• BMB Reports
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• 제40권6호
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• pp.911-920
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• 2007

Tuberculosis, caused by Mycobacterium tuberculosis, continues to be one of the leading infectious diseases to humans. It is urgent to discover novel drug targets for the development of antitubercular agents. The 2-C-methyl-Derythritol-4-phosphate (MEP) pathway for isoprenoid biosynthesis has been considered as an attractive target for the discovery of novel antibiotics for its essentiality in bacteria and absence in mammals. MEP cytidyltransferase (IspD), the third-step enzyme of the pathway, catalyzes MEP and CTP to form 4-diphosphocytidyl-2-C-methylerythritol (CDP-ME) and PPi. In the work, ispD gene from M. tuberculosis H37Rv (MtIspD) was cloned and expressed. With N-terminal fusion of a histidine-tagged sequence, MtIspD could be purified to homogeneity by one-step nickel affinity chromatography. MtIspD exists as a homodimer with an apparent molecular mass of 52 kDa. Enzyme property analysis revealed that MtIspD has high specificity for pyrimidine bases and narrow divalent cation requirements, with maximal activity found in the presence of CTP and $Mg^{2+}$. The turnover number of MtIspD is $3.4 s^{-1}$. The Km for MEP and CTP are 43 and $92{\mu}M$, respectively. Furthermore, MtIspD shows thermal instable above $50^{\circ}C$. Circular dichroism spectra revealed that the alteration of tertiary conformation is closely related with sharp loss of enzyme activity at higher temperature. This study is expected to help better understand the features of IspD and provide useful information for the development of novel antibiotics to treat M. tuberculosis.

• 대한한방소아과학회지
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• 제20권3호
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• pp.143-160
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• 2006

Objectives : As the side effect brought up by internet game addiction, many reports come out, but most of past articles are for middle or high school students. There is seldom a poisoning game treatise to a primary school student, if there is treatise, it is real condition that treatise for lead pipe with psychological reasons is seldom discussion about physical symptoms. This research searches high grade elementary students' game use actual conditions and when divide to general user group, latent danger use group, high dangerous use group, according to serious illness degree of game poisoning, three groups and game poisoning happens, recognized about body symptoms that happen much. Methods : Target population of these questionnaire are fifth and sixth grade elementary student of Seoul city 2 school. Chose 263 elementary students, 144 men, 119 women who understand purpose of research and admit participation is 25 October, 2006 since 1 September, 2006 Results : As poisoning serious illness degree is high, there are many number of game times, much more boys are addicted to internet game than girs, insomnia is apt to happen frequently in game poisoning danger group, and correlation is high by megrim, shoulder ache, digestive trouble. Insomnia, symptoms that show next even if some symptoms show first because there is high correlation between megrim, shoulder ache, digestive trouble is high possibility to happen among four symptoms. Insomnia, megrim, shoulder ache, digestive trouble that happen by internet game poisoning, is apt to increase by increasing addiction. Symptoms treatment can divide by internal treatment that treat insomnia, megrim, digestive trouble, external treatment that is typical symptoms of VDT syndrome shoulder ache, headache, fatigue persimmon. Root treatment is mind symptoms treatment. Game addiction treatment is relationship method 'seven emotions injury treatment' in oriental medicine. 'promote the normal flow of qi' and 'adjustment of suitable emotion' can talk as pivotal point of treatment.

• 대한공업교육학회지
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• 제31권2호
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• pp.233-256
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• 2006

이 연구의 목적은 우리나라 공업기술교과 성격과 내용이 유사한 외국의 교육과정을 비교 분석함으로서 교육과정 개정의 흐름과 방향, 그리고 교과의 목표와 내용체계에 대하여 고찰해 보는 데 있다. 이를 위하여 이 연구에서는 문헌연구를 중심으로 한 연구방법을 수행하였다. 이 연구에서는 우리나라 공업기술교과와 유사한 과목들이 편성되어 운영되고 있는 일본, 미국, 영국, 그리고 뉴질랜드와 호주의 교육과정을 중심으로 분석하였다.이 연구의 결과를 요약하여 정리하면 다음과 같다. 첫째, 우리나라 공업기술교과와 유사한 과목으로는 일본의 '공업기술기초'와 '과제연구', 미국의 '기술', 영국의 '설계와 기술', 그리고 뉴질랜드의 '기술', 호주 뉴사우스웨일즈주의 '설계와 기술' 등이 있었다. 둘째, 교과의 목표와 강조점을 분석한 결과, 우리나라는 공업기술은 공업에 대한 지식과 이해, 그리고 진로탐색에 초점을 두고 있었으나, 일본, 미국, 영국, 뉴질랜드, 호주의 경우에는 과정적 접근 방법에 의한 기술적 문제해결력을 강조하고 있었다. 셋째, 교육내용을 분석한 결과, 우리나라는 전반적인 공업 세계의 영역을 다루고 있었으나, 일본은 인간과 기술 및 환경의 관계, 가공기술과 생산기술, 과제연구를 다루고 있었으며, 미국은 지식과 과정, 그리고 맥락에 의한 내용표준을 제시하고 있었고, 영국, 뉴질랜드, 그리고 호주의 경우에는 설계과정에 초점을 두고 있었다. 이 연구의 결과를 바탕으로 후속 연구를 제언하면 다음과 같다. 첫째, 공업기술교과의 교육과정 운영에 대한 실태분석이 필요하다. 둘째, 공업기술교과의 목표와 내용체계에 대한 전문가와 이해관계자들의 인식과 요구분석이 필요하다.

• 생명과학회지
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• 제34권6호
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• pp.418-425
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• 2024

고형암은 여러 세포 유형의 이질적인 집단으로 구성되며, 암줄기세포는 자가 재생과 분화의 특성을 가지고 있다. 암줄기세포에서는 자가재생을 조절하는 줄기세포 신호전달체계가 과도하게 활성화되어 있어 암줄기세포는 암세포의 증식과 암 진행에 중요하다. 암줄기세포의 정의는 급성골수성백혈병에 의해 처음 제안되었으며, 다양한 연구를 통해 세포 표면 표지 발현에 따라 암 줄기세포를 분류할 수 있게 되었다. 또한, 암줄기세포는 종양 미세환경에서 잠재력을 보존하고 있고, 다양한 종양 미세환경 세포 유형은 정지 상태의 암줄기 세포를 유지하고 암 성장의 조절자 역할을 한다. 현재 사용되는 암 치료 방법은 증식성 세포를 표적으로 하기 때문에 치료에, 저항성을 가지는 휴지기 상태의 암 줄기세포는 재발이나 전이의 위험을 증가시키며, 종양 미세환경의 다양한 신호전달체계는 혈관계와 세포 외 기질을 리모델링함으로써 종양 지지 환경으로의 변화를 유도한다. 따라서, 암을 효과적으로 치료하려면 암줄기세포와 종양 미세환경을 표적 치료해야 하며, 종양 미세환경이 어떻게 면역 반응의 재프로그램을 유도하여 암의 성장, 면역 저항성 및 전이를 촉진하는지 이해하는 것이 중요하다. 따라서 본 총설을 통해 종양 미세환경에서 면역억제를 강화할 수 있는 세포 및 분자 메커니즘에 대한 현재 및 새로운 개념을 요약하고자 한다.

• 한국임상약학회지
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• 제23권2호
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• pp.151-157
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• 2013

Purpose: Warfarin is the most widely used anticoagulant drug for preventing cardiovascular diseases after ischemic stroke and thromboembolism related to atrial fibrillation, artificial heart valves, deep vein thrombosis, and pulmonary embolism. Warfarin is commonly used in combination with other drugs such as diuretics in order to treat the comorbidity. Although several warfarin-diuretics interactions have been reported, the results are conflicting. Therefore, the initial aim of this study was to identify the effects of diuretics on the warfarin response in patients with atrial fibrillation. Methods: One hundred forty six patients with atrial fibrillation who were on anticoagulation therapy with warfarin and maintained INR levels of 2-3 for three consecutive times were followed up, retrospectively. Stable warfarin doses and INR per stable warfarin dose were compared according to age, gender, comorbidity, and concurrent medication. The stable warfarin dose was defined as the maintenance dose of warfarin of the measured patient whose INR was within the target INR range more than 3 times consecutively. Results: The differences of stable warfarin doses in patients with ($3.22{\pm}1.21$ mg/day) and without ($3.58{\pm}1.14$ mg/day) diuretics were marginally significant (P=0.069). On the other hand, stable warfarin doses were $2.97{\pm}1.10$ mg/day in patients with thiazide (n=36) and $3.58{\pm}1.14$ mg/day in patients without diuretics (n=82), which was statistically significant (p=0.009). INR values per stable warfarin dose in patients with diuretics and thiazide were $0.84{\pm}0.31$ and $0.90{\pm}0.34$, respectively, which were statistically different from those without diuretics ($0.72{\pm}0.21$, P=0.010 and P=0.006, respectively). Age, gender, and concurrent use of thiazide diuretics were found to have significant influence on the warfarin response from multivariate analysis. Conclusion: Our study showed that the concurrent use of thiazide diuretics could increase the response of warfarin in patient with atrial fibrillation. Therefore, clinicians should be aware that warfarin dose needs to be adjusted when it is used with thiazide diuretics concomitantly.

• 자원리싸이클링
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• 제33권3호
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• pp.48-56
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• 2024

본 연구에서는 하수슬러지 가스화 고형 잔류물(GSRs)의 순환자원 활용 가능성을 검토하기 위해 대상제품에 대한 물성평가 및 물리적 분리를 수행하였다. 먼저, 본 연구에 사용된 GSRs는 수도권매립지관리공사를 통해 공급되었으며, 일반적으로 GSRs는 수 mm 입자크기의 다공성 펠릿 형태이었다. 또한, 부분적으로 검은 부분은 미연소 및 가스화되지 않은 탄소로 확인되었으며, 평균 탄소 함량은 5%였다. 또한 실리카, 알루미나, 산화인의 성분이 전체 함량의 70% 이상이었다. 습식분쇄 생성물은 금속성분이 단체분리되어있음 확인하였다. 금속성분과 비금속성분의 물리적 분리가 필요하여 최종적으로 부유선별에 적합한 것으로 결정하였다. 이에, 상대적으로 많은 양의 비금속성분이 농축된 금속 성분을 분리하기 위해 양이온 및 음이온 계면활성제를 선택하여 분리 특성을 확인하고자 하였다. 결과적으로, 금속성분 분리보다 실리카, 알루미나, 인 등 비금속 성분의 농축이 더 용이할 것으로 기대된다. 따라서, 가스화 처리된 하수슬러지 잔재물의 물리적 처리에 가능함에 따라 분리산물에 대한 재활용 방안 제안에 따라 순환자원으로서 잠재성이 있을 것으로 판단된다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10439-10444
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• 2015

Many chemotherapeutic agents have been successfully used to treat hepatocellular carcinoma (HCC); however, the development of chemoresistance in liver cancer cells usually results in a relapse and worsening of prognosis. It has been demonstrated that DNA methylation and histone modification play crucial roles in chemotherapy resistance. Currently, extensive research has shown that there is another potential mechanism of gene expression control, which is mediated through the function of short noncoding RNAs, especially for microRNAs (miRNAs), but little is known about their roles in cancer cell drug resistance. In present study, by taking advantage of miRNA effects on the resistance of human hepatocellular carcinoma cells line to cisplatin, it has been demonstrated that miR-340 were significantly downregulated whereas Nrf2 was upregulated in HepG2/CDDP (cisplatin) cells, compared with parental HepG2 cells. Bioinformatics analysis and luciferase assays of Nrf2-3'-untranslated region-based reporter constructor indicated that Nrf2 was the direct target gene of miR-340, miR-340 mimics suppressing Nrf2-dependent antioxidant pathway and enhancing the sensitivity of HepG2/CDDP cells to cisplatin. Interestingly, transfection with miR-340 mimics combined with miR-340 inhibitors reactivated the Nrf2 related pathway and restored the resistance of HepG2/CDDP cells to CDDP. Collectively, the results first suggested that lower expression of miR-340 is involved in the development of CDDP resistance in hepatocellular carcinoma cell line, at least partly due to regulating Nrf2-dependent antioxidant pathway.

• 혜화의학회지
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• 제4권2호
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• pp.335-336
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• 1996

Artemisinin, a new antimalarial to treat patients infected with strains of Plasmodium jalciparum, derived from the plant Artemisia annua Linn, has immunopharmacologic actions such as enhence the PHA -induced lymphocyte transformation rate, increased the weight of spleen but reduced the weight of thymus, reduced phagocytic function of peritoneal macrophage, remarkably reduced the level of serum IgG and hemolysin fonning capacity (sentitized with SRBC), inhibited the activity of Ts cells of donor mice by supraoptimal immunuization(SOI), but enhenced activity of Ts cells of recipient mice by SOI. These results suggested that Ts cells may be the target cells of artemisinin. To the serum complement C3 level of plasmodium berghei-infeted mice, artemisinin (i. m,) could remarkly increase it. The artemisinin also obviously reduced the prostaglandin E(PGE) in the mouse hind paw swelling induced by carrageenin. Numerous studies have demonstrated that pharmacologic doses of PGE attenuate the development of immunocomplex nephritis. Some autologous immune mechanisms may be invoolved In the pathogensis of some types of glomurulonephritis. Glomerular abnormalities can be induced in animals by variety of immunological manipulations. The resulting disorder has many clinical and pathogical similarities to the disease in human. Our purpose was therefore to test the ability of the artemisinin to lessen the severity of rabbit IgG accelerated nephrotoxic serum glomerulonephritis in mice model. Mice which had treated with rabbit IgG and NTS, administrated with saline, showed Significant inceases of urinary protein, cholesterol level, and decrease of serum albumin in NS group. On the contrary, By i.g. adminstration of artemisinin at dose of 12.5, 25 and 50 mg/kg for 14 days after NTS injection, shown that artemisinin inhibited the nephritic changes in some parameters by means of urinary protein(p<0.05, p<0.01) and serum choleterol(p<0.05, p<0.01) and albumin (p<0.05, p<0.01), blood urea nitrogen (p<0.05, p<0.01), serum albumin(p<0.05, p<0.01); Cyclophosphamide(i.p. 10mg/kg for 14d) had almost same effect as the artemisinin had. Morphological studies shown that The picture of kidney from the mouse with NTS-nephritis accerated with rabbit IgG, treated with i.g. saline as the control, the mesangiocapillary were enlarged and proliferated; There were inflammatory cells infiltrating around the glomeruli; The ethelial cell were proliferated in the wall of Bowman's capsule. Histopatholological picture of kidney from the NTS-nephritis accerated with rabbit IgG mouse treated with i.p. 10mg/kg cyclophosphamide as the positive control. No siginicant histopathological evidence were found. Treaded with i.p. 12.5mg/kg artemisinine, the picture shown that mesangiocapillary were lightly proliferated; There were inflammatory cells infiltrating around the glomeruli; Treaded with i.p. 25mg/kg artemisinine, The picture shown that the mesangiocapillary were lightly proliferated; Treaded with i.p. 50mg/kg artemisinine, The picture shown that both the mesangiocapillary proliferated and the inflammatory cells infiltrating around the glomeruli are less than treated with saline, 12.5 and 25 mg/kg artemisinine. On the basis of these studies we conclude that the artemisinin can relieve pathological change caused by NTS-nephritis aacerated with rabbit IgG.

• 대한두경부종양학회지
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• 제16권2호
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• pp.167-171
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• 2000

Objectives: To compare the outcomes of treatment with a focus on the effectiveness of the two primary techniques of radiation used for treating parotid gland malignancies. Materials and Methods: A retrospective analysis of 70 patients with parotid gland cancer treated between 1981-1997. Radiation was delivered through an ipsilateral field of high energy electron and photon in 37 patients(52.9%). Two wedge paired photon was used to treat in 33 patients(47.1%). The median dose was 60 Gy, typically delivered at 1.8-2.0Gy per fraction. The median follow-up times for surviving patients was 60 months. Results: The overall and disease free 5 year survival rates were 71.6% and 69.5%, respectively. Wedge paired photon and photon-electron treatment disease tree 5 year survival rates were 61.1% and 80.5%, respectively. Overall local failure rate was 18.6%. Local failure rate of wedge paired photon technique was higher than that of mixed beam technique. Late complication rate was 37.1%, but most of them were mild grade. Conclusion: Techniques of radiation were associated with local control. The technique of using an ipsilateral field encompassing the parotid bed and treated with high energy electrons often mixed photons was effective with minimal severe late toxicity. To irradiate deep sited tumors, we consider 3-D conformal treatment plan for well encompassing the target volume.

• Bulletin of the Korean Chemical Society
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• 제32권1호
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• pp.201-207
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• 2011

Peroxisome proliferator-activated receptors (PPARs) are members of nuclear receptors and their activation induces regulation of fatty acid storage and glucose metabolism. Therefore, the $PPAR\gamma$ is a major target for the treatment of type 2 diabetes mellitus. In order to generate pharmacophore model, 1080 known agonists database was constructed and a training set was selected. The Hypo7, selected from 10 hypotheses, contains four features: three hydrogen-bond acceptors (HBA) and one general hydrophobic (HY). This pharmacophore model was validated by using 862 test set compounds with a correlation coefficient of 0.903 between actual and estimated activity. Secondly, CatScramble method was used to verify the model. Hence, the validated Hypo7 was utilized for searching new lead compounds over 238,819 and 54,620 chemical structures in NCI and Maybridge database, respectively. Then the leads were selected by screening based on the pharmacophore model, predictive activity, and Lipinski's rules. Candidates were obtained and subsequently the binding affinities to $PPAR\gamma$ were investigated by the molecular docking simulations. Finally the best two compounds were presented and would be useful to treat type 2 diabetes.