (bFGF), promotes hematopoietic fated mesodermal specification from pluripotent human cells. The effect of Activin A treatment relies on the presence of bone morphogenetic protein 4 (BMP4) and both of the hematopoietic cytokines stem cell factor and fms-like tyrosine kinase receptor-3 ligand, and is the consequence of 2 separate mechanisms occurring at 2 different stages of human EB development from mesoderm to blood. While Activin A promotes the induction of mesoderm, as indicated by the upregulation of Brachyury expression, which represents the mesodermal precursor required for hematopoietic development, it also contributes to the expansion of cells already committed to a hematopoietic fate. As hematopoietic development requires the transition through a Brachyury+ intermediate, we demonstrate that hematopoiesis in hESCs is impaired by the downregulation of Brachyury, but is unaffected by its overexpression. These results demonstrate, for the first time, the functional significance of Brachyury in the developmental program of hematopoietic differentiation from hESCs and provide an in-depth understanding of the molecular cues that orchestrate stepwise development of hematopoiesis in a human system.
doi:10.1089/scd.2012.0053
PMCID: PMC3464075  PMID: 22548442
2.  Topical Application of Chrysanthemum indicum L. Attenuates the Development of Atopic Dermatitis-Like Skin Lesions by Suppressing Serum IgE Levels, IFN-γ, and IL-4 in Nc/Nga Mice 
Chrysanthemum indicum L. (CIL) is widely used as an anti-inflammatory agent in Asia and our preliminary study revealed that CIL reduced interleukin (IL)-4 and IL-13 in 2,4-dinitrochlorobenzene (DNCB)-treated HaCaT cells, a human keratinocyte cell line. We investigated the atopic dermatitis (AD) effect of topically applied CIL in mice with AD-like symptoms. After topical application of 1,3-butylen glycol (control), CIL-Low (5%), CIL-High (30%), or 0.1% hydrocortisone (HC) on the AD-like skin lesions in DNCB-treated NC/Nga mice for 5 weeks, the ear thickness, mast cell infiltration, and serum immunoglobulin E (IgE), IgG1, IL-4 and interferon (IFN)-γ were measured. The gene expressions of IL-4, IL-13, and IFN-γ in the dorsal skin were assayed. CIL treatment dosedependently reduced severity of clinical symptoms of dorsal skin, ear thickness, and the number of mast cells and eosinophils. CIL-High significantly decreased serum IgE, IgG1, IL-4, and IFN-γ levels and reduced mRNA levels of IFN-γ, IL-4, and IL-13 in dorsal skin lesion. The improvement by CIL-High was similar to HC, but without its adverse effects such as skin atrophy maceration, and secondary infection. In conclusion, CIL may be an effective alternative substance for the management of AD.
doi:10.1155/2012/821967
PMCID: PMC3291039  PMID: 22454686
3.  Oral Solubilized Ursodeoxycholic Acid Therapy in Amyotrophic Lateral Sclerosis: A Randomized Cross-Over Trial 
Journal of Korean Medical Science  2012;27(2):200-206.
To evaluate the efficacy and safety of ursodeoxycholic acid (UDCA) with oral solubilized formula in amyotrophic lateral sclerosis (ALS) patients, patients with probable or definite ALS were randomized to receive oral solubilized UDCA (3.5 g/140 mL/day) or placebo for 3 months after a run-in period of 1 month and switched to receive the other treatment for 3 months after a wash-out period of 1 month. The primary outcome was the rate of progression, assessed by the Appel ALS rating scale (AALSRS), and the secondary outcomes were the revised ALS functional rating scale (ALSFRS-R) and forced vital capacity (FVC). Fifty-three patients completed either the first or second period of study with only 16 of 63 enrolled patients given both treatments sequentially. The slope of AALSRS was 1.17 points/month lower while the patients were treated with UDCA than with placebo (95% CI for difference 0.08-2.26, P = 0.037), whereas the slopes of ALSFRS-R and FVC did not show significant differences between treatments. Gastrointestinal adverse events were more common with UDCA (P < 0.05). Oral solubilized UDCA seems to be tolerable in ALS patients, but we could not make firm conclusion regarding its efficacy, particularly due to the high attrition rate in this cross-over trial.
doi:10.3346/jkms.2012.27.2.200
PMCID: PMC3271295  PMID: 22323869
Amyotrophic Lateral Sclerosis; Ursodeoxycholic Acid; Cross-Over Trial
4.  Clinical Implications of Mandible and Neck Measurements in Non-Obese Asian Snorers: Ansan City General Population-Based Study 
Objectives
Anthropometric abnormalities of the mandible and neck may contribute to snoring in non-obese Asians. The study evaluated the clinical implications of mandible and neck measurements in non-obese Asian snorers.
Methods
The external mandible and neck measurements (neck circumference, two lengths of neck, mandibular body angle, and lengths of mandibular ramus and body) were compared between snorers and non-snorers in a sample of 2,778 non-obese Koreans (1,389 males, 1,389 females) aged 40 to 69 years (mean, 48.47±7.72 years).
Results
The overall prevalence of snoring was 64.7% (899/1,389) and 48.3% (671/1,389) in non-obese male and female subjects, respectively. In non-obese males, snorers had significantly a greater neck circumference (P<0.0001) and shorter mandibular body length (P=0.0126) than non-snorers. In non-obese females, snorers had significantly greater neck circumferences (P=0.0165), compared with non-snorers. However, there were no statistically significant differences in other variables between non-snorers and snorers.
Conclusion
Anthropometric abnormalities of the mandible and neck, including thick neck circumference in both genders and small mandible size in males, may be relevant contributing factors to snoring in non-obese Asian snorers.
doi:10.3342/ceo.2011.4.1.40
PMCID: PMC3062226  PMID: 21461062
Asian; Population; Snoring; Mandible; Neck
5.  Risk assessment for clinical attachment loss of periodontal tissue in Korean adults 
PURPOSE
The purpose of this study was to assess the prevalence and extent of clinical attachment loss of periodontal tissue and to find out variables related to clinical attachment loss (CAL) in Korean adults older than 40 years of age.
MATERIALS AND METHODS
Data were collected from 2,519 subjects who were part of a cohort study conducted in Ansan city by Korea University Medical School for Korean Genome project. Age, sex, smoking, drinking, fast glucose, blood pressure, obesity and total cholesterol levels were examined. The oral examination included probing pocket depth, gingival recession and CAL of Ramford's teeth. The severity of periodontitis was classified based on the mean value of CAL. The relationship between each risk factor and the severity of CAL was independently estimated using the chi-square test, the test or one-way ANOVA. Multiple regression analysis was used to determine the significance of each factor in the periodontal disease.
RESULTS
The prevalences of clinical attachment between 1 and 3 mm, between 3 and < 5 mm, and ≥ 5 mm were 80.27%, 16.75% and < 1%, respectively. Although the univariate analysis showed age, gender, smoking, fasting glucose, blood pressure and total cholesterol levels were significantly related to the severity of CAL, multiple regression analysis indicated that age (P < .0001), gender (P < .0001) and smoking (P < .05) were only significantly related.
CONCLUSION
Older age, male gender and smoking were significant risk factor for the increase of CAL, and these may be useful indicators of periodontitis high-risk groups.
doi:10.4047/jap.2011.3.1.25
PMCID: PMC3076570  PMID: 21503190
Korean; Periodontal attachment loss; Periodontitis; Epidemiology; Risk factor
6.  Validation of the Korean Integrative Medicine Attitude Questionnaire (IMAQ) 
Korean Journal of Family Medicine  2011;32(3):197-204.
Background
To develop a Korean version of the Integrative Medicine Attitude Questionnaire (IMAQ) in order to evaluate physician attitudes toward integrative medicine/complementary and alternative medicine (CAM).
Methods
We developed a Korean IMAQ through careful translation of the 28-item questionnaire developed by Schmidt et al. A web-based survey was sent via email to 118 primary care physicians in Korea. The complete respose rate wasa 52.5%. The questionnaire's reliability and validity were verified using Cronbach's α, factor analysis, and discriminant analysis.
Results
Although the Korean IMAQ exhibited excellent internal consistency, its validity was insufficient. Our results suggest that Western and Korean physicians may have different understandings of CAM and the concept of holism, as factor analysis showed that incorrectly classified items were mainly part of the holism conceptual domain. Furthermore, the sum of the items within the holism conceptual domain was not significantly different for physicians who had previously received CAM education.
Conclusion
This study developed and tested the first Korean IMAQ. We found that this version of the questionnaire lacks sufficient validity and requires further modification.
doi:10.4082/kjfm.2011.32.3.197
PMCID: PMC3383128  PMID: 22745855
Integrative Medicine; Complementary Medicine; Holism; Medical Education; Attitude
7.  Relationship between tooth loss and carotid intima-media thickness in Korean adults 
PURPOSE
The aim of this study was to examine the relationship between tooth loss and sub-clinical atherosclerosis in Korean adults.
MATERIALS AND METHODS
The subjects were part of a cohort study conducted in Ansan city by the Korea University medical school as part of the Korean Genome project. 749 subjects over than 40 years old were evaluated. After taking panoramic radiography, the amount of tooth loss was calculated. The intima-media thickness (IMT) was assessed by using ultrasonography at the common carotid artery. Traditional cardiovascular risk factors for atherosclerosis were also evaluated. The relationship between tooth loss and the IMT was evaluated using ANOVA with Scheffe's multiple comparison method in univariate analysis. Multiple regression analysis was also performed to determine the significance between the IMT and tooth loss.
RESULTS
With age, tooth loss increased, but there was no significant increase in other traditional cardiovascular risk factors. Univariate analysis revealed the IMT to be positively related with the amount of tooth loss. Regression analysis of the IMT in the anterior and posterior tooth loss revealed that only the posterior tooth loss was significantly related with the IMT at all sites of the common carotid artery (right far wall, P = .015; left far wall, P = .008; right near wall, P < .001; left near wall, P = .001).
CONCLUSION
This study verified the positive relationship between the increased tooth loss at the posterior area and the accumulation of atheroma in arteries.
doi:10.4047/jap.2010.2.4.122
PMCID: PMC3024501  PMID: 21264190
Korean; Tooth loss; Intima-media thickness (IMT); Atherosclerosis
8.  Surveillance of Stool Samples for the Presence of Enterobacter sakazakii among Korean People 
Yonsei Medical Journal  2008;49(6):1017-1022.
Purpose
Enterobacter sakazakii (E. sakazakii) infections are an important cause of life-threatening meningitis, septicemia, and necrotizing enterocolitis in infants. Dried infant formula milk is an important vehicle for E. sakazakii infection. E. sakazakii was isolated in Korea from dried infant formula milk. Although E. sakazakii infection of infants may occur in Korea, its prevalence has not yet been documented. Therefore, we determined the prevalence of E. sakazakii and documented symptoms.
Materials and Methods
Between March and October 2006, 1,146 stool samples were collected from patients at Uijeongbu St. Mary's Hospital. Each fecal swab was dissolved in 10 mL of buffered peptone solution, and enriched culture was streaked onto Druggan-Forsythe-Iversen (DFI) agar. Presumptive E. sakazakii colonies that exhibited a blue-green color during culture on DFI medium were selected. The identity of colonies that developed yellow pigment during culture on TSA was determined using the Vitek system and PCR.
Results
We isolated 4 E. sakazakii strains whose 16S rRNA sequence alignments had a similarity of 99% with those of 3 E. sakazakii ATCC strains.
Conclusion
This is the first report on isolation of E. sakazakii from stool samples and to document the symptoms of Korean patients.
doi:10.3349/ymj.2008.49.6.1017
PMCID: PMC2628025  PMID: 19108027
Enterobacter sakazakii; stool; Korean patients
9.  The prognosis of liver cirrhosis in recent years in Korea. 
Journal of Korean Medical Science  2003;18(6):833-841.
The survival of a recent series of 823 cirrhosis patients who were followed up for a mean of 48 months was analyzed. Cirrhosis was ascribed to alcohol (26%), hepatitis virus B (58%), hepatitis virus C (11%) or both (2%), or was cryptogenic (3%). Features of decompensation were observed in 51% of the patients at entry, and newly developed in 44% of compensated patients within 5 yr. The 5-yr survival after decompensation was 25%. The leading causes of death were liver failure (53%), hepatocellular carcinoma (HCC, 23%), and variceal bleeding (10%). Early detection of HCC significantly improved the survival of cirrhosis patients. Biannual ultrasonography increased the detection rate of small HCC. Mortality of variceal hemorrhage was much lower in patients with Child-Pugh scores from 5 to 8 than in those with scores above 8 (5% vs. 52%). Endoscopic prophylaxis significantly decreased the incidence of first variceal hemorrhage, but the effect was insufficient to improve the rate of survival. Mortality of first spontaneous bacterial peritonitis was 18%. These data suggest that the mortality of major complications of liver cirrhosis has considerably decreased during the last two decades, while there was no remarkable improvement in long-term survival. More efficient management of etiologic factors would be required.
PMCID: PMC3055146  PMID: 14676440

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