• Title/Summary/Keyword: activation volume

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Development of screening systems for modulators on phospholipase-mediated signal transduction

  • Lee, Young-Han-;Min, Do-Sik;Kim, Jae-Ho-;Suh, Pann-Ghill;Ryu, Sung-Ho
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.04a
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    • pp.186-186
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    • 1994
  • Many agonists have been known to activate the hydrolysis of membrane phospholipids through the bindings with corresponding receptors on the various cells. Diacylglycerol and inositol 1,4,5-trisphosphate(IP3) generated by the action of phosphoinositide-specific phospholipase C (PI-PLC) are well known second messengers for the activation of protein kinase C and the mobilization of Ca2+ in many cells. Three types of PI-PLC isozyme (${\alpha}$,${\gamma}$, and $\delta$) and several subtrpes for each type have been identified from mammalian sources by purification of enzymes and cloning of their cDNAs. Each type PI-PLC isozyme is coupled to different receptors and mediators, for example, ${\beta}$-types are coupled to the seven-transmembrane-receptors via Gq family of G-proteins and ${\beta}$-types directly to the receptor tyrosine kinases. Specific modulators for the signaling pathway through each type of PI-PLC should be very useful as potential potential candidates for lend substances in developing novel drugs. To establish the sensitive and convenient screening systems for searching modulators on PI-PLC mediated signaling, two kinds of approaches have been tried. (1) Establishment of in vitro assay condition for each type of PI-PLC isozyme: Overexpression by using vaccinia virus and purification of each isozyme was carried out for the preparation of large amounts of enaymes. Optimum and sensitive assay condition for the measurements of PI-ELC activities were established. (2) Development of the cell lines in which each type of PI-PLC is permanently overexpressed: A fibroblast cell line (3T3${\gamma}$1-7) in which PI-PLC-${\gamma}$1 was overexpressed by using pZip-neo expression vector was developed and used for the measurement of PDGF-induced IP3 formation. The responses for IP3 formed in 3T3${\gamma}$1-7 cells by the treatment of PDGF is 8 times more sensitive than those in control cells. 3T3${\gamma}$l-7 cell is useful for the screening of the inhibitors on the PDGF-induced cellular responses from large number of samples in a small volume(50 ${\mu}$l) and short time(5-15 min). Using these systems, we screened hundreds of herb-extracts for the inhibition of PDGF-induced IP3 formation and selected several extracts that showed the inhibition as the candidates for isolation and characterization of active substances. The determination of the acting point of selected extracts or fractions in the PDGF signaling pathway has been analyzing.

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Atmospheric concentration and mutagenicity of organic pollutants of suspended particulate in Seoul (서울시 대기중 유기오염물질의 농도와 돌연변이원성에 대한 연구)

  • Shin, Dong-Chun;Chung, Yong;Moon, Young-Hahn;Roh, Jae-Hoon
    • Journal of Preventive Medicine and Public Health
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    • v.23 no.1 s.29
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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.

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[$Ca^{2+}-induced$ $Ca^{2+}$ Release from Sarcoplasmic Reticulum Negatively Regulates Myocytic ANP Release in Beating Rabbit Atria

  • Li, Dan;Quan, He Xiu;Wen, Jin-Fu;Jin, Jing-Yu;Park, Sung-Hun;Kim, Sun-Young;Kim, Sung-Zoo;Cho, Kyung-Woo
    • The Korean Journal of Physiology and Pharmacology
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    • v.9 no.2
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    • pp.87-94
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    • 2005
  • It is not clear whether $Ca^{2+}-induced$ $Ca^{2+}$ release from the sarcoplasmic reticulum (SR) is involved in the regulation of atrial natriuretic peptide (ANP) release. Previously, we have shown that nifedipine increased ANP release, indicating that $Ca^{2+}$ entry via voltage-gated L-type $Ca^{2+}$ channel activation decreases ANP release. The purpose of the present study was two-fold: to define the role of SR $Ca^{2+}$ release in the regulation of ANP release and whether $Ca^{2+}$ entry via L-type $Ca^{2+}$ channel is prerequisite for the SR-related effect on ANP release. Experiments were performed in perfused beating rabbit atria. Ryanodine, an inhibitor of SR $Ca^{2+}$ release, increased atrial myocytic ANP release ($8.69{\pm}3.05$, $19.55{\pm}1.09$, $27.31{\pm}3.51$, and $18.91{\pm}4.76$% for 1, 2, 3, and $6{\mu}M$ ryanodine, respectively; all P<0.01) with concomitant decrease in atrial stroke volume and pulse pressure in a dose-dependent manner. In the presence of thapsigargin, an inhibitor of SR $Ca^{2+}$ pump, ryanodine-induced increase in ANP release was not observed. Thapsigargin attenuated ryanodine-induced decrease in atrial dynamic changes. Blockade of L-type $Ca^{2+}$ channel with nifedipine abolished ryanodine-induced increase in ANP release ($0.69{\pm}5.58$% vs. $27.31{\pm}3.51$%; P<0.001). In the presence of thapsigargin and ryanodine, nifedipine increased ANP release and decreased atrial dynamics. These data suggest that $Ca^{2+}$-induced $Ca^{2+}$ release from the SR is inversely involved in the regulation of atrial myocytic ANP release.

Neuronal Activity of the Vestibular Nuclei Following Acute Hypotension in Rats

  • Park, Byung-Rim;Kim, Min-Sun;Baik, Kum-Hyun;Lee, Moon-Young;Choi, Myung-Ae;Lee, Jae-Hyo
    • The Korean Journal of Physiology and Pharmacology
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    • v.6 no.4
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    • pp.199-205
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    • 2002
  • The role of peripheral vestibular receptors in acute hypotension was investigated in anesthetized rats. Acute hypotension was induced by either intravenous infusion of sodium nitroprusside (SNP) or by experimental hemorrhage, and electrical activity and expression of cFos-like immunoreactive (cFL) protein were measured in the medial vestibular nuclei (MVN). Blood pressure decreased proportionately to the does of intravenous SNP and to the volume of the hemorrhage. Blood pressure decreased 10, 30, 50% for the 5, 10, $15{\mu}g/kg$ SNP injection, respectively, and also decreased 30 and 50% after 1- and 2-ml blood loss, respectively, due to hemorrhage. In animals with intact labyrinths, acute hypotension induced by either intravenous infusion of SNP or hemorrhage produced different electrical activities with three different patterns in type I and II neurons of MVN. The responses of type I neurons showed excitatory in 2/3 of recorded neurons and inhibitory or no change in 1/3 of neurons, while the responses of type II neurons showed inhibitory in 2/3 of recorded neurons and excitatory or no change in 1/3 of neurons. In unilateral labyrinthectomized animals, 2/3 of type I neurons ipsilateral to the lesion showed an inhibitory response, and 2/3 of contralateral type I neurons showed an excitatory response after the induction of acute hypotension. The response patterns of type II neurons were opposite from those of the type I neurons. After 30% decrease in blood pressure, cFL protein expressed in the bilateral vestibular nuclei of control animals with intact labyrinths. Expression of cFL protein increased significantly proportionately to the reduction of blood pressure. The unilateral labyrinthectomized animals with acute hypotension produced expression of cFL neurons in contralateral vestibular nuclei to the lesion side, but not in ipsilateral vestibular nuclei. However, cFL protein was not expressed in bilateral vestibular nuclei after acute hypotension in bilateral labyrinthectomized animals. These results suggest that the peripheral vestibular receptors might play a significant role in controlling blood pressure following acute hypotension via activation of type I neurons and inhibition of type II neurons in the vestibular nuclei.

Engineering Performance and Applicability of Environmental Friendly Porous Concrete for a Marine Ranch Using Steel Industry By-products (철강산업 부산물을 활용한 해양목장 조성용 친환경 다공질 콘크리트의 공학적 성능 및 적용성)

  • Lee, Byung-Jae;Jang, Young-Il;Kim, Yun-Yong
    • Journal of the Korea Concrete Institute
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    • v.25 no.1
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    • pp.115-123
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    • 2013
  • The steel industry, a representative industry that significantly consumes raw materials and energy, produces steel as well as a large amount of by-product steel slag through the production process. The vast habitat foundation of marine life has been destroyed due to recent reckless marine development and environment pollution, resulting in intensification of the decline of marine resources, and a solution to this issue is imperative. In order to propose a method to recycle large amounts of by-product slag into a material that can serve as an alternative to natural aggregate, the engineering properties and applicability for each mixing factor of environment friendly porous concrete as a material for the composition of marine ranches were evaluated in this study. The test results for percentage of voids per mixing ratio revealed that the margin of error for all conditions was within 2.5%. The compressive strength test results showed that the most outstanding environmental friendly porous concrete can be manufactured when mixing 30% slag aggregate and 10% specially treated granular fertilizer for the optimum volume fraction. As concrete for marine applications, the best seawater resistance was obtained with mixing conditions for high compression strength. An assessment of the ability to provide a marine life habitat foundation of environmentally friendly porous concrete showed that a greater percentage of voids facilitated implantation and inhabitation of marine life, and the mixing of specially treated granular fertilizer led to active initial implantation and activation of inhabitation. The evaluation of harmfulness to marine life depending on the mixture of slag aggregate and specially treated granular fertilizer revealed that the stability of fish is secured.

Acute Pulmonary Toxicity and Body Distribution of Inhaled Metallic Silver Nanoparticles

  • Kwon, Jung-Taek;Minai-Tehrani, Arash;Hwang, Soon-Kyung;Kim, Ji-Eun;Shin, Ji-Young;Yu, Kyeong-Nam;Chang, Seung-Hee;Kim, Dae-Seong;Kwon, Yong-Taek;Choi, In-Ja;Cheong, Yun-Hee;Kim, Jun-Sung;Cho, Myung-Haing
    • Toxicological Research
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    • v.28 no.1
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    • pp.25-31
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    • 2012
  • The purpose of this study was to determine the acute pulmonary toxicity of metallic silver nanoparticles (MSNPs, 20.30 nm in diameter). Acute pulmonary toxicity and body distribution of inhaled MSNPs in mice were evaluated using a nose-only exposure chamber (NOEC) system. Bronchoalveolar lavage (BAL) fluid analysis, Western blotting, histopathological changes, and silver burdens in various organs were determined in mice. Mice were exposed to MSNPs for 6 hrs. The mean concentration, total surface area, volume and mass concentrations in the NOEC were maintained at $1.93{\times}10^7$ particles/$cm^3$, $1.09{\times}10^{10}\;nm^2/cm^3$, $2.72{\times}10^{11}\;nm^3/cm^3$, and 2854.62 ${\mu}g/m^3$, respectively. Inhalation of MSPNs caused mild pulmonary toxicity with distribution of silver in various organs but the silver burdens decreased rapidly at 24-hrs post-exposure in the lung. Furthermore, inhaled MSNPs induced activation of mitogen-activated protein kinase (MAPK) signaling in the lung. In summary, single inhaled MSNPs caused mild pulmonary toxicity, which was associated with activated MAPK signaling. Taken together, our results suggest that the inhalation toxicity of MSNPs should be carefully considered at the molecular level.

Study of Nonstoichiometric Composition and Physical Properties of $Sr_{1+x}Ho_{1-x}FeO_{4-y}$ System ($Sr_{1+x}Ho_{1-x}FeO_{4-y}$계의 비화학량론적 조성과 그 물성에 관한 연구)

  • Kwang Sun Ryu;Kwang Hyun Ryu;Kwon Sun Roh;Chul Hyun Yo
    • Journal of the Korean Chemical Society
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    • v.37 no.11
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    • pp.923-928
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    • 1993
  • The series of solid solutions in the $Sr_{1+x}Ho_{1-x}FeO_{4-y}$ (x = 0.00, 0.25, 0.50, 0.75 and 1.00) systems with $K_2NiF_4$ type structure have been prepared at 1550$^{\circ}$C under an atmospheric air pressure. The X-ray powder diffraction spectra of these samples assign that the crystallographic phases are tetragonal system over the whole x range. The lattice volume was increased with increasing the substitution amount of the $Sr^{2+}$ ion. The mole ratio of the $Fe^{4+}$ ion to total iron ions or ${\tau}$ value has been determined by Mohr salt titration of the sample and then the y value was calculated from x and ${\tau}$ values. The ${\tau}$ and y values have been increased with x values. The nonstoichiometric chemical formula are formulated from the general formula of $Sr_{1+x}Ho_{1-x}Fe^3_{1-}\;^+_{\tau}Fe_{\tau}^{4+}O_{4-y}$ replaced by x,${\tau}$ and y values. Mossbauer spectra show the mixed valence state and coordination state of $Fe^{3+}\;and\;Fe^{4+}$ ions. It is found out that the magnetic property of the samples is paramagnetic at room temperature. Electrical conductivity varied within the semiconductivity range of 1.0 to 1 ${\times}\;10^{-9}{\Omega}^{-1}cm^{-1}$. Activation energy of the electrical conductivity was decreased with the $\tau$ value. The conduction mechanism should be explained by the hopping model of the conduction electrons between the valence states of $Fe^{3+}\;and\;Fe^{4+}$ ions.

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Influence of the Micropore Structures of PAN-based Activated Carbon Fibers on Nerve Agent Simulant Gas (DMMP) Sensing Property (PAN계 활성탄소섬유의 미세기공 구조가 신경작용제 유사가스(DMMP) 감응 특성에 미치는 영향)

  • Kang, Da Hee;Kim, Min-Ji;Jo, Hanjoo;Choi, Ye Ji;Lee, Young-Seak
    • Applied Chemistry for Engineering
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    • v.29 no.2
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    • pp.191-195
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    • 2018
  • In this study, the influence of microporous structures of activated carbon fibers (ACFs) on dimethyl methylphosphonate (DMMP) gas sensing properties as a nerve agent simulant was investigated. The pore structure was given to carbon fibers by chemical activation process, and an electrode was fabricated for gas sensors by using these fibers. The PAN based ACF electrode, which is an N-type semiconductor, received electrons from a reducing gas such as DMMP, and then electrical resistance of its electrode finally decreased because of the reduced density of electron holes. The sensitivity of the fabricated DMMP gas sensor increased from 1.7% to 5.1% as the micropore volume increased. It is attributed that as micropores were formed for adsorbing DMMP whose molecular size was 0.57 nm, electron transfer between DMMP and ACF was facilitated. In conclusion, it is considered that the appropriate pore structure control of ACFs plays an important role in fabricating the DMMP gas sensor with a high sensitivity.

Mechanistic Analysis of Taxol-induced Multidrug Resistance in an Ovarian Cancer Cell Line

  • Wang, Ning-Ning;Zhao, Li-Jun;Wu, Li-Nan;He, Ming-Feng;Qu, Jun-Wei;Zhao, Yi-Bing;Zhao, Wan-Zhou;Li, Jie-Shou;Wang, Jin-Hua
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.9
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    • pp.4983-4988
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    • 2013
  • Objectives: To establish a taxol-resistant cell line of human ovarian carcinoma (A2780/Taxol) and investigate its biological features. Methods: The drug-resistant cell line (A2780/Taxol) was established by continuous stepwise selection with increasing concentrations of Taxol. Cell morphology was assessed by microscopy and growth curves were generated with in vitro and in vivo tumor xenograft models. With rhodamine123 (Rh123) assays, cell cycle distribution and the apoptotic rate were analyzed by flow cytometry (FCM). Drug resistance-related and signal associated proteins, including P-gp, MRPs, caveolin-1, PKC-${\alpha}$, Akt, ERK1/2, were detected by Western blotting. Results: A2780/Taxol cells were established with stable resistance to taxol. The drug resistance index (RI) was 430.7. Cross-resistance to other drugs was also shown, but there was no significant change to radioresistance. Compared with parental cells, A2780/Taxol cells were significantly heteromorphous, with a significant delay in population doubling time and reduced uptake of Rh123 (p<0.01). In vivo, tumor take by A2780 cells was 80%, and tumor volume increased gradually. In contrast, with A2780/Taxol cells in xenograft models there was no tumor development. FCM analysis revealed that A2780/Taxol cells had a higher percentage of G0/G1 and lower S phase, but no changes of G2 phase and the apoptosis rate. Expression of P-gp, MRP1, MRP2, BCRP, LRP, caveolin-1, PKC-${\alpha}$, Phospho-ERK1/2 and Phospho-JNK protein was significantly up-regulated, while Akt and p38 MARK protein expression was not changed in A2780/Taxol cells. Conclusion: The A2780/Taxol cell line is an ideal model to investigate the mechanism of muti-drug resistance related to overexpression of drug-resistance associated proteins and activation of the PKC-${\alpha}/ERK$ (JNK) signaling pathway.

EFFECT OF PLATELET-RICH PLASMA ON AUTOGENOUS BONE GRAFT FOR BONE FORMATION IN RABBIT (가토 하악골 결손부의 자가골 이식시 혈소판 풍부혈장이 골형성 촉진에 미치는 영향에 관한 연구)

  • Jeon, Min-Su;Kim, Bo-Gyun;Song, Jun-Ho;Yeon, Byong-Moo;Lee, Young-Woo;Noh, Kyung-Lok;Kim, Da-Young;Pang, Ean-O;Kim, Jun-Hyun;Nam, Jeong-Hun;Gang, Tae-In;Lim, Sung-Chul;Park, Young-Ju
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.30 no.2
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    • pp.158-164
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    • 2008
  • Purpose : Recently, various materials were developed for enhancing bone formation capacity. Platelet rich plasma(PRP) is an autologous source with several growth factors and obtained by sequestering and concentrating platelets by gradient density centrifugation. This study was to evaluate the effect of PRP on healing of grafted bone. Materials and methods : Two blood samples were obtained and analysed for measuring platelet counts of normal blood and PRP. In experimental group, two defects of mandibular bone, 10mm in diameter and 4.0mm deep, were created in the mandible and immediately grafted with autogenous bone chips mixed with PRP. In control group, same bone defects were prepared and grafted with autogenous bone chips. Gelform was used for carrier of PRP. 2 weeks, 4 weeks, 8 weeks later, each group was evaluated with histologi-cal and histomorphometric analyses. Results : According to histological observation, experimental group was showed more anastomosing newly-formed woven bone having osteoblastic activation than control group. According to histomorphometric analysis, there were 9.11% more newly-formed bone volume in experimental group than control group at 2 weeks, 7.91% more at 4 weeks, 20.08% more at 8 weeks. Conclusion: Our results demonstrated PRP in autogenous bone graft could enhance the bone formation.