• Title/Summary/Keyword: association/dissociation

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Direct Block of Cloned $K^+$ Channels, Kv1.5 and Kv1.3, by Cyclosporin A, Independent of Calcineurin Inhibition

  • Choi, Bok-Hee;Hahn, Sang-June
    • The Korean Journal of Physiology and Pharmacology
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    • v.9 no.6
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    • pp.353-361
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    • 2005
  • The interaction of cyclosporine A (CsA), an immunosuppressant, with rat brain Kv1.5 (Kv1.5) channels, which were stably expressed in Chinese hamster ovary cells, was investigated using the whole-cell patch-clamp technique. CsA reversibly blocked Kv1.5 currents at +50 mV in a reversible concentrationdependent manner with an apparent $IC_{50}$ of 1.0μM. Other calcineurin inhibitors (cypermethrin, autoinhibitory peptide) had no effect on Kv1.5 and did not prevent the inhibitory effect of CsA. Fast application of CsA led to a rapid and reversible block of Kv1.5, and the onset time constants of the CsA-induced block were decreased in a concentration-dependent manner. The CsA-induced block of Kv1.5 channels was voltage-dependent, with a steep increase over the voltage range of channel opening. However, the block exhibited voltage independence over the voltage range in which channels were fully activated. The rate constants for association and dissociation of CsA were $7.0{\mu}M{-1}s^{-1}$ and $8.1s^{-1}$, respectively. CsA slowed the deactivation time course, resulting in a tail crossover phenomenon. Block of Kv1.5 by CsA was use-dependent. CsA also blocked Kv1.3 currents at +50 mV in a reversible concentration-dependent manner with an apparent $IC_{50}$ of $1.1{\mu}M$. The same effects of CsA on Kv1.3 were also observed in excised inside-out patches when applied to the internal surface of the membrane. The present results suggest that CsA acts directly on Kv1.5 currents as an open-channel blocker, independently of the effects of CsA on calcineurin activity.

Present Status and Future of Spent Fuel Management(1) - National Strategies and Their Implementations (사용후핵연료관리의 현황 및 미래(1) -국가별 관리전략과 그 이행-)

  • Park, Won-Jae;Suk, Tae-Won
    • Journal of Radiation Protection and Research
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    • v.21 no.1
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    • pp.59-72
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    • 1996
  • The continuous expansions and development of nuclear power have led to generation of the significant volume of spent fuels and radioactive wastes. And so, safe and effective management of the spent fuel has been becoming internationally sensitive and significant issue since the early 1990s. Especially, more importance would be added in the view point of international politics, because of recent political changes in the countries of Eastern Europe including dissociation of the former Soviet Union and the difficulties faced by the nuclear industries worldwide. Accordingly, this paper is proposed to show an overview of national strategies and Policies on the spent fuel management, that are being assessed and carried out worldwide at this time. The overview is based on recent developments of the national strategies, their implementations and some related experiences presented in IAEA International meetings and some technical papers.

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Antimuscarine-like Action of Licorice Alkaloidal Fraction on Intestinal Smooth Muscle -Studies of Alkaloid of Glycyrrhiza glabra L. III- (감초(甘草) Alkaloidal Fraction 의 평활근(平滑筋)에 대(對)한 Acetylcholine 길항작용(拮抗作用) -감초 알카로이드에 관한 연구 (제 3 보)-)

  • Kim, Myung-Suk;Oh, Jin-Sup;Hong, Sa-Ack
    • The Korean Journal of Pharmacology
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    • v.5 no.2
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    • pp.121-127
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    • 1969
  • Antimuscarinic agent like antispasmodic actions of licorice alkaloidal fraction, obtained from the Glycyrrhiza glabra L., was compared with that of atropine quantitatively. For this purpose, the author calculated the kinetic constants and $ED_{50}$ for acetylcholine antagonism by these drugs on rat ileum and guinea-fig ileum longitudinal muscle according to Paton's theoretical equations describing the combination of an antagonist drug with its receptors. The results are as follows. 1. On rat ileum. a) Licorice alkaloidal fraction $K_1$ (association rate constant)=$4.078{\times}10^2\;(s^{-1}\;gm^{-1}\;ml)$ $K_2$ (dissociation rate constant)=$6.986{\times}10^{-4}\;(s^{-1})$ $ED_{50}(K_2/K_1)=1.772{\times}10^{-6}(gm/ml)$ b) Atropine $K_1=5.136{\times}10^6$, $K_2=7.714{\times}10^{-4}$, $ED_{50}=1.408{\times}10^{-10}$ 2. On guinea-pig ileum longitudinal muscle a) Licorice alkaloidal fraction $K_1=1.30{\times}10^2$, $K_2=1.25{\times}10^{-3}$ $ED_{50}=9.58{\times}10^{-6}$ b) Atropine $K_1=5.75{\times}10^6$, $K_2=1.54{\times}10^{-3}$ $ED_{50}=2.68{\times}10^{-10}$ Above results present that 1 r of licorice alkaloidal fraction has equal fotency of acetylcholine antagonism with $8.5{\times}10^{-5}r$ of atropine on rat ileum, $2.8{\times}10^{-5}r$ on guinea-pig ileum longitudinal muscle. This facts suggest that the site and numbers of licorice alkaloid receptors of guinea-pig ileum are different from that of rat ileum. Besides, it also gives a suggestion that licorice alkaloidal fraction may be a partial antagonist on guinea-pig ileum in this experimental conditions.

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Sensing of the Insecticide Carbofuran Residues by Surface Plasmon Resonance and Immunoassay (표면플라즈몬공명과 효소면역분석법을 이용한 살충제 카보후란 잔류물 검출)

  • Yang G. M.;Cho N. H.
    • Journal of Biosystems Engineering
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    • v.30 no.6 s.113
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    • pp.333-339
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    • 2005
  • The pesticide is raising public interest in the world, because it causes damage to an environmental pollution and the human health remaining agricultural products and an ecosystem, in spite of the advantages. Particularly, each country restricts the residual pesticide and induces observance about the safety and usage standard so that they can control the amount of pesticide used and defend the safety of agricultural products. The habitual practice for the analysis of the residual pesticide depends on GC (gas chromatography), HPLC (high performance liquid chromatography) and GC/MS (gas chromatography/mass spectroscopy), which triturate the fixed quantity of samples, abstract and purify as a suitable organic solvent. These methods have the highly efficient in aspects of sensitivity and accuracy. On the other hand, they need the high cost, time consuming, much effort, expensive equipment and the skillful management. Carbofuran is highly toxic by inhalation and ingestion and moderately toxic by dermal absorption. As with other carbamate compounds, it is metabolized in the liver and eventually excreted in the urine. The half-life of carbofuran on crops is about 4 days when applied to roots, and longer than 4 days if applied to the leaves. This research was conducted to develop immunoassay for detecting carbofuran residue quickly on the basis of surface plasmon resonance and to evaluate the measurement sensitivity. Gold chip used was CM5 spreaded dextran on the surface. An applied antibody to Immunoassay was GST (glutathione-s-transferase). The association and the dissociation time were 176 second and 215 second between GST and carbofuran. The total analysis time using surface plasmon resonance was 13 minutes including regeneration time, on the other hand HPLC and GC/MS was 2 hours usually. The minimum detection limit of a permissible amount for carbofuran in the country is 0.1 ppm. The immunoassay method using surface plasmon resonance was 0.002 ppm.

Biosynthesis of a Biological Active Single Chain Equine Chorionic Gonado-tropin

  • Min, Kwan-Sik
    • Journal of Life Science
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    • v.11 no.2
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    • pp.103-107
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    • 2001
  • The equine chorionic gonadotropin (eCG) subunits $\alpha$ and ${\beta}$ are transcribed from different genes and associate noncovalently to form the bioactive eCG heterodimer. Dimerization is rate limiting for eCG secretion, and dissociation leads to hormone inactivation. The correct conformation of the heterodimer is alto important for efficient secretion, hormone-specific post-translational modifications, receptor binding and signal transduction. To determine whether ${\alpha}$ and ${\beta}$ subunits can be synthesized as a single polypeptide chain (tethered-eCG) and also display biological activity, the tethered-eCG molecule by fusing the carboxyl terminus of the eCG ${\beta}$-subunit to the amino terminus of the af-subunit was construe-ted and transfected into chinese hamster ovary (CHO-Kl) cells. LH- and FSH-like activities were assayed in terms of testosterone production and aromatase activity in primary cultured rat Leydig cells and granulosa cells, respectively. The tethered-eCG was efficiently secreted and showed similar LH-like activity to the dimeric eCG ${\alpha}$/${\beta}$ and native eCG. FSH-like activity of the tethered-eCG was also shown similarly in comparison with the native and wild type eCG ${\alpha}$/${\beta}$. Our data for the first time suggest that the tethered-eCG can be expressed efficiently and the produced product by the CHO-K1 cells is fully LH- and FSH-like activities in rat in vitro bioassay system. Our results also suggest that this molecular can imply particular models of FSH-like activity not LH-like activity in the eCG. Taken together, these data indicate that the constructs of tethered molecule will be useful in the study of mutants that affect subunit association and/or secretion.

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Effects of Plasticizer to Radioresistance and Electrical Conductivity of Irradiated Polyvinylchlorde (방사선(放射線)으로 조사(照射)된 Polyvinylchloride의 내방사성(耐放射性) 전기전도도(電氣傳導度)에 가소제(可塑劑)가 미치는 영향(影響))

  • Kim, Bong-Heup
    • Journal of Radiation Protection and Research
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    • v.3 no.1
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    • pp.23-28
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    • 1978
  • In order to investigate corelation between contents of dioctylphthalate in polyvinylchloride blent dibutyl tin dilaulate with dibutyl tin maleate as stabilizer and the behaviors of radiation resistance as well as electrical conductivity on irradiated specimens, several observations were carried out. A characteristic peak observed in the range of $1,540-1,640cm^{-1}$ on infrared spectra shows such a sensitive response to radiation as the intensity decreases with increasing doses and that this tendency strongly depressed in the presence of plasticizer. It is seemingly attributed for origin of the peak to the existence of RCOO- ion resulting from dissociation of stabilizere, further the depressive effect of decreasing peak intensity influenced by radiation seems to be caused by resonance absorption in benzen ring being a consistituent of plasticizer. It is also suggestive to be use the peak behavior influenced by radiation as a criterion for the evaluation of radiation resistance of PVC. Further the results obtained from electrical conductivity measurement also exhibit reasonable characteristics explainable with views used for the interpretation of the peak behavior mentioned previousely.

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Peptide Nucleic Acid Probe-Based Analysis as a New Detection Method for Clarithromycin Resistance in Helicobacter pylori

  • Jung, Da Hyun;Kim, Jie-Hyun;Jeong, Su Jin;Park, Soon Young;Kang, Il-Mo;Lee, Kyoung Hwa;Song, Young Goo
    • Gut and Liver
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    • v.12 no.6
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    • pp.641-647
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    • 2018
  • Background/Aims: Helicobacter pylori eradication rates are decreasing because of increases in clarithromycin resistance. Thus, finding an easy and accurate method of detecting clarithromycin resistance is important. Methods: We evaluated 70 H. pylori isolates from Korean patients. Dual-labeled peptide nucleic acid (PNA) probes were designed to detect resistance associated with point mutations in 23S ribosomal ribonucleic acid gene domain V (A2142G, A2143G, and T2182C). Data were analyzed by probe-based fluorescence melting curve analysis based on probe-target dissociation temperatures and compared with Sanger sequencing. Results: Among 70 H. pylori isolates, 0, 16, and 58 isolates contained A2142G, A2143G, and T2182C mutations, respectively. PNA probe-based analysis exhibited 100.0% positive predictive values for A2142G and A2143G and a 98.3% positive predictive value for T2182C. PNA probe-based analysis results correlated with 98.6% of Sanger sequencing results (${\kappa}$-value=0.990; standard error, 0.010). Conclusions: H. pylori clarithromycin resistance can be easily and accurately assessed by dual-labeled PNA probe-based melting curve analysis if probes are used based on the appropriate resistance-related mutations. This method is fast, simple, accurate, and adaptable for clinical samples. It may help clinicians choose a precise eradication regimen.

Selective serotonin reuptake inhibitor escitalopram inhibits 5-HT3 receptor currents in NCB-20 cells

  • Park, Yong Soo;Sung, Ki-Wug
    • The Korean Journal of Physiology and Pharmacology
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    • v.23 no.6
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    • pp.509-517
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    • 2019
  • Escitalopram is one of selective serotonin reuptake inhibitor antidepressants. As an S-enantiomer of citalopram, it shows better therapeutic outcome in depression and anxiety disorder treatment because it has higher selectivity for serotonin reuptake transporter than citalopram. The objective of this study was to determine the direct inhibitory effect of escitalopram on 5-hydroxytryptamine type 3 ($5-HT_3$) receptor currents and study its blocking mechanism to explore additional pharmacological effects of escitalopram through $5-HT_3$ receptors. Using a wholecell voltage clamp method, we recorded currents of $5-HT_3$ receptors when 5-HT was applied alone or co-applied with escitalopram in cultured NCB-20 neuroblastoma cells known to express $5-HT_3$ receptors. 5-HT induced currents were inhibited by escitalopram in a concentration-dependent manner. $EC_{50}$ of 5-HT on $5-HT_3$ receptor currents was increased by escitalopram while the maximal peak amplitude was reduced by escitalopram. The inhibitory effect of escitalopram was voltage independent. Escitalopram worked more effectively when it was co-applied with 5-HT than pre-application of escitalopram. Moreover, escitalopram showed fast association and dissociation to the open state of $5-HT_3$ receptor channel with accelerating receptor desensitization. Although escitalopram accelerated $5-HT_3$ receptor desensitization, it did not change the time course of desensitization recovery. These results suggest that escitalopram can inhibit $5-HT_3$ receptor currents in a non-competitive manner with the mechanism of open channel blocking.

Premenstrual Syndrome and its Relationship with Previous Abuse History and Dissociative Symptoms (월경전기 증후군과 해리증상 및 과거 학대 경험과의 연관성)

  • Kim, Jong-In;Choi, Tae-Kyou;Yoon, Jae-Hang;Suh, Shin-Young
    • Korean Journal of Psychosomatic Medicine
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    • v.16 no.2
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    • pp.112-119
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    • 2008
  • Objectives : Premenstrual syndrome(PMS) is known to occur in more than 80% of reproductive women. Since PMS is closely related to changes in sex hormones, biological factors are suspected to be associated with the syndrome, but there have been no consistent reports regarding biological causes. In that sense, it is postulated that the occurrence of PMS is much dependent on the biological aspects, but that the severity or characteristics of the syndrome is more dependent on the psychological factors. Studies focusing on psychological factors are based on the theory that symptoms of PMS and previous psychologically traumatic events are closely related. If the theory is valid, it can be further postulated that symptom severity of PMS is associated with dissociative symptoms, since traumatic events are known to be related to dissociative symptoms. In this study, we tried to find out the association of PMS symptom severity with previous abuse history and dissociative symptoms. Methods : Subjects for the study were 377 nurses working in Seoul, Kyung-gi, and Kyung-book. 183 subjects who submitted valid data entered the study. The presence and the symptom severity of PMS were rated using Daily Records of Severity of Problems(DRSP) and Shortened Premenstrual Assessment Form(SPAF). Dissociative symptoms were evaluated with Dissociation Experience Scale Korean version(DES-K). Previous physical/verbal abuse, sexual abuse, and parental spouse abuse experience were rated with correspondent abuse scales. Results : Subjects were divided into 3 groups as No PMS group, mild to moderate PMS group, and severe PMS group according to SPAF total score. There was a statistically significant difference in DES-K total score among 3 groups($x^2=14.966$, df=2, p=0.001). Physical/verbal abuse scale($x^2=14.397$, df=2, p=0.001), sexual abuse scale($x^2=8.376$, df=2, p=0.015), and parental spouse abuse scale($x^2=9.322$, df=2, p=0.009) also revealed a significant difference among 3 groups. Symptom severity of PMS using SPAF total score showed a positive correlation both with degree of dissociative experience and previous abuse experience. There was a statistically significant difference in both dissociative experience and previous abuse experience among 3 groups. Conclusion : These results show that there can be a possible association among PMS symptoms, dissociative symptoms, and previous psychologically traumatic experience.

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A study on the growth and characteristics of $AgGaS_2$ single crystal thin film by hot wall epitaxy (HWE 방법에 의한 $AgGaS_2$단결정 박막성장과 특성에 관한 연구)

  • 홍광준;정준우
    • Journal of the Korean Crystal Growth and Crystal Technology
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    • v.8 no.2
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    • pp.211-220
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    • 1998
  • The stochiometric composition of $AgGaS_2$polycrystal source materials for the single crystal thin films were prepared from horizontal furnace. From the extrapolation method of X-ray diffraction patterns, it was found that the polycrystal $AgGaS_2$has tetragonal structure of which lattice constant $a_0\;and \;c_0$ were 5.756 $\AA$ and 10.305 $\AA$, respectively. $AgGaS_2$single crystal thin film was deposited on throughly etched GaAs(100) substrate from mixed crystal $AgGaS_2$by the Hot Wall Epitaxy (HWE) system. The source and substrate temperature were $590^{\circ}C$ and $440^{\circ}C$ respectively, and the growth rate of the single crystal thin films was about 0.5 $mu \textrm{m}$/h. The crystallinity of the grown single crystal thin films was investigated by the DCRC (double crystal X-ray diffraction rocking curve). The optical energy gaps were found to be 2.61 eV for $AgGaS_2$single crystal thin films at room temperature. The temperature dependence of the photocurrent peak energy is well explained by the Varshni equation, then the constants in the Varshni equation are given by${\Alpha};=;8.695{\times}10^{-4};eV/K,and;{\beta};=;332;K$. from the photocurrent spectra by illumination of polarized light of the $AgGaS_2$single crystal thin film, we have found that crystal field splitting $\Delta$Cr was 0.28 eV at 20 K. From the PL spectra at 20 K, the peaks corresponding to free and bound excitons and a broad emission band due to D-A pairs are identified. The binding energy of the free excitons are determined to be 0.2676 eV and 0.2430 eV and the dissociation energy of the bound excitons to be 0.4695 eV.

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