Interleukin-1B(1L-1B) polymorphisms and gastric mucosal levels of IL-Iβ cytokine in Korean patients with gastric cancer

Chang, Young-Woon,Jang, Jae-Young,Kim, Nam-Hoon,Lee, Jae Won,Lee, Hyo Jung,Jung, Woon Won,Dong, Seok-Ho,Kim, Hyo-Jong,Kim, Byung-Ho,Lee, Joung-Il,Rin Chang KYUNG HEE UNIVERSITY MEDICAL CENTER 2006 고황의학상 수상논문집 Vol.21-22 No.-

Interleukin-1B and IL-1 receptor antagonist gene polymorphisms are associated with an increased risk of gastric cancer (GC) in Caucasian populations. However, recent studies could not find any association between IL-1B-511T polymorphism and the risk of GC in Asians. We tested for an association between IL-1 loci polymorphisms with increased gastric mucosal levels of IL-1β and an increased risk of developing GC in a Korean population. Polymorphisms of IL-1A-889, IL-1B-31, IL-1B-511 and IL-1RN were genotyped in 434 controls and 234 patients with GC. Mucosal IL-1β cytokine was measured using an ELISA. The frequencies of IL-1A, IL-1B-511, IL-1B-31 and IL-1RN were not statistically different between controls and all patients with GC. After subclassification of GC, only patients with intestinal-type GC showed a higher frequency of IL-1B-31T homozygotes (OR = 2.2; 95% CI = 1.1-4.3) compared with controls. Risk was also significantly increased in these patients for IL-1B-31T homozygotes compared with patients with diffuse-type GC (OR = 3.4; 95% CI = 1.5-7.7). As in Caucasian populations, linkage disequilibrium between IL-1B-31 and IL-1B-511 was nearly complete, but the pattern of haplotype related to the risk of GC (IL-1B-31T/IL-1B-511C) was opposite (IL-1B-511T/IL-1B-31C). Mucosal IL-1β levels in H. pylori-infected GC patients were higher in patients homozygous for IL-1B-31T compared with IL-1B-31C/T and IL-1B-31C/C. Thus, the combined effects of H. pylori infection and IL-1B-31T/IL-1B-511C polymorphisms with enhanced mucosal IL-1β production contributed to the development of intestinal-type GC in this Korean population.

Free Paper Session : Upper Gastrointestinal Tract 1 ; Prevalence And Risk Factors For Atrophic Gastritis And Intestinal Metaplasia

( Na Young Kim ),( Dong Ho Lee ),( Joo Sung Kim ),( Hyun Chae Jung ),( In Sung Song ),( Kyung Phil Kang ),( Jung Hoon Lee ),( Jae Il Chung ),( Hyun Cheul Choi ),( Taek Man Nam ),( Sang Hyup Lee ),( Yo 대한소화기학회 2007 SIDDS Vol.9 No.-

Background/Aims: The prevalence of gastric cancer and Helicobacter pylori (Hp) infection is high in Korea. This study was performed to evaluate the prevalence rate of atrophic gastritis (AG) and intestinal metaplasia (IM) and their risk factors in the aspect of Hp virulence factors, environmental and host factors in normal population. Methods: The subjects consisted of 389, 135 H. pylori-negative and 254 H. pylori-positive. AG and IM were scored histologically by the Sydney classification in the antrum and body, respectively. Prevalence rate and bacterial factors such as cagA, vacA m1, m2, and oipA; environmental factors such as smoking, alcohol drinking; host factors such as genetic polymorphisms for IL-IB-511, IL-IRN, TNF-A, IL-10-592, IL-10-819, IL-10-1082, IL-8-251, IL-6-572, GSTP1, and p53 codon 72 were evaluated. Risk factors were calculated by multiple logistic regression analysis. Results: The prevalence rate of AG increased from 25%, 0% in the age of 20s, 45% and 22% in the 40s and 50% and 35% in the over 70s in the antrum and body, respectively (p<0.001). In case of IM it increased from 11.1% and 6.4% in the 30s up to 43% and 43% in over 70s in the antrum and body, respectively, (p<0.001). The positive rates of AG and IM were significantly higher in the Hp-positive than in the Hp-negative subjects. Multivariate analysis showed that the risk factors for AG were Hp infection, age ≥60, cagA and vacA m1 positive. In case of IM the risk factors were Hp infection, age ≥60, smoking, spicy food, occupation (unemployed or non professional vs. professional), IL6-572 G carrier over C/C and IL10-592 C/A vs. A/A. Conclusions: The prevalence rate of AG and IM increased proportional to age. The most risk factor for AG and IM was Hp infection. Bacterial factors were important for AG but environmental and host factors were rather important in case of IM.

金久永의 『病因論』에 나타난 의학사상 연구

김정원(Chong Won Kim),김남일(Nam il Kim),차웅석(Wung Seok Cha) 한국의사학회 2017 한국의사학회지 Vol.30 No.1

This paper is a study on the life and clinical reasoning of Kim Goo Young (1958-2014). Offering a new perspective through his interpretation of Donguibogam (東醫寶鑑), Kim introduced his unique theory of Korean medicine, ‘The Theory of Byeongin (病因論)’. Kim recognized the confusing situation of communication between people studying Korean medicine and tried to make a new standard based on the principle that many people can share. ‘The Theory of Byeongin offers a newly constituted 󰡔Donguibogam󰡕 focusing on ‘Byeongin’ (病因, pathologic origin) which can be translated as the cause of a disease. In so doing Kim recognized ‘Byeongin as the most important factor in ‘Byeonjeung’ (辨證, classifying the origin), or the classification method of symptoms. In addition, Kim recognized how ‘Byeongin was considered to be a diseased lifestyle, and tried interpreting. The patient’s lifestyle to treat diseases. As a result, ‘The Theory of Byeongin’ is a theory consisting of an intuitive structure, reducing notable elements like Yin Yang Five Movement theory. The theory s significant characteristic is its easy application in clinical settings due the established core principles which are based on Kim’s insight and clinical experience. This study contributes to the understanding of the theoretical and clinical development of Korean medicine through deeper studies on ‘The Theory of Byeongin and Kim s medical theory.

Interleukin-17이 배양된 류마티스관절염 활막세포에서 vascular endothelial growth factor 생성에 미치는 영향

곽임수 ( Ihm Soo Kwak ),남태수 ( Tae Soo Nam ),나하연 ( Ha Yeon Rha ),서정탁 ( Jeung Tak Suh ),김유선 ( Yoo Sun Kim ),김성일 ( Sung Il Kim ) 대한류마티스학회 2001 대한류마티스학회지 Vol.8 No.3

Objective: To investigate the the effects of interleukin-17 (IL-17) on the production of vascular endothelial growth factor (VEGF) from cultured rheumatoid arthritis synoviocytes. Methods: Fibroblast-like synovial cells(FLS) were prepared from the synovial tissues of rheumatoid arthritis patients and cultured in the presence of IL-17, IL-17 with or without transforming growth factor-β(TGF-β), tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β). VEGF levels were determined in the culture supernatants by sandwitch ELISA. Results: Stimulation of FLS by serial concentration of IL-17, TGF-β, TNF-α, IL-1β increased the production of VEGF by 2.1-2.7, 2.2-3.0, 2.0-2.9, 2.3-3.1 fold over the constitutive levels of unstimulated FLS. Stimulation of FLS by IL-17 with TGF-β or TNF-α or IL-1β also increased the production of VEGF according to culture periods by 1.6-1.8, 1.1-1.9, 1.5-1.7 fold over the levels stimulated with TGF-β or TNF-α or IL-1β, respectively. This results indicated that IL-17 increased the effect of TGF-β, TNF-α, IL-1β on FLS, leading synergistic enhancement of VEGF production. Conclusion: IL-17 may be involved in the neovascularization in rheumatoid synovitis by enhancing the production of VEGF.

Soluble mediators from mesenchymal stem cells suppress T cell proliferation by inducing IL-10

Seung-Ha Yang,Min-Jung Park,Il-Hee Yoon,Su-Young Kim,So-Hee Hong,Jin-Young Shin,Hye-Young Nam,김용희,Bongi Kim,박정규 생화학분자생물학회 2009 Experimental and molecular medicine Vol.41 No.5

Mesenchymal stem cells (MSCs) can inhibit T cell proliferation; however, the underlying mechanisms are not clear. In this study, we investigated the mechanisms of the immunoregulatory activity of MSCs on T cells. Irradiated MSCs co-cultured with either naïve or pre-activated T cells in a mixed lymphocyte reaction (MLR) significantly suppressed T cell proliferation in a dose-dependent manner, irrespective of allogeneic disparity between responders and MSCs. Transwell assays revealed that the suppressive effect was primarily mediated by soluble factors that induced apoptosis. Splenocytes stimulated with alloantigen in the presence of the MSC culture supernatant (CS) produced a significant amount of IL-10, which was attributed to an increase in the number of IL-10 secreting cells, confirmed by an ELISPOT assay. The blockade of IL-10 and IL-10 receptor interaction by anti-IL-10 or anti-IL-10-receptor antibodies abrogated the suppressive capacity of MSC CS, indicating that IL-10 plays a major role in the suppression of T cell proliferation. The addition of 1-methyl-DL-tryptophan (1-MT), an indoleamine 2,3-dioxygenase (IDO) inhibitor, also restored the proliferative capacity of T cells. In conclusion, we demonstrated that soluble mediators from culture supernatant of MSCs could suppress the proliferation of both naïve and pre-activated T cells in which IL-10 and IDO play important roles.

IL-21-Expressing Mesenchymal Stem Cells Prevent Lethal B-Cell Lymphoma Through Efficient Delivery of IL-21, Which Redirects the Immune System to Target the Tumor

Kim, Nayoun,Nam, Young-Sun,Im, Keon-Il,Lim, Jung-Yeon,Lee, Eun-Sol,Jeon, Young-Woo,Cho, Seok-Goo Mary Ann Liebert 2015 STEM CELLS AND DEVELOPMENT Vol.24 No.23

Formulation of a reference coordinate system of threedimensional head & neck images : Part Ⅱ. Reproducibitity Ⅱ부 수평기준면과 정중사상면의 재현성

Kim, Nam-Kug,Park, Jae-Woo,Chang, Young-Il 대한치과교정학회 발행 2005 대한치과교정학회지 Vol.35 No.6

This study was performed to investigate the reproducibility of the horizontal and midsagittal planes, and to suggest a stable coordinate system for three-dimensional (3D) cephalometric analysis. Eighteen CT scans were taken and the coordinate system was established using 7 reference points marked by a volume model, with no more than 4 points on the same plane. The 3D landmarks were selected on V works (Cybermed Inc., Seoul, Korea), then exported to V surgery (Cybermed Inc., Seoul, Korea) to calculate the coordinate values. All the landmarks were taken twice with a lapse of 2 weeks. The horizontal and midsagittal planes were constructed and its reproducibility was evaluated. There was no significant difference in the reproducibility of the horizontal reference planes. But, FH planes were more reproducible than other horizontal planes. FH planes showed no difference between the planes constructed with 3 out of 4 points. The angle of infersection made by 2 FH planes, composed of both Po and one Or showed less than 1° difference. This was identical when 2 FH planes were composed of both Or and one Po. But, the latter cases showed a significantly smaller error. The reproducibility of the midsagittal plane was reliable with an error range of 0.61 to 1.93° except for 5 establishments (FMS-Nc, Na-Rh, Na-ANS, Rh-ANS, and FR-PNS). The 3D coordinate system may be constructed with 3 planes; the horizontal plane constructed by both Po and right Or; the midsagittal plane perpendicular to the horizontal plane, including the midpoint of the Foramen Spinosum and Nc; and coronal plane perpendicular to the horizontal and midsagittal planes, including point clinodale, or sella, or PNS. 본연구는 삼차원 두부 영상을 위치시키기 위한 좌표계를 구성하는 방법에 대한 제안하기 위해, CT data에서 기존의 두부방사선 계측사진에서 쓰이는 점들을 선정하고, 이를 바탕으로 수평, 수직평면의 안정성을 조사하였다. 서울대학교 치과병원에 내원한 환자 18명의 CT자료를 채득하였으며, 모든 환자는 서울대학교 병원 진단방사선과에서 촬영하였다. (Somatom Plus 4: Siemens, Eriange, Germany). V works for surgery 4.0 (Cybermed Inc., Seoul, Korea)을 이용하여 3차원 좌측표를 선정하고, 계측점을 선택하였다. 좌표축을 동일하게 설정하기 위해 7개의 점(reference point)을 4·4·2 pixel size의 voxel로 따로 표시하였다. 계측점을 선정한 후 V surgery (Cybermed Inc., Seoul, Korea)에서 각 점의 좌표값을 추출하였다. 각각의 점들은 2회 반복 선정한 후 점들을 조합하여 수평, 수직평면의 재현성을 평가한 결과 다음과 같은 결론을 얻었다 수평 기준면의 재현도는 S-CI평면을 제외하고는 통계적으로 유의한 차이를 보이지 않았으나, 사잇각은 FH평면이 가장 작게 나타났다. FH평면은 Po과 Or중 어느 3점을 선택하더라도, 통계적으로 유사한 재현도를 보였다. FH1과 FH2의 사잇각과 FH3과 FH4의 사잇각은 1° 이하의 적은 오차를 보이며, FH3과 FH4의 사잇각이 통계적으로 더 작은 차이를 보였다. 정중시상면의 재현도는 FMS-Nc, Na-Rh, Na-ANS, Rh-ANS, FR-PNS를 기준으로 설정한 경우를 제외하면, 0.61~1.93° 의 양호한 값을 보였다. 이상의 결과에 의하면 공간에서 정의되는 평면의 재현도는 평면을 정의하는 점 자체의 식별오차뿐 아니라, 각 점의 위치관게에도 영향을 받는 것을 알 수 있었다. 따라서, 안정적인 3차원 기준좌표계를 구성하려면 양측 Po과 편측 Or으로 구성되는 평면을 수평기준면으로, 수평면에 수직이고, Foramen Spinosum의 중점과 Nc를 포함하는 평면을 수직기준면으로, 수평면과 수직면에 수직이고, clinoidale나 sella, PNS를 지나는 평면을 전두면으로 설정하는 것이 바람직할 것으로 생각된다.

Effects of Phenytoin and Diazepam on the Seizure Activity in the Cortical Dysplasia Animal Models

Kim, Si-Hyung,Choi, In-Sun,Cho, Jin-Hwa,Park, Eun-Ju,Jang, Il-Sung,Choi, Byung-Ju,Kim, Hyun-Jung,Kim, Young-Jin,Nam, Soon-Hyeun The Korean Academy of Oral Biology 2006 International Journal of Oral Biology Vol.31 No.2

Dysplasia-associated seizure disorders are markedly resistant to pharmacological intervention. Relatively little research has been conducted studying the effects of antiepileptic drugs(AEDs) on seizure activity in a rat model of dysplasia. We have used rats exposed to methylazoxymethanol acetate(MAM) in utero, an animal model featuring nodular heterotopia, to investigate the effects of AEDs in the dysplastic brain. Pilocarpine was used to induce acute seizure in MAM-exposed and age-matched vehicle-injucted control animals. Field potential recordings were used to monitor amplitude and numbers population spikes, and paired pulse inhibition in response to stimulation of commissural pathway. Two commonly used AEDs were tested: diazepam 5, 2.5mg/kg;phenytoin 40, 60mg/kg. Diazepam(DZP) and phenytoin(PHT) reduced the amplitude of population spike in control and MAM-exposed rats. However, the amplitude of population spike was nearly eliminated in control rats as compared to the MAM-exposed rats. Pharmaco-resistance was tested by measuring seizure latencies in awake rats after pilocarpine administration(320mg/kg, i.p.) with and without pretreatment with AEDs. Pre-treatment with PHT 60 mg prolonged seizure latency in control rats, but not in MAM-exposed animals. The main findings of this study are that acute seizures initiated in MAM-exposed rats are relatively resistant to standard AEDs assessed in vivo. These data suggest that animal model with cortical dysplasia can be used to screen the effects of potential AEDs.

Anti-inflammatory effect of Apo-9′-fucoxanthinone via inhibition of MAPKs and NF-kB signaling pathway in LPS-stimulated RAW 264.7 macrophages and zebrafish model

Kim, Eun-A,Kim, Seo-Young,Ye, Bo-Ram,Kim, Junseong,Ko, Seok-Chun,Lee, Won Woo,Kim, Kil-Nam,Choi, Il-Whan,Jung, Won-Kyo,Heo, Soo-Jin Elsevier 2018 INTERNATIONAL IMMUNOPHARMACOLOGY Vol.59 No.-

<P><B>Abstract</B></P> <P>In this study, we confirmed the anti-inflammatory effect of Apo-9-fucoxanthinone (AF) in <I>in vitro</I> RAW 264.7 cells and <I>in vivo</I> zebrafish model. In lipopolysaccharide (LPS)-stimulated zebrafish, AF significantly decreased the production of reactive oxygen species (ROS), nitric oxide (NO) and cell death. In addition, the mRNA expression of inducible nitric oxide synthase (iNOS), suppressed cyclooxygenase-2 (COX-2) and an inflammatory cytokines; IL-1β, TNF-α were shown reduction. And AF significantly inhibited NO production and expression of iNOS in LPS-stimulated RAW 264.7 cells. Further, AF suppressed COX-2, prostaglandin E2 (PGE<SUB>2</SUB>), and pro-inflammatory cytokines such as interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) at 25, 50 and 100 μg/mL, respectively. Further mechanistic studies showed that AF suppressed the nuclear factor-kB (NF-kB) pathway and phosphorylation of mitogen-activated protein kinase (MAPK) pathway molecules such as extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). According to the results, AF can be used and applied as a useful anti-inflammatory agent of nutraceutical or pharmaceutical.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Anti-inflammatory effect of Apo-9-fucoxanthinone in <I>in vitro</I> RAW 264.7 cells and <I>in vivo</I> zebrafish </LI> <LI> Apo-9-fucoxanthinone suppressed NO production through NF-kB and MAPKs pathway. </LI> <LI> In LPS-stimulated zebrafish, Apo-9-fucoxanthinone significantly decreased ROS, NO, cell death and pro-inflammatory cytokines. </LI> <LI> Apo-9-fucoxanthinone can be extremely useful as an effective anti-inflammatory agent. </LI> </UL> </P>

Comparison of Cytokine and Nitric Oxide Induction in Murine Macrophages between Whole Cell and Enzymatically Digested Bifidobacterium sp. Obtained from Monogastric Animals

Kim, Dong-Woon,Cho, Sung-Back,Lee, Hyun-Jeong,Chung, Wan-Tae,Kim, Kyoung-Hoon,HwangBo, Jong,Nam, In-Sik,Cho, Yong-Il,Yang, Mhan-Pyo,Chung, Il-Byung The Microbiological Society of Korea 2007 The journal of microbiology Vol.45 No.4

The principal objective of this study was to compare the effects of whole and hydrolyzed cells (bifidobacteria) treated with gastrointestinal digestive enzymes on the activation of cloned macrophages. Seven different strains of Bifidobacterium obtained from swine, chickens, and rats, were digested with pepsin followed by pancreatin and the precipitate (insoluble fraction) and supernatant (soluble fraction) obtained via centrifugation. The RAW 264.7 murine macrophages were incubated with either whole cells, the precipitate, or supernatant at various concentrations. Pronounced increases in the levels of nitric oxide (NO), interleukin $(IL)-1{\beta}$, IL-6, IL-12, and tumor necrosis factor $(TNF)-{\alpha}$ were observed in the whole cells and precipitates, but these effects were less profound in the supernatants. The precipitates also evidenced a slight, but significant, inductive activity for NO and all tested cytokines, with the exception of $(TNF)-{\alpha}$ in the macrophage model as compared with the whole cells. By way of contrast, $(TNF)-{\alpha}$ production when cultured with whole cells (100 ng/ml) resulted in marked increases as compared with what was observed with the precipitates. The results of this study indicated, for the first time, that digested Bifidobacterium sp. can induce the production of NO and several cytokines in RAW 264.7 murine macrophage cells. In the current study, it was demonstrated that Bifidobacterium strains treated with digestive enzymes, as compared with whole cells, are capable of stimulating the induction of macrophage mediators, which reflects that they may be able to modulate the gastrointestinal immune functions of the host.