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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>

      • KCI등재

        Role of the Meckel’s Cartilage in Embryonic Mandibular Development of Mice

        J. W Choi,S. B Han,J. H Sung,H. I Shin 대한구강악안면병리학회 2005 대한구강악안면병리학회지 Vol.29 No.5

        Mecke!'s car t ilage is one of the ea rliest structu re to appear in a mandible derived from the lï rst branchi a l a rch and serves as the primorclium I"or the formation 01‘ mandible‘ mall eus. incus. and sphenomandibular li gament However. its direct role a nd the mechanism in mandibular clevelopment a re not well elucidated. 1'0 address t his Issue‘ we observed morphol ogical and histological changes and gene expression patterns in the Mecke!'s cart ilage 01" a cleveloping mouse. I"rom E13.5 to E18.5 embryos. using skeletal preparation samples a ncl routinely prepa red s lide secti ons for light mi croscopic observation in various sectional planes. The following methods were per |‘ ormecl : H&E staining I"or general hi st이 og i cal observation ‘ Von Kossafor detection of minerali zation. TRAP activ ity staining for locali zaLion 01’ osteoclastic cell s. immunohistochemistry for !Iα@-1 a ncl -9 forevaluati on of enzy matic activity 01" osteoclasLic cell s. a ncl in situ hybricli zation for detection of collagen type 1. Il. ancl X mRNA ex presslon‘ respecLively. AL E1 3.5 Mec kel's cartilage appeared as a V-shaped rod fused a t the micl line and thin minera li zed ma ndibular buccal plaLe was I"ormed lateral to. and at some clistance from. Meckel’s carti lage in an intramembranous ossi lïcation mocle. WiLh the progression of tooth development. t he Meckel’s in carti lage adjacent incisors revealecl hyperLrophi c chonclrocyte di ff"er entiation with minerali zation of the chondroid matrix. The Meckel’s car Li lage was replacecl with bone by o~ L eoc l asLs . showing strong immunoreact ivity for MMP- l ancl -9 from E16 5 Wi Lh ti me‘ Lhis bony replacement of Meckel's cartilage in an endochondral ossification mode was ex Lenclecl up Lo the mid-porLion of Lhe molar sockets til l EI8.5. The bony replacement of minera li zed hypertrophic chondrocyte zone expressing X collagen mHNA conLri buted to the formation of thick mandibular lingual plate . 1'hese f"i ndings suggesL LhaL mandibular formalion and development is closely relatecl with not only Mecke!'s carLi lage. buL also wiLh Lhc developing LooLh. and thaL C'erLai n in f"l uence from the developing tooth may play a role in detcrmin in g Lhe faLc of Meckel’s ca rLi lage cluring ma ndi bular development.

      • Effect of low concentrations of hydrogen peroxide on the contractile responses of rat detrusor smooth muscle strips

        Han, J.H.,Lee, M.Y.,Lee, S.Y.,Chang, I.H.,Kim, H.J.,Kim, W.,Myung, S.C. North-Holland ; Elsevier Science Ltd 2010 european journal of pharmacology Vol.638 No.1

        This study was designed to determine how the contractility of rat detrusor smooth muscle strips changes in the presence of low concentrations of hydrogen peroxide (H<SUB>2</SUB><SUB>2</SUB>. The strips were dissected from the base of Sprague-Dawley rat bladders and their contractile responses to a cumulative increase in H<SUB>2</SUB><SUB>2</SUB>concentration (3x10<SUP>-6</SUP>3x10<SUP>-2</SUP>%) were measured. How the duration of exposure to the fixed concentration of 3x10<SUP>-4</SUP>% H<SUB>2</SUB><SUB>2</SUB>affected contractility was also examined. Moreover, the effect of 3x10<SUP>-4</SUP>% H<SUB>2</SUB><SUB>2</SUB>pretreatment on the response to cumulative increases in the concentrations of phenylephrine or acetylcholine (10<SUP>-8</SUP>10<SUP>-4</SUP>) was assessed. To elucidate the mechanism by which H<SUB>2</SUB><SUB>2</SUB>induced contraction, we examined the effect of pretreatment with 10nM Y-27632, 10μM indomethacin, 10μM SQ29548, 10μM verapamil, 10μM vitamin E, or 1μM Bay-K 8644 on the contractile responses generated by cumulatively increasing the concentration of H<SUB>2</SUB><SUB>2</SUB> H<SUB>2</SUB><SUB>2</SUB>induced contractile responses in Ca<SUP>2+</SUP>free physiological solution were also examined. Low concentrations of H<SUB>2</SUB><SUB>2</SUB>increased the contractile responses of the strips in a dose-dependent manner but increasing treatment duration decreased these responses. H<SUB>2</SUB><SUB>2</SUB>pretreatment significantly augmented the contraction induced by phenylephrine (P<0.05) but had no effect on the response to acetylcholine. Pretreatment with Y-27632, indomethacin, vitamin E, verapamil, and Bay-K 8644 significantly inhibited the H<SUB>2</SUB><SUB>2</SUB>induced contraction (P<0.05). SQ 29548-pretreatment had no effect. H<SUB>2</SUB><SUB>2</SUB>could not increase the contractile responses in Ca<SUP>2+</SUP>free physiological solution. Thus, low concentrations of H<SUB>2</SUB><SUB>2</SUB>may directly affect detrusor smooth muscles and thereby induce detrusor overactivity.

      • Electrocatalytic activity of chemically deposited Cu<sub>x</sub>S thin film for counter electrode in quantum dots-sensitized solar cells

        Lim, I.,Lee, D.Y.,Patil, S.A.,Shrestha, N.K.,Kang, S.H.,Nah, Y.C.,Lee, W.,Han, S.H. Elsevier Science Publishers 2014 Materials chemistry and physics Vol.148 No.3

        The compact (c-Cu<SUB>x</SUB>S) and the porous (p-Cu<SUB>x</SUB>S) with particle decorated films of coppers-ulfidearesynthesized using a chemical bath deposition technique, and the films are characterized using electrochemical techniques. In addition, the chemically deposited Cu<SUB>x</SUB>S films are investigated as a counter electrode in quantum dots-sensitized solar cells (QSSCs). The available redox active reaction sites of the p-Cu<SUB>x</SUB>S film are found to be 57.9% higher than those available in the c-Cu<SUB>x</SUB>S film. From the electrochemical impedance spectroscopy, the effective diffusion coefficients of the polysulfide electrolyte in the c-Cu<SUB>x</SUB>S and p-Cu<SUB>x</SUB>S films are estimated to be 3.67 x 10<SUP>-5</SUP> and 6.35 x 10<SUP>-5</SUP> cm<SUP>2</SUP> s<SUP>-1</SUP>, respectively. These results can be ascribed to the improvement in the available redox active reaction sites and the electrocatalytic activity of the Cu<SUB>x</SUB>S counter electrode. As compared to the c-Cu<SUB>x</SUB>S film, the p-Cu<SUB>x</SUB>S film as a counter electrode exhibits an enhanced photovoltaic performance of the QSSCs with the power conversion efficiency of 3.17%, short-circuit current of 11.89 mA c<SUP>-</SUP>m<SUP>2</SUP>, open-circuit voltage of 0.50 V, and fill factor of 53.29. The improved performance of the QSSCs is ascribed to the improvements on the available redox active reaction sites, electrocatalytic activity and the diffusion coefficients, which are directly related to the surface morphology of the sulfide films.

      • SCISCIESCOPUS

        Decomposition of hydrogen sulfide (H<sub>2</sub>S) on Ni(100) and Ni<sub>3</sub>Al(100) surfaces from first-principles

        Hernandez, J.M.,Lim, D.H.,Nguyen, H.V.P.,Yoon, S.P.,Han, J.,Nam, S.W.,Yoon, C.W.,Kim, S.K.,Ham, H.C. Pergamon Press ; Elsevier Science Ltd 2014 International journal of hydrogen energy Vol.39 No.23

        Spin-polarized density functional theory studies of hydrogen sulfide (H<SUB>2</SUB>S) adsorption and decomposition on Ni(100) and Ni<SUB>3</SUB>Al(100) surfaces were conducted to understand the aluminum (Al) alloying effect on H<SUB>2</SUB>S dissociation. For such purpose, we first determined the near surface structure of fully ordered Ni<SUB>3</SUB>Al alloy along the [100] direction by calculating the Al segregation energy to the surface and then examined the adsorption energies of the adsorbates (H<SUB>2</SUB>S, HS, S, and H) and the activation barriers for the H<SUB>2</SUB>S and HS decomposition by using Climbing Image-Nudged Elastic Band method. We found that regardless of the way to terminate the surface, Al atom in bimetallic Ni<SUB>3</SUB>Al(100) tends to exist in the first surface layer, rather than in the second or third layer, and the Ni<SUB>3</SUB>Al(100) surface can substantially retard the H<SUB>2</SUB>S decomposition by reducing the adsorption energy of sulfur compounds compared to the pure Ni(100) case. Finally, we presented how the Al in Ni<SUB>3</SUB>Al modifies the activity of surface Ni atoms toward the sulfur compounds by calculating the local density of states and charge distribution in alloying components. This work hints the importance of knowing how to properly tailor the reactivity of Ni based materials to enhance the resistance for sulfur poisoning.

      • 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>

      • Structural basis for differential activities of enantiomeric PPARγ agonists: Binding of S35 to the alternate site

        Jang, J.Y.,Koh, M.,Bae, H.,An, D.R.,Im, H.N.,Kim, H.S.,Yoon, J.Y.,Yoon, H.J.,Han, B.W.,Park, S.B.,Suh, S.W. Elsevier Science 2017 Biochimica et biophysica acta. Proteins and proteo Vol.1865 No.6

        <P>Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a member of the nuclear receptor superfamily. It functions as a ligand-activated transcription factor and plays important roles in the regulation of adipocyte differentiation, type 2 diabetes mellitus, and inflammation. Many PPAR gamma agonists bind to the canonical ligand-binding pocket near the activation function-2 (AF-2) helix (i.e., helix H12) of the ligand-binding domain (LBD). More recently, an alternate ligand-binding site was identified in PPAR gamma LBD; it is located beside the 52 loop between the helices H2 ' and H3. We reported previously that the chirality of two optimized enantiomeric PPAR gamma ligands (S35 and R35) differentiates their PPAR gamma transcriptional activity, binding affinity, and inhibitory activity toward Cdk5 (cyclin-dependent kinase 5)-mediated phosphorylation of PPAR gamma at Ser245 (in PPAR gamma 1 numbering; Ser273 in PPAR gamma 2 numbering). S35 is a PPAR gamma phosphorylation inhibitor with promising glucose uptake potential, whereas R35 behaves as a potent conventional PPAR gamma agonist. To provide a structural basis for understanding the differential activities of these enantiomeric ligands, we have determined crystal structures of the PPAR gamma LBD in complex with either S35 or R35. S35 and R35 bind to the PPAR gamma LBD in significantly different manners. The partial agonist S35 occupies the alternate site near the Omega loop, whereas the full agonist R35 binds entirely to the canonical LBP. Alternate site binding of S35 affects the PPAR gamma transactivation and the inhibitory effect on PPAR gamma Ser245 phosphorylation. This study provides a useful platform for the development of a new generation of PPAR gamma ligands as anti-diabetic drug candidates.</P>

      • Sphingosine-1-phosphate-induced Flk-1 transactivation stimulates mouse embryonic stem cell proliferation through S1P<sub>1</sub>/S1P<sub>3</sub>-dependent β-arrestin/c-Src pathways

        Ryu, J.M.,Baek, Y.B.,Shin, M.S.,Park, J.H.,Park, S.H.,Lee, J.H.,Han, H.J. Elsevier 2014 Stem cell research Vol.12 No.1

        Although recent findings showed that the bioactive lipid metabolites can regulate the ES cell functions, the physiological relevance of interaction between sphingosine-1-phosphate (S1P) and Flk-1 and its related signaling molecules are not yet clear in ES cell proliferation. In the present study, S1P<SUB>1-5</SUB> receptors were expressed in mouse ES cells and S1P increased S1P<SUB>1-3</SUB> receptor expression level. S1P treatment stimulated the cellular proliferation in S1P<SUB>1/3</SUB>-dependent manner, located in lipid rafts. In response to S1P, β-arrestin was recruited to S1P<SUB>1/3</SUB> receptor and c-Src was activated. S1P also increased the binding of S1P<SUB>1/3</SUB> receptor with Flk-1. Similar to responses for VEGF, S1P increased Flk-1 phosphorylation, which was blocked by β-arrestin siRNA, and PP2, but not by VEGF-A<SUB>164</SUB> antibody or VEGF siRNA. In addition, S1P induced VEGF expression and VEGFR2 kinase inhibitor (SU1498) blocked the S1P-induced cellular proliferation. However, VEGF-A<SUB>164</SUB> antibody or VEGF siRNA partially blocked S1P-induced cellular proliferation, suggesting that both VEGF-dependent Flk-1 activation and VEGF-independent Flk-1 activation are involved in S1P-induced ES cell proliferation. S1P and VEGF-induced phosphorylation of ERK and JNK were blocked by pretreatment with SU1498. Moreover, inhibition of ERK and JNK blocked S1P-induced cellular proliferation. In conclusion, S1P-elicited transactivation of Flk-1 mediated by S1P<SUB>1/3</SUB>-dependent β-arrestin/c-Src pathways stimulated mouse ES cell proliferation.

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