• Title/Summary/Keyword: Resistant model

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Dexamethasone Does Not Inhibit Airway CXC Chemokine Expression and Neutrophilia in a Murine Model of Asthma - Mechanism of Steroid Resistance in Asthma

  • Lee, Young-Man;Kang, Nam-In;Lee, Hern-Ku
    • IMMUNE NETWORK
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    • v.7 no.1
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    • pp.18-25
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    • 2007
  • Background: Although glucocorticoids (GCs) are effective in controlling asthma in the majority of patients, a subset of asthmatics fails to demonstrate a satisfactory response, even to systemic GC therapy. This population is referred to as being "steroid-resistant". The actual mechanism underlying steroid resistance in asthma remains to be elucidated. Methods: We have investigated how dexamethasone (DEX) regulates asthmatic phenotypes in a murine model of asthma, in which mice received i.p. immunization twice, followed by two bronchoprovocations with aerosolized OVA with a one-week interval, which we have recently described. Results: Pretreatment with DEX resulted in an inhibition of NF-${\kappa}B$ activation in asthmatic lungs, and also inhibited bronchoalveolar lavage (BAL) levels of NF-${\kappa}B$-dependent cytokines such as TNF-${\alpha}$ and CC chemokines [eotaxin and monocyte chemotactic protein (MCP)-1]. DEX was effective in suppressing airway hyperresponsiveness (AHR) at 10 h, Th2-dependent asthmatic phenotypes such as airway eosinophilia, BAL levels of Th2 cytokines (IL-5 and IL-13), and mucin production. However, DEX failed to suppress BAL levels of CXC chemokines [macrophage inflammatory protein-2 (MIP-2) and keratinocyte-derived chemokine (KC)] and airway neutrophilia. Conclusion: Airway neutrophilia is among the phenomena observed in patients with severe GC-resistant asthma. This study will provide insight into the molecular basis for airway neutrophila seen in steroid-resistant asthma. Further studies are required to delineate the underlying mechanism of CXC chemokine expression in asthma.

Earthquake Resistant Performance of a High-rise Shear Wall Apartment Based on Nonlinear Time History Response Analysis (동적 탄소성 지진응답해석에 의한 고층 벽식 아파트의 내진성능 검토)

  • 박성수
    • Journal of the Earthquake Engineering Society of Korea
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    • v.3 no.1
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    • pp.1-8
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    • 1999
  • Dynamic elastoplastic LPM (lumped parameter mass) analyses are carried out in order to investigate the seismic resistant performance of a typical high-rise shear wall apartment subjected to several earthquakes. Three-dimensional nonlinear pushover analysis is adopted to estimate initial elastic stiffness, yielding strength and post-yielding stiffness of each story for the time history analysis of LPM shear model. For the hysteresis of each story, Clough and bilinear models are used with the input of four recorded earthquake ground motions of EI Centro 1940 NS, Taft 1952 EW, Hachinohe 1968 NS and Kobe 1995 NS, of which the amplitudes are scaled down to have the same maximum ground velocity of 12 kine. The result shows that yieldings take place in most storys of the building, i.e. the earthquake resistant capacity of this high-rise shear wall apartment is not sufficient at the event of earthquake M=5~6.

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Development of an Earthquake-Resistant Model for a High-Level Waste Disposal Canister (고준위 폐기물 처분용기 내진 해석 모델 개발)

  • Choi, Young-Chul;Yoon, Chan-Hoon;Kim, Hyun-Ah;Choi, Heui-Joo
    • Tunnel and Underground Space
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    • v.24 no.4
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    • pp.316-324
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    • 2014
  • In the underground 500 m depth, the high level radioactive waste disposal system is made by boring the tunnel in the base rock and putting the high level waste disposal canister that is the surrounding form with the buffer material. According to the many statistics, it is the tendency that the earthquake increases in the Korean peninsula every year. In case that the earthquake is generated, the disposal canister in the rock mass can be broken due to the shearing force in the underground. Furthermore, a major environmental problems can be caused by the radioactive harmful substances. In this study, the earthquake-proof type buffer material was developed with the protection method safely on the earthquake. The main parameter having an effect on the earthquake-resistant performance was analyzed and the earthquake-proof type buffer material was designed. The shear analysis model was developed and the performance of the earthquake-proof type buffer material was evaluated by using ABAQUS.

Experimental Study on Vibration Control of Bracing Dampers using Rubbers (방진원 고무를 이용한 가새형 감쇠기의 진동제어 실험연구)

  • 민경원
    • Proceedings of the Earthquake Engineering Society of Korea Conference
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    • 1998.10a
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    • pp.249-257
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    • 1998
  • Vibration-resistant rubbers, whose elastic and shear behaviors are similar to viscoelastic materials, are used to make bracing dampers to reduce the building vibration. Experimental study is carried out to find the vibration characteristics of the dampers installed in the building model. The natural frequencies and modal damping ratios are obtained from the free vibration test and Fourier analysis. Shaking table test is performed to find the response behavior of the building model under earthquake loading. The present experimental study shows that the bracing dampers have the behavior of viscoelastic dampers, which increase the modal damping ratios and viscoelastic characteristics.

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Prevalence of Positive Carriage of Tuberculosis, Methicillin-resistant $Staphylococcus$ $aureus$, and Vancomycin-resistant $Enterococci$ in Patients Transported by Ambulance: A Single Center Observational Study

  • Ro, Young-Sun;Shin, Sang-Do;Noh, Hyun;Cho, Sung-Il
    • Journal of Preventive Medicine and Public Health
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    • v.45 no.3
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    • pp.174-180
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    • 2012
  • Objectives: An ambulance can be a potential source of contagious or droplet infection of a community. We estimated the prevalence of positive carriage of tuberculosis (TB), methicillin-resistant $Staphylococcus$ $aureus$ (MRSA), and vancomycin-resistant $Enterococci$ (VRE) in patients transported by ambulance. Methods: This was a retrospective observational study. We enrolled all patients who visited a tertiary teaching hospital emergency department (ED). Blood, sputum, urine, body fluid, and rectal swab samples were taken from patients when they were suspected of TB, MRSA, or VRE in the ED. The patients were categorized into three groups: pre-hospital ambulance (PA) group; inter-facility ambulance (IA) group; and non-ambulance (NA) group. Adjusted odds ratio (OR) and 95% confidence intervals (CI) were calculated using a multivariable logistic regression model for the prevalence of each infection. Results: The total number of patients was 89206. Of these, 9378 (10.5%) and 4799 (5.4%) were in the PA and IA group, respectively. The prevalence of TB, MRSA, and VRE infection were 0.3%, 1.1%, and 0.3%, respectively. In the PA group, the prevalence of TB, MRSA, and VRE were 0.3%, 1.8%, and 0.4%. In the IA group, the prevalence of TB, MRSA, and VRE were 0.7%, 4.6%, and 1.5%, respectively. The adjusted ORs (95% CI) of the PA and IA compared to the NA group were 1.02 (0.69 to 1.53) and 1.83 (1.24 to 2.71) for TB, 2.24 (1.87 to 2.69) and 5.47 (4.63 to 6.46) for MRSA, 2.59 (1.78 to 3.77) and 8.90 (6.52 to 12.14) for VRE, respectively. Conclusions: A high prevalence of positive carriage of TB, MRSA, and VRE in patients transported by metropolitan ambulances was found.

Acute Toxicity Evaluation to Daphnia magna of Disease Resistant(OsCK1) Rice (병저항성 GM(OsCK1)벼의 물벼룩(Daphnia magna)에 대한 급성독성 평가)

  • Oh, Sung-Dug;Lee, Kijong;Park, Soo-Yun;Ryu, Tae-Hun;Suh, Sang Jae
    • Korean Journal of Environmental Agriculture
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    • v.33 no.2
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    • pp.121-128
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    • 2014
  • BACKGROUND: The disease resistant (OsCK1) rice was generated by inserting choline kinase (CK1) and phosphinothricin acetyltransferase (PAT) genes isolated from Oryza sativa and Streptomyces hygroscopicus into the genome of the rice, Nakdongbyeo. With the potential problems of safeties, the evaluations on non-target organisms are essentially required for the environmental risk assessment of genetically modified (GM) crops. In the present study, we conducted the evaluation of acute toxicity on Daphnia magna that commonly used as a model organism in ecotoxicological studies for non-target organism evaluation. METHODS AND RESULTS: Effect of acute toxicity to Daphnia magna by each concentration were investigated in the disease resistant (OsCK1) rice and non-genetically modified (non-GM) rice, Nakdongbyeo, as concentration (0, 1,000, 1,800, 3,240, 5,830, 10,500 and 20,000 mg/L). The OsCK1 rice used for the test was confirmed to express the OsCK1/PAT gene by the PCR(Polymerase chain reaction) and western blot analysis. Feeding test showed that no significant differences in cumulative immobility and abnormal response of Daphnia magna fed on OsCK1 rice or non-GM rice. The 48hr-$EC_{50}$ values showed no difference between OsCK1 rice (3,147.18 mg/L) and non-GM rice (3,596.27 mg/L). CONCLUSION: This result suggested that there was no significant difference in toxicity to Daphnia magna between OsCK1 rice and non-GM counterpart.

Epithelial-mesenchymal Transition is Associated with Acquired Resistance to 5-Fluorocuracil in HT-29 Colon Cancer Cells

  • Kim, A-Young;Kwak, Jae-Hwan;Je, Nam Kyung;Lee, Yun-hee;Jung, Young-Suk
    • Toxicological Research
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    • v.31 no.2
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    • pp.151-156
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    • 2015
  • 5-Fluorouracil (5-FU) is commonly used for the therapy of colon cancer; however, acquired resistance to 5-FU is a critical barrier to successful treatment and the primary cause of chemotherapy failure. Epithelial-mesenchymal transition (EMT) is a process whereby cells undergo alterations in morphology and molecular characteristics promoting tumor progression and metastasis. Accumulating evidence shows that transition from epithelial to mesenchymal phenotype in cancer cells is associated with their resistance to chemotherapy. However, it is still poorly understood whether EMT is involved in acquired resistance to 5-FU. In this study, we developed an in vitro cell model, 5-FU-resistant HT-29 colon cancer cells, and characterized the differences in cellular morphology and molecular alterations between parental and resistant cells. In accord with mesenchymal-like morphology of 5-FU-resistant HT-29 cells, the expression of the mesenchymal marker fibronectin was significantly increased in these cells in comparision with that in the parental cells. Of interest, we also found a marked increase in the expression of EMT-inducing transcription factors Twist, Zeb1, and Zeb2. Finally, 5-FU-resistant cells showed enhanced migration in comparison with parental HT-29. Taken together, these results indicate that EMT could be associated with 5-FU resistance acquired by HT-29 cells. A specific role of each transcription factor found in this study will require further investigation.

Picropodophyllotoxin Inhibits Cell Growth and Induces Apoptosis in Gefitinib-Resistant Non-Small Lung Cancer Cells by Dual-Targeting EGFR and MET

  • Jin-Young, Lee;Bok Yun, Kang;Sang-Jin, Jung;Ah-Won, Kwak;Seung-On, Lee;Jin Woo, Park;Sang Hoon, Joo;Goo, Yoon;Mee-Hyun, Lee;Jung-Hyun, Shim
    • Biomolecules & Therapeutics
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    • v.31 no.2
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    • pp.200-209
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    • 2023
  • Patients with non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) amplification or sensitive mutations initially respond to the tyrosine kinase inhibitor gefitinib, however, the treatment becomes less effective over time by resistance mechanism including mesenchymal-epithelial transition (MET) overexpression. A therapeutic strategy targeting MET and EGFR may be a means to overcoming resistance to gefitinib. In the present study, we found that picropodophyllotoxin (PPT), derived from the roots of Podophyllum hexandrum, inhibited both EGFR and MET in NSCLC cells. The antitumor efficacy of PPT in gefitinib-resistant NSCLC cells (HCC827GR), was confirmed by suppression of cell proliferation and anchorage-independent colony growth. In the targeting of EGFR and MET, PPT bound with EGFR and MET, ex vivo, and blocked both kinases activity. The binding sites between PPT and EGFR or MET in the computational docking model were predicted at Gly772/Met769 and Arg1086/Tyr1230 of each ATP-binding pocket, respectively. PPT treatment of HCC827GR cells increased the number of annexin V-positive and subG1 cells. PPT also caused G2/M cell-cycle arrest together with related protein regulation. The inhibition of EGFR and MET by PPT treatment led to decreases in the phosphorylation of the downstream-proteins, AKT and ERK. In addition, PPT induced reactive oxygen species (ROS) production and GRP78, CHOP, DR5, and DR4 expression, mitochondrial dysfunction, and regulated involving signal-proteins. Taken together, PPT alleviated gefitinib-resistant NSCLC cell growth and induced apoptosis by reducing EGFR and MET activity. Therefore, our results suggest that PPT can be a promising therapeutic agent for gefitinib-resistant NSCLC.

Behavior Factor of a Steel Box Bridge with Single Column Piers (단주교각 강박스교량의 거동계수)

  • 박준봉;김종수;국승규
    • Proceedings of the Earthquake Engineering Society of Korea Conference
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    • 2002.03a
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    • pp.228-235
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    • 2002
  • As the response spectrum method generally used in the earthquake resistant design is a linear method, the nonlinear behavior of a structure is to be reflected with a specific factor. Such factors are provided in the "Design Criteria for Roadwaybridges"as response modification factors and in the Eurocode 8, Part 2 as behavior factors. In this study a 5-span steel box bridge with single column piers is selected and the behavior factor is determined. The linear time history analyses are carried out with a simple linear model, where the nonlinear behavior of piers leading to the ductile failure mechanism is considered as predetermined characteristic curves.

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