<i>CYP2C19</i> haplotypes in Koreans as a marker of enzyme activity evaluated with omeprazole

Jin, S. K.,Kang, T. S.,Eom, S. O.,Kim, J.-I.,Lee, H. J.,Roh, J. Blackwell Publishing Ltd 2009 Journal of clinical pharmacy and therapeutics Vol.34 No.4

<P>Summary</P><P>Background and objective: </P><P>CYP2C19 is clinically important in Korea because of the relatively high incidence of poor metabolizers in the population. To fully understand the genetic mechanism of the <I>CYP2C19</I> defect in poor metabolizers, all variants need to be studied simultaneously. The aim of this study was to investigate the usefulness of <I>CYP2C19</I> haplotypes as a marker of CYP2C19 enzyme activity in Koreans.</P><P>Methods: </P><P>We analysed the single nucleotide polymorphisms and haplotypes of the <I>CYP2C19</I> gene in 150 healthy Koreans and found three major (frequency > 0·1) haplotypes (H1, H2 and H3). One oral dose of 40 mg omeprazole (Losec<SUP>®</SUP>) was administered to 30 subjects grouped as H1/H1, H2/H2, H1/H2, H1/H3 and H2/H3. The pharmacokinetics of omeprazole and its metabolites, 5-hydroxyomeprazole and omeprazole sulphone, in those groups was analysed.</P><P>Results and discussion: </P><P>The area under the plasma concentration–time curve (AUC<SUB>0→∞</SUB>) and elimination half-life (<I>T</I><SUB>1/2</SUB>) of omeprazole were significantly greater in the H2/H2 and H2/H3 groups than in the H1/H1 group (<I>P </I><<I> </I>0·05), whereas the metabolic ratios of omeprazole to 5-hydroxyomeprazole were also markedly higher.</P><P>Conclusion: </P><P>Although a specific SNP of <I>CYP2C19</I> may be predictive of enzyme activity, haplotyping is more reliable for identifying poor metabolizers in populations with variant alleles other than <I>CYP2C19*2</I> and <I>*3</I> alleles.</P>

Diagnostic usefulness of a T cell-based assay for latent tuberculosis infection in kidney transplant candidates before transplantation

Kim, S.-H.,Lee, S.-O.,Park, I.-A.,Park, S.J.,Choi, S.-H.,Kim, Y.S.,Woo, J.H.,Park, S.-K.,Park, J.S.,Kim, S.C.,Han, D.J. Blackwell Publishing Inc 2010 Transplant infectious disease Vol.12 No.2

<P>S.-H. Kim, S.-O. Lee, I.-A. Park, S.J. Park, S.-H. Choi, Y.S. Kim, J.H. Woo, S.-K. Park, J.S. Park, S.C. Kim, D.J. Han. Diagnostic usefulness of a T cell-based assay for latent tuberculosis infection in kidney transplant candidates before transplantation.Transpl Infect Dis 2010: <B>12:</B> 113–119. All rights reserved</P><P>Background</P><P>The presence of latent tuberculosis (TB) infection (LTBI) should be evaluated before kidney transplantation. Although a new T cell-based assay for diagnosing LTBI gave promising results, this assay has not yet been compared with the tuberculin skin test (TST) for diagnosing LTBI in renal transplant candidates before transplantation.</P><P>Patients and methods</P><P>All adult patients admitted to a single institute for renal transplantation over a 1-year period were prospectively enrolled. A clinically predictive risk of LTBI was defined as: (i) recent close contact with a person with pulmonary TB; (ii) abnormal chest radiography; (iii) a history of untreated or inadequately treated TB; or (iv) a new infection (i.e., a recent conversion of TST).</P><P>Results</P><P>Of 209 renal recipients, 47 (22%) had a positive TST≥5 mm, 21 (10%) had a positive TST≥10 mm, 65 (30%) had a positive T-SPOT.<I>TB</I> test, and 25 (12%) had an indeterminate T-SPOT.<I>TB</I> test. The induration size of TST was significantly associated with a high positivity rate on T-SPOT.<I>TB</I> (<I>P</I><0.001). Agreement between T-SPOT.<I>TB</I> test and TST≥10 mm was fair (<I>k</I>=0.24, 95% confidence interval 0.11–0.36). However, neither univariate nor multivariate analysis showed any association between the clinical risk for LTBI and positivity on T-SPOT.<I>TB</I> or TST.</P><P>Conclusion</P><P>T-SPOT.<I>TB</I> test was more frequently positive than TST in renal transplant candidates. However, further longitudinal studies are awaited to determine whether the ability of T-SPOT.<I>TB</I> assay to detect LTBI in renal transplant recipients can better predict the development of TB than can TST after transplantation.</P>

Influence of <i>CYP2D6*10</i> on the pharmacokinetics of metoprolol in healthy Korean volunteers

Jin, S. K.,Chung, H. J.,Chung, M. W.,Kim, J.-I.,Kang, J.-H.,Woo, S. W.,Bang, S.,Lee, S. H.,Lee, H. J.,Roh, J. Blackwell Publishing Ltd 2008 Journal of clinical pharmacy and therapeutics Vol.33 No.5

<P>Summary</P><P>Background and objective: </P><P>Genetic polymorphism of <I>CYP2D6</I> leads to differences in pharmacokinetics of CYP2D6 substrates. The <I>CYP2D6*10</I> allele is clinically important in Koreans because of its high frequency in Asians. We investigated whether the pharmacokinetics of metoprolol was altered by the presence of the <I>CYP2D6*10</I> allele in Korean subjects.</P><P>Methods: </P><P>One hundred and seven volunteers were recruited and grouped as <I>CYP2D6*1/*1</I>, <I>CYP2D6*1/*10</I> and <I>CYP2D6*10/*10</I> according to their genotypes. Metoprolol tartrate 100 mg (Betaloc<SUP>®</SUP>) was administered orally once to each subject in these three groups (<I>n</I> = 6, 7 and 5, respectively). The pharmacokinetic parameters of metoprolol and its metabolite, &agr;-hydroxymetoprolol, and the metabolic ratio for the three groups were estimated and compared.</P><P>Results and discussion: </P><P>The area under the plasma concentration–time curve (AUC<SUB>0→∞</SUB>), the maximum plasma concentration (<I>C</I><SUB>max</SUB>) and the elimination half-life (<I>T</I><SUB>1/2</SUB>) of metoprolol and &agr;-hydroxymetoprolol for the <I>CYP2D6*10/*10</I> group were all significantly different from those of the <I>CYP2D6*1/*1</I> group (<I>P</I> < 0·05). The AUC<SUB>0→∞</SUB>s of metoprolol were 443·7 ± 168·1, 995·6 ± 321·4 and 2545·3 ± 632·0 ng·h/mL, and the AUC<SUB>0→∞</SUB>s of &agr;-hydroxymetoprolol were 1232·0 ± 311·2, 1344·0 ± 288·1 and 877·4 ± 103·4 ng·h/mL for groups <I>CYP2D6*1/*1</I>, <I>*1/*10</I> and <I>*10/*10</I>, respectively. The corresponding <I>T</I><SUB>1/2</SUB> values of metoprolol were 2·7 ± 0·5, 3·2 ± 1·3 and 5·0 ± 1·1 h, while those of &agr;-hydroxymetoprolol were 5·4±1·5, 6·0 ± 1·4 and 10·5 ± 4·2 h, respectively. The metabolic ratios of the three groups were significantly different (<I>P</I> < 0·05).</P><P>Conclusion: </P><P>The <I>CYP2D6*10</I> allele altered the pharmacokinetics of metoprolol in Korean subjects and is likely to affect other drugs metabolized by the CYP2D6 enzyme, similarly.</P>

Multi-layered hydrogenated p-type microcrystalline silicon windows for a-Si:H thin film solar cells on opaque substrates

Lee, Y.J.,Lee, S.H.,Schropp, R.E.I.,Lee, K.S.,Lim, J.W.,Yun, S.J. Pergamon Press 2016 International journal of hydrogen energy Vol.41 No.15

<P>The effects of multi-layered p-type microcrystalline (mu c-) Si:H windows on the performance of substrate-type amorphous Si:H thin film solar cells on opaque substrates were investigated. The results were well explained in terms of H-2-plasma-induced damage (HPID) at the p/i-interface and the near-interface region of the light-absorbing layer. The mu c-Si:H was deposited using plasma enhanced chemical vapor deposition in a H-2-rich atmosphere. A high microcrystalline volume fraction was obtained with a high H-2 dilution ratio, which can cause considerable HPID. Cell efficiency was enhanced with a multi-layered p-type mu c-Si:H composed of films with low and high crystalline volume fraction, compared to cells with single-layered mu c-Si:H. In the multi-layered p-type mu c-Si:H, the low crystalline film was placed on an i-Si:H layer to reduce HPID. The present work demonstrated that HPID was reduced at the p/i-interface and the near-interface region of the light-absorbing layer, and that the quality of the p-type mu c-Si:H needs to be a significant consideration to achieve high efficiency. Copyright (C) 2016, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.</P>

돼지 H-FABP 유전자의 다형성 및 경제 형질과의 연관성 구명

최봉환,김태헌,이지웅,조용민,이혜영,조병욱,정일정 한국동물자원과학회 2003 한국축산학회지 Vol.45 No.5

The purpose of this study was to detect association between genetic variation and economic trait in the porcine heart type fatty acid-binding protein gene as a candidate gene for the traits related with growth and meat quality in pigs. The H-FABP is a 15-kDa protein expressed in several tissues with high demand for fat metabolism such as cardiac and skeletal muscle and lactating mammary gland. H-FABP is small intracellular protein involved in fatty acid transport from the plasma membrane to the site of β-oxidation and/or triacylglycerol or phospholipid synthesis. In this study, H-FABP PCR-RFLP was performed in F_(2) population composed of 214 individuals form an intercross between Korean Native Boars and Landrace sows. PCR products form tow primer sets within H-FABP gene were amplified in 850bp and 700bp. Digestion of PCR products with the restriction digestion enzymes HaeⅢ and Hinf Ⅰ, revealed fragment length polymorphisms(RFL. Ps). The genotype frequencies from H-FABP/HaeⅢ was .29 for genotype DD, .53 for genotype Dd, and .15 for genotype dd, respectively. The genotype frequencies of HH, Hh, and hh from H-FABP(hinf Ⅰ was .38, .41, and .20, respectively, in the population.Relationships between their genotypes and economic traits were estimated. In H-FABP/HaeⅢ locus, there were specific genotypes(Dd and dd) associated with economic traits such as body weight. In H-FABP/Hinf Ⅰ Iocus, Genotypes of HH and Hh associated with growth traits such as body weights at 5, 12, and 30 week of age (p<.05 or p<.001) and back fat thickness, body fat including abdominal and trimmed fat (p<.001) and intramuscular fat(p<.05). The 'H'allele was positivecly associated with gaining of body weight and fatness deposition. In conclusion, a significant association of the H-FABP gene from its genetic variation was found on body weight, intramuscular fat and backfat thickness.

Evaluation of the zoonotic potential of a novel reassortant H1N2 swine influenza virus with gene constellation derived from multiple viral sources

Lee, J.H.,Pascua, P.N.Q.,Decano, A.G.,Kim, S.M.,Park, S.J.,Kwon, H.I.,Kim, E.H.,Kim, Y.I.,Kim, H.,Kim, S.Y.,Song, M.S.,Jang, H.K.,Park, B.K.,Choi, Y.K. Elsevier Science 2015 INFECTION GENETICS AND EVOLUTION Vol.34 No.-

In 2011-2012, contemporary North American-like H3N2 swine influenza viruses (SIVs) possessing the 2009 pandemic H1N1 matrix gene (H3N2pM-like virus) were detected in domestic pigs of South Korea where H1N2 SIV strains are endemic. More recently, we isolated novel reassortant H1N2 SIVs bearing the Eurasian avian-like swine H1-like hemagglutinin and Korean swine H1N2-like neuraminidase in the internal gene backbone of the H3N2pM-like virus. In the present study, we clearly provide evidence on the genetic origins of the novel H1N2 SIVs virus through genetic and phylogenetic analyses. In vitro studies demonstrated that, in comparison with a pre-existing 2012 Korean H1N2 SIV [A/swine/Korea/CY03-1½012 (CY03-1½012)], the 2013 novel reassortant H1N2 isolate [A/swine/Korea/CY0423/2013 (CY0423-12/2013)] replicated more efficiently in differentiated primary human bronchial epithelial cells. The CY0423-12/2013 virus induced higher viral titers than the CY03-1½012 virus in the lungs and nasal turbinates of infected mice and nasal wash samples of ferrets. Moreover, the 2013 H1N2 reassortant, but not the intact 2012 H1N2 virus, was transmissible to naive contact ferrets via respiratory-droplets. Noting that the viral precursors have the ability to infect humans, our findings highlight the potential threat of a novel reassortant H1N2 SIV to public health and underscore the need to further strengthen influenza surveillance strategies worldwide, including swine populations.

Trypsin inhibitor 결여 大豆品種의 탐색 및 그의 遺傳育種學的 硏究 : I. Trypsin inhibitors의 전기영동 감정방법에 의한 대두 품종별 비교 및 DEAE-cellulose에 의한 분리 I. Soybean trypsin inhibitors: electrophoretic differences among varieties and their fractionation on DEAE-cellulose

金秀一,李錫河,李弘石,文亢植,羅志英 서울大學校 農科大學 1985 서울대농학연구지 Vol.10 No.1

대두의 단백추출액을 polyacrylamide gel 전기영동에 의하여 분류하고 trypsin inhibitor (T.I) band를 동정하였다. T.I. band는 전기영동한 gel을 trypsin으로 가수분해하거나 추출액에 trypsin을 처리한 후 전기영동하거나 발색기질을 이용하여 gel을 착색시키거나 또는 gel slice의 T.I.activity를 측정하는 등 네 가지 방법을 사용하여 검정하였다. 이중 추출액을 trypsin으로 처리한 후 전기영동하는 방법과 gel slice의 T.I.activity를 측정하는 방법이 가장 적합하였으며 두 방법의 결과를 비교하여 T.I.band를 검정하는 것이 보다 확실하였다. Sephadex G-75 Chromatography 에서 물로 추출한 대두 단백질은 3 fraction으로 분리하였고 T.I.activity는 제 2 fraction 에만 나타났다. Kunitz 및 Bowman-Birk형 inhibitor는 DEAE-cellulose column chromatography로 분리하였다. Kunitz형은 5개의 fraction으로, Bowman-birk형은 4개의 fraction으로 분리되었다. 단백질 추출액과 DEAE-cellulose chormatography에서 분리된 Kuniz 및 Bowman-Birk T.I.의 polyacryamide gel 전기영동 pattern을 비교하여 본 결과, 확실하게 동정된 T.I.band는 band3과 band4로서 각각 Orf등이 발표한 Ti¹과 Ti2에 해당하였으며, 그 외에 band 6과 band 10이 T.I.로 추정되었고 band 1,2,5,7,8,9는 T.I.가 아닌 것으로 판명되었다. trypsin inhibitor 함유량은 총 trypsin units inhibited 값(T.U.I)으로 볼 때 42품종에서 25에서 76까지 품종 간에 차이가 현저하였으며 시비 및 파종기의 영향은 나타나지 않았다. Ti¹ inhibitor 를 보유하고 있는 것은 37품종이었고, Ti²를 보유하는 것은 7품종이었으며, Ti¹과 Ti²를 같이 가지고 있는 품종은 발견되지 않았다. 이러한 품종의 Ti¹,Ti² 보유 pattern은 재배조건에 의해 변화되지 않았다. 2조합의 pattern은 재배조건에 의해 변화되지 않았다. 2조합의 정역교배에서 얻은 F₁ 종자의 전기영동 pattern을 비교해 본 결과, Ti¹품종끼리의 교배종자에서는 정역교배에 상관없이 Ti¹ inhibitor 만 나타났고 Ti¹품종과 Ti²품종의 교배종자에서는 Ti²를 모본으로 한 종자에서는 Ti¹과 Ti² 두 inhibitor가 검출되었으나 여교배에서는 모본의 Ti¹ inhibitor만 검출되었다. 여교배에서 Ti¹만 나타난 것은 분석시료 종자가 적었고 교배의 여부를 확인할 수 없어 모본의 세포질적 영향에 의한 것인지 또는 자가수정에 의한 것인지 분명치 않았다. The protein extracts from soybean seeds were examined by polyacrylamide gel electrophoresis and the trypsin inhibitor (T.I) bands were detected. The water-extractable protein was fractionated into three fractions by Sephadex G-75 gel filtration. The T.I activity was found only in the second fraction. Kunitz and Bowman-Birk inhibitors were fractionated by DEAE-cellulose chromatography into seven and six fractions, respectively. In kunitz inhibitor, 5 fractions were found to have T.I activity and 4 fractions in Bowman-Birk inhibitor. From the and patterns of the protein extracts and those of DEAE-cellulose chromatographic fractions, it was found that band 3 and 4 were T.I. band, corresponding to Ti¹ and Ti² band, respectively. In addition, band 6 and 10 were presumed to be T.I. band. Of the 42 varieties sampled, 35 revealed only Ti¹ band and 7 only Ti² band. The T.I. band patterns were not changed by the culture condition. The T.I. content, when expressed as the number of trypsin units inhibited (T.U.I), showed remarkable differences from 25 to 76 between varieties. The seedtime and fertilization condition had no effect on the T.I. content. Judged from the results of F ₁seeds analysis, we assumed that Ti¹ and Ti²band were controlled by codominant allele at a single locus.

방사성 동위원소옥소(131I)에 의한 갑상선질환의 임상적 연구

이정상,이문호,고창순,노흥규,구인서,서환조,이경자,이홍규 대한핵의학회 1970 핵의학 분자영상 Vol.4 No.2

서울대학교 의과대학 내과학교실 및 방사성 동위원소 진료실에서 1960년 5월부터 1969년 10월까지 진료한 2,658명의 각종 갑상선 질환 환자에 대하여 131I에 의한 각종 갑상선 기능 검사 및 기능 항진증 환자에 대한 131I의 치료 성적을 종합 검토하여 아래와 같은 결론을 얻었다. 1) 2,658명의 갑상선 질환 환자중 독성 미만성 선종이 929명(34.9%)으로 가장 많고 비중독성 미만성 선종 및 비중독성 결절성 선종이 각각 762명(28.7%), 699명(26.3%)이며 기능저하가 210명(7.9%), 독성 결절성 선종이 58명(2.2%)였다. 2) 갑상선 질환의 성별 발생 빈도는 남자 300명(11.4%), 여자 2,358명(88.6%)로서 그 비는 1:8였다. 3) 연령별 발생 빈도는 20∼49세에서 전체의 79.1%인 2,102명이며 기능 항진증의 경우는 79.0%에 달하였다. 4) 각종 갑상선 기능 검사중 131I 섭취율, 131I 혈청내 방사능 BMR치등에 대한 고찰을 하는 한편 기능항진 및 저하증때 나타내는 각종 자학증세를 관찰하였다. 5) 갑상선 기능 항진증 환자 867명에 대하여 131I 치료를 하고 그 중 579명에서 47.8%의 초회 치료율을 확인하였다. 6) 131I 투여 후의 합병증인 기능 저하증의 발생 빈도는 초회 투여에서 6.75%였다. 7) 갑상선의 $quot; A summary of the clinical data of the (131)^I-thyroid function tests and the therapeutic results of 1(31I)^ among the 2,658 patients of various thyroid diseases treated over the past 10 years from May 1960 to Oct. 1969 at the Radioisotope Clinci and Laboratory, SNUH were presented and discussed. 1) The patients examined consisted of 929 cases (34.9%) of diffuse toxic goiter, 762 cases (28.7%) of diffuse nontoxic goiter, 699 cases (26.3%) of nodular nontoxic goiter, 58 cases (2.2%) of nodular toxic goiter and 210 cases (7.9%) of hypothyroidism. 2) There were 300 (11.4%) male and 2358 (88.6%) female, showing a ratio of 1:8. 3) The majority of patients (79.1%) were in the 3rd-5th decade of their lives. 4) The normal ranges, diagnostic values of (131)^I uptake test, 48 hrs serum activity, BMR and main subjective symptoms of various thyroid diseases were discussed. 5) In the 579 patients among 867 cases with hyperthyroidism treated with (131)^I, 47.8% were confirmed to be cured completely after single therapeutic doses. 6) The complications of 131I therapy were discussed and myxedema had developed in 6.75% of our patients. 7) The results of (131)^I thyroid function tests were analysed among the 160 cases of thyroid diseases which were confirmed the diagnosis with histopathological measures.

G.I.S.H. 수술과 복식 전자궁적출술의 비교

지일운,허준용,서호석,박용균,조수용,주갑순,이규완,구병삼 대한산부인과내시경학회 1995 대한산부인과내시경학회잡지 Vol.7 No.1

Effects of dextrorotatory morphinans on brain Na⁺ channels expressed in Xenopus oocytes

Lee, J.H.,Shin, E.J.,Jeong, S.M.,Lee, B.H.,Yoon, I.S.,Lee, J.H.,Choi, S.H.,Kim, Y.H.,Pyo, M.K.,Lee, S.M.,Chae, J.S.,Rhim, H.,Oh, J.W.,Kim, H.C.,Nah, S.Y. North-Holland ; Elsevier Science Ltd 2007 european journal of pharmacology Vol.564 No.1

We previously demonstrated that dextromethorphan (DM; 3-methoxy-17-methylmorphinan) analogs have neuroprotective effects. Here, we investigated the effects of DM, three of its analogs (DF, 3-methyl-17-methylmorphinan; AM, 3-allyloxy-17-methoxymorphian; and CM, 3-cyclopropyl-17-methoxymorphinan) and one of its metabolites (HM; 3-methoxymorphinan), on Na<SUP>+</SUP> channel activity. We used the two-microelectrode voltage-clamp technique to test the effects of DM, DF, AM, CM and HM on Na<SUP>+</SUP> currents (I<SUB>Na</SUB>) in Xenopus oocytes expressing cRNAs encoding rat brain Nav1.2 α and β1 or β2 subunits. In oocytes expressing Na<SUP>+</SUP> channels, DM, DF, AM and CM, but not HM, induced tonic and use-dependent inhibitions of peak I<SUB>Na</SUB> following low- and high-frequency stimulations. The order of potency for the inhibition of peak I<SUB>Na</SUB> was AM-CM > DM=DF. The DM, DF, AM and CM-induced tonic inhibitions of peak I<SUB>Na</SUB> were voltage-dependent, dose-dependent and reversible. The IC<SUB>50</SUB> values for DM, DF, AM and CM were 116.7+/-14.9, 175.8+/-16.9, 38.6+/-15.5, and 42.5+/-8.5 μM, respectively. DM and its analogs did not affect the steady-state activation and inactivation voltages. AM and CM, but not DM and DF, inhibited the plateau I<SUB>Na</SUB> more effectively than the peak I<SUB>Na</SUB> in oocytes expressing inactivation-deficient I1485Q-F1486Q-M1487Q (IFMQ3) mutant channels; the IC<SUB>50</SUB> values for AM and CM in this system were 8.4+/-1.3 and 8.7+/-1.3 μM, respectively, for the plateau I<SUB>Na</SUB> and 43.7+/-5.9 and 32.6+/-7.8 μM, respectively, for the peak I<SUB>Na</SUB>. These results collectively indicate that DM and its analogs could be novel Na<SUP>+</SUP> channel blockers acting on the resting and open states of brain Na<SUP>+</SUP> channels.