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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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Effects of High Glucose and Advanced Glycosylation Endproducts (AGE) on ZO-1 Expression in cultured Glomerular Epithelial Cells (GEpC) (당과 후기당화합물에 의한 사구체 상피세포 ZO-1 발현의 변화)

  • Lee Jin-Seok;Lee Hae- Soo;Yoon Ok-Ja;Ha Tae-Sun
    • Childhood Kidney Diseases
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    • v.8 no.2
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    • pp.138-148
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    • 2004
  • Purpose: Regardless of the underlying diseases, the proteinuric condition demonstrates ultrastructural changes in podocytes with retraction and effacement of the highly specialized interdigitating foot processes. We examined the molecular basis for this alteration of the podocyte phenotypes, including quantitative and distributional changes of ZO-1 protein as a candidate contributing to the pathogenic changes in the barrier to protein filtration. Methods: To investigate whether high glucose and advanced glycosylation endproduct(AGE) induce podocyte cytoskeletal changes, we cultured rat GEpC under 1) normal glucose(5 mM=control) or 2) high glucose(30 mM) or 3) AGE-added or 4) high glucose plus AGE-added conditions. The distribution of ZO-1 was observed by confocal microscope and the change of ZO-1 expression was measured by Western blotting and RT-PCR. Results: By confocal microscopy, we observed that ZO-1 moves from peripheral cytoplasm to inner actin filaments complexes in both AGE-added and high glucose condition. In Western blotting, high glucose or AGE-added condition decreased the ZO-1 protein expression by 11.1%(P>0.05) and 2.3%(P>0.05), respectively compared to the normal glucose condition. High glucose plus AGE-added condition further decreased ZO-1 protein expression to statistically significant level(12%, P<0.05). No significant change was seen in the osmotic control. In RT-PCR, high glucose plus AGE-added condition significantly decreased the expression of ZO-1 mRNA by 12% compared to normal glucose condition. Conclusion: We suggest that both high glucose and AGE-added condition induce the cytoplasmic translocation and suppresses the production of ZO-1 at transcriptional level and these changes may explain the functional changes of podocytes in diabetic conditions.

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매우 치사율이 높은 H5Nl 독감바이러스에 대한 킬러 T임파구 반응에 대한 연구

  • 서상희
    • Proceedings of the Korea Society of Poultry Science Conference
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    • 2002.11a
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    • pp.59-63
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    • 2002
  • 1997년 홍콩 가금시장에서의 H5N1 조류독감바이러스의 발병은 18명의 감염된 사람 중에서 6명의 사람의 생명을 앗아갔다. 이 사건은 조류독감바이러스가 매개체를 통하지 않고 닭에서 바로 사람에게 감염한 처음 있는 사건이다. 홍콩가금시장에서의 역학조사는 H5Nl과 H9N2 조류독감바이러스가 함께 공존한다는 것을 밝혔다. 가금에서는 H5N1과 H9N2 조류독감바이러스가 검출되었다. 우리는 H5N1 조류독감바이러스로부터 자을 방어하는데 H9N2 조류독감바이러스의 역할에 대해 연구했다. H5N1과 H9N2 바이러스의 혼합바이러스를 동시에 자에 접종하면 자은 생존하지 못했다. 그러나, H5N1 조류 독감바이러스감염 이전에 H9N2 조류독감바이러스를 감염한 닭들은 생존할 수 있었다 H9N2 조류 독감바이러스로 감염된 닭으로부터 얻어진 혈청은 H5N1 조류독감바이러스와 교차반응을 일으키지 않는다. H9N2 조류독감바이러스로 감염시킨 닭으로부터 얻어진 T임파구 또는 CD8 T임파구를 감염하지 않은 닭에 주입할 때 닭은 H5N1 조류독감바이러스로부터 생존할 수 있었다. 실험실외 킬러임파구실험은 H9N2 조류독감바이러스로 감염된 닭으로부터 얻어진 T임파구는 H5N1과 H9N2 조류독감바이러스로 감염된 목표세포를 동시에 감지했다. 게다가, 생체내 T임파구의 제거실험은 교차보호면역은 a/b TCR를 가진 CD8 T임파구가 중요한 역할을 하며, a/b TCR (Vbl)형의 T임파구가 목표세포를 감지한다는 것을 증명했다. H9N2 조류독감바이러스에 의한 방어면역은 시간이 지남에 따라 감소를 했고, 감염 100일까지 방어력을 나타냈다. 1997년 조류독감바이러스인 H5N1의 홍콩에서의 발병에 대한 풀리지 않은 것 중의 하나는 약 20%의 조류들이 매우 치사율이 높은 H5N1 독감바이러스를 가지고 있음에도 홍콩가금시장에서의 대부분의 닭들은 건강했다. 얻을 수 있는 정보에 따르면 대부분의 자들은 H5N1조류독감바이러스를 변으로 방출했고, 단지 두 곳의 가금시장에 있는 자들이 질병증상을 보였다. 홍콩가금시장에서 분리된 모든 H5N1 조류독감바이러스를 닭에 감염하면 100%의 치사율을 나타낸다. 바이러스 측면에서의 연구에 따르면, H9N2 조류독감바이러스는 홍콩가금시장에서 두 번째로 많이 분리되었다. H9N2 조류독감바이러스에 대한 연구에 따르면 세 가지 형이 홍콩가금시장에서 검출되었다. 1997년에 가장 많이 분리된 H9N2 조류독감바이러스는 PB1과 PB2가 A/Chicken/HongKong /156/97 (H5N1)과 유전적으로 유사한 A/HongKong/G9/97 (H9N2)형이다. A/Chicken/Hong Kong/156/97(H5N1)의 나머지 유전자는 A/Chicken/HongKong/739/94 (H9N2)와 A/chicken /Hong Kong/G23/97의 유전자와 비슷하다. 하나의 A/Quail/Hong Kong/G1/97은 Quail에서 분리되었고, 두 개의 A/Duck/Hong Kong/Y280/97 (H9N2)은 오리에서 분리되었다. A/Quail/Hong Kong/G1/97 (H9N2)의 6개의 내부유전자는 A/HongKon9/156/97 (H5N1)에 유사하나, A/Duck/ Hongkong/Y280/97 (H9N2)의 유전자는 A/HongKong/156/97 (H5N1)과 유사하지 않다. 킬러임파구는 바이러스로 감염된 목표세포를 MHC에 의존하여 파괴한다. 독감바이러스 특이 킬러임파구는 독감바이러스로 감염된 mice의 폐로부터 독감바이러스를 제거하는데 중요하다고 알려져 있다. 독감바이러스의 HA단백질은 특이 킬러임파구의 주요 목표항원 단백질이 아니다. 내부단백질인 nucleoprotein, polymerase (PB1 PB2, PA), Matrix protein, 그리고 비 구조단백질인 NS1에 대한 특이 킬러임파구의 반응이 사람과 mice에서 보고되었다. 독감바이러스에 대한 mice의 킬러임파구의 인식영역은 제한되어 있다고 알려져 있다. 많은 mice MHC 1은 독감바이러스 단백질의 킬러임파구의 epitope를 표현하지 못한다. 사람 기억킬러임파구는 다양한 종류의 독감바이러스의 단백질을 인식한다고 알려져 있다. 지금까지, 닭에서의 독감바이러스의 킬러임파구에 대한 연구는 되지 않았다.

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Reconstruction of Metabolic Pathway for the Chicken Genome (닭 특이 대사 경로 재확립)

  • Kim, Woon-Su;Lee, Se-Young;Park, Hye-Sun;Baik, Woon-Kee;Lee, Jun-Heon;Seo, Seong-Won
    • Korean Journal of Poultry Science
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    • v.37 no.3
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    • pp.275-282
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    • 2010
  • Chicken is an important livestock as a valuable biomedical model as well as food for human, and there is a strong rationale for improving our understanding on metabolism and physiology of this organism. The first draft of chicken genome assembly was released in 2004, which enables elaboration on the linkage between genetic and metabolic traits of chicken. The objectives of this study were thus to reconstruct metabolic pathway of the chicken genome and to construct a chicken specific pathway genome database (PGDB). We developed a comprehensive genome database for chicken by integrating all the known annotations for chicken genes and proteins using a pipeline written in Perl. Based on the comprehensive genome annotations, metabolic pathways of the chicken genome were reconstructed using the PathoLogic algorithm in Pathway Tools software. We identified a total of 212 metabolic pathways, 2,709 enzymes, 71 transporters, 1,698 enzymatic reactions, 8 transport reactions, and 1,360 compounds in the current chicken genome build, Gallus_gallus-2.1. Comparative metabolic analysis with the human, mouse and cattle genomes revealed that core metabolic pathways are highly conserved in the chicken genome. It was indicated the quality of assembly and annotations of the chicken genome need to be improved and more researches are required for improving our understanding on function of genes and metabolic pathways of avian species. We conclude that the chicken PGDB is useful for studies on avian and chicken metabolism and provides a platform for comparative genomic and metabolic analysis of animal biology and biomedicine.

Mapping and estimating forest carbon absorption using time-series MODIS imagery in South Korea (시계열 MODIS 영상자료를 이용한 산림의 연간 탄소 흡수량 지도 작성)

  • Cha, Su-Young;Pi, Ung-Hwan;Park, Chong-Hwa
    • Korean Journal of Remote Sensing
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    • v.29 no.5
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    • pp.517-525
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    • 2013
  • Time-series data of Normal Difference Vegetation Index (NDVI) obtained by the Moderate-resolution Imaging Spectroradiometer(MODIS) satellite imagery gives a waveform that reveals the characteristics of the phenology. The waveform can be decomposed into harmonics of various periods by the Fourier transformation. The resulting $n^{th}$ harmonics represent the amount of NDVI change in a period of a year divided by n. The values of each harmonics or their relative relation have been used to classify the vegetation species and to build a vegetation map. Here, we propose a method to estimate the annual amount of carbon absorbed on the forest from the $1^{st}$ harmonic NDVI value. The $1^{st}$ harmonic value represents the amount of growth of the leaves. By the allometric equation of trees, the growth of leaves can be considered to be proportional to the total amount of carbon absorption. We compared the $1^{st}$ harmonic NDVI values of the 6220 sample points with the reference data of the carbon absorption obtained by the field survey in the forest of South Korea. The $1^{st}$ harmonic values were roughly proportional to the amount of carbon absorption irrespective of the species and ages of the vegetation. The resulting proportionality constant between the carbon absorption and the $1^{st}$ harmonic value was 236 tCO2/5.29ha/year. The total amount of carbon dioxide absorption in the forest of South Korea over the last ten years has been estimated to be about 56 million ton, and this coincides with the previous reports obtained by other methods. Considering that the amount of the carbon absorption becomes a kind of currency like carbon credit, our method is very useful due to its generality.

Difference in Electrophoretic Phenotypes of Rice Cultivars Selected to Oxyfluorfen (Oxyfluorfen에 대한 내성(耐性) 및 감수성(感受性) 수도품종(水稻品種)의 전기영동(電氣泳動) 표현형(表現型) 차이(差異))

  • Kuk, Y.I;Guh, J.O.;Lee, D.J.;Kim, Y.J.
    • Korean Journal of Weed Science
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    • v.8 no.2
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    • pp.199-207
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    • 1988
  • The study was intended to know any relations between the rice tolerance to oxyfluorfen and varietal speciation in seed protein composition or any enzymatical allelies with or without chemical treatment. Rice varieties used were Chokoto, Aichiasahi, Agabyeo, IR 3941 and Tablei as the tolerant group, and Mushakdanti, Weld Pally, HP 1033, HP 857, and HP 907 as the susceptible, respectively. Electrophoretic methods used were SDS-PAGE for seed protein, 7% PAGE for isozymes (acid phosphatase and peroxidase from rice seedling) and changes in isoenzyme activity (malate dehydrogenase, peroxidase and esterase) as affected by oxyfluorfen treatment ($10^{-4}M$) was also studied. The results are summarized as follows. -Among 19 bands separated in seed proteins, two different rice groups selected in terms of tolerance were clustered in dissimilarity. This was based on 2 facts in that G band was not present in susceptible varieties and that less activity of H, N, O, P, Q, Rand S band was shown. -Among 4 bands separated in acid phosphatase, the presence of (band and lower activity of B band was specific for tolerant varieties. For 4 minor bands separated in peroxidase, the tolerant varieties had no activity in B band and higher activity in A, C, D bands. -Time-course study of isozymes as affected by $10^{-4}M$ oxyfluorfen showed that Chokoto, the tolerant varieties, had little activity in A band and consistently higher activities in Band C bands for malate dehydrogenase. For 5 bands separated in peroxidase, B band was not found in Chokoto while A, C, D, and E bands were consistently present. Esterase was separated into about 4 bands in which Chokoto had maintained higher activities in A, C and D bands.

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Activity and Survival of the Natural Bacteria under the Stressed Conditions Detected by Bioluminescent Phenotype (스트레스 하의 자연세균의 활성 및 생존의 발광표현형을 이용한 탐지)

  • Park, Kyoung-Je;Yoon, Hye-Young;Chun, Se-Jin;Lee, Ho-Sa;Lee, Dong-Hun;Jahng, Deokjin;Lee, Kyu-Ho
    • Korean Journal of Microbiology
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    • v.34 no.3
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    • pp.154-161
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    • 1998
  • To investigate whether the introduced genetic marker is useful to detect the survivalship and activity of the natural bacteria under the stressed conditions, one Gram-negative isolate, KP964 was transformed to the luminous phenotype by transferring luxAB gene. Under the starvation-stress this luminous bacterial culturability (determined by colony-forming-units [CFU] on agar plate) decreased rapidly below the detection limit by 37 days, while its total cell number (determined by AODC) remained almost the same as its initial inocular size. At that time period, the viable cell number was estimated to be 1400 times higher than its CFU number. The bioiuminescence (determined by relative light units [RLU]) produced under the same condition was also monitored and found to decrease more rapidly than the culturability by 5-fold. Under the other stresses, e.g., osmotic shocks, acid shock, and exposure to toxic chemicals, this bacterial strain did not show the reliable correlation between CFU and RLU. These results might not suggest the direct estimation of bioiuminescence from the stressed bacteria be an index of both the survivalship and its activity. However, when the stressed bacterial cells were incubated under the favorable condition by relieving from the existing stress, the potential bioiuminescence (the lag periods before the increase of bioiuminescence, the increase rates of bioiuminescence, and the maximal levels of bioiuminescence) was shown to be highly dependent upon the strengths of the stresses exposed to the bacterial cells. Therefore, analysis of the potential bioiuminescence from the stressed bacteria revealed good relationships with survival as well as activity.

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Biosynthesis of the extracellular enzymes in de novo during the differentiation of Aspergillus niger (검정곰팡이의 형태분화에 따른 세포외성효소의 신생적생합성에 관한 연구)

  • Kim, Jong-Hyup
    • The Korean Journal of Mycology
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    • v.6 no.2
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    • pp.1-10
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    • 1978
  • In de novo biosynthesis of the extracellulor enzymes-proteinsaes, alpha and gluc-amylases during the synchronized differentiation of Aspergillus niger in submerged culture and surface liquid culture were investigated. Gluc-amylase was synthesized in the stage of presporulation in which phialide formation is involved. Proteinase was synthesized both in the stages of conidiophore formation and presporulation. Alpha-amylase was synthesized during presporulation and sporulation stages, the activity of enzyme lasted for seven days on surface liquid culture. It seemed that the synthesis was occured in de novo partly repressed by the catabolite, and its nature was found to be constitutive since it is produced in non-starch medium. Polyacrylamide gel electrophoresis have shown that presporulating and sporulating body produced diverse types of the proteins whereas the earlier stages of vegetative body showed simpler profiles. The uptake of C-14 uracil into RNA and C-14 glutamate into protein were shown to be vigorous in presporulating body rather than those in sporulating body. Coincidence of alpha-amylase biosynthesis in de novo and sporulation may be significant in the study of differentiation in which gene expression is involved.

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A Study on Korean-American Writer Hong-Eun($1880\~1951$) focusing on Mong-yu siga(Traditional Korean Poetry, gasa and sijo of strolling in the dream) (재미작가 홍언의 몽유가사$\cdot$시조에 나타난 작가의식)

  • Park Mi-Young
    • Sijohaknonchong
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    • v.21
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    • pp.77-110
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    • 2004
  • This study is an exploration of a Korean-American writer, Hong-Eun's Mong-yu siga. Hong-Eun immigrated to the United States during the colonial rule of the Japanese government. He was a publisher of The New Korea Times, and contributed various literary works to it. The purpose of this study is to analyze his two Mong-yu sigas published in 1935 and 1947 and elucidate their meanings. Using dream as a primary motif, the intention of Mong-yu mode is to achieve desire which is impossible to reach in reality. While his staying in the United States, Hong-Eun could not return his home country for two reasons, that is, political and financial ones. To return Korea desperately, he wrote sigas by adopting Mong-yu mode. His first attempt was reflected as eight pieces of consecutive poetries titled This Mountain In My Dream, I am Home. This Mountain was published on the 25th of April, 1935 and In My Dream, I am Home was contributed from May the 9th of 1935 to July the fourth of the same year. These works were published in the The New Korea Times' poetry column under the pen name of Donghae-soboo , Representing gasa of the enlightenment era, this poetry depicts historical identity of Chosun dynasty, especially focusing on before and after the 1900s. As a result of it, the poetry sketches the ideology of the Middle Ages. His second attempt was A Country and Hometown written as a form of prelude on the 25th of September, 1947. In addition, A Country in My Dream was published as a form of six pieces of consecutive poetry from October the second to November the sixth of 1947. He chose sijo as a major form of poetry, and the image of the poetry seemed to be the continuation of his first attempt. Confronting the reality of the his own country which is divided, the writer expresses his antagonism toward America and Russia. Although he could eventually return his country later, he rationalized himself by saying that his it is not the ideal place to go. Mong-yu mode is a traditional poetic technique which the intellectuals of the Middle Age used to use as one pattern of allegory. In addition to this, in the period of the enlightenment of Korea, Mong-yu was used to avoid the Japanese censorship and experiment on the diverse ways of writing. In terms of literary history, the significance of Hong-Eun's creation of Mong-yu sigas is that Hong-Eun shares the same intention with Korean intellectuals of the enlightenment period.

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Development of an Automatic 3D Coregistration Technique of Brain PET and MR Images (뇌 PET과 MR 영상의 자동화된 3차원적 합성기법 개발)

  • Lee, Jae-Sung;Kwark, Cheol-Eun;Lee, Dong-Soo;Chung, June-Key;Lee, Myung-Chul;Park, Kwang-Suk
    • The Korean Journal of Nuclear Medicine
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    • v.32 no.5
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    • pp.414-424
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    • 1998
  • Purpose: Cross-modality coregistration of positron emission tomography (PET) and magnetic resonance imaging (MR) could enhance the clinical information. In this study we propose a refined technique to improve the robustness of registration, and to implement more realistic visualization of the coregistered images. Materials and Methods: Using the sinogram of PET emission scan, we extracted the robust head boundary and used boundary-enhanced PET to coregister PET with MR. The pixels having 10% of maximum pixel value were considered as the boundary of sinogram. Boundary pixel values were exchanged with maximum value of sinogram. One hundred eighty boundary points were extracted at intervals of about 2 degree using simple threshold method from each slice of MR images. Best affined transformation between the two point sets was performed using least square fitting which should minimize the sum of Euclidean distance between the point sets. We reduced calculation time using pre-defined distance map. Finally we developed an automatic coregistration program using this boundary detection and surface matching technique. We designed a new weighted normalization technique to display the coregistered PET and MR images simultaneously. Results: Using our newly developed method, robust extraction of head boundary was possible and spatial registration was successfully performed. Mean displacement error was less than 2.0 mm. In visualization of coregistered images using weighted normalization method, structures shown in MR image could be realistically represented. Conclusion: Our refined technique could practically enhance the performance of automated three dimensional coregistration.

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