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ABSTRACT: Most bone mineral density (BMD) loci were reported in Caucasian genome-wide association studies (GWAS). This study investigated the association between 59 known BMD loci (+200 suggestive SNPs) and DXA-derived BMD in East Asian population with respect to sex and site specificity. We also identified four novel BMD candidate loci from the suggestive SNPs. INTRODUCTION: Most GWAS have reported BMD-related variations in Caucasian populations. This study investigates whether the BMD loci discovered in Caucasian GWAS are also associated with BMD in East Asian ethnic samples. METHODS: A total of 2,729 unrelated Korean individuals from a population-based cohort were analyzed. We selected 747 single-nucleotide polymorphisms (SNPs). These markers included 547 SNPs from 59 loci with genome-wide significance (GWS, p value less than 5 × 10(-8)) levels and 200 suggestive SNPs that showed weaker BMD association with p value less than 5 × 10(-5). After quality control, 535 GWS SNPs and 182 suggestive SNPs were included in the replication analysis. RESULTS: Of the 535 GWS SNPs, 276 from 25 loci were replicated (p < 0.05) in the Korean population with 51.6 % replication rate. Of the 182 suggestive variants, 16 were replicated (p < 0.05, 8.8 % of replication rate), and five reached a significant combined p value (less than 7.0 × 10(-5), 0.05/717 SNPs, corrected for multiple testing). Two markers (rs11711157, rs3732477) are for the same signal near the gene CPN2 (carboxypeptidase N, polypeptide 2). The other variants, rs6436440 and rs2291296, were located in the genes AP1S3 (adaptor-related protein complex 1, sigma 3 subunit) and RARB (retinoic acid receptor, beta). CONCLUSION: Our results illustrate ethnic differences in BMD susceptibility genes and underscore the need for further genetic studies in each ethnic group. We were also able to replicate some SNPs with suggestive associations. These SNPs may be BMD-related genetic markers and should be further investigated.
Osteoporosis International 04/2013; · 4.58 Impact Factor
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ABSTRACT: Radioresistance is one of the main determinants of treatment outcome in oral cancer, but the prediction of radioresistance is difficult. The authors aimed to establish radioresistant oral squamous cell carcinoma (OSCC) cell lines to identify genes with altered expression in response to radioresistance. To induce radioresistant cell lines, the authors treated OSCC cell lines with an accumulated dosage of 60Gy over 30 cycles of radiotherapy. They compared the results from cDNA arrays and proteomics between non-radiated and radioresistant cell lines in order to identify changes in gene expression. Western blot analysis was used to validate the results. The cDNA array revealed 265 commonly up-regulated genes and 268 commonly down-regulated genes in radioresistant cell lines, 30 of which were cancer-related genes. Proteomics identified 51 proteins with commonly altered expression in radioresistant cell lines, 18 of which were cancer-related proteins. Both the cDNA array and proteomics indicated that NM23-H1 and PA2G4 were over-expressed. Western blot analysis showed increased expression of NM23-H1, but not PA2G4, in radioresistant cell lines. The authors concluded that NM23-H1 may be a radioresistance-related gene and over-expression of NM23-H1 could serve as a biomarker to predict radioresistance in OSCC.
International Journal of Oral and Maxillofacial Surgery 11/2012; · 1.51 Impact Factor
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ABSTRACT: Background/objectives:Data are limited on cardiovascular disease (CVD) risk prediction models that include dietary predictors. Using known risk factors and dietary information, we constructed and evaluated CVD risk prediction models.Subjects/methods:Data for modeling were from population-based prospective cohort studies comprised of 9026 men and women aged 40-69 years. At baseline, all were free of known CVD and cancer, and were followed up for CVD incidence during an 8-year period. We used Cox proportional hazard regression analysis to construct a traditional risk factor model, an office-based model, and two diet-containing models and evaluated these models by calculating Akaike information criterion (AIC), C-statistics, integrated discrimination improvement (IDI), net reclassification improvement (NRI) and calibration statistic.Results:We constructed diet-containing models with significant dietary predictors such as poultry, legumes, carbonated soft drinks or green tea consumption. Adding dietary predictors to the traditional model yielded a decrease in AIC (delta AIC=15), a 53% increase in relative IDI (P-value for IDI <0.001) and an increase in NRI (category-free NRI=0.14, P <0.001). The simplified diet-containing model also showed a decrease in AIC (delta AIC=14), a 38% increase in relative IDI (P-value for IDI <0.001) and an increase in NRI (category-free NRI=0.08, P<0.01) compared with the office-based model. The calibration plots for risk prediction demonstrated that the inclusion of dietary predictors contributes to better agreement in persons at high risk for CVD. C-statistics for the four models were acceptable and comparable.Conclusions:We suggest that dietary information may be useful in constructing CVD risk prediction models.European Journal of Clinical Nutrition advance online publication, 14 November 2012; doi:10.1038/ejcn.2012.175.
European journal of clinical nutrition 11/2012; · 3.07 Impact Factor
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ABSTRACT: The size effect on crystal structure has been investigated for nanoscale BaTiO3 powders prepared by hydrothermal methods. The powders were composed of both the cubic and tetragonal phases at room temperature.
The relative volume fraction of the tetragonal phase was found to be approximately 30% by X-ray diffraction and Raman spectroscopy.
High resolution transmission electron microscopy (HRTEM) revealed that the surface region of the powders was of the tetragonal
phase, while the core was of the cubic phase.
Metals and Materials International 04/2012; 13(4):329-333. · 1.18 Impact Factor
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ABSTRACT: Although obesity and osteoporosis are important public health problems, the effect of fat mass on bone mass remains controversial. This study demonstrated that fat mass was inversely related to bone mineral content, and abdominal obesity was significantly associated with bone mineral content independent of total fat mass.
Obesity and osteoporosis, two disorders of body composition, have become increasingly important public health problems throughout the world. However, the effect of fat mass on bone mass remains controversial. This study investigates the effect of fat mass and regional fat distribution on bone mass within a community-dwelling cohort.
A total of 3,042 subjects (1,284 men, 362 premenopausal women, and 1,396 postmenopausal women) were studied. Fat mass, percent fat mass, lean mass, percent lean mass, and bone mineral content (BMC) were measured by dual energy X-ray absorptiometry.
Fat mass and percent fat mass decreased significantly across increasing tertiles of BMC in all three subgroups (men, premenopausal and postmenopausal women). In contrast, lean mass and percent lean mass increased significantly across tertiles of BMC in men, and a similar trend was also identified in postmenopausal women. Interestingly, although correlation analysis showed a positive association between fat mass and BMC (p < 0.05), this association became negative after controlling for age and weight (p < 0.05). Finally, in premenopausal and postmenopausal women, subjects with the lowest waist circumference (WC) had the highest BMC in the higher three quartiles of percent fat mass after adjusting for age and weight (p < 0.05), indicating that abdominal obesity is associated with BMC independent of total fat mass.
This study demonstrated that fat mass was inversely related to BMC after removing the mechanical loading effect in Korean men and women. Moreover, abdominal obesity as measured by WC was significantly associated with BMC independent of total fat mass.
Osteoporosis International 10/2011; 23(7):2009-16. · 4.58 Impact Factor
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ABSTRACT: Background Because inflammatory cytokines are known to be potent inducers of matrix metalloproteinases (MMPs), and MMPs themselves can promote inflammation, we speculated that MMP activation might be involved in the pathogenesis of Henoch–Schönlein purpura (HSP) vasculitis.Objectives To investigate the gene expression profile of all known MMPs and tissue inhibitors of metalloproteinases (TIMPs) in children with HSP and to examine the role, if any, of MMPs in the pathogenesis of HSP.Methods Peripheral blood samples were obtained from 10 patients with HSP (nine were in the acute stage, one had HSP nephritis) and four healthy controls. Peripheral blood samples were also taken from the nine patients with HSP when they reached the convalescent stage of the disease. From these samples, total RNA was purified and gene expressions were measured using real-time polymerase chain reaction.Results MMP-8 expression was decreased in patients with arthralgia (P = 0·038), and MMP-3 (P = 0·03) and TIMP-4 expressions (P = 0·016) were elevated in HSP patients with nephritis. Soft tissue oedema was associated with decreased expressions of MMP-26 (P = 0·038) and MMP-28 (P = 0·038). MMP-1, MMP-8, MMP-9, MMP-10, MMP-13, MMP-16 and MMP-26 levels were significantly higher in patients in the acute stage of HSP than in normal controls (P < 0·05). MMP-9 (P = 0·097) and MMP-19 (P = 0·054) levels decreased to borderline significance in patients in the convalescent stage compared with those in the acute stage. The duration of steroid administration was negatively correlated with MMP-1, MMP-2, MMP-7, MMP-10, MMP-12, MMP-19, MMP-23 and TIMP-1 levels (P < 0·05), suggesting a suppressive effect of steroids on the expressions of MMPs and TIMPs.Conclusions This is the first study to describe the expression profile of all known MMPs and TIMPs in children with HSP, and our results suggested that abnormal levels of MMP and TIMP activity may have a role in the pathogenesis of HSP.
British Journal of Dermatology 05/2011; 164(6):1348 - 1355. · 3.67 Impact Factor
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ABSTRACT: Because inflammatory cytokines are known to be potent inducers of matrix metalloproteinases (MMPs), and MMPs themselves can promote inflammation, we speculated that MMP activation might be involved in the pathogenesis of Henoch-Schönlein purpura (HSP) vasculitis.
To investigate the gene expression profile of all known MMPs and tissue inhibitors of metalloproteinases (TIMPs) in children with HSP and to examine the role, if any, of MMPs in the pathogenesis of HSP.
Peripheral blood samples were obtained from 10 patients with HSP (nine were in the acute stage, one had HSP nephritis) and four healthy controls. Peripheral blood samples were also taken from the nine patients with HSP when they reached the convalescent stage of the disease. From these samples, total RNA was purified and gene expressions were measured using real-time polymerase chain reaction. Results: MMP-8 expression was decreased in patients with arthralgia (P = 0·038), and MMP-3 (P = 0·03) and TIMP-4 expressions (P = 0·016) were elevated in HSP patients with nephritis. Soft tissue oedema was associated with decreased expressions of MMP-26 (P = 0·038) and MMP-28 (P = 0·038). MMP-1, MMP-8, MMP-9, MMP-10, MMP-13, MMP-16 and MMP-26 levels were significantly higher in patients in the acute stage of HSP than in normal controls (P < 0·05). MMP-9 (P = 0·097) and MMP-19 (P = 0·054) levels decreased to borderline significance in patients in the convalescent stage compared with those in the acute stage. The duration of steroid administration was negatively correlated with MMP-1, MMP-2, MMP-7, MMP-10, MMP-12, MMP-19, MMP-23 and TIMP-1 levels (P < 0·05), suggesting a suppressive effect of steroids on the expressions of MMPs and TIMPs.
This is the first study to describe the expression profile of all known MMPs and TIMPs in children with HSP, and our results suggested that abnormal levels of MMP and TIMP activity may have a role in the pathogenesis of HSP.
British Journal of Dermatology 03/2011; 164(6):1348-55. · 3.67 Impact Factor
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Journal of perinatology: official journal of the California Perinatal Association 11/2010; 30(11):760-2. · 1.59 Impact Factor
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ABSTRACT: Human papilloma virus (HPV) infection is controversial as a causative factor in oral tongue cancer. This study aimed to clarify whether HPV directly affects the carcinogenesis and biological behaviour of oral tongue cancer by analyzing HPV prevalence, the physical status of the virus and clinicopathological parameters. Archival tissue was obtained from 36 patients diagnosed with T1 and T2 oral tongue cancer and 25 normal controls. HPV genotyping chip and real-time polymerase chain reaction were used to determine the prevalence, phenotype and physical status of HPV to clarify whether HPV directly affects oncogenesis. The results were also compared with clinicopathological parameters. HPV was detected in 36% (13/36) of oral tongue cancer patients, compared with 4% (1/25) of the control. In the HPV-positive group of oral tongue cancers, HPV-16 was the most common type and its prevalence rate was 85% (11/13). Of the HPV-16 infected oral tongue cancers, the integration rate of HPV-16 was 55% (6/11). The HPV-16 positive group showed shallower stromal invasion than the HPV-16 negative group (p=0.045). HPV-16 may be one of the causative factors in early squamous cell oral tongue carcinoma and be associated with its depth of invasion.
International Journal of Oral and Maxillofacial Surgery 07/2010; 39(7):678-83. · 1.51 Impact Factor
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ABSTRACT: Cancer stem cells (CSCs) have been identified in solid tumors and cancer cell lines. In this study, we isolated a series of cancer cell clones, which were heterogeneous in growth rate, cell cycle distribution and expression profile of genes and proteins, from ovarian tumor specimens of a patient and identified a sub-population enriched for ovarian CSCs defined by CD24 phenotype. Experiments in vitro demonstrated CD24(+) sub-population possessed stem cell-like characteristics of remaining quiescence and more chemoresistant compared with CD24(-) fraction, as well as a specific capacity for self-renewal and differentiation. In addition, injection of 5 x 10(3) CD24(+) cells was able to form tumor xenografts in nude mice, whereas equal number of CD24(-) cells remained nontumorigenic. We also found that CD24(+) cells expressed higher mRNA levels of some 'stemness' genes, including Nestin, beta-catenin, Bmi-1, Oct4, Oct3/4, Notch1 and Notch4 which were involved in modulating many functions of stem cells, and lower E-cadherin mRNA level than CD24(-) cells. Altogether, these observations suggest human ovarian tumor cells are organized as a hierarchy and CD24 demarcates an ovarian cancer-initiating cell population. These findings will have important clinical applications for developing effective therapeutic strategies to treat ovarian cancer.
Oncogene 03/2010; 29(18):2672-80. · 6.37 Impact Factor
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ABSTRACT: There are few data available regarding the association between hallux valgus and pain or functional limitation. We determined the prevalence of hallux valgus in a rural Korean population aged between 40 and 69 years, and its association with pain and function. A total of 563 subjects was examined using the foot health status questionnaire, the Short Form-36 questionnaire and weight-bearing anteroposterior radiographs. Hallux valgus was present in 364 subjects (64.7%). It did not significantly correlate with age and was more common in women. Of the 364 subjects, 48 (13.2%) had moderate or greater deformity, defined as a hallux valgus angle > 25 degrees . This was significantly associated with pain, worse function and worse foot health. The putative risk factors associated with painful hallux valgus were female gender, low educational attainment and the presence of pain in the knee.
Journal of Bone and Joint Surgery - British Volume 04/2009; 91(4):494-8. · 2.83 Impact Factor
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ABSTRACT: Nano-grained BaTiO3 ceramics were prepared by two-step sintering; nanoscale BaTiO3 powders of 100 and 500 nm in size were used as starting materials. The phase transition and physical features of the BaTiO3 ceramics were investigated as a function of the grain size and the boundary decoration. With increasing the grain size, the relative volume fraction of a tetragonal phase was increased; this seems to be due to the variation in boundary tension with grain size. The relation of the physical features of the nano-grained BaTiO3 ceramics with the structural variation is discussed in terms of process parameters.
Journal of Nanoscience and Nanotechnology 03/2009; 9(2):1518-21. · 1.56 Impact Factor
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ABSTRACT: In oral tongue cancer, tumor depth is crucial for cervical lymph node metastasis. There is no standardized method to predict tumor invasion or deciding who should undergo selective neck dissection. In this study, calculated MRI invasion depth was compared with histopathologic (HP) invasion depth to find a correlation, and determine a cutoff value of invasion depth that predicts occult neck node metastasis. 50 patients, diagnosed with T1 or T2 oral tongue cancer originating from the lateral border of the tongue, underwent MRI screening and received surgical excision as primary treatment. MRI and HP invasion depths were compared and the cutoff value determined. The invasion depth to determine the presence of nodal metastasis where summation of specificity and sensitivity was greatest was 8.5mm HP, 10.5mm in T1 weighted enhanced axial image, and 11.5mm in T2 weighted MRI axial image. The relation coefficient of T2 weighted MRI invasion depth and HP depth was 0.851, and accuracy 84%, all of which showed higher correlation compared with T1 weighted enhanced axial image. HP depth was significantly correlated with survival rate. The measurement of invasion depth using MRI is a prerequisite for determining a surgical plan in early oral tongue cancer.
International Journal of Oral and Maxillofacial Surgery 03/2009; 38(6):653-60. · 1.51 Impact Factor
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ABSTRACT: The number of cases of the metabolic syndrome is increasing dramatically in Western countries. However, the evaluation of the metabolic syndrome is limited in Asian countries. Thus, our objectives were: 1) to investigate parameters of the metabolic syndrome defined by the National Cholesterol Education Program (NCEP)-Adult Treatment Panel III (ATPIII) in the subjects representing Korean general population and 2) the modification of which factor is most effective in reducing the metabolic syndrome. A total of 10,044 (5024 rural and 5020 urban) Korean men and women in the age range 40-69 yr voluntarily participated in this community-based cross-sectional study (a rural and an urban community was selected). Anthropometric parameters (weight, height, waist and hip circumference and blood pressure), social factors (smoking, alcohol, exercise and education status) as well as biochemical parameters (fasting glucose and insulin, lipids and body composition) were measured. Twenty-six point one per cent of the total subjects were classified as having the metabolic syndrome. Age- and sex-adjusted prevalences were 29.3 and 22.3% in the rural and urban community, respectively (p< 0.01). Abdominal obesity (46.9%) and high blood pressure (45.2%) were major components in the rural community; hypertriglyceridemia (37.6%) and low HDL-cholesterolemia (37.0%) in the urban community. In conclusion, abdominal obesity in the rural community and dyslipidemia in the urban community should be a main subject of intervention, aimed at reducing the prevalence of the metabolic syndrome in Korea. Given the rapid progression of the Korean economy over the past 30 yr, the prevalence of the metabolic syndrome is expected to increase continuously. A strategy to prevent this expected extraordinary event should be conducted at a national level.
Journal of endocrinological investigation 05/2006; 29(4):313-9. · 1.57 Impact Factor
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N H Cho,
C W Ahn,
J Y Park,
T Y Ahn,
H W Lee,
T S Park,
I J Kim,
K Pomerantz,
C Park,
K C Kimm,
D S Choi
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ABSTRACT: We investigated the prevalence and risk factors for developing erectile dysfunction (ED) in 1312 Korean men with diabetes in a multicentre study.
We used the modified International Index for Erectile Function-5 criteria to identify mild, moderate and complete ED. A standardized face-to-face questionnaire was used by trained interviewers, and validated against telephone interviews. We recorded the duration of diabetes, level of glycaemic control, vital signs, complications, exercise and alcohol and smoking habits, and diabetes treatments used. Results The mean age and median duration of diabetes were 53.8 +/- 6.65 and 6 years (range 1-43), respectively. The mean HbA(1c) and fasting glucose levels were 7.9 +/- 1.65% and 8.6 +/- 2.82 mmol/l, respectively. The overall prevalences of mild, moderate, complete ED and all ED (mild-to-complete) were 20.1, 19.5, 25.8 and 65.4%, respectively. ED was more common with age, reaching 79.3% in men aged > 60 years. Subjects aged > 60 years and with a duration of diabetes > 10 years were at greatest risk for all ED (OR = 10.4, 95% CI 5.8-18.5, P < 0.001) and complete ED (OR = 13.2, 95% CI 7.3-23.9, P < 0.001) when compared with the reference group (age 40-50 years with duration < 6 years). Age, duration of diabetes, HbA(1c), insulin use, neuropathy and macrovascular complications were positively associated with ED, but alcohol consumption and exercise habits were negatively associated.
The prevalence of complete ED was approximately six times higher than in the general population.
Diabetic Medicine 02/2006; 23(2):198-203. · 2.90 Impact Factor
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Urology 01/2006; 68:101-102. · 2.43 Impact Factor
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ABSTRACT: Interrelationship between C-reactive protein (CRP) and metabolic syndrome (MS) was evaluated in a community-based cohort of 9773 Koreans aged 40-69 years. Metabolic syndrome was defined by criteria of the National Cholesterol Education Program. CRP was measured by validated high-sensitivity assay. The median CRP level was 1.4 mg/1, and significantly increased as the number of components of MS increased (P trend <0.001). CRP levels were significantly but marginally correlated with waist circumference (r=0.18), triglyceride (r=0.14), blood pressure (r=0.11), HDL-cholesterol (r=-0.10), and fasting glucose (r=0.09) (all P values<0.01). Odds ratios of the highest quartile of CRP for each component of MS; i.e., waist circumference, triglyceride, glucose metabolism, blood pressure, and HDL-cholesterol were 2.36, 1.79, 1.70, 1.32 and 1.28, respectively. The highest quartile of CRP was independently associated with 1.72-fold increased risk of MS in our logistic regression model adjusted for age, sex, BMI, and smoking. This study demonstrated that CRP is a strong associating factor of MS in Korean population. We recommend further evaluation of CRP levels in the other Asian ethnic groups to establish biological plausibility as the risk factor for MS in all ethnic groups.
Diabetes Research and Clinical Practice 11/2005; 70(2):126-33. · 2.75 Impact Factor
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ABSTRACT: In this paper, we have proposed a method for renal cell carcinoma (RCC) grading, using a three-dimensional (3D) quantitative analysis of cell nuclei based on digital image cytometry. We acquired volumetric RCC data for each grade using confocal laser scanning microscopy (CLSM) and developed a method for grading RCC using 3D visualization and quantitative analysis of cell nuclei. First, we used a method of segmenting cell nuclei based on Pun's method. Second, to determine quantitative features, we used a 3D labeling method based on slice information. After applying the labeling algorithm, we determined the measurements of cell nuclei using 3D quantitative analysis. To evaluate which of the quantitative features provided by 3D analysis could contribute to diagnostic information and could increase accuracy in nuclear grading, we analyzed statistical differences in 3D features among the grades. We compared features measured in two dimensions (diameter, area, perimeter, and circularity) with features measured in three dimensions (volume, surface area, and spherical shape factor) between identical cell nuclei by using regression analysis. For 3D visualization, we used a contour-based method for surface rendering. We found a statistically significant correlation between the nuclear grade and the 3D morphological features. Comparing our results to an ideal RCC grading system, we found that our nuclear grading system based on the 3D features of a cell nucleus provides distinct dividing points between grades and also provides data that can be easily interpreted for diagnoses. 3D visualization of cell nuclei offers a realistic display and additional valuable medical information that can lead to an objective diagnosis. This method could overcome the limitations inherent in 2D analysis and could improve the accuracy and reproducibility of quantification of cell nuclei. Our study showed that a nuclear grading system based on the 3D features of a cell nucleus might be an ideal grading system.
Enterprise networking and Computing in Healthcare Industry, 2005. HEALTHCOM 2005. Proceedings of 7th International Workshop on; 07/2005
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ABSTRACT: To clarify the fine structure of koilocytes and correlate this with genetic aberration of the G2 checkpoint.
Three dimensional reconstruction from confocal fluorescent images, together with functional assays for key molecules of the G2 checkpoint-cdc2 and cyclin B1-was performed in human uterine cervical samples. After confirming 22 human papillomavirus (HPV) types using a DNA chip from 30 cervical swabs, previously confirmed as 15 cervical low grade and 15 high grade intraepithelial lesions, the activity of molecules involved in the G2 checkpoint was evaluated using western blotting for cyclin B1, cdc2, and phospho-cdc2 (Y15 and T161), a nuclear extraction fractional assay, and a reverse transcription polymerase chain reaction assay. In addition, three dimensional confocal image restoration was performed on confirmed cervical intraepithelial neoplasia tissue samples.
T161 phospho-cdc2 and cyclin B1 expression was higher in HPV infected cervical lesions than in normal samples. Immunofluorescence, revealed that cyclin B1 was present predominantly in the nuclei of HPV infected cells, confirming the results of the nuclear fractional assay. On restoration of three dimensional confocal images, the multinucleation of koilocytes was revealed to be multilobation of a single nucleus, rather than true multinucleation. This multilobation appeared to be associated with chromosomal instability and aberration of the G2 checkpoint.
The multiple nuclei of koilocytes are in fact multilobation of a single nucleus, and this phenomenon is associated with upregulation of gene products related to the G2 checkpoint.
Journal of Clinical Pathology 07/2005; 58(6):576-82. · 2.31 Impact Factor
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Histopathology 11/2003; 30(6):595 - 598. · 3.08 Impact Factor
