• Journal of Life Science
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• v.27 no.2
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• pp.139-148
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• 2017

The inhibition of tyrosinase, a key enzyme in mammalian melanin synthesis, plays an important role in preventing skin pigmentation and melanoma. Therefore, tyrosinase inhibitors are very important in the fields of medicine and cosmetics. However, only a few tyrosinase inhibitors are currently available because of their toxic effects on skin or lack of selectivity and stability. Therefore, we synthesized a novel series of (E)-2-(substituted benzylidene)-2,3-dihydro-1H-cyclopenta[a]naphthalen-1-one derivatives and evaluated their inhibitory effects on mushroom tyrosinase, with the aim of discovering a novel tyrosinase inhibitor. Among 19 derivatives, MHY3655 ($IC_{50}=0.1456{\mu}M$) showed the strongest inhibitory effect on tyrosinase activity compared to kojic acid ($IC_{50}=17.2{\mu}M$), a well-known tyrosinase inhibitor. In addition, MHY3655 showed competitive inhibition on Lineweaver-Burk plots. We confirmed that MHY3655 strongly interacts with mushroom tyrosinase residues through the docking simulation. Substitutions with a hydroxy group at both R2 and R4 in the phenyl ring indicated that these groups play a major role in the high binding affinity to tyrosinase. Further, MHY3655 did not show cytotoxicity at the concentrations tested in B16F10 melanoma cells. In conclusion, the novel compound MHY3655 potentially shows tyrosinase inhibitory activity, and it could be used as an ingredient in whitening cosmetics.

• Tuberculosis and Respiratory Diseases
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• v.46 no.1
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• pp.44-52
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• 1999

Background : Airway infiltration by inflammatory cells, particularly of eosinophils, is one of the characteristic features of asthma. Several mechanisms for the recruitment of eosinophil is focused on the CD4+ T lymphocyte for the preferential production of Th2-c1erived cytokines. Interleukin-10(IL-10) is identified cytokine with potent antiinflammatory activity. This molecule has been shown to inhibit the release of cytokine from inflammatory cells including Th2 cell, and also to inhibit eosinophil survival. We therefore attempted to determine whether decreased synthesis of IL-10 in the lung of bronchial asthma may contribute to inflammation that is characteristics of this dease. Method: Subjects were patients with bronchial asthma(n=23) and normal controls(n=11). IL-10 produced from peripheral mononuclear cell(PBMC) and in bronchoalveolar lavage(BAL) fluid was measured by ELISA method. Degree of bronchial inflammation was assessed by total cell counts and eosinophil percents in BAL fluid, eosinophil infiltration on bronchial biopsy tissue and $PC_{20}$ for methacholine. Results: The IL-10 level produced by PBMC and in BAL fluid from patient with bronchial asthma were not different with normal controls(respectively, $901.6\pm220.4$ pg/ml, $810.9\pm290.8$ pg/ml for PBMC, $24.5\pm9.5$ pg/mL $30.5\pm13.5$ pg/ml for BAL fluid p>0.05). There were significant negative correlation between IL-10 in BAL fluid and eosinophil percents in BAL fluid or degree of eosinophil infiltration in bronchial biopsy (respectively r=-0.522, r=-0.4486 p<0.05). However there was no difference of IL-10 level according to $PC_{20}$ for methacholine. There were no correlation between IL-10 production by PBMC and peripheral blood eosinophil counts or serum eosinophilic cationic protein levels(respectively r=0.1146, r=0.0769 p>0.05). Conclusion: These observation suggest that IL-10 may participate but not acts the crucial role in regulation of the airway inflammation in bronchial asthma.

• Tuberculosis and Respiratory Diseases
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• v.53 no.3
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• pp.275-284
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• 2002

Background : Gemcitabine is a new anti-cancer agent for treating non-small cell lung cancer. Functioning as an antimetabolite, it induces anti-cancer effects by suppressing DNA synthesis after being incorporated into the DNA as a cytosine arabinoside analogue. When Gemcitabine is incorporated into the DNA, the p53 gene may be activated by induction of the DNA defect. However, there are a few studies on the molecular mechanisms of Gemcitabine-induced cell death. This study examined the role of p53 in Gemcitabine-induced cell death. Methods : A549 and NCl-H358 lung cancer cells were used in this study. The cell viability test was done using a MTT assay at Gemcitabine concentrations of 10nM, 100nM, 1uM, 10uM and 100uM. A FACScan analysis with propium iodide staining was used for the cell cycle analysis. Western blot analysis was done to investigate the extent of p53 activation. For the functional knock-out of p53, stable A549-E6 cells and H358-E6 cells were transfected pLXSN-16E6SD which is over expresses the human papilloma virus E6 protein that constantly degrades p53 protein. The functional knock out of p53 was confirmed by Western blot analysis after treatment with a DNA damaging agent, doxorubicine. Results : Gemcitabine exhibited cell toxicity in dose-dependent fashion. The cell cycle analysis resulted in an S phase arrest. Western blot analysis significant p53 activation in time-dependent manner. Gemcitabine-induced cytotoxicity was reduced by 20-30% in the A549-E6 cells and the 30-40% in H358-E6 cells when compared with the A549-neo and H358-neo control cells. Conclusion : Gemcitabine induces an S phase arrest, as expected for the anti-metabolite, and activates the p53 gene, Furthermore, p53 might play an important role in Gemcitabine-induced cell death. Further investigation into the molecular mechanisms on how Gemcitabine activates the p53 gene and its signaling pathway are recommended.

• Tuberculosis and Respiratory Diseases
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• v.59 no.5
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• pp.487-496
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• 2005

Background : 'Major pulmonary thromboembolism' is defined as right ventricular (RV) dysfunction, with or without shock, accompanied by significant morbidity and mortality. In this study, those with major pulmonary thromboembolism were divided into the shock and RV dysfunction only groups, and then investigated the mortality and complications in thrombolysis or anticoagulation, respectively. Methods : In a retrospective study, between January 1995 and December 2004, 60 eligible patients with a major pulmonary thromboembolism, admitted in Asan Medical Center, were included. Results : A total of 57 patients were treated with medical therapy. Thrombolysis was performed in 13 patients (23%) and anticoagulation in 44 (77%). There were no differences in the APACHEII and SOFA scores between the two groups. 6 (46%) and 11 (25%) patients died in the thrombolysis and anticoagulation groups, respectively (p=0.176). In the 19 patients (33%) showing shock, thrombolysis was performed in 9 (47%) and anticoagulation in 10 (53%). 4 (44%) of the 9 patients treated with thrombolytic agents and 3 (30%) of the 10 treated with anticoagulants died (p=0.650). In the 38 patients (67%) showing RV dysfunction only, thrombolysis was performed in 4 (11%) and anticoagulation in 34 (89%). 2 (50%) of the 4 patients treated with thrombolytics and 8 (24%) of the 34 treated with anticoagulants died (p=0.279). Three patients (23%) who underwent thrombolysis had a major bleeding episode, compared with 2 (5%) who were treated with anticoagulants (p=0.072). Conclusion: The results of our study showed that thrombolysis did not lower mortality and tended to increase major bleeding compared with anticoagulation in both the shock and RV dysfunction only groups. Further evaluation of the efficacy and safety of thrombolytic therapy for major thromboembolism appears warranted in Korea.

• Tuberculosis and Respiratory Diseases
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• v.60 no.1
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• pp.44-48
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• 2006

Background : Isoniazid (INH) is one of the most effective anti-tuberculosis (TB) drugs. In Korea, the dose of INH normally used in patients over 50 kg is 400 mg/day, which differs from the dose recommended by other countries. Indeed, the metabolism of INH shows ethnic variations, and Koreans are predominantly rapid acetylators. However, two reports suggested 300 mg of INH might be sufficient to reach an ideal peak level in Korean patients over 50 kg. Therefore, the aim of this study was to compare the effectiveness and adverse reactions between INH 300 mg and 400 mg in Korean TB patients. Method : Patients who were culture-positive, susceptible to all 1st-line drugs, initially on HREZ, and weighed over 50 kg were selected from patients with pulmonary TB between April 2003 and March 2005. The treatment results and adverse reactions in the INH 300 mg and 400 mg group were compared. Since April 2004, most TB patients at Asan Medical Center were administered INH 300 mg irrespective of the body weight. Results : The study included 123 patients in the 300 mg INH group and 128 in the 400 mg INH group. There were no significant differences between the groups in terms of age, gender, weight, history of TB treatment, initial smear strength, and frequency of cavitary lesions. There was no difference in the treatment duration between the groups. One hundred eleven (90%) patients in the INH 300 mg group and 102 (80%) in the INH 400 mg group completed treatment (p>0.05). There were no differences in the frequency of modification of the initial regimen between groups due to any adverse reactions (300 mg : 9.0%, 400 mg : 13.7%) and hepatotoxicity (300 mg : 2.7% ; 400 mg : 7.8%). Conclusion : Considering treatment results and adverse reactions of two groups, 300mg of INH may be sufficient for treating Korean TB patients. Further studies comparing the frequency of relapse will be needed.

• Korean Journal of Materials Research
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• v.11 no.5
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• pp.419-426
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• 2001

The stochiometric $AgGaSe_2$ polycrystalline mixture of evaporating materials for the $AgGaSe_2$ single crystal thin film was prepared from horizontal furnace. To obtain the single crystal thin films, $AgGaSe_2$ mixed crystal and semi-insulating GaAs(100) wafer were used as source material and substrate for the Hot Wall Epitaxy (HWE) system, respectively. The source and substrate temperature were fixed at$ 630^{\circ}C$ and $420^{\circ}C$, respectively. The thickness of grown single crystal thin films is 2.1$\mu\textrm{m}$. The single crystal thin films were investigated by photoluminescence and double crystal X-ray diffraction(DCXD) measurement. The carrier density and mobility of AgGaSe$_2$ single crystal thin films measured from Hall effect by van der Pauw method are $4.89\Times10^{17}$ cm$^{-3}$ , 129cm2/V.s at 293K, respectively. From the Photocurrent spectrum by illumination of perpendicular light on the c-axis of the AgGaSe$_2$ single crystal thin film, we have found that the values of spin orbit splitting $$\Delta$S_{o}$ and the crystal field splitting $\Delta$C$_{r}$, were 0.1762eV and 0.2474eV at 10K, respectively. From the photoluminescence measurement of AgGaSe$_2$ single crystal thin film, we observed free excision (EX) observable only in high quality crystal and neutral bound exciton ($D^{o}$ , X) having very strong peak intensity. And, the full width at half maximum and binding energy of neutral donor bound excition were 8mev and 14.1meV, respectively. By Haynes rule, an activation energy of impurity was 141 meV.ion energy of impurity was 141 meV.

• Journal of Life Science
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• v.24 no.3
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• pp.297-303
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• 2014

The effects of Eisenia bicyclis extracts on osteoblast differentiation and osteoclast formation were investigated. The proliferation of MC3T3-E1 osteoblastic cells was tested in an MTT assay. Treatment with E. bicyclis ethanol extract increased cell proliferation by approximately 128% at a concentration of 10 ${\mu}g/ml$. The ALP activities in the MC3T3-E1 cells was 179% higher when the E. bicyclis ethanol extract was processed at a concentration of 50 ${\mu}g/ml$. The proliferation of RAW 264.7 osteoclastic cells decreased significantly in response to treatment with the E. bicyclis extracts. Moreover, the proliferation of the RAW 264.7 osteoclastic cells treated with E. bicyclis hot water extract decreased by nearly 80%. In addition, the E. bicyclis extract reduced the number of tartrate-resistant acid phosphatase-positive (TRAP+) multinucleated cells from osteoclastic RAW 264.7 cells. These results indicate that E. bicyclis extracts have an anabolic effect on bone through the promotion of osteoclast differentiation and suggest that the extracts could be used in the treatment of common metabolic bone diseases.

• Journal of The Korean Association For Science Education
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• v.33 no.2
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• pp.266-283
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• 2013

The goal of this study is to explore the characteristics of perceptual change among students majoring in arts on the nature of science and apply the results to science education. According to the study, it is important to consider the results of interaction between learners' aptitude and teaching method. Teaching the nature of science to first grade students explicitly, experimental inquiry strategy was applied to fine arts students, and teaching strategy of scientific history to music students. To find out which elements of the nature of science have come into view on modern philosophy of science, pre and post tests on the nature of science (VNOS-C) were conducted on the students. To find out specifically why views on the nature of science have changed, a case study was conducted focusing on students who showed changes in their views on the elements of the nature of science. In conclusion, this study suggests that by using experimental inquiry strategy and strategy of scientific history properly, it is possible to change students' viewpoints on the elements of the nature of science and on modern philosophy of science. Through explicit instruction, we were able to find some positive conceptual changes on the nature of science and the modern philosophy of science in terms of both quantity and quality. This shows that the students studying arts are experiencing a constructivist conceptual change on the nature of science, and that conceptual ecology and learning strategy are involved in this process. Therefore, it is thought that this study offers an important implication in organizing science education on the nature of science.

• Tuberculosis and Respiratory Diseases
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• v.48 no.6
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• pp.853-869
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• 2000

Background : Following several decades of decline, the incidence of tuberculosis has recent1y begun to increase in many countries of this the control of this disease has been impeded by the emergence of multi-drug resistant tuberculosis (MDR-TB). The development of rapid diagnostic methods and effective new drugs are needed to control MDR-TB. One of the new drugs for MDR-TB is rifabutin (RBU) which has been known to be effective in some patients with MDR-TB. A few reports showed that some types of mutations of the rpoB gene, which were known to be present in 96-98% of rifampicin-resistant M. tuberculosis, were associated with the rifampicin-resistant but RBU-susceptible phenotype. This study was performed to investigate the correlation between RBU susceptibility and the patterns of rpoB gene mutations in Korean MDR-TB. Methods : Sixty-five clinical isolates of multi-drug resistant Mycobacterium tuberculosis, gathered from patients who visited the Asan Medical Center from July 1997 to June 1999, were investigated. Clinical responses to rifabutin-containing regimen were evaluated. An RBU susceptibility test and sequencing analysis of rpoB gene were performed, and the results were analyzed to confirm which mutations correlated with RBU-susceptible MDR-TB. Results : Fifty-three of 56 (95%) clinical isolates of MDR-TB had 60 mutations of the rpoB gene. The most frequent mutations were found at codon 531 (43%), and two mutations were combined in seven clinical isolates. Five of 53 (10%) clinical isolates showed the RBU-susceptible phenotype, and in them the characteristic patterns of point mutations were found at codon 509, 516, and 526. Conclusion : The frequency and pattern of mutations of the rpoB gene of Korean MDR-TB isolates were similar to those in western countries, where the prevalence of tuberculosis is low, but some show RBU-susceptible phenotypes. RBU-susceptible MDR-TB isolates showed the characteristic pattern of mutations of the rpoB gene which could be used to rapidly diagnose RBU susceptibility.

• Journal of the Korean Society of Food Science and Nutrition
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• v.25 no.5
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• pp.855-864
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• 1996

The purpose of this study is to evaluate nutritional status of tube feeding patients, and to investigate the effects of giving enteral nutritional support to them. 83 in-patients have been examined for their nutritional status. The mean caloric density was 0.77kca1/m1. 36.1% to 75.9% of them were malnourished in terms of biochemical assessment. The energy intake showed the significant and positive correlation in all biochemical parameters. And the protein intake showed the significant and positive correlation in total protein, serum albumin, serum iron, hemoglobin, hematocrit and TLC. But age was correlated negatively to serum albumin and transferrin. The amount of energy and protein intake has been significantly increased as the tube feeding duration became longer. Also the effect of enteral nutritional support for 6 weeks has been investigated. Case group(n=8) was administered 250kca1 of polymeric formula in addition to their usual diet, while control group(n=8) kept the amount of their original intake. When comparing the biochemical changes of the case group and those of control group at week 0 and week 6 respectively, it showed significant differences in total protein, serum transferrin and TLC. This study suggests that the malnourished status of tube feeding patients can be improved and even prevented if nutritional support is properly administered.