• Title/Summary/Keyword: MOUSE model

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Accelerated DNA Adduct Formation in the Lung of the Nrf2 Knockout Mouse Exposed to Diesel Exhaust

  • Aoki, Yasunobu;Sato, Hiromi;Nishimura, Noriko;Takahashi, Satoru;Itoh, Ken;Yamamoto, Masayuki
    • Proceedings of the Korea Environmental Mutagen Society Conference
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    • 2002.05a
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    • pp.36-42
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    • 2002
  • Diesel exhaust (DE) has been recognized as a noxious mutagen and/or carcinogen, because its components can form DNA adducts. Mechanisms governing the susceptibility to DE and the efficiency of such DNA adduct formation require clarification. The transcription factor Nrf2 is essential for inducible and/or constitutive expression of a group of detoxification and antioxidant enzymes, and we hypothesized that the nrf2 gene knockout mouse might serve as an excellent model system for analyzing DE toxicity. To address this hypothesis, lungs from nrf2(-/-) and nrf2(+/-) mice were examined for the production of xenobiotic-DNA adducts after exposure to DE (3 $mg/m^{3}$ suspended particulate matter) for 4 weeks. Whereas the relative adduct levels (RAL) were significantly increased in the lungs of both nrf2(+/-) and nrf2(-/-) mice upon exposure to DE, the increase of RAL in the lungs from nrf2(-/-) mice exposed to DE were approximately 2.3-fold higher than that of nrf2(+/-) mite exposed to DE. In contrail, cytochrome P4501Al mRNA levels in the nrf2(-/-)mouse lungs were similar to those in the nrf2(+/-) mouse lungs even after exposure to DE, suggesting that suppressed activity of phase II drug-metabolizing enzymes is important in giving ise to the increased level of DNA adducts in the Nrf2-null mutant mouse subjected to DE. Importantly, severe hyperplasia and accumulation of the oxidative DNA adduct 8-hydroxydeoxyguanosine were observed in the bronchial epidermis of nrf(-/-) mite following DE exposure. These results demonstrate the increased susceptibility of the nrf2 germ line mutant mouse to DE exposure and indicate the nrf2 gene knockout mouse nay represent a valuable model for the assessment of respiratory DE toxicity.

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Cytokine production profiles of a model for fluorouracil and UVB-induced discoid lupus erythematosus in TCR $\alpha$ chain knockout mouse

  • Yoshimasu, Takashi;Hiroi, Akihisa;Ohtani, Toshio;Uede, Koji;Furukawa, Fukumi
    • Journal of Photoscience
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    • v.9 no.2
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    • pp.494-496
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    • 2002
  • Fluorouracil (FU) is well known to induce discoid lupus-like eruption at the sun exposure sites in Japan. It means the associations of UVB with drug induced DLE. It is still obscure which cytokines are involved in the development of DLE. To address the issue, we established a murine model of FU and UVB-induced discoid lupus and could show the Th1 dominant cytokine profiles in DLE model of TCR $\alpha$ chain KO mice treated with FU and UVB.

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Recent Advanced Toxicological Methods for Environmental Hazardous Chemicals (환경 오염물질의 진보된 독성 평가 기법)

  • 류재천;최윤정;김연정;김형태;방형애;송윤선
    • Environmental Analysis Health and Toxicology
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    • v.14 no.1_2
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    • pp.1-12
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    • 1999
  • Recently, several new methods for the detection of genetic damages in vitro and in vivo based on molecular biological techniques were introduced according to the rapid progress in toxicology combined with cellular and molecular biology. Among these methods, mouse lymphoma thymidine kanase (tk) gene forward mutation assay, single cell gel electrophoresis (comet assay) and transgenic animal and cell line model as a target gene of lac I (Big Blue) and lac Z (Muta Mouse) gene mutation are newly introduced based on molecular toxicological approaches. The mouse lymphoma tk$\^$+/-/ gene assay (MOLY) using L5178Y tk$\^$+/-/ mouse lymphoma cell line is one of the mammalian forward mutation assays, and has many advantages and more sensitive than hprt assay. The target gene of MOLY is a heterozygous tk$\^$+/-/ gene located in 11 chromosome, so it is able to detect the wide range of genetic changes like point mutation, deletion, rearrangement, and mitotic recombination within tk gene or deletion of entire chromosome 11. The comet assay is a rapid, simple, visual and sensitive technique for measuring and analysing DNA breakages in mammalian cells, Also, transgenic animal and cell line models, which have exogenous DNA incorporated into their genome, carry recoverable shuttle vector containing reporter genes to assess endogenous effects or alteration in specific genes related to disease process, are powerful tools to study the mechanism of mutation in vivo and in vitro, respectively. Also in vivo acridine orange supravital staining micronucleus assay by using mouse peripheral reticulocytes was introduced as an alternative of bone marrow micronucleus assay. In this respect, there was an International workshop on genotoxicity procedure (IWGTP) supported by OECD and EMS (Environmental Mutagen Society) at Washington D. C. in March 25-26, 1999. The objective of IWGTP is to harmonize the testing procedures internationally, and to extend to finalization of OECD guideline, and to the agreement of new guidelines under the International Conference of Harmonization (ICH) for these methods mentioned above. Therefore, we introduce and review the principle, detailed procedure, and application of MOLY, comet assay, transgenic mutagenesis assay and supravital staining micronucleus assay.

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Effects of Boyangmaksung-bang (BYMSB) on the Membranous Nephropathy Induced by Cationic Bovine Serum Albumin in Mouse Model (보양막성방(補陽膜性方)이 Cationic Boivine Serum Albumin 투여로 유발된 Mouse의 Membranous Nephropathy에 미치는 영향)

  • Lim, Bum-Soo;Cho, Chung-Sik;Kim, Cheol-Jung
    • The Journal of Korean Medicine
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    • v.30 no.2
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    • pp.63-78
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    • 2009
  • Objective: The purpose of experimental study was to prove the effects of Boyangmakseong-bang (BYMSB) treatment on cBSA-induced in a MN mouse model. Methods: We divided mice into 4 groups. The Normal group had no treatment. We used cBSA and induced MN mouse model to the other 3 groups. The Control group was treated with cBSA (9mg/kg i.p) only. The second group, named 'BY-250', was treated with cBSA (9mg/kg i.p) and BYMSB extract (250mg/kg, p.o). The third group, named 'BY-500', was treated with cBSA (9mg/kg i.p) and BYMSB extract (500mg/kg, p.o). After cBSA and BYMSB extract treatment for 4 weeks, the increase in percentage of body weight, proteinuria, serum albumin, total cholesterol, creatinine and BUN of all groups were measured. The CD3+, CD19+, CD4+, CD8+ cell levels of spleen of all groups were analyzed. IgA, IgG, IgM, IL-$1{\beta}$, TNF-${\alpha}$, IL-6 and IFN-${\gamma}$ levels of all groups were gauged. H&E staining, immunofluorescence staining and electron microscopy of kidney were observed. Results: BYMSB showed significant decrease in the 24hrs proteinuria, serum total cholesterol, serum IgG levels and BUN levels, and showed significant increase in the serum albumin levels compared with the control group. BYMSB showed increase in the increasing percentage of body weight and IFN-${\gamma}$ levels compared with the control. BYMSB showed decrease in the CD3+ T cells, CD4+ Th cells, IL-$1{\beta}$, TNF-${\alpha}$ and IL-6 levels, but did not show significant change compared with the control. BYMSB showed considerable decrease in the thickening of the GBM on H&E staining, deposition of IgG on immunofluorescence staining and deposition of electron-density on electron microscopy of kidney compared with the control. Conclusions: According to the above results, it is suggested that BYMSB decreases the symptoms of MN induced by cBSA in a mouse model. Therefore BYMSB seems to be applicable to MN in clinical practice.

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Coronary Arterial Lesions of Kawasaki Disease Observed in a Mouse Model of Sepsis: A Pilot Study and a Review of the Literature (패혈증 마우스 모델에서 가와사키병의 관상동맥 병변 관찰: 예비연구와 문헌고찰)

  • Kim, Joo-Hyun;Kim, Hyo-Jin;Shin, Jung-Ha;Choi, Ui-Yoon;Lee, Soo-Young;Han, Ji-Whan
    • Pediatric Infection and Vaccine
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    • v.24 no.2
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    • pp.102-107
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    • 2017
  • Purpose: Coronary arterial lesions (CALs) were reported to have developed in children with systemic inflammatory diseases, as well as those with Kawasaki disease (KD). The purpose of this study was to confirm that the CAL development in children with KD occurs in a mouse model of sepsis presenting typical systemic inflammatory response syndrome (SIRS). Methods: To induce the sepsis mouse model with SIRS, 6-week-old C57BL/6 mice were intraperitoneally injected with endotoxin. We compared histological findings of the major organs between the control and the sepsis groups and examined CAL in the heart of the septic mice. Results: Infiltrating inflammatory cells were relatively increased in the heart, liver, and kidneys of the sepsis group, compared with those of the control group. We confirmed lymphocytic infiltration in the myocardium (myocarditis) and the pericardial soft tissue of the heart. Furthermore, coronary artery of the septic mouse was identified, but CAL was not observed. Conclusions: In this study, we failed to confirm the existence of CAL in a mouse model of sepsis. However, it is well-known that CALs are seen in many kinds of diseases that cause SIRS. Our findings suggest further investigation into the clinical significance of CAL in various systemic inflammatory diseases, including KD.

Altered Expression of Peroxiredoxin and Thioredoxin in Septic Animal Model (패혈증 동물 모델에서 Peroxiredoxin 및 Thioredoxin의 발현 변화)

  • Kim, Hyung-Jung;Chae, Ho-Zoon;Ahn, Chul-Min;Kim, Sung-Kyu;Lee, Won-Young
    • Tuberculosis and Respiratory Diseases
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    • v.47 no.4
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    • pp.451-459
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    • 1999
  • Background : In sepsis, excessive generation of reactive oxygen species plays key roles in the pathogenesis of acute lung injury. The serum antioxidants such as catalase and MnSOD are elevated in sepsis and considered as predictors of acute respiratory distress syndrome(ARDS) and prognostic factors of sepsis. Peroxiredoxin(Prx) has recently been known as an unique and major intracellular antioxidant. In this study, we evaluated the expression of Prx I and Prx II in mouse monocyte-macrophage cells(RAW 267.7) after treatment of oxidative stress and endotoxin and measured the amount of Prx I, Prx II and thioredoxin(Trx) in peritoneal and bronchoalveolar lavage fluid of septic animal model. Methods : Using immunoblot analysis with specific antibodies against Prx I, Prx II and Trx, we evaluated the distribution of Prx I and Prx II in human neutrophil, alveolar macrophage and red blood cell. We evaluated the expression of Prx I and Prx II in mouse monocyte-macrophage cells after treatment of $5\;{\mu}M$ menadione and $1\;{\mu}g/ml$ lipopolysaccharide(LPS) and measured the amount of Prx I, Prx II and Trx in peritoneal lavage fluid of intraperitoneal septic animals(septic animal model induced with intraperitoneal 6 mg/Kg LPS injection) and those in bronchoalveolar lavage fluid of intraperitoneal septic animals and intravenous septic animals(septic animal model induced with intravenous 5 mg/Kg LPS injection) and compared with the severity of lung inflammation. Results : The distribution of Prx I and Prx II were so different among human neutrophil, alveolar macrophage and red blood cell. The expression of Prx I in mouse monocyte-macrophage cells was increased after treatment of $5\;{\mu}M$ menadione and $1\;{\mu}g/ml$ lipopolysaccharide but that of Prx II was not increased. The amount of Prx I, Prx II and Trx were increased in peritoneal lavage fluid of intraperitoneal septic animals but were not increased in bronchoalveolar lavage fluid of intraperitoneal and intravenous septic animals regardless of the severity of lung inflammation. Conclusion : As intracellular antioxidant, the expression of Prx I is increased in mouse monocyte-macrophage cells after treatment of oxidative stress and endotoxin. The amount of Prx I, Prx II and Trx are increased in local inflammatory site but not increased in injured lung of septic animal model.

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Automatic Analysis of Bone Formation in a Mouse Model of Frontal Bone Defect (전두골 결손 마우스 모델의 골형성 자동 분석)

  • Kang, Sun-Kyung;Jung, Sung-Tae
    • Journal of Korea Multimedia Society
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    • v.18 no.9
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    • pp.997-1007
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    • 2015
  • In this paper, we propose a method for automatically analyzing the bone formation in a mouse model of frontal bone defect. We perforate two holes of 0.8mm diameter in the frontal bone and observe the bone formation process using a micro CT. Because the conventional analysis software of the micro CT does not support automatic analysis of the bone formation status, we have to use a manual analysis method. However the manual analysis is very cumbersome and requires a lot of time, we propose an automatic analysis method. It rotates the image around three axes directions so that the mouse's skull come into regular position. It calculates the cumulative image of the voxel values for the perforated bone surface. It estimates the hole location by finding the darkest point in the cumulative image. The proposed method was applied to 24 CT images of saline administration group and PTH administration group and hole location was estimated. BV/TV index was calculated for the estimated hole to evaluate the bone formation status. Experimental results showed that bone formation process is more active in PTH administration group. The method proposed in this paper could replace successfully the cumbersome and time consuming manual job.

Influence of Word of Mouse and Consumers Attitudes on Consumers' Decision-Making in E-Commerce

  • GUO, Chen;KIM, Hyunsu;KIM, Woohyoung
    • The Journal of Industrial Distribution & Business
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    • v.11 no.8
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    • pp.7-19
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    • 2020
  • Purpose: Prior studies rarely investigated the effects of the Word of Mouse (WoM) information on consumers' motivation and willingness to purchase a product. Furthermore, few scholars have studied how word-of-mouth information works and they fail to find consistent results. Research design, data and methodology: This study uses a multivariate regression model to investigate the influence of WoM on consumer attitudes and consumer decision-making. It categorizes the quality of WoM into source level and acceptance level, to analyze its influence from a new perspective. A total of 400 surveys were completed, resulting in 336 usable questionnaires for analysis. It was collected in 14 cities from all regions in China. This study constructs a theoretical model of WoM influence on consumers' purchase willingness based on a systematic review of the related literature on WoM quality, perceived value, customer trust, and consumers' purchase willingness. Results: Empirical results reveal that the Internet WoM (consumer's source level and acceptance level) indirectly affects consumer behavior by influencing consumer attitudes. Conclusions: This study provides practical significance and value for merchants to develop better WoM marketing and to establish the reliability of WoM websites. Companies should consider online WoM from the perspective of consumers, thereby improving existing marketing strategies.

Improved human hematopoietic reconstitution in HepaRG co-transplanted humanized NSG mice

  • Kim, Jin;Ryu, Bokyeong;Kim, Ukjin;Kim, Chang-Hwan;Hur, Gyeung-Haeng;Kim, C-Yoon;Park, Jae-Hak
    • BMB Reports
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    • v.53 no.9
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    • pp.466-471
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    • 2020
  • Several humanized mouse models are being used to study humanspecific immune responses and diseases. However, the pivotal needs of fetal tissues for the humanized mice model have been huddled because of the demand for ethical and medical approval. Thus, we have verified the hematopoietic and immunomodulatory function of HepaRG and developed a new and easy humanized mouse model to replace the use of fetal liver tissue. HepaRG co-transplanted Hu-NSG mice significantly increased CD45+ lymphocytes and CD19+ B cells and CD3+ T cells than normal Hu-NSG, suggesting enhanced reconstitution of the human immune system. These results have improved the applicability of humanized mice by developing new models easily accessible.