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1.  Simplified fistula dilation technique and modified stent deployment maneuver for EUS-guided hepaticogastrostomy 
AIM: To evaluate the success rates, procedural time and adverse event rates of the modified methods in endoscopic ultrasonography-guided hepaticogastrostomy (EUS-HGS).
METHODS: Twenty-eight patients in a prospective case series who underwent EUS-HGS (phase I). Forty-six patients in a matched case-control study (phase II). The simplified technique for fistula dilation was the primary use of a 4 mm balloon catheter with a stainless steel stylet. The stent deployment was modified by deploying the metal stent inside a bile duct (half of the stent) under EUS and fluoroscopic guidance and gently pulling the echoendoscope after full deployment of the stent inside the echoendoscope channel (remaining portion of the stent) under fluoroscopic guidance. This cohort was compared with a matched historical cohort.
RESULTS: In phase I, the technical and clinical success with the modified method was 96% (27/28) and 89% (24/27 as per-protocol analysis). The overall adverse event rate was 7%. In phase II, there was no difference in technical and clinical success, stent patency and overall adverse events in each group. However, the procedural time (15.3 ± 5.2 min vs 22.3 ± 6.0 min, P < 0.001) and early adverse events (0% vs 26%, P = 0.02) were statistically improved in case cohort compared with control cohort.
CONCLUSION: Compared with the conventional EUS-HGS technique, the procedural time was shorter and early adverse events were less frequent with our simplified and modified technique.
PMCID: PMC4009540  PMID: 24803818
Endoscopic ultrasonography; Biliary drainage; Hepaticogastrostomy; Treatment outcome; Adverse event
2.  Expansive Generation of Functional Airway Epithelium From Human Embryonic Stem Cells 
This study revealed the potential of human embryonic stem cells (hESCs) to produce multipotent lung progenitors using a combined growth factor and physical culture approach. This approach allowed in vivo assessment, which demonstrated that only fully differentiated hESC-derived airway cells were retained in the distal airway, where they aided in physiological recovery in immunocompromised mice receiving airway injury. This study provides a basis for translational applications of hESCs for lung diseases.
Production of human embryonic stem cell (hESC)-derived lung progenitors has broad applicability for drug screening and cell therapy; however, this is complicated by limitations in demarcating phenotypic changes with functional validation of airway cell types. In this paper, we reveal the potential of hESCs to produce multipotent lung progenitors using a combined growth factor and physical culture approach, guided by the use of novel markers LIFRα and NRP1. Lung specification of hESCs was achieved by priming differentiation via matrix-specific support, followed by air-liquid interface to allow generation of lung progenitors capable of in vitro maturation into airway epithelial cell types, resulting in functional characteristics such as secretion of pulmonary surfactant, ciliation, polarization, and acquisition of innate immune activity. This approach provided a robust expansion of lung progenitors, allowing in vivo assessment, which demonstrated that only fully differentiated hESC-derived airway cells were retained in the distal airway, where they aided in physiological recovery in immunocompromised mice receiving airway injury. Our study provides a basis for translational applications of hESCs for lung diseases.
PMCID: PMC3902293  PMID: 24300555
Acute lung injury; Air-liquid interface; Differentiation; Human embryonic stem cells
3.  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.
PMCID: PMC3464075  PMID: 22548442
4.  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.
PMCID: PMC3291039  PMID: 22454686
5.  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.
PMCID: PMC3271295  PMID: 22323869
Amyotrophic Lateral Sclerosis; Ursodeoxycholic Acid; Cross-Over Trial
6.  Clinical Implications of Mandible and Neck Measurements in Non-Obese Asian Snorers: Ansan City General Population-Based Study 
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.
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).
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.
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.
PMCID: PMC3062226  PMID: 21461062
Asian; Population; Snoring; Mandible; Neck
7.  Risk assessment for clinical attachment loss of periodontal tissue in Korean adults 
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.
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.
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.
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.
PMCID: PMC3076570  PMID: 21503190
Korean; Periodontal attachment loss; Periodontitis; Epidemiology; Risk factor
8.  Validation of the Korean Integrative Medicine Attitude Questionnaire (IMAQ) 
Korean Journal of Family Medicine  2011;32(3):197-204.
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).
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.
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.
This study developed and tested the first Korean IMAQ. We found that this version of the questionnaire lacks sufficient validity and requires further modification.
PMCID: PMC3383128  PMID: 22745855
Integrative Medicine; Complementary Medicine; Holism; Medical Education; Attitude
9.  Relationship between tooth loss and carotid intima-media thickness in Korean adults 
The aim of this study was to examine the relationship between tooth loss and sub-clinical atherosclerosis in Korean adults.
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.
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).
This study verified the positive relationship between the increased tooth loss at the posterior area and the accumulation of atheroma in arteries.
PMCID: PMC3024501  PMID: 21264190
Korean; Tooth loss; Intima-media thickness (IMT); Atherosclerosis
10.  Surveillance of Stool Samples for the Presence of Enterobacter sakazakii among Korean People 
Yonsei Medical Journal  2008;49(6):1017-1022.
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.
We isolated 4 E. sakazakii strains whose 16S rRNA sequence alignments had a similarity of 99% with those of 3 E. sakazakii ATCC strains.
This is the first report on isolation of E. sakazakii from stool samples and to document the symptoms of Korean patients.
PMCID: PMC2628025  PMID: 19108027
Enterobacter sakazakii; stool; Korean patients
11.  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

Results 1-11 (11)