Association between chronic hepatitis B virus infection and interleukin-10, tumor necrosis factor-α gene promoter polymorphisms

Cheong, Jae Youn,Cho, Sung Won,Hwang, Il Lan,Yoon, Seung Kew,Lee, June Hyuk,Park, Choon Sik,Lee, Jong Eun,Hahm, Ki Baik,Kim, Jin Hong Blackwell Publishing Asia 2006 Journal of gastroenterology and hepatology Vol.21 No.7

<P>Abstract</P><P>Background: </P><P>The reasons for the viral persistence of hepatitis B virus infection (HBV) are unknown, but are probably related to host immune factors. Cytokines play a significant role in immune defense. The present study was undertaken to investigate the association between HBV infection and polymorphisms of tumor necrosis factor (TNF)-α and interleukin(IL)-10 gene promoter.</P><P>Methods: </P><P>A total of 412 Korean patients with HBV infection (72 inactive carriers, 261 witih chronic hepatitis, 79 with liver cirrhosis) and 204 healthy individuals who recovered from HBV infection, were studied. The polymorphisms in IL-10 gene promoter (−1082, −819, −592), and TNF-α gene promoter (−308, −238) were assessed by single base primer extension assay.</P><P>Results: </P><P>The frequency of C/C genotype at position −592 of IL-10 gene promoter was higher in the HBV clearance group than that in the persistence group in univariate analysis (12.7% vs 7.5%, <I>P</I> = 0.036). The IL-10 gene promoter −592 C/C genotype was related to clearance of HBV infection in logistic regression analysis after adjusting for age and sex (<I>P</I> = 0.003). Genotype frequencies of TNF-α gene promoter at position −308 and −238 were not different between the clearance and the persistence group in univariate analysis, but in multivariate analysis after adjusting for age and sex, −308G/−238G homozygotes were associated with HBV persistence (<I>P</I> = 0.005). Genotype distributions of both gene promoters in inactive carriers were similar to those in patients with chronic progressive liver disease.</P><P>Conclusions: </P><P>The carriers of the −592A allele in the IL-10 promoter and −308G/−238G haplotype homozygotes in the TNF-α promoter region have higher risk of persistent HBV infection.</P>

The Korean Society of Gastroenterology & SIDDS 2040 : Slide Session ;K-LG-11 : Lower GI Tract ; Guggulsterone Ameliorates Colitis by Blocking Crosstalk Between Nf-κb and Trem-1

( Soo Jung Park ),( Ki Cheong Park ),( You Hyun Kang ),( Hyun A Jin ),( Xiu Mei Che ),( Seung Won Kim ),( Sung Pil Hong ),( Tae Il Kim ),( Won Ho Kim ),( Jae Hee Cheon ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: Triggering receptor expressed on myeloid cells (TREM)-1 constitutively expressed in macrophage, and upregulated by bacterial components, such as lipopolysaccharide (LPS), and functions as an amplifying molecule in infi ammatory responses. Recent studies have reported that TREM-1 expression is up-regulated in patients with infi ammatory bowel disease (IBD). In this study, we expected that guggulsterone (GGS) functions as reducer of TREM-1 in macrophage and investigated the anti-infi ammatory effects of GGS via the inhibition of NF-κB/TREM-1 in mononuclear cells using RAW264.7 activated by LPS and TNBS-induced colitis model of knockout mice. Methods: We are checked the mRNA level of TREM-1 and toll like receptor 4 (TLR4) using real time RT-PCR and the protein level of IκBa and phospho-IκBa using western blotting and ELISA, and nuclear translocation of NF-κB using immunofi uorescence. MG132 and TREM-1 antibody were used to determine the interaction of NF-κ B and TREM-1 signaling. Mouse colitis is induced by the administration of TNBS into the colon. Results: GGS treatment decreased the mRNA and protein levels of TREM-1, TLR4, TNF-a, IL-6, IL17, COX-2, and MMP-9 by blocking the phosphorylation and degradation of IκBa as well as nuclear translocation of NF-κB in RAW264.7 macrophage activated by LPS. In the TNBS-induced colitis model, GGS reduced disease activity index (DAI), and infi ammation related protein expressions by suppressing NF-κB and TREM- 1 activation in colon mucosa. Conclusions: GGS blocks the NF-κB signaling pathway by targeting the TREM-1 in RAW264.7 macrophage activated by LPS and TNBS-induced mouse colitis model. Ourresults provide an insight into the mutual relationship NF-κB and TREM-1 signaling pathway. Eventually, these fi ndings shows that GGS has a anti-infi ammatory effects in macrophage cells through the regulation of the TREM-1 and NF-κB signaling, which suggests that GGS is a potential therapeutic agent for the treatment of IBD.

소아의 미세변화형 신증후군 및 초점성 분절성 사구체 경화증 환아에서 혈청 및 요의 용해성 인터루킨-2수용체

하일수,정해일,최용,Ha, Il-Soo,Cheong, Hae-Il,Choi, Yong 대한소아신장학회 1999 Childhood kidney diseases Vol.3 No.1

목 적 : 가능한 교란인자들, 즉 연령, 단백뇨, 스테로이드 사용 등의 영향이 배제된 조건에서 소아의 신증후군, 또는 그 중의 어떤 특성이 혈청이나 요의 용해성 인터루킨-2수용체 (sIL-2R)에 영향을 주는지를 알기 위해 이 연구를 시행하였다. 방 법 : 소아의 일차성 신증후군 중 임상적 혹은 병리소견으로 미세변화형 신증후군으로 진단되거나 병리소견상 초점성 분절성 사구체경화증으로 진단된 환아를 대상으로 이들을 연령 (0-l세, 2-4세, 5세 이상), 단백뇨 및 스테로이드 사용 여부 (PU+Tx-, PU+Tx+, PU-Tx+, PU-Tx-)로 구분하였다. 이들과 대조군의 혈청, 요에서 ELISA법으로 각각 sIL-2R를 정량하고, 요에서는 크레아티닌치도 측정하였다. 각 군의 혈청 sIL-2R치와 요 sIL-2R/크레아티닌 비를 계산하여 비교하였다. 결 과 : 혈청 sIL-2R는 환자와 대조군에서 도두 연령이 어릴수록 높았고, 신증후군에서 대조군보다 높지 않았다. 환자군 중에서 재발한 경우에는 높고 스테로이드 투여 시에는 낮은 경향을 보였다. 요 sIL-2R/크레아티닌 비는 특히 단백뇨가 있을 때 연령이 어릴수록 높았고 (P=0.01), 혈청 치와 마찬가지로 재발과 스테로이드의 영향을 받았다. 혈청 sIL-2R치와 요 sIL-2R/크레아티닌 비는 신 병리소견, 스테로이드 반응도에 따른 차이를 보이지 않았다 (P>0.05). 결 론 : 혈청 sIL-2R치는 연령에 따른 차이가 크고, 신증후군에서 대조군에 비해 높지 않았으나, 재발상태의 환자는 완해 상태의 환자보다 높았고, 스테로이드를 투여할 때에 낮았다. 요 sIL-2R/크레아티닌 비는 특히 단백뇨가 있을 때 혈청 sIL-2R치를 잘 반영하였다. Purpose: This study was designed to investigate the changes in soluble interleukin-2 receptor (sIL-2R) level in sera and urines of children with primary nephrotic syndrome, eliminating the confounding effects of age, proteinuria, and steroid treatment. Methods: Soluble IL-2R was measured by ELISA in sera and urines from patients with minimal change nephrotic syndrome or focal segmental glomerulosclerosis as well as from healthy controls. The serum levels and urinary sIL-2R/creatinine ratios were compared between control group and the 12 patient groups divided by their ages (0-1, 2-4, over 5 years), and presence or absence of proteinuria and/or steroid treatment (PU+Tx-, PU+Tx+, PU-Tx+, PU-Tx-). Results: Though the differences were not statistically significant probably because of the small numbers, serum sIL-2R levels seemed to be higher in younger age groups both in patients and control group. Nephrotic children did not show higher serum levels than normal children. Among the patients, proteinuric condition seemed to raise and steroid treatment tended to suppress the serum sIL-2R levels. Urinary sIL-2R/creatinine ratios were higher in younger age groups, more significantly in patients (P<0.001). Proteinuria and steroid treatment affected the urinary sIL-2R/creatinine ratios by the same way as the serum sIL-2R levels. Serum sIL-2R levels and urinary sIL-2R/creatinine ratios were not different between groups of different histologic findings or steroid responsiveness (P>0.05). Conclusion: Serum sIL-2R levels and the urinary sIL-2R/creatinine ratios were higher in younger age, and they were not higher in nephrotic patients compared to control group. The patients in relapse showed higher levels, while the levels were suppressed with steroid treatment. In proteinuric state, urinary sIL-2R/creatinine ratios reflected serum sIL-2R levels.

Solubility of Carbon Dioxide in Strongly Basic Ionic Liquid

Sung, Jun-Kyung,Kim, Sung-Hyun,Cheong, Min-Serk,Baek, Il-Hyun Korean Chemical Society 2010 Bulletin of the Korean Chemical Society Vol.31 No.10

For the purpose of developing advanced new absorbents for carbon dioxide, ionic liquids (ILs) are considered as alternative materials due to their superior properties to conventional organic solvents. Since low $CO_2$ solubility in ionic liquids is a major concern for their application as absorbents, it is essential to focus on improving $CO_2$ absorbing capability of ILs. In this paper, strongly basic ionic liquids, namely [$C_n$-mim]OPh (n = 2, 4, 6), have been synthesized and studied over a wide range of temperature and pressure changes. [$C_n$-mim]OPh can be easily synthesized from corresponding [$C_n$-mim]Cl and sodium phenoxide and has been found to be good $CO_2$ absorbents.

Mesenchymal Stem Cells Ameliorate Adriamycin Induced Proteinuric Nephropathy

강희경,박소연,하일수,정해일,최용,Kang, Hee-Gyung,Park, So-Yeon,Ha, Il-Soo,Cheong, Hae-Il,Choi, Yong Korean Society of Pediatric Nephrology 2010 Childhood kidney diseases Vol.14 No.1

목 적 : 사구체신염은 흔히 단백뇨를 보이며 특이 치료법이 없고, 만성 신부전으로 발전하는 경우가 많다. 몇몇 연구에서 중간엽 줄기세포(Mesenchymal stem cell, MSC)를 실험적 사구체신염에 투여하여 단백뇨가 호전된 것을 보고한 바 있으나, 이는 신염을 일으키는 약제와 중간엽 줄기세포를 함께 투여하거나 신장에 직접 투여한 것이었다. 본 연구에서는 실험적 신병증에서 단백뇨가 발현된 시점에서 정주 요법으로 MSC를 투여함으로써 MSC의 임상적인 적용 가능성을 탐색하였다. 방 법 : 실험용 생쥐에 Adriamycin을 투여하여 신병증(ADR-GN)을 유발한 후, 2주 후에 대량의 단백뇨를 확인하고 MSC를 생쥐 꼬리의 정맥에 주사하였다. MSC에 의한 질병 완화의 기전을 확인하기 위한 in vitro 실험으로 mixed lymphocyte culture(MLC)에 MSC를 투여하였을 때의 염증 관련 cytokine인 IFN-$\gamma$ and IL-10의 변화를 측정하였다. 결 과 : 실험용 생쥐에 ADR-GN를 유발하고 단백뇨가 보일 때 MSC를 정주한 군에서는 단백뇨의 소실이 더 먼저 관찰되었다. 또한 MSC를 투여받은 군에서의 생존률이 더 나은 경향이 관찰되었다. MLC 에 MSC를 투여하였을 때, 염증을 유발하는 cytokine인 IFN-$\gamma$ 는 감소하고 염증을 억제하는 cytokine인 IL-10는 증가하였다. 결 론 : 이 연구는 이전의 보고들에서 관찰되었던 사구체신염에서의 MSC의 질병완화 효과가 좀더 임상적으로 적용 가능한 방법으로 투여된 경우, 즉 단백뇨가 있을 때 정주 요법으로 투여한 경우에도 관찰됨을 확인하였다. 이러한 효과의 기전과 임상적용에 요구되는 안전성 등에 대한 확인을 위해서는 추가 연구가 필요하겠다. Purpose : Glomerulonephropathy (GN) often manifests as proteinuria and progresses to chronic renal failure without specific therapy. Mesenchymal stem cell (MSC) has been tried as a therapeutic agent in experimental GN, and previous studies showed that administration of MSC concomitantly to the insult inducing GN or via intra-renal administration ameliorated proteinuria. The purpose of this study was to test the therapeutic potential of MSC administered via intravenous route at the time of clinically evident proteinuria. Methods : MSCs were administered intravenously via tail vain into the mice with adriamycin (ADR) induced nephropathy (ADR-GN), two weeks after ADR injection when massive proteinuria was evident. To test the capacity of MSC modulate the cytokine production in the inflammatory milieu, the concentrations of IFN-$\gamma$ and IL-10 were measured in the supernatant of in vitro mixed lymphocyte culture (MLC) with or without additional MSC. Results : MSCs administered intravenously into the proteinuric mice with ADR-GN accelerated the recovery of this experimental GN with disappearance of proteinuria in two weeks when the saline treated (control) mice still showed significant proteinuria. The mice treated with MSC also had a tendency of better survival. Addition of MSC decreased IFN-$\gamma$ and increased IL-10 in the supernatant of MLC. Conclusion : This study showed that MSC had a therapeutic potential even when administered in a more clinically relevant setting into a proteinuric glomerulonephropathy model. Further study to verify the mechanism and long-term safety of this phenomenon is required.

국소성 분절성 사구체 신병증의 동물 모델 (FGS/kist 생쥐) 신 조직의 유전자 발현 양상

강희경,이병섭,이철호,하일수,정해일,최용,Kang, Hee-Gyung,Lee, Byong-Sop,Lee, Chul-Ho,Ha, Il-Soo,Cheong, Hae-Il,Choi, Yong 대한소아신장학회 2011 Childhood kidney diseases Vol.15 No.1

목 적: 국소성 분절성 사구체 경화증(Focal segmental glomerulosclerosis, 이하 FSGS)은 소아신부전의 원인 중 가장 흔한 사구체 질환이다. 일차성 FSGS의 병인은 아직 알려져 있지 않으므로, 저자들은 FSGS의 동물 모델을 대상으로 cDNA 마이크로어레이를 이용한 유전자 발현 양상 분석을 통하여 유전자 발현 수준에서의 FSGS의 질환의 특성을 밝히고자 하였다. 방 법: 사람의 일차성 FSGS와 유사한 질병경과를 보이는 동물모델인 FGS/kist 생쥐의 신피질 조직을 대조군 생쥐(FGS/kist 생쥐의 조상 strain인 RFM/kist 생쥐)와 AB 1700 mouse chip을 이용한 마이크로어레이 실험으로 비교하였다. 결 과: FGS 질병특이 유전자가 62개 추출되었다. 이들은 세포주기/사멸, 면역반응과 지질 대사/혈관 질환과 관련된 유전자들로써, 유전자간 network의 중심유전자가 면역반응(TNF, IL-6/4, IFNg)과 세포사멸 조절 유전자(TP 53), 그리고 지질대사의 중요 유전자인 PPARG이었다. 결 론: 이 연구에서 저자들은 자발적인 FSGS의 임상경과를 보이는 FGS/Kist 생쥐의 신장조직의 유전자 발현의 분석을 통하여 신장세포사멸과 면역반응에 뒤따르는 기질 섬유화, 그리고 지질 대사의 이상과 조기 혈관 질환이 FSGS의 병태생리에 기여할 것임을 다시 확인할 수 있었다. 추가적인 연구가 계속된다면 global transcriptome profiling 기법으로 병인 탐색 및 치료방법 개발 에 의미 있는 결과를 도출할 수 있을 것이다. Purpose: Focal segmental glomerulosclerosis (FSGS) is the most common glomerulopathy causing pediatric renal failure. Since specific treatment targeting the etiology and pathophysiology of primary FSGS is yet elusive, the authors explored the pathophysiology of FSGS by transcriptome analysis of the disease using an animal model. Methods: FGS/kist strain, a mouse model of primary FSGS, and RFM/kist strain, as control and the parent strain of FGS/kist, were used. Kidney tissues were harvested and isolated renal cortex was used to extract mRNA, which was run on AB 1700 mouse microarray chip after reverse transcription to get the transcriptome profile. Results: Sixty two genes were differentially expressed in FGS/kist kidney tissue compared to the control. Those genes were related to cell cycle/cell death, immune reaction, and lipid metabolism/vasculopathy, and the key molecules of their networks were TNF, IL-6/4, IFN${\gamma}$, TP53, and PPAR${\gamma}$. Conclusion: This study confirmed that renal cell death, immune system activation with subsequent fibrosis, and lipid metabolism-related early vasculopathy were involved in the pathophysiology of FSGS. In addition, the relevance of methodology used in this study, namely transcriptome profiling, and Korean animal model of FGS/kist was validated. Further study would reveal novel pathophysiology of FSGS for new therapeutic targets.

思春期前 兒童의 正常 鼻腔 通氣度에 관한 硏究

서정훈,장영일,양원식,남동석 대한치과교정학회 1992 대한치과교정학회지 Vol.22 No.1

This study was designed to analyze normal nasal respiratory resistance in prepubertal children. The subjects consisted of 30 prepubertal children(male:15, female:15).The mean age was 11.4 years in male children and 11.5 years in female children. The results were as follows: 1.The normal nasal respiratory patency was lower than the normal values from RION corp. 2.The normal nasal respiratory airflow rates showed no sexual differences. And there were no differences between inspiration and expiration. 3.Before and after use of nasal decongestants, there were no significant differences of normal nasal respiratory airflow rates and after the administration of nasal decongestants, nasal respiratory patency manifested lower variability. 4.The normal nasal respiratory resistance without nasal decongestants at 150 Pascal in inspiration was 0.30 Pa/cm³/sec(±0.07) and peak nasal inspiratory airflow rate was 1016.83cm³/sec(±223.89). 5.The normal nasal respiratory resistance with nasal decongestant at 150 Pascal in inspiration was 0.25 Pa/cm³/sec(±0.05) and peak nasal inspiratory airflow rate was 1148.33 cm³/sec(±234.29).

교정환자의 관리, 진단, 성장과 치료결과 분석을 위한 software 개발에 관한 연구

장영일,김태우,양원식,김근만,남동석,서정훈 대한치과교정학회 1992 대한치과교정학회지 Vol.22 No.4

It is prerequisite of orthodontists to diagnose malocclusion correctly and make treatment plans accurately for treating maloccluded patients efficiently and earning more stable and better results. Recently computers were introduced in orthodontic diagnosis steps, which enabled orthodontists to get more precise diagnosis, to make more accurate treatment planning and to provide better orthodontic cares for more patients. The authors studied on the diagnostic analysis methods which have been used frequently in Korea and made a diagnostic computer program including the horizontal and/or vertical measurement of length, degrees and proportions in lateral cephalometric radiographs, the analysis of the skeletal and soft-tissue features and the evaluation of the treatment results. We also made a scheduling program for arrangement and management of patients. 40 skeletal and 24 soft-tissue landmarks were selected in a lateral cephalometric radiographs. The available analysis methods in this program are Angular analysis, Linear analysis, Ricketts analysis, Profilogram, Steiner analysis, Tweed analysis, MacNamara analysis, Open bite analysis, Kim's diagnosis, Skeleto-dental cephalometric analysis and Height& weight analysis. We suggested that this diagnostic computer program make it possible for orthodontists to get more rapid and accurate diagnostic analysis and treatment planning and for patient to earn better and more efficient orthodontic service.

초등학교 과학교실 및 과학동아리 관련 현장 조사 및 프로그램 개발 모형 설정

임청환,김남일,권성기,고한중,이성호 한국과학교육학회 2005 한국과학교육학회지 Vol.25 No.2

본 연구의 목적은 과학 교실 및 과학반, 과학동아리 활동과 관련하여 일선 학교 현장에서는 어떤 문제점을 갖고 있으며 어떤 요구가 있는지 조사연구를 통해 알아보고 그 결과를 바탕으로 활동 프로그램을 개발하기 위한 개발 모형을 제시하는 것이었다. 146개 초등학교의 과학 관련 교사를 대상으로 설문 조사하였으며 조사결과, 교사들은 다양한 문제점과 해결 덜'간을 제시하였는데 다음과 같은 시사점을 얻을 수 있었다. 첫째, 다양한 과학 활동에 대한 행·재정적 지원이 절실히 필요하다. 둘째, 과학비전공 교사도 쉽게 다룰 수 있는 활동 프로그램의 제공이 필요하다. 셋째, 재미있는 활동으로 구성된 프로그램이 있어야 한다. 넷째, 프로그램은 준비가 용이한 활동으로 이루어져야 한다. 다섯째, 탐구 활동 중심의 평가 방법이 제시되어야 한다. 이러한 조사 결과를 바탕으로, 교사, 학생, 운영 환경을 축으로 하는 프로그램 개발 맥락을 설정하고 주제 설정, 활동구성, 차시구성, 활동지 구성, 교사용 지침서 구성의 단계로 이루어진 개발 모형을 제안하였다. The purpose of this study was to investigate the needs of elementary school teachers on extra-science programs and to suggest development model for extra-science program. Survey research was conducted on 146 science-related teachers all over the country. As the result, teachers presented several problems and solutions on extra-science activities and programs. The suggestions from the results are as follows. First, more administrative and financial supports are required. Second, it must be the programs with which any teachers, regardless of their major fields, can execute easily. Third, the programs should be interesting for students to do. Fourth, it should be easy to prepare activities and materials, Finally, the inquiry-focused assessment method should be presented in each program. Based on these suggestions, the context of development of programs was established. Three axises of, students, teachers, and environment, were included in the context. The model of development of programs was set up based on the context. It was constructed with six process steps, Confirmation of theme, Composition of work frame, Organization of each period, Worksheets for students, Guidebook for teachers, Completion, and one or two assessment criteria in each process steps. It must be useful to development of extra-science programs that is appropriate to the need of teachers.

상악호선에 torque 부여시 나타나는 상반작용에 관한 유한요소법적 연구

황치일,서정훈 대한치과교정학회 1994 대한치과교정학회지 Vol.24 No.2

This study was designed to investigate the reciprocal movement which was derived form application of active torque in ideal archwire by computer-aided three-dimensional finite element analysis of maxillary teeth and surrounding periodontal ligament composed of 2617 elements and 3725 nodes. Ideal archwire model was also made using the beam elements and the contact between the wire and the bracket slot was made using the gap element. In this study non-linear elastic behaviors of contact between the wire and the bracket slot were considered on. We put the active torque between the lateral and cenral incisor and between the second premolar and the first molar with/without cinch-back. The results were expressed by quantitative and visible ways. The findings of this study were as follows: 1. Reciprocal actions to active torque were complex system consisting of a combination of counter-torque, bucco-lingual linear displacement and tipping, rotation of the teeth, occluso-gingival linear displacement. 2. when active anterior crown labial torque was applied, crown labial tippings of the lateral were the greatest, and those of the central incisor was the next. Crown lingual tippings of the canine and the first premolar, mesial rotations and extrusion of the lateral and distal rotations and intrusion of the canine occurred. When anterior torque with the cinch-back was applied, amount of crown labial tippings of the lateral and central incisor were reduced. Amount of crown lingual tipping of the canine and the first premolar were increased. Mesial tippings and mesial rotations of the second, molar occurred. 3. When active posterior crown lingual torque was applied, crown lingual tippings of the first moalr were the greatest, and crown labial tippings of the second premolar and the first premolar were the next, the crown lingual tipping of the second molar were a little. Mesial rotations of the second premolar occurred but those of the first premolar didn't occurred.