Publications by authors named "Yoon Kyung Park"

31 Publications

Long-term evaluation of temporomandibular disorders in association with cytokine and autoantibody status in young women.

Cytokine 2021 Aug 1;144:155551. Epub 2021 May 1.

Department of Oral Medicine and Oral Diagnosis, School of Dentistry and Dental Research Institute, Seoul National University, 101 Yunkeun-Dong, Chongro-Ku, Seoul 03080, Republic of Korea. Electronic address:

Temporomandibular disorders (TMD) is a chronic pain disease affecting 4-60% of general population. Its suggested etiology includes mechanical overloading to related structures, psychosocial factors, and genetic vulnerability. However, its pathogenesis is yet to be fully understood, especially in cases with a higher level of pain and more associated comorbidities. Recently chronic systemic inflammation and possible autoimmunity has been indicated in several pain conditions as the underlying mechanism of chronicity but this aspect has not been rigorously investigated in TMD. This article focuses on analyzing the levels of cytokines, chemokines, autoantibodies and nonspecific inflammatory markers and comparing their levels according to pain severity and duration in 66 female TMD patients in their 20 s and investigating their association with clinical indices of TMD and comorbidities. The high pain disability group showed decreased range of jaw function and more pain on palpation of capsule areas compared to the low pain disability group. Comorbidities such as anxiety and sleep disturbance were also significantly more prevalent. The level of IL-8 and IgG were significantly higher in the high pain disability group. IL-2, -8, -13, IFN- γ, RANTES, PGE2, and thrombopoietin levels showed a significant effect on indices reflecting jaw function, generalized pain intensity, and health related quality of life. Such results imply that longer pain duration and higher pain intensity is associated with higher levels of systemic inflammation suggesting the possible role of immunologic disturbance as an underlying factor of chronic TMD pain and warranting further investigation for its consideration in diagnosis and treatment.
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http://dx.doi.org/10.1016/j.cyto.2021.155551DOI Listing
August 2021

Modelling and manufacturing of 3D-printed, patient-specific, and anthropomorphic gastric phantoms: a pilot study.

Sci Rep 2020 11 4;10(1):18976. Epub 2020 Nov 4.

Department of Convergence Medicine, Asan Medical Institute of Convergence Science and Technology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 05505, South Korea.

Interventional devices including intragastric balloons are widely used to treat obesity. This study aims to develop 3D-printed, patient-specific, and anthropomorphic gastric phantoms with mechanical properties similar to those of human stomach. Using computed tomography gastrography (CTG) images of three patients, gastric phantoms were modelled through shape registration to align the stomach shapes of three different phases. Shape accuracies of the original gastric models versus the 3D-printed phantoms were compared using landmark distances. The mechanical properties (elongation and tensile strength), number of silicone coatings (0, 2, and 8 times), and specimen hardness (50, 60, and 70 Shore A) of three materials (Agilus, Elastic, and Flexa) were evaluated. Registration accuracy was significantly lower between the arterial and portal phases (3.16 ± 0.80 mm) than that between the portal and delayed phases (8.92 ± 0.96 mm). The mean shape accuracy difference was less than 10 mm. The mean elongations and tensile strengths of the Agilus, Elastic, and Flexa were 264%, 145%, and 146% and 1.14, 1.59, and 2.15 MPa, respectively, and their mechanical properties differed significantly (all p < 0.05). Elongation and tensile strength assessments, CTG image registration and 3D printing resulted in highly realistic and patient-specific gastric phantoms with reasonable shape accuracies.
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http://dx.doi.org/10.1038/s41598-020-74110-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643145PMC
November 2020

Safety and efficacy of a metal stent covered with a silicone membrane containing integrated silver particles in preventing biofilm and sludge formation in endoscopic drainage of malignant biliary obstruction: a phase 2 pilot study.

Gastrointest Endosc 2019 10 18;90(4):663-672.e2. Epub 2019 Jun 18.

Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.

Background And Aims: Membrane-covered self-expandable metal stents (SEMSs) have been developed to prolong the patency of stents by reducing tissue hyperplasia or tumor ingrowth. However, their effectiveness is attenuated by stent clogging as a result of biofilm formation on the inner surface of the membrane. The aim of this pilot study was to evaluate the efficacy and safety of SEMSs covered with a silicone membrane containing integrated silver particles (Ag-P) in malignant distal biliary obstruction.

Methods: Twenty-four patients who underwent SEMS placement because of malignant distal biliary obstruction were enrolled in this single-center pilot study. The main outcomes were technical success, clinical success, adverse events, stent patency, and survival.

Results: The technical and clinical success rates were 100% and 91.7% (22 of 24), respectively. The rates of early and late adverse events were 22.7% and 36.4%, respectively. The primary reintervention rate was 27.3% (6 of 22). Only 1 case involving stent malfunction was associated with sludge impaction. Median stent patency was 179 days. During follow-up, there were no serious adverse events or mortality related to the stents or Ag-P. Serum and urine silver concentrations before and after stent placement and at 32 weeks after placement did not differ. All serum and urine silver concentrations were <3 μg/L (3 ppb) and 5 μg/L (5 ppb), respectively.

Conclusions: SEMSs covered with a silicone membrane containing integrated Ag-Ps may be effective and safe in malignant distal biliary obstruction. Stent dysfunction related to sludge impaction may be less frequent using this new stent. (Clinical Research Information Service identifier: KCT 0002310.).
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http://dx.doi.org/10.1016/j.gie.2019.06.007DOI Listing
October 2019

Characterization and Differentiation of Circulating Blood Mesenchymal Stem Cells and the Role of Phosphatidylinositol 3-Kinase in Modulating the Adhesion.

Int J Stem Cells 2019 Jul;12(2):265-278

Department of Dental Regenerative Biotechnology, School of Dentistry, Seoul National University, Seoul, Korea.

Bone marrow mesenchymal stem cells (BM MSCs) can differentiate into multi-lineage tissues. However, obtaining BM MSCs by aspiration is difficult and can be painful; therefore peripheral blood (PB) MSCs might provide an easier alternative for clinical applications. Here, we show that circulating PB MSCs proliferate as efficiently as BM MSCs in the presence of extracellular matrix (ECM) and that differentiation potential into osteoblast and . Both BM MSCs and PB MSCs developed into new bone when subcutaneously transplanted into immune-compromised mice using hydroxyapatite/tricalcium phosphate as a carrier. Furthermore, LY294002 and Wortmannin blocked mesenchymal stem cell attachment in a dose-dependent manner, suggesting a role of phosphatidylinositol 3-kinase in MSC attachment. Our data showed that the growth of PB MSCs could be regulated by interaction with the ECM and that these cells could differentiate into osteoblasts, suggesting their potential for clinical applications.
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http://dx.doi.org/10.15283/ijsc18136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657952PMC
July 2019

Synergistic Effect of Adipose-Derived Stem Cells and Fat Graft on Wrinkles in Aged Mice.

Plast Reconstr Surg 2019 06;143(6):1637-1646

From the Department of Plastic and Reconstructive Surgery, Seoul National University College of Medicine; the Department of Pediatric Plastic and Reconstructive Surgery, Seoul National University Children's Hospital; and the Department of Plastic and Reconstructive Surgery, Seoul National University Bundang Hospital.

Background: The authors investigated the synergistic effects of adipose-derived stem cells and fat graft on skin wrinkles in a nude mouse model of chronologic aging.

Methods: After 50 weeks of chronologic aging, 44 female BALB/c nude mice were classified into four groups: (1) negative control, (2) mice injected subcutaneously with fat on the back skin (0.5 cm), (3) mice injected with adipose-derived stem cells (1 × 10 cells in 0.5 cm Hanks balanced salt solution), and (4) mice injected with both fat (0.5 cm) and adipose-derived stem cells (1 × 10 cells in 0.5 cm Hanks balanced salt solution). The degree of wrinkling was evaluated using replica analysis, and skin biopsies were performed after 4 weeks. The dermal thickness and density of collagen were determined. Type I procollagen and matrix metalloproteinase levels were determined using real-time polymerase chain reaction and Western blot analysis. Tropoelastin, fibrillin-1, and CD31 levels were evaluated using immunohistochemistry.

Results: Based on the total wrinkle area, there was significant wrinkle reduction in the fat-treated and adipose-derived stem cell with fat-treated groups. Type I procollagen mRNA and collagen levels were significantly higher in the adipose-derived stem cell with fat-treated group than in the adipose-derived stem cell-treated and the fat-treated groups. In addition, the adipose-derived stem cells with fat graft group exhibited significantly higher CD31 expression level than the adipose-derived stem cell-treated and the fat-treated groups.

Conclusion: Both adipose-derived stem cells and fat graft have a wrinkle-reducing effect and synergistically affect collagen synthesis and neovascularization.
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http://dx.doi.org/10.1097/PRS.0000000000005625DOI Listing
June 2019

Patient-derived multicellular tumor spheroids towards optimized treatment for patients with hepatocellular carcinoma.

J Exp Clin Cancer Res 2018 May 25;37(1):109. Epub 2018 May 25.

Cancer Biology Research Laboratory, Institut Pasteur Korea, 16, Daewangpangyo-ro 712 beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 13488, Korea.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and has poor prognosis. Specially, patients with HCC usually have poor tolerance of systemic chemotherapy, because HCCs develop from chronically damaged tissue that contains considerable inflammation, fibrosis, and cirrhosis. Since HCC exhibits highly heterogeneous molecular characteristics, a proper in vitro system is required for the study of HCC pathogenesis. To this end, we have established two new hepatitis B virus (HBV) DNA-secreting HCC cell lines from infected patients.

Methods: Based on these two new HCC cell lines, we have developed chemosensitivity assays for patient-derived multicellular tumor spheroids (MCTSs) in order to select optimized anti-cancer drugs to provide more informative data for clinical drug application. To monitor the effect of the interaction of cancer cells and stromal cells in MCTS, we used a 3D co-culture model with patient-derived HCC cells and stromal cells from human hepatic stellate cells, human fibroblasts, and human umbilical vein endothelial cells to facilitate screening for optimized cancer therapy.

Results: To validate our system, we performed a comparison of chemosensitivity of the three culture systems, which are monolayer culture system, tumor spheroids, and MCTSs of patient-derived cells, to sorafenib, 5-fluorouracil, and cisplatin, as these compounds are typically standard therapy for advanced HCC in South Korea.

Conclusion: In summary, these findings suggest that the MCTS culture system is the best methodology for screening for optimized treatment for each patients with HCC, because tumor spheroids not only mirror the 3D cellular context of the tumors but also exhibit therapeutically relevant pathophysiological gradients and heterogeneity of in vivo tumors.
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http://dx.doi.org/10.1186/s13046-018-0752-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5970513PMC
May 2018

Surface Characterization and Human Stem Cell Behaviors of Zirconia Implant Disks Biomimetic-Treated in Simulated Body Fluid.

Int J Oral Maxillofac Implants 2016 Jul-Aug;31(4):928-38

Purpose: This study investigated the effects of biomimetic deposition on a zirconia surface in simulated body fluid (SBF) and assessed the proliferation and differentiation of human bone marrow mesenchymal stem cells on the SBF-treated zirconia disks.

Materials And Methods: Corrected SBF was prepared according to Kokubo's recipe. Eighty yttrium oxide-stabilized tetragonal zirconia polycrystalline disks were prepared and divided into two groups: (1) the test group with SBF-treated disks and (2) the control group with nontreated disks. Zirconia disks were soaked in SBF for 1, 4, 7, and 14 days at 36.5°C, and the hydroxyapatite (HA) precipitation was verified by analyzing the surface morphology. For more in-depth validation of HA formation, the surface roughness, composition, and crystallization of the 7-day treated disks were analyzed. Human bone marrow mesenchymal stem cells were used to further evaluate cell proliferation, alkaline phosphatase activity, and osteoblast gene expression on the 7-day treated zirconia disks.

Results: Disks showed different surface morphologies after soaking for different time periods. As the SBF soaking time increased, the amount of HA coverage increased gradually, uniformly covering the disks by day 7. There was no difference in surface roughness between the two groups (P > .05). Cell proliferation was higher on the SBF-treated disks (P < .05). At 9 days, alkaline phosphatase activity was higher on the SBF-treated disks (P < .05). Alkaline phosphatase staining was significant on the SBF-treated disks (P < .05). A gene study revealed that alkaline phosphatase and osteocalcin showed higher expression in SBF-treated disks (P < .05); however, collagen type I and runt-related transcription factor 2 did not show significant differences between the two groups (P > .05).

Conclusion: This study demonstrated that biomimetic deposition has an effect on the formation of HA on zirconia disks. The cell attachment, proliferation, and differentiation of SBF-treated zirconia disks was superior to that of nontreated disks, which indicates that SBF-treated zirconia implants have long-term clinical value.
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http://dx.doi.org/10.11607/jomi.4376DOI Listing
June 2017

Induction of tolerance against the arthritogenic antigen with type-II collagen peptide-linked soluble MHC class II molecules.

BMB Rep 2016 Jun;49(6):331-6

Department of Life Sciences, Korea University, Seoul 02841, Korea.

In murine collagen-induced arthritis (CIA), self-reactive T cells can recognize peptide antigens derived from type-II collagen (CII). Activation of T cells is an important mediator of autoimmune diseases. Thus, T cells have become a focal point of study to treat autoimmune diseases. In this study, we evaluated the efficacy of recombinant MHC class II molecules in the regulation of antigen-specific T cells by using a self peptide derived from CII (CII260-274; IAGFKGEQGPKGEPG) linked to mouse I-A(q) in a murine CIA model. We found that recombinant I-A(q)/CII260-274 molecules could be recognized by CII-specific T cells and inhibit the same T cells in vitro. Furthermore, the development of CIA in mice was successfully prevented by in vivo injection of recombinant I-A(q)/CII260-274 molecules. Thus, treatment with recombinant soluble MHC class II molecules in complex with an immunodominant self-peptide might offer a potential therapeutic for chronic inflammation in autoimmune disease such as rheumatoid arthritis. [BMB Reports 2016; 49(6): 331-336].
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070721PMC
http://dx.doi.org/10.5483/bmbrep.2016.49.6.207DOI Listing
June 2016

Eligibility and preference of new oral anticoagulants in patients with atrial fibrillation: comparison between patients with versus without stroke.

Stroke 2014 Oct 21;45(10):2983-8. Epub 2014 Aug 21.

From the Department of Neurology (C.H.Y., Y.K.P., S.J.K., M.-j.L., S.R., G.-M.K., C.-S.C., K.H.L., O.Y.B.) and Department of Cardiology (J.S.K.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.

Background And Purpose: Recent randomized clinical trials (RCTs) have evaluated the benefit of new oral anticoagulants in reducing the risk of vascular events and bleeding complications in patients with atrial fibrillation (AF). However, abundant and strict enrollment criteria may limit the validity and applicability of results of RCTs to clinical practice. We estimated the eligibility for participation in RCTs of an unselected group of patients with AF. In addition, we compared features favoring new oral anticoagulant use between patients with versus without stroke. Randomized Evaluation of Long-Term Anticoagulation Therapy

Methods: We applied enrollment criteria of 4 RCTs (RE-LY, ROCKET-AF, ARISTOTLE, and ENGAGE-AF-TIMI 48) to 695 patients with AF taking warfarin, prospectively and consecutively collected at a university medical center; 500 patients with and 195 patients without stroke. Time in therapeutic range and bleeding risk scheme (anticoagulation and risk factors in atrial fibrillation) were also measured.

Results: The proportions of patients fulfilling the trial enrollment criteria varied, ranging from 39% to 72.8%, depending on the differences in indications/contraindications among studies and presence/absence of stroke. The main reasons for ineligibility for RCTs were hemorrhagic risk (anticoagulation and risk factors in atrial fibrillation [ATRIA] score) (10.8%-40.5%) and planned cardioversion (5.1%-7.7%) for nonstroke patients, and a low creatinine clearance (5.6%-9.2%) and higher risk of bleeding (15.2%-20.8%) for patients with stroke. When compared with nonstroke patients, patients with stroke showed a lower time in therapeutic range (54.4±42.8% versus 65.4±34.9%, especially with severe disability) and a high hemorrhagic risk (ATRIA score) (3.06±2.30 versus 2.18±2.16) (P<0.05 in both cases).

Conclusions: Patients enrolled in RCTs are partly representative of patients with AF in clinical practice. When time in therapeutic range and bleeding tendency with warfarin use were considered, the use of new oral anticoagulants was preferred in patients with stroke than in nonstroke patients, but they were more likely to be excluded in RCTs.
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http://dx.doi.org/10.1161/STROKEAHA.114.005599DOI Listing
October 2014

Lack of association between hepatitis B virus pre-S mutations and recurrence after surgical resection in hepatocellular carcinoma.

J Med Virol 2013 Apr 7;85(4):589-96. Epub 2013 Jan 7.

Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea.

Pre-S mutation of hepatitis B virus (HBV) is known to be a risk factor for hepatocarcinogenesis. A previous study suggested that pre-S mutation(s) may associate with increased recurrence after surgical resection. In the present study, 64 patients with HBV-related hepatocellular carcinoma (HCC) were categorized into two groups according to the presence or absence of pre-S mutation(s). The clinicopathological variables of the two groups were analyzed to assess the relationship between pre-S mutations and postoperative recurrence. Nineteen patients (29.7%) had pre-S mutations;13 had a pre-S deletion, three had a pre-S2 start codon mutation, two patients had both a pre-S deletion, and a pre-S2 start codon mutation, and one patient had a pre-S2 insertion. The two groups did not differ in terms of baseline clinicopathological parameters. Cirrhosis and satellite lesion(s) were predictive factors for postoperative recurrence and poor overall survival. Recurrence-free survival (P = 0.320) and overall survival (P = 0.238) did not differ significantly when pre-S mutations were present. In conclusion, this study did not find evidence supporting the notion that pre-S mutation(s) are associated with postoperative recurrence after surgical resection.
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http://dx.doi.org/10.1002/jmv.23502DOI Listing
April 2013

Effects of dietary supplementation with antimicrobial peptide-P5 on growth performance, apparent total tract digestibility, faecal and intestinal microflora and intestinal morphology of weanling pigs.

J Sci Food Agric 2013 Feb 20;93(3):587-92. Epub 2012 Aug 20.

College of Animal Life Sciences, Kangwon National University, Chuncheon, South Korea.

Background: The increase in drug-resistant bacteria and the ban on antibiotic growth promoters worldwide make the search for novel means of preventing bacterial infection and promoting growth performance imperative. In this sense, antimicrobial peptides are thought to be ideal candidates owing to their antimicrobial properties, broad spectrum of activity and low propensity for development of bacterial resistance. The aim of the present study was to investigate the effect of dietary supplementation with antimicrobial peptide-P5 (AMP-P5) on weanling pig nutrition.

Results: A total of 240 weanling pigs were allotted to four treatments on the basis of initial body weight. There were four replicates in each treatment, with 15 pigs per replicate. Dietary treatments were negative control (NC, basal diet without antimicrobial), positive control (PC, basal diet + 1.5 g kg(-1) apramycin), basal diet with 40 mg kg(-1) AMP-P5 (P5-40) and basal diet with 60 mg kg(-1) AMP-P5 (P5-60). Pigs fed the PC or P5-60 diet showed improved (P < 0.05) overall growth performance, apparent total tract digestibility of dry matter, crude protein and gross energy and reduced (P < 0.05) faecal and intestinal coliforms compared with pigs fed the NC diet.

Conclusion: The results obtained in this study indicate that dietary supplementation with 60 mg kg(-1) AMP-P5 has the potential to improve the growth performance and apparent total tract digestibility of nutrients and reduce coliforms in weanling pigs.
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http://dx.doi.org/10.1002/jsfa.5840DOI Listing
February 2013

Mutation of a positively charged cytoplasmic motif within CD1d results in multiple defects in antigen presentation to NKT cells.

J Immunol 2012 Mar 30;188(5):2235-43. Epub 2012 Jan 30.

School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea.

CD1d is an MHC class I-like molecule that presents glycolipid Ags to types I and II NKT cells. The YxxI motif in the cytoplasmic tail of CD1d contributes to its intracellular localization to the endolysosomal compartment and is important for Ag presentation to type I NKT cells. In this study, we identified the (327-329)RRR motif in CD1d and showed that it is critical for the control of CD1d intracellular trafficking and Ag presentation. The replacement of the arginines in this motif with alanines resulted in the extensive accumulation of CD1d in lysosomes but did not affect the cell surface expression. The defect in its cellular localization was accompanied by defects in Ag presentation to both type I and type II NKT cells. These results demonstrated that the (327-329)RRR motif of CD1d is required for proper cellular distribution of CD1d and optimal Ag presentation to both type I and type II NKT cells.
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http://dx.doi.org/10.4049/jimmunol.1100236DOI Listing
March 2012

Protective potential of resveratrol against oxidative stress and apoptosis in Batten disease lymphoblast cells.

Biochem Biophys Res Commun 2011 Oct 14;414(1):49-52. Epub 2011 Sep 14.

Department of Biotechnology, Hoseo University, 165, Baebang, Asan, Chungnam 336-795, Republic of Korea.

Batten disease (BD) is the most common form of a group of disorders called neuronal ceroid lipofuscinosis, which are caused by a CLN3 gene mutation. A variety of pathogenic lysosomal storage disorder mechanisms have been suggested such as oxidative stress, endoplasmic reticulum (ER) stress, and altered protein trafficking. Resveratrol, a stilbenoid found in red grape skin, is a potent antioxidant chemical. Recent studies have suggested that resveratrol may have a curative effect in many neurodegenerative diseases. Therefore, we investigated the activities of resveratrol at the levels of oxidative and ER stress and apoptosis factors using normal and BD lymphoblast cells. We report that the BD lymphoblast cells contained low-levels of superoxide dismutase-1 (SOD-1) due to the long-term stress of reactive oxygen species. However, when we treated the cells with resveratrol, SOD-1 increased to levels observed in normal cells. Furthermore, we investigated the expression of glucose-regulated protein 78 as an ER stress marker. BD cells underwent ER stress, but resveratrol treatment resolved the ER stress in a dose-dependent manner. We further demonstrated that the levels of apoptosis markers such as apoptosis induce factor, cytochrome c, and cleavage of poly (ADP)-ribose polymerase decreased following resveratrol treatment. Thus, we propose that resveratrol may have beneficial effects in patients with BD.
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http://dx.doi.org/10.1016/j.bbrc.2011.09.019DOI Listing
October 2011

Could HBx protein expression affect signal pathway inhibition by gefitinib or selumetinib, a MEK inhibitor, in hepatocellular carcinoma cell lines?

J Korean Med Sci 2011 Feb 24;26(2):214-21. Epub 2011 Jan 24.

Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Hepatitis B virus X (HBx) protein has been known to play an important role in development of hepatocellular carcinoma (HCC). The aim of this study is to find out whether HBx protein expression affects antiproliferative effect of an epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitor and a MEK inhibitor in HepG2 and Huh-7 cell lines. We established HepG2 and Huh-7 cells transfected stably with HBx gene. HBx protein expression increased pERK and pAkt expression as well as β-catenin activity in both cells. Gefitinib (EGFR-TK inhibitor) inhibited pERK and pAkt expression and β-catenin activity in both cells. Selumetinib (MEK inhibitor) reduced pERK level and β-catenin activity but pAkt expression was rather elevated by selumetinib in these cells. Reduction of pERK levels was much stronger with selumetinib than gefitinib in both cells. The antiproliferative efficacy of selumetinib was more potent than that of gefitinib. However, the antiproliferative effect of gefitinib, as well as selumetinib, was not different between cell lines with or without HBx expression. Signal pathway activation by HBx might not be strong enough to attenuate the antiproliferative effect of EGFR-TK inhibitor. Future experiments are needed to understand the role of HBx protein expression in HCC treatment using molecular targeting agent.
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http://dx.doi.org/10.3346/jkms.2011.26.2.214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031005PMC
February 2011

Lactobacillus casei prevents impaired barrier function in intestinal epithelial cells.

APMIS 2011 Jan 25;119(1):49-56. Epub 2010 Oct 25.

Department of Internal Medicine, Hanyang University Guri Hospital, Gyeonggi-Do, Korea.

The exact effect of probiotics on epithelial barrier function is not well understood. The aims of this study were to evaluate cytokine-induced epithelial barrier dysfunction in intestinal epithelial cells (IECs) and to study the role of probiotics in the prevention of epithelial barrier dysfunction. Caco-2 cells grown on transwell chambers were stimulated with tumor necrosis factor (TNF)-α or interferon (IFN)-γ basolaterally. Probiotic, Lactobacillus casei, was added 1 h before cytokine stimulation. MAPK inhibitors were added 15 min before L. casei stimulation. The electrical resistance and paracellular permeability of Caco-2 monolayers were measured. Distribution of zonula occludens (ZO)-1 protein was assessed by immunofluorescence, and Western blot analyses for ZO-1, p-Akt, and toll-like receptor (TLR) 2 were performed. Both TNF-α and IFN-γ stimulation on Caco-2 cells decreased transepithelial resistance (TER), increased epithelial permeability, and decreased ZO-1 expression of Caco-2 cells. In contrast, pretreatment of L. casei reversed the cytokine-induced dysfunction of TER, epithelial permeability, and ZO-1 expression. Reversal of cytokine-induced dysfunction of TER and intestinal permeability by L. casei was abrogated with MAPK inhibitor treatment. Lactobacillus casei stimulation on Caco-2 cells increased TLR2 and p-Akt expression. Probiotic, L. casei, prevents cytokine-induced epithelial barrier dysfunctions in IECs.
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http://dx.doi.org/10.1111/j.1600-0463.2010.02691.xDOI Listing
January 2011

The requirement of natural killer T-cells in tolerogenic APCs-mediated suppression of collagen-induced arthritis.

Exp Mol Med 2010 Aug;42(8):547-54

School of Life Sciences and Biotechnology, Korea University, Seoul, Korea.

TGF-beta-induced tolerogenic-antigen presenting cells (Tol-APCs) could induce suppression of autoimmune diseases such as collagen-induced arthritis (CIA) and allergic asthma. In contrast, many studies have shown that NKT cells are involved in the pathogenesis of Th1-mediated autoimmune joint inflammation and Th2-mediated allergic pulmonary inflammation. In this study, we investigated the effect of CD1d-restricted NKT cells in the Tol-APCs-mediated suppression of autoimmune disease using a murine CIA model. When CIA-induced mice were treated with Tol-APCs obtained from CD1d+/- or CD1d-/- mice, unlike CD1d+/- APCs, CD1d-/- Tol-APCs failed to suppress CIA. More specifically, CD1d-/- Tol-APCs failed to suppress the production of inflammatory cytokines and the induction of Th2 responses by antigen-specific CD4 T cells both in vitro and in vivo. Our results demonstrate that the presence of CD1d-restricted NKT cells is critical for the induction of Tol-APCs-mediated suppression of CIA.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928927PMC
http://dx.doi.org/10.3858/emm.2010.42.8.055DOI Listing
August 2010

[Mutations within the interferon sensitivity determining region in Korean patients infected with hepatitis C virus genotype 1b].

Korean J Hepatol 2010 Jun;16(2):158-67

Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Background/aims: The treatment response to interferon could differ with mutations in the interferon-sensitivity-determining region (ISDR) in patients infected with hepatitis C virus (HCV) genotype-1b (HCV-Ib). We examined the pattern of ISDR mutations and analyzed whether the number of amino acid substitutions influences the treatment response to peginterferon plus ribavirin in chronic hepatitis or cirrhotic patients infected with HCV-Ib.

Methods: The study population comprised 52 patients who visited Seoul Asan Medical Center and Seoul National University Bundang Hospital from January 2006 to December 2008 and who received peginterferon alpha-2a (n=37) or -2b (n=15) plus ribavirin, and whose serum was stored. We analyzed the early virologic response, end-of-treatment response, and sustained virologic response (SVR), and examined the ISDR using direct sequencing.

Results: The proportions of patients with ISDR mutation types of wild (0 mutations), intermediate (1-3 mutations), and mutant (> or =4 mutations) were 50.0%, 42.3%, and 7.7%, respectively, and the corresponding SVR rates were 63%, 50%, and 67% (p>0.05). The SVR rates were 59.4% and 50.0% in patients with <2 and > or =2 mutations, respectively (p>0.05). On univariate analysis, age was the only predictive factor for SVR (p=0.016). The pretreatment HCV RNA titer tended to be lower in those with SVR, but without statistical significance (p=0.069).

Conclusions: The frequency of ISDR mutations was low in our cohort of Korean patients infected with HCV-Ib. Therefore, ISDR mutations might not contribute to the response to treatment with peginterferon plus ribavirin.
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http://dx.doi.org/10.3350/kjhep.2010.16.2.158DOI Listing
June 2010

TGF-beta-treated antigen presenting cells suppress collagen- induced arthritis through the promotion of Th2 responses.

Exp Mol Med 2010 Mar;42(3):187-94

School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea.

Collagen-induced arthritis (CIA) is mediated by self-reactive CD4(+) T cells that produce inflammatory cytokines. TGF-beta(2)-treated tolerogenic antigen-presenting cells (Tol-APCs) are known to induce tolerance in various autoimmune diseases. In this study, we investigated whether collagen-specific Tol-APCs could induce suppression of CIA. We observed that Tol-APCs could suppress the development and severity of CIA and delay the onset of CIA. Treatment of Tol-APCs reduced the number of IFN-gamma- and IL-17-producing CD4(+) T cells and increased IL-4- and IL-5-producing CD4(+) T cells upon collagen antigen stimulation in vitro. The suppression of CIA conferred by Tol-APCs correlated with their ability to selectively induce IL-10 production. We also observed that treatment of Tol-APCs inhibited not only cellular immune responses but also humoral immune responses in the process of CIA. Our results suggest that in vitro-generated Tol-APCs have potential therapeutic value for the treatment of rheumatoid arthritis as well as other autoimmune diseases.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845003PMC
http://dx.doi.org/10.3858/emm.2010.42.3.019DOI Listing
March 2010

A new reporter vector system based on flow-cytometry to detect promoter activity.

Immune Netw 2009 Dec 31;9(6):243-7. Epub 2009 Dec 31.

School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea.

In this study, we report the development of a new dual reporter vector system for the analysis of promoter activity. This system employs green fluorescence emitting protein, EGFP, as a reporter, and uses red fluorescence emitting protein, DsRed, as a transfection control in a single vector. The expression of those two proteins can be readily detected via flow cytometry in a single analysis, with no need for any further manipulation after transfection. As this system allows for the simultaneous detection of both the control and reporter proteins in the same cells, only transfected cells which express the control protein, DsRed, can be subjected to promoter activity analysis, via the gating out of all un-transfected cells. This results in a dramatic increase in the promoter activity detection sensitivity. This novel reporter vector system should prove to be a simple and efficient method for the analysis of promoter activity.
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http://dx.doi.org/10.4110/in.2009.9.6.243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816957PMC
December 2009

The presence of CD8+ invariant NKT cells in mice.

Exp Mol Med 2009 Dec;41(12):866-72

School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea.

Invariant natural killer T (iNKT) cells develop in the thymus upon recognition of CD1d expressed on developing thymocytes. Although CD4 and CD8 coreceptors are not directly involved in the interaction between CD1d and the T cell receptors (TCRs) of iNKT cells, a conspicuous lack of CD8(+) iNKT cells in mice raised the question of whether CD8(+) iNKT cells are excluded due to negative selection during their thymic development, or if there is no lineage commitment for the development of murine CD8(+) iNKT cells. To address this question, we analyzed iNKT cell-specific TCR V alpha 14(+) transgenic mice, where the V alpha 14 transgene forces the generation of iNKT cells. This allows detailed study of the iNKT cell repertoire. We were able to identify CD8(+) iNKT cells which respond to the NKT cell-specific glycolipid ligand alpha-galactosylceramide. Unlike conventional iNKT cells, CD8(+) iNKT cells produce predominantly IFN-gamma but not IL-4 upon antigen stimulation. We also confirmed the presence of CD8(+) iNKT cells in wild type mice. Our results suggest that CD8(+) NKT cells do exist in mice, although their population size is quite small. Their Th1-skewed phenotype might explain why the population size of this subtype needs to be controlled tightly.
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http://dx.doi.org/10.3858/emm.2009.41.12.092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2802682PMC
December 2009

Natural killer T cells promote collagen-induced arthritis in DBA/1 mice.

Biochem Biophys Res Commun 2009 Dec 6;390(3):399-403. Epub 2009 Sep 6.

School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, South Korea.

The role of NKT cells in the pathogenesis of collagen-induced arthritis (CIA) remains unclear since most studies have used C57BL/6 (B6) mice, which are less susceptible to CIA than mice with a DBA/1 background. To clarify the immunological functions of NKT cells in CIA, it is necessary to analyze in detail the effects of NKT cell deficiency on CIA development in DBA/1 mice. The incidence and severity of CIA were significantly exacerbated in DBA/1CD1d(+/-) mice as compared to DBA/1CD1d(-/-) mice. In DBA/1CD1d(+/-) mice, antigen-specific responses of B and T cells against CII were remarkably increased and inflammatory cytokine levels were also increased in vivo and in vitro. The number of IL-17-producing NKT cells significantly increased in DBA/1CD1d(+/-) mice as the disease progressed. Our results clearly show that NKT cells are involved not only in accelerating the severity and incidence of CIA but also in perpetuating the disease progression.
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http://dx.doi.org/10.1016/j.bbrc.2009.09.008DOI Listing
December 2009

Regulation of secondary antigen-specific CD8(+) T-cell responses by natural killer T cells.

Cancer Res 2009 May 28;69(10):4301-8. Epub 2009 Apr 28.

School of Life Sciences and Biotechnology, Korea University, Sungbukku Anamdong, Seoul, Korea.

The physiologic function of natural killer T (NKT) cells in adaptive immunity remains largely unknown because most studies have used NKT cell agonists. In the present study, the role of NKT cells during the secondary effector phase was investigated separately from the primary immunization phase via adoptive transfer of differentiated effector T cells into naive recipients. We found that secondary antitumor CD8(+) T-cell responses were optimal when NKT cells were present. Tumor-specific CD8(+) effector T cells responded less strongly to tumor cell challenge in NKT cell-deficient recipients than in recipients with intact NKT cells. NKT cell-mediated enhancement of the secondary antitumor CD8(+) T-cell response was concurrent with increased number and activity of tumor-specific CD8(+) T cells. These findings provide the first demonstration of a direct role for NKT cells in the regulation of antigen-specific secondary T-cell responses without the use of exogenous NKT cell agonists such as alpha-galactosylceramide (alpha-GalCer). Furthermore, forced activation of NKT cells with alpha-GalCer during the secondary immune response in suboptimally immunized animals enhanced otherwise poor tumor rejection responses. Taken together, our findings strongly emphasize the importance of NKT cells in secondary CD8(+) T-cell immune responses.
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http://dx.doi.org/10.1158/0008-5472.CAN-08-1721DOI Listing
May 2009

[A case of primary omental torsion presenting as an acute abdominal pain].

Korean J Gastroenterol 2007 Jan;49(1):41-4

Department of Internal Medicine, Hanyang University College of Medicine, Guri, Korea.

Torsion of greater omentum is a rare cause of acute abdomen. However, it should be included in the differential diagnoses in addition to acute cholecystitis, acute appendicitis, cecal diverticulitis, and other variable causes of acute abdomen. Diagnosis is usually made at laparotomy for suspected appendicitis. In some cases, computed tomography demonstrates a successful preoperative detection of omental torsion. We report a case of surgically and pathologically proven torsion with subsequent infarction of greater omentum presented as an acute abdominal pain.
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January 2007

[A case of successful endoscopic injection sclerotherapy with N-butyl-2-cyanoacrylate for ruptured duodenal varices].

Korean J Gastroenterol 2007 May;49(5):336-40

Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.

Duodenal varix is a rare cause of hemorrhage in patients with portal hypertension, however their rupture is serious and often life threatening. Treatments for duodenal variceal bleeding include endoscopic procedures, surgery, or interventional radiologic procedures. We report a case of duodenal varices rupture in a 45-year-old man with alcoholic liver cirrhosis who presented with melena and dizziness. Emergent upper endoscopy revealed large nodular varices with a ruptured erosion on the top in the distal second portion of duodenum. Two consecutive injections with 1.0 mL of n-butyl-2-cyanoacrylate (Histoacryl; Braun-Melsungen, Germany) mixed with 1.0 mL of lipiodol (Laboratoire-Guerbet, France) were performed intravariceally and achieved successful hemostasis. This suggests that endoscopic injection sclerotherapy with histoacryl may be an effective therapeutic option for the control of ruptured duodenal variceal bleeding.
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May 2007

[Pulmonary toxicity by pegylated interferon alpha-2a in a patient with chronic hepatitis C].

Korean J Hepatol 2007 Mar;13(1):103-7

Department of internal medicine, Hanyang University College of medicine, Guri, Korea.

The combination therapy with pegylated interferon alpha and ribavirin has increasingly prescribed for chronic hepatitis C. Although many side effects of interferon such as flu-like symptoms, gastrointestinal and neuropsychiatric symptoms are well known, only several cases of interferon-induced pulmonary toxicity have been reported. Interferon-induced pulmonary toxicity usually develops from 2 weeks to 12 weeks after treatment for HCV infection. Diagnosis is commonly based on clinical findings such as a dry cough, dyspnea, hypoxemia, and a restrictive pattern in pulmonary function testing, bilateral diffuse parenchymal infiltrations, histopathological findings of interstitial pneumonitis, and exclusion of any other causative agents. Prompt withdrawal of the drug is the cornerstone of treatment. We report a case of PEG-IFN alpha-2a induced pulmonary toxicity in a 50-year-old male patient with hepatitis C. To our knowledge, this is the first case of pegylated interferon alpha-2a induced pulmonary toxicity in Korea.
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March 2007

Risk of advanced proximal adenoma and cancer according to rectosigmoid findings in the Korean population.

Dig Dis Sci 2006 Dec 7;51(12):2206-12. Epub 2006 Nov 7.

Division of Gastroenterology and Hepatology, Departments of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.

Colorectal cancer is one of the leading causes of cancer death in the United States and Europe. Recently, the incidence of colorectal cancer has been increasing remarkably in Korea. To reduce the high incidence, screening of colorectal cancer in asymptomatic individuals has been advocated. Sigmoidoscopy is simpler, faster, and better tolerable than total colonoscopy, but the scope cannot reach the proximal colon segment and, therefore, may miss proximal colon cancer. In the present study, we intended to investigate the prevalence of proximal adenoma and cancer according to the findings in rectosigmoid colon and to find their risk factors. Data were collected retrospectively from 1541 consecutive patients who underwent total colonoscopy at the Department of Gastroenterology, Hanyang University, between October 2003 and December 2004. Neoplasms were classified as diminutive adenoma (< or =5 mm), small adenoma (6-9 mm), advanced adenoma (> or =10 mm, with villous component or high-grade dysplasia), and cancer. The sites of neoplasms were defined as rectosigmoid (rectum and sigmoid colon) and proximal (from cecum to descending colon) colon. The prevalence of advanced proximal adenoma was associated with severe rectosigmoid findings. On the other hand, the prevalence of proximal colon cancer did not show such a tendency. Among the 131 patients with proximal advanced adenoma, 66% had no neoplasm in the rectosigmoid colon. Moreover, among the 27 patients with proximal cancer, 52% had no neoplasm in the rectosigmoid colon. Multivariate logistic regression analysis revealed that age, gender, and advanced rectosigmoid adenoma were the risk factors of advanced proximal adenoma, but nothing was associated with the risk for proximal colon cancer. Advanced rectosigmoid adenoma may be the predictor of advanced proximal adenoma, especially in old males. However, nothing is related to the risk for proximal colon cancer. Therefore, colonoscopy may be more adequate for colorectal cancer screening than sigmoidoscopy in the Korean population.
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http://dx.doi.org/10.1007/s10620-006-9295-xDOI Listing
December 2006

Lipid rafts are required for efficient signal transduction by CD1d.

Biochem Biophys Res Commun 2005 Feb;327(4):1143-54

Graduate School of Life Sciences and Biotechnology, Korea University, Anam-Dong, Sungbuk-Ku, Seoul 136-701, Republic of Korea.

Plasma membranes of eukaryotic cells are not uniform, possessing distinct cholesterol- and sphingolipid-rich lipid raft microdomains which constitute critical sites for signal transduction through various immune cell receptors and their co-receptors. CD1d is a conserved family of major histocompatibility class I-like molecules, which has been established as an important factor in lipid antigen presentation to natural killer T (NKT) cells. Unlike conventional T cells, recognition of CD1d by the T cell receptor (TCR) of NKT cells does not require CD4 or CD8 co-receptors, which are critical for efficient TCR signaling. We found that murine CD1d (mCD1d) was constitutively present in the plasma membrane lipid rafts on antigen presenting cells, and that this restricted localization was critically important for efficient signal transduction to the target NKT cells, at low ligand densities, even without the involvement of co-receptors. Further our results indicate that there may be additional regulatory molecule(s), co-located in the lipid raft with mCD1d for NKT cell signaling.
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http://dx.doi.org/10.1016/j.bbrc.2004.12.121DOI Listing
February 2005

Postsplenectomy recurrence of thrombocytopenia with an accessory spleen.

Korean J Intern Med 2004 Sep;19(3):199-201

Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.

Autoimmune thrombocytopenic purpura (AITP) is an autoimmune disorder that results from antiplatelet autoantibodies; these autoantibodies cause platelet destruction in the reticluoendothelial system. Oral corticosteroid therapy is the first line treatment. Splenectomy is the major treatment modality after the failure of more conservative medical therapy. Approximately 15% of the patients will relapse either soon after splenectomy or, as is less common, many years later. The presence of an accessory spleen should be sought. We experienced a patient with a known diagnosis of autoimmune thrombocytopenic purpura who had a worsening thrombocytopenia 11 years after splenectomy. This patient was diagnosed with an accessory spleen. Accessory splenectomy was performed with only a transient elevation of the platelets. We report here on this case with a review of the literature.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4531559PMC
http://dx.doi.org/10.3904/kjim.2004.19.3.199DOI Listing
September 2004

[Incidence of gallbladder stones in renal transplant recipients].

Korean J Gastroenterol 2004 Jul;44(1):42-6

Department of Internal Medicine, Hanyang University College of Medicine, Gyeonggi, Korea.

Background/aims: Gallbladder stone is one of the major cause of morbidity in adults. Renal transplantation has been found to increase the risk of gallbladder stone formation. The real incidence of gallbladder stones in renal transplant recipients is not exactly known. We performed this study to identify the risk factors for cholecystolithiasis.

Methods: We compared the prevalence of gallbladder stone in 222 renal transplantation patients with that in 222 age and sex matched controls. Patients who had chronic liver disease, renal disease, and diabetes were excluded from the control group.

Results: In our study, the incidence of gallbladder stones is 8.6% (19/222 patients) in renal transplantation patients, which was significantly higher than 3.60% (8/222 control) in the control group (p=0.029). In the most of our renal transplantation patients, cholecystolithiasis was asymptomatic. We did not find a difference in age, sex, duration after transplantation, causes of renal failure, resistance index between patients with and without gallbladder stones in renal transplantation patients.

Conclusions: Our results suggest that the incidence of gallbladder stones is higher in renal transplant recipients than non-transplant population in Korea. Further studies will be needed to focus the factors contributing to the gallbladder stone formation after renal transplantation, especially in regard to immunosuppressive drugs.
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July 2004