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The Use of Pharmacogenomic Method for the Prediction of Antidepressant Responsiveness (약리 유전학적 방법을 이용한 항우울제 치료반응성의 예측)

  • Kim, Doh Kwan;Lim, Shinn-Won
    • Korean Journal of Biological Psychiatry
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    • v.9 no.1
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    • pp.25-33
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    • 2002
  • Serotonin transporter(5-HTT) is one of the major action site of antidepressants in neuronal cells. According to the recent studies, it is known that the functional polymorphism in the promoter region of the 5-HTT gene(5-HTT linked polymorphism repetitive element in promoter region, 5-HTTLPR) is associated with antidepressant responsiveness, and the distributions of 5-HTTLPR is various among the different populations. Our preliminary study suggested that it is possible to measure the endophenotype of 5-HTTLPR genotype by examining the pharmacodynamic research of the 5-HTT in platelet membranes. However, there are limitations to predicting the antidepressant responsiveness only from the endophenotypic characteristics of 5-HTT gene promoter polymorphism, and therefore we propose to use the pharmacogenomic methods for overcoming these limitations. We found that the significant correlations existed among the genetic polymorphisms of biogenic amine transporters whose structure and characteristics are similar to the 5-HTT, and the predictable odds ratio of antidepressant responsiveness are increased significantly by combining the effect with other associated polymorphisms, compared to the effect of 5-HTT promoter polymorphism only. These results support the hypothesis that antidepressant treatment has to be individualized according to the genetic and ethnic background of depressed patients. It would be possible to develope the evaluation tools to predict the antidepressant responsiveness and its side effect profile, if scientists reveal the genes related to the action mechanism as well as the metabolism of antidepressants so as to discover the interaction of those genes and contribution of endogenotypes toward antidepressant responsiveness.

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Transformation of Bottle Gourd Rootstock (Lagenaria siceraria Standl.) using GFP gene (GFP유전자를 이용한 대목용 박 형질전환)

  • Lim, Mi-Young;Park, Sang-Mi;Kwon, Jung-Hee;Han, Sang-Lyul;Shin, Yoon-Sup;Han, Jeung-Sul;Harn, Chee-Hark
    • Journal of Plant Biotechnology
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    • v.33 no.1
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    • pp.33-37
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    • 2006
  • Bottle gourd (Lagenaria siceraria Standl.) has been used as a rootstock for the watermelon cultivation because of better growth ability at low temperature and avoidance from contamination of the soil disease. Since the genetic source for the elite rootstock is limited in nature, the genetic engineering method is inevitable to develop new lines especially to obtain the functionally important or multi-disease resistant bottle gourd. Recently, our lab has set up a successful system to transform the bottle gourd. in order to monitor the transformation process, GFP gene is used. Cotyledons of the inbred line 9005, 9006 and G5 were used to induce the shoot under the selection media with MS + 30 g/L sucrose + 3.0 mg/L BAP + 100 mg/L kanamycin + 500 mg/L cefotaxime + 0.5 mg/L $AgNO_3$, pH 5.8. The shoot was developed from the cut side of the explants after 3 weeks on the selection media. The shoot was incubated in the rooting media with 1/2 MS + 30 g/L sucrose + 0.1 mg/L IAA + 50 mg/L kanamycin + 500 mg/L cefotaxime, pH 5.8 and moved to pot for acclimation. Although the shoot development rate was depended on the genotype, the G5 was the best line to be transformed. Monitoring GFP expression from the young shoot under microscope could make the selection much easier to distinguish the transformed shoot from the non-transformed shoots.

A study of neuropeptides related to headaches in children with meningeal irritation signs (수막 자극 증상으로 내원한 환자에서 두통과 관련된 신경 펩타이드에 대한 연구)

  • Seo, Bo Gil;Yoo, Myung Hwan;Shim, Jae Won;Shim, Jung Yeon;Jung, Hye Lim;Park, Moon Soo;Kim, Deok-Soo
    • Clinical and Experimental Pediatrics
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    • v.49 no.5
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    • pp.533-538
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    • 2006
  • Purpose : The headache, one of the symptoms of meningitis, is related to abrupt elevation of intracranial pressure(ICP) or stimulation of intracranial nociceptive structure. However, in cases of mild elevation of ICP or normal findings of cerebrospinal fluid(CSF) analysis, patients sometimes complain of headaches. Therefore, other pathways may contribute to the occurrence of headaches in aseptic meningitis or meningismus. We intend to investigate the role of substance P(SP) and calcitonin gene-related peptide(CGRP) in aseptic meningitis or meningismus. Methods : We measured leukocyte count, the concentration of protein and glucose in CSF and ICP of patients with meningeal irritation sign. We also measured SP and CGRP levels by using immunoassay. We analyzed the relationship between the presence of headache and the value of SP and CGRP. Results : The concentrations of CGRP($18.8{\pm}10.5ng/mL$) in CSF and ICP($14.8{\pm}4.5cmH_2O$) in aseptic meningitis group were significantly higher than in those($14.1{\pm}7.4ng/mL$ and $12.0{\pm}5.1cmH_2O$, respectively) of the meningismus group(P<0.05). There was no significant difference in the SP levels between the two groups. In the aseptic meningitis group, the concentrations of SP and CGRP were significantly higher in the normal ICP group than in the elevated ICP group(P<0.05). Conclusion : Headaches in children with aseptic meningitis or meningismus is considered to be related to the elevation of the CSF levels of SP and CGRP.

Effects of Dietary Cholesterol on Male Reproductive Tracts by Regulating PCSK9 Gene (콜레스테롤 식이가 Pcsk9 유전자 조절을 통해 남성 생식기관에 미치는 영향)

  • Lim, Whasun;Bae, Hyocheol;Song, Gwonhwa
    • Journal of Food Hygiene and Safety
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    • v.31 no.2
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    • pp.113-118
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    • 2016
  • Proprotein convertase subtilisin/kexin type 9 (PCSK9), is a protein mainly secreted by a liver. The PCSK9 plays an important role in low density lipoprotein (LDL) metabolism acting as a repressor of LDL receptor through transportation of the LDLR to the lysosome for degradation. Thus, the PCSK9 inhibitor suppresses PCSK9-regulated degradation of the LDL receptor as a LDL-lowering medicine. However, little is known about the role of PCSK9 in the reproductive system. Therefore, in the present study, we investigated Pcsk9 expression in male reproductive tracts including penises, prostates and testes using rats in response to their diets between a normal diet and a high-fat diet with cholesterol. Based on our previous study, the high-fat diet elevates concentration of total cholesterol and LDL in serum whereas it reduces the concentration of plasma high density lipoprotein (HDL). In addition, it dramatically affects to morphological changes of the male reproductive organs. Consistent with these results, the expression of Pcsk9 was substantially decreased in the penile tissues (P < 0.001) from rats fed a high fat diet as compared to a normal diet. Moreover, it slightly reduced in the prostate and testes (P < 0.05) of rats in response to a high fat diet. Localization of Pcsk9 was predominantly detected in urethral epithelium of penises, cylinder-shaped cells of prostate glands, and spermatogonia, spermatocytes and spermatid of testes of rats. Collectively, results of current study provide invaluable insights into the Pcsk9 gene with respect to its tissue- and cell-specific expression by a high fat diet with cholesterol.

Selection of Insecticide Resistance Markers in Field-collected Populations of Myzus persicae (복숭아혹진딧물 야외개체군의 살충제 저항성 마커 선발)

  • Kim, Ju Il;Kwon, Min;Shim, Jae Dong;Kim, Jeom Soon;Lee, Yeong Gyu;Jee, Sam Nyu;Lee, Jeong Tae;Ryu, Jong Soo;Yoo, Dong Lim;Lee, Gye Jun
    • Korean journal of applied entomology
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    • v.53 no.2
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    • pp.149-156
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    • 2014
  • The resistance levels of the green peach aphid, Myzus persicae (Sulzer), against 10 insecticides was checked and selected the applicable insecticide resistance markers. We conducted our study in 5 cabbage cultivation regions (Pyeongchang, Hongcheon, Bongwha, Muju, and Jeju) of Korea, over 3 successive years (2009-2011). We selected a multi-resistant (MR) strain from among the 5 field-collected populations. We analyzed esterase over-expression and mutation(s) in the target sites, by using native isoelectric focusing (IEF) and quantitative sequencing (QS). We detected esterase over-expression and StoF mutation in the acetylcholinesterase 1 gene (ace1) in all of the field-collected populations, including the MR strain. We did not detect the LtoF mutation, which is a well-known knockdown resistance (kdr) mutation in the para-type sodium channel gene (para), in the MR strain; however, the value of the MR strain for bifenthrin was 3,461-fold higher than that of the susceptible strain. Our results indicate that insecticide resistance is more effectively evaluated using molecular markers than by conducting a bioassay. The molecular markers StoF in ace1 and MtoL in para can easily be applied in diagnostic methods such as QS or PCR amplification of specific alleles (PASA). These methods may be extended to management of M. persicae resistance in the field.

The Effect of Dexamethasone on Gene Expression and Total Amount of Surfactant Protein A (스테로이드제가 Surfactant Protein A의 유전자 발현과 총단백량에 미치는 영향에 관한 실험적 연구)

  • Lim, Byung Sung;Sohn, Jang Won;Yang, Seok Chul;Yoon, Ho Joo;Shin, Dong Ho;Park, Sung Soo
    • Tuberculosis and Respiratory Diseases
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    • v.52 no.4
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    • pp.395-404
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    • 2002
  • Background : Surfactant protein A (SP-A) is important for regulating surfactant secretion, synthesis and recycling. However, It's regulation in vivo is unclear. SP-A has important roles in regulating surfactant metabolism as well as determining its physical properties. Glucocorticoid accelerates the morphologic differentiation of epithelial cells into type II cells and increase the rate of phosphatidylcholine synthesis. Methods : The authors investigated the effects of glucocorticoid on the accumulation of mRNA encoding SP-A and SP-A protein content. Adult rats were given various doses of subcutaneous dexamethasone and sacrificed after 24 hours and one week. SP-A mRNA was measured using a filter hybridization method. The lung SP-A protein content was determined using a double sandwich ELISA assay with polyclonal antiserum raised in rabbits against purified rat SP-A. Results : 1) The accumulation of SP-A mRNA in the dexamethasone treated group 24 hours after 0.2 mg/kg dexamethasone treatment was increased 38.8% compared to the control group. 2) The accumulation of SP-A mRNA in the dexamethasone treated group 1 week after 2 mg/kg dexamethasone treatment was 49.7% higher than the control group(P<0.01). 3) The total lung SP-A level was not altered after 24 hours by the 0.2mg/kg treatment. The total lung SP-A content one week after 2mg/kg dexamethasone administration was 373.7% higher than the control group(P<0.005). Conclusion : Dexamethasone treatment results in an increase in the SP-A mRNA and SP-A protein levels, suggesting that the pretranslational events in vivo may in part contribute to this process.

The Functional and Genetic Defects of IFN-${\gamma}$ Receptor in the Patients with Tuberculosis (결핵환자에서 IFN-${\gamma}$ 수용체의 기능적 및 유전적 이상에 관한 연구)

  • Park, Gye-Young;Hwang, You-Jin;Lim, Young-Hee;An, Chang-Hyeok;Park, Jeong-Woong;Jeong, Seong-Hwan
    • Tuberculosis and Respiratory Diseases
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    • v.52 no.5
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    • pp.497-505
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    • 2002
  • Background : INF-${\gamma}$ plays an important role in the host response to a mycobacterial infection. A complete IFN-${\gamma}$ receptor 1 deficiency is a life threatening condition because it renders patients highly susceptible to a mycobacterial infection. Several mutations in the IFN-${\gamma}$ receptor and STAT1 gene have been identified in the rare mycobacterial infections. These mutations have partial function of the IFN-${\gamma}$ receptor and similar pathologic features to clinical tuberculosis. Materials and Methods : The function of the IFN-${\gamma}$ receptor was evaluated in the patients with clinical tuberculosis. In addition, the DNA coding sequence of the IFNgR1 and STAT1 gene was also analyzed in disseminated tuberculosis patients who might have a defective IFN-${\gamma}$ receptor. Results : The cell surface expression levels of HLA-DR and CD64 in the PMBC after being stimulation with IFN-${\gamma}$ (100IU/ml, 1000IU/ml) were increased in both controls and patients. However, the rate of increase in both groups was similar. The production of TNF-${\alpha}$ in the response to stimulation with LPS was higher in the both groups ($850.7{\pm}687.8$ vs. $836.7{\pm}564.3$ pg/ml). Pretreatment with IFN-${\gamma}$ prior to LPS stimulation resulted in further increase in TNF-${\alpha}$ production between both groups ($2203.5{\pm}242.5$ vs. $2227.5{\pm}560.4$ pg/ml). However, the rate of the increase in TNF-${\alpha}$ production in the both groups was similar. The known mutations in the IFNgR1 and STAT1 coding sequences were not found in the genomic DNA of patients with disseminated tuberculosis. Conclusion : The functional and genetic defects of the IFN-${\gamma}$ receptor were not identified in clinical tuberculosis. This suggests the defective IFN-${\gamma}$ receptor that predispoe patients to a BCG or NTM infection can not alone account for the cases of clinical tuberculosis.

The Effect of Exercise Training on Aβ-42, BDNF, GLUT-1 and HSP-70 Proteins in a NSE/ APPsw-transgenic Model for Alzheimer's Disease. (지구성 운동이 NSE/APPsw 알츠하이머 질환 생쥐의 인지능력, Aβ-42, BDNF, GLUT-1과 HSP-70 단백질 발현에 미치는 영향)

  • Eum, Hyun-Sub;Kang, Eun-Bum;Lim, Yea-Hyun;Lee, Jong-Rok;Cho, In-Ho;Kim, Young-Soo;Chae, Kab-Ryoung;Hwang, Dae-Yean;Kwak, Yi-Sub;Oh, Yoo-Sung;Cho, Joon-Yong
    • Journal of Life Science
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    • v.18 no.6
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    • pp.796-803
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    • 2008
  • Mutations in the APP gene lead to enhanced cleavage by ${\beta}-$ and ${\gamma}-secretase$, and increased $A{\beta}$ formation, which are closely associated with Alzheimer's disease (AD)-like neuropathological changes. Recent studies have shown that exercise training can ameliorate pathogenic phenotypes ($A{\beta}-42$, BDNF, GLUT-1 and HSP70) in experimental models of Alzheimer's disease. Here, we have used NSE/APPsw transgenic mice to investigate directly whether exercise training ameliorates pathogenic phenotypes within Alzheimer's brains. Sixteen weeks of exercise training resulted in a reduction of $A{\beta}-42$ peptides and also facilitated improvement of cognitive function. Furthermore, GLUT -1 and BDNF proteins produced by exercise training may protect brain neurons by inducing the concomitant expression of genes that encode proteins (HSP-70) which suppress stress induced neuron cell damages from APPsw transgenic mice. Thus, the improved cognitive function by exercise training may be mechanistically linked to a reduction of $A{\beta}-42$ peptides, possibly via activation of BDNF, GLUT-1, and HSP-70 proteins. On the basis of the evidences presented in this study, exercise training may represent a practical therapeutic management strategy for human subjects suffering from Alzheimer's disease.

Analysis of Potential Toxigenicity and Phylogeny using Target Genes in Aphanizomenon flos-aquae (Cyanophyceae) strains isolated from the Nakdong River (낙동강에서 분리된 Aphanizomenon flos-aquae (Cyanophyceae) 균주의 목표 유전자를 이용한 잠재적 독소 생성능 및 계통학적 분석)

  • Ryu, Hui-Seong;An, Sung-Min;Lim, Chang-Kun;Shin, Ra-Young;Park, Jong-Guen;Lee, Jung-Ho
    • Korean Journal of Ecology and Environment
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    • v.50 no.1
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    • pp.137-147
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    • 2017
  • The identity of toxin producers remains only hypothesis unless there were identified by strain isolation and analytical confirmation of both the cyanotoxin production and the genetic identity of the monoculture. The purposes of this study were to identify a morphologic and phylogenetic classification in Aphanizomenon flos-aquae strains isolated from the Nakdong River and to investigate the potential ability of the strains to produce toxins such as saxitoxin and cylindrospermopsin using target genes. The 16S rRNA and sxtA, sxtI, cyrA, cyrJ genes were analyzed on two strains (DGUC001, DGUC003) isolated from the Nakdong River. Morphological features of the strains were observed a shape of aggregated trichomes in parallel fascicles which can reach up to macroscopic size and a hyaline terminal cell without aerotope. In addition, the 16S rRNA phylogenetic analyses showed that the strains were identified as the same species with high genetic similarity of 98.4% and grouped within a monospecific andsupported cluster I of Aphanizomenon flos-aquae selected from GenBank of the NCBI. The cyrA and cyrJ genes encoding for the cylindrospermopsin-biosynthesis were not detected in the present study. The sxtA gene was in detected both the two strains, whereas the sxtI gene which had been suggested as a suitable molecular marker to detect saxitoxin-producing cyanobacteria was not found both the strains. Thus, the two strains isolated from Nakdong River were identified as the same species of Aphanizomenon flos-aquae Ralfs ex Bornet et Flahault 1888, the two strains were confirmed as potential non-producing strains of the saxitoxin and cylindrospermopsin.

Effect of Paroxetine and Sertraline Treatment on Forced Swim Test-Induced Behavioral and Immune Changes in the Mouse (마우스 강제수영에 의한 행동 및 면역반응 변화에 대한 Paroxetine과 Sertraline의 효과)

  • Eum, Se-Yeun;Jeong, Min-Ho;Lim, Young-Jin;Kim, Bu-Kyung;Jeong, Soo-Jin;Hahn, Hong-Moo;Choe, Byeong-Moo
    • Korean Journal of Psychosomatic Medicine
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    • v.8 no.1
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    • pp.46-57
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    • 2000
  • Objectives : The purpose of the present study was to examine the effect of subacute treatment with the selective serotonin reuptake inhibitors(paroxetine and sertraline) on immobility in the forced swim test(FST) and on FST-induced changes in immune parameters of the mice. Methods : Authors applied a modified method of FST by Porsolt et al. Over 5 BALB/c mice were used for each group of experiments. To explore the changes in immune parameters by FST, authors investigated the production of anti-rat RBC antibody, concanavalin A(ConA)- or lipopolysaccharide(LPS)-stimulated splenocytes proliferation assay and cytokine gene expression. Results : Both paroxetine and sertraline decreased the duration of immobility in a dose-related manner. FST-performed mice showed a significant decrease in mitogenic responses of splenocytes and a slight increasing tendency in anti-rat RBC antibody response. All these responses were attenuated significantly by paroxetine and attenuated nearly nominal significance level by sertraline. The cytokine profiles of ConA-stimulated splenocytes from FST-performed mice showed stronger expression of IL-4 and weaker expression of IL-2 than control mice, and no changes in the expressions of IFN-$\gamma$ and lymphotoxin. IL-6 and IL-10 were not expressed in both group of mice. The pretreatment of paroxetine and sertraline attenuated the altered cytokine expressions in FST-performed mice to some extent. Some alterations of the expressions of IL-6 and IL-10 were observed in the mice which the selective serotonin reuptake inhibitors had been pretreated. Conclusion : The subacute treatment of paroxetine and sertraline attenuated the FST-induced behavioral and immune changes, and these serotonin reuptake inhibitors may exert some modulating effects on the immune system by the induction of cytokine gene expression, especially IL-6 and IL-10.

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