• Molecules and Cells
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• 제38권6호
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• pp.528-534
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• 2015

Hypoxia-inducible factor (HIF) is a key regulator of tumor growth and angiogenesis. Recent studies have shown that, BIX01294, a G9a histone methyltransferase (HMT)-specific inhibitor, induces apoptosis and inhibits the proliferation, migration, and invasion of cancer cells. However, not many studies have investigated whether inhibition of G9a HMT can modulate HIF-$1{\alpha}$ stability and angiogenesis. Here, we show that BIX01294 dose-dependently decreases levels of HIF-$1{\alpha}$ in HepG2 human hepatocellular carcinoma cells. The half-life of HIF-$1{\alpha}$, expression of proline hydroxylase 2 (PHD2), hydroxylated HIF-$1{\alpha}$ and von Hippel-Lindau protein (pVHL) under hypoxic conditions were decreased by BIX01294. The mRNA expression and secretion of vascular endothelial growth factor (VEGF) were also significantly reduced by BIX01294 under hypoxic conditions in HepG2 cells. BIX01294 remarkably decreased angiogenic activity induced by VEGF in vitro, ex vivo, and in vivo, as demonstrated by assays using human umbilical vein endothelial cells (HUVECs), mouse aortic rings, and chick chorioallantoic membranes (CAMs), respectively. Furthermore, BIX01294 suppressed VEGF-induced matrix metalloproteinase 2 (MMP2) activity and inhibited VEGF-induced phosphorylation of VEGF receptor 2 (VEGFR-2), focal adhesion kinase (FAK), and paxillin in HUVECs. In addition, BIX01294 inhibited VEGF-induced formation of actin cytoskeletal stress fibers. In conclusion, we demonstrated that BIX01294 inhibits HIF-$1{\alpha}$ stability and VEGF-induced angiogenesis through the VEGFR-2 signaling pathway and actin cytoskeletal remodeling, indicating a promising approach for developing novel therapeutics to stop tumor progression.

• 동의생리병리학회지
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• 제22권6호
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• pp.1566-1571
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• 2008

Bone is a dynamic tissue that is constantly resorbed by osteoclasts and then replaced by osteoblasts. Osteoclasts, multinucleated cells of monocyte/macrophage lineage, are responsible for bone disorders, including osteoporosis and rheumatoid arthritis. In this study, we examined the effect of the curcumin on osteoclast survival and bone resorption. We found that curcumin significantly inhibited RANKL-mediated osteoclast survival. DAPI stainingrevealed that curcumin induced the apoptotic features of osteoclasts. Although curcumin did not suppress the phosphorylation of Akt and ERK in osteoclasts treated with RANKL, curcumin induced the cleavage of pro-caspase-9 and -3 its active forms. Also, curcumin inhibited the formation of actin rings of osteoclasts. RANKL-mediated bone resorption was inhibited by the addition of curcumin. Together with the results of this study, these findings suggest that the curcumin inhibited the survival of osteoclasts by activating caspase-9 and -3 and suppressed the bone resorptive activity. Thus, curcumin may be developed as antiresorptive drugs for the treatment of bone-related disorders.

• 한국환경생태학회지
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• 제22권4호
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• pp.396-408
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• 2008

국립산림과학원에서 발간된 임상도에 따르면 파주시 광탄면에 위치한 본 연구대상지는 활엽수 Ⅳ영급으로 분류되었으나 식생조사 결과 영급판정이 어려운 활엽수 천연림으로 구성되어 정밀 임상도 작성의 필요성이 제기되었다. 이에 정밀 현존식생 조사와 식생구조 및 연륜 분석 자료를 기초로 한 정밀 임상도 작성방안을 제안하고자 하였다. 정밀 현존식생유형 분석결과 22개 유형이었으며 자연림은 신갈나무림, 굴참나무림 등 11개 유형, 인공림은 밤나무림 등 6개 유형으로 구분되었다. 영급 판정을 위해 정밀 현존식생도를 바탕으로 방형구 42개와 89개 표본목의 목편을 채취하여 수령을 측정한 결과, 저지대에 입지한 인공림, 참나무류 소경목 지역은 II영급(29.8%), 나머지 지역은 III영급(57.6%)으로 토지이용이 가능하였고 Ⅳ영급 이상(8.8%)은 경계부의 급경사 능선부에 분포하여 토지이용은 불가능하였다. 이상과 같이 소규모 개발 예정지가 활엽수 자연림으로 판정된 경우 보전과 이용 판정에 있어 정밀 현존식생 조사, 식물군집구조 및 표본목 분석을 통한 정밀 임상도를 작성하여야 할 것이다. 정밀 임상도에는 식생의 자연성, 희소성, 다양성 등을 종합적으로 판단할 수 있는 자료가 포함되어 소규모 부지의 개발적정성 판단에 유용할 것으로 사료된다.

• The Korean Journal of Physiology and Pharmacology
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• 제2권6호
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• pp.695-703
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• 1998

$[K^+]_o$ can be increased under a variety of conditions including subarachnoid hemorrhage. The increase of $[K^+]_o$ in the range of $5{\sim}15$ mM may affect tensions of blood vessels and can change their sensitivity to various vasoactive substances. Therefore, it was examined in the present study whether the sensitivity of cerebral arteries to vasoactive substances can be changed with the moderate increase of $[K^+]_o$, using Mulvany-type myograph and $[Ca^{2+}]_c$ measurement. The contractions of basilar artery and branch of middle cerebral artery induced by histamine were not increased with the elevation of $[K^+]_o$ from 6 mM to 9 mM or 12 mM. On the contrary, the contractions induced by serotonin were significantly increased with the elevation of $[K^+]_o$. The contractions were also significantly increased by the treatment with nitro-L-arginine $(10^{-4}$ M for 20 minutes). In the nitro-L-arginine treated arteries, the contractions induced by serotonin were significantly increased with the elevation of $[K^+]_o$ from 6 mM to 12 mM. $K^+-induced$ relaxation was evoked with the stepwise increment of extracellular $K^+$ from 0 or 2 mM to 12 mM by 2 mM in basilar arterial rings, which were contracted by histamine. But $[K^+]_o$ elevation from 4 or 6 mM to 12 mM by the stepwise increment evoked no significant relaxation. Basal tension of basilar artery was increased with $[K^+]_o$ elevation from 6 mM to 12 mM by 2 mM steps or by the treatment with ouabain and the increase of basal tension was blocked by verapamil. The cytosolic free $Ca^{2+}$ level was not increased by the single treatment with serotonin or with the elevation of $[K^+]_o$ from 4 mM to 8 or 12 mM. In contrast to the single treatment, the $Ca^{2+}$ level was increased by the combined treatment with serotonin and the elevation of $[K^+]_o$. The increase of free $Ca^{2+}$ concentration was blocked by the treatment with verapamil. These data suggest that the sensitivity of cerebral artery to serotonin is increased with the moderate increase of $[K^+]_o$ and the increased sensitivity to serotonin is due to the increased $[Ca^{2+}]_i$ induced by extracellular $Ca^{2+}$ influx.

• 대한소아치과학회지
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• 제37권4호
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• pp.519-525
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• 2010

이소맹출(ectopic eruption)은 여러 가지 원인들에 의해 치아가 비정상적 위치로 맹출하는 경우를 말하며, 주로 상악 제1대구치, 하악 측절치 그리고 상악 견치에서 발생된다. 이소맹출 한 상악 제1대구치는 정상보다 근심방향으로 맹출하여, 동측상악 제2유구치의 원심협측 치근을 흡수시키며, 결국 상악 제1대구치는 상악 제2유구치 하방에 걸리게 된다. 상악 제1대구치는 저작기능 및 교합에 중요한 역할을 하고 있으므로, 이소맹출 한 상악 제1대구치는 적절한 위치로 이동이 필요하다. 상악 제1대구치를 적절한 위치로 이동하기 위한 치료방법으로는 brass wire 또는 elastic ring을 이용한 separation, 상악 제2유구치의 원심면 삭제, finger spring을 포함한 고정성 또는 가철성 장치, 상악 제2유구치를 발치한 후 공간유지장치 또는 공간회복장치의 이용 등이 있다. 본 증례들은 강릉대학교 치과병원에 내원한 환자들에서 이소맹출 한 상악 제1대구치를 기성금관의 재시적, brass wire의 적용, active plate를 이용하여 적절한 위치로 이동시켜 양호한 교합을 이루었기에 이를 보고하는 바이다.

• 한국산림과학회지
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• 제81권3호
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• pp.263-272
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• 1992

산지급류하천(山地急流河川)에서는 토석(土石) 등의 이동에 의해 하상퇴적지(河床堆積地)를 형성하게 되며, 현재의 하상면(河床面)은 유역(流域)의 토석이동특성(土石移動特性)을 반영하고 있다. 특히 하상퇴적지(河床堆積地)에 조성되어 있는 천연생(天然生) 동령임분(同齡林分)의 연륜(年輪)은 퇴적지(堆積地) 형성후의 경과년수(經過年數)를 나타낸다. 본 연구에서는 강원도내(江原道內)의 두 개의 산지급류하천(山地急流河川)을 대상으로 하천미지형(河川微地形)과 식물지표(植物指標)에 의해 하상퇴적지(河床堆積地)의 연대학적(年代學的) 해석(解析)을 시도하여 다음과 같은 결과를 얻었다. 1. 산지급류하천(山地急流河川)에 분포하는 하상퇴적지(河床堆積地)의 횡단형상(橫斷形狀)은 계단형상(階段形狀)을 나타내고 있으며, 그 하상면(河床面)에는 상이한 동령임분(同齡林分)이 조성되어 있다. 2. 일반적으로 하상퇴적지(河床堆積地)의 퇴적고(堆積高)에 비례하여 침입하여 있는 수림(樹林)의 연륜수(年輪數)도 증가하였으며, 이는 토사이동(土砂移動)의 규모(規模) 및 빈도(頻度)를 추정하는데에 사용된다. 3. 하상퇴적지(河床堆積地)의 경과년수(經過年數)를 수목(樹木)의 연륜(年輪)에 의해 추정할 수 있으므로 하상퇴적지(河床堆積地)의 시(時) 공간적(空間的) 정보(情報)를 얻는데 식물지표(植物指標)가 유효하게 사용될 수 있다. 4. 퇴적토석량(堆積土石量)은 하상퇴적지(河床堆積地)의 연장(延長), 평균퇴적폭(平均堆積幅), 평균퇴적고(平均堆積高)에 좌우되며, 평균퇴적폭(平均堆積幅), 평균퇴적고(平均堆積高)는 연대(年代)에 비례하여 증가하였다.

• The Korean Journal of Physiology
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• 제28권2호
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• pp.169-179
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• 1994

The effect of extracellular and intracellular pH on vascular tone and $^{45}Ca$ uptake were investigated in aortic strips and dispersed single aortic smooth muscle cells of spontaneously hypertensive rats (SHR) and aged-matched Wistar-Kyoto rats (WKY). The contraction produced by a change of extracellular pH (pHo) in the range of $6.5{\sim}8.3$ was estimated by comparison with the level of vascular tone at pH 7.4. Contraction was induced below pHo 6.5 in WKY, pHo 7.1 in SHR, and over pHo 8.0 on both strains. The amplitude of contraction induced by high pHo (over pHo 7.7) was similar in SHR and WKY, but that induced by low pHo (below pHo 7.1) in SHR was greater than that in WKY. Either high pHo- or low pHo-induced contractions in WKY and SHR were not induced in the Ca-free Tyrode's solution and were induced by the addition of Ca. $^{45}Ca$ uptake increased progressively as pHo was increased from 6.8 to 8.1 in the single aortic smooth muscle cells of WKY and SHR. $NH_4Cl$ induced a gradually developing contraction in a dose-dependent manner $(5\;mM{\sim}30\;mM)$ and the removal of $NH_4Cl$ induced transient contraction was followed by profound relaxation in the aortic rings of both strains. The contractions induced by $NH_4Cl$ or by the removal of $NH_4Cl$ in SHR were significantly greater than that in WKY. These contractions were not induced in Ca-free Tyrode's solution. $^{45}Ca$ uptake was increased by $NH_4Cl$ (20 mM) and was not changed by the removal of $NH_4Cl$ (20 mM) in the aortic strips of WKY and SHR. As a summary of above results, the vascular tone of SHR was more sensitive to the change pHi and pHo than that of WKY. The contractions induced by change of extracellular or intracellular pH depended on extracellular Ca in the aorta of SHR nnd WKY. However, the Ca uptake was in accord with the changes of contraction but increase in contraction by low pH was not accompanied by an increase in Ca uptake in both strains.

• BMB Reports
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• 제38권2호
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• pp.198-205
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• 2005

Resveratrol (RES) and genistein (GEN) are the dietary natural products known to possess chemopreventive property and also the ability to repair DNA damage induced by mutagens/carcinogens. It is believed that the therapeutic activity of these compounds could be primarily due to their interaction with nucleic acids but detailed reports are not available. We here explore the interaction of these drugs with nucleic acids considering DNA and RNA as a potential therapeutic target. The interaction of RES and GEN has been analysed in buffered solution with DNA [saline sodium citrate (SSC)] and RNA [tris ethylene diammine tetra acetic acid (TE)] using UV-absorption and Fourier transform infrared (FTIR) spectroscopy. The UV analysis revealed lesser binding affinity with nucleic acids at lower concentration of RES (P/D = 5.00 and 10.00), while at higher drug concentration (P/D = 0.75, 1.00 and 2.50) hyperchromic effect with shift in the ${\lambda}_{max}$ is noted for DNA and RNA. A major RES-nucleic acids complexes was observed through base pairs and phosphate backbone groups with K = $35.782\;M^{-1}$ and K = $34.25\;M^{-1}$ for DNA-RES and RNA-RES complexes respectively. At various concentrations of GEN (P/D = 0.25, 0.50, 0.75, 1.00 and 2.50) hyperchromicity with shift in the ${\lambda}_{max}$ from 260 $\rightarrow$ 263 om and 260 $\rightarrow$ 270 nm is observed for DNA-GEN and RNA-GEN complexes respectively. The binding constant (from UV analysis) for GEN-nucleic acids complexes could not be obtained due to GEN absorbance overlap with that of nucleic acids at 260 nm. Nevertheless a detailed analysis with regard to the interaction of these drugs (RES/GEN) with DNA and RNA could feasibly be understood by FTIR spectroscopy. The NH band of free DNA and RNA which appeared at $3550-3100\;cm^{-1}$ and $3650-2700\;cm^{-1}$ shifted to $3450-2950\;cm^{-1}$ and $3550-3000\;cm^{-1}$ in DNA-RES and RNA-RES complexes respectively. Similarly shifts corresponding to $3650-3100\;cm^{-1}$ and $3420-3000\;cm^{-1}$ have been observed in DNA-GEN and RNA-GEN complexes respectively. The observed reduction in NH band of free nucleic acids upon complexation of these drugs is an indication of the involvement of the hydroxyl (OH) and imino (NH) group during the interaction of the drugs and nucleic acids (DNA/RNA) through H-bonded formation. The interaction of RES and GEN with bases appears in the order of G $\geq$ T > C > A and A > C $\geq$ T > G. Further interaction of these natural compounds with DNA and RNA is also supported by changes in the vibrational frequency (shift/intensity) in symmetrical and asymmetrical stretching of aromatic rings of drugs in the complex spectra. No appreciable shift is observed in the DNA and RNA marker bands, indicating that the B-DNA form and A-family conformation of RNA are not altered during their interaction with RES and GEN.

• Journal of Chest Surgery
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• 제8권2호
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• pp.149-152
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• 1975

In spite of great advances in surgical treatment during past several decades, surgery of the trachea failed to develop correspondingly, partly because of relative rarity of the tracheal lesions and partly because of difficulties in surgical technique and anesthesia. Surgical diseases of the trachea are largely obstructions due to neoplasm or cicatrical stenosis and tracheal malacia. The present treatment of respiratory failure, using cuffed endotracheal and tracheostomy tubes, has produced, apparently with increasing frequency, tracheal stenosis, tracheomalized tracheal erosion. Surgery is presently the only reasonable way to treat stenotic lesions of the tracheobronchial tree. In the case of tumors, the current trend has been that of radical excision. Primary end-to--end reconstruction of the trachea has been generally recognized as the ideal method of repair following resection. However, for decades it was believed that a maximum of four tracheal rings only might be excised and primary healing achieved with safety. A great variety of procedures, developed by numerous investigations and directed at tracheal substitution, have almost invariably met with discouraging results. A meticulous study done by Grillo and associates on autopsy specimens has shown that an average 6.4cm of mediastinal trachea can be safely resected by full mobilization of the right lung and transplantation of the left main bronchus into the bronchus intermedius. Recently, we experienced a case of successful resection of a tumor of the tracheal carina and primary tracheo-left main bronchial anastomosis at the Department of Thoracic & Cardiovascular Surgery, the National Medical Center in Seoul. The patient, a 29-year-old man, was admitted to the hospital with complaints of dyspnea and cough. On admission, chest film showed hydropneumothorax on the right. After closed thoracostomy, hydropneumothorax disappeared, but hazy densities, developed in the right middle and lower lung fields, resisted to treatment. Bronchoscopy uncovered irregular tumor covering the carina and the right main bronchus, and biopsy indicated well differentiated squamous Cell carcinoma. Operation was performed on July 2, 1975. A right postero-lateral thoracotomy was used. Excision involved the lower trachea, the carina, the left main bronchus and the right lung. This was followed by direct anastomosis between the trachea and the left main bronchus. Bronchography was done on 17th postoperative day revealed good result of operation without stricture at the site ofanastomosis. About one month after the operation symptoms and signs of bronchial irritation with dyspnea developed, and these responded to respiratory care. On 82nd postoperative day, sudden dyspnea developed at night and the patient expired several hours later. Autopsy was not done and the cause of death was uncertain.

• Journal of Information Display
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• 제12권3호
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• pp.145-152
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• 2011

Since the discovery of fullerenes as a class of nanostructure compounds, many potential applications have been suggested for their unusual structures and properties. The isolated pentagon rule (IPR) states that all pentagonal carbon rings are isolated in the most stable fullerene. Fullerenes $C_n$ are a class of spherical carbon allotrope group with unique properties. Electron transfer between fullerenes and other molecules is thought to involve the transfer of electrons between the molecules surrounding the fullerene cage. One class of electron transfer molecules is the methanofullerene derivatives ([6,6]-phenyl $C_{61}$-butyric acid methyl ester (PCBM), 4-(2-ethylhexyloxy)-[6,6]-phenyl $C_{61}$-butyric acid methyl ester (p-EHO-PCBM), and 4-(2-ethylhexyloxy)-[6,6]-phenyl $C_{61}$-butyric acid (p-EHO-PCBA), 10-12). It has been determined that $C_{60}$ does not obey IPR. Supramolecular complexes 1-9 and 10-12 are shown to possess a previously unreported host.guest interaction for electron transfer processes. The unsaturated, cis-geometry, thiocrown ethers, (1-9) (described as [X-UT-Y], where X and Y indicate the numbers of carbon and sulfur atoms, respectively), are a group of crown ethers that display interesting physiochemical properties in the light of their conformational restriction compared with a corresponding saturated system, as well as the sizes of their cavities. Topological indices have been successfully used to construct mathematical methods that relate structural data to various chemical and physical properties. To establish a good relationship between the structures of 1-9 with 10-12, a new index is introduced, ${\mu}_{cs}$. This index is the ratio of the sum of the number of carbon atoms ($n_c$) and the number of sulfur atoms ($n_s$) to the product of these two numbers for 1-9. In this study, the relationships between this index and oxidation potential ($^{ox}E_1$) of 1-9, as well as the first to third free energies of electron transfer (${\Delta}G_{et(n)}$, for n = 1-3, which is given by the Rehm-Weller equation) between 1-9 and PCBM, p-EHO-PCBM, and p-EHO-PCBA (10-12) as [X-UT-Y]@R(where R is the adduct PCBM, p-EHO-PCBM, and p-EHO-PCBA group) (13-15) supramolecular complexes are presented and investigated.