• Title/Summary/Keyword: Mixed-effect model

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Tumor Suppressive Effect of Zoledronic Acid on Human Osteosarcoma Cells in Vivo (인간 골육종 세포주에서 Zoledronic acid의 종양 억제에 대한 생체내 실험)

  • Kim, Jae-Do;Seo, Tae-Hyuck;Lee, Dong-Won;Kwon, Young-Ho;Jang, Jae-Ho;Lee, Young-Goo
    • The Journal of the Korean bone and joint tumor society
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    • v.11 no.1
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    • pp.46-53
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    • 2005
  • Purpose: Bisphosphonates (BPs) are the analogues of endogenous pyrophosphates: they have been used in the treatment of skeletal diseases such as Paget's disease, osteoporosis, and tumorinducing ostelysis, and are used in treatment of osteolytic metastasis of breast cancer recently. They are also used as one of the therapeutic agents for metastasis of prostatic cancer of which metastasis makes the mixed nature of osteolysis and ostegenesis. Although the action mechanism of BPs are well known for diseases with excessive osteoclastic bone resorption, the direct effect of BPs has not been known yet. This study was intended to see the tumor suppression capability of Zoledronic acid(ZOL) using nude mouse with osteosarcoma. Materials and Methods: MG-63 and HOS osteosarcoma cell lines were used and the transforemed MG-63-GFP and HOS-GFP cells, which were made for detection under fluorescent light, were subcutaneously injected to make osteosarcoma. The five 6-week male mice were used for the experiment at each group. After the injection, mice were cultivated until tumor pieces grow up to $3{\times}3{\times}3$ $mm^3$ and ZOL of 120 ug/kg was subcutaneously injected twice a week. Sizes of tumor were measured twice a week and photographed under fluorescent light. Results: In in vivo test with HOS osteosarcoma cell lines, mean size of tumors was 2,520 $mm^3$ in control group and was 131 $mm^3$ in ZOL group, which showed 94% of reduction comparing with the control ; with MG-63 osteosarcoma cell lines, mean size of tumors was 2,866 $mm^3$ in control group and was 209 $mm^3$ in test group with 72% of reduction (p<0.05). Conclusion: In in vivo tests with nude mice, we suggest that ZOL has direct effect on osteosarcoma cells and it would be used as one of the therapeutic agents for osteosarcoma, especially to ZOL-sensitive osteosarcoma cells.

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The Effects of Modafinil on Clinical Features and Sleep Structure of Narcolepsy Patients and Healthy Controls (모다피닐이 기면병 환자와 대조군의 임상 양상과 수면구조에 구조에 미치는 영향)

  • Shin, Hong-Beom;Jeong, Do-Un;Kim, Eui-Joong
    • Sleep Medicine and Psychophysiology
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    • v.13 no.2
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    • pp.67-74
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    • 2006
  • Introduction: Excessive daytime sleepiness and cataplexy are key features of narcolepsy. Modafinil is psychostimulant used in the treatment of narcolepsy. In this study, we evaluated effects of modafinil on nocturnal sleep structure and sleep latency in multiple sleep latency test and clinical features. Methods: Twelve narcoleptic patients (7 male, age: $22.9{\pm}2.6\;yrs$) were participated in the study. All of them had done nocturnal polysomnography (nPSG), multiple sleep latency test (MSLT), clinical symptoms scales and have repeated same procedure after taking 200 mg of modafinil. We have done linear mixed model analysis to describe effects of group, medication and nap time on these measures. Results: Modafinil did not affect clinical scales except PSQI which had been reduced after medication. In this study, Modafinil reduced total sleep time, sleep efficiency and increased wake after sleep onset and percent of arousal during sleep in nocturnal polysomnography and prolonged mean sleep latency in multiple sleep latency tests in both group. Discussion: Modafinil has stimulant effect of central nervous system but its effect on night sleep is less than other psychostimulants such as methylphenidate. We ascertained that modafinil affected total sleep time, sleep efficiency and percent of wake during sleep but did not effect on sleep structure. Modafinil was effective in the management of day time sleepiness. Modafinil can enhance alertness of control group without day time sleepiness.

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Effect of Cooking Processes on the Amount of Salmonella typhimurium in Pork and Korean Japchae and Identification of Critical Control Point in the Processes (조리과정에 따른 살모넬라(Salmonella typhimurium) 식중독균수의 변화 및 중점 관리점 (CCP)의 관찰 - 돼지고기와 잡채를 중심으로 -)

  • 김종규
    • Journal of Food Hygiene and Safety
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    • v.13 no.4
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    • pp.441-447
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    • 1998
  • This study was performed to investigate the changes of amount of S. typhimurium during cooking processes using pork and japchae (a Korean food which is made from meat, vegetables and noodles), and to support a practical application to develop a hazard analysis critical control point (HACCP) model. The pork was purchased in a retail shop, cut ($0.5\;cm\;{\times}\;10\;cm\;{\times}\;10\;cm$, 25 g), tested for Salmonella contamination (results: negative), inoculated with S. typhimurium ($10^{7}\;CFU/g$), then treated in various conditions related to cooking. Mter thawing for 24 hours in various conditions, the number of S. typhimurium was increased to $10^{10}\;CFU/g$ at a refrigerated temperature ($4~10^{\circ}C$), and to $10^{21}\;CFU/g$ at room temperature ($22~29^{\circ}C$). Mter thawing in a microwave oven for 40 seconds, the number of S. typhimurium increased to $10^{8}\;CFU/g$. During the thawing period, the number of S. typhimurium increased over time. At the refrigerated temperature, the number of the bacteria was $10^{10}\;CFU/g$ after 24 hours, $10^{13}\;CFU/g$ after 48 hours, and $10^{20}\;CFU/g$ after 72 hours. At room temperature the number of bacteria reached $10^{11}\;CFU/g$ in 2 hours, $10^{15}\;CFU/g$ in 4 hours, $10^{16}\;CFU/g$ in 8 hours, $10^{18}\;CFU/g$ in 12 hours, and $10^{21}\;CFU/g$ in 24 hours. Mter cooking in a frying pan (150{\pm}7^{\circ}C$) for 3 minutes, the bacterial count was $10^{16}\;CFU/g$. After cooking in hot water for 20 minutes, the bacterial count was $10^{7}\;CFU/g\;at\;60^{\circ}C,\;10^{6}\;CFU/g\;at\;63^{\circ}C,\;and\;10^{4}\;CFU/g\;at\;65^{\circ}C$. The fried pork was mixed with cooked vegetables, noodles, sesame oil, sesame seeds, and seasonings to make Korean japchae. This process took $10{\pm}2$ minutes. The bacterial count in the japchae increased to $10^{7}\;CFU/g$ from the count of $10^{6}\;CFU/g$ of the fried pork before it was mixed with the other ingredients. These results indicate that the amount of S. typhimurium is effected by various different cooking processes. This study can suggest that pork should be cooked in water at over $65^{\circ}C$ for 20 minutes in order to prevent food poisoning, if the pork is contaminated with S. typhimurium. The presence of S. typhimurium in the raw pork is identified in an HA for japchae, and the primary CCP for japchae is inadequate cooking (cooking method and time/temperature). We need to standardize time-temperature-size and amount of pork in cooking japchae, because pork is usually cooked in ordinary frying pans when we make this food.

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Association of SNP Markers on Chromosomes 3 and 9 with Body Weight in Jeju Horses (제주마에서 3번 및 9번 염색체상의 단일염기변이와 생체중과의 관련성 연구)

  • Kim, Nam Young;Yang, Young Hoon;Park, Nam Geon;Yang, Byoung Chul;Son, Jun Kyu;Shin, Sang Min;Woo, Jae Hoon;Shin, Moon Cheol;Yoo, Ji Hyun;Hong, Hyun Ju;Park, Hee Bok
    • Journal of Life Science
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    • v.28 no.7
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    • pp.795-801
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    • 2018
  • This study was conducted to investigate the association of single nucleotide polymorphism (SNP) markers on equine chromosomes (ECA) 3 and 9 with body weight in Jeju horses. We used DNA samples and body weight data of 320 horses provided by the Livestock Promotion Agency, Jeju Special Self-Governing Province, and the Korean Racing Association, respectively. We genotyped all the experimental animals using nine SNP markers located on ECA 3 (BIEC2-808466, BIEC2-808543, BIEC2-808967, and BIEC2-809370) and ECA 9 (BIEC2-1105370, BIEC2-1105372, BIEC2-1105377, BIEC21105505, and BIEC2-1105840). These markers were selected due to their effects on body conformation traits in horses. The joint effect of the genotypes of the two SNP markers (BIEC2-808467 and BIEC2-1105377) regarding body weight were also evaluated. The estimated breeding value (EBV) of body weight was obtained as the dependent variable for association analyses using a linear mixed model. Significant associations were detected between SNP markers (BIEC2-808543, BIEC2-808967, BIEC2-809370, BIEC2-1105370, BIEC2-1105372, and BIEC2-1105377) and the body weight EBV. In addition, the joint genotype effect of the BIEC2-808467 and BIEC2-1105377 on the body weight EBV was significant. These results indicate that the SNP markers, which showed their significant effects on body conformation, can be used as genetic markers to improve the efficiency of the selective breeding program for the body weight traits in Jeju horses.

Growth and Photocurrent Properties of CdIn2S4/GaAs Single Crystal Thin Film by Hot Wall Epitaxy (Hot Wall Epitaxy 법에 의한 CdIn2S4 단결정 박막의 성장과 광전류 특성)

  • Lee, Sang-Youl;Hong, Kwang-Joon;Park, Jin-Sung
    • Journal of Sensor Science and Technology
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    • v.11 no.5
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    • pp.309-318
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    • 2002
  • A stoichiometric mixture of evaporating materials for $CdIn_2S_4$ single crystal thin films was prepared from horizontal electric furnace. To obtain the single crystal thin films, $CdIn_2S_4$ mixed crystal was deposited on thoroughly etched semi-insulating GaAs(100) substrate by the Hot Wall Epitaxy (HWE) system. The source and substrate temperatures were $630^{\circ}C$ and $420^{\circ}C$, respectively. The crystalline structure of the single crystal thin films was investigated by the photoluminescence and double crystal X-ray diffraction (DCXD). The carrier density and mobility of $CdIn_2S_4$ single crystal thin films measured with Hall effect by van der Pauw method are $9.01{\times}10^{16}\;cm^{-3}$ and $219\;cm^2/V{\cdot}s$ at 293 K, respectively. The temperature dependence of the energy band gap of the $CdIn_2S_4$ obtained from the absorption spectra was well described by the Varshni's relation, $E_g(T)=2.7116\;eV-(7.74{\times}10^{-4}\;eV)T^2/(T+434)$. The crystal field and the spin-orbit splitting energies for the valence band of the $CdIn_2S_4$ have been estimated to be 0.1291 eV and 0.0248 eV, respectively, by means of the photocurrent spectra and the Hopfield quasi cubic model. These results indicate that the splitting of the ${\Delta}so$ definitely exists in the ${\Gamma}5$ states of the valence band of the $AgInS_2$/GaAs epilayer. The three photocurrent peaks observed at 10K areascribed to the $A_1$-, $B_1$-, and C1-exciton peaks for n = 1.

The Radioprotective Effect and Mechanism of Captopril on Radiation Induced-Heart Damage in Rats (방사선 조사 후 발생한 흰쥐 심장손상에서 Captopril의 방어역할과 기전)

  • Chang Seung-Hee;Lee Kyung-Ja;Koo Heasoo
    • Radiation Oncology Journal
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    • v.22 no.1
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    • pp.40-54
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    • 2004
  • Purpose : Captopril (angiotension converting enzyme inhibitor) is known to have a radioproptective effect in the lungs, intestines and skin, but its effect in the heart is unclear. To investigate the radioprotectlve efiect and mechanism of captopril on the heart, the histopathological changes and immunohistochemical stains were compared with radiation alone, and radiation combined with captopril, in the rats. Materials and Methods : The histopathological changes and immunohistochemical stains ($TNF{\alpha}$, $TGF{\beta}1$, PDGF and FGF2) were examined in the radiation alone and the combined captopril and radiation groups, 2 and 8 weeks after irradiation. Each group consisted of 8 to 10 rats (Sprague-Dawley). Irradiation (12.5 Gy) was given to the left hemithorax in a single fraction. Captopril (50 mg/Kg/d) mixed with water, was given orally and continuously from the first week prior to, up to the 8th week of the experiment. Results : In the radiation alone group, the ventricle at 2 weeks after irradiation showed prominent edema (p=0.082) and fibrin deposit (p=0.018) compared to the control group. At 8 weeks, the edema was decreased and fibrosis increased compared to those at 2 weeks. The histopathological changes of the combined group were similar to those of the control group, due to the reduced radiation toxicity at 2 and 8 weeks. The endocardial fibrin deposit (p=0.047) in the atrium, and the interstitial fibrin deposit (p=0.019) and edema (p=0.042) of the ventricle were reduced significantly in the combined group compared to those in the radiation alone group at 2 weeks. The expressions of $TNF-{\alpha}$, $TGF-{\beta}1$, PDGF and FGF-2 in the radiation alone group were more increased than in the control group, especially in the pericardium and endocardium of the atrium at 2 weeks. At 8 weeks, the pericardial $TNF-{\alpha}$ and $TGF-{\beta}1$ in the radiation alone group continuously increased. The expressions of $TNF-{\alpha}$, $TGF-{\beta}1$ and PDGF were decreased in the combined group at 2 weeks. At 8 weeks, the expressions of $TNF-{\alpha}$ in the atrial and ventricular pericardia were markedly reduced (p=0.049, p=0.009). Conclusion : This study revealed that the early heart damage induced by radiation can be reduced by the addition of captopril in a rat model. The expressions of $TNF-{\alpha}$, $TGF-{\beta}1$ and PDGF were further decreased in the combined compared to the radiation alone group at both 2 and 8 weeks. From these results, it may be concluded that these cytokines probably play roles in the radioprotective mechanism of captopril from the radiation-induced heart toxicity, similarly to in other organs.

Normative blood pressure references for Korean children and adolescents (한국 소아 청소년 정상 혈압 참고치)

  • Lee, Chong Guk;Moon, Jin Soo;Choi, Joong-Myung;Nam, Chung Mo;Lee, Soon Young;Oh, Kyungwon;Kim, Young Taek
    • Clinical and Experimental Pediatrics
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    • v.51 no.1
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    • pp.33-41
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    • 2008
  • Purpose : It is now understood that blood pressure (BP) measurement in the routine pediatric examination is very important because of the relevance of childhood BP to pediatric health care and the development of adult essential hypertension. There hasn't been a reference table of BP for Korean children and adolescents up to now. This study was to make normative BP references and to provide criteria of hypertension for Korean children and adolescents. Methods : BP measurements were done on 57,433 Koean children and adolescents (male: 29,443, female: 27,990), aged 7 to 20 years, in 2005. Heights and weights were measured simultaneously. Oscillometric devices, Dinamap Procare 200 (GE Inc., Milwaukee, Wi, USA), were used for the measurements. BPs were measured 2 times and mean levels were gathered for the analysis. Outliers of 2,373 subjects with overweight per height, over +3SD, were excluded for the analysis. For the BP centiles adjusted by sex, age and height, fixed modified LMS method which was adopted from the mixed effect model of 2004 Task Force in NHLBI (USA) was used. Results : Normative BP tables for Korean children and adolescents adjusted for height percentiles (5th, 10th, 25th, 50th, 75th, 90th, 95th), gender (male, female) and age(7 to 18 years) were completed. Height centiles of Korean children and adolescents are available from Korean Center for Disease Control and Prevention homepage, http://www.cdc.go.kr/webcdc/. Criteria of hypertension (95th, 99th percentile) and normal range of BP (50th, 90th) adjusted for height percentiles, age and gender were made. Conclusion : This is the first study to make normative BP tables and define hypertension for the Korean children and adolescents. Reliability and accuracy of Dinamap Procare 200 oscillometer for BP measurements remains debatable.

Photocurrent study on the splitting of the valence band and growth of $ZnIn_{2}Se_{4}$ single crystal thin film by hot wall epitaxy (Hot wall epitaxy(HWE)법에 의한 $ZnIn_{2}Se_{4}$ 단결정 박막 성장과 가전자대 갈라짐에 대한 광전류 연구)

  • Hong, Kwang-Joon
    • Journal of the Korean Crystal Growth and Crystal Technology
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    • v.18 no.5
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    • pp.217-224
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    • 2008
  • A stoichiometric mixture of evaporating materials for $ZnIn_2Se_4$ single crystal thin films was prepared from horizontal electric furnace. To obtain the single crystal thin films, $ZnIn_2Se_4$ mixed crystal was deposited on thoroughly etched semi-insulating GaAs(100) substrate by the Hot Wall Epitaxy (HWE) system. The source and substrate temperatures were $630^{\circ}C$ and $400^{\circ}C$, respectively. The crystalline structure of the single crystal thin films was investigated by the photoluminescence and double crystal X-ray diffraction (DCXD). The carrier density and mobility of $ZnIn_2Se_4$ single crystal thin films measured from Hall effect by van der Pauw method are $9.41\times10^{16}cm^{-3}$ and $292cm^2/v{\cdot}s$ at 293 K, respectively. The temperature dependence of the energy band gap of the $ZnIn_2Se_4$ obtained from the absorption spectra was well described by the Varshni's relation, $E_g(T)=1.8622eV-(5.23\times10^{-4}eV/K)T^2/(T+775.5K)$. The crystal field and the spin-orbit splitting energies for the valence band of the $ZnIn_2Se_4$ have been estimated to be 182.7 meV and 42.6 meV, respectively, by means of the photocurrent spectra and the Hopfield quasicubic model. These results indicate that the splitting of the ${\Delta}so$ definitely exists in the ${\Gamma}_5$ states of the valence band of the $ZnIn_2Se_4/GaAs$ epilayer. The three photo current peaks observed at 10 K are ascribed to the $A_{1}-$, $B_{1}-exciton$ for n = 1 and $C_{27}-exciton$ peaks for n = 27.

Effects of PGA-LM on CD4+CD25+foxp3+ Treg Cell Activation in Isolated CD4+ T Cells in NC/Nga Mice (NC/Nga 생쥐에서 분리한 T 세포에서 foxp3+ 세포 활성화에 대한 PGA-LM의 효과)

  • Jang, Soon-Nam;Kim, Kum-Lan;Kang, Sang-Mo
    • Microbiology and Biotechnology Letters
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    • v.37 no.2
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    • pp.160-169
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    • 2009
  • Poly-$\gamma$-glutamic acid ($\gamma$-PGA) was mixed natural flora of Bacillus subtilis, contaminated from cooked soybeans. Also, it was performed to find out the antiallergic activity by using NC/Nga mice, in vitro. The $\gamma$-PGA (PGA-HM : PGA-high molecular weight), Molecular weight 300 kDa, was decomposed and made PGA-LM (PGA-low molecular weight) which has molecular weight below 30 kDa by sonication. Therefore, it was same result between PGA-HM and PGA-LM, and reported PGA-LM as basic result. We found that PGA-LM contains antiallergic efficacy that inhibit B cells and Th2 cells activation from isolated CD4+T cells in NC/Nga atopic dermatitis model mice, and not show a cytotoxicity in the hFCs. To investigate the effects of these PGA-LM in vitro, isolation of splenic B cell and CD4+ T cells in atopic dermatitis mice were used. To elucidate the role of PGA-LM in anti-CD40+ interleukin-4 (IL-4)-mediated B-cell activation, showed that the capacity of B cells to expression IL-$1\beta$, IL-6, and TNF-$\alpha$ mRNA down-regulated, and IL-10 mRNA up-regulation by PGA-LM treatment, but it had no effect on TGF-$\beta$ expression. In addition to CD4+IFN-$\gamma$+ and CD4+CD25+foxp3+, the functions of PGA-LM in the development of the CD4+CD25+foxp3+ and CD4+IFN-$\gamma$+cells, the phenotype and functions of PGA-LM induced CD4+CD25+foxp3+, and CD4+IFN-$\gamma$+cells in CD4+T cells. These results suggested that PGA-LM could change cytokine production and generate CD4+CD25+foxp3+ Tregs in NC/Nga mice, and may be effective for immunotherapy in patients with AD.

Chemoprevention of Helicobacter pylori-associated Gastric Carcinogenesis in a Mouse Model; Is It Possible?

  • Hahm, Ki-Baik;Song, Young-Joon;Oh, Tae-Young;Lee, Jeong-Sang;Surh, Young-Joon;Kim, Young-Bae;Yoo, Byung-Moo;Kim, Jin-Hong;Ha, Sang-Uk;Nahm, Ki-Taik;Kim, Myung-Wook;Kim, Dae-Yong;Cho, Sung-Won
    • BMB Reports
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    • v.36 no.1
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    • pp.82-94
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    • 2003
  • Although debates still exist whether Helicobacter pylori infection is really class I carcinogen or not, H. pylori has been known to provoke precancerous lesions like gastric adenoma and chronic atrophic gastritis with intestinal metaplasia as well as gastric cancer. Chronic persistent, uncontrolled gastric inflammations are possible basis for ensuing gastric carcinogenesis and H. pylori infection increased COX-2 expressions, which might be the one of the mechanisms leading to gastric cancer. To know the implication of long-term treatment of antiinflammatory drugs, rebamipide or nimesulide, on H. pylori-associated gastric carcinogenesis, we infected C57BL/6 mice with H. pylori, especially after MNU administration to promote carcinogenesis and the effects of the long-term administration of rebamipide or nimesulide were evaluated. C57BL/6 mice were sacrificed 50 weeks after H. pylori infection. Colonization rates of H. pylori, degree of gastric inflammation and other pathological changes including atrophic gastritis and metaplasia, serum levels and mRNA transcripts of various mouse cytokines and chemokines, and NF-${\kappa}B$ binding activities, and finally the presence of gastric adenocarcinoma were compared between H. pylori infected group (HP), and H. pylori infected group administered with long-term rebamipide containing pellet diets (HPR) or nimesulide mixed pellets (HPN). Gastric mucosal expressions of ICAM-1, HCAM, MMP, and transcriptional regulations of NF-${\kappa}B$ binding were all significantly decreased in HPR group than in HP group. Multi-probe RNase protection assay showed the significantly decreased mRNA levels of apoptosis related genes and various cytokines genes like IFN-$\gamma$, RANTES, TNF-$\alpha$, TNFR p75, IL-$1{\beta}$ in HPR group. In the experiment designed to provoke gastric cancer through MNU treatment with H. pylori infection, the incidence of gastric carcinoma was not changed between HP and HPR group, but significantly decreased in HPN group, suggesting the chemoprevention of H. pylori-associated gastric carcinogenesis by COX-2 inhibition. Long-term administration of antiinflammatory drugs should be considered in the treatment of H. pylori since they showed the molecular and biologic advantages with possible chemopreventive effect against H. pylori-associated gastric carcinogenesis. If the final concrete proof showing the causal relationship between H. pylori infection and gastric carcinogenesis could be obtained, that will shed new light on chemoprevention of gastric cancer, that is, that gastric/cancer could be prevented through either the eradication of H. pylori or lessening the inflammation provoked by H. pylori infection in high risk group.