<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>

Urinary concentration of transforming growth factor-&bgr;-inducible gene-h3(&bgr;ig-h3) in patients with Type 2 diabetes mellitus

Cha, D. R.,Kim, I. S.,Kang, Y. S.,Han, S. Y.,Han, K. H.,Shin, C.,Ji, Y. H.,Kim, N. H. Blackwell Science Ltd 2005 Diabetic medicine Vol.22 No.1

<P>Abstract</P><P>Aims </P><P>The expression of TGF&bgr;-inducible gene h3(&bgr;ig-h3) has been used to assess the biological activity of TGF&bgr; in the kidney. In this study, we investigated whether the urinary concentration of &bgr;ig-h3 is associated with diabetic nephropathy in patients with Type 2 diabetes mellitus. We also evaluated the relationship between the urinary concentration of &bgr;ig-3 and proteinuria and microalbuminuria (AER) in a normal healthy population and in Type 2 diabetes patients.</P><P>Methods </P><P>Four hundred and seventy-nine Type 2 diabetic patients without non-diabetic kidney diseases and 528 healthy control subjects were enrolled. The study subjects were divided into five groups: a non-diabetic healthy control group with normal ACR (<I>n</I> = 443), a non-diabetic healthy control group with microalbuminuria (<I>n</I> = 85), a normoalbuminuric diabetic group (<I>n</I> = 198), a microalbuminuric diabetic group (<I>n</I> = 155) and an overt proteinuria group (<I>n</I> = 126). Urinary levels of &bgr;ig-h3 were measured by enzyme-linked immunosorbent assay.</P><P>Results </P><P>(i) Urinary excretion of &bgr;ig-h3 was significantly higher in the diabetic groups than in the controls, even in the normoalbuminuric stage (25.02 ± 8.84 vs. 18.67 ± 6.56, <I>P</I> = 0.03). In diabetic patients, urinary &bgr;ig-h3 levels increased significantly as diabetic nephropathy advanced (25.02 ± 8.84 vs. 34.06 ± 24.55 vs. 169.63 ± 57.33, <I>P</I> < 0.001). (ii) Proteinuria was found to be significantly correlated with urinary &bgr;ig-h3 (healthy control; <I>r</I> = 0.137, <I>P</I> = 0.019, diabetic patients; <I>r</I> = 0.604, <I>P</I> < 0.001). ACR was also found to be significantly related with urinary &bgr;ig-h3 in diabetic patients (<I>r =</I> 0.383, <I>P</I> = 0.006). (iii) In diabetic patients, urinary &bgr;ig-h3 was significantly related with systolic and diastolic blood pressure (systolic blood pressure: <I>r</I> = 0.436, <I>P</I> = 0.024; diastolic blood pressure, <I>r</I> = 0.365, <I>P</I> = 0.042), total cholesterol and HbA<SUB>1c</SUB> (cholesterol: <I>r</I> = 0.169, <I>P</I> = 0.03, HbA<SUB>1c</SUB>; <I>r</I> = 0.387, <I>P</I> = 0.044). Logistic regression analyses showed that urinary &bgr;ig-h3 was associated with a significant increase in the risk of microalbuminuria and proteinuria in diabetic patients.</P><P>Conclusions </P><P>Longitudinal monitoring of urinary &bgr;ig-h3 may improve the likelihood of detecting diabetic nephropathy at an earlier stage and &bgr;ig-h3 could be a sensitive marker of diabetic kidney disease progression.</P>

Induction of bone formation by <i>Escherichia coli</i>‐expressed recombinant human bone morphogenetic protein‐2 using block‐type macroporous biphasic calcium phosphate in orthotopic and ectopic rat models

Park, J‐,C.,So, S‐,S.,Jung, I‐,H.,Yun, J‐,H.,Choi, S‐,H.,Cho, K‐,S.,Kim, C‐,S. Blackwell Publishing Ltd 2011 Journal of periodontal research Vol.46 No.6

<P><I>Park J‐C, So S‐S, Jung I‐H, Yun J‐H, Choi S‐H, Cho K‐S, Kim C‐S. Induction of bone formation by</I> Escherichia coli<I>‐expressed recombinant human bone morphogenetic protein‐2 using block‐type macroporous biphasic calcium phosphate in orthotopic and ectopic rat models. J Periodont Res 2011; 46: 682–690. © 2011 John Wiley & Sons A/S</I></P><P><B>Background and Objective: </B> The potential of the <I>Escherichia coli</I>‐expressed recombinant human bone morphogenetic protein‐2 (ErhBMP‐2) to support new bone formation/maturation using a block‐type of macroporous biphasic calcium phosphate (bMBCP) carrier was evaluated in an orthotopic and ectopic rat model.</P><P><B>Material and Methods: </B> Critical‐size (Φ 8 mm) calvarial defects and subcutaneous pockets in 32 Sprague–Dawley rats received implants of rhBMP‐2 (2.5 μg) in a bMBCP carrier or bMBCP alone (control). Implant sites were evaluated using histological and histometric analysis following 2‐ and 8‐wk healing intervals (eight animals/group/interval).</P><P><B>Results: </B> ErhBMP‐2/bMBCP supported significantly greater bone formation at 2 and 8 wk (10.8% and 25.4%, respectively) than the control at 2 and 8 wk (5.3% and 14.0%, respectively) in calvarial defects (<I>p</I> < 0.01). Bone formation was only observed for the ErhBMP‐2/bMBCP ectopic sites and was significantly greater at 8 wk (7.5%) than at 2 wk (4.5%) (<I>p</I> < 0.01). Appositional and endochondral bone formation was usually associated with a significant increase in fatty marrow at 8 wk. The bMBCP carrier showed no evidence of bioresorption.</P><P><B>Conclusion: </B> ErhBMP‐2/bMBCP induced significant bone formation in both calvarial and ectopic sites. Further study appears to be required to evaluate the relevance of the bMBCP carrier.</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>

Effect of Follicle Stimulation Hormone and Luteinizing Hormone on Cumulus Cell Expansion and <i>In Vitro</i> Nuclear Maturation of Canine Oocytes

Lee, H-S,Seo, Y-I,Yin, X-J,Cho, S-G,Lee, S-S,Kim, N-H,Cho, S-K,Kong, I-K KOCH NEFF UND OETINGER 2007 REPRODUCTION IN DOMESTIC ANIMALS Vol.42 No.6

<P>Contents</P><P>In general, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) play important roles in the regulation of cumulus cell expansion and oocyte maturation. We investigated the effects of supplementation of FSH or LH in <I>in vitro</I> maturation (IVM) medium on the incidence of cumulus cell expansion and nuclear maturation in canine oocytes. Cumulus–oocyte complexes (COCs) were cultured in TCM-199 supplemented with 10% foetal bovine serum (FBS), 1 mg/ml cysteine, 0.2 m<SMALL>M</SMALL> pyruvic acid and different concentrations of FSH or LH (control, 0.5, 5 or 50 <I>μ</I>g/ml) at 38.5°C, 5% CO<SUB>2</SUB> in air for 72 h. The cumulus cell expansion was measured by microscopic visualization, and nuclear maturation of denuded oocytes was determined by staining with 10 <I>μ</I>g/ml Hoechst33342 for 30 min. The cumulus cell expansion in the 5 <I>μ</I>g/ml FSH group (397.2 ± 64.3 <I>μ</I>m) was significantly higher than those in the control, 0.5, and 50 <I>μ</I>g/ml FSH groups (168.3 ± 19.1, 286.0 ± 69.7 and 300.0 ± 84.3 <I>μ</I>m, respectively; p < 0.05). However, there was no difference in cumulus cell expansion among the control, 0.5, 5 and 50 <I>μ</I>g/ml LH groups (165.6 ± 20.2, 160 ± 26.5, 172 ± 20.5 and 168 ± 23.1 <I>μ</I>m, respectively; p > 0.05). After 72 h of IVM, the proportion of nuclear development to the MI–MII stage in the 0.5 <I>μ</I>g/ml FSH group (15.1%) was higher than those in the control, 0.5 and 50 <I>μ</I>g/ml FSH groups (0.9%, 6.5% and 8.0%, respectively; p < 0.05). However, there was no significant difference in nuclear maturation to the MI-MII stage among control, 0.5, 5 and 50 <I>μ</I>g/ml LH groups (4.6%, 2.3%, 5.4% and 8.6%, respectively; p > 0.05). This study indicated that a FSH supplement in IVM medium can increase cumulus cell expansion and nuclear maturation, while the nuclear maturation rate remained low. Further studies are required to improve the nuclear development to the MI–MII stages in canine oocytes.</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>

G.I.S.H. 수술과 복식 전자궁적출술의 비교

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

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.

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.

Genetic and phylogenetic characterizations of a novel genotype of highly pathogenic avian influenza (HPAI) H5N8 viruses in 2016/2017 in South Korea

Kim, Y.I.,Park, S.J.,Kwon, H.I.,Kim, E.H.,Si, Y.J.,Jeong, J.H.,Lee, I.W.,Nguyen, H.D.,Kwon, J.J.,Choi, W.S.,Song, M.S.,Kim, C.J.,Choi, Y.K. Elsevier Science 2017 INFECTION GENETICS AND EVOLUTION Vol.53 No.-

<P>During the outbreaks of highly pathogenic avian influenza (HPAI) H5N6 viruses in 2016 in South Korea, novel H5N8 viruses were also isolated from migratory birds. Phylogenetic analysis revealed that the HA gene of these H5N8 viruses belonged to clade 2.3.4.4, similarly to recent H5Nx viruses, and originated from A/Brk/Korea/Gochang1/14(H5N8), a minor lineage of H5N8 that appeared in 2014 and then disappeared. At least four reassortment events occurred with different subtypes (H5N8, H7N7, H3N8 and H10N7) and a chicken challenge study revealed that they were classified as HPAI viruses according to OIE criteria. (C) 2017 Elsevier B.V. All rights reserved.</P>