• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제27권4호
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• pp.314-320
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• 2001

Matrix metalloproteinases have long been viewed as ideal candidates for proteinases that enables tumor cells to permeated basement membrane defenses and invade surrounding tissue. There is growing evidence that the MMPs have an expanded role, as they are important for the creation and maintenance of a microenvironment that facilitates growth and angiogenesis of tumors at primary and metastatic sites. MT-MMPs are not secreted but instead remaining attached to cell surfaces. Although not all of the MT-MMPs are fully characterized, MT-MMPs have important role in localizing and activating secreted MMPs. The MMP genes are transcriptionally responsive to a wide variety of oncogene, growth factors, cytokine, and hormones. Currently, a number of MMP inhibitors are being developed and some have reached clinical trials as anti-metastatic or anti-cancer therapies. MT1-MMP is involved in the activation of proMMP-2. MT1-MMP is significant not only as a tumor marker but as a new target for chemotherapy against cancer. The purpose of this study was to evaluate the effects of protein kinase C inhibitor(genistein) on the proliferation of HT1080 and expression of MT1-MMP mRNA. Human fibrosarcoma cell line HT1080 was cultured and divided 2 groups. The experimental group was treated with $100{\mu}M$ genistein and incubated 12h, 24h for $[3^H]-thymidine$ uptake assay and northern hybridization individually. And the control group was treated with same amount of PBS for the above procedures. $[3^H]-thymidine$ incorporation was measured with ${\beta}$ ray detector. And RT-PCR and northern blotting for MT1-MMP mRNA was performed. The results were as follows 1. $[3^H]-thymidine$ uptake was reduced in experimental group with statistical significance. 2. MT1-MMP mRNA expression was significantly reduced in experimental group. These results showed that protein kinase C inhibitor (genistein) inhibited proliferation of HT1080 and almost completely blocked transcription of MT1-MMP mRNA. So, it is possible to use the protein kinase inhibitor (genistein) as anti-metastatic and anti-proliferative agent.

• 한국조경학회지
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• 제42권1호
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• pp.50-63
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• 2014

생태관광은 환경보전과 지역활성화를 동시에 만족시키는 지속가능한 개발의 대표유형으로 각광을 받고 있다. 생태관광의 긍정적인 환경적, 사회문화적 영향에 대한 연구결과는 발표되고 있으나, 실제 경제적 가치에 대해서는 긍정적 의견과 부정적 의견이 엇갈리고 있으며, 경제적 효과를 높이기 위한 요인에 대한 연구는 거의 이루어지지 않았다. 이에 본 연구에서는 한국 생태관광지 중 가장 많은 방문객수를 기록하고 있는 순천만의 실제 방문객 314명을 대상으로 관광행태와 태도, 그리고 만족도가 그들의 소비활동과 어떤 연관성을 가지는지 분석하였다. 그 결과는 다음과 같다. 첫째, 연계관광 유무, 생태관광 경험 유무, 방문 전 순천만 생태관광에 대한 정보유무는 관광소비활동에 영향을 미쳤으며, 특히 관광소비활동 중 숙박비 지출과 관광행태와의 유의성이 가장 높은 것으로 나타났다. 둘째, 개별관광객(FIT)은 단체관광객보다 적극적인 관광태도를 가지고 있으며 숙박비, 체험 프로그램 이용비 지출이 높은 것으로 나타났다. 셋째, 순천만 관광객은 환경적, 사회문화적, 경제적 순으로 긍정적인 태도를 보였으며, 긍정적인 태도를 지닌 관광객의 체험 프로그램 참여가 높았다. 또한 프로그램 참여자의 기부 의사가 높고, 만족도 또한 가장 높았다. 생태관광객의 지역경제 기여도를 높이기 위해 단체관광보다는 개별관광을 유도하고, 생태관광 체험 프로그램 참여를 독려하는 것이 요구되며, 주변 관광자원과의 연계, 다양한 체험 프로그램 개발, 적극적인 정보 전달과 사전교육의 필요성이 고찰되었다.

• BMB Reports
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• 제30권5호
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• pp.303-307
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• 1997

Grb2, which is composed of a Src homology 2 (SH2) domain and two Src homology 3 (SH3) domains, is known to serve as an adaptor protein in signaling for Ras activation. Thus, a blocker of the Grb2 interactions with other proteins can be a potential candidate for an anticancer drug. In this study, we have developed a high throughput screening method for SH3 domain binding ligands and blockers. Firstly, we made and purified the glutathione S-transferase (GST)-fusion proteins with the Grb2 SH2 and SH3 domains, and the entire Grb2. This method measures the binding of a biotin-labeled oligopeptide, derived from a Grb2/SH3 binding motif in the hSos, to the GST-fusion proteins, which are precoated as glutathione S-transferase fusion protein on a solid phase. When $1\;{\mu}g$ of each fusion protein was used to coat the wells, both N- and C- terminal SH3 the domains as well as the whole of Grb2 were able to interact with the biotin-conjugated ligand peptide, while the SH2 domain and GST alone showed no binding affinity. Although N- and C- terminal SH3 domains showed an increase of binding to the ligand peptide in proportion to the amount of peptide, the GST fusion protein with Grb2 demonstrated much higher binding affinity. GST-Grb2 coating on the solid phase showed a saturation curve; 66 and 84% of the maximal binding was observed at 100 and 300 ng/$100\;{\mu}l$, respectively. This binding assay system was peptide sequence-specific, showing a dose-dependent inhibition with the unlabeled peptide of SH3 binding motif. Several other peptides, such as SH2 domain binding motifs and PTB domain binding motif, were ineffective to inhibit the binding to the biotin-conjugated ligand peptide. These results suggest that our method may be useful to screen for new anticancer drug candidates which can block the signaling pathways mediated by SH3 domain binding.

• Biomolecules & Therapeutics
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• 제15권1호
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• pp.16-26
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• 2007

Tissue plasminogen activator (tPA) is a serine protease catalyzing the proteolytic conversion of plasminogen into plasmin, which is involved in thrombolysis. During last two decades, the role of tPA in brain physiology and pathology has been extensively investigated. tPA is expressed in brain regions such as cortex, hippocampus, amygdala and cerebellum, and major neural cell types such as neuron, astrocyte, microglia and endothelial cells express tPA in basal status. After strong neural stimulation such as seizure, tPA behaves as an immediate early gene increasing the expression level within an hour. Neural activity and/or postsynaptic stimulation increased the release of tPA from axonal terminal and presumably from dendritic compartment. Neuronal tPA regulates plastic changes in neuronal function and structure mediating key neurologic processes such as visual cortex plasticity, seizure spreading, cerebellar motor learning, long term potentiation and addictive or withdrawal behavior after morphine discontinuance. In addition to these physiological roles, tPA mediates excitotoxicity leading to the neurodegeneration in several pathological conditions including ischemic stroke. Increasing amount of evidence also suggest the role of tPA in neurodegenerative diseases such as Alzheimer's disease and multiple sclerosis even though beneficial effects was also reported in case of Alzheimer's disease based on the observation of tPA-induced degradation of $A{\beta}$ aggregates. Target proteins of tPA action include extracellular matrix protein laminin, proteoglycans and NMDA receptor. In addition, several receptors (or binding partners) for tPA has been reported such as low-density lipoprotein receptor-related protein (LRP) and annexin II, even though intracellular signaling mechanism underlying tPA action is not clear yet. Interestingly, the action of tPA comprises both proteolytic and non-proteolytic mechanism. In case of microglial activation, tPA showed non-proteolytic cytokine-like function. The search for exact target proteins and receptor molecules for tPA along with the identification of the mechanism regulating tPA expression and release in the nervous system will enable us to better understand several key neurological processes like teaming and memory as well as to obtain therapeutic tools against neurodegenerative diseases.

• Journal of Preventive Medicine and Public Health
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• 제23권1호
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• pp.43-56
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• 1990

To evaluate the difference of concentration and mutagenicity of organic pollutants between residential and traffic area of Seoul, air samples were collected in Bulkwang (residential) and Shinchon (traffic) area. Samples were analyzed to measure the concentration of extractable organic matters (EOM) and their subfractions and mutagenicities were tested using Salmonella typhimurium TA 98. The concentrations of polycyclic aromatic hydrocarbons (PAHs) were also measured by gas-chromatography and compared between two areas. The results were as follows ; 1. While the concentration of total suspended particulate (TSP) in residential area was below the environmental standard in annual average, the concentration in traffic area was above the standard and was up to its maximum $256{\mu}g/m^3$ in November. The difference of TSP concentrations in both areas of each month was statistically significant (P<0.05). 2. The concentration of fine particle in traffic area was significantly higher compare to that in residential area and showed statistically significant monthly difference in both areas (P<0.05). The proportion of concentration of fine particle to TSP was 55-68%. 3. Mean concentrations of EOM in residential and traffic areas were $4.3{\mu}g/m^3\;and\;5.3{\mu}g/m^3$ respectively. The proportion of amount of EOM from fine particle to EOM from TSP was 70-88%. 4. While the percentage of polar neutral organic compounds (POCN) of fine particle in Bulkwang's sample was higher compare to Shinchon's sample, the percentage of aliphatic compounds of fine particle in Shinchon's sample was higher compare to Bulkwang's sample. The percentages of PAH fraction were as low as 6-10% in both areas. 5. The mutagenic activity of nit concentration of organic matters extracted from fine particle was higher compare to that of coarse particle and was increased when metabolically activated with S9. Mutagenicities with metabolic activation calculated by unit air volume were significantly different between residential and traffic area, $17\;revertants/m^3$\;and\;22\;revertants/m^3$ respectively. 6. The concentrations of benzo(a)pyrene in fine particle of traffic and residential areas were $3.10ng/m^3\;and\;2.02ng/m^3$ respectively. Sixteen PAHs were higher in samples of traffic area compare to residential area and also concentrations of PAHs in fine particle were higher compare to coarse particle.

• The Korean Journal of Physiology and Pharmacology
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• 제2권1호
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• pp.31-39
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• 1998

As it has been reported that the depolarization induced acetylcholine (ACh) release is modulated by activation of presynaptic $A_1$ adenosine heteroreceptor and various lines of evidence suggest the $A_2$ adenosine receptor is present in the hippocampus. The present study was undertaken to delineate the role of adenosine receptors on the hippocampal ACh release. Slices from the rat hippocampus were equilibrated with $[^3H]choline$ and then the release amount of the labelled product, $[^3H]ACh$, which was evoked by electrical stimulation (rectangular pulses, 3 Hz, 2 ms, 24 mA, $5\;V/cm^{-1}$, 2 min), was measured, and the influence of various adenosine receptor-related agents on the evoked tritium outflow was investigated. And also, the drug-receptor binding assay was performed in order to confirm the presence of $A_1$ and $A_2$ adenosine receptors in the rat hippocampus. N-ethylcarboxamidoadenosine (NECA), a potent adenosine receptor agonist with nearly equal affinity at $A_1$ and $A_2$ adenosine receptors, in concentrations ranging from $1{\sim}30\;{\mu}M$, decreased the electrically-evoked $[^3H]ACh$ release in a concentration-dependent manner without affecting the basal rate of release. And the effect of NECA was significantly inhibited by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 2 ${\mu}M$), a selective $A_1$ adenosine receptor antagonist, but was not influenced by 3,7-dimethyl-1-propargylxanthine (DMPX, 5 ${\mu}M$), a specific $A_2$ adenosine receptor antagonist. $N^6-cyclopentyladenosine$ (CPA), a selective $A_1$ adenosine receptor agonist, in doses ranging from 0.1 to 10 ${\mu}M$, reduced evoked $[^3H]ACh$ release in a dose-dependent manner without the change of the basal release. And the effect of CPA was significantly inhibited by 2 ${\mu}M$ DPCPX treatment. 2-P-(2-carboxyethyl)-phenethylamino-5'-N-ethylcarboxamidoadenosine hydrochloride (CGS-21680C), a potent $A_2$ adenosine receptor agonist, in concentrations ranging from 0.1 to 10 ${\mu}M$, did not alter the evoked ACh release. In the drug-receptor binding assay, the binding of $[^3H]2-chloro-N^6-cyclopentyladenosine$ ($[^3H]$CCPA) to the $A_1$ adenosine receptor of rat hippocampal membranes was inhibited by CPA ($K_i$ = 1.22 nM), NECA ($K_i=10.17 nM$) and DPCPX ($K_i=161.86 nM$), but not by CGS-21680C ($K_i=2,380 nM$) and DMPX ($K_i=22,367 nM$). However, the specific binding of $[^3H]CGS-21680C$ to the $A_2$ adenosine receptor was not observed. These results suggest that the $A_1$ adenosine heteroreceptor play an important role in evoked ACh release, but the presence of $A_2$ adenosine receptor is not confirmed in this study.

• 한국콘텐츠학회논문지
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• 제18권2호
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• pp.147-157
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• 2018

최근 네트워크 기술 발전과 함께 IoT 및 소셜 네트워크 서비스의 활성화로 인해 많은 그래프 스트림 데이터가 생성되고 있다. 이와 같은 그래프 스트림에서 객체들 사이의 관계가 동적으로 변화함에 따라 그래프의 변화를 탐지하거나 분석하기 위한 연구들이 진행되고 있다. 본 논문에서는 그래프 스트림에서 이전 슬라이딩 윈도우에서 검출한 빈발 패턴에 대한 정보를 이용해 빈발 패턴을 점진적으로 검출하는 기법을 제안한다. 제안하는 기법은 이전 슬라이딩 윈도우에서 검출된 패턴이 앞으로 몇 슬라이딩 윈도우동안 빈발할지 또는 빈발하지 않을지를 계산하여 빈발 패턴 관리 테이블에 저장한다. 그리고 이 값을 통해 다음 슬라이딩 윈도우에서는 필요한 계산만 수행함으로써 전체 연산량을 감소시킨다. 또한 패턴 간에 간선을 통해 연결되어있는 것만 하나의 패턴으로 인식함으로써 더 유의미한 패턴만을 검출한다. 본 논문에서는 제안하는 기법의 우수함을 보이기 위해 여러 성능 평가를 진행하였다. 그래프 데이터의 크기가 커지고 슬라이딩 윈도우의 크기가 커질수록 중복되는 데이터가 증가되기 때문에 기존 기법보다 빠른 처리 속도를 나타낸다.

• 한국산학기술학회논문지
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• 제21권7호
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• pp.667-674
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• 2020

활성탄에 의한 reactive orange 16 (RO 16) 염료의 흡착은 흡착제의 양, pH, 초기 농도, 접촉시간과 온도를 흡착변수로 사용하여 실험하였으며, 분리계수, 속도상수, 율속단계, 활성화 에너지, 엔탈피, 엔트로피, 자유에너지와 같은 공정 파라미터에 대해 조사하였다. RO 16의 흡착은 활성탄 표면의 양이온 (H⁺)과 RO 16이 가지고 있는 설포네이트 이온 및 수산 이온사이의 정전기적 인력으로 인해 pH 3에서 흡착율이 가장 높았다. 등온자료는 Langmuir, Freundlich 및 Temkin 등온식을 적용하였다. Freundlich 상수(1/n=0.398~0.441)와 Langmuir 분리계수(R_L=0.459~0.491)에 의해 활성탄에 의한 RO 16의 흡착조작은 적절한 제거방법임을 확인하였다. Temkin 식의 흡착에너지 (B_T=0.293~0.576 kJ/mol) 값으로부터 이 흡착공정이 물리흡착공정이라는 것을 알았다. 흡착 동력학 실험은 RO 16의 흡착이 유사이차반응속도식에 잘 맞는 것으로 나타났다. 흡착공정의 율속단계는 입자 내 확산 단계인 것이 확인되었다. 양수값의 엔탈피 변화는 물리흡착임을 나타냈다. 음수값의 깁스 자유에너지 변화는 온도가 올라갈수록 -3.16<-11.60<-14.01 kJ/mol 순으로 작아졌다. 따라서 RO 16의 흡착공정의 자발성이 온도가 증가할수록 높아진다는 것을 보여주었다.

• The Korean Journal of Physiology and Pharmacology
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• 제12권4호
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• pp.155-164
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• 2008

Resveratrol has been known to possess various potent cardiovascular effects in animal, but there is little information on its functional effect on the secretion of catecholamines (CA) from the perfused model of the adrenal medulla. Therefore, the aim of the present study was to determine the effect of resveratrol on the CA secretion from the isolated perfused model of the normotensive rat adrenal gland, and to elucidate its mechanism of action. Resveratrol (10${\sim}100{\mu}$M) during perfusion into an adrenal vein for 90 min inhibited the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (a direct membrane-depolarizer, 56 mM), DMPP (a selective neuronal nicotinic $N_n$ receptor agonist, 100${\mu}$M) and McN-A-343 (a selective muscarinic $M_1$ receptor agonist, 100${\mu}$M) in both a time- and dose- dependent fashion. Also, in the presence of resveratrol (30${\mu}$M), the secretory responses of CA evoked by veratridine 8644 (an activator of voltage-dependent$Na^+$ channels, 100${\mu}$M), Bay-K-8644 (a L-type dihydropyridine $Ca^{2+}$ channel activator, 10${\mu}$M), and cyc1opiazonic acid (a cytoplasmic $Ca^{2+}$-ATPase inhibitor, 10${\mu}$M) were significantly reduced. In the simultaneous presence of resveratrol (30${\mu}$M) and L-NAME (an inhibitor of NO synthase, 30${\mu}$M), the CA secretory evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644 and cyc1opiazonic acid were recovered to a considerable extent of the corresponding control secretion compared with the inhibitory effect of resveratrol alone. Interestingly, the amount of nitric oxide (NO) released from the adrenal medulla was greatly increased in comparison to its basal release. Taken together, these experimental results demonstrate that resveratrol can inhibit the CA secretory responses evoked by stimulation of cholinergic nicotinic receptors, as well as by direct membrane-depolarization in the isolated perfused model of the rat adrenal gland. It seems that this inhibitory effect of resveratrol is exerted by inhibiting an influx of both ions through $Na^+$ and $Ca^{2+}$ channels into the adrenomedullary cells as well as by blocking the release of $Ca^{2+}$ from the cytoplasmic calcium store, which are mediated at least partly by the increased NO production due to the activation of NO synthase.

• The Korean Journal of Physiology and Pharmacology
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• 제2권5호
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• pp.617-628
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• 1998

In order to understand the pathogenetic mechanism of adult respiratory distress syndrome (ARDS), the role of phospholipase A2 (PLA2) in association with oxidative stress was investigated in rats. $Interleukin-1{\alpha}\;(IL-1,\;50\;{\mu}g/rat)$ was used to induce acute lung injury by neutrophilic respiratory burst. Five hours after IL-1 insufflation into trachea, microvascular integrity was disrupted, and protein leakage into the alveolar lumen was followed. An infiltration of neutrophils was clearly observed after IL-1 treatment. It was the origin of the generation of oxygen radicals causing oxidative stress in the lung. IL-1 increased tumor necrosis factor (TNF) and cytokine-induced neutrophil chemoattractant (CINC) in the bronchoalveolar lavage fluid, but mepacrine, a PLA2 inhibitor, did not change the levels of these cytokines. Although IL-1 increased PLA2 activity time-dependently, mepacrine inhibited the activity almost completely. Activation of PLA2 elevated leukotriene C4 and B4 (LTC4 and LTB4), and 6-keto-prostaglandin $F2{\alpha}\;(6-keto-PGF2{\alpha})$ was consumed completely by respiratory burst induced by IL-1. Mepacrine did not alter these changes in the contents of lipid mediators. To estimate the functional changes of alveolar barrier during the oxidative stress, quantitative changes of pulmonary surfactant, activity of gamma glutamyltransferase (GGT), and ultrastructural changes were examined. IL-1 increased the level of phospholipid in the bronchoalveolar lavage (BAL) fluid, which seemed to be caused by abnormal, pathological release of lamellar bodies into the alveolar lumen. Mepacrine recovered the amount of surfactant up to control level. IL-1 decreased GGT activity, while mepacrine restored it. In ultrastructural study, when treated with IL-1, marked necroses of endothelial cells and type II pneumocytes were observed, while mepacrine inhibited these pathological changes. In histochemical electron microscopy, increased generation of oxidants was identified around neutrophils and in the cytoplasm of type II pneumocytes. Mepacrine reduced the generation of oxidants in the tissue produced by neutrophilic respiratory burst. In immunoelectron microscopic study, PLA2 was identified in the cytoplasm of the type II pneumocytes after IL-1 treatment, but mepacrine diminished PLA2 particles in the cytoplasm of the type II pneumocyte. Based on these experimental results, it is suggested that PLA2 plays a pivotal role in inducing acute lung injury mediated by IL-1 through the oxidative stress by neutrophils. By causing endothelial damage, functional changes of pulmonary surfactant and alveolar type I pneumocyte, oxidative stress disrupts microvascular integrity and alveolar barrier.