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The Effect of Nitric Oxide Donor or Nitric Oxide Synthase Inhibitor on Oxidant Injury to Cultured Rat Lung Microvascular Endothelial Cells (산화질소 공여물과 산화질소 합성효소 길항제가 백서 폐미세혈관 내피세포 산화제 손상에 미치는 영향)

  • Chang, Joon;Michael, John R.;Kim, Se-Kyu;Kim, Sung-Kyu;Lee, Won-Young;Kang, Kyung-Ho;Yoo, Se-Hwa;Chae, Yang-Seok
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.6
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    • pp.1265-1276
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    • 1998
  • Background : Nitric oxide(NO) is an endogenously produced free radical that plays an important role in regulating vascular tone, inhibition of platelet aggregation and white blood cell adhesion to endothelial cells, and host defense against infection. The highly reactive nature of NO with oxygen radicals suggests that it may either promote or reduce oxidant-induced cell injury in several biological pathways. Oxidant injury and interactions between pulmonary vascular endothelium and leukocytes are important in the pathogenesis of acute lung injury, including acute respiratory distress syndrome(ARDS). In ARDS, therapeutic administration of NO is a clinical condition providing exogenous NO in oxidant-induced endothelial injury. The role of exogenous NO from NO donor or the suppression of endogenous NO production was evaluated in oxidant-induced endothelial injury. Method : The oxidant injury in cultured rat lung microvascular endothelial cells(RLMVC) was induced by hydrogen peroxide generated from glucose oxidase(GO). Cell injury was evaluated by $^{51}$chromium($^{51}Cr$) release technique. NO donor, such as S-nitroso-N-acetylpenicillamine(SNAP) or sodium nitroprusside(SNP), was added to the endothelial cells as a source of exogenous NO. Endogenous production of NO was suppressed with N-monomethyl-L-arginine(L-NMMA) which is an NO synthase inhibitor. L-NMMA was also used in increased endogenous NO production induced by combined stimulation with interferon-$\gamma$(INF-$\gamma$), tumor necrosis factor-$\alpha$(TNF-$\alpha$), and lipopolysaccharide(LPS). NO generation from NO donor or from the endothelial cells was evaluated by measuring nitrite concentration. Result : $^{51}Cr$ release was $8.7{\pm}0.5%$ in GO 5 mU/ml, $14.4{\pm}2.9%$ in GO 10 mU/ml, $32.3{\pm}2.9%$ in GO 15 mU/ml, $55.5{\pm}0.3%$ in GO 20 mU/ml and $67.8{\pm}0.9%$ in GO 30 mU/ml ; it was significantly increased in GO 15 mU/ml or higher concentrations when compared with $9.6{\pm}0.7%$ in control(p < 0.05; n=6). L-NMMA(0.5 mM) did not affect the $^{51}Cr$ release by GO. Nitrite concentration was increased to $3.9{\pm}0.3\;{\mu}M$ in culture media of RLMVC treated with INF-$\gamma$ (500 U/ml), TNF-$\alpha$(150 U/ml) and LPS($1\;{\mu}g/ml$) for 24 hours ; it was significantly suppressed by the addition of L-NMMA. The presence of L-NMMA did not affect $^{51}Cr$ release induced by GO in RLMVC pretreated with INF-$\gamma$, TNF-$\alpha$ and LPS. The increase of $^{51}Cr$ release with GO(20 mU/ml) was prevented completely by adding 100 ${\mu}M$ SNAP. But the add of SNP, potassium ferrocyanate or potassium ferricyanate did not protect the oxidant injury. Nitrite accumulation was $23{\pm}1.0\;{\mu}M$ from 100 ${\mu}M$ SNAP at 4 hours in phenol red free Hanks' balanced salt solution. But nitrite was not detectable from SNP upto 1 mM The presence of SNAP did not affect the time dependent generation of hydrogen peroxide by GO in phenol red free Hanks' balanced salt solution. Conclusion : Hydrogen peroxide generated by GO causes oxidant injury in RLMVC. Exogenous NO from NO donor prevents oxidant injury, and the protective effect may be related to the ability to release NO. These results suggest that the exogenous NO may be protective on oxidant injury to the endothelium.

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A Simple Dosing Scheme for Intravenous Busulfan Based on Retrospective Population Pharmacokinetic Analysis in Korean Patients

  • Choe, Sang-Min;Kim, Gayeong;Lim, Hyeong-Seok;Cho, Sang-Heon;Ghim, Jong-Lyul;Jung, Jin-Ah;Kim, Un-Jib;Noh, Gyu-Jeong;Bae, Kyun-Seop;Lee, Dong-Ho
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.4
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    • pp.273-279
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    • 2012
  • Busulfan is an antineoplastic agent with a narrow therapeutic window. A post-hoc population pharmacokinetic analysis of a prospective randomized trial for comparison of four-times daily versus once-daily intravenous busulfan was carried out to search for predictive factors of intravenous busulfan (iBu) pharmacokinetics (PK). In this study the population PK of iBu was characterized to provide suitable dosing recommendations. Patients were randomized to receive iBu, either as 0.8 mg/kg every 6 h or 3.2 mg/kg daily over 4 days prior to hematopoietic stem cell transplantation. In total, 295 busulfan concentrations were analyzed with NONMEM. Actual body weight and sex were significant covariates affecting the PK of iBu. Sixty patients were included in the study (all Korean; 23 women, 37 men; mean [SD] age, 36.5 [10.9] years; weight, 66.5 [11.3] kg). Population estimates for a typical patient weighing 65 kg were: clearance (CL) 7.6 l/h and volume of distribution (Vd) 32.2 l for men and 29.1 L for women. Inter-individual random variabilities of CL and $V_d$ were 16% and 9%. Based on a CL estimate from the final PK model, a simple dosage scheme to achieve the target $AUC_{0-inf}$ (defined as median AUC0-inf with a once-daily dosage) of 26.18 $mg/l{\cdot}hr$, was proposed: $24.79{\cdot}ABW^{0.5}mg$ q24h, where ABW represents the actual body weight in kilograms. The dosing scheme reduced the unexplained interindividual variabilities of CL and Vd of iBu with ABW being a significant covariate affecting clearance of iBU. We propose a new simple dosing scheme for iBu based only on ABW.

Effects of Different Physical Frequency on Food-Dependent Exercise Induced Allergy Anaphylaxis (FDEIA) and Related Mechanisms (운동빈도의 차이가 식이유도 운동알레르기 질환과 관련기전에 미치는 영향)

  • Kim, Cheol-Woo;Kwak, Yi-Sub
    • Journal of Life Science
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    • v.22 no.7
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    • pp.897-903
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    • 2012
  • Food allergies have become a serious health concern in the past two decades, especially in developed countries. Foods associated with allergies include vegetables, some fruits, shellfish, wheat, egg, chicken, and nuts. To describe the specific fundamentals, etiological factors, and clinical manifestations, we analyzed the different physical frequency on spleen index in sensitized and regular exercise-trained mice. We also conducted a proliferation assay of lymphocytes to OVA, ROS, ASAS, and we determined the cytokine levels. Female BALB/c mice were bred in the animal laboratory of the P and D university under controlled conditions ($22{\pm}2^{\circ}C$, RH 45-55%, and a 12-hour photoperiod). The animals were 6 weeks old at the start of the study and were fed a standard commercial chow diet from 09:00 to 15:00 for the 8-week study period. All animals had access to distilled deionized water ad libitum. They were divided into four groups: a control group (S; control sensitized, n=25), a low-frequency training group (F2, n=25), a mid-frequency training group (F3, n=25), and a high-frequency training group (F5, n=25) following the treatment of exercise time per week. The results were as follows: The mice spleen index showed the highest grade in the F5 group compared with the other groups; this level showed in an exercise frequency-dependent manner. In the proliferation assay of OVA, the F5 group showed the highest grade compared with the other groups; this level was also showed in an exercise frequency-dependent manner. Peritoneal ROS and ASAS showed a statistically significant increase in the F5 group and decreased in the F2 group compared with the S group. However, there were no significant differences in the F3 group. The highest level of IL-4 was found in the F5 group compared with the other groups. However, the highest level of INF-${\gamma}$ was in the F2 group. The results suggest that FDEIA is positively correlated with the frequency of exercise due to the direct effect of physical exercise on peritoneal ROS and the cytokine profile. Further research is needed on the specific mechanism underlying the combined effects of exercise intensity and frequency on physical-induced allergy anaphylaxis.

Effect of CpG Oligodeoxynucleotides on Airways of Mice with Established Airways Inflammation (기도 염증이 유발된 생쥐에서 CpG Oligodeoxynucleotides가 미치는 효과)

  • Hwang, Hei-Won;Kim, Su-Jin;Kim, Won-Duk;Cho, Sung-Min;Lee, Dong-Suk;Choi, Sung-Min
    • Clinical and Experimental Pediatrics
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    • v.45 no.7
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    • pp.875-883
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    • 2002
  • Purpose : Airways eosinophilia and increased IgE, characteristic features of asthma, result from a predominant Th2 response. In this study, we investigated the effect of CpG oligodeoxynucleotides (ODNs) on the inhibition of airways eosinophilia in mice with established airway inflammation. We also investigated the immunological mechanisms involved. Methods : Groups of BALB/c mice were sensitized intradermally with ovalbumin(OVA). At week 10, airway inflammation was induced by intranasal challenge of the mice with OVA. At week 14, the mice were challenged intranasally again with OVA in the presence and without the presence of CpG ODNs. Mice with saline administration served as negative controls. Bronchoalveolar lavage fluids(BALF) were obtained and eosinophils were counted. Th1 and Th2 cytokines in the spleen cell cultures were measured by ELISA. Serum OVA-specific IgE and IgG2a antibodies were also measured by ELISA. Results : BALF eosinophils were significantly inhibited in the CpG ODNs-treated mice(P<0.01). IgE and IgG2a levels increased significantly in both CpG ODNs-treated and untreated groups as compared to the negative control group; there was, however, no significant difference between the two groups four days after intranasal administration of CpG ODNs. Cytokine analysis revealed decreased production of IL-4, IL-5, and IL-13 and increased production of IL-12 in the CpG ODNs-treated group as compared to the untreated group. Interestingly, $IFN-{\gamma}$ levels were not upregulated in the CpG ODNs-treated group. Conclusion : CpG ODNs vaccination is a potentially useful approach for reversing airways eosinophilia in mice with established airways inflammation.

Recent trends in advanced flight control

  • Kanai, Kimio
    • 제어로봇시스템학회:학술대회논문집
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    • 1996.10a
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    • pp.24.1-24
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    • 1996
  • The development of future aircraft that involves the expanded flight envelop will place increased performance requirements on the design of the flight control system. Maneuvering areas are expanding into flight envelopes characterized by significantly larger levels of modeling uncertainty than encountered in present flight control designs. Conventional flight control techniques that ignore the effects of large parameter variations, modeling uncertainties and nonlinearities, will likely produce designs with poor performance and robustness. Recent advances in modern control theories called advanced control theories, most notably the H$\_$.inf./ synthesis technique, adaptive control and neural network application, offer the promise of a design technique that can produce both high performance and robust controllers for next generation aircraft. This special lecture will survey the recent development in advanced flight control and review the possible application of advanced control theories.

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Design of decentralized $H^\infty$ state estimator using the generalization of $H^\infty$ filter in indefinite inner product spaces (부정 내적 공간에서의 $H^\infty$필터의 일반화를 통한 분산 $H^\infty$상태 추정기의 설계)

  • 김경근;진승희;최윤호;박진배
    • 제어로봇시스템학회:학술대회논문집
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    • 1997.10a
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    • pp.1464-1468
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    • 1997
  • We propose a decentralized state estimation method in the multisensor state estimation problem. The proposed method bounds teh maximum energy gain from uknown external disturbances to the estimation errors in the suboptimal case. And we formulate aternative H/sip .inf./ filter gain equatiions with teh idea that the suboptimal H.$^{\infty}$ filter is the special form of Kalman filter filter whose state equations are defined in indefinite inner product spaces. Using alternative filter gain equations we design the decentralized $H^{\infty}$ state estimator which is composed of local filters and central fusion filter that are suboptimal in the $H^{\infty}$ sense. In addition, the proposed update equations between global and local data can reduce unnecessary calculation burden efficently.y.

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Robust control of positioning systems with a bang-bang actuator (뱅-뱅 액츄에이터를 가진 위치 제어계의 강인 제어)

  • Choe, Jin-Tae;Kim, Jong-Sik
    • Journal of Institute of Control, Robotics and Systems
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    • v.2 no.4
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    • pp.257-263
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    • 1996
  • 본 논문에서는 기계적 위치 제어계에서 다단계 뱅-뱅 액츄에이터의 비선형성에 의한 목표 위치에서의 리미트 사이클을 방지하는 제어방법을 제안한다. 다단계 뱅-뱅 액츄에이터의 선형화된 모델인 기술함수를 이용하여 비선형성을 보상한다. 강인성을 확보하기 위해 루프 형성 기법에 의한 H/sub .inf./ 제어기가 설계된다. 제안된 제어방법은 기존의 선형제어기보다 비선형성이 보상되어 사역대가 작아지므로 최소 제어 가능 구간을 줄일 수 있다. 1축 위치 제어계의 실험을 하여 제안된 제어방법이 리미트 사이클을 줄이고 제어정도를 향상 시키는데 유효함을 입증하였다.

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STRONG UNIQUE CONTINUATION OF THE SCHR$\"{O}$DINGER OPERATOR

  • Kim, Yonne-Mi
    • Bulletin of the Korean Mathematical Society
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    • v.31 no.1
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    • pp.55-60
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    • 1994
  • It is well known that if P(x,D) is an elliptic differential operator, with real analytic coefficients, and P(x,D)u = 0 in an open, connected subset .ohm..mem.R$^{n}$ , then u is real analytic in .ohm. Hence, if there exists x$_{0}$ .mem..ohm. such that u vanishes of .inf. order at x$_{0}$ , u must be identically 0. If a differential operator P(x, D) has the above property, we say that p(x,D) has the strong unique continuation property (s.u.c.p.). If, on the other hand, P(x,D)u = 0 in .ohm., and u = 0 in .ohm.', an open subset of .ohm., implies that u = 0 in .ohm. we say that P(x,D)u = 0 in .ohm., and suppu .contnd. K .contnd. .ohm implies that u = 0 in .ohm. we sat that P(x,D) has the weak unique continuation property (m.u.c.p.).

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LTR properties for output-delayed systems (출력 시간 지연 시스템의 루우프 복구특성)

  • 이상정;홍석민
    • 제어로봇시스템학회:학술대회논문집
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    • 1993.10a
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    • pp.161-167
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    • 1993
  • This paper presents robustness properties of the Kalman Filter ad the associated LQG/LTR method for linear time-invariant systems having delays in both the state and output. A circle condition relating to the return difference matrix associated with the Kalman filter is derived. Using this circle condition, it is shown that the Kalman filter guarantees(1/2, .inf.) gain margin and .+-.60.deg. phase margin, which are the same as those for nondelay systems. However, it is shown that, even for minimum phase plants, the LQG/LTR method can not recover the target loop transfer function. Instead, an upper bound on the recovery error is obtained using an upper bound of the solution of the Kalman filter Riccati equations. Finally, some dual properties between output-delated system and input-delayed systems are exploited.

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Clinical Study on 1 Case of Patient with Astrocytoma (성상세포종 1례(例)에 대한 증례보고)

  • Kang, Tai-Hee;Won, Jin-Hee
    • THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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    • v.6 no.1
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    • pp.181-188
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    • 2000
  • Astrocytomas are tumors that arise from brain cells called astrocytes. These tumors can occur anywhere in the brain and spinal cord. Clinical features and symptoms depend on the location of the tumor and the victim's age. Patients with cerebellar tumors have symptoms that include headache, vomiting and unsteadiness in walking. Tumors in the cerebral hemispheres commonly present with seizures: occasionally there is weakness of the arms and legs. We treated a 33 year-old male patient who complained of dyarthria, TMD, nausea, dysphagia, and facial numbness etc. he had frequent undergone general weakness before above symptoms occurred. He was diagnosed as astrocytoma and multifocal inf and responded well to treatment with Chukdamtang(滌痰湯). acupunture and oriental physical stimulations etc.

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