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      • 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>

      • In vitro antibacterial activity and major bioactive components of Cinnamomum verum essential oils against cariogenic bacteria, Streptococcus mutans and Streptococcus sobrinus

        Choi, O.,Cho, S.K.,Kim, J.,Park, C.G.,Kim, J. China Humanity Technology Publishing House 2016 Asian Pacific journal of tropical biomedicine Vol.6 No.4

        Objective: To evaluate the antibacterial activity of Cinnamomum verum (C. verum) from 32 different essential oils against cariogenic bacteria, Streptococcus mutans (S. mutans) and Streptococcus sobrinus (S. sobrinus). Methods: The antibacterial activities of each essential oil were individually investigated against S. mutans and S. sobrinus. The essential oil of C. verum was selected for further evaluation against S. mutans and S. sobrinus. Gas chromatography mass spectrometry was used to determine the major constituents of C. verum essential oil. In addition, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration of the most effective constituent was investigated. Results: The essential oil from C. verum exhibited the greatest antibacterial activity. Gas chromatography mass spectrometry analysis revealed that the major components of C. verum essential oil were cinnamaldehyde (56.3%), cinnamyl acetate (7.1%) and β-phellandrene (6.3%). The MIC of cinnamaldehyde was measured using broth dilution assays. The MIC of cinnamaldehyde was 0.02% (v/v) against both bacterial strains tested. The minimum bactericidal concentration of cinnamaldehyde against S. mutans and S. sobrinus were 0.2% and 0.1% (v/v), respectively. Conclusions: The essential oil of C. verum and its major component cinnamaldehyde possessed considerable in vitro antibacterial activities against cariogenic bacteria, S. mutans and S. sobrinus strains. These results showed that the essential oil of C. verum and its bioactive component, cinnamaldehyde, have potential for application as natural agents for the prevention and treatment of dental caries.

      • Regulation of cancer cell death by a novel compound, C604, in a c-Myc-overexpressing cellular environment

        Jo, M.J.,Paek, A.R.,Choi, J.S.,Ok, C.Y.,Jeong, K.C.,Lim, J.H.,Kim, S.H.,You, H.J. North-Holland ; Elsevier Science Ltd 2015 european journal of pharmacology Vol.769 No.-

        <P>The proto-oncogene c-Myc has been implicated in a variety of cellular processes, such as proliferation, differentiation and apoptosis. Several c-Myc targets have been studied; however, selective regulation of c-Myc is not easy in cancer cells. Herein, we attempt to identify chemical compounds that induce cell death in c-Myc-overexpressing cells (STF-cMyc and STF-Control) by conducting MTS assays on approximately 4000 chemical compounds. One compound, C604, induced cell death in STF-cMyc cells but not STF-Control cells. Apoptotic proteins, including caspase-3 and poly(ADP-ribose) polymerase (PAPP), were cleaved in C604-treated STF-cMyc cells. In addition, 5W620, HCT116 and NCI-H23 cells, which exhibit higher basal levels of c-Myc, underwent apoptotic cell death in response to C604, suggesting a role for C604 as an inducer of apoptosis in cancer cells with c-Myc amplification. C604 induced cell cycle arrest at the G2/M phase in cells, which was not affected by apoptotic inhibitors. Interestingly, C604 induced accumulation of c-Myc and Cdc25A proteins. In summary, a chemical compound was identified that may induce cell death in cancer cells with c-Myc amplification specifically through an apoptotic pathway. (C) 2015 Elsevier B.V. All rights reserved.</P>

      • <i>CYP2A6</i> and <i>ERCC1</i> polymorphisms correlate with efficacy of S-1 plus cisplatin in metastatic gastric cancer patients

        Park, S R,Kong, S-Y,Nam, B-H,Choi, I J,Kim, C G,Lee, J Y,Cho, S J,Kim, Y W,Ryu, K W,Lee, J H,Rhee, J,Park, Y-I,Kim, N K Nature Publishing Group 2011 The British journal of cancer Vol.104 No.7

        <P><B>Background:</B></P><P>We evaluated the association between polymorphisms of cytochrome P450 2A6 (<I>CYP2A6</I>)/excision repair cross-complementation group 1 (<I>ERCC1</I>)/X-ray repair cross-complementing group 1(<I>XRCC1</I>) and treatment outcomes of metastatic gastric cancer (MGC) patients treated with S-1/cisplatin.</P><P><B>Methods:</B></P><P>Among MGC patients (<I>n</I>=108), who received S-1 (40 mg m<SUP>−2</SUP> b.i.d., days 1–14) and cisplatin (60 mg m<SUP>−2</SUP>, day 1) every 3 weeks, we analysed the wild-type allele (<I>W</I>) and variants (<I>V</I>) of <I>CYP2A6</I> (<I>*4</I>, <I>*7, *9, *10</I>), and the polymorphisms of <I>ERCC1</I> (rs11615, rs3212986) and <I>XRCC1</I> (rs25487).</P><P><B>Results:</B></P><P>Patients having fewer <I>CYP2A6</I> variants had better response rates (<I>W</I>/<I>W vs W</I>/<I>V</I> other than <I>*1/*4 vs V</I>/<I>V</I> or <I>*1/*4</I>=66.7 <I>vs</I> 58.3 <I>vs</I> 32.3% <I>P</I>=0.008), time to progression (TTP) (7.2 <I>vs</I> 6.1 <I>vs</I> 3.5 months, <I>P</I>=0.021), and overall survival (23.2 <I>vs</I> 15.4 <I>vs</I> 12.0 months, <I>P</I>=0.004). <I>ERCC1 19442C</I>><I>A</I> (rs3212986) was also associated with response rate (<I>C/C</I>, 46.7% <I>vs C/A</I>, 55.3% <I>vs A/A</I>, 87.5%) (<I>P</I>=0.048) and TTP (4.4 <I>vs</I> 7.6 <I>vs</I> 7.9 months) (<I>P</I>=0.012). Patients carrying both risk genotypes of <I>CYP2A6</I> (<I>V</I>/<I>V</I> or <I>1/*4</I>) and <I>ERCC1 19442C</I>><I>A</I> (<I>C/C</I>) <I>vs</I> those carrying none showed an adjusted odds ratio of 0.113 (<I>P</I>=0.004) for response, and adjusted hazard ratios of 3.748 (<I>P</I>=0.0001) for TTP and 2.961 (<I>P</I>=0.006) for death.</P><P><B>Conclusion:</B></P><P>Polymorphisms of <I>CYP2A6</I> and <I>ERCC1 19442C</I>><I>A</I> correlated with the efficacy of S-1/cisplatin.</P>

      • SCISCIESCOPUS

        Radotinib induces high cytotoxicity in c-KIT positive acute myeloid leukemia cells

        Heo, S.K.,Noh, E.K.,Kim, J.Y.,Jo, J.C.,Choi, Y.,Koh, S.,Baek, J.H.,Min, Y.J.,Kim, H. North-Holland 2017 European journal of pharmacology Vol.804 No.-

        <P>Previously, we reported that radotinib, a BCR-ABL1 tyrosine kinase inhibitor, induced cytotoxicity in acute myeloid leukemia (AML) cells. However, the effects of radotinib in the subpopulation of c-KIT-positive AML cells were unclear. We observed that low-concentration radotinib had more potent cytotoxicity in c-KIT-positive cells than c-KIT-negative cells from AML patients. To address this issue, cell lines with high c-KIT expression, HEL92.1.7, and moderate c-KIT expression, H209, were selected. HEL92.1.7 cells were grouped into intermediate and high c-HIT expression populations. The cytotoxicity of radotinib against the HEL92.1.7 cell population with intermediate c-HIT expression was not different from that of the population with high c-KIT expression. When H209 cells were grouped into c-KIT expression-negative and c-HIT expression-positive populations, radotinib induced cytotoxicity in the c-KIT-positive population, but not the c-KIT-negative population. Thus, radotinib induces cytotoxicity in c-KIT-positive cells, regardless of the c-KIT expression intensity. Therefore, radotinib induces significant cytotoxicity in c-KIT-positive AML cells, suggesting that radotinib is a potential target agent for the treatment of c-KIT-positive malignancies including AML.</P>

      • Towards high performance unique microstructures of Co<sub>9</sub>S<sub>8</sub>//CoFe<sub>2</sub>O<sub>4</sub> for asymmetric supercapacitor

        Patil, S.J.,Lokhande, A.C.,Park, J.S.,Kim, J.H.,Kim, Y.B.,Choi, B.C.,Park, S.H.,Jung, S.H.,Lee, D.W. Elsevier 2018 Journal of industrial and engineering chemistry Vol.61 No.-

        <P><B>Abstract</B></P> <P>Herein, we have proposed asymmetric supercapacitor device to achieve empirical electrochemical performance based on binder-free Co<SUB>9</SUB>S<SUB>8</SUB> and CoFe<SUB>2</SUB>O<SUB>4</SUB> electrodes. The unique architecture and porous surface of the prepared electrodes were analyzed using electron microscopy and Brunauer–Emmett–Teller technique. Electrochemical properties of Co<SUB>9</SUB>S<SUB>8</SUB> and CoFe<SUB>2</SUB>O<SUB>4</SUB> electrode were employed in a three-electrode cell-configuration that exhibits a capacitance of 817 and 1203Fg<SUP>−1</SUP>, respectively. Co<SUB>9</SUB>S<SUB>8</SUB>//CoFe<SUB>2</SUB>O<SUB>4</SUB> asymmetric supercapacitor reveals a high capacitance of 79.11Fg<SUP>−1</SUP> with 28.88Whkg<SUP>−1</SUP> energy density and superior cyclic stability over 2500 cycles (∼87%). These results suggest that prepared electrodes have a great potential for practical applications.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Unique-microstructures of C<SUB>o9</SUB>S<SUB>8</SUB> and CoFe<SUB>2</SUB>O<SUB>4</SUB> electrodes were prepared. </LI> <LI> C<SUB>o9</SUB>S<SUB>8</SUB>//CoFe<SUB>2</SUB>O<SUB>4</SUB> supercapacitor exhibits an energy density of 28.88Whkg<SUP>−1</SUP>. </LI> <LI> The assembled Co<SUB>9</SUB>S<SUB>8</SUB>//CoFe<SUB>2</SUB>O<SUB>4</SUB> supercapacitor delivers a superior rate capability. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>The Ragone plot shows the electrochemical performance of the Co<SUB>9</SUB>S<SUB>8</SUB>//CoFe<SUB>2</SUB>O<SUB>4</SUB> asymmetric supercapacitor device, and inset shows the BET surface area plot.</P> <P>[DISPLAY OMISSION]</P>

      • SIGN-R1, a C-type lectin, enhances apoptotic cell clearance through the complement deposition pathway by interacting with C1q in the spleen

        Prabagar, M G,Do, Y,Ryu, S,Park, J-Y,Choi, H-J,Choi, W-S,Yun, T J,Moon, J,Choi, I-S,Ko, K,Ko, K,Young Shin, C,Cheong, C,Kang, Y-S Macmillan Publishers Limited 2013 Cell death and differentiation Vol.20 No.4

        Complements, such as C1q and C3, and macrophages in the splenic marginal zone (MZMs) play pivotal roles in the efficient uptake and processing of circulating apoptotic cells. SIGN-R1, a C-type lectin that is highly expressed in a subpopulation of MZMs, regulates the complement fixation pathway by interacting with C1q, to fight blood-borne Streptococcus pneumoniae. Therefore, we examined whether the SIGN-R1-mediated classical complement pathway plays a role in apoptotic cell clearance and immune tolerance. SIGN-R1 first-bound apoptotic cells and this binding was significantly enhanced in the presence of C1q. SIGN-R1–C1q complex then immediately mediated C3 deposition on circulating apoptotic cells in the MZ, leading to the efficient clearance of them. SIGN-R1-mediated C3 deposition was completely abolished in the spleen of SIGN-R1 knockout (KO) mice. Given that SIGN-R1 is not expressed in the liver, we were struck by the finding that C3-deposited apoptotic cells were still found in the liver of wild-type mice, and dramatically reduced in the SIGN-R1 KO liver. In particular, SIGN-R1 deficiency caused delayed clearance of apoptotic cells and aberrant secretion of cytokines, such as TNF-α, IL-6, and TGF-β in the spleen as well as in the liver. In addition, anti-double- and single-stranded DNA antibody level was significantly increased in SIGN-R1-depleted mice compared with control mice. These findings suggest a novel mechanism of apoptotic cell clearance which is initiated by SIGN-R1 in the MZ and identify an integrated role of SIGN-R1 in the systemic clearance of apoptotic cells, linking the recognition of apoptotic cells, the opsonization of complements, and the induction of immune tolerance.

      • SIGN-R1, a C-type lectin, enhances apoptotic cell clearance through the complement deposition pathway by interacting with C1q in the spleen

        MG Prabagar,Y Do,S Ryu,J-Y Park,H-J Choi,W-S Choi,TJ Yun,J Moon,I-S Choi,K Ko,K Ko,C Young Shin,C Cheong,Y-S Kang 한국당과학회 2013 한국당과학회 학술대회 Vol.2013 No.1

        Complements, such as C1q and C3, and macrophages in the splenic marginal zone (MZMs) play pivotal roles in the efficient uptake and processing of circulating apoptotic cells. SIGN-R1, a C-type lectin that is highly expressed in a subpopulation of MZMs, regulates the complement fixation pathway by interacting with C1q, to fight blood-borne Streptococcus pneumoniae. Therefore, we examined whether the SIGN-R1-mediated classical complement pathway plays a role in apoptotic cell clearance and immune tolerance. SIGN-R1 first-bound apoptotic cells and this binding was significantly enhanced in the presence of C1q. SIGN-R1-C1q complex then immediately mediated C3 deposition on circulating apoptotic cells in the MZ, leading to the efficient clearance of them. SIGN-R1-mediated C3 deposition was completely abolished in the spleen of SIGN-R1 knockout (KO) mice. Given that SIGN-R1 is not expressed in the liver, we were struck by the finding that C3-deposited apoptotic cells were still found in the liver of wild-type mice, and dramatically reduced in the SIGN-R1 KO liver. In particular, SIGN-R1 deficiency caused delayed clearance of apoptotic cells and aberrant secretion of cytokines, such as TNF-α, IL-6, and TGF-β in the spleen as well as in the liver. In addition, anti-double- and single-stranded DNA antibody level was significantly increased in SIGN-R1-depleted mice compared with control mice. These findings suggest a novel mechanism of apoptotic cell clearance which is initiated by SIGN-R1 in the MZ and identify an integrated role of SIGN-R1 in the systemic clearance of apoptotic cells, linking the recognition of apoptotic cells, the opsonization of complements, and the induction of immune tolerance.

      • SCOPUSKCI등재

        정상인 및 당뇨병환자에서의 경구당부하시 혈중 Insulin과 C-Peptide의 변동

        이명철,고창순,최성재,김응진,민헌기 대한핵의학회 1977 핵의학 분자영상 Vol.11 No.1

        저자들은 정상인 및 당뇨병환자에서 insulin과 C-peptide의 변동양상의 의의를 관찰하고 또한 비만이 insulin 반응에 영향을 끼치는 것을 보고자 정상인 15명 (비비만형 10명, 비만형 5명), 중등도당뇨병환자 22례 (비비만형 13례, 비만형 9례) 및 중증당뇨병환자 9례, 총 46명을 대상으로 경구적 당부하시험을 시행하고 각 혈중 insulin과 C-peptide를 방사면역법으로 측정하여 다음과 같은 결과를 얻었기에 보고하는 바이다. 1) 10명의 비비만형정상인에서의 insulin치는 공복시 및 100 gm 경구당부하후 30, 60, 90, 120분에서 각각 15.7±3.4, 48.3±9.8, 4.4±6.7, 37.4±6.5 및 26.0±4.2uU/ml(Mean±S.E.)이고 C-peptide는 각각 1.9±0.3, 3.9±0.6, 6.3±0.6, 5.7±0.5 및 4.0±0.5 ng/ml로서 insulin가 C-peptide 평행한 반응을 보였고 insulin은 30분에서 최고치를 나타낸 반면 C-peptide는 60분에서 최고치를 보였다. 2) 비만형정상인 5례에서 insulin은 각각 38.9±12.3, 59.5±12.3, 59.2±17.1, 56.1±20.0 및 48.4±17.2uU/ml이고 C-peptide는 각각 5.5±0.4, 6.8±0.5, 7.9±0.8, 7.9±0.8 및 7.8±2.0ng/ml로서 비비만형에 비하여 반응이 현저히 증가함을 보였다. 3) 13례의 비비만형중등도당뇨병환자의 혈장내 insulin은 각각 27.1±4.9, 44.1±6.0, 37.3±6.6, 35.5±8.1 및 34.7±10.7uU/ml이고 C-peptide는 각각 2.7±0.4, 4.9±0.7, 6.5±0.5, 7.0±0.3 및 6.7±1.0ng/ml로서 비비만형정상군에 비하여 insulin 및 C-peptide의 차이는 없으나 지연되는 양상을 보였다. 4) 비비만형중등도당뇨병환자 9명에서의 insulin은 각각 22.1±7.9, 80.0±19.3, 108.0±27.0, 62.0±17.6 및 55.5±10.1 uU/ml이었으며 C-peptide는 5.2±0.4, 8.0±1.0, 10.4±1.6, 10.4±1.7 및 10.0±10ng/ml로서 insulin과 C-peptide 반응이 비비만형중둥도당뇨병환자군에 비해 각각 항진됨을 볼 수 있었다. 5) 중증당뇨병환자 9례에서의 혈중 insulin은 8.0±3.8, 12.1±3.5, 16.8±4.6, 19.6±5.2 및 15.0±5.0uU/ml이며 C-peptide는 1.6±0.3, 2.4±0.4, 4.1±0.6, 4.0±0.8 및 4.5±0.7ng/ml로서 insulin과 C-peptide가 각각 현저히 감소하였다. 이 각 당뇨병환자군에서의 총 insulin 및 C-peptide 면적, 그리고 insulinogenic index와 C-peptide index를 산출한 결과 당뇨병정도에 따른 유의한 차이를 관찰하였다. The present study was undertaken to evaluate the significance of the insulin and the C-peptide rseponse to oral glucose loads in normal and diabetic subjects and to establish the effects of the obesity. In this study, the authors have measured plasma insulin and C-peptide by means of radioimmunoassay in 10 nonobese normal, 5 obese normal, 13 nonobese moderate diabetic patients, 9 obese moderate diabetic patients and 9 severe diabetic patients. The results obtained were as follows; 1) In 10 nonobese normal subjects, the plasma insulin level at fasting state and at 30, 60, 90, and 120 min after oral glucose loads were 15.7±3.4, 48.3±9.8, 40.4±6.7, 37.4±6.5 and 26.0±4.2uU/ml(Mean±S.E.) and C-peptide were 1.9±0.3, 3.9±0.6, 6.3±0.6, 5.7±0.5 and 4.0±0.5ng/ml. The change of C-peptide was found to go almost parallel with that of insulin and the insulin value reaches to the highest level at 30 min whereas C-peptide reaches to its peak at 60min. 2) The plasma insulin level in 5 obese normal subjects were 38.5±12.3, 59.2±17.1, 56.1±20.0 and 48.4±17.2 uU/ml and the C-peptide were 5.5±0.4, 6.8±0.5, 7.9±0.8, 7.9±0.8 and 7.8±2.0ng/ml. The insulin response appeared to be greater than nonobese normal subjects. 3) In 13 nonobese moderate diabetic patients, the plasma insulin levels were 27.1±4.9, 44.1±6.0, 37.3±6.6, 35.5±8.1 and 34.7±10.7uU/ml and the C-peptide levels were 2.7±0.4, 4.9±0.7, 6.5±0.5, 7.0±0.3 and 6.7±1.0ng/ml. There was little significance compared to nonobese normal groups but delayed pattern is noted. 4) In 9 obese moderated diabetic patients, the plasma insulin levels were 22.1±7.9, 80.0±19.3, 108.0±27.0, 62.0±17.6 and 55.5±10.luU/ml and the C-peptide levels were 5.2±0.4, 8.0±1.0, 10.4±1.6, 10.4±1.7 and 10.1±1.0ng/ml and its response was also greater than that of nonobese moderate diabetic patients. 5) The plasma insulin concentrations in 9 severe diabetic subjects were 8.0±3.8, 12.1±3.5, 16.8±4.6, 19.6±5.2 and 15.0±5.0uU/ml and the C-peptide levels were 1.6±0.3, 2.4/ml and the insulin and C-peptide responses were markedly reduced in severe diabetic groups. 6) There were significant differences between each groups of patients on the magnitude of total insulin or C-peptide areas, the insulinogenic index and the C-peptide index. $quot;

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