• 대한약리학회지
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• 제29권1호
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• pp.1-8
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• 1993

뇌의 허혈-재관류 손상에 있어서 혈소판 활성인자 (PAF, platelet activating factor)의 관련을 증명하기 위하여 흰쥐와 생쥐에서 양측 총경동맥을 10분간 결찰하고 그후 6시간동안 재관류시켜 허혈-재관류 손상을 야기시켰다. 생쥐에 PAF 길항제인 BN52021과 CV6209 (각각 1 mg/kg, i.p.)를 총경동맥결찰 10분전 또는 재관류 시작 1시간 후에 투여시 McGram stroke index는 심하게 억제되었다. 흰쥐와 생쥐에서 뇌허혈-재관류에 의한 뇌수분함량의 증가는 BN52021 또는 CV6209 전처치에 의하여 유의하게 억제되었다. BN52021 전처치는 허혈 후의 혈압변동을 개선시켰을 뿐만 아니라 뇌연막동맥의 확장지연에 대하여도 효과가 있었다. 이러한 실험결과로 보아 PAF가 뇌허혈-재관류 손상의 발생에 내인성 인자로서 중요한 역할을 하는 것으로 사료된다. 나아가 PAF 길항제가 뇌허혈후의 병리학적 후휴증의 개선 내지는 예방에 사용 될 수 있을 것으로 기대된다.

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 2003년도 정기총회 및 학술발표회
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• pp.55-55
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• 2003

P2X$_3$ receptor, a member of P2 purine receptors, is a ligand-gated ion channel activated by extracellular ATP as an endogenous ligand, and highly localized in peripheral and central sensory neurons. The activation of P2X3 receptor by ATP as the pronociceptive effect has been known to initiate the pain signaling involved in chronic inflammatory nociception and neuropathic pain by nerve injury, implicating the possibility of new drug development to control pains. In this study, we have developed a two electrode voltage clamp (TEVC) assay system to evaluate the inhibitory activity of several newly synthesized PPADS and a novel non-ionic antagonist against ATP activation of human P2X3 receptor. PPADS derivatives include several pyridoxine and pyridoxic acid analogs to study the effects of phosphate and aldehyde functional groups in PPADS. All new PPADS analogs were less potent than PPADS at human P2X$_3$ receptors, however, LDD130, a non-ionic analog showed potent antagonistic property with $IC_{50}$/ of 8.34 pM. In order to uncover the structure activity relationships of LDD130, and design new structural analogs, we synthesized and investigated a few structural variants of LDD130, and the results will be discussed in this presentation.

• Preventive Nutrition and Food Science
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• 제12권4호
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• pp.197-201
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• 2007

Genistein is an active component of legumes and other related food shown to be associated with prevention of degenerative diseases such as cancer through inducing signaling pathways. Treatment of genistein resulted in the induction of apoptosis in the cultured cancer cells. This induction of apoptosis was demonstrated by the Tunel assay in these cells. Unveiling the potential of genistein in cytotoxicity via apoptosis when it is treated with estrogen can predict the therapeutic capability of genistein in breast cancers in the presence of endogenous estrogen. We have found that apoptosis induced by genistein treatment in the presence of estrogen is agonistic or antagonistic depending on the concentrations and treatment periods applied in MCF-7 breast cancer cells. For the suppression of cell survival, 24 hr of treatment was required to induce a synergistic agonistic response between estrogen and genistein at low concentrations of genistein. After this period, the agonistic pattern of genistein to estrogen disappeared. The decrement of COX-2 expression in MCF-7 cells treated with genistein was accompanied with the activation of AMPK only at a high concentration of genistein. This association between AMPK activation and down-regulation of COX-2 by genistein was dampened in the presence of estrogen. It was also demonstrated that genistein and estrogen regulate cell survival and apoptosis by modulating p53 and caspase-3 in the opposite direction. These results suggest that genistein has the potential to control breast cancer development, and co-treatment with estrogen can cause agonistic or antagonistic action on breast cancer cell control.

• 대한기관식도과학회:학술대회논문집
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• 대한기관식도과학회 1978년도 제12차 학술대회연제 순서 및 초록
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• pp.8.2-8
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• 1978

언어는 청각을 통해서 발달하는 것으로서 난청이 있어서 듣지 못하는 경우 그 사람의 언어발달은 정지되어 농아자가 되는 경우가 많다. 따라서 언어발달에 미치는 영향 때문에 유아난청의 조기진단 및 치료는 대단히 중요하다고 하겠다. 이에 저자를은 유아난청의 원인을 조사함으로써 유아난청의 예방 및 치료에 도움을 주고자 1977년 1월부터 8월까지 8개월 동안에 본원 외래 난청실로 내방한 만5세 이하의 난청아 185명을 대상으로 하여 자세한 병력과 상세한 임상적 검사 및 Impedance audiometer(Madsen ZO 70)에 의한 청역검사를 실시하고 그 원인에 대한 통계적 고찰을 시도하여 다음과 같은 결과를 얻었다. 1. 유아난청 중 감각신경성난청의 가장 흔한 원인은 유아자신의 감염(123례중, 44례, 35.8%)이었으며 임신중의 모체의 상태(37례 30.1%), 분만시 외상 혹은 두부외상(18례, 14.7%)의 순이었다. 2. 유아난청 중 부음성난청의 가장 흔한 원인은 급성 혹은 만성중이질환이었으며(62례중 32례, 51.6%), 다음으로는 잦은 상기도감염(19례, 30.6%), 아데노이드 증식증(7례, 11.3%)의 순이었다. 3. 유아난청은 외인성원인이 185례중 179례(96.8%), 내인성원인이 6례(3.2%)로 대부분이 외인성 원인이었다.

• 한국병원경영학회지
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• 제7권4호
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• pp.123-151
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• 2002

The objective of this study is to analyze the causal relationship of hospital inpatient's perceived quality, overall satisfaction, service value, and future intention to revisit. To carry out this objective, first we analyzed the dimensions of inpatient care service quality using SERVQUAL scale. The SERVQUAL scale is based on the gap theory, that is, the difference of patients' expectations and the actually received medical care service in hospital. On the basis of this theory, we measured the inpatient's perceived service quality and overall patient satisfaction. Data was gathered from a self-administered questionnaire at a 980 bed university hospital in Inchon City. These questionnaire measuring the service quality were distributed to 250 inpatients. The response rate was 66.4%. A total of 166 questionnaires was finally analyzed. To categorize medical service quality, the factor analysis was performed on 42 items. The reliability and validity of these items was evaluated. Finally to test 6 hypotheses, we analyzed the causal relationship of service quality, overall satisfaction, service value, and intention to revisit through the structural equation modeling(SEM). The major results of this study are as follows. First, the dimension of inpatient service quality was categorized into 7 dimensions, that is, personal caring, communication, access, physical environment, facilities and equipment, cleanliness, appropriateness and health status. Second, the reliability and validity of inpatient service quality items was satisfied. Third, as a result of structural equation modeling, the effect of inpatient's perceived service quality on overall satisfaction, service value, and intention to revisit was statistically significant. And total effect on intention to revisit as the core endogenous variable was perceived service quality(1.100), patient satisfaction(0.006), and service value(0.605).

• 한국임상수의학회지
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• 제25권6호
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• pp.458-465
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• 2008

The purpose of this study is to characterize canine mesenchymal stem cells (MSCs) derived from bone marrow (BM) for use in research on the applications of stem cells in canine models of development, physiology, and disease. BM was harvested antemortem by aspiration from the greater tubercle of the humerus of 30 normal beagle dogs. Canine BM-derived MSCs were isolated according to methods developed for other species and were characterized based on their morphology, growth traits, cell-surface antigen profiles, differentiation repertoire, immunocytochemistry results, and neurotrophic factor expression in vitro. The canine MSCs exhibited a fibroblast-like morphology with a polygonal or spindle-shaped appearance and long processes; further, their cell-surface antigen profiles were similar to those of their counterparts in other species such as rodents and humans. The canine MSCs could differentiate into osteocytes and neurons on incubation with appropriate induction media. RT-PCR analysis revealed that these cells expressed NGF, bFGF, SDF-1, and VEGF. This study demonstrated that isolating canine MSCs from BM, stem-cell technology can be applied to a large variety of organ dysfunctions caused by degenerative diseases and injuries in dogs. Furthermore, our results indicated that canine MSCs constitutively secrete endogenous factors that enhance neurogenesis and angiogenesis. Therefore, these cells are potentially useful for treating dogs affected with various neurodegenerative diseases and spinal-cord injuries.

• 동의생리병리학회지
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• 제21권3호
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• pp.721-727
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• 2007

Scorpion (SCP) has been clinically used for the treatment of endogenous wind to relieve convulsion, clearing away toxins, resolving hard masses and removing obstruction in the collaterals to relieve pain. Recent studies showed that scorpion toxins that affect the activating mechanism of sodium channels and indian black scorpion venom induced anti-proliferative and apoptogenic activity against human leukemic cell lines U937 and K562. There is lack of studies regarding the effects of SCP on the immunological activities. The present study was conducted to evaluate the effect of SCP on the regulatory effects of cytokines and nitric oxide (NO) for the immunological activities in Raw 264.7 cells. After the treatment of SCP MeOH extract dissolved in media for 1 h prior to the addition of lipopolysaccharide (LPS: 1 ${\mu}$g/ml), cell viability was measured by MTT assay, NO production was monitored by measuring the nitrite content in culture medium. Inducible nitric oxide synthase (iNOS) was determined by immunoblot analysis, and levels of cytokine were analyzed by sandwich immunoassays. As results, SCP inhibited the production of nitrite and nitrate (0.3 and 1.0 mg/ml), iNOS and p-$I_KB_{\alpha}$ protein, tumor necrosis factor-${\alpha}$ (0.3 and 1.0 mg/ml), interleukin-1${\beta}$ (0.3 and 1.0 mg/ml) and interleukin-6 (1.0mg/ml) in Raw 264.7 cells activated with LPS. These findings suggest that SCP can produce anti-inflammatory effect, which may play a role in adjunctive therapy in Gram-negative bacterial infections.

• Biomolecules & Therapeutics
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• 제11권4호
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• pp.205-213
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• 2003

Various angiogenesis inhibitors target vascular endothelial cells and block tumor angiogenesis. Angiostatin is a specific endogenous angiogenesis inhibitor in clinical trials, which contains only the first four triple loop structures, known as kringle domains. Its generated by proteolytic cleavage of its parent molecule plasminogen, which itself does not exhibit antiangiogenic activity. Kringle domains from prothrombin, apolipoprotein, hepatocyte growth factor, urokinase and tissue-type plasminogen activator also elicit anti-angiogenic or antitumor activities in several model systems, albeit low amino acid sequence identity between angiostatin and each individual kringle. However, the differential effects of each kringle domain on endothelial cell proliferation, and migration observed in these kringle domains, suggest that the amino acid sequence of the primary structure is still important although kringle architecture is essential for anti-mlgiogenic activity. If it is further studied as to how amino acid sequence and kringle architecture contributes in anti-angiogenic activity, with studies on underlying mechanisms of anti-angiogenesis by kringle-based angiogenesis inhibitors, it will provide basis for the development of new potent anti-angiogenesis inhibitors and improvement of the efficacy of angiogenesis inhibitors.

• Molecules and Cells
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• 제27권4호
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• pp.417-422
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• 2009

Lipoxygenase (LO) metabolites are generated in inflamed tissues. However, it is unclear whether the inhibition of the LO activity regulates the expression of c-Fos protein, a pain marker in the spinal cord. Here we used a carrageenan-induced inflammation model to examine the role of LO in the development of c-Fos expression. Intradermally injected carrageenan caused elevated number of cells exhibiting Fos-like immunoreactivity (Fos-LI) in the spinal dorsal horn, and decreased the thermal and mechanical threshold in Hargreaves and von Frey tests. Pretreatment with an inhibitor of phospholipase A2, that generates the LO substrate, prior to the carrageenan injection significantly reduced the number of Fos-(+) cells. A general LO inhibitor NDGA, a 5-LO inhibitor AA-861 and a 12-LO inhibitor baicalein also exhibited the similar effects. Moreover, the LO inhibitors suppressed carrageenan-induced thermal and mechanical hyperalgesic behaviors, which inidcates that the changes in Fos expression correlates with those in the nociceptive behaviors in the inflamed rats. LO products are endogenous TRPV1 activators and pretreatment with BCTC, a TRPV1 antagonist inhibited the thermal but not the mechanical hypersensitivity. Overall, our results from the Fos-LI and behavior tests suggest that LO products released from inflamed tissues contribute to nociception during carrageenan-induced inflammation, indicating that the LO pathway is a possible target for modulating inflammatory pain.

• Experimental and Molecular Medicine
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• 제50권12호
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• pp.9.1-9.12
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• 2018

Endometriosis is a disease characterized by implants of endometrial tissue outside the uterine cavity and is strongly associated with infertility. Focal adhesion of endometrial tissue to the peritoneum is an indication of incipient endometriosis. In this study, we examined the effect of various cytokines that are known to be involved in the pathology of endometriosis on endometrial cell adhesion. Among the investigated cytokines, transforming growth factor-${\beta}1$ ($TGF-{\beta}1$) increased adhesion of endometrial cells to the mesothelium through induction of ${\alpha}2-6$ sialylation. The expression levels of ${\beta}$-galactoside ${\alpha}2-6$ sialyltransferase (ST6Gal) 1 and ST6Gal2 were increased through activation of $TGF-{\beta}RI/SMAD2/3$ signaling in endometrial cells. In addition, we discovered that terminal sialic acid glycan epitopes of endometrial cells engage with sialic acid-binding immunoglobulin-like lectin-9 expressed on mesothelial cell surfaces. Interestingly, in an in vivo mouse endometriosis model, inhibition of endogenous sialic acid binding by a $NeuAc{\alpha}2-6Gal{\beta}1$-4GlcNAc injection diminished $TGF-{\beta}1$-induced formation of endometriosis lesions. Based on these results, we suggest that increased sialylation of endometrial cells by $TGF-{\beta}1$ promotes the attachment of endometrium to the peritoneum, encouraging endometriosis outbreaks.