• The Korean Journal of Physiology
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• v.21 no.2
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• pp.211-223
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• 1987

Head-down tilt (HDT) at $-6^{\circ}$ has been commonly used as the experimental model in both man and animals to induce the blood shift toward the head or central protion of the body, demonstrating similar physiological effect encountered in the weightlessness in the orbital flight. There are few reports about the physiological response upon the cardiovascular regulatory system or the tolerance to the $(-6^{\circ})$ HDT within a relatively short period less than 1 hour. Therefore, the purpose of this study way to observe the effects of $-6^{\circ}$ HDT on cardiovascular system within 30 minutes and to evaluate early regulatory mechanism for simulated hypogravity. Ten mongrel dogs weighing 8-12 kg were anesthetized with the infusion of 1% ${\alpha}-chloralose$ (100 mg/kg) intravenously, and the postural changes were performed from the supine to the $-6^{\circ}$ head-down Position, then from the head-down to the supine (SUP), and each posture was maintained for 30 minutes. Blood flow $({\dot{Q}})$ through common carotid and femoral arteries were determined by the electromagnetic flowmeter. Mean arterial pressure (MAP), heart rate (HR), respiratory rate , and pH, $P_{O_2}$, $P_{CO_2}$ and hematocrit (Hct) of arterial and venous blood were also measured. The peripheral vascular resistance was calculated by dividing respective MAP values by ${\dot{Q}}$ through both sides of common carotid or femoral arteries. The concentration of plasma epinephrine and norepinephrine was determined by Peuler & Johnson's radioenzymatic method. The results are summarized as follows: In the initial 5 minutes in $-6^{\circ}$ HDT, HR was significantly (p<0.05) increased and MAP slightly decreased. Although ${\dot{Q}}$ and carotid peripheral artery resistance were not significantly changed, ${\dot{Q}}$ through femoral artery was diminished and femoral peripheral artery resistance was elevated. In the SUP, the initial changes of MAP and HR were increased (p<0.05), but those of ${\dot{Q}}$ and peripheral vascular resistance through both common carotid and femoral arteries were not significant. After 10 minutes of each postural change in both HDT and SUP, MAP was maintained almost equal to that of the level of pretilting control. During 60 minutes of both postural changes of HDT and SUP, $P_{O_2}$ and Hct were not changed significantly. However pH tended to increase slowly and $P_{CO_2}$ was gradually decreased. The pH and $P_{CO_2}$ seemed to be related to the increased respiratory rate. Plasma epinephrine concentration was not changed significantly and plasma norepinephrine concentration was slightly decreased in the course of HDT and also at 10 minutes of SUP. However these concentration changes were statistically insignificant. From these results, it may be concluded that the effect of $-6^{\circ}$ HDT for 30 minutes on the cardiovascular system and plasma catecholamine levels of the dog is minimum and it is suggestive that the cardiovascular regulatory mechanism, possibly mediated by so called gravity receptors including baroreceptor and volume receptor, has been properly and adequately operated.

• Radiation Oncology Journal
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• v.22 no.2
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• pp.77-90
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• 2004

Purpose: The purpose of this review Is to provide an update on novel radiation treatments for head and neck cancer Recent Findings: Despite the remarkable advances In chemotherapy and radiotherapy techniques, the management of advanced head and neck cancer remains challenging. Epidermal growth factor receptor (EGFR) Is an appealing target for novel therapies In head and neck cancer because not only EGFR activation stimulates many important signaling pathways associated with cancer development and progression, and importantly, resistance to radiation. Furthermore, EGFR overexpression Is known to be portended for a worse outcome in patients with advanced head and neck cancer. Two categories of compounds designed to abrogate EGFR signaling, such as monoclonal antibodies (Cetuxlmab) and tyrosine kinase inhibitors (ZD1839 and 051-774) have been assessed and have been most extensively studied In preclinical models and clinical trials. Additional TKIs In clinical trials include a reversible agent, Cl-1033, which blocks activation of all erbB receptors. Encouraging preclinical data for head and neck cancers resulted In rapid translation Into the clinic. Results from Initial clinical trials show rather surprisingly that only minority of patients benefited from EGFR inhibition as monotherapy or In combination with chemotherapy. In this review, we begin with a brief summary of erbB- mediated signal transduction. Subsequently, we present data on prognostic-predictive value of erbB receptor expression in HNC followed by preclinlcal and clinical data on the role of EGFR antagonists alone or in combination with radiation In the treatment of HNC. Finally, we discuss the emerging thoughts on resistance to EGFR biockade and efforts In the development of multiple-targeted therapy for combination with chemotherapy or radiation. Current challenges for investigators are to determine (1 ) who will benefit from targeted agents and which agents are most appropriate to combine with radiation and/or chemotherapy, (2) how to sequence these agents with radiation and/or cytotoxlc compounds, (3) reliable markers for patient selection and verification of effective blockade of signaling in vivo, and (4) mechanisms behind intrinsic or acquired resistance to targeted agents to facilitate rational development of multi-targeted therapy, Other molecuiar-targeted approaches In head and neck cancer were briefly described, Including angloenesis Inhibitors, farnesyl transferase inhibitors, cell cycle regulators, and gene therapy Summary: Novel targeted theraples are highly appealing in advanced head and neck cancer, and the most premising strategy to use them Is a matter of intense Investigation.

• Clinical and Experimental Pediatrics
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• v.46 no.7
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• pp.702-709
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• 2003

Purpose : $IFN{\gamma}$ sentitizes many tumor cells to $TNF{\alpha}$ and FASL-mediated apoptosis by enhancing the expression of TNF or FAS/CD95 receptor and modulating the activation of caspase and Bcl-2 family. It has been reported that $IFN{\gamma}$ and $TNF{\alpha}$ synergistically caused differentiation and growth inhibition of neuroblastoma cells. Even though some neuroblastoma cell express FASR/FASL on the cell surface, they could not induce apoptosis by ligation of the FAS/CD95 receptor. But the treatment of $IFN{\gamma}$ is reported to induce apoptosis in some neuroblastoma cell lines through the CD95/CD95L autocrine circuit. In this study, we examined whether $IFN{\gamma}$ could affect $TNF{\alpha}$ and agonistic FAS/CD95 antibody(CH-11)-induced apoptosis against neuroblastoma cell lines that had shown diverse drug sensitivity and resistance. Methods : CHLA-15, CHLA-90 and LA-N-2 neuroblastoma cells were cultured in IMDM and treated with recombinant $IFN{\gamma}$, $TNF{\alpha}$ and CH-11 antibody. Cell viability was measured by DIMSCAN with a fluorescent calcein-AM. Apoptosis was analyzed through flow cytometry using Annexin V-PE and 7-ADD staining and confirmed by pancaspase and caspase-8 blocking experiments. The expression of TNF RI and FAS/CD95 receptor was evaluated by flow cytometry using the corresponding antibody and PE-conjugated secondary antibody. Results : $IFN{\gamma}$ or $TNF{\alpha}$ alone had no demonstrable cytotoxic effects, whereas both cytokines in combination induced apoptosis synergistically in CHLA-15 and CHLA-90 cells. Although there was no cytotoxicity with the ligation of CH-11 alone in CHLA-90 cells, pretreatment of $IFN{\gamma}$ increased the sensitivity of CH-11-mediated apoptosis. The expression of TNFRI and FAS/CD95R were non-specifically enhanced after treatment of $IFN{\gamma}$ without relation to sensitivity to $TNF{\alpha}$ and CH-11. This finding suggest up-regulation of both receptors may contribute to sensitization of $TNF{\alpha}$ and CH-11-mediated apoptosis by $IFN{\gamma}$ in only sensitive cell lines. Conclusion : $IFN{\gamma}$ induced sensitization of $TNF{\alpha}$ and agonistic FAS/CD95 antibody-mediated apoptosis on some neuroblastoma cells through up-regulation of TNFRI and FAS/CD95 receptor.

• Korean journal of applied entomology
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• v.49 no.4
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• pp.277-287
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• 2010

Several species of the genus Aphidius are used in biological control programs against aphid pests throughout the world and their behavior and physiology are well studied. While the importance of sensory organs in their behavior is understood, their antennal structure remains largely unknown. In this study, the external morphology and distribution of the antennal sensilla on the antennal of both female and male adults of A. colemani were described using scanning electron microscopy (SEM). Generally, the filiform antennae of males ($l,515.2{\pm}116.5\;{\mu}m$) are longer than females ($l,275.1{\pm}103.4\;{\mu}m$). Antennae of this species are made up of radicle, scape, pedicel and flagellomeres. Male and female antennae differed in the total number of flagellomeres as 15 in males and 13 in females. The result of SEM observation was characterization and grouping of seven types of receptors into morphological classcs: Bohm bristles, Sensilla placodea, 2 types of S. coeloconica and S. trichodea, and S. basiconica as with a tip pore and with wall pores. In addition, the possible functions of the above sensilla types arc discussed in light of previously published literature; mechanoreception (Bohm bristles, S, coeloconica I & II and S. trichodea) and chemoreception (S. placodea, S. basiconica type I & II).

• Journal of Soil and Groundwater Environment
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• v.12 no.1
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• pp.73-86
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• 2007

Risk-based remediation strategy (RBRS) is a consistent decision-making process for the assessment and response to chemical release based on protecting human health and the environment. The decision-making process described integrates exposure and risk assessment practices with site assessment activities and remedial action selection to ensure that the chosen actions are protective of human health and the environment. The general sequences of events in Tier 1 is as follows: initial site assessment, development of conceptual site model with all exposure pathways, data collection on pollutants and receptors, and identification of risk-based screening level (RBSL). If site conditions do not meet RBSL, it needs further site-specific tier evaluation, Tier 2. In most cases, only limited number of exposure pathways, exposure scenarios, and chemicals of concern are considered the Tier 2 evaluation since many are eliminated from consideration during the Tier 1 evaluation. In spite of uncertainties due to the conservatism applied to risk calculations, limitation in site-specific data collections, and variables affecting the selection of target risk levels and exposure factors, RBRS provides us time- and cost-effectiveness of the remedial action. To ensure reliance of the results, the development team should consider land and resource use, cumulative risks, and additive effects. In addition, it is necessary to develop appropriate site assessment guideline and reliable toxicity assessment method, and to study on site-specific parameters and exposure parameters in Korea.

• The Korean Journal of Pharmacology
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• v.24 no.2
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• pp.203-216
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• 1988

To delineate the mechanisms of vasoconstriction and vasodilation in cerebral arteries the effects of some vasoconstrictors and calcium antagonists on the basilar artery (BA) and arterial circle of Willis (WC) were examined and also the role of endothelium in the action of these drugs was investigated in pigs, cats and rabbits. In pig cerebral arteries, dose-dependent contractile responses were elicited by KCI, histamine, 5-hydroxytryptamine (5-HT) and angiotensin, but norepinephrine (NE), phenylephrine (PE) and epinephrine (EP) elicited dose-dependent contractions only under pretreatment with propranolol 10-6 M. The magnitudes of maximal contractile effects of these drugs were different from each other, and 5-H~ was the largest and angiotensin the smallest. Some calcium antagonists dose-dependently inhibited KCI (35 mM)-induced contraction and the order of potency in inhibiting the contraction was nifedipine > > diltiazem > flunarizine > oxybutynin > isosorbide dinitrate (ISDN) > glyceryl trinitrate. 5-HT (10-6 M)-induced contraction was dosedependently inhibited by nifedipine but slightly inhibited by diltiazem and ISDN. In rings with intact endothelium, KCI (35 mM)-induced contraction was not affected by acetylcholine (ACh) but $PGF_{2{\alpha}}$ (lO-SM)-induced contraction was dose-dependently relaxed by ACh and adenosine. This endothelium-dependent relaxation was not affected by nifedipine (l0-6M)-pretreatment but markedly inhibited by methylene blue (50,uM)-pretreatment. In the porcine arterial rings without endothelium, ACh had no effect or even contracted the $PGF_{2{\alpha}}-induced$ contraction. However, the dosedependent relaxing effect of ACh appeared when the deendothelized porcine ring and rabbit thoracic aorta with intact endotheli urn were simultaneously suspended into a bath and this relaxing effect was also inhibited by methylene blue-pretreatment. In cat cerebral arteries, 5-HT and NE elicited dose-dependent contractile responses and ACh also produced dose-dependent contraction regardless of the existence of endothelium. ACh-induced contraction was most prominent. 5-HT (IO-SM)induced contraction was not relaxed but contracted additionally by ACh even in the intact endothelial ring. In rabbit cerebral arteries, 5-HT and NE elicited dose-dependent contractile responses and 5-HT-induced contraction was more prominent. In the intact endothelial preparations, 5-HT (lO-s M)-induced contraction was markedly relaxed by the addition of ACh( IO-SM) and this endothelium-dependent relaxing effect was inhibited by atropine (l0-7M)-pretreatment but notaffected by diltiazem (l0-6M)-pretreatment. These results suggest that ACh elicits endotheliumdependent relaxing effect mediated by muscarinic receptors in cerebral arteries of pig and rabbit, and that ACh acts as vasoconstrictor in cat cerebral artery.

• Journal of Dental Rehabilitation and Applied Science
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• v.19 no.2
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• pp.87-96
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• 2003

The purposes of this study were to find out the optimum intensity of magnetic field where magnetism could promote the activity of osteoblast, and to discover the possibility of clinical application in the areas of dental implants and bone grafts by confirming the effect of clinically increasing bone formation. In this experiment, we used the Neodymium magnet, which had magnetic power six times as strong as the current ones and enabled the resistances against the demagnetization up to 20 to 50 times to be minimized with the size of 1mm in sight. In order to culture cells, a specially designed device was used. It was made to adjust the distance and accordingly to control the intensity of the magnetic field, by placing the cell culture plate in the center with a magnet of 1mm long and thick installed on the both ends. Using MC3T3-E1 cell, a kind of osteoblast-like cell, we cultured, for 24 hours, not only the test group which had been cultured under the magnetic fields with different intensity of 5, 10, 50, 100, 500, and 1000 Gauss, but also the control group excluding the influences of the magnetic field. After observing the cell's form and the density of the culture medium through an inverted microscope, we made a series of proceedings needed for the immunofluoroscence staining, such as fixation, normal serum reaction, primary antibody reaction, and secondary antibody reaction. And with a fluorescence microscope, we observed those-above and compared the frequency of expression of IFG-1 receptor. To make a Western immunoblotting analysis, the cells cultured under the same condition as the above had the procedure of the lysis buffer and the acrylamide gel electrophoresis was carried out. Protein transferred into the nitrocellulose membrane and tested on the primary and the secondary antibody reactions was observed and compared. The results were as follows: When observed through an inverted microscope, the nuclear divisions of the cells under the magnetic field of 10 Gauss were the most active, and the density of the cells could be observed the most enormously. As the result of an immunofluoroscence staining of IGF-1 receptor, the expression of IFG-1 was the most frequently observed under the magnetic field of 10 Gauss. On the other hand, few differences of consideration were made between the test group cultured under the magnetic fields of 5, 500, and 1000 Gauss and the control group. In respect of the expression of IFG-1 receptor, the test group cultured under the magnetic fields of 50 and 100 Gauss were higher than the control group, and lower than that cultured under the magnetic field of 10 Gauss.(p<0.05) According to the Western immunoblotting analysis, the band of IFG-1 receptor which had 85KDa of molecular weight was the darkest. Judging from the above-mentioned results, the growth factor receptor of an osteoblast cell which was an important criterion for the bone formation was increased in maximum under the magnetic field of 10 Gauss. Moreover it was observed that the optimum intensity of magnetic field in which magnetism made the activity of the osteoblast cell increase was about 10 Gauss.

• Journal of Life Science
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• v.31 no.9
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• pp.787-795
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• 2021

Eupatorium chinensis var. simplicifolium (EUC) has anti-inflammatory and antioxidant effects. Young sprouts of EUC have been used as food for a long time, and the whole EUC plant has been used as an herbal remedy in oriental medicine. Arteriosclerosis, or chronic inflammation in arterial vessels, is a cardiovascular disease and is involved in various disorders. Cardiovascular diseases such as restenosis and neuropathic hyperplasia are mainly caused by abnormal growth and movement due to multiple growth factors in vascular smooth muscle cells (VSMCs). Platelet-derived growth factor (PDGF) is a mitogen released from damaged vessel walls and is involved in the proliferation and migration of VSMCs. To determine the effects of EUC on the abnormal proliferation and migration of VSMCs, the present study investigated intracellular signaling pathways in PDGF-BB-induced VSMCs treated with and without EUC. Pretreating PDGF-BB-induced VSMCs with EUC tended to effectively decrease cell proliferation and migration. Subsequently, the intracellular growth-related signaling pathways of AKT, phospholipase C gamma (PLC-γ), and mitogen-activated protein kinase (MAPK) were investigated using western blotting to confirm inhibited phosphorylation. Furthermore, flow cytometry data showed that EUC blocked the cell cycle of VSMCs. These results suggest that EUC can inhibit the proliferation and migration of VSMCs by controlling the cell cycle and growth factor receptors. Furthermore, this indicates that EUC can be used as a preventative against cardiovascular disease resulting from abnormal proliferation and migration of VSMCs.

• Journal of Environmental Impact Assessment
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• v.25 no.6
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• pp.414-431
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• 2016

There are numerous closed and abandoned mines in Korea, from which diverse heavy metals (e.g., As, Cd, Cu, Pb, Zn) are released into the surrounding soil, groundwater, surface water, and crops, potentially resulting in detrimental effects on the health of nearby residents. Therefore, we performed human risk assessments of two abandoned metal mines, Yanggok (YG) and Samsanjeil (SJ). The exposure parameters used in this assessment were specific to residents near mines and the included exposure pathways were relevant to areas around metal mines. The computed total excess carcinogenic risks for both areas exceeded the acceptable carcinogenic risk ($1{\times}10^{-6}$), indicating that these areas are likely unsafe due to a carcinogenic hazard. In contrast, the non-carcinogenic risks of the two areas differed among the studied receptors. The hazard indices were higher than the unit risk (=1.0) for male and female adults in YG and male adults in SJ, suggesting that there are non-carcinogenic risks for these groups in the study areas. However, the hazard indices for children in YG and female adults and children in SJ were lower than the unit risk. Consumption of groundwater and crops grown in the area were identified as major exposure pathways for carcinogenic and non-carcinogenic hazards in both areas. Finally, the dominant metals contributing to carcinogenic and non-carcinogenic risks were As and As, Cu, and Pb, respectively. In addition, the carcinogenic and non-carcinogenic risks of YG were evaluated to be 10 and 4 times higher than those of SJ, respectively, resulted from the relatively higher exposure concentration of As in groundwater within SJ area. Because of lacking of several exposure parameters, some of average daily dose (ADD) could not be computed in this study. Furthermore, it is likely that the ADDs of crop-intake pathway included some errors because they were calculated using soil exposure concentrations and bioconcentration factor (BCF) rather than using crop exposure concentrations.

• Clinical and Experimental Pediatrics
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• v.46 no.2
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• pp.143-153
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• 2003

Purpose : Infection with Shiga-like toxin (SLT)-producing Escherichia coli, an emerging human pathogen found particularly in young children under 5 years of age, causes a spectrum of illnesses with high morbidity and mortality, ranging from diarrhea to hemorrhagic colitis and hemolytic uremic syndrome. Host mediators play an important role in the pathogenesis of SLT-I toxicity. The experiments described here were designed to investigate the effect of SLT-I on TNF-${\alpha}$ production and to understand the effect of TNF-${\alpha}$ on GB3 expression. We also further examine the relationship between the Gb3 level and the differential susceptibility of cells to the cytotoxic action of SLT-I. Methods : The effect of purified SLT-1 from E. coli O157 : H7 (ATCC 43890) on tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) production in Raw264.7 cells was investigated. Many mediators regulate endothelial cell membrane expression of the glycolipid globotriaosyleramide (Gb3), which serves as the toxin receptor, suggesting that the host response to the toxin or other bacterial products may contribute to pathogenesis by regulating target cell sensitivity to the toxins. Therefore, the relationships between Gb3 expression and cytotoxicity against SLT-I on three types of cells were evaluated. Results : Detectable levels of TNF-${\alpha}$ were produced as early as six hours after induction and continued to increase during 48 hours by SLT-I. It was also found that Vero cells and dendritic cells (DC2.4 cells) expressed high levels of Gb3, 83% and 68%, respectively, and that Raw264.7 cells had a low level of Gb3 (29%) and appeared refractory to cytotoxicity against SLT-I. Vero cells and DC2.4 cells expressing high levels of Gb3 were highly susceptible to SLT-I. Furthermore, macrophages showed a resistance to SLT-I cytotoxicity, despite the fact that Gb3 expression was enhanced. Conclusion : These results strongly suggest that the expression of Gb3 is necessary but not sufficient to confer sensitivity of macrophages to SLT-I and further underpin the important role of SLT-I and its Gb3 receptors in the pathogenesis of E. coli O157 infection.