Seong Yeon Kim

Konkuk University Medical Center, Changnyeong, South Gyeongsang, South Korea

Are you Seong Yeon Kim?

Claim your profile

Publications (102)279.05 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Among the various diagnostic criteria for insulinoma, the ratio criteria have been controversial. However, the amended insulin-glucose ratio exhibited excellent diagnostic performance in a recent retrospective cohort study, although it has not yet been validated in other patient cohorts. We examined the diagnostic performance of the current criteria of the Endocrine Society, insulin-glucose ratio, C-peptide-glucose ratio, and amended ratios in terms of differentiating insulinomas.
    Endocrinology and metabolism (Seoul, Korea). 07/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: The short Synacthen test (SST) is widely used as alternative test to the insulin tolerance test (ITT) to investigate central adrenal insufficiency (CAI), but the methodology and cut-off values of the SST are controversial. Our aim was to evaluate the cut-off value of the ITT in normal subjects and to assess the different cutoff values of the high-dose SST (250 μg, HDT) and the low-dose SST (1 μg, LDT) in subjects with suspected CAI SUBJECTS AND METHODS: We conducted ITTs in 208 normal subjects to establish the cut-off value for the ITT, and 28 of those subjects underwent the HDT and LDT. From 1999 to 2007, 182 patients with suspected CAI were recruited and underwent ITTs, LDTs and HDTs to establish cut-off values and compare the diagnostic accuracy between the LDT and HDT. The 95(th) percentile of the peak cortisol level during the ITT in the normal control subjects was 14.8 μg/dl. Receiver-operator characteristics (ROC) analysis revealed that the optimal cut-off values of peak cortisol in the LDT and HDT in patients with suspected CAI were 15.8 and 17.4 μg/dl, respectively. However, the cut-off values from normative data (mean-2SD) were 18.3 μg/dl for the LDT and 20.5 μg/dl for the HDT in normal control. The optimal cut-off values of SSTs needed to be individualized according to the type of SST and tested patient population. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 01/2014; · 3.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 17α-hydroxylase/17,20-lyase deficiency is a rare form of congenital adrenal hyperplasia, characterized by hypertension and sexual infantilism and caused by loss-of-function mutations in CYP17A1. This study investigated the clinical and molecular characteristics of six adults with 17α-hydroxylase/17,20-lyase deficiency and the functional consequences of a novel CYP17A1 mutation. Six phenotypic females, three with 46,XY and three with 46,XX karyotypes, presented with primary amenorrhea and hypertension. All had elevated levels of plasma adrenocorticotropic hormone, serum gonadotropin, progesterone, and 11-deoxycorticosterone, and reduced testosterone and dehydroepiandrosterone sulfate (DHEA-S). All coding exons and flanking intronic sequences of CYP17A1 were directly sequenced using genomic DNA. Wild-type and mutant CYP17A1 cDNAs were inserted into the pcDNA3.1/V5-His-P450c17 vector, and transiently expressed in COS-7 cells. This was followed by an assessment of 17α-hydroxylase and 17,20-lyase activities by measuring the conversions of progesterone to 17-hydroxyprogesterone and 17-hydroxypregnenolone to DHEA. The mutation analysis identified one patient with compound heterozygosity for p.H373L and p.W406L, one with compound heterozygosity for p.H373L and p.A174E, three with compound heterozygosity for p.Y329fs and p.H373L, and one with homozygosity for p.H373L. An in vitro functional analysis of the novel p.W406L mutation revealed a complete loss of 17α-hydroxylase/17, 20-lyase activities. p.H373L was the most common mutation among these Korean patients, consistent with the high allele frequency of p.H373L in Chinese and Japanese populations, suggesting possible founder effects in Asian countries. The novel p.W406L mutation caused a complete loss of both catalytic activities, indicating that this amino acid is critical for P450c17 function.
    Metabolism: clinical and experimental 10/2013; · 3.10 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of our study was to assess the frequency of germline mutations and develop the genetic testing strategy in patients with apparently sporadic pheochromocytoma/paraganglioma (PPGL) in Korea. We included 53 patients diagnosed with nonsyndromic PPGL without a family history of PPGLs in three referral centers from 2004 to 2011. Succinate dehydrogenase complex B (SDHB), succinate dehydrogenase complex D (SDHD), Von Hippel-Lindau (VHL), and RET genes were examined by direct sequencing and multiple ligation-dependent probe amplification. The study patients were composed of 26 men and 27 women, and mean age was 50.1 ± 13.5 years. The frequency of germline mutations was 13.2% (7/53): RET (n =2), VHL (n = 1), SDHB (n = 2), SDHD (n = 2). Six of seven mutation carriers were diagnosed before the age of 50 years. One of two patients harboring an SDHB mutation had malignant PPGLs. One patient with multifocal head and neck PGL and PHEO carried a SDHD mutation. The carriers of germline mutations in patients with apparently sporadic PPGL were 13.2% in our study. We recommend genetic testing in patients under 50 years and SDHD genetic testing in patients with multifocal PPGLs. In malignant PPGLs, SDHB genetic testing may be performed.
    Clinical Genetics 10/2013; · 4.25 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Constitutive androstane receptor (CAR) was originally identified as xenobiotic sensor that regulates the expression of cytochrome P450 genes. However, recent studies suggest that this nuclear receptor is also involved in the regulation of energy metabolism including glucose and lipid homeostasis. This study investigated the role of CAR in the regulation of bone mass in vivo using CAR(-/-) mice. Endogenous mRNA expression of CAR was observed in both primary osteoblasts and osteoclast precursors. CAR(-/-) mice have exhibited significant increase in whole body bone mineral density (BMD) by 9.5% (p < 0.01) and 5.5% (p < 0.05) at 10 and 15 weeks of age, respectively, compared with WT mice in males. Microcomputed tomography analysis of proximal tibia demonstrated a significant increase in trabecular bone volume (62.7%), trabecular number (54.1%) in male CAR(-/-) mice compared with WT mice. However, primary culture of calvarial cells exhibited no significant changes in osteogenic differentiation potential between CAR(-/-) and WT. In addition, the number of tartrate-resistant acid-phosphatase positive osteoclasts in the femur and serum level of CTx was not different between CAR(-/-) and WT mice. The higher BMD and microstructural parameters were not observed in female mice. Interestingly, serum level of testosterone in male CAR(-/-) mice was 2.5-fold higher compared with WT mice and the mRNA expressions of Cyp2b9 and 2b10 in the liver, which regulate testosterone metabolism, were significantly down-regulated in male CAR(-/-) mice. Furthermore, the difference in BMD between CAR(-/-) and WT mice disappeared at 8 weeks after performing orchiectomy. CAR(-/-) mice also exhibited significant increase in serum1,25(OH)2 D3 levels but Cyp 27B1 which converts 25(OH)D3 to 1,25(OH)2 D3 was significantly down-regulated compared to WT mice. These results suggest that in vivo deletion of CAR resulted in higher bone mass, which appears to be a result from reduced metabolism of testosterone due to down-regulation of Cyp2b. J. Cell. Physiol. © 2013 Wiley Periodicals, Inc.
    Journal of Cellular Physiology 09/2013; · 4.22 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Women with a history of gestational diabetes mellitus (GDM) are at increased risk of future development of type 2 diabetes. Recently, over 65 genetic variants have been confirmed to be associated with diabetes. We investigated whether this genetic information could improve the prediction of future diabetes in women with GDM. This was a prospective cohort study consisting of 395 women with GDM who were followed annually with an OGTT. A weighted genetic risk score (wGRS), consisting of 48 variants, was assessed for improving discrimination (C statistic) and risk reclassification (continuous net reclassification improvement [NRI] index) when added to clinical risk factors. Among the 395 women with GDM, 116 (29.4%) developed diabetes during a median follow-up period of 45 months. Women with GDM who went on to develop diabetes had a significantly higher wGRS than those who did not (9.36 ± 0.92 vs 8.78 ± 1.07; p < 1.56 × 10(-7)). In a complex clinical model adjusted for age, prepregnancy BMI, family history of diabetes, blood pressure, fasting glucose and fasting insulin concentration, the C statistic marginally improved from 0.741 without the wGRS to 0.775 with the wGRS (p = 0.015). The addition of the wGRS to the clinical model resulted in a modest improvement in reclassification (continuous NRI 0.430 [95% CI 0.218, 0.642]; p = 7.0 × 10(-5)). In women with GDM, who are at high risk of diabetes, the wGRS was significantly associated with the future development of diabetes. Furthermore, it improved prediction over clinical risk factors.
    Diabetologia 09/2013; · 6.49 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Growing evidence shows the possibility of role of microRNAs (miRNA) in regulating bone mass. We investigated the change of miRNAs and mRNA expression profiles in bone tissue in ovariectomized mice model and evaluated regulatory mechanism of bone mass mediated by miRNAs in estrogen deficiency state. Eight-week old female C3H/HeJ mice underwent ovariectomy (OVX) or sham operation (Sham-op) and their femur and tibia were harvested to extract total bone RNAs after 4 weeks for microarray analysis. Eight miRNAs (miR-127, -133a, -133a*, -133b, -136 -206, -378, -378*) were identified to be upregulated after OVX while one miRNA (miR-204) was downregulated. Concomitant analysis of mRNA microarray revealed that 658 genes were differentially expressed between OVX and Sham-op mice. Target prediction of differentially expressed miRNAs identified potential targets and integrative analysis using the mRNA microarray results showed that PPARγ and CREB pathways are activated in skeletal tissues after ovariectomy. Among the potential candidates of miRNA, we further studied the role of miR-127 in vitro, which exhibited the greatest changes after OVX. We also studied the effects of miR-136, which has not been studied in the context of bone mass regulation. Transfection of miR-127 inhibitor has enhanced osteoblastic differentiation in UAMS-32 cells as measured by alkaline phosphatase activities and mRNA expression of osteoblast-specific genes while miR-136 precursor has inhibited osteoblastic differentiation. Furthermore, transfection of both miR-127 and miR-136 inhibitors enhanced the osteocyte-like morphological changes and survival in MLO-Y4 cells while precursors of miR-127 and -136 has aggravated dexamethasone-induced cell death. Both of the precursors enhanced osteoclastic differentiation in bone marrow macrophages, indicating that both miR-127 and -136 are negatively regulating bone mass. Taken together, these results suggest a novel insight into the association between distinct miRNAs expression and their possible role through regulatory network with mRNAs in the pathogenesis of estrogen deficiency induced osteoporosis.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 08/2013; · 6.04 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Context:The widespread use of thyroid tests in asymptomatic individuals identifies many patients with transient subclinical hypothyroidism.Objective:To determine the effect of seasonal change on serum TSH levels and the transition between subclinical hypothyroid and euthyroid status.Design, Setting, and Subjects:This was a retrospective longitudinal study of 1751 subclinical hypothyroid and 28096 euthyroid subjects aged over 18 years who underwent serial thyroid function tests at a health screening center between October 2003 and May 2011. Main Outcome Measures:Age-adjusted geometric mean values of the TSH level by month were calculated using linear mixed models. Adjusted odds ratios of test season and multiple baseline clinical factors were determined using generalized estimating equations.Results:During median 36 months of follow-up, 57.9% of subclinical hypothyroid subjects reverted to euthyroidism, and 4.3% of euthyroid subjects developed subclinical hypothyroidism. The monthly distribution of follow-up TSH levels indicated a biphasic pattern, i.e., an increase during the winter-spring season and a decrease during the summer-fall season, with a maximal TSH difference of 0.69 mIU/L in subclinical hypothyroid and 0.30 mIU/L in euthyroid subjects. Normalization of subclinical hypothyroidism was increased 1.4-fold in follow-up tests during the summer-fall follow-up, whereas subclinical hypothyroidism increased 1.4-fold in euthyroid subjects during the winter-spring follow-up.Conclusions:The season in which thyroid testing was performed was independently related to the transition between subclinical hypothyroid and euthyroid status. Seasonal variations in TSH concentration should be considered before deciding on treatment of subclinical hypothyroidism, particularly in the areas with a wide annual temperature range.
    The Journal of Clinical Endocrinology and Metabolism 06/2013; · 6.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We investigated characteristics associated with the efficacy of dipeptidyl peptidase-4 inhibitors (DPP4i) in Korean patients with type 2 diabetes. We reviewed medical records of 477 patients who had taken sitagliptin or vildagliptin longer than 40 weeks. Response to DPP4i was evaluated with HbA1c change after therapy (ΔHbA1c). The Student's t-test between good responders (GR: ΔHbA1c > 1.0%) and poor responders (PR: ΔHbA1c < 0.5%), a correlation analysis among clinical parameters, and a linear multivariate regression analysis were performed. The mean age was 60 yr, duration of diabetes 11 yr and HbA1c was 8.1%. Baseline fasting plasma glucose (FPG), HbA1c, C-peptide, and creatinine were significantly higher in the GR compared to the PR. Duration of diabetes, FPG, HbA1c, C-peptide and creatinine were significantly correlated with ΔHbA1c. In the multivariate analysis, age (r(2) = 0.006), duration of diabetes (r(2) = 0.019), HbA1c (r(2) = 0.296), and creatinine levels (r(2) = 0.024) were independent predictors for the response to DPP4i. Body mass index and insulin resistance were not associated with the response to DPP4i. In conclusion, better response to DPP4i would be expected in Korean patients with type 2 diabetes who have higher baseline HbA1c and creatinine levels with shorter duration of diabetes.
    Journal of Korean medical science 06/2013; 28(6):881-7. · 0.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Farnesoid X receptor (FXR) is a nuclear receptor, which functions as a bile acid sensor controlling bile acid homeostasis. We investigated the role of FXR in regulating bone metabolism. We identified the expression of FXR in calvaria and bone marrow cells, which gradually increased during osteoblastic differentiation in vitro. In male mice, deletion of FXR (FXR(-/-) ) in vivo resulted in a significant reduction in bone mineral density by 4.3∼6.6% in mice 8 to 20 weeks of age compared with FXR(+/+) mice. Histological analysis of the lumbar spine showed that FXR deficiency reduced the bone formation rate as well as the trabecular bone volume and thickness. Moreover, TRACP staining of the femurs revealed that both the osteoclast number and osteoclast surface were significantly increased in FXR(-/-) mice compared with FXR(+/+) mice. At the cellular level, induction of alkaline phosphatase (ALP) activities was blunted in primary calvarial cells in FXR(-/-) mice compared with FXR(+/+) mice in concert with a significant reduction in Col1a1, ALP, and Runx2 gene expressions. Cultures of bone marrow derived macrophages from FXR(-/-) mice exhibited an increased number of osteoclast formations and protein expression of NFATc1. In female FXR(-/-) mice, although BMD was not significantly different from that in FXR(+/+) mice, bone loss was accelerated after an ovariectomy compared with FXR(+/+) mice. In vitro, activation of FXR by bile acids (CDCA or 6-ECDCA) or FXR agonists (GW4064 or Fexaramine) significantly enhanced osteoblastic differentiation through the upregulation of Runx2 and enhanced ERK and β-catenin signaling. FXR agonists also suppressed osteoclast differentiation from bone marrow macrophages. Finally, administration of a farnesol diet (1%) marginally prevented OVX-induced bone loss and enhanced bone mass gain in growing C57BL/6J mice. Taken together, these results suggest that FXR positively regulates bone metabolism through both arms of the bone remodeling pathways, i.e. bone formation and resorption.
    Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 04/2013; · 6.04 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Context:Women with a history of gestational diabetes mellitus (GDM) are at increased risk of type 2 diabetes (T2DM). However, the time to progression to diabetes differs individually.Objective:We investigated the clinical and genetic risk factors that are associated with T2DM early or late post partum after GDM pregnancy.Design and Setting:This was a hospital-based prospective cohort study that enrolled GDM women.Patients and Outcome Measures:A total of 843 GDM subjects were followed for the development of T2DM. Clinical risk factors were investigated during pregnancy, 2 months post partum, and annually thereafter. GDM subjects were genotyped for 21 known T2DM-associated genetic variants, and their genotype frequencies were compared with elderly nondiabetic controls.Results:At 2 months post partum, 105 (12.5%) subjects had T2DM (early converters). Among the 370 remaining subjects who underwent more than 1 year of follow-up, 88 (23.8%) had newly developed T2DM (late converters). Independent risk factors for early converters were higher prepregnancy body mass index, higher area under the curve of glucose during an antepartum oral glucose tolerance test, lower fasting insulin concentration, and decreased β-cell function. Independent risk factors for late converters were higher prepregnancy body mass index and higher glucose area under the curve. Variants in CDKN2A/2B and HHEX were associated with early conversion, whereas variants in CDKAL1 were associated with late conversion.Conclusions:Obesity was a risk factor for both early and late T2DM converters. However, early converters had more pronounced defects in β-cell function, which might be explained, in part, by differences in genetic predisposition.
    The Journal of Clinical Endocrinology and Metabolism 03/2013; · 6.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We report here the cases of two females with Graves' disease who developed insulin autoimmune syndrome after treatment with methimazole. The patients exhibited a sudden altered mental state after treatment with methimazole for approximately 4 weeks. Patients had hypoglycemia with serum glucose below 70 mg/dL, and laboratory findings showed both high levels of serum insulin and high titers of insulin autoantibodies. The two women had never been exposed to insulin or oral antidiabetic agents, and there was no evidence of insulinoma in imaging studies. After glucose loading, serum glucose, and total insulin levels increased abnormally. One of the patient was found to have HLA-DRB1*0406, which is known to be strongly associated with methimazole-induced insulin autoimmune syndrome. After discontinuation of methimazole, hypoglycemic events disappeared within 1 month. Insulin autoantibody titer and insulin levels decreased within 5 months and there was no further development of hypoglycemic events. We present these cases with a review of the relevant literature.
    Endocrinology and metabolism (Seoul, Korea). 03/2013; 28(1):55-60.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Osteoblasts are derived from mesenchymal progenitors. Differentiation to osteoblasts and adipocytes is reciprocally regulated. Transcriptional coactivator with a PDZ-binding motif (TAZ) is a transcriptional coactivator that induces differentiation of mesenchymal cells into osteoblasts while blocking differentiation into adipocytes. To investigate the role of TAZ on bone metabolism in vivo, we generated transgenic mice that overexpress TAZ under the control of the procollagen type 1 promoter (Col1-TAZ). Whole body bone mineral density (BMD) of 6- to 19-week-old Col-TAZ mice was 4% to 7% higher than that of their wild-type (WT) littermates, whereas no difference was noticed in Col.1-TAZ female mice. Microcomputed tomography analyses of proximal tibiae at 16 weeks of age demonstrated a significant increase in trabecular bone volume (26.7%) and trabecular number (26.6%) with a reciprocal decrease in trabecular spacing (14.2%) in Col1-TAZ mice compared with their WT littermates. In addition, dynamic histomorphometric analysis of the lumbar spine revealed increased mineral apposition rate (42.8%) and the serum P1NP level was also significantly increased (53%) in Col.1-TAZ mice. When primary calvaria cells were cultured in osteogenic medium, alkaline phosphatase (ALP) activity was significantly increased and adipogenesis was significantly suppressed in Col1-TAZ mice compared with their WT littermates. Quantitative real-time polymerase chain reaction analyses showed that expression of collagen type 1, bone sialoprotein, osteocalcin, ALP, osterix, and Runx2 was significantly increased in calvaria cells from Col1-TAZ mice compared to their WT littermates. In vitro, TAZ enhanced Runx2-mediated transcriptional activity while suppressing the peroxisome proliferator-activated receptor gamma signaling pathway. TAZ also enhanced transcriptional activity from 3TP-Lux, which reflects transforming growth factor-beta (TGF-β)-mediated signaling. In addition, TAZ enhanced TGF-β-dependent nuclear translocation of Smad2/3 and Smad4. Taken together, these results suggest that TAZ positively regulates bone formation in vivo, which seems to be mediated by enhancing both Runx2 and TGF-β signaling.
    PLoS ONE 02/2013; 8(2):e56585. · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of the present study was to examine the effect of micellar systems on the absorption of beta-lapachone (b-lap) through different intestinal segments using a single-pass rat intestinal perfusion technique. B-lap was solubilized in mixed micelles composed of phosphatidylcholine and sodium deoxycholate, and in sodium lauryl sulfate (SLS)-based conventional micelles. Both mixed micelles and SLS micelles improved the in situ permeability of b-lap in all intestinal segments tested although the mixed micellar formulation was more effective in increasing the intestinal absorption of b-lap. The permeability of b-lap was greatest in the large intestinal segments. Compared with SLS micelles, the effective permeability coefficient values measured with mixed micelles were 5- to 23-fold higher depending on the intestinal segment. Our data suggest that b-lap should be delivered to the large intestine using a mixed micellar system for improved absorption.
    Korean Journal of Physiology and Pharmacology 02/2013; 17(1):9-13. · 1.00 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Leptin plays a critical role in the central regulation of bone mass. Ghrelin counteracts leptin. In this study, we investigated the effect of chronic intracerebroventricular administration of ghrelin on bone mass in Sprague-Dawley rats (1.5 μg/day for 21 days). Rats were divided into control, ghrelin ad libitum-fed (ghrelin ad lib-fed), and ghrelin pair-fed groups. Ghrelin intracerebroventricular infusion significantly increased body weight in ghrelin ad lib-fed rats but not in ghrelin pair-fed rats, as compared with control rats. Chronic intracerebroventricular ghrelin infusion significantly increased bone mass in the ghrelin pair-fed group compared with control as indicated by increased bone volume percentage, trabecular thickness, trabecular number and volumetric bone mineral density in tibia trabecular bone. There was no significant difference in trabecular bone mass between the control group and the ghrelin ad-lib fed group. Chronic intracerebroventricular ghrelin infusion significantly increased the mineral apposition rate in the ghrelin pair-fed group as compared with control. In conclusion, chronic central administration of ghrelin increases bone mass through a mechanism that is independent of body weight, suggesting that ghrelin may have a bone anabolic effect through the central nervous system.
    PLoS ONE 01/2013; 8(7):e65505. · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Umbilical cord blood (UCB) has recently been recognized as a new source of mesenchymal stem cells (MSCs) for use in stem cell therapy. We studied the effects of systemic injection of human UCB-MSCs and their conditioned medium (CM) on ovariectomy (OVX)-induced bone loss in nude mice. Ten-week-old female nude mice were divided into six groups: Sham-operated mice treated with vehicle (Sham-Vehicle), OVX mice subjected to UCB-MSCs (OVX-MSC) or human dermal fibroblasts (OVX-DFB) transplantation, OVX mice treated with UCB-MSCs CM (OVX-CM), zoledronate (OVX-Zol), or vehicle (OVX-Vehicle). Although OVX-Vehicle group exhibited significantly less bone mineral density (BMD) gain compared with Sham-Vehicle group, transplantation of hUCB-MSCs (OVX-MSC group) has effectively prevented OVX-induced bone mass attenuation. Notably, OVX-CM group also showed BMD preservation comparable to the OVX-MSC group. In addition, micro-CT analysis demonstrated improved trabecular parameters in both OVX-MSC and OVX-CM groups compared to OVX-Vehicle or OVX-DFB group. Histomorphometric analysis showed increased bone formation parameters, accompanied by increased serum procollagen type-I N-telopeptide levels in OVX-MSC and OVX-CM mice. However, cell trafficking analysis failed to demonstrate engraftment of MSCs in bone tissue 48 hrs after cell infusion. In vitro, hUCB-MSC CM increased alkaline phosphatase activity in human bone marrow-derived MSCs and mRNA expression of collagen type 1, Runx2, osterix, and alkaline phosphatase in C3H10T1/2 cells. Furthermore, hUCB-MSC CM significantly increased survival of osteocyte-like MLO-Y4 cells while it inhibited osteoclastic differentiation. To summarize, transplantation of hUCB-MSCs could effectively prevented OVX-mediated bone loss in nude mice which appears to be mediated by paracrine mechanism rather than direct engraftment of the MSCs.
    Tissue Engineering Part A 12/2012; · 4.64 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to design self-microemulsifying tablets for pH-independent fast release of poorly soluble candesartan cilexetil (CDC). To improve the solubility of CDC, a self-microemulsifying drug delivery system (SMEDDS) was prepared composed of Capryol 90, Tween 80 and tetraglycol at a ratio of 5:35:60. Drug containing SMEDDS was adsorbed onto Fujicalin and Neusilin UFL2, respectively, used as solidification carriers and subsequently compressed into tablets (self-microemulsifying tablet, SMET). SMET using Fujicalin exhibited immediate CDC release in pH 1.2 medium while Neusilin UFL2-based SMET showed fast release, especially at pH 6.5. Thus, optimized SMET could be produced with one layer of Fujicalin and the other layer with Neusilin UFL2, demonstrating CDC release of 75% of the initial dose within 15 min in all pH conditions (1.2, 4.5, and 6.5). The average diameter of emulsion droplets formed from SMET was less than 200 nm. It was thus expected that Fujicalin and Neusilin UFL2-based bi-layer SMET would overcome low oral bioavailability of CDC due to its limited solubility at physiological pH conditions in the gastrointestinal tract.
    Pharmazie 11/2012; 67(11):917-24. · 0.96 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: CONTEXT: It was previously reported in Korea that there were 1.4 case per million per year of acromogly. This was low in comparison to the extrapolated values of western European countries. We expected that the incidence of acromegaly would be much higher now due to recently improved medical facilities, diagnostic tools, and coverage of medical insurance to all the population of South Korea. OBJECTIVE: The purpose of this nationwide survey was to examine the incidence and prevalence of acromegaly patients, mode of treatment, and outcome of surgical treatment of recent 5 years. DESIGN AND PATIENTS: We requested and collected the medical records of all possible acromegaly patients from 74 secondary or tertiary medical institutes in Korea from 2003 to 2007 retrospectively. MEASUREMENTS: Date of diagnosis and treatment, tumor size, pre- and postoperative hormonal level, treatment modality and usage of medication were collected. RESULTS: During 5 years, 1350 acromegaly patients had been registered. The average annual incidence was 3.9 cases per million during this period, and prevalence had increased up to 27.9 cases per million in 2007. Male:female ratio was 1:1.2, and mean age at diagnosis was 44.1 years. Macroadenoma was dominant (82.9%). Transsphenoidal adenoidectomy was used the most as primary treatment (90.4%). CONCLUSIONS: This Korean acromegaly survey offers a realistic overview of the predominant epidemiological characteristics of acromegaly in Korea. Annual incidence was at a similar level with western countries. Efforts to diagnose and control the disease earlier are recommended. © 2012 Blackwell Publishing Ltd.
    Clinical Endocrinology 08/2012; · 3.40 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This study was conducted to review the clinical characteristics of parathyroid carcinoma (PC) and to evaluate potential preoperative predictive factors for PC in patients with primary hyperparathyroidism (PHPT). We performed a retrospective review of electronic medical records of 194 patients with pathologically confirmed PHPT in affiliated teaching hospitals of Seoul National University from January 2000 to March 2011. Adenoma was diagnosed in 171 patients, hyperplasia in 12, and carcinoma in 11. Several biochemical measurements were higher in patients with PC than in patients with benign disease, including serum total calcium (P < 0.001), intact parathyroid hormone (P = 0.003), and alkaline phosphatase (ALP) (P < 0.001). Tumors were larger in PC than in benign disease (P < 0.001). Multivariate analysis revealed that serum ALP level (P < 0.001) and tumor size were associated with PC (P = 0.03). Tumor size and serum ALP level were evaluated as preoperative predictive factors for PC using ROC analyses: a tumor size of 3.0 cm (sensitivity 90.9%, specificity 92.1%) and serum ALP level of 285 IU/L (83.3%, 97.0%) had predictive value for the diagnosis of PC in patients with PHPT. In conclusion, elevated serum ALP and a large parathyroid mass at the time of diagnosis can be helpful to predict PC in patients with PHPT.
    Journal of Korean medical science 08/2012; 27(8):890-5. · 0.84 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Distinguishing between unilateral and bilateral adrenal lesions is mandatory for surgical treatment of primary aldosteronism (PA). Adrenal venous sampling (AVS) is considered the gold standard for identification and localization of the lesion or lesions causing PA. The objective of the present study was to determine the usefulness of AVS in PA patients. From January 2001 to October 2011, 86 patients with the biochemical diagnosis of PA were retrospectively analyzed. The study group included 45 males and 41 females with a mean age of 50.7 ± 12.6 years, and all patients underwent adrenal computed tomography (CT) and AVS. The catheterization success rate of AVS was 82.69 % (86/104). In addition, AVS revealed bilateral lesions in 15/75 patients with unilateral abnormalities diagnosed by CT. These patients underwent medical treatment instead of surgery. One patient had an adrenal mass on the right side, but AVS localized the lesion on the left side. This patient underwent left adrenalectomy. Furthermore, AVS revealed a unilateral lesion in 2/5 patients with bilateral abnormalities demonstrated by CT. These patients underwent unilateral adrenalectomy. Finally, AVS demonstrated localization in 1/6 of patients with no CT abnormalities who were subjected to surgery. Fifty-three patients with unilateral lesion and one patient with bilateral hypersecretion underwent surgical removal of the affected gland(s). All patients had resolution of hypokalemia and clinical improvement of hypertension. Many patients (19/86, or 22.09 %) would have been inappropriately managed if decision making had been based solely on CT findings. Therefore, AVS is recommended before determining definitive PA management.
    World Journal of Surgery 06/2012; 36(10):2522-7. · 2.23 Impact Factor

Publication Stats

1k Citations
279.05 Total Impact Points

Institutions

  • 2013
    • Konkuk University Medical Center
      Changnyeong, South Gyeongsang, South Korea
  • 2012–2013
    • Chung-Ang University
      • College of Pharmacy
      Seoul, Seoul, South Korea
  • 1999–2013
    • Seoul National University Hospital
      • Department of Internal Medicine
      Seoul, Seoul, South Korea
  • 2000–2011
    • Seoul National University
      • Department of Internal Medicine
      Sŏul, Seoul, South Korea
  • 2004
    • Korea University
      Sŏul, Seoul, South Korea
    • Soonchunhyang University
      Onyang, South Chungcheong, South Korea