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Cha, Hoon-Suk,Bae, Eun-Kyung,Ahn, Joong-Kyong,Lee, Jae-Joon,Ahn, Kwang-Sung,Koh, Eun-Mi Korean Society for Biochemistry and Molecular Bion 2010 Experimental and molecular medicine Vol.42 No.6
Inadequate apoptosis contributes to synovial hyperplasia in rheumatoid arthritis (RA). Recent study shows that low expression of Puma might be partially responsible for the decreased apoptosis of fibroblast-like synoviocytes (FLS). Slug, a highly conserved zinc finger transcriptional repressor, is known to antagonize apoptosis of hematopoietic progenitor cells by repressing Puma transactivation. In this study, we examined the expression and function of Slug in RA FLS. Slug mRNA expression was measured in the synovial tissue (ST) and FLS obtained from RA and osteoarthritis patients. Slug and Puma mRNA expression in FLS by apoptotic stimuli were measured by real-time PCR analysis. FLS were transfected with control siRNA or Slug siRNA. Apoptosis was quantified by trypan blue exclusion, DNA fragmentation and caspase-3 assay. RA ST expressed higher level of Slug mRNA compared with osteoarthritis ST. Slug was significantly induced by hydrogen peroxide ($H_2O_2$) but not by exogenous p53 in RA FLS. Puma induction by $H_2O_2$ stimulation was significantly higher in Slug siRNA-transfected FLS compared with control siRNA-transfected FLS. After $H_2O_2$ stimulation, viable cell number was significantly lower in Slug siRNA-transfected FLS compared with control siRNA-transfected FLS. Apoptosis enhancing effect of Slug siRNA was further confirmed by ELISA that detects cytoplasmic histone-associated DNA fragments and caspase-3 assay. These data demonstrate that Slug is overexpressed in RA ST and that suppression of Slug gene facilitates apoptosis of FLS by increasing Puma transactivation. Slug may therefore represent a potential therapeutic target in RA.
차신웅,용석중,박진현,신계철 대한내과학회 1990 대한내과학회지 Vol.38 No.1
Adenosine deaminase(ADA) is an enzyme whcih catalyzes the irreversible hydrolytic deamination of adenosine to produce inosine and ammonia. Recent investigations have demonstrated that the deamination of ADA activities in pleural fluid, cerebrospinal fluid and ascites is useful in the differential diagnosis of tumberculosis in those fluids. In this study, serum ADA activities were measured in 13 cases of miliary tuberculosis, 40 pulmonary turberculosis, 17 cases of pneumonia, 13 cases of pneumoconiosis, 8 cases of metastatic lung cancer and 40 cases of normal controls. The results obtained were as follows: 1) The mean serum ADA activity in miliary tuberculosis 93.85±33.93 U/L, pulmpnary tuberculosis was 38. 85±11.99 U/L, pneumonia 25.02±7.57 U/L, pneumonia 26.71±8.91 U/L, metastatic lung cancer was 27.48±9.38 U/L and normal control 19.22±4.03 U/L. 3) The serum ADA activity above 70 U/L had a sensitiveity of 77% and a specificity of 93% when used as a screening test for miliary tuberculosis compared to pulmonary tuberculosis. 4) There was no statistical correlation between the serum ADA activity and the SGOT, SGPT, and alkaline phosphatase in miliary tuberculosis. 5) After antituberculous therapy, serum ADA activity tended to slightly decreased for 4 weeks but marked decrease after 8 weeks. It is suggested that measurement of ADA activity in serum is an available test which is relatively easily performed for diagnosis of miliary tuberculosis.
Ahn, Joong Kyong,Hwang, Ji-Won,Bae, Eun-Kyung,Lee, Jaejoon,Jeon, Chan Hong,Koh, Eun-Mi,Cha, Hoon-Suk Kluwer Academic/Plenum Publishers 2012 INFLAMMATION Vol.35 No.2
<P>Fibroblast-like synoviocytes (FLS) play an important role in the pathogenesis of rheumatoid arthritis. Raf kinase inhibitor protein (RKIP) negatively regulates the Raf/MEK/ERK and NF-관B pathway. The role of RKIP in rheumatoid FLS is unknown. The purpose of the present study was to investigate the function of RKIP in rheumatoid FLS. Rheumatoid FLS were transfected with either RKIP-expressing plasmids or RKIP small interfering RNA (siRNA). RKIP protein was detected in rheumatoid synovial tissue (ST) and FLS. RKIP overexpression significantly decreased IL-6 mRNA expression in TNF-관-stimulated rheumatoid FLS. RKIP overexpression also showed a decreased trend in IL-8, MMP-1, and MMP-3 mRNA expression in TNF-관-stimulated rheumatoid FLS. RKIP silencing resulted in significantly increased MMP-1 and MMP-3 mRNA expression in TNF-관-stimulated rheumatoid FLS. RKIP silencing also increased IL-6 and IL-8 mRNA expression in TNF-관-stimulated rheumatoid FLS, but this increase did not reach statistical significance. TNF-관-induced ERK and NF-관B activation was suppressed in FLS with RKIP overexpression. RKIP silencing resulted in a significantly higher invasion index in TNF-관-stimulated rheumatoid FLS compared to controls. These results suggest that RKIP might be a potential therapeutic target for rheumatoid arthritis.</P>
Ahn, Joong Kyong,Kim, Jungyeon,Hwang, Jiwon,Song, Juhwan,Kim, Kyoung Heon,Cha, Hoon-Suk MDPI 2017 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.18 No.11
<P>Diagnosing Behcet’s disease (BD) is challenging because of the lack of a diagnostic biomarker. The purposes of this study were to investigate distinctive metabolic changes in urine samples of BD patients and to identify urinary metabolic biomarkers for diagnosis of BD using gas chromatography/time-of-flight–mass spectrometry (GC/TOF−MS). Metabolomic profiling of urine samples from 44 BD patients and 41 healthy controls (HC) were assessed using GC/TOF−MS, in conjunction with multivariate statistical analysis. A total of 110 urinary metabolites were identified. The urine metabolite profiles obtained from GC/TOF−MS analysis could distinguish BD patients from the HC group in the discovery set. The parameter values of the orthogonal partial least squared-discrimination analysis (OPLS-DA) model were <I>R</I><SUP>2</SUP><I>X</I> of 0.231, <I>R</I><SUP>2</SUP><I>Y</I> of 0.804, and <I>Q</I><SUP>2</SUP> of 0.598. A biomarker panel composed of guanine, pyrrole-2-carboxylate, 3-hydroxypyridine, mannose, <SMALL>L</SMALL>-citrulline, galactonate, isothreonate, sedoheptuloses, hypoxanthine, and gluconic acid lactone were selected and adequately validated as putative biomarkers of BD (sensitivity 96.7%, specificity 93.3%, area under the curve 0.974). OPLS-DA showed clear discrimination of BD and HC groups by a biomarker panel of ten metabolites in the independent set (accuracy 88%). We demonstrated characteristic urinary metabolic profiles and potential urinary metabolite biomarkers that have clinical value in the diagnosis of BD using GC/TOF−MS.</P>
Ahn, Joong Kyong,Huang, Bo,Bae, Eun-Kyung,Park, Eun-Jung,Hwang, Ji-Won,Lee, Jaejoon,Koh, Eun-Mi,Cha, Hoon-Suk Oxford University Press 2013 Rheumatology Vol.52 No.8
<P><B>Objectives.</B> To investigate the effect of α-defensin-1 on the expression of IL-6, IL-8 and MMPs as well as the signal transduction mechanisms responsible for their expression in RA fibroblast-like synoviocytes (FLS).</P><P><B>Methods.</B> The concentrations of α-defensin-1 in SF were measured by ELISA. In RA FLS, mRNA expression of IL-6, IL-8 and MMPs and activation of signalling molecules were examined by real-time PCR, western blotting and electrophoretic mobility shift assay.</P><P><B>Results.</B> Concentrations of SF α-defensin-1 were significantly increased in RA patients compared with OA patients. The levels of mRNA expression of IL-6, IL-8, MMP-1 and MMP-3 were significantly increased in RA FLS treated with α-defensin-1 compared with controls. Furthermore, α-defensin-1 activated JNK and ERK in RA FLS, respectively. Treatment of RA FLS with ERK or JNK inhibitors prior to α-defensin-1 treatment resulted in reduced expression of IL-6, IL-8, MMP-1, and MMP-3 compared with controls. Remarkably, treatment of RA FLS with an ERK inhibitor prior to α-defensin-1 stimulation significantly reduced production of IL-6 and MMP-1 by approximately 71% and 98% compared with controls, respectively. The JNK inhibitor significantly suppressed α-defensin-1-induced MMP-1 production by approximately 73% compared with controls. Finally, there was a significant induction of NF-κB DNA binding activity in response to α-defensin-1.</P><P><B>Conclusion.</B> Our results suggest that α-defensin-1 may play a role in RA pathogenesis by regulating the production of MMPs as well as IL-6 and IL-8. These processes were dependent on the regulation of the JNK and/or ERK and NF-κB pathways.</P>
류마티스 섬유모세포양 활막세포에서 저산소증이 시토카인 생산에 미치는 영향
안중경 ( Joong Kyung Ahn ),전찬홍 ( Chan Hong Jeon ),고재현 ( Jae Hyun Koh ),김진희 ( Jin Hee Kim ),최화정 ( Hwa Jung Choi ),안광성 ( Kwang Sung Ahn ),차훈석 ( Hoon Suk Cha ),유석희 ( Suk Hee Yu ),고은미 ( Eun Mi Koh ) 대한류마티스학회 2003 대한류마티스학회지 Vol.10 No.1
Objective: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by increased production of cytokines, proliferation of fibroblast-like synoviocytes (FLS) and joint destruction. It is well known that the involved joints in RA are hypoxic. Hypoxia may play a role in the pathogenesis of RA. We thought that hypoxia might alter the production of cytokines by FLS and these changes could affect the biologic behaviors of FLS. Based on that, we investigated whether hypoxia affects the production of cytokines in FLS and the effect of these changes on matrix metalloproteinases (MMPs) expression. Methods: Fibroblast-like synoviocytes from human rheumatoid synovial tissue obtained duringjoint replacement surgery were cultured in vitro. Hypoxic culture was performed by incubating cells in BBL(R) Gaspak pouch(TM) anaerobic system. After incubation under hypoxic condition for 24 hr, the concentrations of various cytokines in culture supernatants were determined by ELISA. To determine the effect of highly expressed cytokines on MMP expression, we performed ELISA of MMP-1, MMP-2 and MMP-3 in cultured FLS, after stimulation with respective cytokines. Results: In hypoxic state, IL-6, IL-8 and vascular endothelial growth factor (VEGF) concentrations were significantly increased compared to those in normoxic condition. However, there were little differences in IL-1, IL-2, IL-4, TNF-α and TGF-β. Stimulation of FLS with IL-6 and IL-8 showed the increased concentrations of MMP-1, MMP-2 and MMP-3. Conclusion: Hypoxic environment of rheumatoid synovium might affect FLS to produce proinflammatory and proangiogenic cytokine such as IL-6 and IL-8. These cytokines again could stimulate MMPs production in FLS leading to joint destruction.
안중경 ( Joong Kyung Ahn ),고재현 ( Jae Hyun Koh ),전찬홍 ( Chan Hong Jeon ),차훈석 ( Hoon Suk Cha ),김영호 ( Young Ho Kim ),고은미 ( Eun Mi Koh ) 대한류마티스학회 2002 대한류마티스학회지 Vol.9 No.4
Intestinal pseudo-obstruction is an uncommon and poorly understood complication of systemic lupus erythematosus. It is characterized by acute or chronic symptoms suggestive of the obstruction of small or large intestine without any radiologic, surgical or endoscopic evidence of mechanical obstruction. Although the exact pathogenesis of intestinal pseudo-obstruction in SLE remains unknown, it can be caused by derangement of the visceral smooth muscle, enteric nerves or visceral autonomic nervous system. Concomitant involvement with dilatation of gastrointestinal and genitourinary tract highly suggests of intestinal pseudo-obstruction in systemic lupus erythematosus. There is an apparent association between lupus-related intestinal pseudo-obstruction and ureterohydronephrosis. The management of intestinal pseudo-obstruction consists of high dose corticosteroid, adequate nutrition, hydration and prokinetics. Early recognition of intestinal pseudo-obstruction in systemic lupus erythematosus and the use of adequate dose of corticosteroid are important. We report a case of systemic lupus erythematosus presenting as intestinal pseudo-obstruction.